CASE REPORT article
Front. Oncol.
Sec. Hematologic Malignancies
This article is part of the Research TopicToward the Future Management of Patients with Chronic Lymphocytic LeukemiaView all 17 articles
Richter Transformation to Classical Hodgkin Lymphoma Following Recurrent Disseminated Histoplasmosis in Chronic Lymphocytic Leukemia: A Case Report
Provisionally accepted
- 1Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, United States
- 2Bronson Methodist Hospital, Kalamazoo, United States
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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.
Keywords: case report, Chronic lymphocytic leukemia (CLL), Histoplasmosis, Hodgkin's lymphoma, Richter transformation
Received: 28 Sep 2025; Accepted: 26 Jan 2026.
Copyright: © 2026 Haj, Said, Al-Assil, Stone and Omaira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mohamed Said
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