ABSTRACT
Introduction Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and potential life-threatening syndrome characterized by excessive immune activation and cytokine release. In adults, infections, inflammatory diseases and more rarely hematological malignancies can trigger the onset of HLH. We describe a rare case of intravascular diffuse large B cell lymphoma (DLBCL) associated with HLH. Case presentation A 53-year-old woman, presenting with high fever since 3 weeks and asthenia, was admitted to the hospital. She had a negative medical and travel history. On physical examination, generalized edema and hypotension were noted. An extensive bacterial and viral work-up (including COVID-19) was negative. During admission, the patient developed progressive anasarca and an episode of epileptic convulsions. Laboratory results showed increasing cytopenia, major hyperferritinemia, hypofibrinogenemia and hypertriglyceridemia. A bone marrow examination showed prominent hemophagocytosis. Cerebrospinal fluid examination showed the presence of aberrant monocytes, indicating CNS involvement. Genetic analysis to detect hemophagocytosis-associated mutations was negative. PET-CT revealed increased FDG uptake in both adrenal glands, hypophysis, bone marrow and spleen. Biopsy of the adrenal gland was not contributive. Brain MRI showed two cerebral masses radiologically suggestive for meningioma, confirmed by histology. The patient was refractory to high-dose corticotherapy and treatment was adapted to the HLH-94 protocol. A blind skin biopsy showed the presence of a population of pathological B-lymphocytes with aberrant immunophenotype (CD20+/Pax5+/Bcl6+/Bcl2+/cMYC-) in and around the small blood vessels leading to the diagnosis of intravascular DLBCL. Treatment was adjusted to lymphoma-specific immune-chemotherapy upon which a gradual clinical improvement was noted. After four cycles R-CHOP, three cycles of high dose methotrexate and high dose Endoxan for stem cell mobilisation, treatment was intensified with two cycles R-DHAP because of laboratory signs of persistent hemophagocytosis. Thereafter, the patient received an autologous stem cell transplantation (auto-HCT) after BEAM chemotherapy. End of treatment PET-CT and skin biopsy documented complete remission of the lymphoma. Because of slow hematological recovery, repeated bone marrow examinations were done and showed hypoplasia and persistent hemophagocytosis. Dexamethasone in combination with eltrombopag led to a gradual hematological response. At 20 months after auto-HCT, the patients stay in complete remission of the DLBCL and are independent of corticotherapy, with acceptable hematological parameters and no clinical signs of HLH. Discussion In the absence of infection, HLH is a diagnostic challenge frequently leading to delayed identification of the primary trigger, if any. A characteristic image on PET-CT with increased uptake in adrenal glands and hypophysisis led us to perform a blind skin biopsy to diagnose intravascular DLBCL, a rare subtype of lymphoma. Our case also shows that 1) HLH is very difficult to manage without dealing with the primary trigger and 2) HLH can persist for prolonged periods of time after successful treatment of the primary cause and may require specific therapy for sufficient control.