MYC-positive follicular lymphoma complicated by refractory lactate and clonal evolution: a case report

TL;DR

A rare aggressive case of follicular lymphoma with high lactate levels and clonal evolution is reported, highlighting the need for new treatment strategies.

Contribution

Identifies an ultra-aggressive variant of follicular lymphoma driven by MYC overexpression and metabolic dysregulation.

Findings

The patient exhibited refractory lactic acidosis and rapid clonal evolution within 4 months of diagnosis.

MYC overexpression correlated with tumor activity and treatment resistance across multiple therapies.

The case highlights the fatal outcome of metabolic dysregulation in follicular lymphoma.

Abstract

Follicular lymphoma (FL) typically follows an indolent clinical course, however, a subset of patients develops an aggressive and treatment refractory phenotype. Here we report a fatal case of a 46-year-old male with FL grade 3A characterized by recurrent severe tumor-associated lactic acidosis (>15 mmol/L) and rapid therapeutic failure. The patient presented with B symptoms, extensive lymphadenopathy, profound hyperlactatemia, and serum IgM-κ monoclonal protein. Immunohistochemistry confirmed FL grade 3A diagnosis and revealed MYC protein overexpression within 4 months, manifesting new nodal lesions, markedly elevated lactate levels, sustained MYC overexpression, and emergence of both IgG-κ and IgM-κ monoclonal proteins, a serological signature of ongoing clonal evolution. Subsequent treatments (R-CHOP, R-CDOP, BR, and G-EPOCH) over 6 months failed to achieve durable disease control. The clinical course was dominated by refractory, recurrent type B lactic acidosis that correlated directly with tumor activity. The patient ultimately died of fulminant lactic acidosis complicated by tumor lysis syndrome, 7 months after initial diagnosis. This case identifies an ultra-aggressive variant of FL defined by MYC-driven metabolic dysregulation and dynamic clonal evolution, underscoring the need for early recognition and development of novel therapeutic strategies targeting metabolic reprogramming.

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