A Challenging Crosstalk between HLH and TCRHLCL

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal condition characterized by immune hyperactivation. Malignancies (like lymphomas), autoimmune diseases, and infections can all cause secondary HLH. Adults are most susceptible to lymphoma-associated HLH. T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare subtype (1-3%)of diffuse large B-cell lymphoma (1,2) characterized by a small number of neoplastic CD20⁺ B cells in a background of abundant reactive T cells and histiocytes(1,3). In an advanced stage, it typically presents with involvement of the spleen, liver, and marrow. The histiocyte-rich environment in THRLBCL may promote immune evasion, creating a complex tumor immune “crosstalk” that can trigger secondary HLH.

Materials and Methods/Case Presentation/Objective: Case Presentation

A 25-year-old male presented with persistent fevers, drenching night sweats, and abdominal pain. On exam, he had diffuse lymphadenopathy and splenomegaly. Laboratory tests showed severe pancytopenia, and the features were consistent with HLH-2004 criteria. Initial workup for infections and autoimmune disease was unrevealing. An axillary lymph node biopsy and bone marrow biopsy showed hemophagocytosis but no malignancy. To clear this dilemma, we repeated the lymph node biopsy with an excisional sample. This biopsy revealed large atypical B cells in a background of many T cells and macrophages, confirming THRLBCL. Staging showed Stage 4B disease with widespread nodal involvement.

Results/Description/Main Outcome Measures: Management and Outcome

After diagnosis, we initiated therapy addressing both conditions. The patient was treated with high-dose corticosteroids and cyclophosphamide as prephase chemotherapy. When the patient stabilized, we administered six cycles of R-CHOP chemotherapy for THRLBCL. Supportive measures included transfusion support and infection prophylaxis with antimicrobials. Therapy was completed without major complications, and the patient achieved complete remission on PET-CT. Fertility preservation was discussed before therapy, highlighting the impact of intensive treatment on young patients.

Conclusions: This case highlights the bidirectional relationship between THRLBCL and HLH. Malignancy-associated HLH can mask an underlying lymphoma, and conversely, lymphoma can trigger secondary HLH. Awareness of this association is critical, as early diagnosis and treatment can be life-saving. Outcomes in lymphoma-associated HLH have historically been poor; one series reported only ~17% complete remission despite aggressive treatment(4). Our report underscores the uncommon occurrence of HLH secondary to THRLBCL and the need for prompt intervention. It also touches on ethical considerations like balancing aggressive treatment intensity against fertility preservation.

References

Swerdlow SH, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th Ed. IARC; 2017.

Achten R, et al. T-cell/histiocyte-rich large B-cell lymphoma: a distinct clinicopathologic entity. J Clin Oncol. 2002 Mar 1;20(5):1269-77. doi: 10.1200/JCO.2002.20.5.1269. PMID: 11870169.

Robert S. Ohgami, et al. Large B-Cell Lymphomas Poor in B Cells and Rich in PD-1+ T Cells Can Mimic T-Cell Lymphomas, American Journal of Clinical Pathology, Volume 142, Issue 2, August 2014, Pages 150–156, https://doi.org/10.1309/AJCPFJWKQ6GTVQE6

Han, AR., Lee, H.R., Park, BB. et al. Lymphoma-associated hemophagocytic syndrome: clinical features and treatment outcome. Ann Hematol 86, 493–498 (2007). https://doi.org/10.1007/s00277-007-0278-6