A Semiquantitative Scoring System May Allow Biopsy Diagnosis of Pulmonary Large Cell Neuroendocrine Carcinoma: Experience With Tissue Microarrays

Objectives: The aim of this study was to devise reproducible biopsy criteria for distinguishing pulmonary large cell neuroendocrine carcinoma (LCNEC) from non-small cell lung carcinoma (NSCLC). Methods: Tissue microarrays of LCNEC and NSCLC were generated from resection specimens and used as biopsy surrogates. They were stained for neuroendocrine markers, Ki-67, napsin-A, andp40, and independently analyzed by standardized morphologic criteria by four pathologists. Tumors were scored based on morphology, neuroendocrine marker expression, and Ki-67 proliferative index. Results: The average total score for LCNEC was significantly higher than for NSCLC (5.65 vs 0.51, P < .0001). Utilizing a cutoff score of 4 or higher showed 100% sensitivity and 99% specificity for LCNEC diagnosis, with an excellent agreement among four pathologists (98%). Conclusions: The proposed semiquantitative approach based on a combination of specific morphologic and immunophenotypic features may be a useful tool for biopsy diagnosis of LCNEC. Key Words: Large cell neuroendocrine carcinoma of the lung; Biopsy diagnosis; Scoring criteria