Extrapulmonary neuroendocrine small and large cell carcinomas: a review of controversial diagnostic and therapeutic issues

Abstract

Summary Extrapulmonary neuroendocrine carcinoma (EPNEC) is a heterogeneous and rare group of high-grade neoplasms occurring in different organs. They usually share a poor prognosis, but diagnostic and therapeutic options still include several controversial issues, due to the rarity of this condition and to differences in architecture and cell size, being some cases pure small cell carcinomas, other pure large cell neuroendocrine carcinomas and some others combined/mixed neuroendocrine carcinomas with a conventional non-neuroendocrine carcinoma. In addition, the therapeutic strategy varies in different organs (surgery and/or chemotherapy and/or radiation therapy and/or targeted treatments), and clinicians and pathologists are asked to interact to reach an accurate classification of every single case, as well as the most appropriate selection of the treatment options, even considering different time points of each EPNEC natural history. This overview highlights controversial pathological and clinical issues and summarizes possible solutions to most of such EPNEC-related problems.

Mixed Adenoneuroendocrine Carcinomas of the Gastrointestinal Tract: Targeted Next-Generation Sequencing Suggests a Monoclonal Origin of the Two Components

“…MANEC histogenetic definition represents a current controversial issue among pathologists [1,2,4,5,6,7,8]. Two main theories have been formulated: (a) these tumors might arise independently in a synchronous or metachronous fashion, or (b) they might derive from a common, multipotent stem/progenitor cell.…”

Neuroendocrine Tumors of the Kidney: A Single Institution Experience

“…They are frequently associated with horseshoe kidney (2). Poorly-differentiated NET such as small cell carcinomas most often originate in the urinary bladder, prostate, or gastrointestinal tract (3, 4), but these high-grade neoplasms can arise in virtually any organ, either de novo or through transformation of a lower grade tumor. Extrapulmonary small cell carcinoma accounts for 2.5-5% of all small cell carcinomas, and approximately 1000 new cases are diagnosed every year in the Unites States (5).…”

Neuroendocrine carcinomas: Cytological mimics and diagnostic dilemmas

“…Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms ranging from low to high grade and from well to poorly differentiated entities . They show varying grades of histo‐morphology depending upon the primary organ of involvement . The significant differences in classification and grading of neuroendocrine tumours are commonly present between the lung and rest of the extra‐pulmonary sites.…”

“…In most other sites, the neuroendocrine tumours are classified into three grades, whereas, the pulmonary tumours have a different set of terms and classification, including carcinoid, atypical carcinoid, large cell carcinoma, large cell neuroendocrine carcinoma and small cell neuroendocrine carcinoma . The extra‐pulmonary neuroendocrine carcinomas are aggressive . In general terms, neuroendocrine carcinomas (NECs) denote tumours of higher grade, with high mitotic activity and poor differentiation …”