T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Complicated by Hemophagocytic Lymphohistiocytosis Following an Initial Diagnosis of Kikuchi-Fujimoto Disease: A Case Report
Kikuchi-Fujimoto disease (KFD) is a benign necrotizing lymphadenitis that can closely mimic lymphoma. T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is an aggressive large B-cell lymphoma characterized by < 10% scattered malignant B cells among predominantly reactive T-cells and histiocytes. Both KFD and lymphoma can rarely be associated with hemophagocytic lymphohistiocytosis (HLH). In that setting, overlapping fever, cytopenias, hepatosplenomegaly, and elevated inflammatory markers can further obscure the diagnosis. Here, we describe a young man initially diagnosed with KFD who subsequently developed secondary HLH and was ultimately found to have THRLBCL on splenic biopsy and upon re-review of the original lymph node biopsy and molecular clonality testing.
Materials and Methods/Case Presentation/Objective:
A 31-year-old man with no past medical history presented with 8-12 weeks of a nonpainful right axillary mass, briefly tender during self-limited viral illness, without fevers, night sweats, or weight loss. Three months later, he underwent surgical excision of presumed lipomas, and three axillary masses measuring up to 5.5 cm were removed. Pathology showed features suggestive of histiocytic necrotizing lymphadenitis, including effaced nodal architecture, necrosis, karyorrhectic debris, crescentic histiocytes, plasmacytoid dendritic cells, apoptotic bodies, and absence of neutrophils, eosinophils, or granulomas, and a pathological diagnosis of Kikuchi lymphadenitis was made.
Results/Description/Main Outcome Measure(s):
Two months following excision, he developed persistent fevers, chills, night sweats, fatigue, dry cough, and lost approximately 8kg. Outpatient evaluation by rheumatology and gastroenterology showed progressive cytopenias, transaminitis, low IgG/IgA, and ferritin up to 15,910ng/mL. The patient was hospitalized for expedited workup. On admission, labs showed WBC 1.02K/uL, hemoglobin 10.3g/dL, platelets 138K/uL, ALP 801IU/L, LDH 539U/L, triglycerides 196mg/dL, ferritin 20,615ng/mL, and D-dimer 2,509ng/mL. Autoimmune serologies and broad infectious testing were unrevealing except for low-level EBV PCR positivity consistent with prior remote exposure. CT showed hepatomegaly (25cm), splenomegaly (18.5cm), and multiple splenic hypodensities. HScore rose from 208-234 to 287, consistent with >99% probability of reactive HLH, and soluble IL-2 receptor was 11,823U/mL. Bone marrow biopsy showed normocellular marrow with trilineage maturation and occasional hemophagocytic macrophages, with negative flow cytometry and cytogenetics. Dexamethasone 20mg daily and anakinra 100mg twice daily were initiated. Thereafter, MRI indicated splenomegaly (19cm) with multiple splenic masses up to 9cm. Splenic biopsy revealed an atypical lymphoid infiltrate consistent with THRLBCL. NIH re-review of the original axillary biopsy showed scattered atypical CD20+/CD79a+ B cells in a T-cell/histiocyte-rich background, with clonal B-cell and polyclonal T-cell receptor gamma rearrangements, revising the diagnosis to THRLBCL. The patient was promptly started on R-CHOEP (rituximab, cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) chemoimmunotherapy, with improvement in symptoms and all laboratory parameters. An interim PET/CT scan following three treatment cycles was consistent with complete metabolic remission. Measurable residual disease testing by clonoSEQ also showed no detectable disease. He is scheduled to complete an additional three cycles.
Conclusion(s).:
THRLBCL can closely mimic KFD on initial pathology, as both present with lymph node effacement, abundant reactive T cells, and histiocytes. Persistent B symptoms, new lesions, hepatosplenomegaly, pancytopenia, and/or HLH should prompt reconsideration of isolated KFD. Repeat biopsy and molecular clonality testing may reduce diagnostic delay and expedite lymphoma-directed therapy.
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