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Updated: Jul 16, 2026
Cell-Free DNA Extraction of Vitreous and Aqueous Humor Specimens for Diagnosis and Monitoring of Vitreoretinal Lymphoma
Published on: January 12, 2024
Primary intraocular lymphoma: improving the diagnostic procedure
Anni Karma1, Eva O von Willebrand, Petri V Tommila
1Department of Ophthalmology, University of Helsinki, Helsinki, Finland. anni.karma@fimnet.fi
Insights
Diagnosing primary intraocular lymphoma (PIOL) is challenging. Proper vitreous sample handling and expert cytopathology are crucial for accurate PIOL diagnosis, especially in elderly patients with severe bilateral uveitis.
Area of Science:
- Ophthalmology
- Oncology
- Pathology
Background:
- Primary intraocular lymphoma (PIOL) is a rare extranodal non-Hodgkin lymphoma.
- Delayed diagnosis of PIOL often leads to poor visual outcomes and systemic spread.
Purpose of the Study:
- To analyze the clinical features of PIOL.
- To evaluate cytochemical and immunocytochemical findings in vitreous specimens.
- To identify reasons for delayed PIOL diagnosis.
Main Methods:
- Prospective study of 11 patients diagnosed with PIOL between 2000 and 2005.
- Analysis of clinical features, diagnostic workup, and vitreous biopsy findings.
- Comparison of diagnostic yield between alcohol-fixed and unfixed vitreous samples.
Main Results:
- The median age of patients was 61 years, with a median delay of 8 months from symptom onset to diagnosis.
- Severe bilateral vitreitis was a common clinical finding.
- Alcohol fixation of vitreous samples resulted in non-diagnostic results in 4 out of 12 biopsies.
Conclusions:
- Severe bilateral vitreitis in elderly patients is characteristic of PIOL.
- Alcohol fixation of vitreous specimens can hinder PIOL diagnosis.
- Optimal vitreous sample handling and expert cytopathological examination are critical for PIOL diagnosis.
Objective:
To analyze the clinical features of primary intraocular lymphoma (PIOL) and to describe cytochemical and immunocytochemical findings of the vitreous specimens as well as the reasons for delayed diagnosis of PIOL.
Design:
Prospective noncomparative study.
Participants:
Eleven patients referred to the uveitis or medical retina units, Department of Ophthalmology, University of Helsinki, were diagnosed as having PIOL between 2000 and 2005. The median follow-up of the patients was 32 months.
Methods:
Clinical features and diagnostic workup of uveitis were described. Twelve vitrectomies were performed on 9 patients. The first 5 biopsies were fixed in an equal volume of 50% alcohol. The specimens of the next 7 vitrectomies were handled without alcohol, and tissue culture medium was added to the samples.
Main Outcome Measures:
Clinical features of PIOL, intervals from ocular symptoms and from first ophthalmological examination to diagnosis, and the role of a proper handling of the vitreous sample in the diagnosis of PIOL.
Results:
Six females (54%) and 5 males (46%) (median age, 61 years) were included. Ten patients had ocular symptoms for 1 to 30 months (median, 8) before the first contact with an ophthalmologist. Uveitis was bilateral in 9 patients. Vitreitis was seen in all patients, and it was severe in 8. Fundus lesions dominated in 3 patients. Six patients lost useful vision in one eye before the diagnosis of PIOL. Cytologic and immunohistochemical stainings prepared of the unfixed vitreous specimens showed PIOL in 6 patients. The samples fixed in alcohol were nondiagnostic in 4 patients, and in them, verification of diagnosis was based on brain biopsy (3) or cerebrospinal fluid (1) findings. Seven patients died due to primary nervous system lymphoma.
Conclusions:
Diagnosis of PIOL is difficult but can be improved. Severe bilateral vitreitis in an elderly patient is a characteristic finding of PIOL. Alcohol fixation may jeopardize the identification of PIOL cells in the vitreous sample. Optimal handling of the vitreous specimens and examination of the slides by an experienced cytopathologist are critical in the diagnostic workup of PIOL.
