Classical Hodgkin Lymphoma (cHL) typically manifests through swollen lymph nodes, yet unusual cases do arise with atypical presentations. This report focuses on the management of a challenging case of refractory cHL, where the disease initially presented in the liver. The case underscores the effectiveness of a customized, multimodal treatment strategy.

A 59-year-old man was diagnosed with stage 4A cHL after a liver biopsy confirmed the disease. His initial PET-CT scans showed extensive involvement, with spread to cervical lymph nodes, nasopharyngeal and oropharyngeal regions, as well as diffuse splenic activity. The patient underwent six cycles of ABVD chemotherapy, but follow-up PET-CT scans revealed disease progression, confirming primary refractory status. Subsequently, he was given salvage therapy with BV-DHAP, followed by high-dose chemotherapy and an autologous stem cell transplant (ASCT). Post-ASCT PET-CT scans demonstrated a significant metabolic response, with near-complete resolution of previous lesions, though splenomegaly persisted. Currently, the patient is undergoing maintenance therapy with brentuximab vedotin and has completed seven cycles successfully.

This case illustrates key challenges in the treatment of refractory cHL, particularly with atypical liver involvement, stressing the importance of considering lymphoma in cases of unexplained liver lesions. When the standard ABVD regimen failed, prompt initiation of aggressive salvage therapy was crucial in halting disease progression. The role of serial PET-CT imaging was pivotal in monitoring treatment effectiveness and guiding further clinical decisions. The tailored combination of salvage chemotherapy, ASCT, and maintenance with brentuximab vedotin showcases the evolving strategies in handling refractory cHL. Despite a significant overall response, the persistence of splenomegaly post-ASCT highlights the need for vigilant follow-up. This case emphasizes the potential for successful remission in refractory cHL through personalized, comprehensive treatment approaches, while also recognizing the need for continued exploration of emerging therapies.