The Spectrum of Neuroendocrine Differentiation Among Gastrointestinal Carcinoids

2000 ◽  
Vol 124 (4) ◽  
pp. 570-576
Author(s):  
Terence N. Moyana ◽  
Jim Xiang ◽  
A. Senthilselvan ◽  
Andrew Kulaga
Keyword(s):  
Statistical Significance ◽  
Tertiary Care ◽  
Neuroendocrine Differentiation ◽  
Prognostic Indicators ◽  
Histologic Grading ◽  
Metastatic Behavior ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Degree Of Association ◽  
Mib 1

Abstract Context.—The advent of panneuroendocrine markers has helped to better depict the heterogeneity of gastrointestinal carcinoids. Consequently, it has been proposed that these tumors constitute a histologic spectrum that includes well-, moderately, and poorly differentiated carcinoids. However, the reproducibility of this grading system and its prognostic importance have sometimes been called into question. Objective.—To investigate the potential utility of cell proliferation and oncoprotein markers in augmenting the histologic classification. Design and Setting.—Retrospective study; tertiary care teaching hospital. Methods.—Fifty-eight patients with 41 well-differentiated, 12 moderately differentiated and 5 poorly differentiated carcinoids from various topographic sites of the gastrointestinal tract were selected and immunostained for panneuroendocrine markers, MIB-1, p53, and bcl-2. Main Outcome Measures.—Degree of association between histologic grading, MIB-1, p53, and bcl-2 immunoreactivity and carcinoid metastatic behavior. Results.—The group comprised 30 males and 28 females whose mean age was 52.7 years (range, 14–81). Mean follow-up time was 85.8 months. All 58 patients tested positive for chromogranin A and/or synaptophysin. The group was divided into nonmetastatic (42/58, or 72.4%) and metastatic (16/58, or 27.6%) cases. Histologic grading tended to be associated with metastatic spread, but this occurrence of metastases did not attain statistical significance (P = .08). Positivity for MIB-1 (P = .004) and p53 (P = .04) was significantly associated with metastatic behavior, whereas bcl-2 was not (P = 0.63). Conclusions.—Although an organoid pattern and neuroendocrine immunophenotype help to define the spectrum of gastrotestinal carcinoids, this study suggests that the histologic grading of these tumors has some limitations with respect to predicting metastatic behavior. However, MIB-1 and p53 can compliment histologic grading as prognostic indicators in this regard while bcl-2 appears to be less useful.

Dedifferentiated Liposarcoma With a Paraganglioma-like Histologic Pattern: A Case Report and Review of the Literature

2004 ◽  
Vol 128 (7) ◽  
pp. 788-791
Author(s):  
Dating Liu ◽  
Guillermo Quinonez ◽  
Steven Latosinsky
Keyword(s):  
Neuron Specific Enolase ◽  
Malignant Neoplasm ◽  
Neuroendocrine Differentiation ◽  
Growth Patterns ◽  
Dedifferentiated Liposarcoma ◽  
Tissue Mass ◽  
Histologic Pattern ◽  
History Of ◽  
Poorly Differentiated ◽  
Well Differentiated

Abstract A 53-year-old man presented with a 4-month history of increasing abdominal discomfort and distension. A large retroperitoneal mass was found on imaging. Image-guided needle core biopsy demonstrated a poorly differentiated malignant neoplasm. A 30 × 32 × 33-cm soft tissue mass was removed. Microscopically, the tumor consisted of predominantly epithelioid malignant cells arranged in a paraganglioma-like growth pattern. Immunohistochemically, these cells were strongly positive for neuron-specific enolase. Stains for synaptophysin and chromogranin, however, were negative. There was no ultrastructural evidence of neuroendocrine differentiation. Adjacent sarcomatous areas were composed of spindled cells arranged in storiform and fibrosarcoma-like growth patterns. A small area of well-differentiated liposarcoma was identified, and a diagnosis of dedifferentiated liposarcoma was established. To the best of our knowledge, this represents the first reported case of dedifferentiated liposarcoma with a paraganglioma-like histologic pattern. A brief review focusing on the morphologic variations of dedifferentiated liposarcoma is also presented.

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.

Mediastinoscopy: The Predictive Survival Value in Staging Carcinoma of the Lung

1978 ◽  
Vol 87 (4) ◽  
pp. 544-550 ◽  
Author(s):  
Louis W. Welsh ◽  
John J. Welsh
Keyword(s):  
Lung Cancer ◽  
Behavior Pattern ◽  
Diagnostic Procedures ◽  
World Health ◽  
Average Life Span ◽  
Metastatic Behavior ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Diagnosis Of Lung Cancer ◽  
Health Organization

One hundred and thirty-seven cases of Stage III lung cancer established by mediastinoscopy have been followed to determine their survival. The tissue was classified according to World Health Organization schema and the degree of dedifferentiation graded from well to poorly differentiated. Two percent of the presented cases are well-differentiated tumors; the remaining 98% are moderately well-differentiated (11%), or poorly differentiated or small cell tumors (87%). The degree of anaplasia suggests an increasingly aggressive metastatic behavior pattern. The average life span is approximately 5 1/2 months in all groups and subgroups which were studied. Recommendations are presented for the utilization of mediastinoscopy in Stage I and II cases. Further considerations are suggested for priority of diagnostic procedures in establishing the diagnosis of lung cancer.

Νεοαγγείωση καρκίνου παχέος εντέρου

2002 ◽  
Author(s):  
Πέτρος Παυλόπουλος
Keyword(s):  
Shape Factor ◽  
Malignant Tumors ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Morphometric Parameters ◽  
Critical Event ◽  
Prognostic Information ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Axis Length

Background: Neovascularization reportedly is correlated with metastasis, recurrence, and prognosis in many types of solid tumors. Microvessel quantification in so-called "hot spots" has been studied extensively as the only factor reflecting angiogenesis in various malignant tumors. The objective of this study was to evaluate multiple morphometric microvascular characteristics in addition to microvessel density (MVD) in colorectal carcinomas to provide a better approach to examining the relation between angiogenesis and clinicopathologic factors and prognosis. Methods: Histologic sections from 106 colorectal adenocarcinomas and 17 adenomas, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, total vascular area (TVA), and microvascular branching, as well as several morphometric parameters related to the vessel size (area, major axis length, minor axis length, perimeter, Feret diameter), shape (compactness, shape factor) or immunostaining intensity (proportion of intensely stained areas in relation to the total immunostained surface). Of the 123 cases investigated, 103 finally were evaluable in the statistical analysis, responding to the criteria of a high quality image depiction. Results: Carcinomas presented higher counts of microvessels compared to adenomas. MVD appeared to decrease with increasing Dukes stage. Carcinomas of lower Dukes stages (A and B) had a higher mean MVD than those of advanced stages (C and D). Although the difference did not reach statistical significance, well-differentiated neoplasms had lower MVD values than poorly differentiated ones. MVD was significantly correlated with the shape factor and compactness. All the morphometric parameters related to the size of microvessels had lower values in the group of adenomas. These parameters where significantly increased with progressing Dukes stage. Carcinomas with a higher histological differentiation had a significantly reduced TVA as compared to tumors with moderate or poor differentiation. Well-differentiated tumors had significantly lower values of shape factor and higher values of compactness in relation to poorly differentiated neoplasms. The vascular branching counts were significantly higher in carcinomas than in adenomas, and remained unaffected through progressing Dukes stages. Adenomas presented a more intense immunoreaction to FVIII as compared to carcinomas. Branching counts and TVA were the only factors of prognostic significance. Conclusions: This study provides evidence that neovascularization is an early critical event in colorectal tumorigenesis, reaching a maximum level early in the malignant process. Its prognostic significance is better assessed by quantification of TVA and the branching pattern of microvessels, whereas MVD does not provide significant prognostic information for colorectal carcinoma patients.

scholarly journals Role of EGFR and HER-2/NEU Expression in Gall Bladder Carcinoma

2021 ◽  
Author(s):  
Chhanda Das ◽  
Madhumita Mukhopadhyay ◽  
Srijana Subba ◽  
Ashis Kumar Saha ◽  
Biswanath Mukhopadhyay
Keyword(s):  
Gall Bladder ◽  
Bladder Carcinoma ◽  
Tertiary Care ◽  
Molecular Therapy ◽  
Tumor Type ◽  
Care Hospital ◽  
Gall Bladder Carcinoma ◽  
Poorly Differentiated ◽  
Her 2 ◽  
Well Differentiated

Abstract Background Gall bladder carcinoma (GBC) is the most common malignancy of the biliary tract. Being known for its geographical and racial variations, and compared with the global statistics, its incidence is higher in the Indian subcontinent, mainly in the northern and eastern regions, accounting for 80 to 95% of cases. Aims and Objectives This study was conducted to evaluate the clinic-pathological spectrum and expression of EGFR and HER-2/NEU in GBCs and to understand their relation to prognosis, paving the way for targeted therapies for better treatment outcomes and patient survival. Materials and Methods This is a prospective study performed in a tertiary care hospital in 30 resected specimens of GBC cases recorded in our Department of Pathology from November 2017 to November 2019. Clinical history including the radiological reports and demographic parameters were included in the study pro forma. Immunohistochemical (IHC) staining for EGFR and HER-2/NEU was performed on all the selected cases. Clinicopathologic parameters like age, sex, histologic type, perineural, and lymphovascular invasion were compared and correlated with EGFR and HER-2/NEU status. Results Expression of EGFR was found in 93.33% of cases, which showed a highly significant correlation with histological tumor type (p = 0.000). HER-2/NEU expression was found in 56.66% of cases, which also showed a significant correlation with histological tumour type (p = 0.021). We found most of the cases with strong EGFR immunoreactivity (3+) were poorly differentiated tumors and most of the cases showing weak immunoreactivity for EGFR (1+) were well-differentiated. Conversely, in case of HER-2/NEU immunoreactivity, strong staining (3+) was seen in well-differentiated tumors and weak staining (1+) in poorly differentiated tumors. A significant correlation was also found between EGFR and HER-2/NEU expression (p = 0.000) and between cholelithiasis and EGFR expression (p = 0.033). Conclusion EGFR is expressed in most cases of GBC. Its expression is more in poorly differentiated carcinomas as compared to the well-differentiated carcinomas, whereas HER-2/NEU expression is more in well-differentiated carcinomas. Therefore, they may serve as independent prognostic factors and also as targets for molecular therapy in GBCs.

Preoperative CEA and TAG-72 Serum Levels as Prognostic Indicators in Resectable Gastric Carcinoma

1996 ◽  
Vol 11 (3) ◽  
pp. 165-171 ◽  
Author(s):  
A. González ◽  
F. Vizoso ◽  
M.T. Allende ◽  
M.T. Sánchez ◽  
J.L. Balibrea ◽  
...  
Keyword(s):  
Overall Survival ◽  
Gastric Carcinoma ◽  
Serum Levels ◽  
Stage I ◽  
Stage Ii ◽  
Prognostic Indicators ◽  
Survival Duration ◽  
Preoperative Serum ◽  
Poorly Differentiated ◽  
Well Differentiated

We evaluated in 74 patients with resectable primary gastric carcinoma, the prognostic value of the preoperative circulating serum levels of CEA and TAG-72. Serum levels of CEA were above the cutoff level of 6 ng/ml in 18.9% of patients; TAG-72 levels were higher than 6 U/ml in 31% of patients. Pretreatment mean CEA levels were significantly lower (p<0.01) in patients with stage I tumors (2.9 ± 0.3 ng/ml) than in those with more advanced tumors (stage II: 14.5 ± 6.8 ng/ml; stage HI-TV: 6.8 ± 1.5 ng/ml). Similarly, significant differences in mean TAG-72 serum levels were found between stage I (3.5 ± 1.8 U/ml) and stage II and stage III-IV (30.4 ± 20.7 U/ml and 26.1 ± 9.7 U/ml, respectively) (p<0.05). In addition, TAG-72 levels were also higher in poorly differentiated and moderately differentiated tumors (38.5 ± 20.1 U/ml and 23.1 ± 9.4 U/ml, respectively) than in well differentiated tumors (4.4 ± 0.9 U/ml) (p<0.05). The results further indicated that high preoperative serum levels of CEA predicted shorter relapse-free survival duration (p<0.01), and that high TAG-72 levels were associated with shorter relapse-free and overall survival (p < 0.0001 and p < 0.0005, respectively). In addition, separate Cox multivariate analysis showed that preoperative TAG-72 was, after stage, the strongest factor to predict both relapse-free and overall survival (p < 0.0001 and p < 0.005, respectively) in patients with gastric cancer.

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.

Motility of leukemic lymphocytes

1990 ◽  
Vol 48 (3) ◽  
pp. 368-369
Author(s):  
Manoj Raje ◽  
Karvita B. Ahluwalia
Keyword(s):  
Quantitative Data ◽  
Laser Doppler Velocimetry ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Cellular Space ◽  
Differentiated Cells ◽  
Poorly Differentiated ◽  
Solid Tissues ◽  
Well Differentiated ◽  
Reduced Mobility

In Acute Lymphocytic Leukemia motility of lymphocytes is associated with dissemination of malignancy and establishment of metastatic foci. Normal and leukemic lymphocytes in circulation reach solid tissues where due to in adequate perfusion some cells get trapped among tissue spaces. Although normal lymphocytes reenter into circulation leukemic lymphocytes are thought to remain entrapped owing to reduced mobility and form secondary metastasis. Cell surface, transmembrane interactions, cytoskeleton and level of cell differentiation are implicated in lymphocyte mobility. An attempt has been made to correlate ultrastructural information with quantitative data obtained by Laser Doppler Velocimetry (LDV). TEM of normal & leukemic lymphocytes revealed heterogeneity in cell populations ranging from well differentiated (Fig. 1) to poorly differentiated cells (Fig. 2). Unlike other cells, surface extensions in differentiated lymphocytes appear to originate by extrusion of large vesicles in to extra cellular space (Fig. 3). This results in persistent unevenness on lymphocyte surface which occurs due to a phenomenon different from that producing surface extensions in other cells.

HER2 OVEREXPRESSION IN ENDOSCOPIC BIOPSY SAMPLE OF GASTRIC ADENOCARCINOMA BY IMMUNOHISTOCHEMISTRY

2012 ◽  
pp. 109-118
Author(s):  
Viet Nho Le ◽  
Van Huy Tran ◽  
Cong Thuan Dang ◽  
Van To Ta
Keyword(s):  
Gastric Adenocarcinoma ◽  
Undifferentiated Carcinoma ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Endoscopic Biopsy ◽  
Her2 Overexpression ◽  
Tubular Adenocarcinoma ◽  
Signet Ring ◽  
Poorly Differentiated ◽  
Well Differentiated

Background and aim: HER2 overexpression by immunohistochemistry is a prognostic maker in gastric cancer and helps to select candidates benefitted from targeted therapy with trastuzumab. This study is aimed at the assessing HER2 overexpression and its relationship with endoscopic and histopathological findings of gastric adenocarcinoma. Objectives and methods: Biopsy samples from 92 gastric cancer patients were examined for HER2 status by immunohistochemical staining. Results: 6.5% of tumors were cardia tumors and 93.5% were non-cardia tumors. Using the Lauren classification, 51.1% were intestinal type and 48.9% were diffuse type. Using WHO classification, 54.3% were tubular adenocarcinoma, 7.6% were mucinous adenocarcinoma, 15.2% were signet-ring cell carcinoma, and 22.8% were undifferentiated carcinoma. 32.6% were well-differentiated, 15.2% were moderately-differentiated, and 52.2% were poorly-differentiated carcinoma. HER2 was positive in 20.7% of gastric carcinomas, 50% cardia tumors and 18.6% non-cardia tumors. HER2 positivity among polypoid, fungating, ulcerated, and infiltrative types were 38.5%, 29.7%, 9.1% and 0%, respectively. HER2 overexpression in intestinal type was higher than that in diffuse type (31.9% vs. 8.9%, p = 0.009). HER2 overexpression in tubular adenocarcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, and undifferentiated carcinoma was 28.0%, 14.3%, 7.1% and 14.3%, respectively. HER2 overexpressions were different between differentiation degrees: 30% of well-differentiated tumors, 35.7% moderately-differentiated tumors, and 10.4% of poorly-differentiated tumors (p = 0.037). Conclusions: HER2 overexpression was found in 20.7% of endoscopic biopsy sample of gastric adenocarcinoma and was associated with endoscopic gross characteristic, Lauren histologic type and differentiation degree.

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