New study could improve testing and treatment for rare brain, spinal cord, and eye cancers

by Association for Diagnostics & Laboratory Medicine (ADLM)

edited by Sadie Harley, reviewed by Andrew Zinin

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A new study has identified hepatitis A virus cellular receptor 1 (HAVCR1) as a biomarker that could make it easier to diagnose rare but aggressive forms of brain and eye cancer earlier and with fewer invasive tests.

Published in Clinical Chemistry, the findings suggest the biomarker could help physicians make treatment decisions sooner and with greater confidence, while giving clinical laboratories a new tool to track treatment response and detect relapse.

Primary central nervous system lymphoma (PCNSL), a rare cancer that affects the brain, spinal cord, or eyes, has one of the poorest prognoses among cancers that originate in white blood cells.

Despite advances in imaging, molecular characterization, and treatment, cases of this type of cancer have steadily increased over the past five decades. The diagnostic accuracy of measuring interleukin (IL) levels, the current, most effective method for detecting PCNSL, is limited to approximately 80–90%.

Patients with primary vitreoretinal lymphoma (PVRL) in particular—a rare form of PCNSL confined to the eyes—face additional diagnostic challenges. For one, PVRL frequently mimics uveitis, inflammation that affects the middle layer of tissue in the eye.

Unlike other types of PCNSL, where tumor tissue can often be obtained for evaluation, the scarcity and fragility of PVRL cells also limits reliable testing.

As a result, the diagnosis of PVRL is often delayed, taking up to two years from the onset of symptoms and typically requiring multiple biopsies, compared with 35 days for PCNSL. Because PVRL is associated with a high risk of progression to intracranial PCNSL in 60–90% of cases, early diagnosis is especially important for those with this condition; timely and appropriate treatment reduces the risk of neurological complications and death.

To find a biomarker that could aid in earlier diagnosis of PCNSL, and especially PVRL, a group of researchers from Fudan University in Shanghai, China, set out to determine which proteins consistently differ between patients with these types of lymphoma and those without.

Using advanced protein-screening technology, they analyzed eye fluid and cerebrospinal fluid samples from 199 patients with PVRL and PCNSL and 179 with inflammatory or noncancerous conditions or no conditions.

The study showed that HAVCR1 repeatedly stood out, with its levels being much higher in patients with PVRL and PCNSL than in people without these conditions.

In eye fluid samples from patients with PVRL, HAVCR1 achieved diagnostic accuracy approximately 92–100% of the time, and in cerebrospinal fluid from patients with PCNSL, accuracy reached 97–99%. Further, HAVCR1 accurately distinguished lymphoma from uveitis, outperforming commonly used markers such as IL-10 and IL-6, which can give unclear results when inflammation is present.

Importantly, HAVCR1 levels dropped after successful treatment and remained high in patients whose disease did not fully respond to treatment, suggesting that the biomarker could also be useful for monitoring treatment response.

Additional analyses showed that HAVCR1 is produced primarily by the tumor cells themselves, strengthening its reliability as a cancer‑specific marker. Altogether, these findings suggest that HAVCR1 could enable earlier diagnosis, decrease the need for invasive biopsies, and improve monitoring of patients with PCNSL and PVRL.

"HAVCR1 is a robust fluid-based biomarker for PCNSL and PVRL and has been validated in multiple cohorts and sample types," the researchers wrote. Although more research must be done to ensure validity of HAVCR1's usefulness and reproducibility across laboratories, the biomarker is a promising candidate for clinical use.

"Its superior diagnostic accuracy compared with existing cytokine assays, together with its dynamic responsiveness to treatment, highlights its dual value in both diagnosis and disease monitoring," the researchers said.

Publication details

Shengjie Li et al, Tumor-Derived HAVCR1 As a Reliable Fluid Biomarker for the Diagnosis of CNS Lymphoma, Clinical Chemistry (2026). DOI: 10.1093/clinchem/hvag036

Journal information: Clinical Chemistry

Key medical concepts

Primary Central Nervous System LymphomaUveitis

Clinical categories

OncologyOphthalmology Provided by Association for Diagnostics & Laboratory Medicine (ADLM) Who's behind this story?

Sadie Harley

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