Choroidal Melanoma Diagnosis: A Comprehensive Guide for Effective Detection

Introduction

Choroidal melanoma, a malignant tumor arising from the choroid, is the most prevalent primary intraocular malignancy in adults and the second most common type of melanoma in the body. Early and accurate Choroidal Melanoma Diagnosis is crucial for effective management and improving patient outcomes. This article provides an in-depth review of the current diagnostic approaches for choroidal melanoma, drawing upon clinical expertise and advanced diagnostic techniques. We will explore the epidemiology, genetic factors, and various diagnostic modalities, including ophthalmoscopy, ultrasonography, angiography, and other ancillary tests, to provide a comprehensive understanding of choroidal melanoma diagnosis. This information is vital for healthcare professionals and individuals seeking to understand this complex ocular condition.

Epidemiology of Choroidal Melanoma

Uveal melanoma, including choroidal melanoma, is considered an uncommon disease. The incidence of primary choroidal melanoma is approximately 6 cases per million people in the United States and slightly higher in Scandinavian countries like Denmark, at about 7.5 cases per million per year. This malignancy predominantly affects individuals of Caucasian descent with Northern European ancestry. The occurrence of choroidal melanoma in Black populations is notably rare, while Hispanics and Asians exhibit an intermediate risk compared to Whites and Blacks. It is exceptionally rare in children, with the median age at diagnosis being around 55 years. Interestingly, choroidal melanoma is slightly more prevalent in men across most age groups, except for the 20 to 39-year-old demographic where women show a slight predilection. While cutaneous nevi are recognized risk factors for skin melanoma, the association between uveal nevi and choroidal melanoma development is considered low. Factors that may indicate the transformation of a choroidal nevus into melanoma include increased thickness, subretinal fluid, presence of symptoms, orange pigment, proximity to the optic disc margin, ultrasonographic hollowness, and absence of halo. Hormonal influences and ultraviolet light exposure have been investigated as potential risk factors, but their roles in uveal melanoma remain inconclusive. Host factors, particularly ancestry and pigmentation, are considered the strongest known risk factors. Familial occurrence of uveal melanoma is rare, and further research is warranted to investigate occupational and chemical exposures as potential modifiable risk factors.

Genetic Factors in Choroidal Melanoma

Uveal melanomas are characterized by a relatively homogenous genetic profile, with a limited number of tumor-specific cytogenetic aberrations. These genetic alterations can have prognostic significance, correlating with the tumor’s metastatic potential. Recurrent chromosomal aberrations in uveal melanoma include losses of chromosome 1p, monosomy of chromosome 3, losses of 6q and 8p, and gains of 6p and 8q. Loss of chromosome 1p has been observed in metastatic choroidal melanoma, and the combined loss of 1p and chromosome 3 is associated with decreased patient survival. Monosomy 3 is considered an early genetic event in uveal melanoma development and is a strong predictor of survival outcomes. Loss of chromosome 3 is frequently linked to the amplification of 8q, often manifesting as isochromosome 8q. These genetic findings are increasingly important in understanding the biology and prognosis of choroidal melanoma.

Diagnostic Modalities for Choroidal Melanoma Diagnosis

Accurate choroidal melanoma diagnosis relies on a combination of patient history, clinical examination, and advanced imaging techniques.

1. Patient History: While patient history alone is not sufficient for definitive choroidal melanoma diagnosis, it plays a crucial role in differentiating it from simulating lesions. Many patients with choroidal melanoma are asymptomatic, with tumors detected during routine eye examinations. Symptomatic patients may report visual disturbances such as vision loss, flashes of light (photopsia), and visual field defects. Decreased vision can result from tumor encroachment on the fovea, exudative retinal detachment affecting the macula, or tumor contact with the lens. Severe pain is uncommon in melanoma unless complications like inflammation, extensive extraocular extension, or neovascular glaucoma are present. A history of non-ocular malignancy should raise suspicion for metastasis, although uveal melanoma patients can also have other primary neoplasms.

2. Clinical Examination and Indirect Ophthalmoscopy (IO): Indirect ophthalmoscopy through a dilated pupil is the cornerstone of choroidal melanoma diagnosis. It is reported to correctly diagnose melanoma in over 95% of cases. The classic ophthalmoscopic appearance of choroidal melanoma is a pigmented, dome-shaped or collar button-shaped mass, often accompanied by exudative retinal detachment. While typically pigmented, choroidal melanomas can exhibit variable pigmentation or even be amelanotic (non-pigmented). Characteristic features include orange pigment (lipofuscin) at the retinal pigment epithelium level and exudative retinal detachment, especially in tumors exceeding 4 mm in thickness. Large melanomas, particularly those involving the ciliary body, may have prominent episcleral vessels. Recognizing atypical features is crucial for differential diagnosis. Significant hemorrhage associated with a mass is uncommon in melanoma. Multiple choroidal tumors are more suggestive of metastasis or lymphoid lesions rather than primary melanoma. A distinct orange-purple tumor color is more typical of choroidal hemangioma or early choroidal osteoma. Dense black pigmentation is more often associated with retinal pigment epithelium hypertrophy or hyperplasia. Complete absence of pigmentation should prompt consideration of choroidal hemangioma or metastasis. Significant intraocular inflammation is also atypical for melanoma and more indicative of inflammatory conditions.

3. Ultrasonography (A-mode and B-mode): Combined A-mode and B-mode ultrasonography is a vital ancillary test in choroidal melanoma diagnosis.

   Alt text: B-scan ultrasound image showing a mushroom-shaped choroidal melanoma, indicated by an arrow, located nasally, with visible sub-retinal fluid.

   On A-scan ultrasonography, choroidal melanomas typically exhibit medium to low internal echoes with smooth sound attenuation. Vascular pulsations within the tumor can also be detected. B-scan ultrasonography reveals three classic characteristics of choroidal melanoma: an acoustically silent zone within the melanoma, choroidal excavation, and orbital shadowing. For tumors thicker than 3 mm, combined A- and B-scan ultrasonography achieves a diagnostic accuracy exceeding 95%. Choroidal nevi, in contrast, appear echo-dense and minimally vascular on ultrasound.

   Alt text: B-scan ultrasound image demonstrating a dome-shaped choroidal melanoma, marked by an arrow, located temporally to the optic disc in the macular region, with a shallow, elevated, highly reflective membrane at the tumor apex.

4. Fluorescein Angiography (FA): Fluorescein angiography has limited accuracy in primary choroidal melanoma diagnosis. However, larger tumors may exhibit characteristic patterns that, while not pathognomonic, can be suggestive. These patterns include intrinsic tumor circulation (double circulation), extensive leakage with progressive fluorescence, late staining of the lesion, and multiple pinpoint leaks (“hot spots”) at the retinal pigment epithelium level.

5. Optical Coherence Tomography (OCT): Optical coherence tomography provides detailed cross-sectional imaging of the retina and choroid, aiding in differentiating choroidal melanoma from nevi. OCT findings in melanomas may include serous retinal detachment, debris on the posterior retina, normal retinal thickness, and intact photoreceptors. Nevi, conversely, often demonstrate photoreceptor loss (in about 50% of cases), absolute scotoma, retinal atrophy and thinning, and pigment epithelial detachment (in approximately 15% of cases).

6. Autofluorescence Imaging: Autofluorescence imaging can help visualize lipofuscin, the orange pigment often associated with choroidal melanomas. Melanomas typically show clumps of hyperautofluorescence corresponding to clinically visible orange pigment. Nevi, in contrast, typically do not exhibit autofluorescence.

7. Indocyanine Green Angiography (ICGA): Indocyanine green angiography is useful for visualizing the microcirculation of choroidal melanomas, providing additional diagnostic information.

8. Other Ancillary Tests: While ultrasonography is the primary ancillary test, other imaging modalities have a limited role in routine choroidal melanoma diagnosis. High-resolution computed tomography (CT) is less accurate and more expensive than ultrasonography. Magnetic resonance imaging (MRI) and nuclear magnetic resonance spectroscopy are not routinely used in the diagnosis of choroidal melanoma. Invasive techniques such as radioactive phosphorus uptake tests and fine needle biopsy are generally avoided for initial diagnosis due to limitations and potential complications. Radioactive phosphorus uptake tests have high false negative and false positive rates and are no longer recommended. Fine needle aspiration cytology (FNAC) is reserved for cases where therapeutic intervention is planned and diagnosis cannot be established by non-invasive methods, due to the risk of needle track seeding and interpretative challenges.

Differential Diagnosis: Lesions Simulating Choroidal Melanoma

Several ocular lesions can mimic choroidal melanoma, requiring careful differential diagnosis. These include: choroidal nevus, choroidal metastasis, choroidal hemangioma, choroidal osteoma, melanocytoma, benign lymphoid tumor, choroidal hemangio-pericytoma, choroidal leiomyoma, extramacular disciform lesion, ruptured arteriolar macroaneurysm, localized choroidal detachment, retinal pigment epithelial hypertrophy, posterior scleritis, hemorrhagic retinal detachment, massive retinal gliosis, and retinal glioma. A thorough clinical evaluation and appropriate use of diagnostic modalities are essential to distinguish choroidal melanoma from these simulating conditions.

Treatment Options for Choroidal Melanoma

Treatment strategies for choroidal melanoma are tailored to individual patient and tumor characteristics, considering factors such as tumor size, location, involvement of ocular structures, visual acuity in both eyes, and presence of metastasis.

Treatment for Small Choroidal Melanoma

For small choroidal melanomas, particularly those in the posterior fundus, several treatment options are available. These include:

• Laser Photocoagulation: Using laser energy to destroy tumor cells.
• Photodynamic Therapy (PDT): Utilizing a photosensitizing agent activated by light to target tumor cells.
• Plaque Radiation Therapy (Brachytherapy): Delivering localized radiation via a radioactive plaque surgically attached to the sclera near the tumor.
• External Beam Charged Particle Radiation Therapy: Using proton or helium ion beams to deliver targeted radiation.
• Transpupillary Thermotherapy (TTT): Applying heat to the tumor using infrared laser.
• Local Tumor Resection: Surgical removal of the tumor.
• Enucleation: Surgical removal of the eye.

Treatment for Medium and Large Choroidal Melanoma

For medium and large choroidal melanomas, treatment options include:

• Enucleation: Historically, enucleation was the standard treatment, particularly for large tumors, those causing glaucoma, or those invading the optic nerve. Studies have shown that preoperative external beam radiation therapy followed by enucleation does not significantly improve survival compared to enucleation alone.
• Plaque Brachytherapy: Plaque brachytherapy is a frequently used eye-sparing treatment. Radioactive isotopes like iodine-125 are commonly used. Complications of radiotherapy can include radiation retinopathy, cataract, vitreous hemorrhage, and neovascular glaucoma.
• External Beam Charged Particle Radiation Therapy: Proton beam therapy offers precise radiation delivery and can be used for larger tumors. However, it is associated with a risk of maculopathy, especially for tumors near the macula.
• Gamma Knife Surgery: Gamma knife radiosurgery is emerging as a potential treatment option for medium-sized choroidal melanomas.
• Eyewall Resection (Sclerouvectomy): Surgical removal of the tumor along with adjacent sclera and retina, followed by scleral grafting.
• Orbital Exenteration: Radical surgery involving removal of the eye and orbital contents, reserved for cases with extensive orbital extension and poor prognosis.

The choice of treatment is complex and individualized, balancing tumor control, vision preservation, and patient quality of life.

Prognosis and Survival in Choroidal Melanoma

Uveal melanoma size is the most significant clinical prognostic factor. Larger basal tumor diameter, epithelioid cell type, mitotic rate, closed vascular loops, and extraocular extension are associated with poorer prognosis. Genetic factors, particularly chromosome 3 loss, also play a crucial role in predicting metastatic risk. Despite various treatment modalities, survival rates for uveal melanoma have not substantially improved in recent decades. Metastasis rates at 5 and 10 years post-treatment are approximately 25% and 34%, respectively. Common sites of metastasis include the liver (90%), lung (24%), and bone (16%). Liver metastasis carries a poor prognosis, with a median survival of about 6 months.

Conclusion

Accurate choroidal melanoma diagnosis is achievable through a combination of non-invasive techniques, including indirect ophthalmoscopy and A- and B-scan ultrasonography. These methods minimize the need for invasive procedures like FNAC, reducing the risk of complications. While CT, MRI, and nuclear magnetic resonance spectroscopy have limited roles in routine diagnosis, ongoing research may refine their applications. Treatment approaches for choroidal melanoma range from observation for small, stable lesions to various interventions like laser therapy, radiation therapy, and enucleation, depending on tumor size, location, and patient factors. Treatment decisions should be individualized, considering both tumor characteristics and patient preferences, with the goals of tumor control, vision preservation, and maintaining quality of life.

Footnotes

Source of Support: Nil

Conflict of Interest: No.

References

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