The panel of syntaxin 1 and insulinoma‐associated protein 1 outperforms classic neuroendocrine markers in pulmonary neuroendocrine neoplasms

BACKGROUND: Neuroendocrine neoplasm (NEN) is an epithelial cell neoplasm that can give a histopathological appearance resembling high-grade colorectal adenocarcinoma. Immunohistochemical assays with specific neuroendocrine markers of chromogranin A and synaptophysin are required to establish a definite diagnosis of NEN. AIM: This study aimed to determine whether there was an expression of chromogranin A, synaptophysin and Ki67 which indicated the presence of neuroendocrine neoplasms in samples that have been diagnosed as high-grade colorectal adenocarcinoma. MATERIALS AND METHODS: A study of the expression of chromogranin A, synaptophysin and Ki67 in paraffin blocks was carried out as a result of biopsy and tissue surgery of 70 samples of colorectal tumor specimens diagnosed with colorectal adenocarcinoma. Descriptive analyses were used to assess the study results of the amount of chromogranin A, synaptophysin, and sample characteristics. RESULTS: We discovered that eight (8) samples (11.4%) were NEN from 70 previously diagnosed samples as high-grade colorectal adenocarcinoma using immunohistochemical assay with neuroendocrine markers, namely chromogranin A and synaptophysin. CONCLUSION: The final diagnosis obtained from 8 samples diagnosed as NEN were Neuroendocrine tumor (NET) G1, G2, and G3, respectively 1.4% and LCNEC 7.1% based on the specific neuroendocrine markers of chromogranin A, synaptophysin and Ki67.

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Clinical Routine Application of the Second-generation Neuroendocrine Markers ISL1, INSM1, and Secretagogin in Neuroendocrine Neoplasia: Staining Outcomes and Potential Clues for Determining Tumor Origin

Endocrine Pathology ◽

10.1007/s12022-020-09645-y ◽

2020 ◽

Vol 31 (4) ◽

pp. 401-410

Author(s):

Carl Christofer Juhlin ◽

Jan Zedenius ◽

Anders Höög

Keyword(s):

Second Generation ◽

Neuroendocrine Differentiation ◽

Diagnostic Process ◽

Neuroendocrine Neoplasms ◽

Clinical Routine ◽

Who Grade ◽

Primary Tumors ◽

Tissue Specific ◽

Neuroendocrine Markers ◽

Immunohistochemical Markers

AbstractNeuroendocrine neoplasms (NENs) have traditionally been identified via expression of proteins associated to the regulation of secretory vesicles and granules. We report the clinical usage of the “second-generation” proteins ISL LIM homeobox 1 (ISL1), INSM transcriptional repressor 1 (INSM1), and secretagogin (SECG) as immunohistochemical markers of neuroendocrine differentiation since their introduction in clinical routine and compare the results with the established proteins chromogranin A (CGA) and synaptophysin (SYP). In total, 161 tumors, including 139 NENs and 22 “non-NENs” (unrelated tumors with an initial suspicion of NEN), were informatively stained for ISL1, and subsets were also interrogated for INSM1 and/or SECG. Diffuse or focal positive immunoreactivity was noted for ISL1 in 91/139 NENs (65%) and in 6/22 (27%) non-NENs, for INSM1 in 76/85 NENs (89%) and in 2/5 (40%) non-NENs, and for SECG in 49 out of 64 NENs (77%) and in 0/5 non-NENs (0%). Generally, ISL1, INSM1, and SECG exhibited sensitivities in line with or slightly below that of CGA and SYP—largely attributable to tissue-specific patterns regarding tumoral origin. Moreover, for pancreatic and small intestinal NENs, the two largest subgroups, ISL1 staining results were consistent irrespectively of tumor source and WHO grade. We verify previously suggested immunohistochemical schemes of neuroendocrine markers of first- and second-generations to facilitate the diagnostic process for NENs and confirm that the second-generation neuroendocrine markers display tissue-specific patterns. We therefore recommend their implementation in tertiary endocrine pathology centers, not least to aid in the identification of primary tumors when analyzing metastases.

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INSM1 Is a Highly Specific Marker of Neuroendocrine Differentiation in Primary Neoplasms of the Gastrointestinal Tract, Appendix, and Pancreas

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa014 ◽

2020 ◽

Vol 153 (6) ◽

pp. 811-820 ◽

Cited By ~ 6

Author(s):

Kelsey E McHugh ◽

Sanjay Mukhopadhyay ◽

Erika E Doxtader ◽

Christopher Lanigan ◽

Daniela S Allende

Keyword(s):

Goblet Cell ◽

Neuroendocrine Differentiation ◽

Neuroendocrine Neoplasms ◽

Specific Marker ◽

Low Grade ◽

Ki 67 ◽

Neuroendocrine Markers ◽

Primary Neoplasms ◽

Poorly Differentiated ◽

Well Differentiated

Abstract Objectives INSM1 has been described as a sensitive and specific neuroendocrine marker. This study aims to compare INSM1 with traditional neuroendocrine markers in gastrointestinal neuroendocrine neoplasms. Methods Retrospective review (2008-2018) was used to retrieve paraffin-embedded tissue from 110 gastrointestinal neuroendocrine neoplasms and controls that was subsequently stained with INSM1, synaptophysin, chromogranin, CD56, and Ki-67. Results INSM1 was positive in 16 of 17 (94.1%) gastric, 17 of 18 (94.4%) pancreatic, 13 of 18 (72.2%) small bowel, 17 of 21 (81.0%) colonic, and 26 of 36 (72.2%) appendiceal tumors. INSM1 was positive in 58 of 70 (82.9%) well-differentiated neuroendocrine tumors, 17 of 20 (85.0%) poorly differentiated neuroendocrine carcinomas, 8 of 11 (72.7%) low-grade goblet cell adenocarcinomas (grade 1), and 6 of 9 (66.7%) high-grade goblet cell adenocarcinomas (grade 2/3). INSM1 sensitivity for neuroendocrine neoplasms (80.9%) was less than that of synaptophysin (99.1%), chromogranin (88%), and CD56 (95.3%); specificity was higher (95.7% vs 86.0%, 87.3%, and 86.0%, respectively). Conclusions INSM1 is a useful marker of neuroendocrine differentiation in gastrointestinal neuroendocrine and mixed neuroendocrine neoplasms. Compared with traditional neuroendocrine markers, INSM1 is less sensitive but more specific.

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