Lung neuroendocrine neoplasms: recent progress and persistent challenges

Abstract

This review summarizes key recent developments relevant to the pathologic diagnosis of lung neuroendocrine neoplasms, including carcinoids, small cell lung carcinoma (SCLC), and large cell neuroendocrine carcinoma (LCNEC). Covered are recent insights into the biological subtypes within each main tumor type, progress in pathological diagnosis and immunohistochemical markers, and persistent challenging areas. Highlighted topics include highly proliferative carcinoids and their distinction from small cell and large cell neuroendocrine carcinomas (NECs), the evolving role of Ki67, the update on the differential diagnosis of NEC to include thoracic SMARCA4-deficient undifferentiated tumors, the recent data on SCLC transcriptional subtypes with the emergence of POU2F3 as a novel marker for the diagnosis of SCLC with low/negative expression of standard neuroendocrine markers, and the update on the diagnosis of LCNEC, particularly in biopsies. There has been remarkable recent progress in the understanding of the genetic and expression-based profiles within each type of lung neuroendocrine neoplasm, and it is hoped that these insights will enable the development of novel diagnostic, prognostic, and predictive biomarkers to aid in the pathologic assessment of these tumors in the future.

Pleomorphic Carcinoid: A Pitfall in Diagnosis on Small Biopsy Specimens

“…Neuroendocrine neoplasms account for approximately 20% of lung tumors, with 2% consisting of typical and atypical carcinoids that encompass the low-grade NETs. 1 Typical carcinoids or NETs are generally straightforward to diagnose, consisting of bland, uniform, round cells with neuroendocrine architecture and chromatin with no associated mitoses or necrosis. 2 Neuroendocrine atypia, which is often emphasized in other neuroendocrine entities, is not usually described in typical carcinoid cases.…”

CT Texture Analysis of Pulmonary Neuroendocrine Tumors—Associations with Tumor Grading and Proliferation

“…Traditional markers for neuroendocrine tumors comprise synaptophysin, chromogranin A, and CD56 (NCAM1). Another interesting marker is insulinoma-associated protein 1 (INSM1), which reflects true neuroendocrine differentiation [ 31 ]. For future studies, it would be of interest, whether these histopathological parameters could also be reflected by quantitative imaging analysis, including the biological heterogeneity of pNET [ 32 ].…”

Bronchial Carcinoids: From Molecular Background to Treatment Approach

“…Lung NETs encompass four histologic subtypes whose terminology and defining criteria have been endorsed over the last three classifications by the World Health Organization (WHO). This classification differentiates TCs, ACs, LCNEC, and SCLC [22,23]. The diagnosis of these four different types of lung NETs is mainly based on the mitotic count per 2 mm 2 , the presence of necrosis, and a wide constellation of cellular and architectural features fulfilling NET morphology [24].…”