Large-cell neuroendocrine carcinoma of the lung: Proposed criteria for cytologic diagnosis

Abstract

The category of large‐cell neuroendocrine carcinoma (LCNEC) of the lung, proposed to expand the traditional scheme of typical carcinoid, atypical carcinoid (AC), and small‐cell carcinoma (SCC), based on histologic features, has not been defined in cytology. We attempt to describe LCNEC cytologically. Cytologic features in 16 histologically confirmed LCNECs in fine‐needle aspiration biopsies, cell blocks, bronchial brushes, washes, and sputum specimens stained with Diff‐Quik, Papanicolaou, hematoxylin‐eosin, chromogranin, and synaptophysin were analyzed. Three poorly differentiated nonsmall‐cell carcinomas, 4 SCCs, and 2 atypical carcinoids were studied similarly. Twenty specimens from 16 histologically confirmed cases of LCNEC with original cytologic diagnoses including high‐grade neuroendocrine carcinoma, large‐cell carcinoma, nonsmall‐cell carcinoma, poorly differentiated carcinoma, adenocarcinoma, and SCC, were examined. Features included flattened three‐dimensional clusters with peripheral palisading, moderate to large single cells with scant (alcohol‐fixed) or moderate (air‐dried) cytoplasm; and large, oval, or polygonal nuclei with irregular contours, thickened nuclear membranes, and finely or coarsely granular chromatin, showing some molding and crush artifact. Nucleoli were generally present, and occasionally prominent. Mitosis and necrosis were apparent. Neuroendocrine stains were applied to all specimens, with at least one marker, commonly synaptophysin, positive in 18/20 specimens. LCNEC can be diagnosed in cytologic material, using morphology confirmed by immunocytochemistry. Treatment can be offered on the basis of cytologic examination. Diagn. Cytopathol. 2001;24:58–64. © 2001 Wiley‐Liss, Inc.

Cytological characteristics of pulmonary large cell neuroendocrine carcinoma

“…However, in cytological specimens, the cytoplasm was reported to be scant or stripped in the alcohol-fixed specimens [8], and the existence of both abundant cytoplasm and cytoplasmic stripping was reported in cytological specimens of LCNECs [7,9]. In our study, a large amount of clearly identified cytoplasm was frequently observed in all of LCNECs, and in one of seven SCLCs (14%).…”

“…Nuclear chromatin is fine and granular in bronchial brush cytology of LCNECs [7]. However, it is coarse and granular in fine-needle aspiration materials [7,8]. The difference in these results may be due to the different methods used to collect tumor cells.…”

Clinical responses of large cell neuroendocrine carcinoma of the lung to cisplatin-based chemotherapy

“…Of the 87 patients, only five who had received cisplatin-based chemotherapy for recurrent tumor that was evaluable for the response. While LCNEC is difficult to diagnose prior to the start of treatment on the basis of the findings in biopsy or cytological specimens, the architectural neuroendocrine features may, more or less, be reflected in these small samples [19,20]. We, therefore, conducted a review of 567 autopsy cases of lung cancer, and identified 15 cases of LCNEC who had received cisplatin-based chemotherapy.…”

Update on small cell carcinoma and its differentiation from squamous cell carcinoma and other non-small cell carcinomas

“…However, criteria have been proposed to diagnose LCNEC based on cytology. 47 The term 'large cell carcinoma, with neuroendocrine morphology' can be used for tumors resembling LCNEC by light microscopy but lacking proof of neuroendocrine differentiation by electron microscopy or immunohistochemistry. 10 The term 'combined LCNEC' is appropriate for those tumors containing components of other histological types of NSCLC, such as adenocarcinoma or squamous cell carcinoma.…”