Major criteria:
(1) poorly-differentiated non-small cell lung carcinoma with no evidence of acinar or squamous differentiation
(2) Ki-67 labeling index > 40%
(3) presence of one or more neuroendocrine markers (synaptophysin, chromogranin A, NCAM)
The tumor cells should show:
(1) a nucleus larger than the size of 3 small resting lymphocytes
(2) relatively abundant cytoplasm
(3) fine nuclear chromatin
(4) prominent nucleoli
Minor criteria:
(1) frequent massive necrosis
(2) intercellular clefts (spaces) and/or discohesiveness
(3) neuroendocrine growth pattern (rosettes, trabecular, peripheral palisading, organoid nesting)
Frequent mitoses may also be present.