Anaplastic Large Cell Lymphoma (ALK-negative) Following Diffuse Large B-Cell Lymphoma: A Rare Sequential Occurrence

Introduction/Background/Significance: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, typically managed with R-CHOP chemotherapy. While transformation within the B-cell lineage (e.g., follicular lymphoma to DLBCL) is well described, lineage conversion from B-cell lymphoma to T-cell lymphoma is exceedingly rare. Composite or sequential lymphomas involving different lineages occur in < 5% of cases and pose significant diagnostic and therapeutic challenges. Only isolated case reports describe anaplastic large cell lymphoma (ALCL), usually ALK-negative, arising after treated DLBCL

Materials and Methods/Case Presentation/Objective: A 64-year-old man with no significant past medical history presented with three weeks of fevers, drenching night sweats, a 20-pound unintentional weight loss, and generalized body aches. He was noted to have diffuse lymphadenopathy on examination.

Initial workup, including a CT chest, abdomen, and pelvis, revealed widespread lymphadenopathy and a suspicious right middle lobe pulmonary nodule. An excisional biopsy of a left inguinal lymph node showed diffuse large B-cell lymphoma with strong CD30 expression and a high proliferation index (Ki-67 >90%), but negative for ALK and pan–T-cell markers. The patient was initiated on R-CHOP chemotherapy and tolerated five cycles, complicated only by mild peripheral neuropathy.

Eight months after initial treatment, interval imaging demonstrated new hepatic masses, pulmonary nodules, and persistent bulky retroperitoneal adenopathy, prompting repeat tissue evaluation.

Results/Description/Main Outcome Measures: A liver core biopsy revealed an anaplastic large cell lymphoma, ALK-negative, with a T/null cell immunophenotype (CD4+, CD30+, CD43+, negative for B-cell markers). A repeat groin lymph node excision confirmed ALK-negative anaplastic large cell lymphoma. There was no evidence of composite disease at initial diagnosis, indicating a sequential development of two distinct lymphoma subtypes.

Conclusions: This case highlights the rare occurrence of a T-cell lymphoma emerging after a B-cell lymphoma diagnosis. The mechanism of such lineage change is unclear but may involve therapy-related clonal selection, treatment-induced mutagenesis, or unrecognized minor T-cell clones at presentation that later emerge as dominant disease.

Importantly, the clinical course raised suspicion for a change in tumor biology, emphasizing the need for repeat biopsy in patients with atypical progression or relapse. The transition to ALK-negative anaplastic large cell lymphoma carries prognostic significance, as this subtype is associated with poorer treatment response and overall survival compared to ALK-positive disease.