To investigate the clinicopathological and immunohistochemical features and differential diagnosis of ALK⁺ large B cell lymphoma (ALK⁺ LBCL).

The clinical data of two patients treated at the Tai′an City Central Hospital were analyzed retrospectively. The histopathologic features and immunophenotype of ALK⁺ LBCL were observed and the related literature was reviewed.

The age of the two male patients was 45 and 50 years old, respectively. Both of them presented with multiple enlarged lymph nodes on the neck. Lymphadenectomy biopsy showed that lymph node structure was destroyed and tumor cells were arranged in nests or invading the lymphatic sinus. The tumor cells were large in size with an immunoblastic or plasmablastic microscopical appearance. They did not express B-lineage markers (CD20, CD79α, and PAX-5) or T-lineage markers (CD3 and CD5). However, ALK, EMA, and plasmacytic markers, including CD138, CD38, and MUM-1, were characteristically expressed. Two patients were alive during the follow-up period of 6-11 months.

ALK⁺ LBCL is a rare aggressive B-cell lymphoma with unique morphologic, immunohistochemical, and cytogenetic characteristics. As it overlaps with many tumors in morphology and immunophenotype, the chance of misdiagnosis is relatively high. ALK inhibitors may become a new treatment option for ALK⁺ LBCL.