Clinicopathological Report

Non-contiguous recurrence or secondary choroidalmelanoma following plaque radiotherapyMauricio Maia MD, Dante J Pieramici MD, Kah-Guan Au Eong MMed(Ophth) FRCS, Andrew P Schachat MD,Eduardo B Rodrigues MD and W Richard Green MDThe Wilmer Ophthalmological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

ABSTRACT

Non-contiguous local recurrence of posterior uveal mela-noma occurs rarely after plaque therapy. A 50-year-old whitefirst presented with choroidal melanoma. He underwenttherapy with episcleral iodine-125 radioactive plaque therapy.Nine years later fundus evaluation revealed a new pigmentedlesion in the inferotemporal equatorial area. Patient was con-sidered to have a non-contiguous recurrent melanoma andthe eye was enucleated. Histologic microscopic examinationdisclosed a 3 ¥ 1.8 mm densely pigmented tumour internal tothe choroid at the equator. The tumour was composed oflarge round cells with round nuclei, prominent nucleoli, abun-dant cytoplasm and spindle-shaped cells with spindle-shapednuclei and prominent nucleoli.The tumour extended throughthe retina. The superior nasal area of plaque therapy hadextensive chorioretinal atrophy with loss of retinal pigmentepithelium, thinning of the retina and thinning and depigmen-tation of the choroids.Within this area of atrophy, there was apigmented lesion composed by densely packed, spindle-shaped cells with spindle-shaped nuclei. Our patient illustratednon-contiguous recurrence of choroidal melanoma, suchfinding raises concerns about physiopathology and treatmentof choroidal melanoma.

Key words: non-contiguous recurrence, plaque radio-therapy; Uveal melanoma; vitreoretinal surgery.

INTRODUCTION

The 5-year recurrence rate of choroidal melanoma afterIodine-125 has been reported to range from 2% to 10%, andlocal recurrence tends to appear as an extension of the origi-nal lesion.1–3 However, non-contiguous local recurrence ofposterior uveal melanoma is a rare finding that has beenreported within 1–2 years after cobalt plaque therapy.3

Herein we describe an unusual case of a non-contiguouschoroidal melanoma recurrence 9 years following primarytreatment with iodine-125 plaque radiotherapy despiteregression of primary tumour.

CASE REPORT

A 50-year-old white man was referred with symptoms offloaters and decreased visual acuity in the left eye owing to amushroom-shaped choroidal melanoma associated with sub-retinal and vitreous haemorrhage. The tumour was located atthe equator superonasally and measured 10 ¥ 9 mm basallyand 4 mm thickness. There was surrounding subretinal andvitreous haemorrhage (Fig. 1a). His best-corrected visualacuity was 6/6 in the right eye and 6/9 in the left eye. Heelected to have episcleral iodine-125 radioactive plaquetherapy.

Three years after treatment, there was no vitreous haem-orrhage and no tumour was evident. Six years after treat-ment, the tumour remained regressed and vision was 6/6.When seen 9 years after treatment (patient with symptomsof floaters), vision had not changed and fundus evaluationrevealed an extensive region of chorioretinal atrophy with acentral, non-elevated, pigmented area at the site of the pre-vious melanoma (Fig. 1b,c). A new dome-shaped pigmentedlesion was present in the inferotemporal equatorial area. Thenew lesion was irregular, had low internal reflectivity, mea-sured 5.5 mm in diameter and 2.2 mm in height byultrasonography. Chest radiograph and liver function testswere normal. Six months later, the tumour had increased insize and occasional pigmented cells were noted in the vitre-ous (Fig. 1d). The tumour now measured 5.7 mm at the baseand 3.3 mm in height (Fig. 2). The vision was 6/9. Patientwas considered to have a non-contiguous recurrent mela-noma with possible vitreous seeding and the eye wasenucleated.

External examination was unremarkable except for a5 ¥ 4 mm defect in transillumination inferior temporal (at theequator. A large area of increased translucency with a

� Correspondence: Dr Eduardo B Rodrigues, Avenue Trompowsky 420/1005, Florianópolis, Brazil. Email: edubrodriguess@yahoo.com.br

Received 23 January 2007; accepted 9 May 2007.

Clinical and Experimental Ophthalmology 2007; 35: 657–660doi: 10.1111/j.1442-9071.2007.01531.x

© 2007 The AuthorsJournal compilation © 2007 Royal Australian and New Zealand College of Ophthalmologists

7 ¥ 4 mm central area of reduced translucency was present inthe superior nasal quadrant. The eye was opened obliquely ina plane parallel to the centre of these two areas of reducedtranslucency revealing a 5 mm (anterior posterior) by 3 mm(thick) darkly, pigmented tumour at the equator inferiortemporally. A 15 ¥ 15 mm area of depigmentation with a6 ¥ 4 mm central, flat-pigmented area was present in thesuperior nasal quadrant. Microscopic examination discloseda 3 mm (anterior posterior) by 1.8 mm (height) densely pig-mented tumour located internal to the choroid at the equatortemporally (Fig. 3a).

The tumour extended through the retina, into the vitreousand clusters of melanophages were present within as well asthe area of probable vitreous seeding (Fig. 3b). The tumourwas composed of large round cells with round nuclei, promi-nent nucleoli, abundant cytoplasm and indistinct cell borders(intermediate epithelioid cells) and spindle-shaped cells withspindle-shaped nuclei and prominent nucleoli (spindle Bcells) (Fig. 3c). Normal appearing blood vessels were presentthroughout the tumour. No longitudinal, arcs, loops or net-works were apparent and clusters of tumour cells with somemelanophages were present along the inner retinal surface

a

c

b

d

Figure 1. Clinical findings of theprimary choroidal melanoma andthe recurrent tumour. (a) Fundusphotograph shows the appearanceof the choroidal melanoma (arrows).Vitreous haemorrhage obscuresview. (b) Appearance of regressedprimary tumour after I-125 radio-therapy with chorioretinal atrophyas well as a flat and pigmented area(arrow). Optic nerve is shown(arrowhead). (c) Chorioretinalatrophy 9 years after I-125 radio-therapy and the regressed primarytumour (arrow). (d) Appearance ofinferior temporal tumour (arrow)with apparent vitreous seeding.

a b

c

Figure 2. Ultrasonography of therecurrent tumour in the left eye. (a)No choroidal thickening is presentin the area of the treated tumoursuperior nasal. (b) A dome-shaped5.7 ¥ 5.9 mm (base) tumour at theinferotemporal equatorial area isobserved. (c) The lesion has amedium to low internal reflectivity.Kappa angle is present.

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posterior to the tumour (Fig. 3d). Most tumour cells stainedpositively for HMB 45 and S 100. Macrophages within thetumour and along the inner surface of the retina stainedpositively for HAM 56. The tumour extended through theretina (Fig. 4).

The superior nasal area of plaque therapy had extensivechorioretinal atrophy with loss of retinal pigment epithe-lium, thinning of the retina and thinning and depigmentationof the choroid (Fig. 5a). Within this area of atrophy, therewas a pigmented lesion that measured about 10 mm(anterior-posterior) and up to 110 mm in maximal thickness.This lesion was composed by densely, packed, slender,spindle-shaped cells with spindle-shaped nuclei that hadno nucleoli or central chromatin strips and scattered mel-anophages (Fig. 5b). The last clinical evaluation in January2002 disclosed no clinical evidence of metastasis. Chestradiograph and liver function tests were normal. Evaluationof the right eye was unremarkable.

DISCUSSION

Most irradiated melanomas undergo tumour regression.4 Therisk of non-continuous recurrence is less than 1%, whichusually occurs within 1–2 years after plaque placement.3

Several mechanisms have been postulated to explain the

non-contiguous recurrence: the tumour cells released intosubretinal fluid, haematogenous spread, secondary radiation-induced malignances and susceptibility to uveal melanomaformation.5 We hypothesized that this tumour spread via

a b

dc

Figure 3. Histopathological findings of the recurrent melanoma. (a) The recurrent non-contiguous melanoma (arrow) at the inferiortemporal equator. (haematoxilin eosin, original magnification ¥1.2). (b) The recurrent melanoma is located internal to the Bruch’s membrane,has normal appearing blood vessels and several foci of melanophages (arrow) and extends through the retina and into the vitreous cavity.Arrowhead shows the area of probable vitreous seeding (haematoxylin eosin. Original magnification ¥10). (c) Area of recurrent tumour withlarge cells with rounds nuclei, prominent nucleoli and moderate amount of cytoplasm with indistinct borders (haematoxylin and eosin, originalmagnification ¥360). (d) Clusters of tumour cells along inner surface of retina near the posterior pole (haematoxylin and eosin, originalmagnification ¥544).

Figure 4. The recurrent melanoma is located internal to theBruch’s membrane, has normal appearing blood vessels and foci ofmelanophages. The tumour and extends through the retina (arrow).Choroid is shown (arrowhead – haematoxylin eosin. Original mag-nification ¥20).

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vitreous seeding and gravitational deposition. The presenceof the vitreous haemorrhage initially suggests that tumourcells may have had access to the vitreous cavity. Alternatively,one could argue that this tumour spread via the subretinalspace as subretinal fluid and haemorrhage was present involv-ing the initial tumour. However, the location of the secondarytumour was quite distant to any area of pre-existing subretinalhaemorrhage or fluid. It is known that most of choroidalmelanomas with subretinal fluid do not develop recurrencesaway from the original tumour. Additionally, non-contiguousrecurrence can be seen in eyes with tumours that were notassociated with vitreous haemorrhages or extension throughthe retina.3–7 So, the correct mechanism for this recurrence orsecondary tumour remains unclear.

This case of probable non-contiguous melanoma recur-rence emphasizes the importance of continued careful followup of patients having undergone radioactive plaque therapy,even if the primary tumour is successfully treated. Data aboutnon-contiguous melanoma recurrences have been previouslyreported. In these cases the recurrences occurred within1–2 years after plaque treatment and the primary tumour hadnot fully regressed at the time of recurrences. Additionally,three of these patients died owing to metastases varyingbetween 3 and 6 months after diagnosis of the secondarytumour.3 Our patient had no clinical or laboratory evidencesof metastases (3 years of follow up only) and his non-contiguous tumour recurred years after total regression ofthe primary tumour. In summary, this unusual case of prob-able non-contiguous uveal melanoma recurrence followingregression of the primary tumour after I-125 radioactiveplaque treatment generates concerns about physiopathology,treatment and follow up of these patients.

ACKNOWLEDGEMENTS

This study was supported in part by the National MedicalResearch Council – Singapore Totalisator Board MedicalResearch Fellowship (Dr Au Eong) and the IndependentOrder of Odd Fellows, Winston Salem, North Caroline(Dr Green).

REFERENCES

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2. Roberston SM. Response pattern after Iodine 125 brachitherapy.Arch Ophthalmol 1999; 117: 771–6.

3. Duker JS, Augsburger JJ, Shields JA. Noncontiguous local recur-rence of posterior uveal melanoma after cobalt 60 episcleralplaque therapy. Arch Ophthalmol 1989; 107: 1019–22.

4. Gunduz K, Shieds CL, Shields JA, Cater J, Freire JE, Brady LW.Radiation complications and tumor control after plaque radio-therapy of choroidal melanoma with macular involvement. Am JOphthalmol 1999; 127: 579–89.

5. Lois N, Shields CL, Shields JA, De Potter P, Ramsey MS.Trifocal Uveal Melanoma. Am J Ophthalmol 1997; 124: 848–50.

6. Spencer WH. Optic nerve extension of intraocular neoplasms.Am J Ophthalmol 1975; 80: 465–71.

7. Kim JW, Damato BE, Hiscott P. Noncontiguous tumor recur-rence of posterior uveal melanoma after transscleral localresection. Arch Ophthalmol 2002; 120: 1659–64.

a bFigure 5. Histopathological find-ings of the primary melanoma afterplaque treatment. (a) Superior nasalarea of plaque therapy with chori-oretinal atrophy (haematoxyin andeosin, original magnification ¥ 136).(b) Flat pigmented lesion in thecentre of the chorioretinal atrophyof the plaque treated area is com-posed of densely packed, slenderspindle-shaped cells with no nucleior central chromatin strips. Scat-tered pigmented macrophages arepresent (haematoxylin and eosin,original magnification ¥544).

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