scholarly journals Second-Generation Neuroendocrine Immunohistochemical Markers: Reflections from Clinical Implementation

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 874
Author(s):  
Carl Christofer Juhlin
Keyword(s):  
Neuroendocrine Tumors ◽  
Second Generation ◽  
Neuroendocrine Differentiation ◽  
Clinical Experiences ◽  
Clinical Implementation ◽  
Immunohistochemical Markers ◽  
Metastatic Lesions ◽  
Poorly Differentiated ◽  
Focal Expression ◽  
Neuroendocrine Carcinomas

When analyzing tumors by histopathology, endocrine pathologists have traditionally been restricted to a few key immunohistochemical markers related to secretory vesicles in order to pinpoint neuroendocrine differentiation—most notably Chromogranin A (CGA) and Synaptophysin (SYP). Although proven of great clinical utility, these markers sometimes exhibit tissue-specific patterns depending on tumor origin, and non-neuroendocrine tumors might sometimes display focal expression. Moreover, CGA and SYP might be partially or totally absent in highly proliferative neuroendocrine carcinomas, making the diagnosis particularly challenging on small biopsies of metastatic lesions with unknown location of the primary tumor. The advent of second-generation neuroendocrine markers ISL LIM Homeobox 1 (ISL1), INSM Transcriptional Repressor 1 (INSM1) and Secretagogin (SECG) have expanded the pathology toolbox considerably, constituting markers that often retain expression even in poorly differentiated neuroendocrine carcinomas. As non-neuroendocrine tumors seldom express these antigens, the specificity of ISL1, INSM1 and SECG make them welcome additions to clinical practice. In this commentary, recent advances of this field as well as initial clinical experiences from a tertiary neuroendocrine center are discussed.

scholarly journals 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

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.

Pulmonary Neuroendocrine Carcinomas

2002 ◽  
Vol 126 (5) ◽  
pp. 545-553 ◽  
Author(s):  
Qin Huang ◽  
Alona Muzitansky ◽  
Eugene J. Mark
Keyword(s):  
Neuroendocrine Tumors ◽  
Neuroendocrine Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
The Body ◽  
Low Grade ◽  
Typical Carcinoid ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated ◽  
Neuroendocrine Carcinomas

Abstract Context.—Primary pulmonary neuroendocrine tumors are traditionally classified into 3 major types: typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LC) or small cell neuroendocrine carcinoma (SC). Confusion arises frequently regarding the malignant nature of TC and the morphologic differentiation between AC and LC or SC. Objective.—To provide clinicopathologic evidence to streamline and clarify the histomorphologic criteria for this group of tumors, emphasizing the prognostic implications. Patients.—To minimize variability in diagnostic criteria and treatment plans, we analyzed a group of patients whose diagnosis and treatment occurred at a single institution. We reviewed 234 cases of primary pulmonary neuroendocrine tumors and thoroughly studied 50 cases of resected tumors from 1986 to 1995. Results.—On the basis of morphologic characteristics and biologic behaviors of the tumors, we agree with many previous investigators that these tumors are all malignant and potentially aggressive. Based on our accumulated data, we have modified Gould criteria and reclassified these tumors into 5 types: (1) well-differentiated neuroendocrine carcinoma (otherwise called TC) (14 cases, with less than 1 mitosis per 10 high-power fields [HPF] with or without minimal necrosis); (2) moderately differentiated neuroendocrine carcinoma (otherwise called low-grade AC) (6 cases, with less than 10 mitoses per 10 HPF and necrosis evident at high magnification); (3) poorly differentiated neuroendocrine carcinoma (otherwise called high-grade AC) (10 cases, with more than 10 mitoses per 10 HPF and necrosis evident at low-power magnification); (4) undifferentiated LC (5 cases, with more than 30 mitoses per 10 HPF and marked necrosis); and (5) undifferentiated SC (15 cases, with more than 30 mitoses per 10 HPF and marked necrosis). The 5-year survival rates were 93%, 83%, 70%, 60%, and 40% for well, moderately, and poorly differentiated, and undifferentiated large cell and small cell neuroendocrine carcinomas, respectively. We found nodal metastasis in 28% of TC in this retrospective review, a figure higher than previously recorded. Conclusion.—Using a grading system and terms comparable to those used for many years and used for neuroendocrine tumors elsewhere in the body, we found that classification of pulmonary neuroendocrine carcinomas as well, moderately, poorly differentiated, or undifferentiated provides prognostic information and avoids misleading terms and concepts. This facilitates communication between pathologists and clinicians and thereby improves diagnosis and management of the patient.

scholarly journals Multimodal Management of Grade 1 and 2 Pancreatic Neuroendocrine Tumors

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 433
Author(s):  
Ugo Marchese ◽  
Martin Gaillard ◽  
Anna Pellat ◽  
Stylianos Tzedakis ◽  
Einas Abou Ali ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Postoperative Morbidity ◽  
Current Data ◽  
Pancreatic Neuroendocrine Tumors ◽  
Tips And Tricks ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Multimodal Management ◽  
Neuroendocrine Carcinomas

Pancreatic neuroendocrine tumors (p-NETs) are rare tumors with a recent growing incidence. In the 2017 WHO classification, p-NETs are classified into well-differentiated (i.e., p-NETs grade 1 to 3) and poorly differentiated neuroendocrine carcinomas (i.e., p-NECs). P-NETs G1 and G2 are often non-functioning tumors, of which the prognosis depends on the metastatic status. In the localized setting, p-NETs should be surgically managed, as no benefit for adjuvant chemotherapy has been demonstrated. Parenchymal sparing resection, including both duodenum and pancreas, are safe procedures in selected patients with reduced endocrine and exocrine long-term dysfunction. When the p-NET is benign or borderline malignant, this surgical option is associated with low rates of severe postoperative morbidity and in-hospital mortality. This narrative review offers comments, tips, and tricks from reviewing the available literature on these different options in order to clarify their indications. We also sum up the overall current data on p-NETs G1 and G2 management.

scholarly journals Neuroendocrine neoplasms of the pancreas: diagnosis and pitfalls

2021 ◽  
Author(s):  
Björn Konukiewitz ◽  
Moritz Jesinghaus ◽  
Atsuko Kasajima ◽  
Günter Klöppel
Keyword(s):  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Molecular Profile ◽  
Neuroendocrine Neoplasms ◽  
Histological Differentiation ◽  
Pancreatic Neuroendocrine Neoplasms ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Diagnostic Pitfalls ◽  
Neuroendocrine Carcinomas

AbstractCommon to neuroendocrine neoplasms of the pancreas is their expression of synaptophysin, chromogranin A, and/or INSM1. They differ, however, in their histological differentiation and molecular profile. Three groups can be distinguished: well-differentiated neuroendocrine neoplasms (neuroendocrine tumors), poorly differentiated neuroendocrine neoplasms (neuroendocrine carcinomas), and mixed neuroendocrine-non-neuroendocrine neoplasms. However, the expression of synaptophysin and, to a lesser extent, also chromogranin A is not restricted to the neuroendocrine neoplasms, but may also be in a subset of non-neuroendocrine epithelial and non-epithelial neoplasms. This review provides the essential criteria for the diagnosis of pancreatic neuroendocrine neoplasms including diagnostic clues for the distinction of high-grade neuroendocrine tumors from neuroendocrine carcinomas and an algorithm avoiding diagnostic pitfalls in the delineation of non-neuroendocrine neoplasms with neuroendocrine features from pancreatic neuroendocrine neoplasms.

scholarly journals Bilateral Neuroendocrine Carcinoma of Breast: A Case Report

2021 ◽  
Vol 59 (244) ◽  
pp. 1320-1322
Author(s):  
Sulochana Neupane ◽  
Sanam Dhakal ◽  
Shripad Walawalakar ◽  
Surya Bahadur Parajuli ◽  
Sulav Sapkota
Keyword(s):  
Ductal Carcinoma ◽  
Neuroendocrine Differentiation ◽  
Radical Mastectomy ◽  
Left Breast ◽  
Breast Cancers ◽  
Breast Carcinomas ◽  
Breast Lump ◽  
History Of ◽  
Poorly Differentiated ◽  
Neuroendocrine Carcinomas

Primary neuroendocrine carcinomas of the breast are rare of all breast carcinomas. They may be welldifferentiated, poorly differentiated, or invasive breast cancers with neuroendocrine differentiation. They are staged and treated similarly to conventional breast cancer. Herein, we report a case of invasive ductal carcinoma with neuroendocrine differentiation of the breast in a 73 years female with a history of breast lump initially in the lower inner quadrant of left breast and a month later, similar lump at the same site in right breast. Patient underwent Modified Radical Mastectomy bilaterally followed by adjuvant chemotherapy based on Carboplatin and Etoposide regimen.

scholarly journals Neuroendocrine Tumors of the Breast

2017 ◽  
Vol 141 (11) ◽  
pp. 1577-1581 ◽  
Author(s):  
Lauren Elizabeth Rosen ◽  
Paolo Gattuso
Keyword(s):  
Differential Diagnosis ◽  
Breast Carcinoma ◽  
Neuroendocrine Tumors ◽  
Neuroendocrine Differentiation ◽  
Small Cell ◽  
Breast Carcinomas ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Invasive Breast Carcinomas ◽  
Metastatic Neuroendocrine Tumor

Primary neuroendocrine tumors of the breast are a rare and underrecognized subtype of mammary carcinoma. Neuroendocrine tumors of the breast occur predominately in postmenopausal women. The tumors are subclassified into well-differentiated and poorly differentiated neuroendocrine tumors, and invasive breast carcinoma with neuroendocrine features. Well-differentiated tumors show architectural similarity to carcinoids of other sites but lack characteristic neuroendocrine nuclei. Poorly differentiated neuroendocrine tumors are morphologically identical to small cell carcinoma of the lung. Neuroendocrine differentiation, seen in up to 30% of invasive breast carcinomas, is most commonly associated with mucinous and solid papillary carcinomas. The diagnosis of neuroendocrine differentiation requires expression of the neuroendocrine markers synaptophysin or chromogranin. The main differential diagnosis is a metastatic neuroendocrine tumor from an extramammary site. Neuroendocrine tumors of the breast are treated similarly to other invasive breast carcinomas. Although no consensus has been reached on the prognosis, most studies suggest a poor outcome.

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