Large cell carcinoma of the lung: clinically oriented classification integrating immunohistochemistry and molecular biology

作者：Rossi G, Mengoli MC, Cavazza A, Nicoli D, Barbareschi M, Cantaloni C, Papotti M, Tironi A, Graziano P, Paci M, Stefani A, Migaldi M, Sartori G, Pelosi G · 发表于：Virchows Archiv : an international journal of pathology · 年份：2014 · DOI：10.1007/s00428-013-1501-6 · 研究领域：Adult、Aged、Anaplastic Lymphoma Kinase、Carcinoma, Large Cell、Female、Humans、Immunohistochemistry、Lung Neoplasms、Male、Middle Aged、Molecular Biology、Mutation

This study aimed at challenging pulmonary large cell carcinoma (LLC) as tumor entity and defining different subgroups according to immunohistochemical and molecular features. Expression of markers specific for glandular (TTF-1, napsin A, cytokeratin 7), squamous cell (p40, p63, cytokeratins 5/6, desmocollin-3), and neuroendocrine (chromogranin, synaptophysin, CD56) differentiation was studied in 121 LCC across their entire histological spectrum also using direct sequencing for epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and FISH analysis for ALK gene translocation. Survival was not investigated. All 47 large cell neuroendocrine carcinomas demonstrated a true neuroendocrine cell lineage, whereas all 24 basaloid and both 2 lymphoepithelioma-like carcinomas showed squamous cell markers. Eighteen out of 22 clear cell carcinomas had glandular differentiation, with KRAS mutations being present in 39 % of cases, whereas squamous cell differentiation was present in four cases. Eighteen out of 20 large cell carcinomas, not otherwise specified, had glandular differentiation upon immunohistochemistry, with an exon 21 L858R EGFR mutation in one (5 %) tumor, an exon 2 KRAS mutation in eight (40 %) tumors, and an ALK translocation in one (5 %) tumor, whereas two tumors positive for CK7 and CK5/6 and negative for all other markers were considered adenocarcinoma. All six LCC of rhabdoid type expressed TTF-1 and/or CK7, thr...