Subtypes of small cell carcinoma of the lung: morphometric, ultrastructural, and immunohistochemical analyses

Fifty-three surgically resected small cell carcinomas of the lung were studied morphometrically, electron microscopically, immunohistochemically, and in terms of possible site of origin. Four subtypes of small cell carcinomas were identified: oat cell carcinoma (OAT), small cell carcinoma of the intermediate cell type (INT), combined oat cell carcinoma, and undifferentiated carcinoma of the small cell type (UCS). The latter type is presumed to be non-neuroendocrine. Morphometric analysis showed considerable overlap among OAT, INT, and UCS with respect to nuclear area, cell area, and nuclear/cytoplasmic ratio. Ultrastructurally, significantly more carcinomas categorized as OAT and INT contained neurosecretory granules than did those in the UCS category (P less than 0.01 and 0.05, respectively). Cells with tonofibrils were more frequent in UCSs than in OATs and INTs. Immunohistochemically, fewer UCSs than OATs contained cells with gastrin-releasing peptide, neuron-specific enolase, and Leu-7 (P = 0.5, P less than 0.05, and P less than 0.05, respectively). UCSs were located more frequently at the periphery of the lung than were OATs (P less than 0.01) and INTs (P = 0.06). These findings suggest that UCS may be a pathologic entity distinct from the typical neuroendocrine-type small cell carcinoma and that this subtype probably corresponds to small cell carcinoma with a "large cell component," and to very poorly differentiated adenocarcinoma and squamous cell carcinoma of the small cell type.