The cytodiagnosis of well-differentiated neuroendocrine carcinoma. A distinct clinicopathologic entity

Well-differentiated neuroendocrine carcinoma (WDNE) has been recognized as a distinct variant of pulmonary neuroendocrine carcinoma, with characteristic histopathologic and clinical features that separate it from both carcinoid and small-cell carcinoma (SCC). Histologic review of tumors in long-term survivors (greater than two years) with an initial diagnosis of SCC has shown that the majority of these cases are, in fact, better classified as WDNE; the distinction of WDNE from SCC has, therefore, important prognostic and therapeutic implications. A retrospective review of 200 cytologies originally diagnosed as SCC was undertaken in an attempt to characterize the cytomorphologic features of WDNE. The cytologic criteria that distinguished cases of WDNE included polygonal-to-fusiform cells with a variable amount of lacy cytoplasm, oval nuclei with coarsely dispersed chromatin and frequent chromocenters, and mild nuclear and cytoplasmic anisomorphism. The majority of malignant cells were arranged either in acinarlike clusters or in epithelial sheets with evidence of palisading. Twenty-two cases were reclassified cytologically as WDNE and were accurately distinguished from all other neoplastic and SCC cases on repeated double-blind review. Clinical and histologic data confirmed the diagnosis of WDNE in all cases; it can be concluded that SCC and SDNE are cytologically distinct entities.