MYD88 L265P mutation in intraocular lymphoma: A potential diagnostic marker.

PURPOSE: Vitreoretinal lymphoma (VRL) is the most common intraocular lymphoma (IOL). This can be either primary or secondary to the central nervous system lymphoma. The diagnosis of primary intraocular lymphoma (PIOL) currently relies on clinical diagnosis and cytological analysis of the vitreous or subretinal biopsy. Although most cases are diagnosed without much issue, the limited amount of vitreous fluid, subjectivity in cytological reporting, and special expertise in ocular pathology make the diagnosis challenging. MYD88 L265P mutation has been implicated to have diagnostic utility in PIOL. In this study, we screened consecutive vitreous biopsies for the presence of MYD88 L265P mutation to understand its diagnostic utility compared to conventional cytological analysis. METHODS: Cytological analysis and MYD88 L265P mutation by PCR-based sequencing and restriction fragment length polymorphism (RFLP) were carried out on consecutive vitreous and subretinal biopsies collected from 21 patients. The diagnostic utility of the cytology and MYD88 L265P mutation analysis were compared. RESULTS: Out of the 21 patients, 15 had clinical suspicion of having PIOL. Out of these suspected cases of PIOL, nine were confirmed on follow-up, while six were diagnosed as other intraocular pathologies. Diagnostic utility of MYD88 L265P mutation analysis revealed a sensitivity of 88.9%, specificity of 91.6%, positive and negative predictive value of 88.9% and 91.7%, respectively. Diagnostic accuracy of 90.5% was achieved with the mutation analysis that shows the superiority of MYD88 in both ruling in and ruling out PIOL. The diagnostic utility of MYD88 L265P mutation was superior to conventional cytological analysis. CONCLUSION: The analysis of MYD88 L265P mutation is reliable and efficient in the diagnosis of PIOL.

Major histocompatibility antigens and antigen-processing molecules in retinoblastoma.

BACKGROUND: Malignant transformation of cells is frequently associated with abnormalities in human leukocyte antigen (HLA) expression. These abnormalities may play a role in the clinical course of the disease, because HLAs mediate interactions of tumor cells with cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Retinoblastoma is the most common intraocular malignant tumor in childhood and is characterized by direct spread to the optic nerve and orbit as well as hematogeneous and lymphatic spread. Little is known about the role of HLA expression in the progression of this malignant disease. METHODS: HLA Class I antigen, beta2-microglobulin (beta2-m), HLA Class II antigens, and the antigen-processing molecules (APMs) of the HLA Class I pathway, including proteasomal subunits (low-molecular mass polypeptide 2 [LMP-2] and LMP-10), the transporter-associated protein (TAP-1) subunit, the binding protein tapasin, and the chaperone molecule calnexin, were studied in 30 archival retinoblastoma specimens by immunohistochemistry. Immunoanalysis was performed based on the International Histocompatibility Working Group Project Description. RESULTS: HLA Class I antigen, beta2-m, HLA Class II antigen, and APMs were positive in 12 tumors with no invasion and were decreased in 13 tumors with choroidal and optic nerve invasion. The difference in HLA and APM expression between the 2 groups was statistically significant (P < 0.001). CONCLUSIONS: Decreased expression of HLA was observed in aggressive tumors and in poorly differentiated tumors. The current findings support a role for both CTLs and NK cell-mediated control of tumor growth in the clinical course of retinoblastoma.