# 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.

## Key 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.