Identification of prognostic immunophenotypic features in cancer stromal cells of high-grade neuroendocrine carcinomas of the lung

Neuroendocrine carcinomas (NEC) are rare tumors with a rising incidence. They show poorly differentiated morphology with a high proliferation rate (Ki-67 index). They frequently arise in the lung (small and large-cell lung cancer) but rarely from the gastrointestinal tract. Due to their rarity, very little is known about digestive NEC and few studies have been conducted. Therefore, most of therapeutic recommendations are issued from work on small-cell lung cancers (SCLC). Recent improvement in pathology and imaging has allowed for better detection and classification of high-grade NEN. The 2019 World Health Organization (WHO) classification has described a new entity of well-differentiated grade 3 neuroendocrine tumors (NET G-3), with better prognosis, that should be managed separately from NEC. NEC are aggressive neoplasms often diagnosed at a metastatic state. In the localized setting, surgery can be performed in selected patients followed by adjuvant platinum-based chemotherapy. Concurrent chemoradiotherapy is also an option for NEC of the lung, rectum, and esophagus. In metastatic NEC, chemotherapy is administered with a classic combination of platinum salts and etoposide in the first-line setting. Peptide receptor radionuclide therapy (PRRT) has shown positive results in high-grade NEN populations and immunotherapy trials are still ongoing. Available therapies have improved the overall survival of NEC but there is still an urgent need for improvement. This narrative review sums up the current data on digestive NEC while exploring future directions for their management.

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A subset of high-grade pulmonary neuroendocrine carcinomas shows up-regulation of matrix metalloproteinase-7 associated with nuclear β-catenin immunoreactivity, independent of EGFR and HER-2 gene amplification or expression

Virchows Archiv ◽

10.1007/s00428-005-0044-x ◽

2005 ◽

Vol 447 (6) ◽

pp. 969-977 ◽

Cited By ~ 10

Author(s):

Giuseppe Pelosi ◽

Aldo Scarpa ◽

Giulia Veronesi ◽

Lorenzo Spaggiari ◽

Barbara Del Curto ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Gene Amplification ◽

High Grade ◽

Matrix Metalloproteinase 7 ◽

Her 2 ◽

Neuroendocrine Carcinomas

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CDX2 Is a Useful Marker of Intestinal-Type Differentiation: A Tissue Microarray–Based Study of 629 Tumors From Various Sites

Archives of Pathology & Laboratory Medicine ◽

10.5858/2005-129-1100-ciaumo ◽

2005 ◽

Vol 129 (9) ◽

pp. 1100-1105 ◽

Cited By ~ 7

Author(s):

Lindsey B. De Lott ◽

Carl Morrison ◽

Saul Suster ◽

David E. Cohn ◽

Wendy L. Frankel

Keyword(s):

Squamous Cell ◽

Signet Ring Cell ◽

Squamous Cell Carcinomas ◽

Intestinal Type ◽

High Grade ◽

Poorly Differentiated Neuroendocrine Carcinoma ◽

Poorly Differentiated ◽

Lung Adenocarcinomas ◽

Colorectal Adenocarcinomas ◽

Neuroendocrine Carcinomas

Abstract Context.—CDX2, a critical nuclear transcription factor for intestinal development, is expressed in intestinal epithelium and adenocarcinomas. Objectives.—To determine if CDX2 is a useful marker for intestinal-type differentiation and to correlate tumor histology with CDX2 staining in colorectal adenocarcinomas. Design.—Tissue microarrays from 71 colorectal adenocarcinomas, 31 hepatocellular carcinomas, 47 lung adenocarcinomas, 55 squamous cell carcinomas of the lung, 69 neuroendocrine carcinomas of the lung and 43 of the pancreas, 57 pancreatic adenocarcinomas, and 256 endometrial adenocarcinomas were stained with antibody against CDX2. Results.—CDX2 staining was positive in 51 (71.8%) of 71 colorectal cancers, including 38 (74.5%) of 51 well- or moderately differentiated tumors and 13 (65.0%) of 20 high-grade tumors. Of the high-grade tumors, 5 (71.4%) of 7 mucinous, 3 (100%) of 3 signet ring cell, and 5 (50.0%) of 10 poorly differentiated tumors were positive. Other tumors showing occasional CDX2 staining included 1 of 30 well- or moderately differentiated neuroendocrine carcinomas of the lung and 2 of 43 from the pancreas, 1 of 47 lung adenocarcinomas, 3 of 57 pancreatic adenocarcinomas, and 15 of 256 endometrial carcinomas. Hepatocellular, poorly differentiated neuroendocrine carcinoma of the lung and squamous cell carcinomas of the lung were not immunoreactive for CDX2. Conclusions.—CDX2 is a useful marker for intestinal-type differentiation, is rarely seen in tumors from the other sites evaluated, and may be useful in determining the site of origin for some metastatic tumors. However, CDX2 is not a sensitive marker for poorly differentiated colorectal carcinoma.

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Esophageal neuroendocrine carcinoma presenting as a rare cause of dysphagia

Case Reports in Internal Medicine ◽

10.5430/crim.v5n2p1 ◽

2018 ◽

Vol 5 (2) ◽

pp. 1

Author(s):

Sylvester Luu ◽

Brian C. Benson ◽

Kelly A. Haeusler ◽

Robert O. Brady ◽

Katherine M. Cebe ◽

...

Keyword(s):

Radiation Therapy ◽

Neuroendocrine Carcinoma ◽

Poor Prognosis ◽

Gastroesophageal Junction ◽

Prior History ◽

High Grade ◽

Active Smoking ◽

Platinum Based Chemotherapy ◽

History Of ◽

Neuroendocrine Carcinomas

A 60-year-old male with prior history of laryngeal carcinoma and active smoking presented with six months of solid food dysphagia. Endoscopy showed a large, friable gastroesophageal junction mass. Biopsies revealed a high-grade, poorlydifferentiated neuroendocrine carcinoma. He was subsequently started on platinum based chemotherapy and radiation therapy and his tumor decreased dramatically in size. This case is unique as neuroendocrine carcinomas (NECs) are rarely found in the esophagus and usually have a poor prognosis at time of diagnosis.

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