Work

Aqueous humor liquid biopsy identifies malignant transformation of retinocytoma in an adult patient

Year: 2026

Type: article

Abstract: ABSTRACT Purpose To report a rare case of adult-onset retinoblastoma arising from malignant transformation of retinocytoma and to highlight the diagnostic utility of the aqueous humor liquid biopsy. Observation A 34-year-old woman presented with three months of floaters and flashes in the left eye. Examination revealed a peripheral amelanotic retinal lesion with retinal pigment epithelial changes, calcification, and vitreous debris. Aqueous humor biopsy analyzed with the LBSeq4Kids platform demonstrated chromosomal aneuploidy consistent with tumor-derived DNA, although the copy number profile was not characteristic of retinoblastoma or other malignancies. Germline and plasma-based testing were non-diagnostic, and systemic evaluation revealed no evidence of an occult malignancy. Over 3 months, the lesion demonstrated subtle growth from 1.32 to 1.55 mm in thickness with more vitreous debris and calcification, raising concern for retinoblastoma. However, the patient’s age, atypical clinical features, and non-canonical molecular findings created diagnostic uncertainty. Following multidisciplinary review, pars plana vitrectomy and retinectomy were performed for histopathologic confirmation. The tumor was completely excised. Pathology demonstrated a neuroendocrine tumor surrounded by well-differentiated “fleurettes,” consistent with retinoblastoma arising from retinocytoma. Given the potential risk of occult extraocular extension following biopsy, the patient underwent adjuvant external beam radiation therapy to the left orbit. Three months after surgery, the LBSeq4Kids targeted sequencing panel was clinically validated and became available for the aqueous humor liquid biopsy, enabling detection of pathogenic variants in a panel of cancer-associated genes. Subsequent retrospective analysis of the original aqueous humor biopsy using the newly validated assay identified two pathogenic RB1 variants, confirming the retinoblastoma diagnosis. At more than 1 year after diagnosis, the patient remains disease-free. Conclusion and Importance Adult-onset retinoblastoma is exceedingly rare and may arise through malignant transformation of retinocytoma. This case highlights the complementary roles of two clinically available aqueous humor-based molecular assays with somatic copy number analysis serving as a sensitive marker of intraocular malignancy and targeted sequencing panel providing greater diagnostic specificity for tumor classification. In the future, these minimally invasive assays can aid in the differential diagnosis of atypical intraocular tumors and may provide an alternative to direct intraocular tumor biopsy.

Source: American Journal of Ophthalmology Case Reports

DOI: 10.1016/j.ajoc.2026.102688