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Clinicopathologic Reports, Case Reports, and Small Case Series
March 2002

Choroidal Melanoma Treated With Cryotherapy

Arch Ophthalmol. 2002;120(3):393-395. doi:

The treatment of small choroidal melanocytic tumors is evolving because of the recognition of risk factors for growth and metastasis.13 Ideally, the treatment of small melanocytic tumors would completely eradicate the tumor without compromising visual acuity. Cryotherapy has been used in a limited fashion for the treatment of choroidal melanomas.46 Lincoff et al4 and Brovkina et al5 evaluated cryotherapy in small series of patients with medium-sized and large melanomas, but exudative retinal detachment and incomplete tumor destruction compromised treatment. We report the clinical and histopathologic findings in a patient treated with cryotherapy for a small, growing choroidal melanocytic tumor 125 months before death from unrelated causes.

Report of a Case

The patient was initially seen in August 1988 for a routine eye examination and was found to have a pigmented juxtapapillary choroidal lesion (Figure 1). By January 24, 1989, the lesion had clearly enlarged. Examination at that time showed visual acuity of 20/20 and a normal anterior segment. A pigmented juxtapapillary lesion was located inferonasal and adjacent to the optic nerve (Figure 2). Echography demonstrated that the tumor measured 1.8 mm in thickness, 7.5 mm in longitudinal diameter, and 6.0 mm in transverse diameter. The patient was enrolled in a trial of cryotherapy for treatment of small choroidal melanocytic tumors, and the tumor was treated on March 15, 1989, using a double freeze-thaw cryotherapy with a conventional retinal cryoprobe. The optic nerve was included in the treatment. On the first postoperative day, the patient's vision was no light perception. The tumor diminished in thickness, but a small area of pigmentation remained in the center of the treatment scar. This area of pigmentation was treated again on August 10, 1993. The tumor regressed to a flat chorioretinal scar after the second cryotherapy treatment. Periodic liver function tests and chest x-ray films were obtained and indicated no suggestion of metastatic disease. There was no clinical evidence of recurrence of the tumor (Figure 3). The patient died of cardiovascular disease 125 months after his initial treatment. No autopsy was performed, but the eyes were obtained for histopathologic study.

Figure 1
 Funduscopic appearance of peripapillary
pigmented lesion in August 1988.

Funduscopic appearance of peripapillary pigmented lesion in August 1988.

Figure 2
 Funduscopic appearance of lesion
in January 1989 demonstrating enlargement of tumor. Note extension of the
tumor beyond the adjacent retinal vein.

Funduscopic appearance of lesion in January 1989 demonstrating enlargement of tumor. Note extension of the tumor beyond the adjacent retinal vein.

Figure 2
 Funduscopic photograph of the
retinal and choroidal scar 6 years after cryotherapy to lesion. Note the pallor
of the optic nerve head.

Funduscopic photograph of the retinal and choroidal scar 6 years after cryotherapy to lesion. Note the pallor of the optic nerve head.

The left globe was fixed in 10% neutral buffered formalin and processed for light microscopy. Serial sections were prepared through the entire extent of the chorioretinal scar and studied for evidence of residual tumor.

Microscopic examination showed near full-thickness atrophy of the retina and choroid in the area of the cryotherapy (Figure 4). The retina in the area of cryotherapy consisted of a thin layer of glial cells with some migration of hyperplastic retinal pigment epithelium into the retina (Figure 5). There was a thin monolayer of cells on the surface of the retina (epiretinal membrane). A few large vessels were present in the choroid, but there was atrophy of the small and medium-sized choroidal blood vessels. Occasional pigment-containing macrophages were found within the choroid, but no tumor cells were present, and no tumor cells were evident in the sclera or retina. The optic nerve was atrophic, and loss of axons and myelin and thickening of the pial septae were evident (Figure 6). The sclera in the area of cryotherapy was of normal thickness (Figure 7).

Figure 4
 Microscopic examination shows
the junction (arrowhead) of the treated (left side of figure) and untreated
(right side of figure) retina and choroid. Note the loss of all retinal layers
in the area of treatment. Also apparent is the loss of most of the choroidal
vessels, with preservation of some of the large choroidal vessels. The retina
and choroid are artefactitiously detached from the sclera (hematoxylin-eosin,
original magnification times200).

Microscopic examination shows the junction (arrowhead) of the treated (left side of figure) and untreated (right side of figure) retina and choroid. Note the loss of all retinal layers in the area of treatment. Also apparent is the loss of most of the choroidal vessels, with preservation of some of the large choroidal vessels. The retina and choroid are artefactitiously detached from the sclera (hematoxylin-eosin, original magnification times200).

Figure 5
 Microscopic appearance of the
retina and choroid in the center of the area of cryotherapy, showing no remaining
tumor cells. The retina is reduced to a thin layer of cells and fibrous tissue.
A few pigmented macrophages are present within the retina and choroid. The
small and medium-sized choroidal blood vessels are absent, but a large choroidal
vessel remains (asterisk) (hematoxylin-eosin, original magnification times400).

Microscopic appearance of the retina and choroid in the center of the area of cryotherapy, showing no remaining tumor cells. The retina is reduced to a thin layer of cells and fibrous tissue. A few pigmented macrophages are present within the retina and choroid. The small and medium-sized choroidal blood vessels are absent, but a large choroidal vessel remains (asterisk) (hematoxylin-eosin, original magnification times400).

Figure 6
 Microscopic examination shows
that the optic nerve is markedly atrophic. Marked thickening of the pial septae
is apparent, and only a few areas of myelinated nerve fibers remain (arrowhead)
(hematoxylin-eosin, original magnificationtimes200).

Microscopic examination shows that the optic nerve is markedly atrophic. Marked thickening of the pial septae is apparent, and only a few areas of myelinated nerve fibers remain (arrowhead) (hematoxylin-eosin, original magnificationtimes200).

Figure 7
 Microscopic examination shows
that the sclera in the area of treatment is of normal thickness; however,
the retina and choroid are markedly thinned (between arrowheads) (hematoxylin-eosin,
original magnification times200).

Microscopic examination shows that the sclera in the area of treatment is of normal thickness; however, the retina and choroid are markedly thinned (between arrowheads) (hematoxylin-eosin, original magnification times200).

Comment

The results of our histopathologic study of this case are consistent with complete destruction of this small, growing choroidal melanoma by freezing. Careful study of serial sections failed to disclose any remaining tumor cells. Hidayat et al6 have reported the mechanism of cellular injury in rapid freezing of uveal melanomas to be plasmalemmal breaks, dissolution of cytoplasmic matrix, and damage to cellular organelles, suggesting a lethal effect on melanoma cells.6 Similar mechanisms of cell injury were undoubtedly responsible for the damage evident to the optic nerve and the retina overlying the tumor.

Exudative complications of cryotherapy that have been observed in the treatment of medium-sized and large melanomas were not found in this case. The lack of these complications may be due to the smaller size of the tumor and to the sequential application of less intense cryotherapy than was used in the earlier studies. Also, no apparent damage to the sclera occurred as a result of the cryotherapy.

The complete tumor destruction seen in this case indicates that cryotherapy may be useful as a primary treatment for small, growing choroidal melanomas or as an adjunct for treating recurrences of melanomas treated primarily with radioactive plaque.

This study was supported in part by an unrestricted grant from Research to Prevent Blindness, New York, NY.

Corresponding author and reprints: David J. Wilson, MD, Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Blvd, Portland, OR 97201-4197 (e-mail: wilsonda@ohsu.edu).

References
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McLean  IW In discussion of: Shields CL, Shields JA, Kiratli H, De Potter P, Cater JR. Risk factors for growth and metastasis of small choroidal melanocytic lesions. Ophthalmology. 1995;1021351- 1361Article
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Collaborative Ocular Melanoma Study Group, Factors predictive of growth and treatment of small choroidal melanoma: COMS Report No. 5. Arch Ophthalmol. 1997;1151537- 1544Article
4.
Lincoff  HMcLean  JLong  R The cryosurgical treatment of intraocular tumors. Am J Ophthalmol. 1967;63389- 399
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Brovkina  AFZiangirova  GGKornarov  BA Cryodestruction of choroidal melanomas [in Russian]. Vestn Oftalmol. March-April1977;61- 63
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Hidayat  AALaPiana  FGKramer  KKWhitmore  PVWertz  FDRao  NA The effect of rapid freezing on uveal melanomas. Am J Ophthalmol. 1987;10366- 80
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