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Richter transformation to classical Hodgkin lymphoma following recurrent disseminated histoplasmosis in chronic lymphocytic leukemia: a Case Report

Year: 2026

Type: article

Abstract: Background: Richter Transformation (RT) is the rare progression of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) into a more aggressive lymphoma, occurring in only about 5-10% of cases. RT has a poor prognosis with rapid progression and resistance to standard therapies. PET/CT scans are crucial in detecting RT with increased SUVmax indicating more aggressive disease. Case presentation: A 65-year-old male with 13q deletion CLL developed three relapses over the course of 13 years from initial CLL diagnosis, and work up of the third relapse revealed disseminated histoplasmosis. He improved with Ibrutinib for CLL and Amphotericin B for histoplasmosis. Four and seven years later, the patient re-presented with histoplasmosis reinfections, confirmed by PET/CT and biopsy, and treated with antifungals for each reinfection. One year later (21 years from initial CLL diagnosis), he presented with malignant hypercalcemia and retroperitoneal lymphadenopathy (LAD) for which biopsy revealed RT to classic Hodgkin's Lymphoma (cHL). Given his impaired renal function, his treatment regimen included AVD chemotherapy and nivolumab, from which he eventually recovered. Discussion/conclusion: CLL patients are inherently immunocompromised due to hypogammaglobulinemia, increasing their susceptibility to opportunistic infections like histoplasmosis. These infections can recur, be refractory, and may even coincide with RT. This unusual case of RT after chronic disseminated histoplasmosis reinfections involved lymph nodes and eventually hypercalcemia. Vigilant monitoring and patient education on risk avoidance are recommended strategies for mitigating risk of histoplasmosis. Providers may also consider Itraconazole prophylaxis. Further research is warranted to better understand the relationship between chronic opportunistic infections and the oncogenic progressions in CLL patients.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1714656

Authors: Delour Haj, Mohamed Said, Talal Al-Assil, Steven Stone, Mohammad Omaira

Institution: Western Michigan University

Language: English

Topic: Chronic Lymphocytic Leukemia Research

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801