The 5th edition of the World Health Organization (WHO) Classification of Tumours of the Eye and Orbit is the latest step in standardizing the diagnostic practice worldwide. Building upon the 4th edition, published in 2018, the 5th edition introduces new chapters on the eyelid and orbital tumors, and consolidates sections on hematolymphoid tumors, soft tissue and bone tumors, metastases and genetic tumor predisposition syndromes into dedicated chapters. Written in the format of the other 5th edition volumes, a systematic approach is taken to describe the defining characteristics of each tumor type and its staging, with the addition of macroscopic appearance, cytology, diagnostic molecular pathology, and essential and desirable diagnostic criteria. This volume highlights recent advances in the etiology, pathogenesis, and diagnosis of tumors of the eye and ocular adnexa. Radiologic and ophthalmic features are also emphasized. Moreover, the 5th edition includes updates on the classification scheme for certain tumors, such as vascular anomalies, and introduces tumors that have been recently identified in the eye and ocular adnexa. This editorial summarizes the major general changes in the 5th edition of the WHO classification of Tumours of the Eye and Orbit, and the specific updates in each taxonomic category, with an emphasis on advances in understanding tumor pathogenesis, diagnostic and prognostic criteria, and novel immunohistochemical and molecular markers.

PURPOSE: To characterize demographic, clinical, and histopathologic features of ocular adnexal lymphoma (OAL) at a single institution. METHODS: Retrospective review of all patients with pathologic diagnosis of OAL between 2015 and 2020. RESULTS: There were 133 patients with OAL, with a median age of 65 years (range 23–97) and a slight female predominance (male: female = 1:1.46), (n = 79, 59%). The majority of tumors were non-Hodgkin B-cell lymphomas (n = 131, 99%), most frequently Extranodal Marginal Zone B-Cell Lymphoma (EMZL, n = 93, 70%), followed by follicular lymphoma (n = 21, 16%), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 7, 5%), diffuse large B-cell lymphoma (n = 5, 4%), and mantle cell lymphoma (n = 5, 4%). The most frequently involved sites included the orbit (n = 85, 64%) and conjunctiva (n = 43, 32%). Information was available on oncologic staging in 78 (59%), treatment in 82 (62%), and follow-up in 75 (56%) patients. By the Ann-Arbor classification system, patients were classified as IE (54/78, 69%), IIE (9/78, 12%), IIIE (6/78, 8%), and IVE (9/78, 12%). The most common treatments included external beam radiotherapy (standard and ultra-low-dose) (48/82, 59%), biologics (22/82, 27%), and surgical excision with cryotherapy (14/82, 17%) (some patients had >1 therapy). Median follow-up time was 24 months (range 0–221 months). Recurrence was observed in 13% (10/75) with a median time to recurrence of 60 months (95% confidence interval 47–73 months). Excision with cryotherapy as a sole treatment modality was associated with earlier recurrence (P = 0.003). CONCLUSION: In this largest single-center study of OAL, we found that most OAL were Ann-Arbor Stage IE EMZL, occurring in older patients with a female predominance. Early recurrence was noted in tumors treated with excision and cryotherapy alone.

Vitreoretinal lymphoma (VRL) is a rare ocular pathology that is notorious for mimicking chronic uveitis, which is a seemingly benign condition in comparison. The most common form of VRL is the diffuse large B-cell type, and there has been a high mortality rate. This dismal prognosis can be improved significantly if the disease is diagnosed early, but until now there is no consensus on an appropriate diagnostic algorithm. We conducted a retrospective search of PubMed Central^® and analyzed results from thirty-three studies that were published between 2011–2021. The chosen studies incorporated some popular testing tools for VRL, and our analyses focused on comparing the average sensitivity of five diagnostic methods. The methods included cytology including ancillary immunohistochemistry, Myeloid Differentiation Factor 88 (MyD88) mutation analysis, polymerase chain reaction (PCR) for monoclonal rearrangements of immunoglobulin heavy chain (IgH) and T-cell Receptor (TCR) genes, flow cytometry, and IL10 and IL6 analysis. Across the varied diagnostic methods employed in thirty-three studies explored in this analysis, MyD88 mutation assay emerged as a strong contender given its sensitivity and low coefficient of variation. There is an imminent need for the introduction of newer assays that can further improve the sensitivity of identifying MyD88 mutation in cancer cells seen in the vitreous.