Gastrointestinal-Predominant ALK-Negative Systemic Anaplastic Large Cell Lymphoma Presenting as Fever of Unknown Origin: Case Report

Anaplastic large cell lymphoma (ALCL) is a CD30-positive mature T-cell lymphoma. ALK-negative systemic ALCL typically affects older adults, with aggressive clinical behavior. Predominant gastrointestinal involvement is rare and may present with nonspecific systemic symptoms, posing diagnostic challenges, particularly when manifesting as fever of unknown origin. We report a case of a patient with ALK-negative systemic ALCL and predominant gastrointestinal involvement. The patient had a history of indolent cutaneous extranodal marginal zone B-cell lymphoma. The patient presented with a prolonged, intermittent fever and constitutional symptoms. The initial evaluations, including computed tomography, 18F-fluorodeoxyglucose positron emission tomography/computed tomography, and bone marrow examination, were not diagnostic. The persistent fever, which was accompanied by newly developed gastrointestinal symptoms and progressive hypoalbuminemia, prompted an endoscopic evaluation that revealed multiple ulcerofungating gastric lesions. Histopathological examination demonstrated the diffuse proliferation of large atypical lymphoid cells with high CD30 expression, no ALK expression, a high Ki-67 proliferation index, and clonal T-cell receptor gene rearrangement. These findings were consistent with ALK-negative systemic ALCL. Staging then revealed multifocal gastrointestinal involvement. The patient was treated with brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone, following which the febrile episodes improved. This case illustrates an uncommon gastrointestinal-predominant presentation of ALK-negative systemic ALCL presenting as fever of unknown origin. This case underscores the importance of continued diagnostic reassessment and symptom-guided tissue acquisition when conventional staging studies are not initially diagnostic, particularly in patients with a history of indolent lymphoma.