Aqueous humor liquid biopsy identifies malignant transformation of retinocytoma in an adult patient
7 affiliations
- 1Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- 2The Vision Center, Department of Ophthalmology, Children's Hospital Los Angeles, Los Angeles, CA, USA
- 3Department of Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- 4Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA
- 5Department of Hematology-Oncology, Children's Hospital Los Angeles, Los Angeles, CA, USA
- 6Department of Pathology & Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA
- 7Department of Radiation Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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; the platform enabled 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: 1) somatic copy number analysis serves as a sensitive marker of intraocular malignancy, and 2) targeted sequencing panel provides 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.
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BibTeX
@article{hong2026aqueous,
title = {{Aqueous humor liquid biopsy identifies malignant transformation of retinocytoma in an adult patient}},
author = {Kendra L. Hong and Michelle Lin and Douglas Chigane and Elaine Huang and Atrey Khoche and Rahul S. Iyengar and Rodrigo A. Brant Fernandes and Gino In and Maria Sibug Saber and Jaclyn A. Biegel and Laura Kagami and Liya Xu and Patricia Chevez-Barrios and Andrew S. Lim and Jesse L. Berry},
journal = {American Journal of Ophthalmology Case Reports},
year = {2026},
month = oct,
doi = {10.1016/j.ajoc.2026.102688},
url = {https://doi.org/10.1016/j.ajoc.2026.102688},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Aqueous humor liquid biopsy identifies malignant transformation of retinocytoma in an adult patient
AU - Kendra L. Hong
AU - Michelle Lin
AU - Douglas Chigane
AU - Elaine Huang
AU - Atrey Khoche
AU - Rahul S. Iyengar
AU - Rodrigo A. Brant Fernandes
AU - Gino In
AU - Maria Sibug Saber
AU - Jaclyn A. Biegel
AU - Laura Kagami
AU - Liya Xu
AU - Patricia Chevez-Barrios
AU - Andrew S. Lim
AU - Jesse L. Berry
PY - 2026
DA - 2026/10/20
JO - American Journal of Ophthalmology Case Reports
DO - 10.1016/j.ajoc.2026.102688
UR - https://doi.org/10.1016/j.ajoc.2026.102688
AB - 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; the platform enabled 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: 1) somatic copy number analysis serves as a sensitive marker of intraocular malignancy, and 2) targeted sequencing panel provides 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.
SN - 2451-9936
ER -