scholarly journals INSM1 Expression in Breast Neoplasms with Neuroedocrine Features

2021 ◽  
Author(s):  
Jasna Metovic ◽  
Isabella Castellano ◽  
Eleonora Marinelli ◽  
Simona Osella-Abate ◽  
Anna Sapino ◽  
...  
Keyword(s):  
Chromogranin A ◽  
Mixed Type ◽  
Breast Tumors ◽  
Negative Control ◽  
Neuroendocrine Neoplasms ◽  
Breast Cancers ◽  
Pathological Characteristics ◽  
Poorly Differentiated ◽  
Well Differentiated

AbstractAccording to the 2019 WHO classification of breast tumors, neuroendocrine neoplasms (NENs) are classified into well-differentiated NE tumors (NET) and poorly differentiated NE carcinomas (NEC), while other breast cancers (BCs) of special and no special type with neuroendocrine (NE) features are not incorporated in this scheme anymore. We aimed to assess whether INSM1, a novel NE marker, could have a role in breast NEN subtyping. We selected 63 BCs operated from 2003 to 2018, classified as BCs with NE features, with available clinico-pathological data. Following 2019 WHO criteria, this cohort was reclassified into 37 NETs/NECs, the remaining 26 tumors representing solid-papillary (7), mucinous (7), and mixed type (12) carcinomas with NE differentiation. Chromogranin A (CGA) and synaptophysin (SYN) immunostains were reviewed, and INSM1 was tested by immunohistochemistry. Thirty CGA- and SYN-negative no special type BCs served as negative control. INSM1 was expressed in 52/63 cases of the whole cohort (82.54%). INSM1 positive and negative cases had no significantly different clinico-pathological characteristics. INSM1 expression was not significantly different between the newly reclassified NET/NEC group and other BCs with NE features. No immunoexpression was observed in control BCs. The sensitivity and specificity of INSM1 for the NE phenotype was 82.5% and 100%, respectively, compared to 61.9% and 100% for CGA, and 95.2 and 100% for SYN. In conclusion, INSM1 is as accurate as traditional NE biomarkers to identify NE differentiation in BC. In analogy to standard NE markers, INSM1 could not distinguish NET and NEC from the other BC histotypes with NE differentiation.

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.

Intestinal-Type Adenocarcinoma of the Sinonasal Tract: A Clinicopathologic Study of 18 Cases

1993 ◽  
Vol 79 (3) ◽  
pp. 205-210 ◽  
Author(s):  
Carmelo Urso ◽  
Maria Benedetta Ninu ◽  
Alessandro Franchi ◽  
Milena Paglierani ◽  
Roberto Bondi
Keyword(s):  
Intestinal Type ◽  
Presenting Symptoms ◽  
Clinicopathologic Study ◽  
Clinicopathologic Findings ◽  
Poorly Differentiated ◽  
Intestinal Type Adenocarcinoma ◽  
Aggressive Tumors ◽  
Well Differentiated ◽  
Colonic Adenocarcinomas

Background Intestinal-type adenocarcinoma (ITAC) of the nose and paranasal sinuses is a relatively rare tumor. It commonly affects subjects exposed to wood or leather dust. Methods The authors present the clinicopathologic findings of 18 cases of sinonasal ITACs and review the proposed histologic classifications. Results All patients, except one, were males; mean age was 60 years (range, 41-79); in 9 cases an occupational exposure to wood or leather dust was found. Common presenting symptoms were epistaxis, nasal obstruction and rhinorrhea. Histologically, tumors were divided into four groups: well-differentiated (G1) ITACs = 3 cases; moderately differentiated (G2) ITACs = 8 cases; poorly differentiated (G3) ITACs = 2 cases; mucinous (M) ITACs = 5 cases. Immunocytochemically, 16/17 cases were positive for carcinoembryonal antigen, 1/17 for somatostatin, and 0/16 cases for gastrin. Conclusions Sinonasal ITACs are aggressive tumors, often diagnosed in a relatively advanced stage. Owing the close similarity of the microscopic aspects, a histologic classification of ITACs analogous to that of colonic adenocarcinomas is proposed.

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

2020 ◽  
Vol 153 (6) ◽  
pp. 811-820 ◽  
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.

scholarly journals Co-existence of gastric adenocarcinoma and neuroendocrine carcinoma: a rare entity

2017 ◽  
Vol 7 (2) ◽  
pp. 1221-1223 ◽  
Author(s):  
Nirajan Mainali ◽  
Niraj Nepal ◽  
Prabesh Kumar Choudhary ◽  
Amrita Sinha ◽  
Saroj Rajbanshi ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Partial Gastrectomy ◽  
Endoscopic Biopsy ◽  
World Health ◽  
Neuroendocrine Neoplasms ◽  
World Health Organization Classification ◽  
Well Differentiated ◽  
Health Organization ◽  
Histopathology Examination

A mixed adenoneuroendocrine carcinoma is a tumor composed of both adenocarcinoma and neuroendocrine carcinoma components, with each comprising  at least one-third of the lesion, as defined by the World Health Organization classification of neuroendocrine neoplasms in 2010.. A 67-years-old male was admitted to the hospital with symptoms suggesting gastric cancer. Histopathology examination from endoscopic biopsy revealed adenocarcinoma. Later partial gastrectomy specimen examination the lesion show presence of well differentiated adenocarcinoma along with neuro endocrine carcinoma.

Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms

2011 ◽  
Vol 18 (S1) ◽  
pp. S1-S16 ◽  
Author(s):  
Günter Klöppel
Keyword(s):  
Gastrointestinal Tract ◽  
Neuroendocrine Tumours ◽  
Neuroendocrine Tumour ◽  
Tnm Stage ◽  
Neuroendocrine Neoplasms ◽  
Gastroenteropancreatic Neuroendocrine Neoplasms ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Neuroendocrine Carcinomas

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are composed of cells with a neuroendocrine phenotype. The old and the new WHO classifications distinguish between well-differentiated and poorly differentiated neoplasms. All well-differentiated neoplasms, regardless of whether they behave benignly or develop metastases, will be called neuroendocrine tumours (NETs), and graded G1 (Ki67 <2%) or G2 (Ki67 2–20%). All poorly differentiated neoplasms will be termed neuroendocrine carcinomas (NECs) and graded G3 (Ki67 >20%). To stratify the GEP-NETs and GEP-NECs regarding their prognosis, they are now further classified according to TNM-stage systems that were recently proposed by the European Neuroendocrine Tumour Society (ENETS) and the AJCC/UICC. In the light of these criteria the pathology and biology of the various NETs and NECs of the gastrointestinal tract (including the oesophagus) and the pancreas are reviewed.

scholarly journals Label-free classification of colon cancer grading using infrared spectral histopathology

2016 ◽  
Vol 187 ◽  
pp. 105-118 ◽  
Author(s):  
C. Kuepper ◽  
F. Großerueschkamp ◽  
A. Kallenbach-Thieltges ◽  
A. Mosig ◽  
A. Tannapfel ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Label Free ◽  
Infrared Spectral ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Free Classification ◽  
Cancer Grading ◽  
Spectral Histopathology ◽  
Good Agreement

In recent years spectral histopathology (SHP) has been established as a label-free method to identify cancer within tissue. Herein, this approach is extended. It is not only used to identify tumour tissue with a sensitivity of 94% and a specificity of 100%, but in addition the tumour grading is determined. Grading is a measure of how much the tumour cells differ from the healthy cells. The grading ranges from G1 (well-differentiated), to G2 (moderately differentiated), G3 (poorly differentiated) and in rare cases to G4 (anaplastic). The grading is prognostic and is needed for the therapeutic decision of the clinician. The presented results show good agreement between the annotation by SHP and by pathologists. A correlation matrix is presented, and the results show that SHP provides prognostic values in colon cancer, which are obtained in a label-free and automated manner. It might become an important automated diagnostic tool at the bedside in precision medicine.

scholarly journals Pancreatic Neuroendocrine Neoplasms: Landscape and Horizon

2020 ◽  
Vol 144 (7) ◽  
pp. 816-828
Author(s):  
Laura H. Tang
Keyword(s):  
Neuroendocrine Neoplasms ◽  
Specific Gene ◽  
Important Distinction ◽  
Pancreatic Neuroendocrine Neoplasms ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Initial Description ◽  
Definition Of ◽  
Hereditary Conditions

Context.— Since the initial description of pancreatic endocrine physiology and the recognition of islet cell tumors in the 1800s, there have been noteworthy advances in the pathobiology of pancreatic neuroendocrine neoplasms (PanNENs), and definition of the important distinction between well-differentiated neuroendocrine tumor (PanNET) and poorly differentiated neuroendocrine carcinoma (PanNEC). The evolving knowledge has resulted in a continuous update in terminology, classification, and grading system for this group of neoplasms. Pancreatic neuroendocrine tumors associated with hereditary conditions have been linked to unique molecular and genetic events, and sporadic PanNETs have specific gene signatures. Based on accumulative experience and knowledge, therapeutic strategies have been defined for this group of neoplasms. Objective.— To review the evolution and description of the pathologic-genomic evolution of PanNENs, and to facilitate accurate pathologic interpretation for the corresponding clinical management. Data Sources.— Literature review of published studies and author's own work. Conclusions.— Evolving experience and knowledge have established subtypes of pancreatic neuroendocrine neoplasms, based on their genotype and phenotype. Accurate pathologic interpretation of the specific neoplasm has significant implications for therapy and prognosis.

Clinicopathological characteristics of subsequent breast cancers in patients with benign breast disease

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1061-1061
Author(s):  
R. Santana-Davila ◽  
D. W. Visscher ◽  
C. M. Vachon ◽  
M. Frost ◽  
R. A. Vierkant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Benign Breast Disease ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Breast Disease ◽  
Low Grade ◽  
Breast Cancers ◽  
Poorly Differentiated ◽  
Well Differentiated

1061 Background: Benign breast disease (BBD) is a significant risk factor for breast cancer (BC); however little is known about the aggressiveness of the BCs these patients develop. Shared features between select atypias and low-grade DCIS have led some to speculate that a history of BBD portends the development of well-differentiated BCs. Methods: The Mayo BBD cohort includes 9,376 women who had benign breast biopsies from 1967–1991. Data on BC events were obtained from medical records and questionnaires. Tissue from the BCs was reviewed by a single breast pathologist (DWV). Results: Our cohort included 6,244 patients with nonproliferative disease (NP), 2,801 women with proliferative disease without atypia (PDWA), and 331 with atypical hyperplasias (AH). With a median of 18 years of follow-up, 799 patients with BBD have developed breast cancer, 416 initially had NP, 313 had PDWA, and 70 AH. BC tissue was available for 703 of the women. The cancers were invasive ductal in 76.1% (n = 535), invasive lobular in 9.4% (n = 66), and DCIS alone in 14.5% (n = 102) patients. Grade is currently available for 500 women, and is well differentiated in 29.4% (n = 150), moderately differentiated in 42.7% (n = 218) and poorly differentiated in 27.8% (n = 142). In 537 cases the malignant tissue had a concurrent benign component consisting of NP in 24% (n = 129), PDWA in 25.1% (n = 135), and AH in 50.8% (n = 273). In regards to tumor size, 69.6% had T1 tumors, 24.9% T2 tumors, and 5.5% T3 disease. Metastasis to lymph nodes occurred in 25% of patients. Median time to BC was 12.3 years and did not differ across the different benign entities. Breast cancer developed within 5 years from the initial BBD in 163 women (20%). In this group, tumor size was greater (p = 0.02), and there were more poorly differentiated tumors (p = 0.006) than in those who later developed BC. Conclusions: In the BCs that have developed in our BBD cohort, we do not see a preponderance of well-differentiated, good-risk BCs. Patients diagnosed within 5 years of BBD appear to have BCs with more aggressive features. No significant financial relationships to disclose.

Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index > 20%

2018 ◽  
Vol 108 (2) ◽  
pp. 109-120 ◽  
Author(s):  
Atsuko Kasajima ◽  
Björn Konukiewitz ◽  
Naomi Oka ◽  
Hiroyoshi Suzuki ◽  
Akira Sakurada ◽  
...  
Keyword(s):  
Survival Rates ◽  
Disease Free Survival ◽  
Japanese Patients ◽  
Clinicopathological Parameters ◽  
Neuroendocrine Neoplasms ◽  
Free Survival ◽  
Tumor Group ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Disease Free

The clinicopathological features of lung neuroendocrine neoplasms (NEN) with a high proliferative index at the border area between atypical carcinoid and neuroendocrine carcinoma have not been investigated so far. The aim of this study was, therefore, to search for lung NENs which are well differentiated but show Ki67 values that overlap with those of poorly differentiated (PD)-NENs. Resected lung NENs from 244 Japanese patients were reviewed, and Ki67 indices were assessed in all tumors. The data were then correlated to clinicopathological parameters and patient outcome. Among 59 (24%) well-differentiated (WD)-NENs and 185 (76%) lung PD-NENs, 7 were defined as WD-NENs with Ki67 indices > 20%. The Ki67 indices of these tumors (mean 29%, range 24–36) were significantly lower than those of PD-NENs (mean 74%, range 34–99). All WD-NENs with Ki67 > 20% lacked abnormal p53 and loss of retinoblastoma 1 (Rb1) expression. In contrast, many PD-NENs expressed p53 (48%) and showed loss of Rb1 (86%). The 2- and 5-year disease-free survival rates in WD-NEN patients with Ki67 > 20% were lower than those of WD-NEN patients with Ki67 ≤20% (p < 0.01 for disease-free and overall survival). No statistical differences were detected between outcome of WD-NEN patients with Ki67 > 20% and those of PD-NEN. It is concluded that WD-NEN patients with Ki67 > 20% share the morphological and immunohistochemical features of WD-NEN patients with Ki67 ≤20%, but they have a worse prognosis, suggesting that this tumor group requires particular attention in future classifications and probably new therapeutic regimes.

Gastric neuroendocrine neoplasms and related precursor lesions

2014 ◽  
Vol 67 (11) ◽  
pp. 938-948 ◽  
Author(s):  
Stefano La Rosa ◽  
Alessandro Vanoli
Keyword(s):  
Neuroendocrine Tumours ◽  
Wide Spectrum ◽  
Clinicopathological Features ◽  
Neuroendocrine Neoplasms ◽  
Precursor Lesions ◽  
Comprehensive Overview ◽  
Ecl Cell ◽  
Poorly Differentiated ◽  
Neuroendocrine Carcinomas

Gastric neuroendocrine neoplasms (NENs) are a heterogeneous group of tumours showing different clinicopathological features and behaviour, implying a wide spectrum of therapeutic options. They are currently classified using the 2010 WHO classification of digestive neuroendocrine neoplasms into G1-neuroendocrine tumours (NETs), G2-NETs, neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs). However, most gastric NENs are composed of ECL-cells (ECL-cell NETs) that can be preceded by ECL-cell hyperplastic and dysplastic lesions, whose oncologic potential has not yet been completely elucidated. ECL-cell NETs differ considerably in terms of prognosis depending on the proliferative status and clinicopathological background. The integration of both aspects in the diagnostic pathway may help to better classify tumours in different prognostic categories, especially when diagnosing them in small bioptic specimens. NECs are all poorly differentiated, highly aggressive carcinomas, while MANECs can show different morphological features that are directly associated with different prognoses. Precursor lesions of such carcinomas are not entirely understood. In this review, the clinicopathological features of gastric NENs and related precursor lesions will be described to give the reader a comprehensive overview on this topic.

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