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Lymphoid Enhancer Binding Factor 1 (LEF1) and Paired Box Gene 8 (PAX8): A Limited Immunohistochemistry Panel to Distinguish Solid Pseudopapillary Neoplasms and Pancreatic Neuroendocrine Tumors. Appl Immunohistochem Mol Morphol 2021; 28:776-780. [PMID: 32723981 DOI: 10.1097/pai.0000000000000830] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Solid pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine tumors (PanNETs) are distinctive entities. However, due to overlapping morphologies, distinguishing them remains a diagnostic challenge. Our study investigates the utility of immunohistochemistry for nuclear lymphoid enhancer binding factor 1 (LEF1) and paired box gene 8 (PAX8) in differentiating these 2 entities. LEF1 and PAX8 immunohistochemistry were performed on fine-needle aspiration cell blocks and surgical resection specimens diagnosed as SPN or PanNET at our institution from January 2007 to August 2016. Eight SPN and 25 PanNET cell blocks and 17 SPN and 34 PanNET surgical resection specimens were examined. On cell blocks, positive staining for LEF1 had high frequency, sensitivity, and specificity for SPN (88%, 88%, and 88%) as did positive staining for PAX8 for PanNET (76%, 76%, and 75%). The findings on surgical resection specimens were consistent with those from cell blocks (LEF1+ in SPN: 100%, 100%, and 97%; PAX8+ in PanNET: 59%, 59%, and 100%). A combined LEF1+/PAX8- phenotype showed high sensitivity and specificity for SPN (cell block: 63% and 100%; surgical specimen: 100% and 98%) as did a LEF1-/PAX8+ phenotype for PanNET (cell block: 64% and 100%; surgical specimen: 59% and 100%). SPN and PanNET exhibit opposite immunophenotypic profiles with LEF1+/PAX8- in SPN and LEF1-/PAX8+ in PanNET. The combination of these 2 stains provides an effective means of distinguishing these 2 entities.
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Guo W, Farzaneh T, Lee W, Nael A, Li X, Chandan VS. A limited panel of INSM1 and LEF1 immunostains accurately distinguishes between pancreatic neuroendocrine tumor and solid pseudopapillary neoplasm. Pathol Res Pract 2021; 223:153462. [PMID: 34048981 DOI: 10.1016/j.prp.2021.153462] [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: 04/10/2021] [Revised: 05/01/2021] [Accepted: 05/02/2021] [Indexed: 02/07/2023]
Abstract
Solid pseudopapillary neoplasm (SPN) and well differentiated pancreatic neuroendocrine tumor (PNET) can show significant cytomorphological overlap. In this study, we evaluated the role of INSM1 and LEF1 immunohistochemical stains in distinguishing between these two tumors. 22 SPN and 25 PNET surgically resected cases were stained for both INSM1 and LEF1. All the 22 cases of SPN showed strong and diffuse nuclear staining for LEF1 (in >95 % of tumor cells), while all 25 PNET were negative for LEF1. All 25 PNET cases were positive for INSM1 (moderate to strong intensity nuclear staining in >50 % of the tumor cells), while all 22 cases of SPN were negative for INSM1. The results of our study show that a limited panel comprising of INSM1 and LEF1 immunostains accurately distinguishes between SPN and PNET.
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Affiliation(s)
- Wenchang Guo
- Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, United States
| | - Ted Farzaneh
- Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, United States
| | - Whayoung Lee
- Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, United States
| | - Ali Nael
- Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, United States; Department of Pathology, Children Hospital of Orange County (CHOC), Orange, CA, United States
| | - Xiaodong Li
- Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, United States
| | - Vishal S Chandan
- Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, United States.
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Ardengh JC, Lopes CV, Venco FE, Machado MA. Diagnosis of pancreatic solid pseudopapillary neoplasms using cell‐blocks and immunohistochemical evaluation of endoscopic ultrasound‐guided fine needle aspiration biopsy specimens. Cytopathology 2020; 32:50-56. [DOI: 10.1111/cyt.12905] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 08/09/2020] [Accepted: 08/17/2020] [Indexed: 12/11/2022]
Affiliation(s)
- José Celso Ardengh
- Division of Surgery and Anatomy Ribeirão Preto Medical School University of São Paulo Ribeirão Preto Brazil
- Endoscopy Unit Hospital 9 de Julho São Paulo Brazil
| | - César Vivian Lopes
- Department of Gastroenterology and Digestive Endoscopy Santa Casa Hospital Porto Alegre Brazil
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Takase Y, Naito Y, Okabe Y, Ishida Y, Yamaguchi T, Abe H, Murata K, Ito T, Tanigawa M, Kawahara A, Yano H, Akiba J. Insulinoma-associated protein 1 expression in pancreatic neuroendocrine tumours in endoscopic ultrasound-guided fine-needle aspiration cytology: An analysis of 14 patients. Cytopathology 2018; 30:194-200. [PMID: 30290028 DOI: 10.1111/cyt.12640] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 09/23/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Insulinoma-associated protein 1 (INSM1) has been reported to be a useful marker for diagnosing pancreatic neuroendocrine tumours (PNETs). However, INSM1 expression in endoscopic ultrasound-guided fine needle aspiration cytology has not been examined. We evaluated INSM1 expression in the cytology of cases diagnosed with PNETs. METHODS We immunocytochemically stained INSM1 and Ki-67 in 14 PNET cases, and according to the 2017 World Health Organisation criteria, seven PNET Grade 1 cases, four Grade 2 cases and three Grade 3/neuroendocrine carcinoma cases were identified. As a control for INSM1 and Ki-67 expression, we used cytological specimens from 15 cases of pancreatic ductal adenocarcinoma. RESULTS In PNET cases, INSM1-expressing tumour cells were identified in all cytological specimens of PNET. The median INSM1 expression rate in Grade 1 cases was 49.8% (mean ± standard deviation: 55.1 ± 12.5%, min: 39.3%, max: 74.1%), and in Grade 2 and Grade 3/neuroendocrine carcinoma cases was 81.1% (mean ± standard deviation: 77.6 ± 18.6%, min: 50.3%, max: 100%). However, there was no correlation between INSM1 and Ki-67 expression (r = -0.15). The median expression rate in PNET cases was 64.3%, which was significantly higher than that in pancreatic ductal adenocarcinoma cases (P < 0.0001). CONCLUSION INSM1 immunocytochemistry of cytological specimens obtained from endoscopic ultrasound-guided fine needle aspiration cytology can accurately diagnose PNETs; therefore, INSM1 could be an important diagnostic tool in assessing therapeutic strategies, including molecular-targeted therapy.
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Affiliation(s)
- Yorihiko Takase
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan
| | - Yoshiki Naito
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.,Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Yoshinobu Okabe
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Yusuke Ishida
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Tomohiko Yamaguchi
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan
| | - Hideyuki Abe
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan
| | - Kazuya Murata
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan
| | - Takaaki Ito
- Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Masahiko Tanigawa
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Akihiko Kawahara
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan
| | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Jun Akiba
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan
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Foo WC, Harrison G, Zhang X. Immunocytochemistry for SOX-11 and TFE3 as diagnostic markers for solid pseudopapillary neoplasms of the pancreas in FNA biopsies. Cancer Cytopathol 2017; 125:831-837. [PMID: 29045075 DOI: 10.1002/cncy.21931] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 08/27/2017] [Accepted: 09/14/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare malignant tumors that can be sampled via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Although diagnosing SPNs can be straightforward in cases with a classic morphology and a typical immunoprofile, challenges can occur with morphologic variants or limited specimens. Recently, 2 immunohistochemical stains, SRY-related high-mobility group box 11 (SOX-11) and transcription factor E3 (TFE3), have been demonstrated to be highly sensitive and specific for SPNs in pancreatic resection specimens. The current study evaluates the diagnostic utility of these stains with EUS-FNA. METHODS Thirteen EUS-FNA specimens from SPNs with sufficient material for immunocytochemistry were identified from 2000 to 2016. These cases were compared with 13 EUS-FNA specimens of non-SPN pancreatic neoplasms. Immunocytochemistry for SOX-11, TFE3, and β-catenin was performed on all cell blocks and then was scored independently by 2 pathologists in a masked manner. RESULTS Nuclear reactivity for SOX-11 was detected in 13 of 13 SPNs and in 0 of 13 non-SPNs; this resulted in sensitivity and specificity values of 100%, a positive predictive value (PPV) of 1, and a negative predictive value (NPV) of 1. Nuclear reactivity for TFE3 was detected in 9 of 13 SPNs and in 0 of 13 non-SPNs; this resulted in a sensitivity of 69.2%, a specificity of 100%, a PPV of 1, and an NPV of 0.765. Nuclear reactivity for β-catenin was detected in 13 of 13 SPNs and in 1 of 13 non-SPNs; this resulted in a sensitivity of 100%, a specificity of 92.3%, a PPV of 0.929, and an NPV of 1. CONCLUSIONS SOX-11 is a sensitive and specific immunocytochemical stain for SPNs in EUS-FNA specimens, and it may be useful as a diagnostic marker for distinguishing SPNs from its cytologic mimics. Cancer Cytopathol 2017;125:831-7. © 2017 American Cancer Society.
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Affiliation(s)
- Wen-Chi Foo
- Department of Pathology, Duke University Medical Center, Durham, North Carolina
| | - Grant Harrison
- Department of Pathology, Duke University Medical Center, Durham, North Carolina
| | - Xuefeng Zhang
- Department of Pathology, Duke University Medical Center, Durham, North Carolina
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Ohara Y, Oda T, Hashimoto S, Akashi Y, Miyamoto R, Enomoto T, Satomi K, Morishita Y, Ohkohchi N. Pancreatic neuroendocrine tumor and solid-pseudopapillary neoplasm: Key immunohistochemical profiles for differential diagnosis. World J Gastroenterol 2016; 22:8596-8604. [PMID: 27784972 PMCID: PMC5064041 DOI: 10.3748/wjg.v22.i38.8596] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Revised: 07/04/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To reveal better diagnostic markers for differentiating neuroendocrine tumor (NET) from solid-pseudopapillary neoplasm (SPN), focusing primarily on immunohistochemical analysis.
METHODS We reviewed 30 pancreatic surgical specimens of NET (24 cases) and SPN (6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pan-cytokeratin, E-cadherin, progesterone receptor, vimentin, α-1-antitrypsin, CD10, and β-catenin.
RESULTS E-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles.
CONCLUSION E-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.
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Yang F, Yu X, Bao Y, Du Z, Jin C, Fu D. Prognostic value of Ki-67 in solid pseudopapillary tumor of the pancreas: Huashan experience and systematic review of the literature. Surgery 2015; 159:1023-31. [PMID: 26619927 DOI: 10.1016/j.surg.2015.10.018] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2015] [Revised: 10/13/2015] [Accepted: 10/13/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Solid pseudopapillary tumor of the pancreas (SPTP) is considered to have a low Ki-67 proliferation index, which may explain the generally good clinical outcome. The aim of our study was to evaluate whether Ki-67 has prognostic value in SPTP. METHODS A case series study of patients with SPTP treated in our institution from June 2002 to April 2014 was conducted. Prognostic factors for clinical outcomes were analyzed by the use of clinical decision and survival analysis. In addition, we performed a systematic review and pooled analysis to evaluate our results. RESULTS The institutional data included 71 patients (13 male and 58 female) ranging in age from 12 to 64 years (median, 31 years). Three patients developed local recurrence and/or liver metastasis after initial surgery. The 5-year recurrence-free survival rate was 93.6%. One patient died of disease, with the 5-year disease-specific survival rate of 98.5%. Ki-67 index ≥ 4% was found significantly associated with the survival of SPTP. Twenty-six studies comprising 163 patients were included in the pooled analysis based on our inclusion criteria. A total of 15 cases showed a Ki-67 index ≥ 4%. Kaplan-Meier survival analysis confirmed that Ki-67 index ≥ 4% was significantly associated with poorer recurrence-free survival and disease-specific survival (both P < .001). CONCLUSION This study highlighted a potential role of Ki-67 in predicting adverse outcome of patients with SPTP and should be considered as part of routine histological reporting of SPTP.
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Affiliation(s)
- Feng Yang
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital affiliated to Fudan University, Shanghai, China
| | - Xinzhe Yu
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital affiliated to Fudan University, Shanghai, China
| | - Yun Bao
- Department of Pathology, Huashan Hospital affiliated to Fudan University, Shanghai, China
| | - Zunguo Du
- Department of Pathology, Huashan Hospital affiliated to Fudan University, Shanghai, China
| | - Chen Jin
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital affiliated to Fudan University, Shanghai, China
| | - Deliang Fu
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital affiliated to Fudan University, Shanghai, China.
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Takahashi Y, Hiraoka N, Onozato K, Shibata T, Kosuge T, Nimura Y, Kanai Y, Hirohashi S. Solid-pseudopapillary neoplasms of the pancreas in men and women: do they differ? Virchows Arch 2006; 448:561-9. [PMID: 16523258 DOI: 10.1007/s00428-006-0174-9] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2006] [Accepted: 02/06/2006] [Indexed: 12/17/2022]
Abstract
Solid-pseudopapillary neoplasms (SPNs) of the pancreas are uncommon and occur preferentially in young women. The question whether the features of SPNs occurring in men differ from those in women has not yet been studied. For a better understanding of the clinicopathological features of SPNs of both sexes, we studied a series of 14 tumors surgically resected at a Japanese hospital within a period of 14 years. This series was composed of seven men and seven women. All these SPNs demonstrated nuclear and cytoplasmic accumulation of beta-catenin protein in immunohistochemistry and 86% of them had activating mutations of beta-catenin gene. No pancreatic neuroendocrine tumors showed such immunohistochemical findings and genetic alterations. In our series, most SPNs in women showed encapsulation by thick fibrous tissue and massive degenerative changes. Most SPNs in men exhibited solid components without prominent degenerative changes, even though they were of a similar size to those in women. These findings suggest that SPNs in men tend to be a solid mass with slower progression of degenerative changes during their growth compared to that in women. Nuclear accumulation of beta-catenin appears to be a useful marker of SPN, which allows male SPNs to be correctly diagnosed despite their less typical features.
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Affiliation(s)
- Yu Takahashi
- Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
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