Neuroendocrine carcinoma of the lung expressing anaplastic lymphoma kinase on high-sensitivity immunohistochemistry: A case report

It has been reported that anaplastic lymphoma kinase (ALK) protein is expressed in a proportion of non-small-cell carcinomas (mainly adenocarcinomas). By contrast, high-sensitivity immunohistochemistry (IHC) rarely detects ALK protein expression in neuroendocrine carcinomas (NECs) of the lung, which include small-cell carcinomas and large-cell neuroendocrine carcinomas (LCNECs). We herein present a case of NEC that was identified as ALK-positive via high-sensitivity IHC. A 51-year-old man was diagnosed with small-cell carcinoma in the upper lobe of the right lung. Although high-sensitivity IHC revealed that the tumor weakly expressed the ALK protein, no fusion gene with ALK was found using fluorescence in situ hybridization (FISH). Standard chemotherapy was administered to the patient. Six months after the first visit to the hospital for the tumor, another tumor was identified in the upper lobe of the left lung. The tumor was resected and diagnosed as NEC displaying LCNEC-like characteristics. This NEC also moderately expressed ALK protein by high-sensitivity IHC, without exhibiting fusion genes with ALK on FISH. These data suggest that the presence of ALK fusion genes should be confirmed by FISH or reverse transcription polymerase chain reaction, even if high-sensitivity IHC for ALK protein is positive in lung cancer.