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Clinicopathological correlation of choroidal melanoma in Indian population: A study of 113 cases.
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PMID:  22557876     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
AIM: To correlate the clinical presentation, tumor characteristics, and histopathological findings of choroidal melanoma in the Indian population
MATERIALS AND METHODS: A retrospective analysis of 113 patients of choroidal melanoma over a period of 10 years was done. Patient demography, clinical presentation, tumor characteristics, and histopathological findings were correlated.
RESULTS: Among 113 patients histopathologically diagnosed with choroidal melanoma over 10 years, most were males. The mean age was 45.9 ± 14.84 years among which 6 (5.3%) patients were less than 20 years. Thirty-six (31.8%) patients were misdiagnosed. The mean basal diameter was 12.41 ± 1.4 mm. Mixed cell type was seen in 71 (63%) patients, while 28 (25%) patients had spindle cell type. Epithelioid cell type was present in 11 (10%) patients and necrotic cell type was seen in 3 (2%) patients. Enucleation was the primary treatment modality in 107 (94.6%) patients, while exenteration was done in 6 (5.3%) patients. Three patients with epithelioid cell type with orbital extension underwent exenteration. The mean follow-up period was 14 months. No mortality was reported at the end of 5 years in patients with longer follow-up.
CONCLUSIONS: Malignant melanoma of the choroid is a rare occurrence. They can occur in younger age group and can be misdiagnosed. Mixed cell type is commonest. Diffuse tumors with epithelioid cell type are likely to have orbital extension.
Authors:
Maneesh Dhupper; Jyotirmay Biswas; Lingam Gopal; S Krishna Kumar; Vikas Khetan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oman journal of ophthalmology     Volume:  5     ISSN:  0974-7842     ISO Abbreviation:  Oman J Ophthalmol     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-05-04     Completed Date:  2012-10-02     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101519430     Medline TA:  Oman J Ophthalmol     Country:  India    
Other Details:
Languages:  eng     Pagination:  42-5     Citation Subset:  -    
Affiliation:
Bhagwan Mahavir Vitreo Retina Services, Sankara Nethralaya, Nungambakkam, Chennai, Tamil Nadu, India.
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Journal Information
Journal ID (nlm-ta): Oman J Ophthalmol
Journal ID (iso-abbrev): Oman J Ophthalmol
Journal ID (publisher-id): OJO
ISSN: 0974-620X
ISSN: 0974-7842
Publisher: Medknow Publications & Media Pvt Ltd, India
Article Information
Copyright: © 2012 Dhupper M, et al
open-access:
Print publication date: Season: Jan-Apr Year: 2012
Volume: 5 Issue: 1
First Page: 42 Last Page: 45
ID: 3339674
PubMed Id: 22557876
Publisher Id: OJO-5-42
DOI: 10.4103/0974-620X.94766

Clinicopathological correlation of choroidal melanoma in Indian population: A study of 113 cases
Maneesh Dhupperaff1
Jyotirmay Biswasaff1
Lingam Gopalaff1
S. Krishna Kumaraff1
Vikas Khetanaff1
Bhagwan Mahavir Vitreo Retina Services, Sankara Nethralaya, Nungambakkam, Chennai, Tamil Nadu, India
Correspondence: Correspondence: Dr. Vikas Khetan, Sankara Nethralaya, 18, College Road, Nungambakkam, Chennai, Tamil Nadu, India. E-mail: drvk@snmail.org

Introduction

Choroidal melanoma is the commonest primary intraocular tumor but is rare in the Indian population. Its incidence in the world is 0.02–0.06%.[1] It is more prevalent in western population than Asian.[25] The most common age group affected is between 40 and 60 years.[6] Choroidal melanoma has been rarely reported in children.[7, 9] Apart from a small case series and case reports, no large study on Choroidal melanoma in India has been conducted.[5, 6] It presents unilaterally and is slightly more frequent in men. Blurred vision, pain, and floaters are common symptoms, but it may be an incidental finding on ophthalmoscopy. Mixed cell is the predominant histopathological type. Distant metastasis to the liver is commonest followed by lungs, skin, and bone. The tumor is easily misdiagnosed and can be mistreated if not properly evaluated and investigated. This retrospective analysis of 113 cases has been done to evaluate the clinical and histopathological characteristics in patients of choroidal melanoma between 2000 and 2010 at a tertiary referral care center in South India.


Materials and Methods

A retrospective analysis over a period of 10 years, from January 2000 to January 2010, of patients with histologically proven diagnosis of malignant melanoma of choroid was done at our institute. The study was conducted adhering to the guidelines of the Declaration of Helsinki and received approval from the institution review board of our institute.

Out of 150 patients with clinical diagnosis of choroidal melanoma, 113 met the inclusion criteria for the study and underwent enucleation/exenteration with a minimum follow-up of 1 year after surgery. Demographic and clinical details including patient age, gender, laterality, ocular findings, time elapsed since diagnosis, investigations done, period between diagnosis and surgery, treatment given, and follow-up period were studied.

The enucleated eyes were fixed in 10% neutral buffered formalin and subjected to histopathological study. Vortex veins were identified and sectioned separately to identify the presence of melanoma cells. Gross examination was done under a microscope (Nikon HFX-II A Optiphot) followed by making sections with the help of microtome (Leica RM 2245). Largest basal diameter and height of the tumor and location of the tumor (choroid alone or involving other structures) were recorded. Histopathological features noted included shape of the tumor and cell type, necrotic changes, scleral, and extrascleral extension.

Baseline systemic evaluation along with magnetic resonance imaging (MRI), ultrasound abdomen, and liver function tests were done in all patients at the time of diagnosis and/or before surgery. Patients were advised to come for periodic follow-up every 3 months for the first two visits and then every 6 months.


Results

Of the 113 cases in our report, 69 (61%) patients were male. The mean age at presentation was 45.94 ± 14.85 years (range 2–76 years). Among these, 58 (51.3%) patients were in the 40–60 years age group, while 6 (5.3%) patients were less than 20 years old. Table 1 shows the age range of the patients. Among the involved, 53 were right eyes and 60 were left eyes. Thirty-six (31.8%) patients were misdiagnosed as other ocular ailments and were diagnosed with choroidal melanoma at our institute [Table 2]. There were no patients with any preexisting or secondary malignancies in our study.

The commonest complaints were blurring of vision (101 patients, 89.4%) and pain (45 patients, 39.8%), while complete visual loss was noted in only 6 (5.3%) patients. Anterior segment was quiet in most of the patients (106 patients, 94%). Anterior uveitis, rubeosis, and sentinel vessels were found in 4 (3.5%) patients. One patient with angle neovascularization was found to have extrascleral extension and optic nerve invasion. The most frequent findings on fundus examination were presence of an elevated mass (69 patients, 61%) and exudative retinal detachment (65 patients, 57.5%). Mild vitreous hemorrhage was present in 24 (21.2%) patients.{Table 1}{Table 2}

The dome shape [Figure 1] was the most common shape encountered (96 patients, 86.1%). Histological findings showed that mixed cell type [Figure 2] was most common (72 patients, 63.7%) followed by spindle cell type (28 patients, 24.7%) [Figure 3]. Epithelioid cell type [Figure 4] was seen in 11 (9.7%) patients. Necrosis was seen in only two (1.8%) cases. The mean basal diameter was 12.41 ± 1.41 mm (range 4–21 mm), while the mean height was 8.91 ± 4.16 mm (range 2–19 mm). Most of the tumors were medium-sized (78 patients, 69%), while 32 (28.3%) patients had large-sized tumors and 3 (2.6%) patients had small-sized tumors. Among medium-sized tumors, nine patients had small size but were peripapillary in location.

Of all the large-sized tumors, 85% were mixed cell type. Most patients (84, 74.3%) had no extrascleral extension.

Scleral invasion was found in 22 (19.5%) patients. Optic nerve involvement was found in seven (6.2%) patients. The mean intraocular pressure (IOP) in these patients was 24 mm Hg (range 20–48 mmHg). Vortex vein involvement was seen in five (4.4%) patients.

Three (2.6%) patients with orbital invasion had medium-sized tumors with diffuse shape and epithelioid cell type on histology. The primary treatment done in these patients was exenteration as orbital involvement was picked up on MRI before surgery.

Enucleation followed by ball implant was the preferred primary treatment in 107 (94.6%) patients, of which 3 patients underwent conservative management before surgery in the form of plaque brachytherapy, transpupillary thermotherapy, and external beam radiotherapy. Exenteration was performed in six (5.3%) patients. Unfortunately, three patients with small size tumors were taken up for enucleation as conservative management was not available at the time of presentation.

Mean period between presentation and surgery was 11.3 ± 3.8 days. Patients who underwent conservative treatment had a longer duration period between presentation and enucleation. Mean follow-up period was 14 months (range 12–96 months). Around 14 (12.4%) patients were lost to follow-up after 1 year. No mortality was reported at the end of 5 years in patients with long follow-up. Three patients with orbital invasion were followed up for 8 years after surgery with no metastasis or mortality.


Discussion

Choroidal melanoma, although commonest primary intraocular tumor, is rare and even rarer in the Asian population.[15] Two studies[6, 8] conducted earlier in the same institute have shown clinicopathological profile of patients with choroidal melanoma between 1987 and 2001. It usually occurs in elderly patients,[2] but in Asians it has been found in young and middle-aged people. An earlier study by Biswas et al.[8] has compared the age of presentation and male: female ratio among Chinese, Caucasians, Afro-Americans, Japanese, Hispanics, and Asian Indians and concluded that Asians present with choroidal melanoma at a younger age than Caucasians and Americans. This study shows the mean age of presentation was 45.94 ± 14.85 years and nearly 38 (33.6%) patients were below 40 years of age, of which 6 were less than 20 years. This is in contrast to the collaborative ocular melanoma study where mean age of eligible patients was 60 years.[8, 9]

Choroidal melanoma is so infrequent and masquerading that it is easily misdiagnosed. In our study, 36 (31.8%) patients were misdiagnosed. The most common misdiagnosis was retinal detachment (26 patients, 23%). One patient was treated as a case of recurrent retinal detachment and underwent vitreous surgery before diagnosis and enucleation. Earlier studies have reported only a few cases of misdiagnosis.[5] Other misdiagnoses included retinoblastoma, central serous chorioretinopathy, and glaucoma.

The commonest symptom was blurring of vision (101 patients, 89.4%) followed by pain (45 patients, 39.8%). Visual loss can be accounted for by destruction of photoreceptor cells due to disrupted choroidal circulation and associated retinal ischemia. Also, presence of fluid in subretinal space and retinal detachment can cause decrease in vision. Enlargement of choroidal mass in the eye can cause pain by direct impingement on the ciliary nerves or by increase in the intraocular pressure.

Anterior segment examination showed rubeosis in four patients, while inflammation was seen in three patients only. Posterior segment evaluation showed presence of elevated mass and retinal detachment in most of the patients although in some patients both findings were also seen. Deranged liver function tests were present in six (5.3%) patients, of which four had fatty liver. The remaining two patients had increased alkaline phosphatase levels which were considered insignificant by the oncologist.

Our study showed dome-shaped melanoma as the commonest type (98 patients, 86.7%) and was a predominant feature of large-shaped tumors. Mushroom-shaped tumors were the second most common finding. The diffuse form was seen in five (4.4%) patients[1013] and was seen in all three patients with orbital extension. Histology showed mixed cell as the predominant type of choroidal melanoma followed by spindle cell type. Epithelioid cell type was seen in 11 patients and was seen in all patients with orbital invasion. Patients with optic nerve invasion had raised IOP and exudative retinal detachment (71.4%) as major finding.[14] Our study showed a larger number of patients with extrascleral involvement (11%) as compared to earlier studies.[7, 8]


Conclusion

Choroidal melanoma is a rare tumor in the Indian population; however, its frequency in the young population is on the rise. It can be easily misdiagnosed and has a poor prognosis if detected late. In our study, mixed cell was the most common histological type of melanoma observed. Our study showed that diffuse choroidal melanoma predominantly had epithelioid cell type and orbital invasion. Although large choroidal tumors are mostly managed by enucleation, there is a trend in treatment of medium-sized tumors with brachytherapy based on supportive long-term studies.[15]


Notes

Source of Support: Nil

Conflict of Interest: No.

Acknowledgement

We sincerely acknowledge the help and support given by the Dept. of Pathology, Sankara Nethralaya, and thank the radiologists for their inputs.


References
1. Duke-Elder S,Perkins ES. Diseases of uveal tract in System of OphthalmologyYear: 19669LondonHenry Kimpton843
2. Egan KM,Seddon JM,Glynn RJ,Gragoudas ES,Albert DM. Epidemiologic aspects of uveal melanomaSurv OphthalmolYear: 198832239513279559
3. Kuo PK,Puliafito CA,Wang KM,Liu HS,Wu BF. Uveal melanoma in ChinaInt Ophthalmol ClinYear: 19822257717107133
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5. Manohar S,Ramachandran R,Das T,Namperumalsamy P. Malignant melanoma of choroidIndian J OphthalmolYear: 1991397031916986
6. Biswas J,Subramanian K,Shanmugam MP. Uveal melanoma in Asian Indians: A clinicopathological studyArch OphthalmolYear: 2002120522311934337
7. Shields JA. Diagnosis and Management of Intraocular TumoursYear: 1983St. LouisCV Mosby789
8. The collaborative ocular melanoma study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma. I: Characteristics of patients enrolled and not enrolled. COMS report No.9Am J OphthalmolYear: 1998125767789645715
9. Shields CL,Shields JA,Milite J,Potter PD,Sabbagh R,Menduke H. Uveal melanoma in teenagers and children - A report of 40 casesOphthalmologyYear: 199198166261800926
10. Biswas J,Raghavendran R,Ratra V,Krishnakumar S,Gopal L,Shanmugam MP. Diffuse malignant melanoma of the choroid simulating metastatic tumour in the choroidIndian J OphthalmolYear: 2000481374011116511
11. McLean IW,Foster WD,Zimmerman LE. Uveal melanoma: Location, size, cell type and enucleation as risk factors in metastasisHum PatholYear: 198213123327076200
12. Grossniklaus HE,Albert DM,Green WR,Conwas BP,Hovland KR. Collaborative ocular melanoma study group. Clear cell differentiation in choroidal melanoma. COMS report. No. 8Arch OphthalmolYear: 199711589489230830
13. Shields CL,Shields JA,Deport P,Cater J,Tardio D,Barret J. Diffuse choroidal melanoma - Clinical features predictive of metastasisArch OphthalmolYear: 1996114956638694731
14. Lindegaard J,Isager P,Prause JU,Heegaard S. Optic nerve invasion of uveal melanomaAPMISYear: 200711511617223846
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Figures

[Figure ID: F1]
Figure 1 

A single, well-defined elevated, grayish-brown mass present 7 DD in size in the inferotemporal quadrant, 2 DD from the macula with ILM straie at the macula



[Figure ID: F2]
Figure 2 

Mixed cells type with both epithelioid cells and Spindle cells, ×100



[Figure ID: F3]
Figure 3 

Spindle cells seen in tight bundles. Spindle-A cells visible with a slender nucleus and appear very thin. Spindle-B cells have a bigger nucleus and a more prominent and eosinophillic nucleolus, ×100



[Figure ID: F4]
Figure 4 

Epithelioid cells with large nuclei and prominent nucleoli, ×100



Tables
[TableWrap ID: T1] Table 1 

Age distribution



[TableWrap ID: T2] Table 2 

Cases misdiagnosed




Article Categories:
  • Original Article

Keywords: Choroidal melanoma, India, malignant melanoma of choroid, uveal tumors.

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