Large Cell Neuroendocrine Carcinoma (LCNEC) vs Atypical Carcinoid: LCNEC has larger foci of necrosis (usually) and greater mitotic activity (> 10 mitoses/2 sq.mm; average of 75 mitoses/2 sq.mm) than atypical carcinoid. LCNEC vs Small Cell Lung Carcinoma (SCLC): The distinction is made on H&E-stained slides. LCNEC has large cell size, more abundant pink cytoplasm, low nuclear-to-cytoplasmic ratio, vesicular, coarse, or clumped nuclear chromatin, and usually prominent nucleoli. SCLC has small cell size (less than 3 times the diameter of small resting lymphocytes), scant cytoplasm, finely granular chromatin, and inconspicuous/absent nucleoli. LCNEC vs Adenocarcinoma, Basaloid Squamous Cell Carcinoma & Other Non-small Cell Carcinomas: Adenocarcinomas and basaloid squamous cell carcinoma of the lung generally lack neuroendocrine differentiation. Basaloid squamous cell carcinoma is positive for p40 and CK5/6 and negative for TTF-1. Other tumors that enter into the differential diagnosis of LCNEC include metastases from endometrium, ovary, pancreas, breast, prostate, and colon. The image shows LCNEC under bronchial epithelium.