Anaplastic large cell lymphoma presenting as hemophagocytic lymphohistiocytosis

ABSTRACT

INTRODUCTION: HLH is a rare syndrome with an incidence of 1.2 cases per 1,000,000 individuals per year. Diagnosis of HLH is challenging given its varied presentation and strict diagnostic criteria. DESCRIPTION A 40 year-old female with no medical history presented with two weeks of shortness of breath and cervical lymphadenopathy. She was evaluated in the ED on two separate occasions with workup significant for CT chest findings of mediastinal and axillary lymphadenopathy, pulmonary nodules and a left pleural effusion. Within one week, she presented a third time with worsening shortness of breath, fatigue and fevers. She was febrile, tachycardic, hypoxemic, leukopenic and thrombocytopenic. A repeat CT chest revealed increased lymphadenopathy and pleural effusion. She was started on empiric broad spectrum antibiotics and admitted to the hospital. Infectious workup, pleural fluid cytology and peripheral blood flow cytometry were negative. Bone marrow biopsy had markedly increased histiocytes and hemophagocytosis, but no evidence of malignancy. She developed progressive hypoxemia requiring intubation, shock requiring vasopressors and multiorgan failure. Fevers persisted with worsening pancytopenia, DIC, and markedly elevated inflammatory markers, notably a ferritin >33000. Further workup revealed positive Covid antibodies, elevated parvovirus IgG, elevated fungal markers and Candida in respiratory cultures. Secondary HLH due to sepsis or following COVID infection in the setting of malignancy was suspected. A course of antifungals and high dose steroids was given without improvement. Etoposide was considered, but avoided given possible sepsis, multiorgan failure and pancytopenia. A lymph node biopsy was performed with evidence of hemophagocytosis and ALK-positive anaplastic large cell lymphoma. Despite aggressive treatment, she developed progressive multiorgan failure resulting in death. Autopsy confirmed anaplastic large cell lymphoma with metastasis to the lymph nodes, lungs, epicardium and stomach. DISCUSSION: Malignancy is a known etiology of HLH in adults, however, few cases of ALK-positive anaplastic large cell lymphoma presenting as HLH have been reported. The rapid progression of HLH in this case stresses the importance of early diagnosis and treatment of HLH while pursuing an aggressive malignancy workup.