Abstract :
Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK LBCL) is an exceedingly rare and aggressive subtype of diffuse large B-cell lymphoma characterized by distinctive clinical and immunophenotypic features. It predominantly affects younger individuals and often presents with extranodal involvement, which can pose diagnostic challenges due to its diverse morphology and overlapping immunoprofiles with other hematologic malignancies. This case report describes a 46-year-old male presenting with a progressive oropharyngeal mass originating from the right tonsillar fossa, an uncommon site for ALK LBCL. Histopathological examination revealed a diffuse infiltrate of medium-sized lymphoid cells, with immunohistochemistry demonstrating positivity for ALK1, MUM1, CD138, and BOB1, alongside a high proliferative index, while lacking expression of classical B-cell markers such as CD20 and PAX5. Differential diagnosis included ALK ALCL, plasmablastic lymphoma, DLBCL-NOS, and plasma cell neoplasms; however, immunophenotypic and molecular features confirmed ALK LBCL. This case underscores the essential importance of thorough immunohistochemical profiling in diagnosing atypical presentations of ALK LBCL and highlights the need to include this entity in the differential diagnosis of CD20-negative lymphoid tumors in extranodal locations. Identifying such rare manifestations is crucial for accurate diagnosis and for informing appropriate targeted treatment approaches.