Search

Purpose: To highlight the increasing importance of gene fusions in the diagnosis, prognosis, and therapy of ocular adnexal tumors., Design: Perspective., Methods: A focused review of gene fusions, their pathogenic mechanism, and gene fusion detection methods in lacrimal gland and primary orbital and ocular adnexal soft tissue tumors; reappraisal of diagnostic, prognostic, and therapeutic approach to ocular adnexal tumors in light of emerging molecular genetic data., Results: The widespread implementation of fluorescence in situ hybridization and next-generation sequencing methods in pathology practice has led to identification of recurrent gene rearrangements and fusions in a variety of tumors. As a result, molecular genetic methods have become the gold standard for diagnosis of tumors with overlapping histology and immunophenotype, such as small round blue cell tumors. Identification of canonic gene fusions has led to development of sensitive and specific immunohistochemical markers, such as STAT6 in solitary fibrous tumor. In addition to diagnostic accuracy, gene fusions have prognostic implications, such as unfavorable prognosis of PAX3-FOXO1 fusion in alveolar rhabdomyosarcoma. Finally, recognition of gene fusions as a driving mechanism in neoplasia has led to development of U.S. Food and Drug Administration-approved targeted therapies, such as TRK inhibitors for NTRK fusion-positive cancers., Conclusion: The discovery of recurrent gene fusions in various tumors, including those involving ocular adnexa, has led to a deeper insight into the molecular mechanisms of these neoplasms, revolutionizing our approach to their diagnosis, prognostication, and therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Secretory carcinoma has been described in the breast, salivary glands, skin, and other organs, but has not been reported in the lacrimal gland to date. Since lacrimal and salivary glands show similar tumors, we hypothesized that lacrimal secretory carcinoma may exist but has been misclassified in the past., Design: We undertook a retrospective review of all lacrimal gland tumors at 2 tertiary institutions with centralized ocular pathology practices., Methods: A total of 350 lacrimal tumors were reviewed by the authors. Candidate tumors were tested for ETV-NTRK rearrangement by fluorescence in situ hybridization and the presence of the translocation was confirmed by next-generation sequencing., Results: We identified a single case of secretory carcinoma. The diagnosis was confirmed by demonstrating specific immunohistochemical profile and the presence of ETV6-NTRK3 gene fusion, which is characteristic of secretory carcinoma of other sites. The tumor occurred in a young man who was treated with surgery alone with no recurrence during 12 years of follow-up., Conclusion: Secretory carcinoma is a new lacrimal gland carcinoma type that should be added to the spectrum of low-grade lacrimal gland tumors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To investigate the feasibility of integrating molecular analysis into standard histopathology for lacrimal gland adenoid cystic carcinoma (ACC), and to gain insights into the molecular pathogenesis of this tumor and its response to intraarterial cytoreductive chemotherapy (IACC) that is of clinical use., Design: A retrospective, comparative case series., Methods: setting: Institutional. patient population: Nine consecutive patients with lacrimal gland ACC were treated with IACC, followed by orbital exenteration and chemoradiotherapy. This case series was compared with a series of seven patients treated by conventional local therapies. intervention procedure: Gene analysis was performed on microdissected tissue samples. Mutational allelotyping targeting nine genomic loci was performed with 15 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes serving as markers for the presence of gene deletion. main outcome measure: A fractional mutation index was used to compare the acquired mutational load between different tumors having nonidentical patterns of microsatellite informativeness., Results: Allelic imbalance (loss of heterozygosity [LOH]) for microsatellite markers at 1p36 was the single most common site affected by imbalance in this series, followed by LOH in temporal sequence involving 9p21, 22q12, 10q23, and 9q22., Conclusions: Microdissection genotyping holds promise as a clinical tool in integrating molecular analysis into standard histopathology to advance the understanding of lacrimal gland ACC tumorigenesis. A unique time course for temporal mutation acquisition in ACC is proposed, consisting of 1p36 loss first. Allelic loss for microsatellite markers at 1p36 may be a common as well as an early event in ACC formation and progression.