Ocular Oncology and Pathology最新文献

Background: Patients with treated uveal melanoma or suspicious choroidal naevi require a long period of follow-up to detect and treat malignant change in a timely manner. Ocular oncology patients are often managed in highly specialized services and such follow-up can create a significant burden on a service.

Summary: The availability of high-quality imaging has increased acceptability of virtual clinics in other subspecialist areas of ophthalmology. Multi-modal imaging is an important tool for monitoring choroidal lesions and review of imaging by consultant ocular oncologist has been found to be highly sensitive and specific for detecting change of choroidal lesions. Virtual clinics can improve patient access to care, reducing barriers such as time, travel and financial costs. Our experience of virtual oncology clinics in the Scottish Ocular Oncology Service (SOOS) found a high level of patient satisfaction provided results are communicated to patients in a timely manner.

Key messages: There is a need for increased capacity in both triaging and monitoring of choroidal naevomelanocytic lesions and virtual clinics provide an efficacious solution to this. Change in practice is challenging, however, with increased accessibility to high-quality imaging modalities, standardized assessment protocols, and focus on patient communication the role of virtual services in ocular oncology is promising.

Background: The study of ophthalmic pathology plays a crucial role in the diagnosis and management of ocular diseases. Ophthalmic pathology, as a discipline, plays many roles in patient care, including diagnosing diseases, interpreting the significance of clinical findings, and guiding patient management. It also plays a critical role in research by elucidating disease mechanisms, such as those underlying glaucoma, the world's second-leading cause of blindness. It contributes to the development of new or modified therapeutic approaches in glaucoma.

Summary: This paper highlights the crucial role of pathology in understanding the pathophysiology of normal-tension glaucoma and childhood glaucoma. It also reviews the use of pathologic specimens to elucidate the mechanisms of bleb complications after trabeculectomy and failure of glaucoma shunts.

Key messages: Studying pathologic changes in ocular tissues remains crucial in understanding glaucoma and can lead to changes in clinical practice, ultimately improving patient care. Correlation of pathological findings in ocular tissues with gene expression and proteomics is one approach to understanding the mechanisms leading to glaucoma. The findings from such an approach could potentially be applied in precision medicine-based therapy.

Background: Retinal capillary hemangioblastoma (RCH) is a benign tumor that frequently appears as the first manifestation in patients with von Hippel-Lindau (VHL) disease, potentially resulting in significant vision loss. Thus, recognizing and managing it promptly is crucial.

Summary: New imaging techniques, including widefield optical coherence tomography (OCT) and OCT angiography, improve diagnostic accuracy and monitoring, facilitating early treatment and better prediction of visual outcomes. While traditional therapies such as laser photocoagulation, cryotherapy, and vascular endothelial growth factor inhibitors serve as the cornerstones of RCH therapy, new approaches, including tyrosine kinase inhibitors and hypoxia-inducible factor inhibitors, also exhibit promising results in treating resistant or recurrent tumors. Furthermore, genetic testing and counseling are beneficial for identifying patients linked to VHL disease, allowing early detection of systemic manifestations of this syndrome and enabling proper therapeutic management.

Key messages: This review consolidates the epidemiology, pathophysiology, clinical imaging, diagnostic evaluation, and treatment of RCH, emphasizing new insights pertinent to clinical practice and patient care.

Introduction: Malignant eyelid tumors, despite being rare, are on the rise, especially in the older population, with risk factors including ultraviolet light exposure. Trends have been notable to be different among different genders, races, age groups, etc. Therefore, analyzing temporal trends in the incidence of eyelid cancers, including malignant melanoma (MM), Merkel cell carcinoma (MCC), and sebaceous gland carcinoma (SGC), and predicting future patterns would definitely improve our understanding of the disease.

Methods: A retrospective study was conducted on the Surveillance, Epidemiology, and End Results (SEER) database spanning 2000-2021. Time series models were applied to estimate incidence rates (IRs) per 100,000. The best models were selected based on root mean square error (RMSE) and Akaike information criterion. Poisson regression was used to assess the impact of gender and age ≥60 on IRs.

Results: The autoregressive integrated moving average (ARIMA)(0,1,0) model (RMSE = 0.0144, Akaike information criterion = -100.23) showed an increasing overall trend in eyelid cancers IRs from 2000 to 2015, declining slightly until 2020 (IR = 0.1028), then rising again in 2021. The 10-year forecast predicts an increase to 0.13 (95% PI: 0.11-0.15). For MM, error, trend, seasonal (M,N,N) model indicated a gradual IR rise until 2010, followed by a decline, and subsequent rise to 0.068 in 2020; predicted to reach 0.081 (95% PI: 0.062-0.100) by 2022. For MCC, neural network autoregression (2,2) model showed IR stability (0.003-0.008), with a slight drop in 2021 (IR = 0.006), and predicted to decrease to 0.01 (95% PI: 0-0.01). For SGC, ARIMA(0,0,0) model demonstrated a decline in IR in 2011 (IR = 0.0192), increase until 2019, then decrease in 2021 (IR = 0.0246), with a predicted 10-year decrease to 0.026 (95% PI: 0.019-0.032). Poisson regression revealed that age ≥60 significantly increased IRR for both MM and SGC (17.0 and 25.4, respectively). Gender was nonsignificant for all three cancers.

Conclusion: Incidence of eyelid cancers revealed variable temporal trends, with a slight overall increase projected. Age ≥60 is a strong risk factor, particularly for MM and SGC.

Introduction: Medulloepithelioma is a rare tumour arising from the primitive medullary epithelium affecting predominantly children.

Case presentations: We present 2 patients with ocular medulloepithelioma presenting in the first 2 years of life with strabismus, leukocoria and a large ocular mass occupying the globe. The clinical presentation and imaging initially raised suspicion for retinoblastoma and enucleation was performed. Histopathology confirmed the diagnosis of teratoid medulloepithelioma in both cases and genetic testing found a germline DICER1 mutation in one of them.

Conclusion: These cases highlight the importance of considering medulloepithelioma in the differential diagnosis of intraocular tumours and underscore the value of genetic evaluation for underlying DICER1 mutations.

Introduction: Retinocytomas are rare benign intraocular tumors that may mimic spontaneously regressed retinoblastoma (Rb).

Materials and methods: This was a retrospective monocentric study of patients with retinocytoma in a French tertiary ocular oncology center, with an inclusion period from January 1999 to January 2024.

Results: Sixteen patients with retinocytoma were identified, and 1,351 Rbs were diagnosed during the same 25-year period. Age at diagnosis ranged from 11 months to 75 years (mean 28.1 years). Thirteen cases were asymptomatic, while three presented with floaters, decreased visual acuity, or strabismus. Clinical presentation was a whitish or grayish retinal tumor with a translucent (87%) and/or fragmented appearance (76%) at diagnosis. A proportion of lesions were surrounded by atrophy (52%) and/or pigmentation (30%). Eleven patients had unilateral retinocytoma (one of which was multifocal), and five had bilateral lesions. Eight patients had a known family history of Rb. Patients were followed regularly and underwent genetic counseling. The eight patients with a family history had a germline pathogenic variation of the RB1 gene. None showed malignant transformation during follow-up (mean 79.5 months, median 35.5 months).

Conclusion: The presentation of retinocytoma is most often asymptomatic. Thus, diagnosis may be delayed to far later ages than expected with Rb. Retinocytoma may be associated with germline pathogenic variants of the RB1 gene, and follow-up is recommended due to rare but possible malignant transformation.

Introduction: Conjunctival papillomatosis (CP) is a benign epithelial tumor of the conjunctiva that is often associated with human papillomavirus infection. Treatment of CP poses challenges owing to its tendency for local recurrence despite a multitude of treatment options. Although human papillomavirus (HPV) vaccine was originally developed for prevention, it garnered interest for its potential therapeutic role in treating recurrent HPV-associated lesions. A few case reports have described conjunctival papilloma lesion regression after HPV vaccination, offering an alternative treatment option.

Case presentation: We present 3 patients with CP who demonstrated no clinical response to 9-valent HPV vaccination.

Conclusion: These findings highlight some of the limitations of the vaccine in the context of CP.

Background: Belzutifan is an orally administered small molecule inhibitor of HIF-2-alpha that has been approved for use in von Hippel-Lindau (VHL)-associated renal cell carcinoma, central nervous system (CNS) hemangioblastomas, and pancreatic neuro-endocrine tumors. While use of the drug for treatment of VHL-associated retinal hemangioblastomas (RH) remains off-label, numerous case reports, case series, and a clinical trial sub-analysis have demonstrated excellent results in using the drug to control these tumors.

Summary: We review the literature that has been published on the use of belzutifan for RH in patients with VHL. These studies have described good efficacy for treating RH and preventing the development of new ocular tumors. The efficacy for juxtapapillary and macular tumors that can be difficult to treat has been particularly promising. Dose reductions are commonly required due to side effects which most commonly include anemia and fatigue.

Key messages: While early reports are encouraging, the optimal dose of the drug for controlling RH along with the duration of therapy, role as a neoadjuvant, and ways to incorporate use of the drug into the treatment and screening paradigms for VHL-associated ocular disease are evolving.

Introduction: Most uveal melanomas (UMs) are readily diagnosed based on their characteristic features, but they can occasionally pose a diagnostic challenge, such as when they present as an inflammatory mass. We present 2 patients who presented with an intraocular mass that was initially diagnosed as an inflammatory or infectious process and subsequently found to represent a UM.

Case presentations: Two cases of UM masquerading as uveitis are described.

Conclusion: UM should be considered in the differential diagnosis of an intraocular inflammatory mass. Diagnosis may require tumor biopsy.

Introduction: Uveal melanocytomas are benign melanocytic proliferations characterized histologically by large polyhedral cells, abundant intracytoplasmic melanin, small centrally located nuclei, and low nuclear-to-cytoplasmic ratios (N:C). Activating missense changes of the G-protein subunits, GNAQ/GNA11, drive uveal melanocytic proliferation and are characteristic molecular mutations found in intraocular nevi including melanocytomas, as well as malignant uveal melanomas. Sequencing of uveal melanocytic proliferations from biopsies or enucleations identifies these mutations and complements traditional histochemical approaches to classify and diagnose the uveal melanocytic neoplasm as well as offering valuable clinical prognoses about patient outcomes.

Case presentation: A 56-year-old female presented with gradual, painless vision loss in the left eye. On exam, a large (11.1 × 12.8 × 10.6 mm by ocular ultrasound), hyperpigmented ciliochoroidal mass was found in the superior nasal quadrant abutting the lens. The patient elected for enucleation given the tumor's large size and vision loss in the affected eye. An fine needle aspiration (FNA) biopsy of the fresh mass, collected immediately after enucleation, revealed no mutations in the 7-gene DecisionDX-UMSeq panel. Histologic and immunohistochemical evaluation of pupil-optic nerve cross-sections from the formalin fixed paraffin embedded enucleation revealed a ciliary body melanocytoma. DNA extracted from the melanocytoma enucleation cross-sections was sequenced for 197-clinically actionable tumor genes through the Stanford's Actionable Mutation Panel for Solid Tumors (STAMP). The sequencing results confirmed no mutations in GNAQ, GNA11, and the other uveal melanoma genes tested via the DecisionDX-UMSeq panel but identified missense variants of unknown significance in three genes previously not reported in uveal melanocytic neoplasms.

Conclusion: To our knowledge, this is the first reported uveal melanocytoma lacking GNAQ/GNA11 oncogenic variants or other known uveal melanocytic neoplasm driver mutations. This case supports that there are additional to-be-identified molecular pathways and genes that drive uveal melanocyte proliferations.