Small Biopsy and Cytology of Pulmonary Neuroendocrine Neoplasms: Brief Overview of Classification, Immunohistochemistry, Molecular Profiles, and World Health Organization Updates

Abstract

Pulmonary neuroendocrine neoplasms comprise ~20% of all lung tumors. Typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma represent the 4 major distinct subtypes recognized on resections. This review provides a brief overview of the cytomorphologic features and the 2021 World Health Organization classification of these tumor types on small biopsy and cytology specimens. Also discussed are the role of immunohistochemistry in the diagnosis and molecular signatures of pulmonary neuroendocrine tumors.

Top IHC/ISH Hacks for and Molecular Surrogates of Poorly Differentiated Sinonasal Small Round Cell Tumors

“…There is an ongoing effort to apply and validate novel lung small-cell (SCLC) molecular subtyping and biomarker-driven therapy for SNEC. According to RNA expression with validation at the protein levels of the transcription factors ASCL1 , NEUROD1 , POU2F3, and YAP1 , four SCLC subtypes have emerged: SCLC-A (ASCL1-driven), SCLC-N (NEUROD1-driven), SCLC-P (ASCL1/NEUROD1-double negative with POU2F3 expression), and SCLC-Y (YAP1-related and NOS) and SCLC-I (inflamed gene signature), which share the last subtype [65 – 69] . SCLC-Is exhibit the greatest response to the addition of immunotherapy to chemotherapy, while the other subtypes each have distinct vulnerabilities, including to inhibitors of PARP, Aurora kinases, or BCL-2 [68] .…”