|Year : 2017 | Volume
| Issue : 3 | Page : 135-144
Choroidal melanoma: A short review with an Indian perspective
Bikramjit P Pal, Saili Garge, Vikas Khetan
Department of Vitreoretina, Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, India
|Date of Web Publication||5-Oct-2017|
Department of Vitreoretina, Shri Bhagwan Mahavir Vitreoretinal Services, Medical Research Foundation, Sankara Nethralaya, Chennai - 600 006, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Choroidal melanoma (CM), the most common intraocular tumor in adults, is still a rarity in Asia. Having a high propensity for metastasis with a poor survival, recognizing it early is essential. Although it has typical clinical features, there are instances of simulating lesions. Fine-needle aspiration biopsy can be a valuable tool not only to confirm our clinical suspicion but also aid in prognosticating it. From days of histopathological prognostic markers, we are moving on to genetic markers which are reliably providing insights, helping us in providing a better care for our patients. Eye preservation has taken an all new important meaning in CM with many centers opting for different modalities of radiation. Herein, we try to provide a short synopsis of CM looking into its epidemiology, clinical features, diagnosis, and management. We also look briefly into the role of fine-needle biopsy in managing CM. Being a tertiary referral ocular center in India, we do come across CM; we have shared the preliminary reports of our analysis of managing CM over a 9-year period.
Keywords: Choroidal melanoma, survival, treatment
|How to cite this article:|
Pal BP, Garge S, Khetan V. Choroidal melanoma: A short review with an Indian perspective. Oman J Ophthalmol 2017;10:135-44
| Introduction|| |
Choroidal melanoma (CM), the most common primary intraocular tumor of adults, is still not that common. With an estimated worldwide incidence of 7095 cases, Asia and Africa contribute the least, a contrast when comparing its numbers in retinoblastoma. Despite being a rarity, it is imperative for an ophthalmologist to recognize this clinical entity. Herein, we briefly review CM and also report preliminary results of managing 97 such tumors from our center over a 9-year period.
| Epidemiology|| |
The annual incidence of uveal melanoma has been reported to be 5–6 cases/million which has remained stable for the last 50 years.,, The incidence in Asia and Africa has been estimated to be 0.2–0.4 per million contributing approximately 1600 cases per year. The mean age of presentation is around 45–80 years as reported in non-Hispanic Caucasians with an occurrence a decade or two earlier in Asians,,, the cause of which is unknown. In our evaluation of 97 CMs, we found a similar finding. The youngest in our cohort was an 18-month Asian girl who presented with pigmentary intraocular mass with exudative retinal detachment having no perception of light (PL) and secondary ocular inflammation. Enucleated specimen showed a bilobed pigmentary choroidal mass with mixed type of melanoma cells. Viable tumor cells were seen infiltrating the optic nerve head (ONH) with extension beyond the lamina cribrosa. A detailed description of the case can be found elsewhere. The mean age of presentation was 45.3 years (range 18 months to 84 years). Although there has been no gender discrimination, few studies have found a larger diameter in men when compared to women. Fifty-two (54%) of our cohort were male and 45 (46%) were female.
Blond hair with light eyes and skin along with higher latitudes (low levels of ultraviolet radiation) are some of the accepted risk factors for CM. Few theories have been cited for less occurrence of CM at lesser latitudes., One proposes the role of a darkly pigmented choroid in absorbing the harmful ultraviolet radiation along with better disposal of free radicals generated in uveal melanocytes. Another theory proposes a protective role of Vitamin D which is generated during exposure to ultraviolet radiation at lower latitudes.
A recent hereditary cancer syndrome which has received lot of attention is the “BRCA1-associated protein-1 (BAP1)” tumor predisposition syndrome. Those affected are at risk of developing not only uveal melanoma but also malignant mesothelioma, cutaneous melanoma, breast carcinoma, and renal cell carcinoma.,
| Ocular Predisposing Factors|| |
Choroidal nevi with a reported incidence of 6.5% have a risk of a malignant transformation in 1 in 8845 cases., Researchers have estimated the chances of transformation in 1 in 5 cases. Although being benign, various clinical features have been described for identifying the risk factors in its malignant transformation and differentiating it from a small melanoma. A recent study contemplates the role of estrogens in pathogenesis and its possible role of choroidal nevus and its possible role in its malignant transformation.
Congenital oculodermal melanocytosis (Nevus of Ota) presenting with increased pigmentation of the episcleral tissues carries a lifetime risk of 1 in 400 of harboring a uveal melanoma. Seven (7.2%) of our patients had documented Nevus of Ota. Other ocular risk factors include melanocytoma of ONH. None of our cohort to our best of knowledge had a previous melanocytoma.
| Genetics in Uveal Melanoma|| |
Apart from retinoblastoma, uveal melanoma is one of the very few intraocular tumors currently being investigated looking into the role of genetics and epigenetics in its pathogenesis.
Uveal melanoma can have loss of chromosome 3, 1p, 6q, 8, or 9p. Alternatively, there can be a gain of 1q, 6p, or 8q. Among the aforementioned chromosomes, role of chromosome 3 has been the determinant factor as its loss has been shown to reduce the survival from 100% to 50%. Gain of 8 and loss of 1 have also been shown to reduce survival. Chromosome 6 with its gain has shown a better prognosis.,
Gene expression profiling has been used to classify uveal melanoma at a genetic level into two groups., Class 1 includes tumors with disomy 3 and gain of 6p. This is associated with a better prognosis and less chances of metastasis. Class 2 includes tumors with monosomy 3, 1, and 8p with a gain of 8q and is associated with a poorer prognosis.
Role of microRNAs (miRNA) has also been documented to correlate between monosomy 3 and its metastatic potential. The use of chromogenic in situ hybridization to study miRNA expression has shown its lesser expression in tumors having monosomy 3 and hence having higher metastatic potential.,
Various genes have also been implicated in the metastatic role of uveal melanoma. The most prominent has been BAP1 located in chromosome 3. Its role as a familial tumor predisposition syndrome has already been cited. Other genes such as SF3B1 and EIF1AX have been associated with a better prognosis. The role of genes such as GNAQ and GNA11 is uncertain as mutations of the same genes are universally present in all the uveal melanomas and also in benign lesions such as choroidal nevi.,
| Clinical Features and Diagnosis|| |
With an estimated size of tumor as small as 1.5 mm thickness and 3 mm in basal diameter having metastatic potential, early diagnosis of CM becomes critical.
Twenty-five percent of CM are asymptomatic. In other patients, it presents with flashes, floaters, or visual diminution. Pain from secondary glaucoma is rare. Prominent episcleral vessels (sentinel vessels) are more common in ciliary body melanoma. Clinically, CM can present as a dome- or a mushroom-shaped mass or be lobulated. Presentation as a diffuse mass occurs in <5%. Usually, they are pigmented in 55% cases, mixed pigmentation in 30%, and predominantly amelanotic in 15%.
To begin with, CM begins as a dome-shaped lesion. The slow-growing tumor then causes secondary changes in the overlying retinal pigment epithelium (RPE), with accumulation of lipofuscin pigments and drusen. The secondary degenerative changes in RPE lead to flashes. With continuous growth of tumor in some cases, there occurs break in the Bruch's membrane with a classical collar stud or mushroom shape. With time, the tumor can spread anteriorly and also invade the retina to enter the vitreous space and also extraocularly. In very rare occurrence, there may be spread to the ONH. Chronic secondary retinal detachment and subsequent ischemia lead finally to a painful blind eye if untreated.
Diagnosis of CM is essentially clinical although there can be few mimicking lesions. Misdiagnosis has reduced significantly from the earlier reported 12.5%–0.48% as reported in the collaborative ocular melanoma study (COMS). The most common pseudomelanoma has been a nevus. As stated before, the pneumonic “To Find Small Ocular Melanoma Using Helpful Hints Daily-TFSOM UHHD” is an useful tool which can be used by clinicians in differentiating between the two. Other common pseudomelanomas are peripheral exudative hemorrhagic chorioretinopathy, congenital hypertrophy of RPE, circumscribed choroidal hemangioma, melanocytoma, and scleritis with secondary choroidal indentation., There have also been reports of hypermature cataracts mimicking as melanoma.
Fundus photography (fundus fluorescein [FF]) [Figure 1]a has been a cornerstone in not only documenting and monitoring suspicious lesions, but also it plays a crucial role in follow-up of treated tumors and for detecting a recurrence. Panoret 1000 a widefield imaging modality uses transscleral illumination in capturing 100° of the retina. Although an excellent imaging modality, currently it is unavailable. RetCam 120 (Clarity Medical Systems, USA) has its limitations in hazy media and currently is restricted to a pediatric age group. Ultra-widefield imaging modality “Optos” (Dunfermline, UK) captures 200° of the retina. Although useful, it has its limitations in providing a falsely color-coded images. Clinicians when using these current modalities should be aware of their respective limitations.
|Figure 1: (a) Montage of the left eye of a 50-year-old male having a large superotemporal choroidal melanoma with associated exudative retinal detachment and pigment dispersion. (b) Fundus fluorescein angiography of the same patient depicting hyperfluorescence and leaks from the tumor. (c) Indocyanine green angiogram of the same patient depicting classic dual circulation. (d) “A” with “B” mode of ultrasound showing typical features of a mass having solid consistency with low-to-medium internal echoes, acoustic hollowness, and choroidal excavation. (e) A typical mushroom-shaped choroidal melanoma with associated retinal detachment|
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Ultrasonography (USG) of the eye with clinical examination provides a reliable tool for melanoma confirmation. Typical features [Figure 1]d and [Figure 1]e consist of a choroidal mass exhibiting solid consistency having low-to-medium internal reflectivity and a regular internal structure. This characteristic feature is attributed to its homogeneous cellular structure. Associated acoustic hollowness suggesting lower reflectivity at tumor base and choroidal excavation secondary to tumor infiltration of choroid are other peculiar features of CM. FF angiography and indocyanine green angiogram are other diagnostic tools which aid in its diagnosis by showing a “double circulation” [Figure 1]b and [Figure 1]c. Fundus autofluorescence shows evidence of RPE irregularities and is supportive of a mass showing activity.
With advent of spectral domain and swept-source optical coherence tomogram (OCT), it has been easier to distinguish a small melanoma and nevus. Enhanced depth OCT shows much accurate tumor measurement when compared to USG in smaller lesions. Features such as a smooth dome-shaped elevation with associated subretinal fluid and shaggy photoreceptors are not characteristic but supportive of a malignant mass rather being a benign one.
| Clinical Features of Our Cohort|| |
Ninety-seven patients were included in our study. A complete evaluation of our cohort is still underway with the following results summing up the preliminary findings. Results of survival, metastasis will be reported shortly. Fifty (51.54%) patients had CM of the left eye and 47 (48.45%) had involvement in the right. Among the study group, the most common presenting complaint was progressive loss of vision seen in 90 (92.78%) patients, followed by severe eye pain in 11 (11.34%), flashes in 9 (9.28%), and floaters in 8 (8.25%). Five (5.15%) patients had no complaints at presentation. Photopsia/metamorphopsia and redness of the eye were present in 3 (3.09%) each. Visual acuity was graded as follows. Patients having visual acuity worse than 6/6 but better than 6/18 were labeled mild visual impairment. Those having vision <6/60 but better than 6/18 were labeled moderate impairment. Visual acuity <1/60 but >6/60 was termed severe impairment. Those with vision between 1/60 and PL were termed as profound visual loss. We termed patients as blind when PL was nonrecordable. Normal was defined as visual acuity as 6/6 or better. Twelve (12.37%) patients had normal vision, 28 (28.87%) had mild, 17 (17.53%) had moderate, 7 (7.22%) had severe loss of vision, 31 (31.96%) had profound loss of vision, and 2 (2.06%) had no PL. Dilated conjunctival/episcleral vessels were observed in 15 patients (15.46%).
Most common site of tumor occurrence was found in the inferotemporal quadrant (ITQ), 17 (17.53%). Superotemporal quadrant (STQ) involvement was seen in 16 (16.49%) patients. Superonasal quadrant (SNQ), posterior pole involvement, and inferonasal quadrant involvement were seen in 15 (15.46%), 12 (12.37%), and 10 (10.31%) patients, respectively. Six (6.19%) patients had tumor involving both STQ and ITQ quadrants and 5 (5.15%) patients had both SNQ and STQ involvement. Five (5.15%) patients had a juxtapapillary tumor. One (1.03%) patient had lesion anterior to equator. One (1.03%) patient had tumor involving both posterior pole and equator. One of our patients had a large tumor involving STQ, ITQ, and equator together. Thirteen (13.40%) patients had ciliary body involvement.
Among the cohort, 75 (77.31%) patients had dome-shaped tumors while 17 (17.52%) were mushroom-shaped tumors. Two (2.09%) patients had bilobed tumors with 3 (3.09%) having a diffusely infiltrative tumor. Eight-nine (91.75%) patients were predominantly pigmented CMs while 8 (8.25%) were predominantly amelanotic on clinical examination.
Seven of our patients had features suggestive of Nevus of Ota/oculodermal melanocytosis. Three were male and four were female. Age of patients ranged between 28 and 62 years. Six patients had a diffusely infiltrative growth pattern with 6 being predominantly melanotic. One melanoma was small, 3 were medium sized, and 2 were large. One patient record had missing data concerning tumor thickness.
| Classification of Uveal Melanoma|| |
COMS classified CM into three groups: small, medium, and large. Although clinically informative, the classification does not “stage” the tumor. Tumor, node, and metastasis (TNM) classification with its 7th edition classifies uveal melanoma taking into account its clinical profile along with status of metastasis. The latest TNM also encourages to add the histopathological and genetic information when staging a tumor. In contrast to COMS, TNM staging can change with the development of metastasis and as the tumor progressxses.
Tumors are graded from 1 to 4 depending on thickness and largest basal diameter (LBD) [Figure 2]. Each grade is further subclassified based on ciliary body involvement and presence or absence of extraocular involvement (> or >5 mm). Once staged, a probable survival index can be mapped. Kaplan–Meier survival estimates for T1 tumors at 10 years and is approximately 89%. Stage 1 tumors have a 96% 5-year survival rates. Metastasis rates were 2, 4, and 8 times higher in T2, T3, and T4 tumors when compared to T1 tumors.
|Figure 2: (a) Tumour Grading based on LBD and thickness, (b) Kaplan Meier survival index based on grading|
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| Screening Protocols for Choroidal Melanoma|| |
With only 26% of uveal melanoma with metastasis patients being symptomatic and 2% having metastasis during the initial diagnosis of ocular pathology, importance of a regular screening protocol cannot be overemphasized. With an average 5-year cumulative metastatic rates varying between 25% and 38%, and a median survival less than a year postmetastasis detection, role of regular screening has been questioned. Most common sites for metastasis are liver (91%), followed by lungs (28%) and bone in 18%. With liver and lungs being the most common sites for extraocular spread, screening involving both organs becomes a natural choice.
Liver function tests (LFTs) commonly used are alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALK), lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase (γGT). LDH and AST should be considered predictive when values are 80% above normal. ALK and γGT are considered abnormal when values are just above normal. LFT are high specific (98%–99%) but lack sensitivity (14%) and individual laboratories have different reference values.
Imaging tests such as X-ray chest and hepatic USG are very specific but have low sensitivity (1.8 and 14%, respectively). A recent study has shown 96% sensitivity, 88% specificity, 99% negative predictive value, and 45% positive predictive value of abdominal USG in screening for hepatic metastasis. With 50% having normal LFT presenting with metastasis and between 20% and 70% having at least one deranged LFT, a combination of LFT and abdominal USG provides a comprehensive screening tool. Computerized tomography (CT) and magnetic resonance imaging (MRI) can be used to confirm metastasis and also when contemplating an intervention.
We follow a semiannual screening with LFT and abdominal USG. Yearly X-ray chest (although less sensitive and specific) is also performed with CT and MRI performed when needed. Since this is a preliminary report of our results, all-cause mortality and metastasis-related mortality are yet to be determined.
| Histopathology|| |
Callender initially classified uveal melanoma into six types: spindle A, spindle B, fascicular, mixed, epithelioid, and indeterminate. Following the original classification, there was a reported disagreement of 13% which led to its modification. Distinction between spindle A and B was also getting blurred in view of a similar prognosis between the two. Hence, the modified Callender's classification currently being used classifies it as spindle, epithelioid, and mixed [Figure 3]. Epithelioid type carries the worst prognosis in view of poor cohesiveness among the cells. Sections are generally stained with hematoxylin and eosin with mitotic rate commented per 40 high-power fields. Apart from tumor cells, there are also varying number of lymphocytes and macrophages contributing to prognosis of a tumor. Other histopathological features include microvascular density, mean diameter of 10 largest nucleoli, and extravascular matrix patterns.
|Figure 3: Depicting pathological features of choroidal melanoma. (a) Mixed type (×40). (b) Spindle type (×40 H and E). (c) Epithelioid type|
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A detailed histopathological analysis of our cohort can be found in [Table 1].
| Fine-Needle Aspiration Biopsy in Choroidal Melanoma|| |
The diagnosis of CM is essentially clinical; although there are instances where it may be uncertain with supportive investigations having conflicting results. Apart from its use in cases to confirm its diagnosis, fine-needle aspiration biopsy (FNAB) plays a vital role in prognosis in terms of its metastatic potential. With 50% of CM metastasizing, the role of FNAB is undisputed whereby it provides knowledge about its chromosome 3 status the major determinant in metastasis. Knowledge of tumorigenic metastatic potential can be used to customize follow-up. Molecular research, suspected tumor regrowth after previous treatment, and patient insistence in confirming its malignant potential are other uses of FNAB.
FNAB can be performed either transclerally or through a transvitreal route each having its own merit. Tumor thickness plays an important role in providing a successful specimen, with reports indicating a thickness >3 mm to be ideal, whereas others have reported it to be 5 mm. The procedure is performed with a 25 g for transvitreal and 30 g for transscleral route with an attached tubing to 5 or 10 ml syringe. Ideally, episcleral brachytherapy is done at the same sitting.
Reported overall positivity rates after FNAB have been >90% in tumors with thickness >2 mm.,, The most common complication associated is vitreous hemorrhage occurring in 46% cases. Other complications rarely associated are rhegmatogenous retinal detachment and endophthalmitis. Although rare, there have been instances of tumor seeding at the site of biopsy., The use of smaller needle gauge, making less scleral passes, and application of cryotherapy at the needle site with use of brachytherapy at the same sitting have been postulated to decrease this serious complication.
Although FNAB is an excellent modality for prognosticating tumors, its use is more relevant in centers seeing a larger number of CMs. In India and Asia, where the incidence of CM is low, routine use of this modality is perhaps questionable.
We employed FNAB to aid in diagnosis in 6 (6.1%) of our patients. Out of these two had presumptive diagnosis of posterior scleritis, one each had an initial diagnosis of metastasis, choroidal hemangioma, subretinal abscess, and endophthalmitis.
| Collaborative Ocular Melanoma Study|| |
No review article on CM can be complete without a mention about COMS. In an era of nonstandardized management of ocular melanoma along with speculation arising from role of enucleation in increasing mortality stemmed from the Zimmerman's hypothesis, a large randomized trial was need of the hour. COMS was a large multicentric randomized trial which provided newer insights into this enigmatic tumor [Table 2].
The term “ocular melanoma” in COMS is perhaps a misnomer as the trial specifically looked into primary CMs. Tumors of the conjunctiva, iris, primary ciliary body melanomas, diffuse, or ring melanomas were excluded from the study. Similarly, melanomas invading the angle or anterior chamber were excluded from the study. In view of strict inclusion and exclusion criteria, patients having history of any other primary cancer or patients having history of prior treatment were also exempted. Only patients more than 21 years having unilateral primarily CM were included in the study.
COMS classified CM into three groups. Small melanomas were defined as one having an apical height between 1 and 2.4 mm (changed from initial upper limit of 3 mm) and LBD between 5 and 16 mm. Any suspected choroidal lesion <5 mm was regarded as a possible nevus. Medium sized melanomas were defined as one having apical height between 2.5 and 10 mm (changed from initial 3–8 mm) with LBD <16 mm. Any tumor having LBD >16 mm and height >10 mm was regarded large.
Although COMS was a landmark trial, it had its pitfalls. Melanomas predominantly of choroid were included in the study; tumors of iris, those involving the ciliary body, conjunctiva, ring, and diffuse types were excluded from the study. Although COMS showed no statistical difference in survival between enucleation and preenucleation radiation, the role of tumor doubling time and occurrence of micrometastasis which ultimately decreases patient survival leaves much to be answered from these local forms of treatment.
| Management|| |
Indeterminate thin choroidal lesions which exhibit minimal risk factors (absence of subretinal fluid and orange pigment, with RPE irregularities) can be observed. Patients having multiple comorbid conditions preventing surgery, those having short life expectancy, or those not opting for any intervention can also be given an option of observation.
| Transpupillary Thermotherapy|| |
In the current era of management of uveal melanoma, transpupillary thermotherapy (TTT) has a limited role. Its use is mainly restricted to treating parts of tumor after radiotherapy (sandwich therapy) or minor or suspected recurrences after radiotherapy. Tumors treated primarily by TTT found high recurrence rate varying between 19% at 3 years and 33%–42% at 10 years. Risk factors associated with recurrences are increased tumor thickness, inability to achieve a flat scar, presence of subretinal fluid, and proximity to ONH. Small pigmented CM (<3 mm thickness) which is away from ONH and macula and has minimal risk factors can be given an option of TTT although observation is another option
| Radiotherapy|| |
Radiotherapy, and its varieties episcleral plaque brachytherapy, charge particle radiation (proton, helium, and carbon), and stereotactic surgery, forms the main bulk in managing CM. Most common modality of radiotherapy employed is plaque radiotherapy. Radioisotopes commonly used are iodine-125 (I125), ruthenium-106 (RU 106), and palladium-103 (Pd 103). Ruthenium emits B-rays whereas iodine is a gamma-ray emitter. Choice of the use of particular isotope depends on the tumor size and thickness, location from structures such as ONH and macula, and availability. Ruthenium plaques are employed in tumors which are <6 mm in thickness. Iodine isotope is the plaque of choice in those >6 mm and even those up to 14 mm have been plaqued. Dose for uveal melanoma varies between 70 and 100 Gy depending on thickness and LBD. Most common used plaques are circular although “notched” and “slotted” plaques are available for juxtapapillary tumors. Charged particle radiation such as proton beam employs 60 Gy in four daily fractions and is best suited for tumors in the peripapillary area.
Excellent tumor controls are reported after radiotherapy (>90%). The major complications after radiotherapy are neovascular glaucoma, radiation-related retinopathy and neuropathy, long-standing exudative retinal detachment, and cataract.
| Transscleral Resection|| |
Transscleral resection (TSR) of CM is a viable although a technically demanding modality of treatment. Tumors with thickness >6 mm and basal diameter <17 mm, with <1/3 of ciliary body involvement, not involving the ONH with goal on preserving some form of visual acuity can be dealt with TSR. Studies comparing TSR with brachytherapy have found higher recurrences in the former although with a better visual acuity. TSR has also found its role in “toxic tumor syndrome” a peculiar complication seen after radiation therapy. It consists of severe exudation, nonresolving retinal detachment, and secondary glaucoma with the tumor acting as the nidus for inflammation. TSR has been shown to be an effective modality in treating such cases with excellent resolution of the aforementioned clinical features. Complications associated with TSR are rhegmatogenous retinal detachment, vitreous hemorrhage, and tumor recurrences.
| Endoresection|| |
With risk of tumor seeding, endoresection and its role in the management of CM are controversial. In general, tumors <10 mm in LBD, with <2–3 clock hours of ONH involvement and those motivated to preserve vision, can be given this option. Greater tumor thickness is not a contraindication. In a study by Konstantinidis et al., endoresection gave excellent tumor control (recurrence rate of 3.2%) in well-selected cases. This modality is either employed after radiation to remove the residual tumor or is done along with brachytherapy at the same sitting.
| Enucleation|| |
With fallacy of Zimmermann's hypothesis proven, enucleation has been playing an important role in managing CM. Primary enucleation for CM can be planned in large tumors (having thickness >12 mm and LBD >18 mm), in those presenting with moderate extrascleral extension and those completely encircling the ONH. It can be planned as a secondary intervention in cases of painful blind eye after radiotherapy and cases presenting with extensive recurrences. Reported secondary enucleation rates have varied between 3.9% and 31.2% with a recent paper citing 19%.
Various treatment modalities were used for management our cohort. Majority of our patients had a large melanoma with primary enucleation with ball implant being the most common modality of treatment used in 67 (69.08%) patients. Two (2.06%) patients were observed. Episcleral brachytherapy with iodine-125 was used in 26 (26.80%) of our patients. Two (2.06%) had exenteration in view of local spread. Secondary enucleation rate was 23.52% (8) in our patients. The most common cause of secondary enucleation in our study population was secondary glaucoma. The second most common cause was tumor recurrence. Radiation retinopathy was observed in 14 (53.8%) necessitating antivascular endothelial growth factor injections. On assessing final vision in patients who underwent eye salvage procedures, 5 (14.7%) vision remained same, whereas in 4 (11.76%), there was improvement in vision, while 25 (73.52%) vision deteriorated after treatment.
A complete evaluation of tumor characteristics and metastatic rate with survival rates is still being evaluated.
A short tabular form showing various treatment modalities is depicted in [Table 3].
| Conclusion|| |
With high mortality and a poor prognosis, CM is indeed a tumor which needs early recognition with prompt treatment. Further genetic insights may reveal secrets which will not only help in its better understanding but also help in its better management.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Kivela T. Incidence, prevalence and epidemiology of ocular melanoma. In: Murray TG, Boldt HC, editors. Ocular Melanoma: Advances in Diagnostic and Therapeutic Strategies. 1st
ed. London: Future Medicine; 2014. p. 20-38.
Bergman L, Seregard S, Nilsson B, Ringborg U, Lundell G, Ragnarsson-Olding B. Incidence of uveal melanoma in Sweden from 1960 to 1998. Invest Ophthalmol Vis Sci 2002;43:2579-83.
Stang A, Parkin DM, Ferlay J, Jöckel KH. International uveal melanoma incidence trends in view of a decreasing proportion of morphological verification. Int J Cancer 2005;114:114-23.
Singh AD, Turell ME, Topham AK. Uveal melanoma: Trends in incidence, treatment, and survival. Ophthalmology 2011;118:1881-5.
Biswas J, Krishnakumar S, Shanmugam MP. Uveal melanoma in Asian Indians: A clinicopathological study. Arch Ophthalmol 2002;120:522-3.
Kashyap S, Venkatesh P, Sen S, Khanduja S, Shrey D, Tinwala S, et al.
Clinicopathologic characteristics of choroidal melanoma in a North Indian population: Analysis of 10-year data. Int Ophthalmol 2014;34:235-9.
Dhupper M, Biswas J, Gopal L, Kumar SK, Khetan V. Clinicopathological correlation of choroidal melanoma in Indian population: A study of 113 cases. Oman J Ophthalmol 2012;5:42-5.
] [Full text]
Khetan V, Gopal L, Krishnakumar S, Biswas J. Bifocal malignant melanoma of the choroid in a 1.5-year-old child. Retin Cases Brief Rep 2008;2:239-40.
Damato BE, Coupland SE. Differences in uveal melanomas between men and women from the British Isles. Eye (Lond) 2012;26:292-9.
Virgili G, Gatta G, Ciccolallo L, Capocaccia R, Biggeri A, Crocetti E, et al.
Incidence of uveal melanoma in Europe. Ophthalmology 2007;114:2309-15.
Hu DN, McCormick SA, Yu GP. Latitude and uveal melanoma. Ophthalmology 2008;115:757.
Klebe S, Driml J, Nasu M, Pastorino S, Zangiabadi A, Henderson D, et al.
BAP1 hereditary cancer predisposition syndrome: A case report and review of literature. Biomark Res 2015;3:14.
Rai K, Pilarski R, Cebulla CM, Abdel-Rahman MH. Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases. Clin Genet 2016;89:285-94.
Singh AD, Kalyani P, Topham A. Estimating the risk of malignant transformation of a choroidal nevus. Ophthalmology 2005;112:1784-9.
Kivelä T, Eskelin S. Transformation of nevus to melanoma. Ophthalmology 2006;113:887-8.e1.
Shields CL, Shields JA. Clinical features of small choroidal melanoma. Curr Opin Ophthalmol 2002;13:135-41.
Qiu M, Shields CL. Relationship between female reproductive factors and choroidal nevus in US women: Analysis of data from the 2005-2008 National Health and Nutrition Examination Survey. JAMA Ophthalmol 2015;133:1287-94.
Singh AD, De Potter P, Fijal BA, Shields CL, Shields JA, Elston RC. Lifetime prevalence of uveal melanoma in white patients with oculo (dermal) melanocytosis. Ophthalmology 1998;105:195-8.
Shields JA, Demirci H, Mashayekhi A, Shields CL. Melanocytoma of optic disc in 115 cases: The 2004 Samuel Johnson Memorial Lecture, part 1. Ophthalmology 2004;111:1739-46.
Read J, Wadt KA, Hayward NK. Melanoma genetics. J Med Genet 2016;53:1-14.
Field MG, Harbour JW. Recent developments in prognostic and predictive testing in uveal melanoma. Curr Opin Ophthalmol 2014;25:234-9.
van Essen TH, van Pelt SI, Versluis M, Bronkhorst IH, van Duinen SG, Marinkovic M, et al.
Prognostic parameters in uveal melanoma and their association with BAP1 expression. Br J Ophthalmol 2014;98:1738-43.
Coupland SE, Lake SL, Zeschnigk M, Damato BE. Molecular pathology of uveal melanoma. Eye (Lond) 2013;27:230-42.
Onken MD, Worley LA, Tuscan MD, Harbour JW. An accurate, clinically feasible multi-gene expression assay for predicting metastasis in uveal melanoma. J Mol Diagn 2010;12:461-8.
Onken MD, Worley LA, Char DH, Augsburger JJ, Correa ZM, Nudleman E, et al.
Collaborative Ocular Oncology Group report number 1: Prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmology 2012;119:1596-603.
Radhakrishnan A, Badhrinarayanan N, Biswas J, Krishnakumar S. Analysis of chromosomal aberration (1, 3, and 8) and association of microRNAs in uveal melanoma. Mol Vis 2009;15:2146-54.
Venkatesan N, Kanwar J, Deepa PR, Khetan V, Crowley TM, Raguraman R, et al.
Clinico-pathological association of delineated miRNAs in uveal melanoma with monosomy 3/Disomy 3 chromosomal aberrations. PLoS One 2016;11:e0146128.
Eskelin S, Kivela T. Uveal melanoma: Implications of tumor doubling time. Ophthalmology 2001;108:830-1.
Shields CL, Kels JG, Shields JA. Melanoma of the eye: Revealing hidden secrets, one at a time. Clin Dermatol 2015;33:183-96.
Shields CL, Kaliki S, Furuta M, Mashayekhi A, Shields JA. Clinical spectrum and prognosis of uveal melanoma based on age at presentation in 8,033 cases. Retina 2012;32:1363-72.
Damato BE, Coupland SE. Ocular melanoma. Saudi J Ophthalmol 2012;26:137-44.
Eide N, Syrdalen P, Scheie D, Chen Y, Elgjo K, Kerty E, et al.
Uveal melanomas with optic nerve extension: Report of two cases diagnosed by transvitreal biopsy, one of them with a multicentric tumour. Acta Ophthalmol Scand 2001;79:322-5.
Accuracy of diagnosis of choroidal melanomas in the Collaborative Ocular Melanoma Study. COMS report no 1. Arch Ophthalmol 1990;108:1268-73.
Shields JA, Mashayekhi A, Ra S, Shields CL. Pseudomelanomas of the posterior uveal tract: The 2006 Taylor R. Smith Lecture. Retina 2005;25:767-71.
Shields JA, Augsburger JJ, Brown GC, Stephens RF. The differential diagnosis of posterior uveal melanoma. Ophthalmology 1980;87:518-22.
Shields CL, Pellegrini M, Kligman BE, Bianciotto C, Shields JA. Ciliary body and choroidal pseudomelanoma from ultrasonographic imaging of hypermature cataract in 20 cases. Ophthalmology 2013;120:2546-51.
Pe'er J, Sancho C, Cantu J, Eilam S, Barzel I, Shulman M, et al.
Measurement of choroidal melanoma basal diameter by wide-angle digital fundus camera: A comparison with ultrasound measurement. Ophthalmologica 2006;220:194-7.
Schalenbourg A, Zografos L. Pitfalls in colour photography of choroidal tumours. Eye (Lond) 2013;27:224-9.
Byrne SF, Green RL. Ultrasound of the Eye and Orbit. 2nd
ed. Philadelphia: Mosby; 2002. p. 115-42.
Mrejen S, Fung AT, Silverman RH, Kendall C, Freund KB. Potential pitfalls in measuring the thickness of small choroidal melanocytic tumors with ultrasonography. Retina 2013;33:1293-9.
Shields CL, Pellegrini M, Ferenczy SR, Shields JA. Enhanced depth imaging optical coherence tomography of intraocular tumors: From placid to seasick to rock and rolling topography – The 2013 Francesco Orzalesi Lecture. Retina 2014;34:1495-512.
Kivelä T, Kujala E. Prognostication in eye cancer: The latest tumor, node, metastasis classification and beyond. Eye (Lond) 2013;27:243-52.
Eskelin S, Pyrhönen S, Summanen P, Prause JU, Kivelä T. Screening for metastatic malignant melanoma of the uvea revisited. Cancer 1999;85:1151-9.
Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, et al.
Screening for metastasis from choroidal melanoma: The Collaborative Ocular Melanoma Study Group Report 23. J Clin Oncol 2004;22:2438-44.
Kaiserman I, Amer R, Pe'er J. Liver function tests in metastatic uveal melanoma. Am J Ophthalmol 2004;137:236-43.
Choudhary MM, Gupta A, Bena J, Emch T, Singh AD. Hepatic ultrasonography for surveillance in patients with uveal melanoma. JAMA Ophthalmol 2016;134:174-80.
Callender GR. Malignant melanocytic tumors of the eye. A study of histologic types in 111 cases. Trans Am Acad Ophthalmol Otolaryngol 1931;36:131.
McLean IW, Foster WD, Zimmerman LE, Gamel JW. Modifications of Callender's classification of uveal melanoma at the Armed Forces Institute of Pathology. Am J Ophthalmol 1983;96:502-9.
McCannel TA, Chang MY, Burgess BL. Multi-year follow-up of fine-needle aspiration biopsy in choroidal melanoma. Ophthalmology 2012;119:606-10.
Cohen VM, Dinakaran S, Parsons MA, Rennie IG. Transvitreal fine needle aspiration biopsy: The influence of intraocular lesion size on diagnostic biopsy result. Eye (Lond) 2001;15(Pt 2):143-7.
Sellam A, Desjardins L, Barnhill R, Plancher C, Asselain B, Savignoni A, et al.
Fine needle aspiration biopsy in uveal melanoma: Technique, complications, and outcomes. Am J Ophthalmol 2016;162:28-34.e1.
Singh AD, Medina CA, Singh N, Aronow ME, Biscotti CV, Triozzi PL. Fine-needle aspiration biopsy of uveal melanoma: Outcomes and complications. Br J Ophthalmol 2016;100:456-62.
Mashayekhi A, Lim RP, Shields CL, Eagle RC Jr., Shields JA. Extraocular extension of ciliochoroidal melanoma after transscleral fine-needle aspiration biopsy. Retin Cases Brief Rep 2016;10:289-92.
Schefler AC, Gologorsky D, Marr BP, Shields CL, Zeolite I, Abramson DH. Extraocular extension of uveal melanoma after fine-needle aspiration, vitrectomy, and open biopsy. JAMA Ophthalmol 2013;131:1220-4.
Zimmerman LE, McLean IW, Foster WD. Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells. Br J Ophthalmol 1978;62:420-5.
Singh AD, Kivelä T. The collaborative ocular melanoma study. Ophthalmol Clin North Am 2005;18:129-42.
Mashayekhi A, Shields CL, Rishi P, Atalay HT, Pellegrini M, McLaughlin JP, et al.
Primary transpupillary thermotherapy for choroidal melanoma in 391 cases: Importance of risk factors in tumor control. Ophthalmology 2015;122:600-9.
Puusaari I, Damato B, Kivela T. Transcleral resection versus iodine brachytherapy for uveal melanomas that are large because of tumour height. Graefes Arch Clin Exp Ophthalmol 2007;245:522-33.
American Brachytherapy Society – Ophthalmic Oncology Task Force. Electronic address: Paulfinger@eyecancer.com; ABS – OOTF Committee. The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma. Brachytherapy 2014;13:1-14.
Finger PT, Chin KJ, Tena LB. A five-year study of slotted eye plaque radiation therapy for choroidal melanoma: Near, touching, or surrounding the optic nerve. Ophthalmology 2012;119:415-22.
Kivelä T, Puusaari I, Damato B. Transscleral resection versus iodine brachytherapy for choroidal malignant melanomas 6 millimeters or more in thickness: A matched case-control study. Ophthalmology 2003;110:2235-44.
Konstantinidis L, Groenewald C, Coupland SE, Damato B. Trans-scleral local resection of toxic choroidal melanoma after proton beam radiotherapy. Br J Ophthalmol 2014;98:775-9.
Konstantinidis L, Groenewald C, Coupland SE, Damato B. Long-term outcome of primary endoresection of choroidal melanoma. Br J Ophthalmol 2014;98:82-5.
Fabian ID, Tomkins-Netzer O, Stoker I, Arora AK, Sagoo MS, Cohen VM. Secondary enucleations for uveal melanoma: A 7-year retrospective analysis. Am J Ophthalmol 2015;160:1104-10.e1.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]