scholarly journals Tissue Is the Issue - A Case of Malignant Insulinoma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1042-A1042
Author(s):  
Tania Arous ◽  
Sara Gianfagna ◽  
Jaydira Del Rivero ◽  
Inga Harbuz-Miller
Keyword(s):  
Neuroendocrine Tumors ◽  
Neuroendocrine Carcinoma ◽  
Metastatic Disease ◽  
The Body ◽  
Pancreatic Neuroendocrine Tumors ◽  
Inherited Disorders ◽  
Left Ankle ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Platinum Based Chemotherapy ◽  
Well Differentiated

Abstract Introduction: Insulinomas are rare, functioning pancreatic neuroendocrine tumors, predominantly benign (90%). Most are sporadic, but they can occur as part of inherited disorders. Large size insulinomas are more likely to be malignant. 68Gallium (Ga)-DOTATATE scan is an essential tool in diagnosis and treatment of pancreatic neuroendocrine tumors. However, tissue diagnosis is the ultimate prognosis predictor and treatment guide. Clinical Case: An 80-year-old man presented with left ankle fracture after a syncopal episode. In the past several months he reported multiple episodes of lightheadedness. He denied history of diabetes. Past medical and surgical history included prostate cancer, gastroesophageal reflux disease and bilateral orchiectomy for undescended testes. His left ankle appeared swollen, otherwise the exam was unremarkable: he was well-nourished, the abdomen was soft and nontender, there were no palpable masses. He was noted to have several episodes of hypoglycemia. Hypoglycemia work up included negative sulfonylurea screen, plasma glucose 51 mg/dl (60-99 mg/dl), insulin of 31 uIU/ml (3-25 uIU/ml), proinsulin 85.4 pmol/L (<8 pmol/L), C peptide 3.4 ng/ml (1.1-4.4 ng/ml). Abdominal Computed Tomography with contrast showed a 4.7 x 3.1 cm exophytic mass in the body of pancreas, a 5.3 x 5 cm mass in the head of pancreas and multiple ill-defined hepatic lesions concerning for metastatic disease. 68Ga-DOTATATE scan revealed an avid pancreatic mass and multiple avid foci throughout the liver suspicious for metastatic disease. Octreotide and intravenous dextrose were started for the treatment of persistent hypoglycemia. He underwent Whipple procedure and resection of the metastatic liver lesions. Postoperatively hypoglycemia resolved. The pathology revealed large cell pancreatic neuroendocrine carcinoma with areas of well differentiated tumor and multiple liver metastatic neuroendocrine carcinoma, Ki-67 of 50-80% was reported in the primary tumor and metastatic lesions. Discussion: Metastatic insulinomas carry a significant morbidity and mortality risk. Surgical resection to decrease tumor burden can reduce the risk of hypoglycemia. Histopathology is essential in treatment decision making. Surprisingly our patient’s pathology revealed poorly differentiated neuroendocrine carcinoma, changing the prognosis and treatment. Treatment with platinum-based chemotherapy and etoposide is the standard of care for aggressive neuroendocrine neoplasms. Despite hypoglycemia resolution following surgery and good DOTATATE uptake by the well differentiated neuroendocrine tumor portion, our patient’s prognosis remained poor in view of the high-grade carcinoma. Due to complicated hospital course, and decreased functional status patient was not a candidate for chemotherapy immediately post hospital discharge.

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.

Neuroendocrine Tumors of the Rectum: A 10-Year Review of Management

2011 ◽  
Vol 77 (2) ◽  
pp. 198-200 ◽  
Author(s):  
Jason R. Moore ◽  
Brian Greenwell ◽  
Kaylee Nuckolls ◽  
David Schammel ◽  
Nicholas Schisler ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Local Excision ◽  
Neuroendocrine Carcinoma ◽  
Residual Disease ◽  
Muscularis Propria ◽  
Positive Margins ◽  
Pathologic Evaluation ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated ◽  
Well Differentiated

Neuroendocrine tumors of the rectum constitute ∼19 per cent of gastrointestinal neuroendocrine tumors (NETs). The histologic characteristics of the tumor seem to be an indicative prognostic factor. Optimal treatment of NETS of the rectum has been widely debated, but more recent studies suggest that treatment depends upon the size. The medical records of 37 patients with NETS of the rectum were retrospectively reviewed. We reviewed their presentation, surgical treatment, pathology, and outcome. All pathological specimens were reviewed. Neuroendocrine tumors of the rectum were classified as either well-differentiated tumors, well-differentiated neuroendocrine carcinoma, or poorly differentiated neuroendocrine carcinoma. Evaluating tumor size, we found 35/37 patients had tumors less than 1 cm, 1 patient had a tumor between 1 and 2 cm, and one had a tumor greater than 2 cm. Pathologic evaluation of the tumors revealed that 35 of the tumors invaded the submucosa only, one invaded the muscularis propria, and one invaded the perirectal adipose tissue. The histopathologic features of the tumors revealed that 34 of the tumors were well-differentiated NETS with benign features, one tumor had invaded the submucosa, with angioinvasion, and two tumors were neuroendocrine carcinoma. Thirty-five patients underwent local excision. Eleven had reexcisions for positive margins. Two patients had local excision for recurrence, and one patient underwent low anterior resection (4 cm). Twelve patients had negative margins, 25 had positive margins. Eleven patients underwent reexcision. Six had no evidence of residual disease, and five had persistent positive margins and were offered no further treatment. Nineteen patients had positive margins and did not have reexcision. They all had tumors < 1 cm. Despite half of the lesions being resected with final pathologic positive margins, we have seen no significant influence on recurrence or overall survival. This raises the question of margin clearance in early lesions.

scholarly journals FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

2021 ◽  
Author(s):  
Jane E. Rogers ◽  
Michael Lam ◽  
Daniel M. Halperin ◽  
Cecile G. Dagohoy ◽  
James C. Yao ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Prior Therapy ◽  
Well Differentiated ◽  
Grade 3 ◽  
Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

scholarly journals Poorly Differentiated Small-Cell-Type Neuroendocrine Carcinoma of the Prostate: A Case Report and Literature Review

2018 ◽  
Vol 11 (3) ◽  
pp. 676-681 ◽  
Author(s):  
Kishore Kumar ◽  
Rafeeq Ahmed ◽  
Chime Chukwunonso ◽  
Hassan Tariq ◽  
Masooma Niazi ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Tumor Grade ◽  
Small Cell ◽  
The Body ◽  
Neuroendocrine Cells ◽  
Cell Type ◽  
Variable Response ◽  
Ki 67 ◽  
Platinum Based Chemotherapy ◽  
Poorly Differentiated

Neuroendocrine cells are widespread throughout the body and can give rise of neuroendocrine tumors due to abnormal growth of the chromaffin cells. Neuroendocrine tumors divide into many subtypes based on tumor grade (Ki-67 index and mitotic count) and differentiation. These tumors can be further divided into secretory and nonsecretory types based on the production of peptide hormone by tumor cells. Poorly differentiated small-cell-type neuroendocrine tumors are one of the subtypes of neuroendocrine tumors. These tumors are less common; however, they tend to be locally invasive and aggressive in behavior with poor overall median survival. Treatment of the nonsecretory small-cell type is modeled to small-cell lung cancer with a regimen consisting of platinum-based chemotherapy and etoposide with variable response. Here, we present a case of poorly differentiated small-cell neuroendocrine tumor originating from the prostate.

Erratum to: KI-67 heterogeneity in well differentiated gastro-entero-pancreatic neuroendocrine tumors: when is biopsy reliable for grade assessment?

Endocrine ◽  
2017 ◽  
Vol 57 (3) ◽  
pp. 503-503
Author(s):  
Federica Grillo ◽  
Luca Valle ◽  
Diego Ferone ◽  
Manuela Albertelli ◽  
Maria Pia Brisigotti ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Well Differentiated ◽  
Grade Assessment

scholarly journals Expression of the phosphorylated variant of the AKT1-kinase (p-AKT1) in well-differentiated pancreatic neuroendocrine tumors: immunohistochemical evaluation

2018 ◽  
Vol 46 (4) ◽  
pp. 314-322
Author(s):  
V. V. Delektorskaya ◽  
O. N. Solov'eva ◽  
G. Yu. Chemeris ◽  
Yu. I. Patyutko
Keyword(s):  
Liver Metastases ◽  
Neuroendocrine Tumors ◽  
Treatment Effectiveness ◽  
Disease Free Survival ◽  
Immunohistochemical Analysis ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
New Treatment ◽  
Well Differentiated ◽  
High Level

Background:Well-differentiated pancreatic neuroendocrine tumors (pNETs) represent a group of rare epithelial neoplasms with a highly variable clinical course. AKT1 is one of the most frequently activated protein kinases in pNETs, which promotes the tumor growth and is of interest as a prognostic factor and a target for new treatment approaches.Aim:To study the expression of the phosphorylated variant of AKT1-kinase (p-AKT1) in primary pNETs and their liver metastases and to correlate the results with various clinical and pathological parameters and the disease prognosis.Materials and methods:P-AKT1 expression was studied by the immunohistochemical analysis of the primary lesions and liver metastases in 52 pNETs patients.Results:A high level of cytoplasmic and/or nuclear immunoreactivity was detected in 24/52 of the primary pNETs (46.2%) and in 16/27 of their liver metastases (59.3%). p-AKT1 expression was observed in 3 (21.4%) of NET grade (G) 1, in 14 (46.7%) of NET G2, and in 7 (87.5%) of NET G3. p-AKT1 expression was more frequently identified in pNET G3 category and increased during the tumor progression in metachronous liver metastases, as compared to the corresponding primary tumor. In addition, p-AKT1 positivity was significantly associated with an increase of grade from G1 to G3 (p = 0.004), the Ki-67 index (p = 0.029), the pTNM stage (p = 0.0008), perineural invasion (p = 0.031) and a decrease in disease-free survival (p = 0.05).Conclusion:The results suggest that p-АКТ1 plays an important role in the pathogenesis of pNETs and may be an additional criterion for assessment of the prognosis and treatment effectiveness in this type of tumors.

scholarly journals Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors

Oncogenesis ◽  
2021 ◽  
Vol 10 (12) ◽  
Author(s):  
Angela M. Carter ◽  
Nilesh Kumar ◽  
Brendon Herring ◽  
Chunfeng Tan ◽  
Rachael Guenter ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Islet Cells ◽  
Tumor Development ◽  
Heterogeneous Population ◽  
Targeted Therapeutics ◽  
Pancreatic Neuroendocrine Tumors ◽  
The Past ◽  
Regulated Expression ◽  
Well Differentiated ◽  
Conditional Mouse Model

AbstractPancreatic neuroendocrine tumors (PanNETs) are a heterogeneous population of neoplasms that arise from hormone-secreting islet cells of the pancreas and have increased markedly in incidence over the past four decades. Non-functional PanNETs, which occur more frequently than hormone-secreting tumors, are often not diagnosed until later stages of tumor development and have poorer prognoses. Development of successful therapeutics for PanNETs has been slow, partially due to a lack of diverse animal models for pre-clinical testing. Here, we report development of an inducible, conditional mouse model of PanNETs by using a bi-transgenic system for regulated expression of the aberrant activator of Cdk5, p25, specifically in β-islet cells. This model produces a heterogeneous population of PanNETs that includes a subgroup of well-differentiated, non-functional tumors. Production of these tumors demonstrates the causative potential of aberrantly active Cdk5 for generation of PanNETs. Further, we show that human PanNETs express Cdk5 pathway components, are dependent on Cdk5 for growth, and share genetic and transcriptional overlap with the INS-p25OE model. The utility of this model is enhanced by the ability to form tumor-derived allografts. This new model of PanNETs will facilitate molecular delineation of Cdk5-dependent PanNETs and the development of new targeted therapeutics.

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