A growing body of literature has identified distinct subgroups within neuroendocrine carcinomas of the lung. POU2F3, a tuft cell marker, is best described in small cell lung carcinoma, but is noted to be expressed in between 12–20% of large cell neuroendocrine carcinomas as well as a smaller proportion of squamous cell carcinomas of lung origin and thymic tumours. 1 Importantly, POU2F3-expressing neuroendocrine carcinomas of both small and large cell morphology show decreased expression of neuroendocrine markers by immunohistochemistry 2 and can show nonstandard morphology. 3 We describe a path to diagnosis of a case of POU2F3-associated large cell neuroendocrine carcinoma, through initial biopsy to resection. Awareness of the nonstandard morphologic and immunohistochemical features is critical in detecting this emerging subtype, to ensure patients receive effective treatment.
Hilliard et al. (Sun,) studied this question.