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Deng R, Li NJ, Bai LL, Nie SH, Sun XW, Wang YS. Postoperative radiotherapy for thymus salivary gland carcinoma: A case report. World J Clin Cases 2022; 10:9484-9492. [PMID: 36159414 PMCID: PMC9477657 DOI: 10.12998/wjcc.v10.i26.9484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 06/12/2022] [Accepted: 07/31/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Salivary gland cancer is a rare disease in which cancer cells form in the tissues of the salivary glands. It mostly occurs in the glands that have secretion functions, such as the parotid gland, sublingual gland and submandibular gland. This is very rare when it occurs in other nonsecreting glands. Here, we report one case of salivary gland carcinoma occurring in the thymus and discuss related diagnoses and treatment progress.
CASE SUMMARY One 33-year-old middle-aged man presented with a thymus mass without any clinical symptoms when he underwent regular physical examination. Later, the patient was admitted to the hospital for further examination. Computed tomography (CT) showed that there was a mass of 3 cm × 2.8 cm × 1.5 cm in the thymus area. The patient had no symptom of discomfort or tumor- related medical history before. After completing the preoperative examinations, it was confirmed that the patient had indications for surgery. The surgeon performed a transthoracoscope "thymectomy + pleural mucostomy" for him. During the operation, the tumor tissue was quickly frozen, and the symptomatic section showed a malignant tumor. The final pathological result suggested thymus salivary gland carcinoma- mucoepidermoid carcinoma (MEC). In the second month after surgery, we performed local area radiotherapy for the patient, with a total radiation dose of 50.4 Gy/28Fx. After 12 mo of surgery, the patient underwent positron emission tomography-CT examination, which indicated that there was no sign of tumor recurrence or metastasis. After 16 mo of operation, CT scan re-examination showed that there was no sign of tumor recurrence or metastasis. As of the time of publication, the patient was followed up for one and a half years. He had no sign of tumor recurrence and continued to survive.
CONCLUSION The incidence of MEC in the thymus is low, and its diagnosis needs to be combined with clinical features and imaging methods. Histopathological analysis plays a key role in the diagnosis of the disease. Patients with early-stage disease have a good prognosis and long survival period. In contrast, patients with advanced-stage disease have a poor prognosis and short survival period. Combining radiotherapy and chemotherapy in inoperable patients may prolong survival.
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Affiliation(s)
- Rui Deng
- Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Department of Thoracic Oncology, West China Hospital, Sichuan University, Cheng Du 610041, Sichuan Province, China
| | - Nan-Jing Li
- Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Cheng Du 610041, Sichuan Province, China
| | - Liang-Liang Bai
- Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Department of Thoracic Oncology, West China Hospital, Sichuan University, Cheng Du 610041, Sichuan Province, China
| | - Shi-Hong Nie
- Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Cheng Du 610041, Sichuan Province, China
| | - Xiao-Wen Sun
- Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Cheng Du 610041, Sichuan Province, China
| | - Yong-Sheng Wang
- Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Department of Thoracic Oncology, West China Hospital, Sichuan University, Cheng Du 610041, Sichuan Province, China
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Nonaka T, Takei H. Immunohistochemical Profile of Polymorphous Adenocarcinoma of Minor Salivary Gland: A Systematic Review and Meta-Analysis. Head Neck Pathol 2022; 16:980-990. [PMID: 35507302 PMCID: PMC9729680 DOI: 10.1007/s12105-022-01453-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 03/21/2022] [Indexed: 12/16/2022]
Abstract
Polymorphous adenocarcinoma (PAC) is a rare variant of minor salivary gland tumors. Because of its architectural diversity, histological diagnosis of PAC can be difficult especially for small biopsies, and immunohistochemistry is of great help in differentiating it from its histologic mimics. The aim of this study is to conduct a systematic literature review to identify reliable immunohistochemical markers for PAC. We conducted an electronic literature search of the MEDLINE, ScienceDirect, SpringerLink, and Wiley Online Library databases, covering the literature published in the period between 1988 and 2021. The eligibility criteria included case reports and retrospective studies of PAC cases with details of immunohistochemical markers. Following the search and selection process, 32 studies with 409 cases were included in this systematic review. Overall, > 90% positivity was observed for pan-cytokeratin (CK) (97.3%), CK7 (96.8%), CK7/8 (97.4%), E-cadherin (90.0%), Vimentin (92.5%), S100 (97.0%), p63 (91.7%), and SOX10 (100%), while little to no positivity was observed for CK20 (0.0%), p40 (0.0%), and GFAP (5.0%). The average MIB-1 labeling index was 3.78%. The results of this systematic review indicate that CK7+/CK20-, p63+/p40-, S100+, Vimentin+, and GFAP- immunophenotype have diagnostic value for PAC. In addition, the use of S100, MSA, p40, and c-Kit provide additional layers of information helpful to differentiate PAC from adenoid cystic carcinoma, one of challenging differential diagnoses.
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Affiliation(s)
- Taichiro Nonaka
- Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
| | - Hidehiro Takei
- Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA
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3
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Higgins KE, Cipriani NA. Practical immunohistochemistry in the classification of salivary gland neoplasms. Semin Diagn Pathol 2021; 39:17-28. [PMID: 34750022 DOI: 10.1053/j.semdp.2021.10.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 10/28/2021] [Indexed: 12/24/2022]
Abstract
Diagnosis of salivary gland neoplasms can be challenging for surgical pathologists due to low incidence of tumors as well as overlapping histologic features. On small biopsy, the most important information to be conveyed for clinical management is the distinction between a benign/low grade tumor and a high grade carcinoma. This review will discuss the differential diagnosis of salivary gland tumors based on four broad morphologic patterns: basaloid/tubular/cribriform, (micro)cystic/secretory/mucinous, solid-nested/clear-spindled, and oncocytic/oncocytoid. With the assistance of immunohistochemistry, demonstration of the number of cell types (mainly epithelial versus myoepithelial/basal) can further subclassify tumors within these morphologic categories. Additional tumor-specific immunomarkers are useful in some cases. Underlying tumor-specific genetic anomalies can be of value, however, immunohistochemical correlates are only available for some. When used judiciously, in the correct morphologic context, and with knowledge of their limitations, immunohistochemical stains can aid in differentiating tumors with similar morphology.
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Affiliation(s)
- Kathleen E Higgins
- The University of Chicago Department of Pathology 5841 S. Maryland Ave. MC 6101 Chicago, IL 60637 United States of America
| | - Nicole A Cipriani
- The University of Chicago Department of Pathology 5841 S. Maryland Ave. MC 6101 Chicago, IL 60637 United States of America.
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Kawakami F, Nagao T, Honda Y, Sakata J, Yoshida R, Nakayama H, Inoue S, Kitajima M, Ikeda O, Nakaguro M, Mikami Y. Microsecretory adenocarcinoma of the hard palate: A case report of a recently described entity. Pathol Int 2020; 70:781-785. [PMID: 32687666 DOI: 10.1111/pin.12987] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 06/18/2020] [Accepted: 06/28/2020] [Indexed: 12/14/2022]
Abstract
We report a case of microsecretory adenocarcinoma of the hard palate. The patient is a 37-year-old woman with a 15 mm submucosal tumor, which was incidentally found by her primary care dentist, in her hard palate. Preoperative magnetic resonance imaging revealed a tumor exhibiting high signal on T2-weighted image, which was gradually enhanced on dynamic study. Histologically, the tumor border was ill-defined without fibrous capsule and adjoined minor salivary gland with permeative infiltration at the tumor periphery. The tumor comprised intercalated duct-like cells with polygonal narrow eosinophilic to clear cytoplasm and small, uniform oval nuclei. These cells formed small infiltrative microcysts, tubules and fascicular cords collecting pale basophilic secretions and small vacuoles setting in an abundant fibromyxoid stroma. The tumor cells were positive for CK AE1+AE3, S-100 protein, and p63, while are completely negative for p40, alpha-SMA, and calponin. The MEF2C-SS18 fusion was identified by reverse transcriptase-polymerase chain reaction followed by Sanger sequencing. The combination of characteristic histology, immunophenotype, and presence of MEF2C-SS18 fusion indicated the diagnosis of microsecretory adenocarcinoma of the hard palate, an entity described only recently. Post-operative course was uneventful and there was no evidence of disease at 4 months after surgery.
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Affiliation(s)
- Fumi Kawakami
- Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan
| | - Toshitaka Nagao
- Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan
| | - Yumi Honda
- Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan
| | - Junki Sakata
- Department of Otolaryngology-Head and Neck Surgery, Kumamoto University, Kumamoto, Japan
| | - Ryoji Yoshida
- Department of Otolaryngology-Head and Neck Surgery, Kumamoto University, Kumamoto, Japan
| | - Hideki Nakayama
- Department of Otolaryngology-Head and Neck Surgery, Kumamoto University, Kumamoto, Japan
| | - Seijiro Inoue
- Department of Diagnostic Radiology, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Mika Kitajima
- Department of Medical Imaging Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Osamu Ikeda
- Department of Diagnostic Radiology, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Masato Nakaguro
- Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Aichi, Japan
| | - Yoshiki Mikami
- Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan
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Comparison of p63 and p40 (ΔNp63) as Basal, Squamoid, and Myoepithelial Markers in Salivary Gland Tumors. Appl Immunohistochem Mol Morphol 2016; 24:501-8. [DOI: 10.1097/pai.0000000000000222] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Kuzenko YV, Romanuk AM, Dyachenko OO, Hudymenko O. Pathogenesis of Warthin's tumors. Interv Med Appl Sci 2016; 8:41-48. [PMID: 28386459 DOI: 10.1556/1646.8.2016.2.2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
INTRODUCTION Warthin's tumor, also known as papillary cystadenoma lymphomatosum, monomorphic adenoma, or adenolymphoma, is a benign cystic tumor of the salivary glands containing abundant lymphocytes and lymph node-like stroma. It is named after the pathologist Aldred Scott Warthin, who described two cases in 1929. OBJECTIVE The aim of this study is to analyze the pathogenesis of Warthin's tumor. METHODS A total of 15 patients with Warthin's tumor were studied. Hematoxylin and eosin stains, which have been used for at least a century and are still essential for recognizing various tissue types and the morphologic changes for cancer diagnosis, were used. Warthin's tumor was evaluated for the expression of MGMT, CD3, HSP90AA1, MMP-1, Bcl-2, CD79A, IgG, Ki-67, p53, IgM, OPN, S100, myeloperoxidase, and VEGF by immunohistochemistry. RESULTS Immunohistochemical staining confirmed that the immune cells within the follicles of Warthin's tumor were positive for MGMT (10.0 ± 0.34%), Ki-67 (13.3 ± 0.45%), Bcl-2 (42.6 ± 8.33), and p53 (11.6 ± 2.3). The immune cells associated with CD3 were present at the stroma of residual cells (47.3 ± 3.89); however, they were not present in the epithelium cell layers. B cells (CD79A) consistent with germinal centers were present within the immune cells and formed follicles (43.2 ± 13.5%). CONCLUSIONS Histopathological analysis of the stroma and parenchyma revealed balanced distribution of epithelial and stromal component. Epithelial component of the Warthin's tumor is the trigger for the tumor process. This study indicates that the Warthin tumor is a consequence of inflammatory etiology.
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Affiliation(s)
- Yevhen V Kuzenko
- Department of Pathology, Medical Institute of Sumy State University , Sumy, Ukraine
| | - Anatoly M Romanuk
- Department of Pathology, Medical Institute of Sumy State University , Sumy, Ukraine
| | | | - Olena Hudymenko
- Department of Pathology, Medical Institute of Sumy State University , Sumy, Ukraine
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Argyris PP, Wetzel SL, Greipp P, Wehrs RN, Knutson DL, Kloft-Nelson SM, García JJ, Koutlas IG. Clinical utility of myb rearrangement detection and p63/p40 immunophenotyping in the diagnosis of adenoid cystic carcinoma of minor salivary glands: a pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol 2016; 121:282-9. [DOI: 10.1016/j.oooo.2015.10.016] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 10/05/2015] [Accepted: 10/11/2015] [Indexed: 01/04/2023]
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8
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Bagulkar BB, Gawande M, Chaudhary M, Gadbail AR, Patil S, Bagulkar S. XIAP and Ki-67: A Correlation Between Antiapoptotic and Proliferative Marker Expression in Benign and Malignant Tumours of Salivary Gland: An Immunohistochemical Study. J Clin Diagn Res 2015; 9:EC01-4. [PMID: 25859460 DOI: 10.7860/jcdr/2015/11690.5604] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Accepted: 01/14/2015] [Indexed: 11/24/2022]
Abstract
BACKGROUND Impaired balance between cell proliferation and apoptosis is crucial to the development of malignant neoplasm. The purpose of this study was to evaluate and compare the expression of X-Linked inhibitor of apoptotic protein (XIAP) (antiapoptotic marker) and Ki-67 (proliferative marker) expression in benign and malignant salivary gland (SG) tumours. MATERIALS AND METHODS The study consisted of 40 cases of benign SG tumours and 50 cases of malignant SG tumours. The immunohistochemistry was carried out by using Ki-67 antibody (clone MIB-1) and XIAP antibody in all the groups. RESULTS XIAP expression was significantly higher in malignant SG tumours than benign SG tumours (p = 0.016). Ki-67 LI was significantly higher in malignant SG tumours than benign SG tumours (p = 0.0002). Statistically significant positive correlation between Ki-67 count and XIAP expression was noted in benign and malignant SG tumours (p = 0.000). CONCLUSION As the expression of an antiapoptotic marker (XIAP) increases, the expression of a proliferative marker (Ki-67) also increases from benign to malignant SG tumours. Thus, targeted therapy of XIAP may play a future role in the management of SG malignancy.
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Affiliation(s)
- Bhupesh Bhayyaji Bagulkar
- Assistant Professor, Department of Oral and Maxillofacial Pathology and Microbiology, Sri Aurobindo College of Dentistry , Indore, Madhya Pradesh, India
| | - Madhuri Gawande
- Professor, Department of Oral and Maxillofacial Pathology & Microbiology, Sharad Pawar Dental College & Hospital, Datta Meghe Institute of Medical Sciences , Sawangi (M), Wardha, Maharashtra, India
| | - Minal Chaudhary
- Professor and Head, Department of Oral and Maxillofacial Pathology & Microbiology, Sharad Pawar Dental College & Hospital, Datta Meghe Institute of Medical Sciences , Sawangi (M), Wardha, Maharashtra, India
| | - Amol Ramchandra Gadbail
- Associate Professor, Department of Oral and Maxillofacial Pathology & Microbiology, Sharad Pawar Dental College & Hospital, Datta Meghe Institute of Medical Sciences , Sawangi (M), Wardha, Maharashtra, India
| | - Swati Patil
- Professor, Department of Oral and Maxillofacial Pathology & Microbiology, Sharad Pawar Dental College & Hospital, Datta Meghe Institute of Medical Sciences, Sawangi (M) , Wardha, Maharashtra, India
| | - Smita Bagulkar
- Lecturer, Department of Oral and Maxillofacial Surgery, Sri Aurobindo College of Dentistry , Indore, Madhya Pradesh, India
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9
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Rooper L, Sharma R, Bishop JA. Polymorphous low grade adenocarcinoma has a consistent p63+/p40- immunophenotype that helps distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma. Head Neck Pathol 2014; 9:79-84. [PMID: 24969705 PMCID: PMC4382474 DOI: 10.1007/s12105-014-0554-4] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 06/21/2014] [Indexed: 11/30/2022]
Abstract
Polymorphous low grade adenocarcinoma (PLGA) is a tumor of minor salivary glands that exhibits considerable morphologic overlap with adenoid cystic carcinoma and cellular pleomorphic adenoma, especially in small biopsy specimens. Unlike these other tumor types. PLGAs do not harbor a myoepithelial component, yet their frequent positivity for p63 diminishes the usefulness of this particular myoepithelial marker as a discriminating immunostain. p40 is an antibody that recognizes ΔNp63, a p63 isoform that is more specific for true myoepithelial differentiation. As such, p40 immunostaining could help distinguish PLGAs from adenoid cystic carcinomas and pleomorphic adenomas. In this study, p63 and p40 immunohistochemistry was performed on paraffin embedded, formalin fixed tissue from 11 PLGAs, 101 adenoid cystic carcinomas, and 31 pleomorphic adenomas. All 11 PLGAs (100 %) were positive for p63 but completely negative for p40. Among adenoid cystic carcinomas, 91 of 101 (90 %) were positive for p63 and 90/101 (89 %) were positive for p40. The single discordant p63+/p40- adenoid cystic carcinoma exhibited solid architecture and high grade features not typically seen in PLGA. Among pleomorphic adenomas, 21/31 (68 %) were positive for p63 and 13/31 (42 %) were positive for p40. For the pleomorphic adenomas, the discordant p63+/p40- staining pattern was seen only in the overtly mesenchymal chondromyxoid stroma. The cellular epithelial component of the pleomorphic adenomas demonstrated concordant p63+/p40+ or p63-/p40- immunophenotypes. PLGA consistently exhibits a p63+/p40- immunophenotype that can help distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma, tumors that characteristically demonstrate concordant p63 and p40 immunostaining patterns. A p63/p40 immunohistochemical panel can provide a valuable tool for making the distinction between these morphologically similar but clinically divergent entities.
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Affiliation(s)
- Lisa Rooper
- />Departments of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD USA
| | - Rajni Sharma
- />Departments of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD USA
| | - Justin A. Bishop
- />Departments of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD USA , />Departments of Otolaryngology/Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD USA , />The Johns Hopkins University School of Medicine, 401 N. Broadway, Weinberg 2249, Baltimore, MD 21231 USA
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Argyris PP, Gopalakrishnan R, Pambuccian SE, Tosios KI, Koutlas IG. Polymorphous low-grade adenocarcinoma of the upper lip with metachronous myoepithelioma of the buccal mucosa. Oral Surg Oral Med Oral Pathol Oral Radiol 2013; 117:e441-8. [PMID: 24268388 DOI: 10.1016/j.oooo.2013.08.030] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Revised: 08/21/2013] [Accepted: 08/29/2013] [Indexed: 01/05/2023]
Abstract
Examples of multiple minor salivary gland tumors, synchronous or metachronous, are uncommon. We report a patient who initially presented with polymorphous low-grade adenocarcinoma (PLGA) and subsequently with myoepithelioma. A 91-year-old white woman presented in 2009 with a 1-cm, firm, nontender, well-circumscribed nodule of the left side of the upper lip extending to the anterior buccal mucosa. Excisional biopsy revealed PLGA. While the margins were positive, further treatment was not recommended due to the patient's age. In 2011, the patient returned with a 1.5-cm, asymptomatic mass of the left buccal vestibule. Excision of the lesion revealed a circumscribed proliferation of epithelioid and plasmacytoid cells arranged in spherical or whorl-like islands and immersed in a mucinous stroma, consistent with myoepithelioma. The PLGA recurred 3 years after initial diagnosis. Excision was again associated with positive margins, and again no further treatment was recommended. A few months later, at a scheduled follow-up appointment, she presented with a painless nodule of the left upper lip, consistent with recurrent PLGA. One month later, the patient died of unrelated causes. We also present a literature review of multiple minor salivary gland tumors.
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Affiliation(s)
- Prokopios P Argyris
- Division of Oral and Maxillofacial Pathology, School of Dentistry, University of Minnesota, Minneapolis, MN, USA
| | - Rajaram Gopalakrishnan
- Division of Oral and Maxillofacial Pathology, School of Dentistry, University of Minnesota, Minneapolis, MN, USA
| | - Stefan E Pambuccian
- Department of Laboratory Medicine and Pathology, Fairview-University Medical Center, University of Minnesota, Minneapolis, MN, USA
| | - Konstantinos I Tosios
- Department of Oral Pathology and Medicine, School of Dentistry, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis G Koutlas
- Division of Oral and Maxillofacial Pathology, School of Dentistry, University of Minnesota, Minneapolis, MN, USA.
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Woo SB. Diseases of the oral mucosa. MCKEE'S PATHOLOGY OF THE SKIN 2012:362-436. [DOI: 10.1016/b978-1-4160-5649-2.00011-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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de Biase D, Morandi L, Degli Esposti R, Ligorio C, Pession A, Foschini MP, Eusebi V. p63 short isoforms are found in invasive carcinomas only and not in benign breast conditions. Virchows Arch 2010; 456:395-401. [PMID: 20225093 DOI: 10.1007/s00428-010-0900-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2009] [Revised: 02/10/2010] [Accepted: 02/21/2010] [Indexed: 02/05/2023]
Abstract
Two N-terminal isoforms characterize the p63 protein: the transactivating isoform TAp63 and the amino-terminal truncated isoform DeltaNp63. Two further N-terminal isoforms lacking exon 4 (d4TAp63 and DeltaNp73L) have been reported. Purpose of the study was to investigate the molecular expression of N-terminal p63 isoforms in benign and malignant breast tissues. Eighteen randomly selected cases of invasive breast carcinoma (IBC) of luminal type, two cases of in situ duct carcinoma (DCIS/DIN), and 20 specimens of normal and benign breast tissues were studied. All cases were immunostained for p63. Reverse polymerase chain reaction and nested PCR were performed to evaluate p63 N-terminal expression patterns. These isoforms whenever present were validated by sequencing. All cases of normal breast, benign lesions, and the two cases of DCIS/DIN expressed DeltaNp63 and TAp63 isoforms only. The two variants lacking exon 4 (DeltaNp73L and d4TAp63) were not found. All invasive carcinomas expressed the DeltaNp63 and TAp63 isoforms as well as the two short isoforms lacking exon 4 which were found in 11 (d4TAp63) and four (DeltaNp73L) cases. The present cases of luminal-type IBC showed p63 isoforms together with short variants lacking exon 4. These isoforms were not observed in non-neoplastic breast tissue. Presence of p63 in invasive breast carcinomas of luminal type, as seen at molecular level, suggests caution to include p63 as a marker of basal-like carcinomas.
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Affiliation(s)
- Dario de Biase
- Department of Haematology and Oncological Sciences L. and A. Seragnoli, Section of Anatomic Pathology at Bellaria Hospital, University of Bologna, Via Altura 3, 40139 Bologna, Italy
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Ramer N, Wu H, Sabo E, Ramer Y, Emanuel P, Orta L, Burstein DE. Prognostic value of quantitative p63 immunostaining in adenoid cystic carcinoma of salivary gland assessed by computerized image analysis. Cancer 2010; 116:77-83. [PMID: 19877114 DOI: 10.1002/cncr.24657] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
BACKGROUND In a long-term retrospective immunohistochemical study of adenoid cystic carcinoma (ACC) of salivary gland, we investigated the relation of p63 immunodetection to prognosis. Although it is generally agreed that the solid pattern is the most aggressive pattern of growth, ACCs with predominantly cribriform or tubular patterns have an unpredictable clinical course, with a relatively favorable 5-year survival but a low 20-year survival. METHODS Formalin-fixed paraffin sections from 35 cases of ACC showing a predominantly better differentiated histopathology, ie, cribriform or tubular patterns of growth, were immunostained for p63. Automated image analysis was used to quantify p63 positivity, using a modification of a previously developed algorithm. RESULTS Patients alive for more than 10 years had a lower extent of p63 expression than those who died of disease. Kaplan-Meier analysis revealed that separation of patients with morbidity and mortality from those alive with no evidence of disease, could be achieved at a cutoff of 35% p63 positivity (P = .0031, log-rank test). Multivariate analysis using the Cox proportional hazard model revealed p63 and tumor stage to be independent predictors of survival (P = .012 and P = .0003, respectively). CONCLUSIONS To our knowledge, the present study is the first to report prognostic significance of p63 in salivary gland ACC and the first report of a robust and well-studied immunohistochemical stain performable on routinely fixed and processed tissue with prognostic utility.
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Affiliation(s)
- Naomi Ramer
- Department of Pathology, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
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14
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Weiler C, Reu S, Zengel P, Kirchner T, Ihrler S. Obligate basal cell component in salivary oncocytoma facilitates distinction from acinic cell carcinoma. Pathol Res Pract 2009; 205:838-42. [PMID: 19646823 DOI: 10.1016/j.prp.2009.06.019] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2009] [Revised: 06/17/2009] [Accepted: 06/26/2009] [Indexed: 11/29/2022]
Abstract
The differential diagnosis between benign salivary oncocytoma (ONC) and low-grade malignant acinic cell carcinoma (ACC) can be difficult due to a significant histomorphological overlap of the structural and cytological presentation of both tumor types. To the best of our knowledge a comprehensive study comparing (immuno-)histological markers in cases of difficult differential diagnosis between ONC and ACC has not yet been performed. We investigated a panel of different immunohistochemical (CK5/6, CK14, CK7, CK18, p63 and Ki67) and histochemical (PAS, alpha-amylase) markers in 12 cases of ONC and 19 cases of ACC. The statistically significant stronger expression of CK7 in ONC and stronger expression of PAS and alpha-amylase in ACC in routine practice each is hampered by a pronounced overlap between both tumor groups. The obligate presence of an additional small basal cell component in all cases of ONC, demonstrable with p63 and CK5/6, enables a straightforward distinction from ACC, being constantly devoid of a basal cell component. Unexpectedly, CK14 is not a suitable marker for a reliable proof of these basal cells. The detection of this basal cell component in ONC in routine Hematoxylin-eosin stain is difficult and in some cases not possible; therefore, immunohistochemistry with p63 or CK5/6 is recommended for selected cases.
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Affiliation(s)
- Christoph Weiler
- Institute of Pathology, Ludwig Maximilian University, Munich, Germany.
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Carlos-Bregni R, Vidaurre EC, Carolina Netto A, León JE, Almeida OP. Primary Intraosseous Adenoid Cystic Carcinoma of the Mandible: Histopathological and Immunohistochemical Analysis. Pathol Oncol Res 2009; 15:659-64. [DOI: 10.1007/s12253-009-9168-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2008] [Accepted: 04/07/2009] [Indexed: 01/18/2023]
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Foschini MP, Cocchi R, Morandi L, Marucci G, Pennesi MG, Righi A, Tosi AL, de Biase D, Pession A, Montebugnoli L. E-cadherin loss and Delta Np73L expression in oral squamous cell carcinomas showing aggressive behavior. Head Neck 2008; 30:1475-82. [PMID: 18704970 DOI: 10.1002/hed.20908] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND This article sought to investigate the existence of parameters useful for predicting lymph node metastases in cases of surgically resected oral squamous cell carcinomas (OSCCs). METHODS Fifty-eight cases were studied for E-cadherin and the truncated dominant-negative isoform of p63 (Delta Np63) with immunohistochemistry. In addition, the p63 gene expression profile was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) to disclose the presence of the truncated variant Delta Np73L. RESULTS E-cadherin expression was the most powerful parameter related to the presence of lymph node metastases at presentation. Twenty-four of 38 (63%) cases showing low E-cadherin expression had lymph node metastases at presentation compared with 5 of 20 (25%) (p <.01) cases showing high E-cadherin expression. The high predictive value was also maintained when a low expression of E-cadherin was associated with immunohistochemical high expression of DeltaNp63. The association between low E-cadherin expression and Delta Np73L (as seen with reverse transcriptase-polymerase chain reaction) was highly predictive for developing lymph node metastases, especially in small tumors (T1\T2). When this association occurred, metastases developed in 62.5% of cases during the follow-up compared with 16.1% in those which did not show low E-cadherin expression and presence of Delta Np73L. CONCLUSION This study shows that low E-cadherin expression is useful for predicting lymph node metastases in cases of OSCC. The predictive value is enhanced when low E-cadherin positivity is associated with DeltaNp63 and Delta Np73L expression.
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Affiliation(s)
- Maria P Foschini
- Institute of Pathological Anatomy, University of Bologna, Bellaria Hospital, Bologna, Italy.
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Hoch BL, Wu M, Lewis M, Gan L, Burstein DE. An immunohistochemical study of XIAP expression in pleomorphic adenoma and carcinoma ex pleomorphic adenoma. J Oral Pathol Med 2008; 37:634-8. [DOI: 10.1111/j.1600-0714.2008.00680.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Bell D, Luna MA. Warthin adenocarcinoma: analysis of 2 cases of a distinct salivary neoplasm. Ann Diagn Pathol 2008; 13:201-7. [PMID: 19433301 DOI: 10.1016/j.anndiagpath.2008.02.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Carcinomas arising in or from the epithelial component of preexisting parotid Warthin tumors (WTs) are rare; the other histologic types of carcinoma found to arise from WTs are adenocarcinoma not otherwise specified, undifferentiated, mucoepidermoid, squamous cell, and oncocytic. The aim of this study is to describe the clinicopathologic features of a distinct salivary gland neoplasm, previously undescribed, with a striated duct phenotype arising from WT. We have designated this neoplasm "Warthin adenocarcinoma" (WA). In this retrospective study, we searched the surgical pathology files of the Department of Pathology at The University of Texas M.D. Anderson Cancer Center for cases of malignant WT and salivary adenocarcinoma not otherwise specified diagnosed from January 1, 1985, through December 31, 2006, and evaluated patients' medical records and pathologic material. We obtained tissue sections and immunohistochemically stained them with antibodies against p63; Bcl-2; cytokeratin (CK)903, CK7, CK14, and CK18; antimitochondrial antibody (AMA); smooth muscle actin; calponin; S-100; and Ki-67. We identified 2 cases of WA; both patients were women, 44 and 60 years of age, with 4.0- and 4.5-cm tumors in the left parotid gland. Histologically, the tumors were composed of bilayered duct-like structures: The inner layer was formed by a single row of columnar oxyphilic cells expressing CK7, CK14, CK18, and AMA. The outer layer was composed of multiple layers of small round dark cells with scanty cytoplasm that expressed p63, Bcl-2, and CK903 and were focally positive for AMA and negative for myoepithelial markers. The Ki-67 proliferative indices were 20%; and 25%. A residual WT with transition to carcinoma was identified in both cases. Treatment had consisted of total parotidectomy with postoperative irradiation. Patients were free of disease 1 and 3 years after treatment. Warthin adenocarcinoma is a unique salivary gland carcinoma representing the malignant epithelial counterpart of WT. The identification of additional cases would help to better elucidate the line of differentiation of the tumor and further define its natural history.
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Affiliation(s)
- Diana Bell
- Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
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McHugh JB, Hoschar AP, Dvorakova M, Parwani AV, Barnes EL, Seethala RR. p63 immunohistochemistry differentiates salivary gland oncocytoma and oncocytic carcinoma from metastatic renal cell carcinoma. Head Neck Pathol 2007; 1:123-31. [PMID: 20614263 PMCID: PMC2807526 DOI: 10.1007/s12105-007-0031-4] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2007] [Accepted: 09/26/2007] [Indexed: 11/27/2022]
Abstract
Metastatic renal cell carcinoma (RCC) can pose diagnostic challenges in the head and neck often resembling benign and malignant oncocytic lesions. Immunohistochemical panels have been reported to help with this differential but are not entirely specific or sensitive. We have noticed that p63 routinely stains salivary gland oncocytomas but not metastatic RCC. Nineteen oncocytomas, 9 cases of oncocytosis, 9 oncocytic carcinomas and 16 head and neck metastatic RCC were studied. Morphologic features evaluated were cytoplasmic character (clear versus oncocytic), Fuhrman nuclear grade, mitotic rate, growth pattern, presence of lumens/blood lakes and stromal characteristics. Tumors were stained with antibodies to p63, renal cell carcinoma marker (RCCm), CD10, and vimentin. Eight benign oncocytic tumors (29%) had clear cell features while 6 metastatic RCC (37%) had oncocytic features. Median Fuhrman nuclear grade was 2 in oncocytoma and oncocytosis and 3 both oncocytic carcinoma and metastatic RCC. Mitotic rates were only significantly different between benign oncocytic tumors and metastatic RCC. All oncocytomas had lumina compared to half of metastatic RCC, all of which also demonstrated blood lakes. Seven benign oncocytic tumors (25%) and 5 oncocytic carcinomas (56%) had RCC-like vascular stroma. All primary salivary gland tumors were positive for p63, predominately in basal cell-type distribution. None of the metastatic RCC was positive. RCCm was entirely specific but lacked sensitivity for metastatic RCC while CD10 and vimentin showed variable sensitivity and specificity. While clinical history and morphology usually are adequate, demonstration of p63 staining can definitively exclude metastatic RCC from the differential diagnosis of similar appearing tumors in salivary glands, namely oncocytoma and oncocytic carcinoma, with 100% specificity and sensitivity. While RCCm, CD10, and vimentin performed adequately, they were significantly less reliable than p63 with both false positives and false negatives.
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Affiliation(s)
- Jonathan B McHugh
- Department of Pathology, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0054, USA.
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Seethala RR, Barnes EL, Hunt JL. Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract. Am J Surg Pathol 2007; 31:44-57. [PMID: 17197918 DOI: 10.1097/01.pas.0000213314.74423.d8] [Citation(s) in RCA: 191] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
To further define the clinicopathologic spectrum of epithelial-myoepithelial carcinoma (EMCa), we report the gross, histologic, and immunophenotypic characteristics of 61 tumors seen within a 30-year-period. The mean age at presentation was 60.9 years, with a female predominance (1.5:1). The most common sites were parotid (62.1%), sinonasal mucoserous glands (10.3%), palate (8.6%), and submandibular (8.6%). Most EMCas showed a characteristic nodular/multinodular growth pattern and classic biphasic tubular histology. However, new morphologies in EMCa such as ancient change (8.2%), "Verocay"-like change (3.3%), and sebaceous differentiation (13.1%) were noted. Specific histologic variants were dedifferentiated EMCa (3.3%), oncocytic EMCa (8.2%), EMCa ex pleomorphic adenoma (1.6%), double-clear EMCa (3.3%), and EMCa with myoepithelial anaplasia (3.3%). All cytokeratin cocktails selectively highlighted the epithelial component well. Of the myoepithelial markers, p63, smooth muscle actin and vimentin performed best. Bcl-2 and c-kit were frequently positive (66.7% and 69.2%, respectively). p53 was highly expressed only in 1 dedifferentiated EMCa. The recurrence rate was 36.3% (median disease-free survival 11.34 y), but death was rare with 5-year and 10-year disease-specific survivals of 93.5% and 81.8%, respectively. The most important univariate predictors of recurrence were margin status (log rank P=0.006), angiolymphatic invasion (P=0.002), tumor necrosis (P=0.004), and myoepithelial anaplasia (P=0.038). Thus, EMCa is generally a low-grade tumor with a broader morphologic spectrum than previously thought, with several key features predictive of recurrence. Immunohistochemistry can aid diagnosis by highlighting the biphasic nature of the tumor.
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Affiliation(s)
- Raja R Seethala
- Head and Neck/Endocrine Division, Department of Pathology, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
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Williams SB, Ellis GL, Warnock GR. Sialoblastoma: a clinicopathologic and immunohistochemical study of 7 cases. Ann Diagn Pathol 2007; 10:320-6. [PMID: 17126248 DOI: 10.1016/j.anndiagpath.2006.02.008] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Sialoblastoma is a rare congenital or perinatal salivary tumor that varies in histologic features and biologic potential. Seven cases from the files of the Armed Forces Institute of Pathology are presented. These tumors occurred in 4 males and 3 females with ages ranging from prenatal to 6 months at the time of discovery. Five lesions originated from the parotid gland; 2 lesions were from the submandibular gland. All lesions presented as nodular to multinodular swellings and ranged in size from 2.0 to 7.0 cm. The principal sign or symptom was rapid growth. Two histologic patterns with differing behavior predominated: (1) a favorable pattern had semiencapsulation of cytologically benign basaloid tumor cells with intervening stroma; and (2) an unfavorable histology of anaplastic basaloid tumor cells, minimal stroma, and broad pushing to infiltrative periphery. Four and three tumors had favorable and unfavorable growth patterns, respectively. One unfavorable lesion had vascular invasion, and another demonstrated perineural invasion. All 3 tumors with unfavorable histology recurred. Tumor cells in 3 cases were immunohistochemically reactive for keratin, S-100, smooth muscle actin, and calponin to varying degrees. All 3 tumors were reactive for p63. alpha-Fetoprotein was expressed in 2 unfavorable tumors. Ki67 was expressed at 3% in a favorable tumor and 40% and 80% in the 2 unfavorable lesions. Treatment involved surgical excision. One patient received adjuvant chemotherapy. Two sialoblastomas resulted in recurrences within a year and another developed a recurrence after 4 years. One sialoblastoma developed lung metastasis within 1 month of the original biopsy. Although a clinical correlation is suggested by a favorable/unfavorable histologic grading system the biologic behavior is nonetheless considered unpredictable.
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Affiliation(s)
- Stephen B Williams
- Department of Oral and Maxillofacial Pathology, Armed Forces Institute of Pathology, Washington, DC 20306, USA.
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