Neuroendocrine neoplasms of the lung: The latest updates

Table 1 Histologic, immunohistochemical and cytological features of lung neuroendocrine neoplasms

	Typical carcinoid	Atypical carcinoid	Carcinoid with high mitotic/proliferation index	LCNEC	SCLC
Definition	Well-differentiated neuroendocrine morphology, no necrosis, mitotic index < 2 mitoses/2 mm2	Well-differentiated neuroendocrine morphology, necrosis (punctate) and/or mitotic index 2-10 mitoses/2 mm2	Well-differentiated morphology, mitotic index > 10 mitoses/2 mm2 and/or Ki-67 > 30%	High-grade NSCLC with neuroendocrine morphology, cytology (prominent nucleoli and/or moderate to abundant cytoplasm) and a mitotic count of > 10 mitoses/2 mm2	Small cells (usually less than the size of 3 resting lymphocytes) with scant cytoplasm, granular nuclear chromatin with absent or inconspicuous nucleoli and > 10 mitoses/2 mm2
Cytology
Cell size	Variable	Variable	Variable	Large	Small (less than 3 resting lymphocytes)
Nuclear chromatin	Finely granular texture (salt and pepper)	Finely granular texture (salt and pepper)	Finely granular texture (salt and pepper)	Coarse to vesicular	Finely granular texture, evenly distributed
Nucleoli	Occasional, small	Common, small	Common, small	Common, large	Absent or inconspicuous
Cytoplasm	Variable	Variable	Variable	Abundant	Scarce
Histology
Morphology	Organoid, trabecular, rosette formation, nested, insular	Organoid, trabecular, rosette formation, nested, insular	Organoid, trabecular, rosette formation, nested, insular	Organoid, trabecular, palisading	Sheet-like, diffuse
Mitotic count/2 mm2	0-1	2-10	> 10	> 10 (50-60)	> 10 (70-80)
Proliferation index (Ki-67)	< 10%	10%-25%	> 30%	25%-80%	70%-100%
Necrosis	Absent	Focal, punctate	Focal, punctate	Extensive	Geographic
IHC
Synpatophysin	+++	+++	+++	+++	+/-
CgA	+++	++	+	+	+/-
INSM1	+++	+++	+++	+++	+++
RB1	WT	WT	WT	WT/lost	Lost
P53	WT	WT	WT	Aberrant	Aberrant

LCNEC: Large cell neuroendocrine cancer; SCLC: Small cell lung cancer; NSCLC: Non-small cell lung cancer; IHC: Immunohistochemical; CgA: Chromogranin A; INSM1: Insulinoma-associated protein 1; WT: Wilms tumor. Adapted from[13]. Citation: Vocino Trucco G, Righi L, Volante M, Papotti M. Updates on lung neuroendocrine neoplasm classification. Histopathology 2024; 84: 67-85. Copyrights© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.