ALK-positive pulmonary adenocarcinoma with signet ring features (PASRF) and polygonal cell morphology simultaneously...

Pulmonary adenocarcinoma with signet ring features (PASRF) is relatively rare and often harbors anaplastic large cell kinase gene (ALK) rearrangements. As patients with ALK+ lung adenocarcinoma typically present at advanced stages, it is important to detect ALK+ PASRF at metastatic sites to ensure ALK-targeted therapy can be best applied. In this study, we report a case of PASRF with polygonal cell morphology in an 85-year-old female who had metastasized to the supraclavicular lymph node and was treated with Alectinib, a novel small molecule tyrosine kinase inhibitor targeting ALK. Biopsy of the node revealed numerous microscopic neoplastic cells which had formed nests or cords, in addition to signet ring cells (60%), and another morphology of polygonal cells (40%) which contained eosinophilic cytoplasm. Mitotic images were common, and necrosis was observed. Immunohistochemically, both morphology tumor cells were diffusely positive for TTF1, CK7, and Napsin A, and most of the two were positive for P40, P63, and CK5/6 and negative for CK20 and CDX2. Co-expression of TTF-1, CK7, Napsin A, and P40, P63, and CK5/6 were overtly present, and Alcian blue-periodic acid-Schiff (AB-PAS) staining showed intracytoplasmic mucin in the two cells. In addition, ALK rearrangements were detected by ALK (clone D5F3) immunohistochemical assay and fluorescence in situ hybridization (FISH), A final diagnosis of metastatic ALK-positive PASRF with polygonal cell morphology to the supraclavicular lymph node was made, and the patient was treated with Alectinib, which brought a reduction in tumor size and good results.