Ocular Oncology and Pathology最新文献

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.

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.

Introduction: Choroidal osteoma is a rare benign tumor where mature bone replaces the choroid. Possible causes include inflammation, trauma, hormones, disorders of calcium metabolism, environmental factors, genetics, or osseous choristoma. This paper discusses 4 cases and literature regarding choroidal osteoma occurring concurrently with or secondary to uveal pathologies including uveitis and pachychoroid spectrum.

Case presentations: In case 1, a 41-year-old man with central serous chorioretinopathy (CSCR) in both eyes (OU) developed a choroidal osteoma in the left eye (OS) 8 years after the initial visit. Type 1 macular neovascularization (MNV) developed 4 years later at age 53. In case 2, a 50-year-old woman with CSCR OU developed a choroidal osteoma OS 15 years after the initial visit. The lesion gradually enlarged over another 15 years of observation. In case 3, a 24-year-old woman with Vogt-Koyanagi-Harada disease treated with systemic corticosteroids for 6 months developed choroidal osteoma OU and type 2 MNV in the right eye (OD) 16 years after the initial visit. In case 4, a 55-year-old man with concurrent posterior scleritis and choroidal osteoma OS developed type 1 MNV 13 years after the initial visit. He had a history of unknown uveitis treated with high-dose corticosteroid therapy 21 years previously. In all 5 eyes, the presence of osseous tissue in the choriocapillaris and Sattler's layer was confirmed by optical coherence tomography, B-mode ultrasound, or computed tomography. These lesions demonstrated observed growth in basal diameter and/or maturation process of bone tissue throughout the follow-up period.

Conclusion: We observed 5 eyes of four patients with choroidal osteoma in the choriocapillaris and Sattler's layer of the choroid secondary to CSCR, Vogt-Koyanagi-Harada disease, or posterior scleritis over a long follow-up period of 12-30 years. Secondary choroidal osteoma, ectopic bone in the choroid, can result from the transformation of mesenchymal cells stimulated by osteoprogenitors, such as bone morphogenetic proteins. Secondary choroidal osteoma should be recognized as a rare long-term complication of uveal pathologies.

Background: Although uncommon, tumors of the iris and ciliary body present significant diagnostic challenges because of their variable appearance and overlap between benign and malignant features and the difficulty of directly visualizing lesions located in the posterior iris or ciliary body using conventional methods.

Summary: The advent of high-resolution anterior segment imaging, particularly ultrasound biomicroscopy (UBM), has greatly enhanced the ability of clinicians to evaluate these lesions in vivo. This review synthesizes current evidence on the utility of UBM in the diagnosis, classification, and management of both iris and ciliary body tumors. The emphasis is placed on differentiating melanotic from amelanotic lesions, recognizing imaging characteristics that suggest malignancy and comparing UBM with other anterior segment modalities, such as gonioscopy and anterior segment optical coherence tomography. This study provides a detailed discussion of tumor morphology, growth patterns, and secondary complications, supplemented by illustrative examples from clinical practice.

Key message: UBM serves as a noninvasive, reproducible, and dynamic view of lesions located deep within the anterior segment, particularly those obscured from direct examination, thereby guiding both diagnosis and longitudinal management.

Introduction: Renal cell carcinoma (RCC) is a rare cause of ophthalmic metastasis. Immune checkpoint blockers (ICBs) such as ipilimumab and nivolumab (ipi/nivo) are first-line therapies for advanced RCC. There are limited efficacy reports of ICBs for RCC choroidal metastases (CMs).

Case one: A 43-year-old male with metastatic (lung) clear cell RCC presented with left eye scleritis and a 3.4 mm choroidal mass. One week after starting ipi/nivo, the lesion rapidly expanded to 11.9 mm with vitritis, subtotal exudative retinal detachment (ERD), and features of necrosis (heterogenous echogenicity). The lesion regressed over 10 months to 1.29 mm with resolution of ERD and improved visual acuity from counting fingers to 20/50.

Case two: A 63-year-old male with clear cell RCC presented with a right eye 7.2 mm choroidal mass and subretinal haemorrhage. The lesion enlarged to 10.9 mm with ERD and heterogenous echogenicity after starting ipi/nivo, which then regressed to 2.4 mm by 7 months, leaving retinal folds. Vision declined to hand motions and remained stable.

Conclusion: Ipi/nivo can induce rapid and sustained regression of RCC CM but may cause profound intraocular inflammation, collateral damage to surrounding structures, and subsequent vision loss. This response may be enhanced in the presence of pre-existing scleritis.

Introduction: The brachytherapy plaques used for uveal melanoma treatment are reused following sterilization processes. Here, we report patients with adverse reaction following a new cleaning procedure for brachytherapy plaques.

Case presentations: The brachytherapy plaque sewn on the outer eyewall would be removed following the delivery of calculated radiation dose. They are reused following standard calibration testing and sterilization processes. From September 2021 to January 2022, 6 patients treated with ruthenium-106 plaque brachytherapy presented with severe unilateral pain, eyelid swelling, and conjunctival injection with hemorrhage 1-2 days following plaque insertion. The surgeons observed a frosted appearance of the plaques in contrast to the normal shiny look during removal. The unusual severe postoperative reactions and the frosted appearance of plaques led to further investigations. A change in sterilization procedures with the use of LifeClean™ instead of PeraSafe™ was noticed. Ruthenium-106 brachytherapy plaques contain a uniformly distributed radioactive source covered by a thin silver shield. A test was performed by using two plates of pure silver that underwent its respective cleaning procedure using either PeraSafe™ or LifeClean™.

Conclusion: The test results demonstrated formation of silver chloride with LifeClean™, while no such formation was demonstrated with PeraSafe™. We did not observe any new cases of severe postoperative reaction or frosting of plaques after changing back to PeraSafe™. Chlorine salt deposits probably contributed to severe inflammatory reaction of ocular surface.

Background: Early and accurate diagnosis of choroidal tumors including benign nevi, melanomas, and vascular lesions is essential for effective clinical management. Conventional imaging techniques such as fundus photography, optical coherence tomography, fundus autofluorescence, and ultrasonography have greatly advanced the accuracy of choroidal tumor assessment but do have limitations. Hyperspectral imaging (HSI) is a noninvasive modality capturing high-resolution spectral data across multiple wavelengths and has shown promise in various medical fields. Its emerging use in ophthalmology may offer novel insights, although clinical evidence remains preliminary.

Summary: This review explores the principles of HSI and its early investigational role in ocular oncology. Although clinical evidence remains limited, HSI may help improve lesion differentiation, tumor margin delineation and potentially provide indirect biochemical insights. When combined with existing imaging techniques, HSI could support a more comprehensive and individualized diagnostic approach. Key challenges and future directions are discussed.

Key messages: HSI is a promising, noninvasive imaging innovation with potential to enhance choroidal tumor characterization. While still primarily investigational, further clinical validation is essential to determine its role in ophthalmic practice.