Fig. 3.

Histomorphologic and immunohistochemical features of lung neuroendocrine carcinomas. LCNEC features organoid aggregates with peripheral palisading and plentiful mitoses (a), but even SCLC-like appearance (b). LCNEC is usually positive for INSM1 (c), while retinoblastoma nuclear decoration is often missing (d). SCLC is composed of small-sized tumor cells with prominent nuclear molding, inconspicuous nucleoli, and abundant necrosis (e), but spindling of neoplastic cells may be on record (f). Synaptophysin is largely retained in this case (g), along with INSM1 labeling (h), while chromogranin A is usually reduced to negative (g, inset), just like does retinoblastoma that is consistently unreactive (h, inset). Differential diagnosis between carcinoids (i) and SCLC (j) may be demanding upon morphology in cytology samples, but Ki-67 staining helps to operate such a separation confidently showing low expression in carcinoid (i, inset) and high expression in SCLC (j inset). Note that distinction of typical and atypical carcinoids rests on mitotic count and/or punctate necrosis, while neuroendocrine carcinomas are especially distinguished according to cell size appreciation.