Synchronous Hodgkin lymphoma and follicular lymphoma: a case report.

Classical Hodgkin lymphoma (cHL) and folicular lymphoma (FL) are biologically distinct B-cell lymphomas that rarely occur synchronously. Their coexistence presents diagnostic challenges and may require repeated tissue sampling to establish the correct diagnosis and guiade appropriate treatment.

A 49-year-old woman presented in May 2023 with cervical lymphadenopathy and night sweats. PET/CT demonstrated hypermetabolic supra and infradiaphragmatic lymph nodes, multifocal skeletal involvement, and a hypermetabolic lesion involving the T4 vertebral body with extension into the spinal canal. Contrast-enhanced magnetic resonance imaging confirmed spinal cord compression, and pathological T4 vertebral fracture.
In April 2024, a diagnosis of cHL nodular sclerosis subtype, was established by right axillary lymph node biopsy. Immunohistochemistry demonstrated CD30 positivity and weak PAX5. The disease was staged as IVB, and treatment with brentuximab vedotin plus AVD was initiated. After completion of six cycles, PET/CT demonstrated persistent hypermetabolic activity in the T4 vertebral lesion, as well as cervical and abdominal lymphadenopathy (Deauville 5). Repeat biopsy of a supraclavicular lymph node confirmed persistent cHL (CD15+, CD30+, PAX5+, BCL2-, CD20-).
In November 2024, the patient received radiotherapy to the T4 vertebral lesion (20 fractions) and subsequently initiated pembrolizumab, completing eight cycles. Restaging PET/CT in May 2025 demonstrated a metabolic response at the thoracic spine but evidence of disease progression, with increased supra and infradiaphragmatic lymphadenopathy, newly developed pulmonary nodules, and hypermetabolic involvement of the right femur (Deauville 5). A right inguinal lymph node biopsy performed in June 2025 established the diagnosis of FL (ICC 2022 Grade 1), with a Ki-67 of 10% and an immunophenotype: CD20+, CD10+, BCL2+, BCL6+, CD30-, and CD3-. The patient completed six cycles of Rituximab-Bendamustine. Follow up PET/CT (March 2026) demonstrated a complete metabolic response (Deauville 3), after which maintenance rituximab was initiated.

Both cHL and FL derive from germinal center B cells; however, they represent biologically distinct entities. 
Composite lymphoma refers to the coexistence of two or more distinct lymphoma types within the same anatomical site. 
Cases of cHL have been reported in association with FL, as well as with B-cell lymphomas-including mantle cell, marginal zone, diffuse large B and less communly T-cell lymphomas. 
The most common presentation is cHL following FL with an interval of 12-276 months. These cases may present as composite, synchronous or sequential lymphomas. 
Some cases share genetic alterations, including BCL2 and BCL6 rearrangements, immunoglobulin gene clonality, and mutations in CREBBP, KMT2D, EP300, and ARID1A, supporting a common clonal origin. The diagnosis of synchronous lymphoma is challenging because of their distinct morphological and immunophenotypic features. Immunohistochemestry plays a crucial role in distinguishing subtypes. 

The synchronous occurrence of cHL and non-Hodgkin lymphoma is rare, accounting for fewer than 0.5% of all lymphomas, and represents a significant diagnosis and therapeutic challenge. This case highlights the importance of repeat biopsy in patients with persistent or progressive lymphadenopathy showing a discordant response to treatment, as it may reveal a distinct lymphoma requiring a different therapeutic approach.