Classical Hodgkin Lymphoma Following Well-Controlled Chronic Myeloid Leukemia in a Young Adult: A Rare Case Presenting with Hepatic Dysfunction
Tyrosine kinase inhibitors (TKIs) like imatinib have revolutionized chronic myeloid leukemia (CML) management, converting a fatal malignancy into a manageable chronic condition. However, long-term TKI therapy has raised concerns regarding genomic stability and an elevated risk of second primary malignancies (SPMs). While solid tumors and secondary acute myeloid leukemias are documented post-TKI therapy, concurrent or subsequent lymphoid malignancies, specifically Classical Hodgkin Lymphoma (cHL), remain exceedingly rare. Theories pointing to either a common uncommitted multipotent hematopoietic progenitor or TKI-induced immune modulation impairing lymphoid oncogenesis surveillance. Diagnostically, distinguishing a true de novo secondary lymphoma from an extramedullary lymphoid blast crisis of CML is critical, as management strategies and prognoses differ drastically. This case is highly significant due to the unusually short latency (15 months) between CML diagnosis and advanced-stage cHL development in a young adult, challenging the typical paradigm of late-onset SPMs in older cohorts.
Materials and Methods/Case Presentation/Objective:
We present a 22-year-old male, with no signifiant past medical history, who developed Stage IV cHL during frontline TKI therapy for chronic-phase CML. The patient originally presented with progressive fatigue, weight loss, and splenomegaly. Chronic-phase CML was confirmed via bone marrow biopsy and quantitative real-time PCR (RT-PCR) showing a BCR-ABL1 transcript level of 88.2% and t(9;22)(q34;q11). He was treated with standard frontline imatinib (400 mg daily), achieving complete hematologic and optimal molecular responses. After 13 months of starting treatment, he presented with hemoptysis, drenching night sweats, fevers, and right supraclavicular lymphadenopathy. Diagnostic workup included RT-PCR for BCR-ABL1, liver function tests (LFTs), contrast-enhanced computed tomography (CECT) of the chest, abdomen, and pelvis, an excisional biopsy of the supraclavicular node, and a staging bone marrow biopsy.
Results/Description/Main Outcome Measure(s):
At the time of systemic symptom development, surveillance RT-PCR confirmed deep and sustained molecular control of CML with undetectable BCR-ABL1 transcripts (0.0%). CECT imaging revealed extensive supradiaphragmatic lymphadenopathy, hepatosplenomegaly, and patchy hepatic lesions, correlating with elevated LFTs (alkaline phosphatase 340 U/L, total bilirubin 2.4 mg/dL). Histopathological evaluation of the supraclavicular node revealed a polymorphous reactive background infiltrated by large, multilobulated Reed-Sternberg (RS) cells. Immunohistochemical analysis of these RS cells demonstrated strong positivity for CD30, CD15, while testing negative for CD45, CD3, CD20, MPO, and EBER-ISH for Epstein-Barr virus. The staging bone marrow biopsy confirmed focal infiltration by CD30-positive RS cells, establishing a diagnosis of concurrent Stage IV cHL. The patient maintained daily imatinib therapy to prevent CML relapse and successfully initiated standard multi-agent systemic chemotherapy without dose modifications.
Conclusion(s).: This case illustrates an exceptionally rare presentation of advanced-stage cHL arising shortly after imatinib initiation in a young adult with CML. The rapid development and young age contrast sharply with typical post-TKI second primary malignancies, which usually manifest after years of therapy in older populations. This suggests either a true synchronous subclinical occurrence or an accelerated lymphomagenesis pathway driven by early TKI-associated immune dysregulation. Ultimately, integrating careful histopathological, IHC, and molecular testing was mandatory to exclude an extramedullary blast crisis, showing that new constitutional symptoms or lymphadenopathy in CML patients requires prompt tissue biopsy despite sustained deep molecular remission.
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