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Wolde Sellasie S, Amendola S, Guidobaldi L, Pedicini F, Nardone I, Piticchio T, Zaccaria S, Scappaticcio L, Leoncini A, Uccioli L, Trimboli P. High Sensitivity of Fine-Needle Aspiration Calcitonin in Detecting Medullary Thyroid Carcinoma Is Independent of Predefined Decisional Thresholds. Diagn Cytopathol 2025; 53:197-203. [PMID: 39797433 DOI: 10.1002/dc.25440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 12/09/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025]
Abstract
The measurement of Calcitonin (Ctn) in fine-needle aspiration (FNA) washout fluids (FNA-Ctn) has demonstrated excellent sensitivity, significantly higher than FNA cytology, in detecting medullary thyroid carcinoma (MTC). However, the absence of a fixed cutoff value for FNA-Ctn poses a limitation. This study aimed to investigate whether the sensitivity of FNA-Ctn in detecting MTC varies with different cutoffs reported in the literature. A single-centre series of MTCs was retrospectively reviewed. The preoperative FNA-Ctn levels were re-evaluated using various thresholds previously reported in the literature, and the corresponding FNA-Ctn sensitivities were compared. Twenty-one MTCs were included (69% women; median age 59 years; median serum Ctn value 86 pg/mL; median MTC major diameter 10 mm). The median FNA-Ctn value was 2000 pg/mL (interquartile range 49-250). MTCs nodules were assessed at high risk (ACR TI-RADS 5) in 50% of cases, while 47.6% were cytologically malignant. Additionally, 42.9% of cases were assessed as stage III according to Union for International Cancer Control staging system (UICC). Serum Ctn was significantly lower in stage I (p = 0.04). FNA-Ctn was positively correlated with serum Ctn (Rho = 0.45; p = 0.04), while ACR TI-RADS assessment with MTC stage (Rho = 0.69; p = 0.003). FNA-Ctn sensitivity ranged from 95% to 100% based on the previously proposed FNA-Ctn cutoffs. The high sensitivity of FNA-Ctn in detecting MTC did not significantly differ when applying the previously proposed cutoffs. Given the absence of a universally applicable FNA-Ctn decisional threshold, institutions should establish their own diagnostic cutoffs. Future guidelines should incorporate these concepts to enhance clinical decision-making and patient outcomes.
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Affiliation(s)
- Sium Wolde Sellasie
- Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
- PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy
| | - Stefano Amendola
- Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Leo Guidobaldi
- UOC of Pathologic Anatomy and Cytodiagnostic, Sandro Pertini Hospital, Rome, Italy
| | | | - Isabella Nardone
- Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
- PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy
| | - Tommaso Piticchio
- Endocrinology Section, Department of Clinical and Experimental Medicine, Garibaldi Nesima Hospital, University of Catania, Catania, Italy
- Department of Medicine and Surgery, University Kore of Enna, Enna, Italy
| | - Simona Zaccaria
- Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
- PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy
| | - Lorenzo Scappaticcio
- Division of Endocrinology and Metabolic Diseases, AOU University of Campania Luigi Vanvitelli, Naples, Italy
| | - Andrea Leoncini
- Servizio di Radiologia e Radiologia Interventistica, Istituto di Imaging Della Svizzera Italiana (IIMSI), Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland
| | - Luigi Uccioli
- Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Pierpaolo Trimboli
- Servizio di Endocrinologia e Diabetologia, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland
- Facoltà di Scienze Biomediche, Università della Svizzera Italiana (USI), Lugano, Switzerland
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Cameselle-Teijeiro JM, Sobrinho-Simões M. Histopathology of C Cells and Medullary Thyroid Carcinoma. Recent Results Cancer Res 2025; 223:9-50. [PMID: 40102253 DOI: 10.1007/978-3-031-80396-3_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/20/2025]
Abstract
C cells are the neuroendocrine cell component of the thyroid gland that embryologically arise from the pharyngeal endoderm. Normal C cells are concentrated in the upper two-thirds of both lateral lobes, appear singly or in small groups dispersed in, among or peripherally to the follicles, and are involved in the production of calcitonin. Reactive C-cell hyperplasia should be differentiated from proliferation of atypical C cells (neoplastic C-cell hyperplasia) which is considered an intraepithelial neoplasia of C cells/medullary carcinoma in situ, a precursor lesion associated to familial medullary thyroid carcinoma (MTC). MTC typically exhibits a lobular and/or trabecular growth pattern with amyloid deposits; however, due to its great histological variability, immunohistochemical positivity for calcitonin, carcinoembryonic antigen, calcitonin-gene-related peptide, insulinoma-associated protein 1, and/or other markers is necessary to confirm diagnosis. Investigation of germline RET proto-oncogene mutation is mandatory to identify familial MTC. Somatic RET mutations or fusions as well as RAS mutations in cytological and/or biopsy samples may represent therapeutic targets. Mixed medullary and follicular-derived cell carcinoma is a heterogeneous group of tumors which needs to be distinguished from collision tumors.
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Affiliation(s)
- José Manuel Cameselle-Teijeiro
- Department of Pathology, Clinical University Hospital of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Galician Healthcare Service (SERGAS), University of Santiago de Compostela, Santiago de Compostela, Spain.
| | - Manuel Sobrinho-Simões
- Department of Pathology, Medical Faculty, Institute of Molecular Pathology and Immunology (IPATIMUP), i3S-Institute for Research & Innovation in Health, University of Porto, Porto, Portugal
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Giovanella L, Tuncel M, Aghaee A, Campenni A, De Virgilio A, Petranović Ovčariček P. Theranostics of Thyroid Cancer. Semin Nucl Med 2024; 54:470-487. [PMID: 38503602 DOI: 10.1053/j.semnuclmed.2024.01.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 01/29/2024] [Accepted: 01/30/2024] [Indexed: 03/21/2024]
Abstract
Molecular imaging is pivotal in evaluating and managing patients with different thyroid cancer histotypes. The existing, pathology-based, risk stratification systems can be usefully refined, by incorporating tumor-specific molecular and molecular imaging biomarkers with theranostic value, allowing patient-specific treatment decisions. Molecular imaging with different radioactive iodine isotopes (ie, I131, I123, I124) is a central component of differentiated carcinoma (DTC)'s risk stratification while [18F]F-fluorodeoxyglucose ([18F]FDG) PET/CT is interrogated about disease aggressiveness and presence of distant metastases. Moreover, it is particularly useful to assess and risk-stratify patients with radioiodine-refractory DTC, poorly differentiated, and anaplastic thyroid cancers. [18F]F-dihydroxyphenylalanine (6-[18F]FDOPA) PET/CT is the most specific and accurate molecular imaging procedure for patients with medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells. In addition, [18F]FDG PET/CT can be used in patients with more aggressive clinical or biochemical (ie, serum markers levels and kinetics) MTC phenotypes. In addition to conventional radioiodine therapy for DTC, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC. Moreover, peptide receptor theranostics showed promising results in patients with advanced and metastatic radioiodine-refractory DTC and MTC, respectively. The current appropriate role and future perspectives of molecular imaging and theranostics in thyroid cancer are discussed in our present review.
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Affiliation(s)
- Luca Giovanella
- Department of Nuclear Medicine, Gruppo Ospedaliero Moncucco, Lugano, Switzerland; Clinic for Nuclear Medicine, University Hospital Zürich, Zürich, Switzerland.
| | - Murat Tuncel
- Department of Nuclear Medicine, Hacettepe University, Ankara, Turkey
| | - Atena Aghaee
- Department of Nuclear Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alfredo Campenni
- Nuclear Medicine Unit, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy
| | - Armando De Virgilio
- Department of Head and Neck Surgery Humanitas Research Hospital, Rozzano, Italy
| | - Petra Petranović Ovčariček
- Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia; School of Medicine, University of Zagreb, Zagreb, Croatia
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Liu S, Zhao H, Li X. Serum Biochemical Markers for Medullary Thyroid Carcinoma: An Update. Cancer Manag Res 2024; 16:299-310. [PMID: 38617188 PMCID: PMC11011642 DOI: 10.2147/cmar.s440477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 03/21/2024] [Indexed: 04/16/2024] Open
Abstract
INTRODUCTION Medullary thyroid carcinoma (MTC), a rare malignancy, requires early diagnosis for optimal patient outcomes. An important aspect of MTC diagnosis is the assessment of serum biomarkers. This review aimed to evaluate the use of serum biomarkers in the diagnosis, prognosis, and follow-up of MTC. METHODS A thorough search of PubMed covering 1975 to 2022 was conducted to identify English-language articles on MTC serum biomarkers. RESULTS The review revealed that calcitonin (Ctn) and carcinoembryonic antigen (CEA) remain the most important serum biomarkers for MTC diagnosis and management. Despite limited studies on procalcitonin (PCT), its stability and ability to exclude interference from inflammation make it a valuable potential marker of MTC. Although the positive rate of serum CA19-9 levels in MTC patients was not high, it can be used as an indicator of poor prognosis in advanced MTC. Other serum markers, including chromogranin A, gastrin-releasing peptide precursor, and neurospecific enolase, did not show any unique value in MTC diagnosis and management. CONCLUSION Taken together, this review emphasized the importance of serum biomarkers, particularly Ctn and CEA, in the diagnosis and management of MTC. PCT shows promise as a valuable potential marker, whereas CA19-9 can be used as a prognostic indicator of advanced MTC. Further research is needed to validate the significance of these serum biomarkers in MTC and determine the effects of confounding factors on their levels. Clinicians should consider using these markers in MTC diagnosis, prognosis, and follow-up, particularly for patients with advanced disease.
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Affiliation(s)
- Shuzhou Liu
- Department of Head & Neck Surgery, Hainan General Hospital, Haikou, 570311, People’s Republic of China
| | - Hao Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100010, People’s Republic of China
| | - Xiaoyi Li
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100010, People’s Republic of China
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Ogmen BE, Ince N, Aksoy Altınboga A, Akdogan L, Polat SB, Genc B, Menekse E, Aydin C, Topaloglu O, Ersoy R, Cakir B. An old friend, a new insight: Calcitonin measurement in serum and aspiration needle washout fluids significantly increases the early and accurate detection of medullary thyroid cancer. Cancer Cytopathol 2024; 132:161-168. [PMID: 37950525 DOI: 10.1002/cncy.22779] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/24/2023] [Accepted: 10/25/2023] [Indexed: 11/12/2023]
Abstract
BACKGROUND The sensitivity of cytological (CY) evaluation after fine-needle aspiration (FNA) for detecting medullary thyroid carcinoma (MTC) is a subject of controversy. The routine use of serum calcitonin (CT) in patients with thyroid nodules is not universally adopted. The authors conducted CT screening of FNA washout fluid (FNA-CT) to address the diagnostic challenges. The objective was to assess the contributions of serum CT, FNA cytology (FNA-CY), and FNA-CT to the diagnosis. METHODS Between February 2019 and June 2022 (group 1), the authors prospectively screened the CT of patients with thyroid nodules. Both FNA-CY and FNA-CT were performed for patients with persistently elevated CT values. The sensitivity of FNA-CY, serum CT, and FNA-CT for accurate diagnosis was evaluated. Additionally, the authors retrospectively examined data from patients with thyroid nodules before CT screening (2008-2019) (group 2). They compared the characteristics of MTC patients in groups 1 and 2. RESULTS MTC was identified in 30 patients (0.25%) in group 1 and 19 (0.07%) in group 2. A FNA-CT cutoff value of 4085.5 pg/mL detected MTC with a sensitivity of 96.8%, and a serum CT cutoff value of 28.3 pg/mL detected MTC with a sensitivity of 86.7%. In contrast, FNA-CY detected MTC with a sensitivity of 42.4%. In group 1, 18 patients (60%) with MTC were diagnosed with microcarcinoma, whereas only two patients (10.5%) in group 2 had microcarcinoma. CONCLUSIONS This study detected MTC earlier by routinely measuring serum CT in all patients with nodular thyroid disease and performing FNA-CT in those with elevated values. FNA-CT and serum CT sensitivities were significantly higher than those of FNA-CY. This study revealed different FNA-CT cutoff values compared to other studies, emphasizing the need for determining clinic-specific cutoff values.
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Affiliation(s)
- Berna Evranos Ogmen
- Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University, Faculty of Medicine, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Nurcan Ince
- Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University, Faculty of Medicine, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Aysegul Aksoy Altınboga
- Department of Pathology, Ankara Yildirim Beyazit University, Faculty of Medicine, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Leyla Akdogan
- Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University, Faculty of Medicine, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Sefika Burcak Polat
- Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University, Faculty of Medicine, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Birgul Genc
- Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University, Health Sciences Institute, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Ebru Menekse
- Department of Surgery, University of Health Sciences, Faculty of Medicine, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Cevdet Aydin
- Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University, Faculty of Medicine, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Oya Topaloglu
- Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University, Faculty of Medicine, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Reyhan Ersoy
- Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University, Faculty of Medicine, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Bekir Cakir
- Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University, Faculty of Medicine, Ankara Bilkent City Hospital, Ankara, Turkey
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Samardzic VS, Macvanin MT, Zafirovic SS, Obradovic MM, Gluvic ZM, Grubin J, Gao X, Essack M, Isenovic ER. Nitric oxide, thyroglobulin, and calcitonin: unraveling the nature of thyroid nodules. Front Endocrinol (Lausanne) 2023; 14:1241223. [PMID: 37842300 PMCID: PMC10569474 DOI: 10.3389/fendo.2023.1241223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 09/11/2023] [Indexed: 10/17/2023] Open
Abstract
Background Thyroid nodules (TN) are localized morphological changes in the thyroid gland and can be benign or malignant. Objective The present study investigates the relationships between biochemical markers in serum (s) and their homologs in washout (w) after fine-needle aspiration biopsy (FNAB) of the TN of interest and their correlation with cytology specimen findings. Methods We investigated the relationships between serum biochemical markers nitric oxide (NO), thyroglobulin (TG), and calcitonin (CT), their homologs in washout after FNAB of the TN of interest, and cytology findings of biopsy samples classified according to the Bethesda system for thyroid cytopathology in this study, which included 86 subjects. Results Washout TG (TGw) level positively correlates with the cytology finding of the biopsy. A higher level of TGw correlates with higher categories of the Bethesda classification and indicates a higher malignant potential. The levels of serum NO (NOs), serum TG (TGs), serum CT (CTs), and washout CT (CTw) do not correlate with the cytology finding of the biopsy, and the higher levels of washout NO (NOw) correspond to the more suspicious ultrasound findings. Conclusion The findings of our study suggest that TGw and NOw could be used as potential predictors of malignancy in TN.
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Affiliation(s)
- Vladimir S. Samardzic
- Clinic for Internal Medicine, Department of Endocrinology and Diabetes, Zemun Clinical Hospital, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Mirjana T. Macvanin
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Sonja S. Zafirovic
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Milan M. Obradovic
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Zoran M. Gluvic
- Clinic for Internal Medicine, Department of Endocrinology and Diabetes, Zemun Clinical Hospital, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jasmina Grubin
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, Belgrade, Serbia
| | - Xin Gao
- Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
- Computer Science Program, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
| | - Magbubah Essack
- Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
- Computer Science Program, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
| | - Esma R. Isenovic
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
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Zuraeva ZT, Nikankina LV, Kolesnikova GS, Abdulhabirova FM, Beltsevich DG, Malysheva NM, Mikheenkov AA. [Calcitonin measurement in fine-needle washout fluids in detecting medullary thyroid cancer]. PROBLEMY ENDOKRINOLOGII 2023; 69:9-15. [PMID: 37448242 DOI: 10.14341/probl13236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 03/02/2023] [Accepted: 03/03/2023] [Indexed: 07/15/2023]
Abstract
BACKGROUND The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy wash-out fluid is a promising tool in the diagnosis of medullary thyroid cancer. AIMS We assessed the potential usefulness and the diagnostic significance of Ct-FNAB alone in comparison with cytology in the diagnosis and localization of primary or metastatic MTC. MATERIALS AND METHODS For this purpose, we retrospectively examined data from 67 patients with suspicious thyroid nodules and/or lymph nodes who ultimately underwent surgical treatment at the Endocrinology Research Centre in 2015-2020. The primary endpoint of the study was to evaluate the diagnostic accuracy of Ct-FNAB when compared to cytological examination. The secondary endpoint was to determine the optimal diagnostic level for use in clinical practice. RESULTS The obtained results showed that high Ct-FNAB concentrations were present in all histologically proven MTC, either in thyroid gland (sensitivity 92.5%, specificity 100%) or neck masses (sensitivity 88.5%, specificity 100%). The optimal diagnostic threshold for Ct-FNAB values from thyroid nodes was > 122 pg/ml, from lymph nodes >35.8 pg/ml. CONCLUSIONS Our findings suggest that Ct-FNAB is a highly reliable diagnostic procedure to identify primary and recurrent/metastatic MTC. The actual relevance of this technique in the management of MTC needs further longitudinal studies in a larger number of patients.
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Velez Torres JM, Tjendra Y, Kerr DA. A Triumvirate:: Correlating Thyroid Cytopathology, Molecular Testing, and Histopathology. Surg Pathol Clin 2023; 16:1-14. [PMID: 36739157 DOI: 10.1016/j.path.2022.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Risk stratification is essential in the preoperative evaluation and management of thyroid nodules, most of which are benign. Advances in DNA and RNA sequencing have shed light on the molecular drivers of thyroid cancer. Molecular testing of cytologically indeterminate nodules has helped refine risk stratification, triage patients for surgery, and determine the extent of surgery. Molecular platforms with high negative predictive values can help identify nodules that may be spared surgery and can be managed conservatively. Here we discuss the importance of integrating cytomorphologic, molecular, and histologic features to help avoid errors and improve patient management.
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Affiliation(s)
- Jaylou M Velez Torres
- Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, 1400 NW 12(th) Avenue, Miami, FL 33136, USA. https://twitter.com/JaylouVelez
| | - Youley Tjendra
- Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, 1400 NW 12(th) Avenue, Miami, FL 33136, USA. https://twitter.com/Y_Tjendra
| | - Darcy A Kerr
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA; Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
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Li R, Wang Y, Zhao Z, Li X, Liu Z. A bibliometric analysis based on Web of Science from 2012 to 2021: Current situation, hot spots, and global trends of medullary thyroid carcinoma. Front Oncol 2023; 13:1119915. [PMID: 36959786 PMCID: PMC10029728 DOI: 10.3389/fonc.2023.1119915] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 02/22/2023] [Indexed: 03/09/2023] Open
Abstract
Background Medullary thyroid carcinoma (MTC) is a special type of thyroid carcinoma derived from the C cell of the thyroid gland. Because of the poor prognosis of MTC, a large number of studies on MTC have been conducted in the last 10 years. To better comprehend, it is necessary to clarify and define the dominant countries, organizations, core journals, important authors, and their cumulative research contributions, as well as the cooperative relationships between them. Method English publications with article type article or review about MTC from January 2012 to December 2021 was retrieved from Web of Science core collection, and VOSviewer, CiteSpace, and Microsoft Excel were applied for bibliometric study. Result A total of 1208 articles and reviews were included in this study. The 1208 papers were written by 6364 authors from 1734 organizations in 67 countries, published in 408 journals, and cited 24118 references from 3562 journals. The number of publications was essentially flat from 2012-2021, with the largest proportion of publications coming from the U.S., followed by Italy and China. Thyroid was the most productive journal, and Journal of clinical endocrinology & metabolism was the most cited journal. University of Texas MD Anderson Cancer Center was the most productive institution and Luca Giovanella, was the most productive author. Diagnostic tools, surgical treatment, non-surgical treatment, genetics and relationship with other endocrine diseases were the main research interests in this field. Prognosis has been a cutting-edge topic since 2017. Conclusion As a thyroid cancer with poor prognosis, MTC has received continuous attention in recent years. Current MTC studies mainly focused on disease intervention, mechanism research and prognosis. The main point of this study is to provide an overview of the development process and hot spots of MTC in the last decade. These might provide ideas for further research in the MTC field.
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Affiliation(s)
- Ruyin Li
- Department of General Surgery, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yingjiao Wang
- Department of Breast Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Zirui Zhao
- Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaobin Li
- Department of General Surgery, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- *Correspondence: Xiaobin Li, ; Ziwen Liu,
| | - Ziwen Liu
- Department of General Surgery, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- *Correspondence: Xiaobin Li, ; Ziwen Liu,
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Wang M, Chen H, Wang Y, Lei J, Li Z. Diagnostic value and cost-effectiveness of FNA-CT versus FNAC for medullary thyroid carcinoma. Clin Endocrinol (Oxf) 2022; 98:709-718. [PMID: 36394172 DOI: 10.1111/cen.14852] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/08/2022] [Accepted: 11/15/2022] [Indexed: 11/18/2022]
Abstract
OBJECTIVE To evaluate the diagnostic performance and cost-effectiveness of calcitonin assays in fine-needle aspiration washout fluid (FNA-CT) compared to fine-needle aspiration cytology (FNAC) for medullary thyroid carcinoma (MTC). METHODS A total of 27,404 patients from three medical centres between January 2020 and May 2022 were screened for serum calcitonin (sCT). Of whom, 223 patients met endpoints and were enroled for analyses. Based on sCT levels, patients were divided into two groups (group 1: 10 pg/ml< sCT ≤100 pg/ml and group 2: sCT > 100 pg/ml). The diagnostic performance and cost-effectiveness of FNA-CT and FNAC were compared. RESULTS Most patients (N = 25,228; 92.1%) with thyroid nodules had normal sCT levels. In group 1, 24 and 167 nodules were diagnosed as MTC and non-MTC lesions, respectively. FNA-CT showed better performance in diagnosing MTC than FNAC in terms of sensitivity (100.0% vs. 58.3%), negative predictive value (100.0% vs. 94.3%), and overall accuracy (100.0% vs. 94.7%). In group 2, 67 and 7 nodules were diagnosed as MTC and non-MTC lesions, respectively. The diagnostic performance of FNA-CT was superior to FNAC in terms of sensitivity (100.0% vs. 64.2%), negative predictive value (100.0% vs. 22.6%), and overall accuracy (100.0% vs. 67.6%). Furthermore, analysis from the decision tree model showed that FNA-CT was a cost-effective tool for diagnosing MTC lesions. CONCLUSIONS FNA-CT can serve as an auxiliary and cost-effective approach for patients with indeterminate sCT levels to detect occult MTC lesions. FNA-CT can be recommended for patients with sCT >100 pg/ml to overcome the high false-negative rate of FNAC.
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Affiliation(s)
- Mingjun Wang
- Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hedan Chen
- Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yichao Wang
- Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jianyong Lei
- Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zhihui Li
- Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Nikas IP, Kazamias G, Vrontaki M, Rapti AS, Mastorakis E. Medullary thyroid carcinoma diagnosed with liquid-based cytology and immunocytochemistry. J Immunoassay Immunochem 2022; 43:502-515. [PMID: 35475413 DOI: 10.1080/15321819.2022.2070025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy that arises from the parafollicular cells (C cells) secreting calcitonin. This study summarizes our experience in the diagnosis of MTC with ultrasound-guided thyroid FNA, subsequently processed with liquid-based cytology (LBC) and immunocytochemistry (ICC). We searched our laboratory archives for thyroid FNA cases with an interpretation of positive or suspicious for MTC, during the period 2004-2018. A total of 20 cases (18 thyroid FNAs; two lymph node FNAs) were selected and included in this study. These displayed high cellularity and a discohesive pattern, with a few loose syncytial groups. There was some variation in the cell size and shape both across and within our cases. Most MTCs (n = 15) exhibited a predominant plasmacytoid/epithelioid cell morphology, whereas five of our cases showed a spindle cell pattern. Of interest, none of eight MTC microcarcinomas (≤1 cm) showed a spindle cell morphology. Amyloid was found in 11/20 cases (55%), while binucleation/multinucleation in 17/20 (85%), and nuclear pseudoinclusions in 3/20 MTC cases (15%). Nuclei exhibited a granular, "salt and pepper" chromatin in all cases. ICC was performed in 18/20 cases (90%). Calcitonin, CEA, TTF1, and Chromogranin were positive wherever applied, whereas thyroglobulin and CK19 were negative. In conclusion, ultrasound-guided thyroid FNA - processed with LBC and ICC - is a reliable modality to detect MTC preoperatively, facilitating the management of such patients.
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Affiliation(s)
- Ilias P Nikas
- School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Georgios Kazamias
- Department of Pathology, "Venizeleio-Pananeio" General Hospital, Heraklion, Crete, Greece
| | - Maria Vrontaki
- Department of Cytopathology, "Venizeleio-Pananeio" General Hospital, Heraklion, Crete, Greece
| | - Aleka S Rapti
- Department of Pathology, "Venizeleio-Pananeio" General Hospital, Heraklion, Crete, Greece.,Department of Cytopathology, "Venizeleio-Pananeio" General Hospital, Heraklion, Crete, Greece
| | - Emmanouil Mastorakis
- Department of Cytopathology, "Venizeleio-Pananeio" General Hospital, Heraklion, Crete, Greece
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Ahmed M, Abi-Raad R, Fu L, Holt EH, Adeniran AJ, Cai G. Performing Calcitonin Immunocytochemistry on an Additional ThinPrep Slide in Fine-Needle Aspiration Diagnosis of Medullary Thyroid Carcinoma. Am J Clin Pathol 2022; 157:426-433. [PMID: 34596209 DOI: 10.1093/ajcp/aqab141] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 07/27/2021] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES This study reviewed the institutional experience of performing calcitonin immunostain on an additional ThinPrep slide in fine-needle aspiration (FNA) diagnosis of medullary thyroid carcinoma (MTC). METHODS Thyroid FNA cases with MTC suspected or included in the differential diagnosis during cytologic evaluation and calcitonin immunostain performed were retrieved and reviewed. RESULTS Calcitonin immunostain was performed in 132 cases with 41 positive, 81 negative, and 10 indeterminate results. All calcitonin-positive cases had a cytologic diagnosis of MTC while all calcitonin-negative cases were cytologically classified as non-MTCs except for two cases suspicious for MTC. In 10 cases with an indeterminate calcitonin result, diagnoses of non-MTC and suspicious for MTC were rendered in 6 and 4 cases, respectively. Histopathologic follow-up was available in 85 (64%) cases. All cytologically diagnosed MTC cases were confirmed on histopathology. In 3 MTC cases with an indeterminate calcitonin result, 1 case was misclassified cytologically as follicular neoplasm. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of calcitonin immunostain were all 100% for diagnosing MTC. CONCLUSIONS Our study demonstrates the feasibility of performing calcitonin immunostain on an additional ThinPrep slide. Calcitonin immunocytochemistry is a valuable adjunct test for FNA diagnosis and differential diagnosis of MTC.
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Affiliation(s)
- Muhammad Ahmed
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | - Rita Abi-Raad
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | - Liying Fu
- Department of Pathology, Scripps Green Hospital, La Jolla, CA,USA
| | - Elizabeth H Holt
- Department of Internal Medicine, Endocrinology Section, Yale University School of Medicine, New Haven, CT, USA
| | | | - Guoping Cai
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
- Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA
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13
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Giovanella L, Deandreis D, Vrachimis A, Campenni A, Petranovic Ovcaricek P. Molecular Imaging and Theragnostics of Thyroid Cancers. Cancers (Basel) 2022; 14:1272. [PMID: 35267580 PMCID: PMC8909041 DOI: 10.3390/cancers14051272] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 02/22/2022] [Accepted: 02/25/2022] [Indexed: 02/06/2023] Open
Abstract
Molecular imaging plays an important role in the evaluation and management of different thyroid cancer histotypes. The existing risk stratification models can be refined, by incorporation of tumor-specific molecular markers that have theranostic power, to optimize patient-specific (individualized) treatment decisions. Molecular imaging with varying radioisotopes of iodine (i.e., 131I, 123I, 124I) is an indispensable component of dynamic and theragnostic risk stratification of differentiated carcinoma (DTC) while [18F]F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) helps in addressing disease aggressiveness, detects distant metastases, and risk-stratifies patients with radioiodine-refractory DTC, poorly differentiated and anaplastic thyroid cancers. For medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells, [18F]F-dihydroxyphenylalanine (6-[18F]FDOPA) PET/CT and/or [18F]FDG PET/CT can be used dependent on serum markers levels and kinetics. In addition to radioiodine therapy for DTC, some theragnostic approaches are promising for metastatic MTC as well. Moreover, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC while new theragnostic approaches showed promising preliminary results for advanced and aggressive forms of follicular-cell derived thyroid cancers (i.e., peptide receptor radiotherapy). In order to help clinicians put the role of molecular imaging into perspective, the appropriate role and emerging opportunities for molecular imaging and theragnostics in thyroid cancer are discussed in our present review.
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Affiliation(s)
- Luca Giovanella
- Clinic for Nuclear Medicine and Molecular Imaging, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland
| | - Desiree’ Deandreis
- Division of Nuclear Medicine, Department of Medical Sciences, AOU Città della Salute e della Scienza, University of Turin, 10126 Turin, Italy;
| | - Alexis Vrachimis
- Department of Nuclear Medicine, German Oncology Center, University Hospital of the European University, Limassol 4108, Cyprus;
| | - Alfredo Campenni
- Nuclear Medicine Unit, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, 98121 Messina, Italy;
| | - Petra Petranovic Ovcaricek
- Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, 10000 Zagreb, Croatia;
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14
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Mason D, Leimbach R, Kitz R, Vietor R, Vietor N. Calcitonin-secreting pancreatic neuroendocrine tumor in a patient with elevated thyroid fine-needle aspirate calcitonin washout: A case report and review of the literature. Clin Case Rep 2022; 10:e05296. [PMID: 35106164 PMCID: PMC8784917 DOI: 10.1002/ccr3.5296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 12/06/2021] [Accepted: 12/11/2021] [Indexed: 11/10/2022] Open
Abstract
We report the unique case of a patient with previously proven non-functional PanNET and Graves' disease with thyroid nodules. The patient had elevated intranodular calcitonin, but no MTC or c-cell hyperplasia on thyroidectomy. They were found to have calcitonin secreting PanNET. This case presents a false-positive intranodular calcitonin.
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Affiliation(s)
- Darryl Mason
- F. Edward Hebert School of MedicineUniformed Services UniversityBethesdaMarylandUSA
| | - Robert Leimbach
- Department of EndocrinologyWalter Reed National Military Medical CenterBethesdaMarylandUSA
| | - Robert Kitz
- Department of PathologyWalter Reed National Military Medical CenterBethesdaMarylandUSA
| | - Robert Vietor
- F. Edward Hebert School of MedicineUniformed Services UniversityBethesdaMarylandUSA
| | - Nicole Vietor
- Department of EndocrinologyWalter Reed National Military Medical CenterBethesdaMarylandUSA
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15
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Trimboli P, Giannelli J, Marques B, Piccardo A, Crescenzi A, Deandrea M. Head-to-head comparison of FNA cytology vs. calcitonin measurement in FNA washout fluids (FNA-CT) to diagnose medullary thyroid carcinoma. A systematic review and meta-analysis. Endocrine 2022; 75:33-39. [PMID: 34606057 PMCID: PMC8763758 DOI: 10.1007/s12020-021-02892-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 09/22/2021] [Indexed: 12/01/2022]
Abstract
PURPOSE The sensitivity of cytology after fine needle aspiration (FNA-cytology) in detecting medullary thyroid carcinoma (MTC) is low. To overcome this problem, measuring calcitonin (CT) in washout fluid of FNA (FNA-CT) has been largely diffused and showed good performance. However, no evidence-based study exists comparing systematically the sensitivity of FNA-cytology and FNA-CT. This study aimed to systematically review the literature and collect data allowing a head-to-head comparison meta-analysis between FNA-cytology and FNA-CT in detecting MTC lesions. METHODS The online databases of PubMed/MEDLINE and Scopus were searched until June 2021. Original articles reporting the use of both FNA-cytology and FNA-CT in the same series of histologically proven MTC lesions were included They were extracted general features of each study, number of MTC lesions (nodule and neck lymph nodes), and true positive and false negatives of both FNA-cytology and FNA-CT. RESULTS Six studies were included. The sensitivity of FNA-cytology varied from 20% to 86% with a pooled value of 54% (95% CI 35-73%) and significant heterogeneity. The sensitivity of FNA-CT was higher than 95% in almost all studies with a pooled value of 98% (95% CI 96-100%) without heterogeneity. The sensitivity of FNA-CT was significantly higher than that of FNA-cytology. CONCLUSIONS FNA-CT is significantly more sensitive than FNA-cytology in detecting MTC. Accordingly, FNA-CT represents the standard method to use in patients with suspicious MTC lesions, combined with cytology.
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Affiliation(s)
- Pierpaolo Trimboli
- Servizio di Endocrinologia e Diabetologia, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland.
- Facoltà di Scienze Biomediche, Università della Svizzera Italiana (USI), Lugano, Switzerland.
| | - Jacopo Giannelli
- Division of Endocrinology, Diabetes and Metabolism, Department of Medical Science, University of Turin, Turin, Italy
| | - Bernardo Marques
- Endocrinology Department, Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, EPE, Lisbon, Portugal
| | - Arnoldo Piccardo
- Nuclear Medicine Department, Ente Ospedaliero "Ospedali Galliera", Genoa, Italy
| | - Anna Crescenzi
- Department of Pathology, University Hospital Campus Bio-Medico, Rome, Italy
| | - Maurilio Deandrea
- UO Endocrinologia, Diabetologia e Malattie del metabolismo, AO Ordine Mauriziano Torino, Torino, Italy
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16
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Salh AM, Ahmed SF, Omar SS, Hassan SH, Mohammed SH, Kakamad FH. Medullary thyroid carcinoma with normal serum calcitonin and carcinoembryonic levels; a case with review of literature. INTERNATIONAL JOURNAL OF SURGERY OPEN 2022. [DOI: 10.1016/j.ijso.2022.100443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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17
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Liu Z, Zhou W, Han R, Zhou W, Zhang J, Li H, Wan Z, Jin Y, Shen L, Zhou Y, Wang S, Chen X, Ye L. Cytology versus calcitonin assay in fine-needle aspiration biopsy wash-out fluid (FNAB-CT) in diagnosis of medullary thyroid microcarcinoma. Endocrine 2021; 74:340-348. [PMID: 34028648 DOI: 10.1007/s12020-021-02759-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 05/06/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE Widespread use of sensitive ultrasound examination led to an increasing detection of medullary thyroid microcarcinoma (micro-MTC). This prospective study evaluated the diagnostic accuracy of Fine-needle Aspiration Biopsy Cytology (FNAB-C) and calcitonin assay in Fine-needle Aspiration Biopsy wash-out fluid (FNAB-CT) in thyroid nodules less than 1 cm with elevated serum calcitonin(sCT). METHODS 87 thyroid nodules from 60 patients with elevated sCT (>10 pg/ml) were included and 51 were thyroid nodules less than 1cm. FNAB-CT and FNAB-C were performed to distinguish medullary thyroid carcinoma (MTC) lesions before surgery, histopathologic diagnoses served as main reference standards. RESULTS FNAB-CT had a greater performance over FNAB-C for preoperative diagnosis of MTC (diagnostic accuracy: 98.85 vs 61.90%, sensitivity: 98.55 vs 55.07%, specificity: 100 vs 97.44%), especially for micro-MTC: FNAB-C established a sensitivity and diagnostic accuracy of 48.78 and 58% respectively, while FNAB-CT reached 97.56% sensitivity and 98.04% diagnostic accuracy. CONCLUSIONS FNAB-CT demonstrated high diagnostic accuracy in diagnosing micro-MTC. Patients with microscopic thyroid nodules and elevated sCT level should perform FNAB-CT to exclude the diagnosis of MTC lesions.
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Affiliation(s)
- Ziyuan Liu
- Shanghai Clinical Center for Endocrine & Metabolic Diseases, Department of Endocrine & Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Wenzhong Zhou
- Shanghai Institute of Endocrine & Metabolic Diseases, Shanghai, China
| | - Rulai Han
- Shanghai Institute of Endocrine & Metabolic Diseases, Shanghai, China
| | - Wei Zhou
- Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Jie Zhang
- Shanghai Clinical Center for Endocrine & Metabolic Diseases, Department of Endocrine & Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Haorong Li
- Shanghai Clinical Center for Endocrine & Metabolic Diseases, Department of Endocrine & Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Zhihan Wan
- Shanghai Clinical Center for Endocrine & Metabolic Diseases, Department of Endocrine & Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Yan Jin
- Shanghai Institute of Endocrine & Metabolic Diseases, Shanghai, China
| | - Liyun Shen
- Shanghai Clinical Center for Endocrine & Metabolic Diseases, Department of Endocrine & Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Yulin Zhou
- Shanghai Clinical Center for Endocrine & Metabolic Diseases, Department of Endocrine & Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Shu Wang
- Shanghai Clinical Center for Endocrine & Metabolic Diseases, Department of Endocrine & Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Xi Chen
- Department of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
| | - Lei Ye
- Shanghai Clinical Center for Endocrine & Metabolic Diseases, Department of Endocrine & Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
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18
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Carcinoembryonic Antigen Increase in a Patient with Colon Cancer Who Have Achieved Complete Remission and Negative 18F-FDG PET/CT: Don't Forget the Thyroid! ACTA ACUST UNITED AC 2021; 28:2987-2992. [PMID: 34436027 PMCID: PMC8395414 DOI: 10.3390/curroncol28040261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 07/27/2021] [Accepted: 08/04/2021] [Indexed: 11/30/2022]
Abstract
Serum carcinoembryonic antigen (CEA) is a tumor marker especially used to follow a patient with colorectal cancer. However, it is non-specific and could be increased in several cancers and some benign conditions. We report the case of a 70-year-old man followed since 2014 for a left colon adenocarcinoma with the persistence of an increased CEA. There was no evidence of recurrence, but a right lobar thyroid nodule without a significantly increased uptake was incidentally discovered on the CT scan of 18F-fluorodeoxyglucose (18F-FDG) PET/CT. We suspected a medullary thyroid carcinoma (MTC) explaining the persistent elevation of CEA. Plasma calcitonin levels were 47 ng/L (N < 10). Fine needle aspiration cytology found atypia of undetermined significance and the patient was reluctant to undergo surgery without any further exploration. We performed a 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT preoperatively which revealed a punctiform focus of the right thyroid lobe corresponding to a pT1aN1aMxR0 medullary thyroid carcinoma, histopathologically confirmed. This case highlights that despite the potential usefulness of 18F-FDG PET/CT in case of an unknown source of elevated CEA this imaging may be falsely negative as in the case of MTC and should lead to further explorations.
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19
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Askari E, Pourabdollah Toutkaboni M, Haseli S, Rezaei M, Tabarsi P, Marjani M, Moniri A, Khalili N. Not all that is miliary is tuberculosis: Metastatic medullary thyroid carcinoma mimicking miliary tuberculosis. Clin Case Rep 2021; 9:e04231. [PMID: 34026193 PMCID: PMC8123563 DOI: 10.1002/ccr3.4231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 01/23/2021] [Accepted: 04/14/2021] [Indexed: 11/06/2022] Open
Abstract
Medullary carcinoma of the thyroid should be considered in the differential diagnosis of miliary pattern of micronodules on chest imaging, irrespective of clinical features.
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Affiliation(s)
- Elham Askari
- Chronic Respiratory Diseases Research CenterNational Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Mihan Pourabdollah Toutkaboni
- Chronic Respiratory Diseases Research CenterNational Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Sara Haseli
- Chronic Respiratory Diseases Research CenterNational Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Mitrasadat Rezaei
- Virology Research CenterNational Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Payam Tabarsi
- Clinical Tuberculosis and Epidemiology Research CenterNational Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Majid Marjani
- Clinical Tuberculosis and Epidemiology Research CenterNational Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Afshin Moniri
- Virology Research CenterNational Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Neda Khalili
- School of MedicineTehran University of Medical SciencesTehranIran
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20
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Leimbach RD, Hoang TD, Shakir MKM. Diagnostic Challenges of Medullary Thyroid Carcinoma. Oncology 2021; 99:422-432. [PMID: 33878761 DOI: 10.1159/000515373] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 02/17/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND Medullary thyroid carcinoma (MTC) comprises 1-2% of all thyroid cancers, yet 15% of all thyroid cancer-related deaths. While up to 20% of cases may be predicted due to autosomal dominant germline mutations, 80% of cases are sporadic. However, due to non-specific presenting symptoms and diagnostic imaging, prompt diagnosis and treatment has remained elusive. This article will further investigate the limitations of MTC diagnosis and look into future areas for diagnostic improvement. METHODS Relevant articles were identified using a systematic PubMed and Google Scholar search. RESULTS Prophylactic total thyroidectomy for the 20% of MTC cases that are present in autosomal dominant disorder provides definitive treatment. Serum calcitonin (Ctn) screening has several technical limitations due to population variability and laboratory assay interference, but advances in laboratory technology and combined use with fine needle aspiration increase its sensitivity. Other serum assays such as carcinoembryonic antigen and procalcitonin have limited applicability. Thyroid ultrasound remains the gold standard for the initial diagnostic planning, with limited application for CT, MRI, and PET imaging. CONCLUSION With complete surgical resection the only definitive treatment, early MTC diagnosis has presented an elusive challenge, mainly due to its relative rarity and difficulty in finding an economic screening strategy. Careful family history combined with fine needle aspiration with serum Ctn analysis can improve diagnostic sensitivity and specificity to greater than 95%.
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Affiliation(s)
- Robert D Leimbach
- Division of Endocrinology, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.,Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Thanh D Hoang
- Division of Endocrinology, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.,Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Mohamed K M Shakir
- Division of Endocrinology, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.,Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
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21
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Gan FJ, Zhou T, Wu S, Xu MX, Sun SH. Do medullary thyroid carcinoma patients with high calcitonin require bilateral neck lymph node clearance? A case report. World J Clin Cases 2021; 9:1343-1352. [PMID: 33644201 PMCID: PMC7896685 DOI: 10.12998/wjcc.v9.i6.1343] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 08/24/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In clinical work, 85%-90% of malignant thyroid diseases are papillary thyroid cancer (PTC); thus, clinicians neglect other types of thyroid cancer, such as medullary thyroid carcinoma (MTC).
CASE SUMMARY We report a 53-year-old female patient with a preoperative calcitonin level of 345 pg/mL. There was no definitive diagnosis of MTC by preoperative fine-needle aspiration cytology or intraoperative frozen pathology, but the presence of PTC and MTC was confirmed by postoperative paraffin pathology. The patient underwent total thyroidectomy and bilateral central lymph node dissection. Close follow-up at 1.5 years after surgery revealed no signs of recurrence or metastasis.
CONCLUSION The issue in clinical work-up regarding types of thyroid cancer provides a novel and challenging idea for the surgical treatment of MTC. In the absence of central lymph node metastasis, it is worth addressing whether patients with high calcitonin can undergo total thyroidectomy and bilateral central lymph node dissection without bilateral lateral neck lymph node dissection.
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Affiliation(s)
- Feng-Jiao Gan
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Tie Zhou
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Shun Wu
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Meng-Xi Xu
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Su-Hong Sun
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
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22
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Tong MY, Li HS, Che Y. Recurrent medullary thyroid carcinoma treated with percutaneous ultrasound-guided radiofrequency ablation: A case report. World J Clin Cases 2021; 9:864-870. [PMID: 33585633 PMCID: PMC7852637 DOI: 10.12998/wjcc.v9.i4.864] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 11/29/2020] [Accepted: 12/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Treatment for neck lymph node metastases after adequate initial surgery in medullary thyroid carcinoma (MTC) has been controversial. Ultrasound (US)-guided radiofrequency ablation (RFA) has been widely used in recurrent well-differentiated thyroid carcinoma. Here, we report for the first time the use of RFA in a patient with recurrent MTC.
CASE SUMMARY We report the case of a 56-year-old woman with cervical lymph node metastases of MTC. Four years previously, she had undergone a total thyroidectomy and neck lymph node dissection. A neck US revealed many enlarged nodes during the follow-up period. Moreover, the serum calcitonin jumped to 198.17 pg/mL, which strongly indicated the recurrence of MTC. Subsequently, two metastatic lymph nodes were confirmed by US-guided fine-needle aspiration-cytology and fine-needle aspiration-calcitonin, and then the patient was treated with RFA. Four months later, the neck US and a contrast-enhanced US showed obvious shrinkage in the ablation zones, and the serum calcitonin dropped to 11.80 pg/mL.
CONCLUSION This case suggests that RFA may be an effective and safe treatment for local recurrent MTC.
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Affiliation(s)
- Meng-Ying Tong
- Department of Ultrasound, First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
| | - Hu-Sha Li
- Department of Ultrasound, First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
| | - Ying Che
- Department of Ultrasound, First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
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23
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Kim SJ, Yun HJ, Shin SJ, Lee YS, Chang HS. Serum Calcitonin-Negative Medullary Thyroid Carcinoma: A Case Series of 19 Patients in a Single Center. Front Endocrinol (Lausanne) 2021; 12:747704. [PMID: 34803914 PMCID: PMC8602843 DOI: 10.3389/fendo.2021.747704] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 10/20/2021] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION Medullary thyroid carcinoma (MTC) is a rare cancer that accounts for 5% of thyroid cancers. Serum calcitonin is a good biomarker for MTC, which is used for diagnosis, prognosis, and monitoring of recurrence. Calcitonin-negative MTC (CNMTC) is rare but confounds diagnostic and prognostic directions. This study introduces 19 cases of CNMTC in a single center. METHOD From 2002 March to 2020 July, more than 76,500 patients had undergone thyroid surgery due to thyroid cancer at the Severance Hospital, and a total of 320 patients were diagnosed with MTC (0.4%). Serum calcitonin levels were obtained from every patient who was suspected with MTC. These patients had undergone either bilateral total thyroidectomy or unilateral thyroidectomy with central compartment lymph node dissection, and additional modified radical lymph node dissection if lateral lymph node metastasis was positive. Postoperative monitoring and out-patient clinic follow-up were performed with obtaining the serum calcitonin levels. RESULT Nineteen patients tested negative for calcitonin preoperatively (6%). The mean preoperative calcitonin level was 5.1pg/mL if undetectable level is regarded as 0pg/mL. Only two patients were males, and the female bias was significant (p = 0.017). No one except two patients with modified radical neck dissection showed central compartment lymph node metastasis. Every patient's postoperative calcitonin level remained low. The median follow-up period was 71 months. There was no recurrence and only one fatality, and the overall survival rate was 95%. CONCLUSION Since incidence of CNMTC is not negligible, MTC should not be ruled out in the diagnostic phase even if serum calcitonin is negative in preoperative examination. We presented 19 cases of CNMTC whose prognosis in general were favorable. Markers of serum and immunohistochemical samples other than calcitonin should be actively examined.
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Affiliation(s)
- Sun Jung Kim
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyeok Jun Yun
- Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Institute of Refractory Thyroid Cancer, Yonsei University College of Medicine, Seoul, South Korea
| | - Su-Jin Shin
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Yong Sang Lee
- Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Institute of Refractory Thyroid Cancer, Yonsei University College of Medicine, Seoul, South Korea
- *Correspondence: Yong Sang Lee,
| | - Hang-Seok Chang
- Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Institute of Refractory Thyroid Cancer, Yonsei University College of Medicine, Seoul, South Korea
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Censi S, Di Stefano M, Repaci A, Benvenuti T, Manso J, Pagotto U, Iacobone M, Barollo S, Bertazza L, Galuppini F, Benna C, Pennelli G, Plebani M, Faggian D, Colombo C, Fugazzola L, Mian C. Basal and Calcium-Stimulated Procalcitonin for the Diagnosis of Medullary Thyroid Cancers: Lights and Shadows. Front Endocrinol (Lausanne) 2021; 12:754565. [PMID: 34721303 PMCID: PMC8548712 DOI: 10.3389/fendo.2021.754565] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 09/01/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Procalcitonin (proCt) was recently proposed as an alternative or in addition to calcitonin (Ct) in medullary thyroid cancer (MTC) diagnostics. METHODS Serum basal Ct (bCt) and proCt (bproCt) levels were measured before surgery from a consecutive series of patients with (n=43) and without (n=75) MTC, retrospectively collected in Padua. Serum bproCt, bCt and stimulated proCt and Ct (sproCt and sCt) were measured in another consecutive series of 33 patients seen at three tertiary-level institutions undergoing a calcium stimulation test prior to surgery, 20 of them with a final diagnosis of MTC, and 13 with non-MTC nodular disease. RESULTS Median bproCt levels were higher in MTC than in non-MTC. A positive correlation was found for bproCt with bCt (P<0.01, R2 = 0.75), and with tumor size (P<0.01, R2 = 0.39). The cut-off for bproCt differentiating between MTC and non-MTC patients was >0.07 ng/ml (sensitivity: 85.7%, specificity: 98.9%, positive predictive value [PPV]: 98.2%, negative predictive value [NPV]: 90.6%, P<0.01). While bproCt was >0.07 ng/ml in 38/39 (97.4%) patients with MTC >10 mm, it was above said cut-off only in 15/23 (65.2%) patients with tumors ≤10 mm. A sproCt >0.19 ng/ml was able to identify MTC [sensitivity: 90.0%, specificity:100.0%, PPV: 100.0%, NPV: 86.7% (P<0.01)]. CONCLUSIONS Our data suggest that bproCt can be a good adjunct to Ct for MTC diagnostic purposes. In consideration of its high specificity, it can be used in combination with Ct in MTC diagnostics, particularly in the case of mildly elevated basal Ct levels.
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Affiliation(s)
- Simona Censi
- Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Marta Di Stefano
- Division of Endocrine and Metabolic Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Auxologico Italiano, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Andrea Repaci
- Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Teresa Benvenuti
- Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Jacopo Manso
- Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Uberto Pagotto
- Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maurizio Iacobone
- Endocrine Surgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Susi Barollo
- Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Loris Bertazza
- Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Francesca Galuppini
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Clara Benna
- Surgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Gianmaria Pennelli
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Mario Plebani
- Laboratory Medicine, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Diego Faggian
- Laboratory Medicine, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Carla Colombo
- Division of Endocrine and Metabolic Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Auxologico Italiano, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Laura Fugazzola
- Division of Endocrine and Metabolic Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Auxologico Italiano, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Caterina Mian
- Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
- *Correspondence: Caterina Mian,
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Bai Y, Niu D, Yao Q, Lin D, Kakudo K. Updates in the advances of sporadic medullary thyroid carcinoma: from the molecules to the clinic. Gland Surg 2020; 9:1847-1856. [PMID: 33224860 DOI: 10.21037/gs-2019-catp-21] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy that originates in parafollicular cells. It is well-known that a quarter of MTC are involved in hereditary multiple endocrine neoplasia type 2 syndromes, whereas most MTC are sporadic. Unlike the commonly encountered gastrointestinal or pulmonary neuroendocrine tumors, most sporadic MTCs have distinct genetic alterations featured by somatic changes of either Rearranged during Transfection (RET) or RAS point mutation. The increasing application of next-generation sequencing, whole-exome sequencing, and other molecular detection techniques enables us to understand MTC comprehensively concerning its detailed molecular changes and their clinical correlations. This article reviews the advances in genetic alterations and their prognostic impact in sporadic MTC among different populations and discusses the associated tumor immune microenvironments and the potential role of immunotherapy targeting PD-L1/PD-1 in treating MTC. Furthermore, the current multikinase inhibitor targeting therapy for sporadic MTC has been summarized here and its efficacy and drug toxicity are discussed. Updates in advance of the role of calcitonin/procalcitonin/calcitonin-related polypeptide alpha (CALCA) gene transcripts in diagnosing and handling MTC are also mentioned. The treatment of advanced MTC is still challenging and might require a combination of several modalities.
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Affiliation(s)
- Yanhua Bai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Dongfeng Niu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Qian Yao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Dongmei Lin
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Kennichi Kakudo
- Department of Pathology and Thyroid Disease Center, Izumi City General Hospital, Izumi, Japan
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Dabelić N, Jukić T, Fröbe A. Medullary Thyroid Cancer - Feature Review and Update on Systemic Treatment. Acta Clin Croat 2020; 59:50-59. [PMID: 34219884 PMCID: PMC8212605 DOI: 10.20471/acc.2020.59.s1.06] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Medullary thyroid carcinoma (MTC) is a rare malignancy that originates from parafollicular (C cells) of the thyroid and accounts for 2-4% of all thyroid malignancies. MTC may be sporadic or inherited, the latter as part of the MEN 2 syndromes. Germline mutations in the RET proto-oncogene (REarranged during Transfection) are driver mutations in hereditary MTC, whereas somatic RET mutations and, less frequently, RAS mutations, have been described in tumor tissues of sporadic MTC. Genetic screening for germline mutations in RET proto-oncogene identifies gene carriers of germline mutations. That enables primary prevention (the avoidance of disease onset by total prophylactic thyroidectomy), or at least secondary prevention (early detection) of the disease. Radical surgery with complete tumor resection is still pivotal in attaining cure for MTC. Despite recent advances, the treatment of advanced, metastatic, and progressive MTC remains challenging. Metastatic MTC can have an indolent clinical course; therefore, it is necessary to assess which patient to cure and when to initiate the treatment. Multidisciplinary boards of various specialists involved in the diagnostics and therapy of the patients with MTC in highly specialized centers with a high volume of patients provide optimal patient management. Multikinase inhibitors (MKI) vandetanib and cabozantinib were approved for the treatment of progressive or symptomatic metastatic/unresectable MTC. Although these treatments have been shown to improve progression-free survival (PFS) with higher overall response rates (ORR) compared with placebo, no MKI has been shown to increase the overall survival (OS) yet, except in the subgroup of patients with RETM918T-mutations on cabozantinib therapy. As these drugs are nonselective, significant off-target toxicities may occur. Recently, next-generation small-molecule tyrosine kinase inhibitors (TKIs) have been developed. These highly selective RET-inhibitors are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. The selective RET-inhibitor selpercatinib has been very recently registered for the treatment of RET-mutated thyroid cancer.
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Affiliation(s)
| | - Tomislav Jukić
- 1Department of Oncology and Nuclear Medicine, Sestre Milosrdnice University Hospital Centre, Zagreb, Croatia; 2University of Zagreb, School of Medicine; 3University of Zagreb, School of Dental Medicine
| | - Ana Fröbe
- 1Department of Oncology and Nuclear Medicine, Sestre Milosrdnice University Hospital Centre, Zagreb, Croatia; 2University of Zagreb, School of Medicine; 3University of Zagreb, School of Dental Medicine
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The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults. Ann Surg 2020; 271:e21-e93. [PMID: 32079830 DOI: 10.1097/sla.0000000000003580] [Citation(s) in RCA: 276] [Impact Index Per Article: 55.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To develop evidence-based recommendations for safe, effective, and appropriate thyroidectomy. BACKGROUND Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the US. METHODS The medical literature from 1/1/1985 to 11/9/2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content. RESULTS These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches to Thyroidectomy, Laryngology, Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation. CONCLUSIONS Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.
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Al-Qurayshi Z, Foggia MJ, Pagedar N, Lee GS, Tufano R, Kandil E. Thyroid cancer histological subtypes based on tumor size: National perspective. Head Neck 2020; 42:2257-2266. [PMID: 32275122 DOI: 10.1002/hed.26159] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Revised: 03/10/2020] [Accepted: 03/24/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Thyroid tumor size is an important prognostic factor. The aim of this study is to examine the histological subtypes and management of thyroid cancer based on tumor size (≤4 cm vs >4 cm). METHODS Retrospective cohort study utilizing the National Cancer Database, 2004-2014. RESULTS A total of 152 387 patients were included, 13 614 (8.9%) of whom had a tumor size >4 cm. Histological subtypes of tumors >4 cm were: 69.6% papillary thyroid carcinoma, 17.5% FTC, 7.9% HCC, and 2.8% medullary thyroid carcinoma (MTC). High-volume hospitals for thyroid surgery were less likely to perform two-stage thyroidectomy, particularly for tumors ≤4 cm. Low-volume hospitals had a higher risk of staged thyroidectomy for MTC ≤4 cm (19.8%) compared with high-volume hospitals (8.7%) (P < .001). CONCLUSIONS This study describes the prevalence of thyroid cancer subtypes. In the era of a conservative approach to differentiated thyroid carcinoma, there could be a potential increase in the risk of staged thyroidectomy.
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Affiliation(s)
- Zaid Al-Qurayshi
- Department of Otolaryngology-Head & Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - Megan J Foggia
- Department of Otolaryngology-Head & Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - Nitin Pagedar
- Department of Otolaryngology-Head & Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - Grace S Lee
- Endocrine and Oncological Surgery Division, Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
| | - Ralph Tufano
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Emad Kandil
- Endocrine and Oncological Surgery Division, Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
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Costante G, Meringolo D. Calcitonin as a biomarker of C cell disease: recent achievements and current challenges. Endocrine 2020; 67:273-280. [PMID: 31925733 DOI: 10.1007/s12020-019-02183-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 12/29/2019] [Indexed: 12/19/2022]
Abstract
The neoplastic proliferation of parafollicular thyroid cells (C cells) may occur as either medullary thyroid carcinoma (MTC) or C cell hyperplasia (CCH) and is generically defined C cell disease. Since Calcitonin (CT) expression is fully maintained in neoplastic C cells, this hormone represents a sensitive marker for neoplasia of C cell derivation such as CCH and MTC. Serum CT levels display a high prognostic value and accurate estimation of tumor burden, allowing early detection of persistence/relapse and representing a reliable marker of response to treatment. Indeed, elevated CT levels can occur in other non-C cell-related conditions (i.e., other malignancies, systemic diseases, and pharmacological treatments). Moreover, some de-differentiated, more aggressive MTCs may present disproportionately low-circulating CT levels, as compared with tumor burden. During the postsurgical follow-up of MTC patients, CT levels usually parallel tumor progression and their increase unambiguously announces persistence/relapse. In this respect, CT Doubling Time (DT) has been proposed as prognostic factor of potential use for the identification of more aggressive MTCs. The present review will summarize the novel achievements on the clinical suitability of CT as a biomarker in clinical oncology and will point the attention to the most recent results concerning the usefulness and the possible drawbacks of circulating CT as a surrogate marker for the identification of rapidly progressing MTC patients, such as those candidate to targeted therapies. The emerging role of circulating CT as a parameter of response to local and systemic therapies will also be illustrated.
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Affiliation(s)
- Giuseppe Costante
- Endocrinology Clinic, Department of Medicine - Institut Jules Bordet Comprehensive Cancer Center, Université Libre de Bruxelles, Bruxelles, Belgium.
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Kaplan J, Khadra H, Sholl AB, Kandil E. DIAGNOSTIC UTILITY OF HUMAN CHORIONIC GONADOTROPIN WASHOUT IN CERVICAL LYMPH NODE FINE-NEEDLE ASPIRATION FOR METASTATIC TESTICULAR CANCER. AACE Clin Case Rep 2020; 5:e201-e203. [PMID: 31967034 DOI: 10.4158/accr-2018-0445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Accepted: 12/07/2018] [Indexed: 11/15/2022] Open
Abstract
Objective This case report will describe the first adjunct use of directly measuring the concentration of human chorionic gonadotropin (HCG) in fine-needle aspiration (FNA) washout for diagnosing metastatic non-semi-nomatous germ cell tumor (NSGCT) of the testicle in a patient with cervical lymphadenopathy. Methods We present the clinical, laboratory, imaging, and pathologic findings, along with a review of the literature. Results A 23-year-old, otherwise healthy man who first presented with left testicular discomfort and swelling was diagnosed with NSGCT after undergoing a left orchiectomy. A few years later, the patient presented with a 2-cm left supraclavicular mass. Upon ultrasound of the thyroid and soft tissues of the neck, a 1-cm left thyroid nodule was revealed, as well as a 2.8-cm left supraclavicular lymph node, which was cystic in nature and worrisome for metastatic disease given the patient's history of metastatic NSGCT. The results of the FNA of the left thyroid nodule were benign, however the results from the supraclavicular mass were nondiagnostic. Due to the nondiagnostic FNA results, another aspiration with cytopathology and HCG evaluation washout was performed. The HCG aspirate came back with a value of 162 mIU/mL, despite the patient's negative serum HCG results. Conclusion This case demonstrates a novel way to diagnose metastatic testicular germ cell tumors utilizing FNA-HCG washout. Future prospective trials are needed to further elucidate this important finding.
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Marques B, Cunha N, Martins RG, Elvas AR, Couto J, Santos J, Martins T, Moniz AP, Ilhéu O, Valido F, Rodrigues F. Lymph Node Metastases of Medullary Thyroid Cancer: Role of Calcitonin in the Washout Fluid of Fine-Needle Aspiration. Int J Endocrinol 2020; 2020:9267972. [PMID: 32322267 PMCID: PMC7160716 DOI: 10.1155/2020/9267972] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 12/29/2019] [Accepted: 02/20/2020] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION The diagnostic value of calcitonin (CT) measurement in fine-needle aspirate washout (FNA-CT) for medullary thyroid cancer (MTC) lymph node (LN) metastases remains to be determined. It may increase the diagnostic sensitivity, but data on this subject is sparse. OBJECTIVE Our study aimed to evaluate the utility of FNA-CT in the diagnosis of LN metastases of MTC. METHODS We retrospectively investigated, in our institutional database, 69 consecutive FNA LN cytology from 42 patients who underwent FNA cytology and CT measurement in needle washout for suspicious LN between 2012 and 2017. RESULTS From the total of 69 FNA, 30 (43.4%) were performed in patients with personal history of MTC. MTC was detected in 19 FNA cytology (27.5%), and CT was detectable in needle washout in 23 cases (median = 2014 pg/mL; interquartile range = 490-15111 pg/mL). Based on the combined results of FNA-CT and FNA cytology, LN surgical resection was performed in 33 cases (47.8%). Histology reported MTC LN metastases in 21 lesions (63.6%). Regarding the diagnosis of MTC LN metastases, FNA cytology showed sensitivity of 81.8% and specificity of 97.9%, and FNA-CT demonstrated sensitivity of 100% and specificity of 97.9%. We determined through ROC analysis an optimal FNA-CT cut-off value of 23 pg/mL for the diagnosis of LN metastases (sensitivity 100%; specificity 100%). CONCLUSIONS FNA-CT may be a valuable diagnostic tool for detection of MTC LN metastases, along with FNA cytology, and it should be included in the clinical workup of neck adenopathies in patients with MTC or with thyroid nodules.
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Affiliation(s)
- Bernardo Marques
- Endocrinology Department, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Coimbra, Portugal
| | - Nuno Cunha
- Laboratory Medicine Department, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Coimbra, Portugal
| | - Raquel G. Martins
- Endocrinology Department, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Coimbra, Portugal
| | - Ana Rita Elvas
- Endocrinology Department, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Coimbra, Portugal
| | - Joana Couto
- Endocrinology Department, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Coimbra, Portugal
| | - Jacinta Santos
- Endocrinology Department, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Coimbra, Portugal
| | - Teresa Martins
- Endocrinology Department, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Coimbra, Portugal
| | - Ana Paula Moniz
- Pathology Department, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Coimbra, Portugal
| | - Olga Ilhéu
- Pathology Department, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Coimbra, Portugal
| | - Frederico Valido
- Laboratory Medicine Department, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Coimbra, Portugal
| | - Fernando Rodrigues
- Endocrinology Department, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Coimbra, Portugal
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Gambardella C, Offi C, Clarizia G, Romano RM, Cozzolino I, Montella M, Di Crescenzo RM, Mascolo M, Cangiano A, Di Martino S, Candela G, Docimo G. Medullary thyroid carcinoma with double negative calcitonin and CEA: a case report and update of literature review. BMC Endocr Disord 2019; 19:103. [PMID: 31619220 PMCID: PMC6794852 DOI: 10.1186/s12902-019-0435-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 09/24/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Medullary thyroid carcinoma is a malignant uncommon and aggressive tumour of the parafollicular C cells. In about 75% of cases it is sporadic while, in case of RET mutation, it is associated to multiple endocrine neoplasia type 2 (25% of cases). The biochemical features of medullary thyroid carcinoma include the production of calcitonin and carcinoembryogenic antigen. The above-mentioned features are useful in the diagnostic process as well as in the follow up and in the prognostication of the disease. Even if calcitonin elevation is strongly associated to MTC, it can also be found increased in many pathological different conditions as pregnancy, lactation, C-cells hyperplasia, autoimmune thyroiditis, end stage renal disease, lung and prostate cancer and several neuroendocrine tumours. Major medullary thyroid tumours are usually connected to high doses of circulating calcitonin, in fact non-secretory variants have hardly been described. CASE PRESENTATION We herein report the case of a 59 years old male, who had undergone total thyroidectomy for multinodular goiter with negative preoperative calcitonin, showing medullary thyroid carcinoma at definitive pathology. To the best of our knowledge, this is the first case documenting a non-secretory medullary thyroid carcinoma, with double negative markers at the time of diagnosis and at the relapse. CONCLUSION A Literature review underlining pathological hypothesis, differential diagnosis and alternative and innovative biomarkers to identify non-secretory medullary thyroid carcinoma was carried out.
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Affiliation(s)
- Claudio Gambardella
- Division of Thyroid Surgery - Department of Medical and Advanced Surgical Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini, 5, 80131 Naples, Italy
- Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Chiara Offi
- Division of Thyroid Surgery - Department of Medical and Advanced Surgical Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Guglielmo Clarizia
- Division of Thyroid Surgery - Department of Medical and Advanced Surgical Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Roberto Maria Romano
- Division of Thyroid Surgery - Department of Medical and Advanced Surgical Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Immacolata Cozzolino
- Pathology Unit, Department of Mental and Physical Health and Preventive, Medicine University of Campania “Luigi Vanvitelli”, School of Medicine, Piazza Miraglia 2, 80138 Naples, Italy
| | - Marco Montella
- Pathology Unit, Department of Mental and Physical Health and Preventive, Medicine University of Campania “Luigi Vanvitelli”, School of Medicine, Piazza Miraglia 2, 80138 Naples, Italy
| | - Rosa Maria Di Crescenzo
- Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Massimo Mascolo
- Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Angelo Cangiano
- Division of Thyroid Surgery - Department of Medical and Advanced Surgical Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Sergio Di Martino
- Division of Thyroid Surgery - Department of Medical and Advanced Surgical Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Giancarlo Candela
- Division of Thyroid Surgery - Department of Medical and Advanced Surgical Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini, 5, 80131 Naples, Italy
| | - Giovanni Docimo
- Division of Thyroid Surgery - Department of Medical and Advanced Surgical Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini, 5, 80131 Naples, Italy
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Thomas CM, Asa SL, Ezzat S, Sawka AM, Goldstein D. Diagnosis and pathologic characteristics of medullary thyroid carcinoma-review of current guidelines. Curr Oncol 2019; 26:338-344. [PMID: 31708652 PMCID: PMC6821118 DOI: 10.3747/co.26.5539] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background Medullary thyroid carcinoma (mtc) is a rare malignancy of the thyroid gland, and raising awareness of the recommended diagnostic workup and pathologic characteristics of this malignancy is therefore important. Methods We reviewed the current clinical practice guidelines and recent literature on mtc, and here, we summarize the recommendations for its diagnosis and workup. We also provide an overview of the pathology of mtc. Results A neuroendocrine tumour, mtc arises from parafollicular cells ("C cells"), which secrete calcitonin. As part of the multiple endocrine neoplasia (men) type 2 syndromes, mtc can occur sporadically or in a hereditary form. This usually poorly delineated and infiltrative tumour is composed of solid nests of discohesive cells within a fibrous stroma that might also contain amyloid. Suspicious nodules on thyroid ultrasonography should be assessed with fine-needle aspiration (fna). If a diagnosis of mtc is made on fna, patients require baseline measurements of serum calcitonin and carcinoembryonic antigen. Calcitonin levels greater than 500 pg/mL or clinical suspicion for metastatic disease dictate the need for further imaging studies. All patients should undergo dna analysis for RET mutations to diagnose men type 2 syndromes, and if positive, they should be assessed for possible pheochromocytoma and hyperparathyroidism. Summary Although the initial diagnosis of a suspicious thyroid nodule is the same for differentiated thyroid carcinoma and mtc, the remainder of the workup and diagnosis for mtc is distinct.
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Affiliation(s)
- C M Thomas
- Department of Otolaryngology-Head and Neck Surgery, University Health Network, Toronto, ON
- Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON
| | - S L Asa
- Department of Pathology, Case Western Reserve University, Cleveland, OH, U.S.A
- Department of Pathology, University Health Network, Toronto, ON
| | - S Ezzat
- Department of Medicine and Oncology, University of Toronto, Toronto, ON
| | - A M Sawka
- Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, ON
| | - D Goldstein
- Department of Otolaryngology-Head and Neck Surgery, University Health Network, Toronto, ON
- Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON
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Zhu J, Li X, Wei X, Yang X, Zhao J, Zhang S, Guo Z. The application value of modified thyroid imaging report and data system in diagnosing medullary thyroid carcinoma. Cancer Med 2019; 8:3389-3400. [PMID: 31070290 PMCID: PMC6601574 DOI: 10.1002/cam4.2217] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 04/16/2019] [Accepted: 04/17/2019] [Indexed: 12/20/2022] Open
Abstract
Medullary thyroid carcinoma (MTC) is highly malignant and quite different from the most common papillary thyroid carcinoma (PTC). However, most of the ultrasonic evaluation systems mainly aim at PTC at present. This study aims to evaluate the applicability of modified TI-RADS in diagnosing MTC and compare the sonographic differences of MTC, PTC, and benign nodules. Three thousand two hundred and forty-two thyroid nodules images confirmed by pathology were categorized according to modified TI-RADS and ACR TI-RADS classification. The performances of two TI-RADS were assessed by ROC curves. The correlations between classifications with the pathology and the consistency of different doctors were evaluated. The ultrasonic differences of MTC, PTC, and benign nodules were analyzed. As a result, the number of high suspicious US features increased, the malignant risk of nodules also increased of two classifications, with significant differences between categories (P < 0.001). Spearman correlation coefficients were 0.751 (modified TI-TADS) and 0.744 (ACR TI-RADS). Areas under the ROC curve of the modified TI-RADS and ACR TI-RADS were 0.960 and 0.872 (P < 0.001). At Best cut off points, the diagnostic value of modified TI-RADS was higher than that of ACR TI-RADS with a higher specificity, PPV, accuracy, and Youden index). By using modified TI-RADS to diagnose MTC and PTC, the sensitivity, specificity, NPV, accuracy, and Youden index were higher in MTC than PTC. The Kendall's correlation coefficients were 0.962, 0.930, and 0.987. MTC had special ultrasonography characters compared with PTC and benign nodules. These results suggest that modified TI-RADS is better than ACR TI-RADS in diagnosing thyroid carcinomas. Diagnostic value to MTC of modified TI-RADS is slightly higher than that to PTC, and the categorical results of different doctors were consistent. MTC had several particular features contrast to PTC and benign nodules.
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Affiliation(s)
- Jialin Zhu
- Department of Ultrasound Diagnosis and Treatment, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjinChina
| | - Xing Li
- Department of Ultrasound Diagnosis and Treatment, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjinChina
| | - Xi Wei
- Department of Ultrasound Diagnosis and Treatment, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjinChina
| | - Xueling Yang
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjinChina
| | - Jing Zhao
- Department of Ultrasound Diagnosis and Treatment, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjinChina
| | - Sheng Zhang
- Department of Ultrasound Diagnosis and Treatment, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjinChina
| | - Zhi Guo
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjinChina
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Gambardella C, Offi C, Patrone R, Clarizia G, Mauriello C, Tartaglia E, Di Capua F, Di Martino S, Romano RM, Fiore L, Conzo A, Conzo G, Docimo G. Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma? BMC Endocr Disord 2019; 19:45. [PMID: 31142313 PMCID: PMC6541563 DOI: 10.1186/s12902-019-0367-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 04/08/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Medullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels. METHODS Using the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale. RESULTS Fourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8-38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients. CONCLUSIONS Calcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma.
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Affiliation(s)
- Claudio Gambardella
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Chiara Offi
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Renato Patrone
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Guglielmo Clarizia
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Claudio Mauriello
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Ernesto Tartaglia
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Francesco Di Capua
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Sergio Di Martino
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Roberto Maria Romano
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Lorenzo Fiore
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Alessandra Conzo
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Giovanni Conzo
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
| | - Giovanni Docimo
- Division of General and Oncologic Surgery, Department of Cardiothoracic Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Via Sergio Pansini 5, 80131 Naples, Italy
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Guo QQ, Zhang SH, Niu LJ, Zhang YK, Li ZJ, Chang Q. Comprehensive evaluation of medullary thyroid carcinoma before surgery. Chin Med J (Engl) 2019; 132:834-841. [PMID: 30829709 PMCID: PMC6595859 DOI: 10.1097/cm9.0000000000000160] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Medullary thyroid carcinoma (MTC) is a rare disease, but it exhibits more aggressive behaviors. The aim of this study was to improve the diagnostic accuracy of MTC before surgery by analyzing the clinical and ultrasonic data of patients with MTC. METHODS The study included 71 patients (96 lesions) with histopathologically proven MTC between April 2011 and September 2016 in the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College. The clinical characteristics and sonographic findings were retrospectively reviewed and compared between the ultrasonic correct diagnosis group and the ultrasonic misdiagnosis group with the t test or Mann-Whitney U test for quantitative parameters and the χ test or Fisher exact test for qualitative parameters. RESULTS Compared with the ultrasonic correct diagnosis group, the proportion of the cystic change in the ultrasonic misdiagnosed group was high (25.0% vs. 4.2%), the uncircumscribed margin and irregular shape proportions were low (20.8%, 58.3% vs. 74.7%, 87.3%), calcification was relatively rare (20.8% vs. 56.3%), and rich vascularity was relatively rare (25.0% vs. 78.9%). CONCLUSIONS In the case of atypical MTC, such as cystic change, circumscribed margin, regular shape, no calcification, no rich vascularity, and normal cervical lymph nodes, MTC is easily misdiagnosed as benign by ultrasound. Therefore, ultrasound, cytology and serum calcitonin should be comprehensively evaluated for a preoperative diagnosis of MTC.
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Affiliation(s)
- Qian-Qian Guo
- Department of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Shao-Hang Zhang
- Department of Ultrasound, Beijing Haidian Hospital, Haidian Section of Peking University Third Hospital, Beijing 100080, China
| | - Li-Juan Niu
- Department of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yu-Kang Zhang
- Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
| | - Zheng-Jiang Li
- Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Qing Chang
- Department of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Kihara M, Hirokawa M, Kudo T, Hayashi T, Yamamoto M, Masuoka H, Higashiyama T, Fukushima M, Ito Y, Miya A, Miyauchi A. Calcitonin measurement in fine-needle aspirate washout fluid by electrochemiluminescence immunoassay for thyroid tumors. Thyroid Res 2018; 11:15. [PMID: 30450128 PMCID: PMC6208047 DOI: 10.1186/s13044-018-0059-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Accepted: 10/17/2018] [Indexed: 12/17/2022] Open
Abstract
Purpose For the differential diagnosis of medullary thyroid carcinoma (MTC) on thyroid nodules, ultrasound-guided fine-needle aspiration cytology is a useful and safe procedure, but its diagnostic accuracy is not high enough. As an ancillary method to accurately diagnose MTC, the calcitonin in fine-needle aspirate washout fluid (FNA-Ct) is used. However, no data are available about cut-off values of FNA-Ct using the currently available electrochemiluminescence immunoassay (ECLIA). Methods We investigated 180 thyroid nodules in 141 patients. After smearing, the syringe and needle used for the FNA were rinsed with normal saline (0.5 mL). The calcitonin in the washout was measured by ECLIA. Results The FNA-Ct in the non-MTC nodules of MTC patients, non-MTC nodules of non-MTC patients, and MTC nodules were 10.6-2100 pg/mL (median 24.6 pg/mL), < 0.5-21.0 pg/mL (median < 0.5 pg/mL), and 94.9-4,070,000 pg/mL (median 177,000 pg/mL), respectively. A receiver operating characteristic analysis of the MTC nodules and the non-MTC nodules of the non-MTC patients indicated that the cut-off value was 21.0 pg/mL, leading to 100% sensitivity and 100% specificity. Conclusions This is the first study to determine the cut-off value of FNA-Ct with an ECLIA, and we propose that the optimal cut-off value is 21.0 pg/mL.
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Affiliation(s)
- Minoru Kihara
- 1Departments of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Hyogo 650-0011 Japan
| | - Mitsuyoshi Hirokawa
- 2Departments of Diagnostic Pathology, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Hyogo 650-0011 Japan
| | - Takumi Kudo
- 3Departments of Internal Medicine, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Hyogo 650-0011 Japan
| | - Toshitetsu Hayashi
- 2Departments of Diagnostic Pathology, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Hyogo 650-0011 Japan
| | - Masatoshi Yamamoto
- 1Departments of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Hyogo 650-0011 Japan
| | - Hiroo Masuoka
- 1Departments of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Hyogo 650-0011 Japan
| | - Takuya Higashiyama
- 1Departments of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Hyogo 650-0011 Japan
| | - Mitsuhiro Fukushima
- 1Departments of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Hyogo 650-0011 Japan
| | - Yasuhiro Ito
- 1Departments of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Hyogo 650-0011 Japan
| | - Akihiro Miya
- 1Departments of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Hyogo 650-0011 Japan
| | - Akira Miyauchi
- 1Departments of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Hyogo 650-0011 Japan
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Giovanella L, Imperiali M, Piccardo A, Taborelli M, Verburg FA, Daurizio F, Trimboli P. Procalcitonin measurement to screen medullary thyroid carcinoma: A prospective evaluation in a series of 2705 patients with thyroid nodules. Eur J Clin Invest 2018; 48:e12934. [PMID: 29635700 PMCID: PMC6001787 DOI: 10.1111/eci.12934] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 03/31/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND To prospectively evaluate the role of procalcitonin (PCT) in screening of patients with thyroid nodules for medullary thyroid carcinoma (MTC). MATERIALS AND METHODS We measured PCT in 2705 patients with thyroid nodules referred to our centre between January 2011 and December 2017. Those with a positive PCT were operated after positive confirmatory tests such as fine-needle aspiration, measurement of calcitonin (CT) in serum and fine-needle aspiration washouts or CT stimulation testing. Patients with a negative PCT were operated based on the results of further diagnostics. The diagnostic performance of PCT was evaluated, and the best cut-off level was selected by ROC curve analysis. RESULTS Among 2705 patients, 9 with positive serum PCT (ie, above 0.1 μg/L) and 370 with negative PCT underwent thyroid surgery. MTC was histologically confirmed in all patients with positive PCT but not found in patients with negative PCT. Serum PCT levels were significantly higher in patients with MTC (median 0.64 μg/L, range 0.16-12.9 μg/L) than in those without (median 0.075 μg/L, range 0.075-0.16 μg/L; P < .0001). ROC curves were plotted to calculate the optimal PCT value separating patients with MTC from those without. The best cut-off was 0.155 μg/L with sensitivity, specificity, positive and negative predictive values as well as accuracy of 100%, 99.7%, 91.7%, 100% and 99.7%, respectively. Positive and negative likelihood ratios were 329 and zero, respectively. CONCLUSIONS Measurement of PCT is a sensitive and accurate method for detecting MTC in patients with thyroid nodules and can thus be a reliable alternative to CT measurement.
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Affiliation(s)
- Luca Giovanella
- Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.,Laboratory for Clinical Chemistry, Department of Laboratory Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.,Medical School, University of Zurich, Zurich, Switzerland
| | - Mauro Imperiali
- Laboratory for Clinical Chemistry, Department of Laboratory Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Arnoldo Piccardo
- Department of Nuclear Medicine, Ente Ospedaliero "Ospedali Galliera", Genova, Italy
| | - Monica Taborelli
- Laboratory for Genetics and Cytogenetics, Department of Laboratory Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | | | - Federica Daurizio
- Laboratory for Clinical Pathology, Department of Laboratory Medicine, Udine University Hospital, Udine, Italy
| | - Pierpaolo Trimboli
- Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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Suzuki A, Hirokawa M, Takada N, Higuchi M, Ito A, Yamao N, Hayashi T, Kuma S, Miyauchi A. Fine-needle aspiration cytology for medullary thyroid carcinoma: a single institutional experience in Japan. Endocr J 2017; 64:1099-1104. [PMID: 28883261 DOI: 10.1507/endocrj.ej17-0238] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Many cytological studies on medullary thyroid carcinoma (MTC) have been reported; however, such studies in large series of patients with MTC have not been performed. We investigated MTC at a single institution in Japan using fine-needle aspiration cytology (FNAC), and aimed to establish a preoperative diagnostic algorithm for MTC. FNAC was performed in 119 of 149 patients with MTC (79.9%) who ultimately underwent surgical resection. Moreover, 22 of 56 hereditary MTC (39.3%) were diagnosed preoperatively without FNAC by their high serum calcitonin levels or increased response to calcium stimulation (11 cases each), as well as RET mutation analysis. On FNAC, 76.5% of nodules were categorized as 'malignancy' or 'suspicious for malignancy'. The sensitivity and specificity of calcitonin measurement in aspiration needle wash-out fluid and in immunocytochemical staining for calcitonin were 96.3% and 92.3% respectively. We proposed an algorithm for preoperative diagnosis of MTC utilizing FNAC: When thyroid nodules are highly suspicious for MTC by their clinical and ultrasonographic features, serum calcitonin measurement with or without a calcium stimulation test is required. Furthermore, FNAC should be performed for patients who do not have those findings. When there is a possibility of MTC at the time of FNAC, calcitonin measurement using needle wash-out fluid is a reliable diagnostic tool. When MTC is suspected on cytological examination, immunocytochemical staining for calcitonin is useful for confirming MTC diagnosis.
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Affiliation(s)
- Ayana Suzuki
- Department of Clinical Laboratory, Kuma Hospital, Kobe, Japan
| | | | - Nami Takada
- Department of Clinical Laboratory, Kuma Hospital, Kobe, Japan
| | - Miyoko Higuchi
- Department of Clinical Laboratory, Kuma Hospital, Kobe, Japan
| | - Aki Ito
- Department of Clinical Laboratory, Kuma Hospital, Kobe, Japan
| | - Naoki Yamao
- Department of Clinical Laboratory, Kuma Hospital, Kobe, Japan
| | - Toshitetsu Hayashi
- Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe, Japan
| | - Seiji Kuma
- Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe, Japan
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Trimboli P, D'Aurizio F, Tozzoli R, Giovanella L. Measurement of thyroglobulin, calcitonin, and PTH in FNA washout fluids. Clin Chem Lab Med 2017; 55:914-925. [PMID: 27802177 DOI: 10.1515/cclm-2016-0543] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Accepted: 09/20/2016] [Indexed: 12/20/2022]
Abstract
Different imaging tools, circulating endocrine markers, and fine-needle aspiration (FNA) cytology are of great importance in the diagnosis and follow-up of different thyroid and parathyroid diseases. Sometimes, however, they are conflicting or inconclusive: interestingly, measuring endocrine markers (i.e. thyroglobulin, calcitonin, parathyroid hormone) in fluids from FNA proved to be a very useful complementary diagnostic tool in such cases. The determination of endocrine markers in fluids other than serum/plasma has been developed in the last years. Although studies have reported overall satisfactory results, a good standardization of procedures has not yet been reached, and further efforts should be made in order to better define pre-analytical, analytical, and post-analytical aspects. Here we reviewed critically the literature on the measurement of FNA endocrine markers, focusing on laboratory issues, such as preparation of the sample, choice of solution, and technical features of determination of these markers. Indeed, information for use of FNA-Tg, FNA-CT, and FNA-PTH in clinical practice was also provided.
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Censi S, Cavedon E, Fernando SW, Barollo S, Bertazza L, Zambonin L, Zaninotto M, Faggian D, Plebani M, Mian C. Calcitonin measurement and immunoassay interference: a case report and literature review. Clin Chem Lab Med 2017; 54:1861-1870. [PMID: 27166721 DOI: 10.1515/cclm-2015-1161] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 04/13/2016] [Indexed: 02/03/2023]
Abstract
Calcitonin (CT) is currently the most sensitive serological marker of C-cell disease [medullary thyroid carcinoma (MTC) and C-cell hyperplasia]. Starting with a report on a case that occurred at our institution, this review focuses on trying to explain the reasons behind the poor specificity and sensitivity of the various CT immunoassays. A 15-year-old patient was referred to our institution in May 2014 for moderately elevated CT levels. Thyroid ultrasonography (US) documented a colloidal goiter. Secondary causes of the hypercalcitoninemia (hyperCT) were ruled out. The mismatch between the clinical picture and the laboratory results prompted us to search for other reasons for the patient's high CT levels, so we applied the heterophilic blocking tube (HBT) procedure to the patient's sera before the CT assay. Using this pretreatment step, his serum CT concentration dropped to <1 ng/L, as measured at the same laboratory. Measuring plasma CT has an important role in screening for C-cell disease, but moderately elevated serum CT levels need to be placed in their clinical context, bearing in mind all the secondary causes of C-cell hyperplasia and the possibility of laboratory interference, before exposing patients to the risks and costs of further tests.
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Affiliation(s)
- James A Fagin
- From the Department of Medicine and Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York (J.A.F.); and the Genetics Branch, National Cancer Institute, Bethesda, MD (S.A.W.)
| | - Samuel A Wells
- From the Department of Medicine and Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York (J.A.F.); and the Genetics Branch, National Cancer Institute, Bethesda, MD (S.A.W.)
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Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedüs L, Paschke R, Valcavi R, Vitti P. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ASSOCIAZIONE MEDICI ENDOCRINOLOGI MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES--2016 UPDATE. Endocr Pract 2016; 22:622-39. [PMID: 27167915 DOI: 10.4158/ep161208.gl] [Citation(s) in RCA: 728] [Impact Index Per Article: 80.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Thyroid nodules are detected in up to 50 to 60% of healthy subjects. Most nodules do not cause clinically significant symptoms, and as a result, the main challenge in their management is to rule out malignancy, with ultrasonography (US) and fine-needle aspiration (FNA) biopsy serving as diagnostic cornerstones. The key issues discussed in these guidelines are as follows: (1) US-based categorization of the malignancy risk and indications for US-guided FNA (henceforth, FNA), (2) cytologic classification of FNA samples, (3) the roles of immunocytochemistry and molecular testing applied to thyroid FNA, (4) therapeutic options, and (5) follow-up strategy. Thyroid nodule management during pregnancy and in children are also addressed. On the basis of US features, thyroid nodules may be categorized into 3 groups: low-, intermediate-and high-malignancy risk. FNA should be considered for nodules ≤10 mm diameter only when suspicious US signs are present, while nodules ≤5 mm should be monitored rather than biopsied. A classification scheme of 5 categories (nondiagnostic, benign, indeterminate, suspicious for malignancy, or malignant) is recommended for the cytologic report. Indeterminate lesions are further subdivided into 2 subclasses to more accurately stratify the risk of malignancy. At present, no single cytochemical or genetic marker can definitely rule out malignancy in indeterminate nodules. Nevertheless, these tools should be considered together with clinical data, US signs, elastographic pattern, or results of other imaging techniques to improve the management of these lesions. Most thyroid nodules do not require any treatment, and levothyroxine (LT4) suppressive therapy is not recommended. Percutaneous ethanol injection (PEI) should be the first-line treatment option for relapsing, benign cystic lesions, while US-guided thermal ablation treatments may be considered for solid or mixed symptomatic benign thyroid nodules. Surgery remains the treatment of choice for malignant or suspicious nodules. The present document updates previous guidelines released in 2006 and 2010 by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE) and Associazione Medici Endocrinologi (AME).
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Trimboli P, Giovanella L. Serum calcitonin negative medullary thyroid carcinoma: a systematic review of the literature. Clin Chem Lab Med 2016; 53:1507-14. [PMID: 25781697 DOI: 10.1515/cclm-2015-0058] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2015] [Accepted: 02/13/2015] [Indexed: 01/30/2023]
Abstract
Generally, calcitonin (CT) values below the upper reference limit rule-out medullary thyroid carcinoma (MTC) with very high accuracy. However, sparse cases of serum-calcitonin-negative MTC (CT-NEG-MTC) have been reported. Here we reviewed CT-NEG-MTC reported in literature, discussed the potential causes and proposed a practical laboratory and clinical approach. A comprehensive literature search was conducted by using the terms "medullary thyroid carcinoma" AND "non-secreting calcitonin" OR "undetectable calcitonin". The search was updated until December 2014. Original articles that described CT-NEG-MTC were eligible for inclusion. Only MTC cases with preoperative CT below the upper reference limit were included in the present review. Eleven papers with 18 CT-NEG-MTC cases (age 50 years, size 26 mm) were retrieved. Four patients with poorly differentiated MTC died within 3 years. Different CT assays were employed and different reference values were adopted. Preoperative serum CT values were below the institution cut-off levels in all cases, and undetectable in four patients. In some papers negative CT results were confirmed by additional tests. Further laboratory investigations were performed in some of the included studies. In patients with well founded suspicious of MTC and within the reference limits/undetectable CT other laboratory investigations [carcinoembryonic antigen (CEA), procalcitonin, CT stimulation, CT in washout of nodule's aspiration] have to be performed. Surgical approach to CT-NEG-MTC does not differ from those secreting CT. Postoperative follow-up of these rare cases should include periodical imaging and measurement of all potential markers. Patients with poorly differentiated MTC are at higher risk of disease-related death, and require more aggressive follow-up strategy.
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Learned KO, Lev-Toaff AS, Brake BJ, Wu RI, Langer JE, Loevner LA. US-guided Biopsy of Neck Lesions: The Head and Neck Neuroradiologist’s Perspective. Radiographics 2016; 36:226-43. [DOI: 10.1148/rg.2016150087] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Nasrollah N, Trimboli P, Bianchi D, Taccogna S. Neck schwannoma diagnosed by core needle biopsy: a case report. J Ultrasound 2015; 18:407-10. [PMID: 26550065 PMCID: PMC4630276 DOI: 10.1007/s40477-014-0112-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2014] [Accepted: 06/02/2014] [Indexed: 12/16/2022] Open
Abstract
Here we present a case of a 58 year old man referred to our hospital to undergo neck and thyroid ultrasonography (US) following palpable neck mass. US revealed a solid hypoechoic nodule in right thyroid lobe, and a solid lesion on the right laterocervical neck region with ultrasound suspicious features of neoplastic lymph node. In order to achieve a diagnosis of the neck mass and to get a proper evaluation of the thyroid nodule, we decided to perform a fine-needle aspiration (FNA) of both lesions. At cytopathologic examination the thyroid nodule appeared as benign, while cytologic sampling of the neck lesion was inadequate for a proper evaluation. Thus, we performed core needle biopsy (CNB) of the neck lesion like recently proposed for thyroid lesions; also, to definitively exclude malignancy of thyroid nodule, this also underwent CNB. Histologic report of CNB confirmed benign thyroid nodule, while the neck lesion revealed a proliferation of neuronal type consistent with schwannoma. The patient has been addressed to clinical and ultrasonographic follow-up. CNB appears as a safe and minimally-invasive approach to diagnose indeterminate neck masses and avoid unnecessary diagnostic surgery.
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Affiliation(s)
- N. Nasrollah
- />Section of Surgery, Ospedale Israelitico, Via Fulda, 14, 00148 Rome, Italy
| | - P. Trimboli
- />Section of Endocrinology and Diabetology, Ospedale Israelitico, Rome, Italy
| | - D. Bianchi
- />Section of Surgery, Policlinico Tor Vergata, Rome, Italy
| | - S. Taccogna
- />Section of Pathology, Ospedale Israelitico, Rome, Italy
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LIU QIONG, PANG HUA, HU XIAOLI, LI WENBO, XI JIMEI, XU LU, ZHOU JING. Construction of human single-chain variable fragment antibodies of medullary thyroid carcinoma and single photon emission computed tomography/computed tomography imaging in tumor-bearing nude mice. Oncol Rep 2015; 35:171-8. [DOI: 10.3892/or.2015.4345] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 09/04/2015] [Indexed: 11/06/2022] Open
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Trimboli P, Guidobaldi L, Bongiovanni M, Crescenzi A, Alevizaki M, Giovanella L. Use of fine-needle aspirate calcitonin to detect medullary thyroid carcinoma: A systematic review. Diagn Cytopathol 2015; 44:45-51. [PMID: 26481456 DOI: 10.1002/dc.23375] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Accepted: 09/24/2015] [Indexed: 01/28/2023]
Abstract
BACKGROUND The measurement of calcitonin in washout fluids of thyroid nodule aspirate (FNA-calcitonin) has been reported as accurate to detect medullary thyroid carcinoma (MTC). The results from these studies have been promising and the most updated version of ATA guidelines quoted for the first time that "FNA findings that are inconclusive or suggestive of MTC should have calcitonin measured in the FNA washout fluid." Here we aimed to systematically review published data on this topic to provide more robust estimates. RESEARCH DESIGN AND METHODS A comprehensive computer literature search of the medical databases was conducted by searching for the terms "calcitonin" AND "washout." The search was updated until April 2015. RESULTS Twelve relevant studies, published between 2007 and 2014, were found. Overall, 413 thyroid nodules or neck lymph nodes underwent FNA-calcitonin, 95 were MTC lesions and 93 (97.9%) of these were correctly detected by this measurement regardless of their cytologic report. CONCLUSIONS The present study shows that the above ATA recommendation is well supported. Almost all MTC lesions are correctly detected by FNA-calcitonin and this technique should be used to avoid false negative or inconclusive results from cytology. The routine determination of serum calcitonin in patients undergoing FNA should improve the selection of patients at risk for MTC, guiding the use of FNA-calcitonin in the same FNA sample and providing useful information to the cytopathologist for the morphological assessment and the application of tailored ancillary tests.
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Affiliation(s)
- Pierpaolo Trimboli
- Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.,Section of Endocrinology and Diabetology, Ospedale Israelitico, Rome, Italy
| | | | | | - Anna Crescenzi
- Section of Pathology, University Hospital Campus Bio Medico, Rome, Italy
| | - Maria Alevizaki
- Department of Clinical Therapeutics, Endocrine Unit, School of Medicine, Alexandra General Hospital, Athens University, Athens
| | - Luca Giovanella
- Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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Wells SA, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, Lee N, Machens A, Moley JF, Pacini F, Raue F, Frank-Raue K, Robinson B, Rosenthal MS, Santoro M, Schlumberger M, Shah M, Waguespack SG. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015; 25:567-610. [PMID: 25810047 PMCID: PMC4490627 DOI: 10.1089/thy.2014.0335] [Citation(s) in RCA: 1410] [Impact Index Per Article: 141.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
INTRODUCTION The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. METHODS The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. RESULTS The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. CONCLUSIONS The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice.
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Affiliation(s)
- Samuel A. Wells
- Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Sylvia L. Asa
- Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Henning Dralle
- Department of General, Visceral, and Vascular Surgery, University Hospital, University of Halle-Wittenberg, Halle/Saale, Germany
| | - Rossella Elisei
- Department of Endocrinology, University of Pisa, Pisa, Italy
| | - Douglas B. Evans
- Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Robert F. Gagel
- Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Nancy Lee
- Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Andreas Machens
- Department of General, Visceral, and Vascular Surgery, University Hospital, University of Halle-Wittenberg, Halle/Saale, Germany
| | - Jeffrey F. Moley
- Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Furio Pacini
- Section of Endocrinology and Metabolism, Department of Internal Medicine, Endocrinology and Metabolism and Biochemistry, University of Siena, Policlinico Santa Maria alle Scotte, Siena, Italy
| | - Friedhelm Raue
- Endocrine Practice, Moleculargenetic Laboratory, Medical Faculty, University of Heidelberg, Heidelberg, Germany
| | - Karin Frank-Raue
- Endocrine Practice, Moleculargenetic Laboratory, Medical Faculty, University of Heidelberg, Heidelberg, Germany
| | - Bruce Robinson
- University of Sydney School of Medicine, Sydney, New South Wales, Australia
| | - M. Sara Rosenthal
- Departments of Internal Medicine, Pediatrics and Behavioral Science, University of Kentucky, Lexington, Kentucky
| | - Massimo Santoro
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita' di Napoli “Federico II,” Napoli, Italy
| | - Martin Schlumberger
- Institut Gustave Roussy, Service de Medecine Nucleaire, Université of Paris-Sud, Villejuif, France
| | - Manisha Shah
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio
| | - Steven G. Waguespack
- Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Trimboli P, Treglia G, Guidobaldi L, Romanelli F, Nigri G, Valabrega S, Sadeghi R, Crescenzi A, Faquin WC, Bongiovanni M, Giovanella L. Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis. Clin Endocrinol (Oxf) 2015; 82:280-5. [PMID: 25047365 DOI: 10.1111/cen.12563] [Citation(s) in RCA: 108] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2014] [Revised: 07/08/2014] [Accepted: 07/16/2014] [Indexed: 01/28/2023]
Abstract
BACKGROUND The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates. RESEARCH DESIGN AND METHODS A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms 'medullary thyroid' AND 'cytology', 'FNA', 'FNAB', 'FNAC', 'fine needle' or 'fine-needle'. The search was updated until 21 March 2014, and no language restrictions were used. RESULTS Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as 'MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6-60·1%). The included studies were statistically heterogeneous in their estimates of DR (I-square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: -3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta-analysis. CONCLUSIONS The presented meta-analysis demonstrates that FNAC is able to detect approximately one-half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results.
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Affiliation(s)
- Pierpaolo Trimboli
- Section of Endocrinology and Diabetology, Ospedale Israelitico, Rome, Italy; Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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