# Deceptive initial presentation of systemic DLBCL with CNS progression following Oligometabolic PET/CT: case report

**Authors:** Rui Yuan, Ya Yu, Qian Yang, Jun Chen, Kunlan Long, Peiyang Gao

PMC · DOI: 10.3389/fonc.2026.1735699 · Frontiers in Oncology · 2026-03-02

## TL;DR

A woman with aggressive lymphoma initially showed subtle PET/CT results but later developed severe neurological and inflammatory symptoms, highlighting the need for early diagnosis and safe biopsy methods.

## Contribution

This case report introduces a novel diagnostic approach using extracranial biopsy to avoid high-risk brain procedures in aggressive lymphoma with CNS progression.

## Key findings

- Subthreshold PET/CT findings can indicate aggressive lymphoma despite low SUVmax values.
- Extracranial biopsy of accessible lymph nodes can confirm CNS lymphoma without requiring brain biopsy.
- Persistent lactic acidosis and hyperferritinemia are early signs of aggressive lymphoma progression.

## Abstract

We present a diagnostically challenging case of a 51-year-old woman with systemic diffuse large B-cell lymphoma (DLBCL) that progressed to secondary central nervous system (CNS) involvement. The initial presentation was notable for a whole-body PET/CT scan showing only subtle, diffuse fluorodeoxyglucose uptake in lymph nodes and bone marrow (SUVmax <5.0), below conventional thresholds for malignancy. Four months later, the patient developed an acute encephalopathic illness accompanied by multiorgan dysfunction and a severe hyperinflammatory state consistent with hemophagocytic lymphohistiocytosis. Hallmark laboratory features included refractory lactic acidosis, extreme hyperferritinemia, markedly elevated lactate dehydrogenase, and profound CD4+ lymphopenia. Cranial imaging revealed rapidly progressive, non−specific parenchymal lesions. A definitive diagnosis of the non−germinal center B−cell (non−GCB) subtype of DLBCL was secured via biopsy of a readily accessible facial lymph node—rather than high−risk brain biopsy—illustrating a pivotal diagnostic principle. This case highlights that unexplained persistent lactic acidosis, extreme hyperferritinemia, and even subthreshold PET/CT findings can be sentinel signs of an underlying aggressive lymphoma. It emphasizes the need for high clinical suspicion and the pursuit of safe, extracranial biopsy sites to enable early diagnosis and intervention in such diagnostically elusive cases.

## Linked entities

- **Proteins:** CD4 (CD4 molecule)
- **Chemicals:** fluorodeoxyglucose (PubChem CID 53716604)
- **Diseases:** diffuse large B-cell lymphoma (MONDO:0018905), hemophagocytic lymphohistiocytosis (MONDO:0015540), lactic acidosis (MONDO:0006040)

## Full-text entities

- **Genes:** CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}
- **Diseases:** lactic acidosis (MESH:D000140), lymphopenia (MESH:D008231), multiorgan dysfunction (MESH:D009102), malignancy (MESH:D009369), aggressive lymphoma (MESH:D008223), hyperferritinemia (MESH:D000085583), hemophagocytic lymphohistiocytosis (MESH:D051359), DLBCL (MESH:D016403)
- **Chemicals:** fluorodeoxyglucose (MESH:D019788)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12989377/full.md

## References

23 references — full list in the complete paper: https://tomesphere.com/paper/PMC12989377/full.md

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Source: https://tomesphere.com/paper/PMC12989377