Leiomyoma - Ciliary Body Tumor. A Case Report.

AIM: To demonstrate a rare case of ciliary body leiomyoma in our patient Case report: A 72-year-old female reported to our clinic for a preventive examination, upon which we found a dome-shaped grey-brownish mass on the retinal periphery. After completing gonioscopic and ultrasound examinations, we referred the patient to a specialist facility. Due to a finding of suspicious malignant melanoma, we completed the MRI scan and recommended enucleation of the eyeball. A histopathological examination showed a leiomyoma of the ciliary body. CONCLUSION: The aim of this case report is to demonstrate the difficulty of intraocular leiomyoma diagnosis. Only immunohistochemical examination differentiated the tumor from malignant melanoma and determined the diagnosis of ciliary body leiomyoma. Perhaps because of the extreme rarity of this type of tumor, we often neglect to consider a diagnosis of leiomyoma.

Tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment: a case report.

BACKGROUND: Ocular tuberculosis is a relatively rare extrapulmonary manifestation of tuberculosis. This vision-threatening disease is extremely challenging to diagnose, particularly because it can mimic other diseases. We report a case of tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment. CASE REPORT: A 52-year-old female presented with bullous retinal detachment in her left eye, and ultrasound biomicroscopy (UBM) verified the presence of a lesion with ciliary body granulomatous inflammation. The T-SPOT was positive, and the purified protein derivative (PPD) test was strongly positive (diameter of 20 mm). Following the administration of oral anti-tuberculosis regimen combined with prednisone, the retina gradually became reattached, the ciliary body granuloma became significantly reduced in size, and the visual acuity of the patient noticeably improved. CONCLUSIONS: Tuberculous ciliary body granulomas can cause bullous exudative retinal detachment and can be diagnosed with UBM. Early and full-course anti-tuberculosis treatment (ATT) combined with corticosteroid therapy can improve the patient prognosis.

Anterior segment swept-source optical coherence tomography and ultrasound biomicroscopy in iris and ciliary body lesions.

OBJECTIVES: Differentiation of iris and ciliary body lesions as benign or malignant and cystic or solid is important. The aim of this study was to compare anterior segment swept-source optical coherence tomography (AS SS-OCT) and ultrasound biomicroscopy (UBM) findings in iris and ciliary body tumors. RESEARCH DESIGN AND METHODS: Forty-two eyes of 38 cases with iris and ciliary body tumors imaged with UBM and AS SS-OCT between September 2018 and September 2023 were evaluated retrospectively. RESULTS: Of 42 eyes, 14 had melanoma, 14 iris pigment epithelial (IPE) cysts, 7 nevi, 3 Lisch nodules, 2 iris stromal cysts, 1 pars plana cysts, and 1 iris mammillations. An equivalent (100%) visualization of the anterior tumor margin was obtained with both techniques. Compared to AS SS-OCT, UBM was superior for posterior margin visualization in melanocytic tumors and IPE cysts. Bland-Altman plots demonstrated good agreement between UBM and AS SS-OCT for melanocytic tumors < 2.5 mm in base diameter and < 2 mm in thickness. CONCLUSIONS: Although, UBM is the gold standard for ciliary body and iridociliary tumors. AS SS-OCT should be considered as an excellent alternative to UBM, especially in minimally elevated iris lesions.

Local resection via partial lamellar sclerouvectomy for ciliary body tumors - a case series.

BACKGROUND: Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. METHODS: Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. RESULTS: Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00-10.00) and the mean tumor thickness was 3.50 mm (range: 2.00-5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. CONCLUSIONS: Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

CRISPR-Cas9-mediated deletion of carbonic anhydrase 2 in the ciliary body to treat glaucoma.

The carbonic anhydrase 2 (Car2) gene encodes the primary isoenzyme responsible for aqueous humor (AH) production and plays a major role in the regulation of intraocular pressure (IOP). The CRISPR-Cas9 system, based on the ShH10 adenovirus-associated virus, can efficiently disrupt the Car2 gene in the ciliary body. With a single intravitreal injection, Car2 knockout can significantly and sustainably reduce IOP in both normal mice and glaucoma models by inhibiting AH production. Furthermore, it effectively delays and even halts glaucomatous damage induced by prolonged high IOP in a chronic ocular hypertension model, surpassing the efficacy of clinically available carbonic anhydrase inhibitors such as brinzolamide. The clinical application of CRISPR-Cas9 based disruption of Car2 is an attractive therapeutic strategy that could bring additional benefits to patients with glaucoma.

Pigmented medulloepithelioma of the optic nerve: A challenging diagnostic entity.

Because of its rarity, the diagnosis of optic nerve medulloepithelioma poses a real diagnostic challenge. Medulloepithelioma is a congenital tumor that derives from the primitive medullary epithelium present in the neural tube and the optic vesicle. Its classical location is the ciliary body. Cases of retinal or optic nerve locations have been rarely reported in the literature. Only 11 cases have been published in the English literature. Herein, we report the case of a 2-year-old boy who underwent enucleation of the right eye for a presumed diagnosis of right-eye retinoblastoma, based on the presence of leukocoria on ophthalmological examination. Pathological examination showed an optic nerve medulloepithelioma. A review of the literature is also discussed in our work.

Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye.

Changes in the anterior segment of the eye due to type 2 diabetes mellitus (T2DM) are not well-characterized, in part due to the lack of a reliable animal model. This study evaluated changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites, and ciliary body vasculature, in a rat model of T2DM compared with human eyes. Male Sprague-Dawley rats were fed a high-fat diet (45% fat) or normal diet, and rats fed the high-fat diet were injected with streptozotocin intraperitoneally to generate a model of T2DM. Cataract formation and corneal endothelial cell density were assessed using microscopic analysis. Diabetes-related rat aqueous humor alterations were assessed using metabolomics screening. Transmission electron microscopy was used to assess qualitative ultrastructural changes ciliary process microvessels at the site of aqueous formation in the eyes of diabetic rats and humans. Eyes from the diabetic rats demonstrated cataracts, lower corneal endothelial cell densities, altered aqueous metabolites, and ciliary body ultrastructural changes, including vascular endothelial cell activation, pericyte degeneration, perivascular edema, and basement membrane reduplication. These findings recapitulated diabetic changes in human eyes. These results support the use of this model for studying ocular manifestations of T2DM and support a hypothesis postulating blood-aqueous barrier breakdown and vascular leakage at the ciliary body as a mechanism for diabetic anterior segment pathology.

Intraocular schwannoma: case series of 28 patients and literature review.

PURPOSE: Intraocular schwannoma is a rare tumour, which is often misdiagnosed. We presented the demographics and clinical characteristics of patients with intraocular schwannoma. METHODS: Retrospective case series were collected between May 2005 and July 2021 in Beijing Tongren Hospital. RESULTS: A total of 28 patients were diagnosed with intraocular schwannoma on histopathological examination of surgical specimen. The median age was 39 years (range: 12-64). Fourteen patients were female and 14 were male. Among the all subjects, 21/28 patients (75.0%) presented as visual loss, and 3/28 patients (10.7%) had visual field loss. Intraocular schwannoma presented as nonpigmented mass in the ciliary body in 12/28 cases (42.9%), in the choroid in 9/28 cases (32.1%), and in ciliochoroid in 7/28 cases (25.0%). Intraocular schwannoma was often clinically misdiagnosed as uveal melanoma, which occurred in 16/28 patients (57.1%). Tumour excision with pars plana vitrectomy was performed for all included patients. Endoresection with lens removal was performed for tumours in the choroid, while transscleral resection was performed for tumours located in ciliary body or ciliochoroid. Increased light transmission was detected in 12/28 cases (42.9%). In the consecutive follow-up (median: 73 months, range: 7-193 months), no cases of recurrence or metastatic disease were detected. CONCLUSIONS: Intraocular schwannoma is a rare benign tumour. It usually presents as nonpigmented mass, which can easily be misdiagnosed as nonpigmented uveal melanoma.

Intraocular medulloepithelioma clinical features and management of 11 cases.

AIMS: To describe the clinical features, imaging characteristics, histopathology, treatment and outcomes of intraocular medulloepithelioma. METHODS: Medical records of 11 patients with clinically or histopathologically confirmed medulloepithelioma were retrieved and reviewed. Clinical features, diagnostic challenges, imaging characteristics, management, histopathology and prognosis were assessed. RESULTS: The median age of the patients at initial diagnosis was 4 years, with the most common manifestations being leukocoria (five eyes), loss of vision (four eyes), ocular pain (one eye) and ophthalmic screening (one eye). The clinical signs include a grey-white ciliary body lesion, cataract or lens subluxation, secondary glaucoma and evident cysts. The ultrasound biomicroscopy (UBM) imaging most commonly displays ciliary body mass with intratumoural cysts (nine eyes). Three patients underwent surgery for cataract or glaucoma while the tumours were incidentally found. Two of the three patients managed by eye preserve treatments eventually required enucleation because of local tumour recurrence or phthisis. One patient treated with intra-arterial chemotherapy and cryotherapy had successful tumour regression and globe salvage. CONCLUSIONS: Initial misdiagnosis, delay in diagnosis and subsequent misdirected management is not uncommon in medulloepithelioma. The presence of multiple cysts in the tumour and retrolental neoplastic cyclitic membrane detected by UBM can offer certain information. Selective intra-arterial melphalan may prevent further tumour growth, but longer follow-up is necessary until treatment efficacy is fully evaluated.

Improved Staging of Ciliary Body and Choroidal Melanomas Based on Estimation of Tumor Volume and Competing Risk Analyses.

PURPOSE: The current, 8th edition of the American Joint Committee on Cancer (AJCC) anatomic classification and staging model for uveal melanoma does not fully separate survival estimates for patients with advanced stages of the disease (e.g., IIIB and IIIC). Furthermore, some tumors in higher size categories have a smaller volume than tumors in lower categories. Therefore, we developed a novel model for prognostication of metastatic mortality based on estimations of tumor volume. DESIGN: Retrospective, multicenter case series of patients with uveal melanoma involving the choroid, ciliary body, or both. PARTICIPANTS: Six thousand five hundred twenty-eight consecutively registered patients treated at 3 tertiary ocular oncology centers on 2 continents between 1981 and 2022. METHODS: Data on survival, tumor size, and extent were collected for all 6528 patients. Tumor volume was estimated using a simple equation based on largest basal diameter and thickness. Volume-based size categories and stages were developed and validated in independent patient cohorts using competing risk analyses, and correlations with cytogenetic and cytomorphologic features were examined. MAIN OUTCOME MEASURE: Cumulative incidence of metastatic death. RESULTS: The 6528 patients were distributed over 7 stages based on estimated tumor volume and anatomic extent (V stages IA, IB, IIA, IIB, IIIA, IIIB, and IIIC), with a 15-year incidence of metastatic death ranging from 7% to 77%. A new category, V1min, and corresponding stage IA, were introduced, indicating an excellent prognosis. Metastatic mortality in V stage IIIC was significantly higher than that in V stage IIIB (P = 0.03), whereas incidence curves crossed for patients in AJCC stages IIIC vs. IIIB (P = 0.53). Univariable and multivariable competing risk regressions demonstrated higher Wald statistics for V stages compared with AJCC stages (1152 vs. 1038 and 71 vs. 17, respectively). The frequency of monosomy 3, gain of chromosome 8q, and epithelioid cytomorphologic features increased with tumor volume (R2 = 0.70, R2 = 0.50, and R2 = 0.71, respectively; P < 0.001) and showed similar correlations with both AJCC and V stages. CONCLUSIONS: Anatomic classification and staging of ciliary body and choroidal melanomas based on estimation of tumor volume improves prognostication of metastatic mortality. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intraocular medulloepithelioma: an unusual and challenging entity in paediatric population.

Intraocular medulloepithelioma is a rare, congenital tumour of the non-pigmented ciliary epithelium. It most frequently arises from the ciliary body but can also have its origin from the retina, iris and optic nerve. The age when lesion first appears is typically around 2-10 years. Nearly 50-60% of patients having this lesion may also have secondary features such as cataract and neovascular glaucoma. Those with extrascleral medulloepithelioma are at risk for metastasis. Systemic correlation of the tumour with pleuropulmonary blastoma/DICER1 gene is reported in the literature. Here, we report a case of a 15 years old boy with one year history of right eye proptosis and painful red right eye along with decreased vision for one week. He was assessed and operated for cataract elsewhere three years back. The ophthalmology team managed him for endophthalmitis with intravenous antibiotics, followed by 2 sessions of cryotherapy and finally an enucleation of right eye was performed due to severe pain and no vision in the involved eye. His left eye, general physical examination and systemic evaluation were normal. Histopathology revealed the diagnosis of 'malignant teratoid medulloepithelioma'. Therefore, evaluation of systemic associations for DICER1 gene mutations was performed by the oncology team. For high risk feature of scleral invasion on histopathology, he was treated with chemotherapy. Since the tumour is of rare occurrence; an international expert team with vast research experience in PPB/DICER1 associated tumours was also contacted. He was registered in International PPB/DICER1 registry where a detailed central radiology and pathology review was performed. Genetic counseling and surveillance plan was also suggested by the international registry.

[Adenocarcinoma of nonpigmented ciliary body epithelium (clinical cases)]. / Adenokartsinoma iz bespigmentnogo epiteliya tsiliarnogo tela (klinicheskie nablyudeniya).

The article presents two clinical cases of adenocarcinoma of nonpigmented epithelium of the ciliary body, which is a very rare malignant tumor of the organ of vision with distinctive features. Surgical treatment is necessary to verify this tumor and assess the degree of its aggressiveness in terms of the prognosis of the disease, with subsequent pathomorphological and immunohistochemical studies. The article also discusses the epidemiological aspects, morphological features, clinical manifestations of this pathological condition, as well as possible treatment options and features of follow-up monitoring of this group of patients.

Tumor Profiles of Late Presentation Uveal Ring Melanoma With Novel Characteristics - A Case Series.

Purpose: The purpose of this study was to investigate the clinical features, tumor characteristics, including histopathology and cytogenetic analysis, and management of patients with uveal ring melanoma in New Zealand. Methods: A retrospective review was conducted on all uveal melanoma cases treated in a single national oncology center in New Zealand. The study period was from January 1, 2013 to December 31, 2022 (10 years). Written consent was obtained from all patients included in this case series. Results: Uveal ring melanoma of ciliary body origin (n = 4) comprised 0.7% of all uveal melanomas (n = 571). Ethnicity distribution was three patients of New Zealand European ancestry and one patient of Chinese/Pasifika ancestry. Three patients (75%) were symptomatic at presentation (spontaneous hyphema, glaucoma, and cataract), whereas one was asymptomatic but subsequently developed painful refractory glaucoma. All eyes underwent enucleation. Three eyes had primary iris biopsies with subsequent enucleation for refractory glaucoma and pain and one eye underwent primary enucleation. All cases demonstrated malignant tumor characteristics including diffuse 270 to 360-degree ciliary body ring growth pattern, epithelioid-cell type and presence of either BAP-1 expression loss or gain of MYC gene. Two cases (50%) developed distant organ metastasis - liver, parotid gland, and breast. Of those, one patient was deceased at the time of follow-up whereas one had completed treatment for metastases. Conclusions: Uveal ring melanoma is a rare tumor that is highly invasive and malignant. When detected, prompt definitive treatment should be advocated, and patient counselling should be given regarding the high risk of developing a painful, blind eye with increased risk of metastasis in the absence of treatment.

Ocular metastasis from renal malignancies - A comprehensive review.

The most common cause of intraocular mass is metastasis from other tumors. Renal malignancies, though rare, have a substantial number of cases with ocular metastasis, few of which were misdiagnosed. Many a times renal malignancies present with ocular manifestations before the primary diagnosis. Here in this article, we comprehensively reviewed 106 cases of ocular metastasis from renal malignancies published till date to the best of our knowledge. The eye is a rare site for distant metastasis because of the lack of a lymphatic system. The most common ocular structures to get involved in distant metastasis are the uveal tract, i.e., choroid, iris, and ciliary body. The most common renal tumor which metastasizes to eyes is renal cell carcinoma (RCC). RCC accounts for less than 2% of all ophthalmic metastases. Out of total 106 cases, the type of renal malignancy was known in 95 cases only, of which 92 had RCC, 1 Wilm's tumor, 1 rhabdoid tumor, and 1 medullary carcinoma. The age ranged widely from 2 weeks old to 81 years old. The male to female ratio was 3.4:1. In total, 67.4% of cases had a previous history of RCC, while the rest 32.6% primarily presented with ophthalmic manifestations first. Treatment modalities included enucleation of the eye, debulking surgery followed by radiotherapy and/or chemotherapy and/or immunotherapy.

Morroniside Ameliorates Endotoxin-Induced Uveitis by Regulating the M1/M2 Polarization Balance of Macrophages.

Background: Inflammation is closely associated with the pathogenesis of various ocular diseases. Uveitis is a condition characterized by the inflammation of the uvea and ocular tissues that causes extreme pain, decreases visual acuity, and may eventually lead to blindness. The pharmacological functions of morroniside, isolated from Cornus officinalis, are multifarious. Morroniside exerts various therapeutic effects, e.g., it ameliorates inflammation. However, the specific anti-inflammatory effect of morroniside on lipopolysaccharide-induced uveitis has not been reported widely. In this study, we investigated the anti-inflammatory effect of morroniside on uveitis in mice. Methods: An endotoxin-induced uveitis (EIU) mouse model was constructed and treated with morroniside. The inflammatory response was observed using slit lamp microscopy, and histopathological changes were observed by hematoxylin-eosin staining. The cell count in the aqueous humor was measured using a hemocytometer. The concentrations of TNF-α, IL-6, and IL-1ß in the ciliary body and retina were measured using ELISA kits. The expression of iNOS and Arg-1 in the ciliary body and retina was measured by immunofluorescence costaining, and western blotting was performed to measure the protein expression of JAK2, p-JAK2, STAT3, and p-STAT3 in the ciliary body and retina. Results: Morroniside effectively ameliorated the inflammatory response in EIU mice. Furthermore, morroniside significantly reduced the concentrations of IL-1ß, IL-6, and TNF-α in the ciliary body and retina. Morroniside treatment significantly reduced the expression of iNOS in the ciliary body and retinal tissues. It also significantly inhibited p-JAK2 and p-STAT3 expression and promoted Arg-1 expression. In addition, morroniside boosted the effect of JAK inhibitors on the above indices. Conclusions: Collectively, these findings suggest that morroniside may protect against LPS-induced inflammation in uveitis by promoting M2 polarization through the inhibition of the JAK/STAT pathway.

Multipurpose ultrasonographic characteristics of primary uveal MALT lymphoma.

PURPOSE: To investigate the ultrasonographic features in patients with primary uveal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Medical records of 12 patients (13 eyes) diagnosed with primary uveal MALT lymphoma between September 2014 and September 2021 were retrospectively reviewed. Ultrasonography, B-scan ultrasonography, color Doppler flow imaging, and ultrasound biomicroscopy findings were retrieved from the medical records. RESULTS: Mean age of the included patients was 59.4 ± 8.6 years. Typical ultrasonographic features of the choroidal infiltrates were flat, diffuse, and thickened, with low and homogenous internal reflectivity and with rich arterial blood flow from posterior ciliary arterioles. The mean thickness of the choroidal infiltrates was 1.34 ± 0.68 mm (n = 13). Most of the affected eyes had posterior episcleral extensions, with a mean thickness of 1.66 ± 1.21 mm (n = 12). Typical crescent-like posterior episcleral extensions were detected in nine eyes (69.2%). In six eyes, the blood flow from the choroidal infiltrates communicated with the episcleral extensions. In the ciliary body, the mean thickness of the infiltrates was 1.08 ± 0.43 mm (n = 9), and seven eyes (77.8%) had 360° ring-like infiltrations. The initial best-corrected visual acuity (BCVA) was significantly correlated with the final BCVA after treatment (p < 0.001). CONCLUSION: Multipurpose ultrasonographic imaging revealed the unique characteristics of the primary uveal MALT lymphoma and is helpful in the diagnosis of this rare disease.

IgG4-related ophthalmic disease masquerading as ciliary body tumors and scleritis in both eyes: a case report.

BACKGROUND: To report a rare case of IgG4-related ophthalmic disease (IgG4-ROD) manifesting as intraocular masses and scleritis in both eyes in a 61-year-old male and to investigate the changes in multimodal imaging features of the lesion sites and helper T-cell type 1 (Th 1)/Th 2/Th 17 cytokine levels in the aqueous humor. CASE PRESENTATION: A patient with IgG4-ROD seemingly manifested with an intraocular tumor in the left eye and sequentially, with an inflammatory mass in the ciliary body and scleritis in the right eye. The patient complained of vision loss of 6 months duration in the left eye at his first visit. With a preliminary diagnosis of an intraocular tumor, enucleation of the left eyeball and histopathological examination were performed. Approximately 3 months later, the patient started to experience headache, eye pain, and declining vision in the right eye. Ophthalmic imaging revealed a ciliary mass and scleritis. Th 1/Th 2/Th 17 cytokine levels and multimodal imaging findings were analyzed before and after corticosteroid treatment. Histopathological examination and immunohistochemistry (IHC) of the enucleated left eye demonstrated lymphoplasmacytic infiltration with an IgG4+/IgG+ cell ratio of approximately 40%, pointing to the diagnosis of probable IgG4-ROD. Long-term treatment with corticosteroids led to significant improvement in the signs and symptoms of the left eye. Th 1/Th 2/Th 17 cytokine profile monitoring of the aqueous humor and multimodal imaging of the right eye showed gradual regression of the mass and attenuation of ocular inflammation during treatment. CONCLUSIONS: Patients with an atypical presentation of IgG4-ROD, such as intraocular masses and scleritis, are likely to experience a significant delay in diagnosis. This case demonstrates the significance of IgG4-ROD in the differential diagnosis of intraocular tumors and ocular inflammation. IgG4-RD is a newly diagnosed disease with multi-organ involvement and little is known about its pathogenesis, particularly in the eye. The present case will open new challenges in the clinico-pathological diagnosis and research of this disease. Combined investigations of multimodal imaging and cytokine level detection of intraocular fluid provide a new and effective way to monitor disease progression.

Large ciliary body melanocytoma with pseudocysts: a case report.

BACKGROUND: To describe the correlation between standardized A-scan echography and histopathology in a ciliary body melanocytoma. CASE PRESENTATION: We present a case of a large ciliary body melanocytoma with significant growth, vision loss, and elevated intraocular pressure that was diagnosed clinically as a melanoma, but the standardized A-scan findings correlated to the histopathological description of a melanocytoma with multiple pseudocysts. CONCLUSIONS: The reflectivity of this melanocytoma by standardized A-scan was consistent with multiple pseudocysts on pathological evaluation. This echographic pattern guided the differential diagnosis. Standardized A-scan is an important diagnostic tool in the differentiation of ciliary body melanocytomas from melanomas.

Cytogenetic Abnormalities for Predicting the Risk of Metastases in Choroidal and Ciliary Body Melanoma.

Purpose: Choroidal melanoma (CM) and ciliary body melanoma (CBM) are the two most common subtypes of uveal melanoma. Starting from the observation that CBM tends to have a higher metastatic potential than CM, we hypothesized that specific cytogenetic abnormalities could be associated with tumor location - reflecting distinct genetic signatures that would drive the risk of distant spread. Methods: Chromosomal alterations were investigated by molecular cytogenetic techniques in 217 and 97 patients with CM and CBM, respectively. Cox proportional hazards regression analysis was used to identify the independent predictors of distant metastasis. Results: Patients with CBM had larger tumor sizes (P < 0.001), higher disease stages (P < 0.001), and more frequently showed distant metastasis (P = 0.002) than those with CM. On analyzing the entire study cohort, we found that specific chromosomal alterations - including chromosome 8p loss (P < 0.001), 1p loss (P < 0.001), and monosomy 3 (P < 0.005) - were independent predictors of distant metastasis. Based on a decision-tree learning algorithm, we identified three specific subgroups of patients with uveal melanoma at high risk of distant spread. Monosomy 3 occurred significantly more frequently in patients with T3 CBM tumors. Conclusions: Specific cytogenetic abnormalities - including chromosome 8p loss, 1p loss, and monosomy 3 - are independent risk factors for distant metastasis in uveal melanoma. Larger tumor size at presentation and monosomy 3 contribute to a higher metastatic risk in patients with CBM.