A Diagnostic and Therapeutic Odyssey: Sequential Transformation From Follicular Lymphoma to MYC-Rearrangement-Negative High-Grade B-Cell Lymphoma With Burkitt-Like Morphology in a Profoundly Immunosuppressed HIV-Positive Patient

INTRODUCTION: HIV-associated lymphomas are characterized by marked biological heterogeneity and often aggressive behavior, yet sequential evolution across multiple distinct entities in the setting of profound immunosuppression remains exceptionally rare and therapeutically challenging.

CASE PRESENTATION: A 41-year-old man, ECOG 0, presented with a bulky left axillary mass, 10 kg weight loss and night sweats. PET-CT delineated a 140×95×230 mm infiltrative axillary/chest-wall mass (SUVmax 26.86) extending cranio-caudally from the infraclavicular level to the plane of the T8-T9 intervertebral disc, with hepatic involvement. The tumor drained yellow-white pus through a cutaneous fistulous opening, with MRSA superinfection.

Axillary and hepatic biopsies were interpreted as stage IVB follicular lymphoma grade 2 (CD20⁺, CD10⁺, BCL6⁺, BCL2⁻), FLIPI 4. Concurrent HIV infection was identified (baseline HIV RNA 10,700 copies/mL; LDH 1,867 U/L; uric acid 9.30 mg/dL), prompting dolutegravir/lamivudine initiation. HIV RNA became undetectable by month 2 (CD4 36 cells/mm³) and remained suppressed throughout successive therapies, despite persistent profound CD4 lymphopenia (latest documented count: 94 cells/mm³).

DESCRIPTION: Six R-CHOP cycles were administered, with rituximab added after ART initiation. Second-opinion review of the original tissue subsequently revised the diagnosis to FL grade 3B (Ki-67 ~80%). Post-treatment PET-CT revealed marked dimensional regression to 90×60×60 mm, with persistent/progressive avidity (SUVmax 30.96; Deauville 5), metabolically active supradiaphragmatic lymphadenopathy and hepatic metabolic CR, determining radiotherapy initiation.

RT was complicated by grade 3 radiation dermatitis. The axillary mass became encircled by indurated erythematous skin with proliferative change, covered by fetid purulent secretions and complicated by left axillary cellulitis; wound cultures subsequently yielded Enterococcus faecalis and Corynebacterium amycolatum. Progression suspicion prompted hepatic and axillary mass re-biopsy, demonstrating CD20-negative GCB-DLBCL (CD10⁺, BCL6⁺, MUM1⁻, BCL2⁻, MYC ~45%, Ki-67 >90%).

After two GDP cycles, PET-CT documented partial response (SUVmax 9.70, 50×40×48 mm). Autologous SCT was pursued, but mobilization failed (peak CD34⁺ 14 cells/µL). One additional GDP cycle and one IGEV cycle preceded repeat PET-CT, which showcased metabolic progression (SUVmax 21.79; Deauville 5).

Re-biopsy revealed CD20-positive, BCL2-negative HGBL with Burkitt-like morphology (CD10⁺, MYC >70%; Ki-67 >95%). One R-CODOX-M/R-IVAC cycle was administered pending MYC FISH. After negative marrow and tissue results, treatment was switched to R-Hyper-CVAD cycle A. The 11q status was not assessed. Klebsiella pneumoniae bacteremia, accompanied by hemodynamic instability was resolved with broad-spectrum antibiotics.

Cycle B was withheld after chest CT scan and subsequent PET-CT confirmed progression, with an enlarged prepectoral mass (85×52 mm; SULmax 14.1), new supradiaphragmatic lymph nodes and Deauville 5. Two cycles of Pola-BR were administered as a bridge to glofitamab initiation, while treatment access was secured through a successful court order, routine public reimbursement being unavailable.

CONCLUSIONS: This case documents a four-stage diagnostic trajectory - FL grade 2 - revised FL grade 3B - CD20-negative GCB-DLBCL - MYC-rearrangement-negative HGBL with Burkitt-like morphology - within 14 months, with virological suppression failing to restore immunological competence. It reinforces the value of iterative re-biopsy at successive progression, the diagnostic challenge posed by the MYC-overexpressing but MYC-rearrangement-negative aggressive B-cell lymphoma and the complexity of delivering intensive chemoimmunotherapy alongside ART amid recurrent infections.