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Spontaneous regression of cancer is a rare occurrence that has been documented with several cancers, including cutaneous melanoma.1 In cutaneous melanoma the regression is typically partial, occasionally displaying transient dermal inflammation with subsequent pink-gray atrophic changes. Rarely does cutaneous melanoma spontaneously disappear completely, and relapse is common.2
Observations of spontaneous regression of choroidal melanoma are exceedingly rare. Of over 8000 patients with choroidal melanoma cared for at the Ocular Oncology Service at Wills Eye Hospital, Philadelphia, Pa, we have personally witnessed and photographically documented spontaneous regression in only 3 patients. We suspect that there may be additional cases of tumor regression that remain subclinical with partial necrosis, not appreciated on ophthalmoscopy or ultrasonography.
Report of Cases
A 60-year-old man noted pain and photopsia in his left eye for 3 days in September 1995. Superonasal conjunctival chemosis and episcleral hyperemia were noted. Funduscopy revealed a minimally pigmented choroidal mass measuring 6.0 mm at the base and 2.2 mm in thickness, with an overlying serous retinal detachment. On ultrasonography, the mass showed acoustic solidity, choroidal excavation, and echolucency in the overlying episcleral tissue. The patient returned 2 months later without pain or chemosis; the choroidal mass had flattened to 1.2 mm in thickness, and the serous retinal detachment had resolved.
In April 1996, the choroidal mass had enlarged to 2.8 mm in thickness, and the patient was referred to us in September 1996. On examination, the left fundus demonstrated a lightly pigmented choroidal mass measuring 11.0 mm at the base with prominent subretinal fluid. A necrotic central area within the tumor surrounded by a viable peripheral rim was noted. Ultrasonography revealed an excavated, acoustically hollow mass measuring 4.0 mm in thickness. The diagnosis of spontaneously regressed choroidal melanoma with recurrence was made. The tumor was treated with plaque radiotherapy.
A 45-year-old man noted redness, irritation, and pain in his left eye of 1 day's duration in March 1998 (Figure 1). Funduscopy revealed a superonasal, juxtapapillary pigmented choroidal mass measuring 14.5 mm at the base and 7.6 mm in thickness. Ocular B-scan ultrasonography revealed an acoustically hollow choroidal mass with overlying episcleral echolucency. A periocular corticosteroid injection was administered for relief of inflammatory pain.
A 45-year-old man noted redness, irritation, and pain in his left eye of 1 day's duration. A, March 1998. A juxtapapillary choroidal mass with overlying serous retinal detachment obscuring the optic disc is found. The ultrasonographic thickness was 7.6 mm. B, April 1998. After resolution of symptoms, the variably pigmented choroidal mass has spontaneously regressed, exposing the optic disc. The ultrasonographic thickness was 5.3 mm. C, June 1998. The choroidal mass continues to spontaneously regress with overlying retinal pigment epithelium alterations. The ultrasonographic thickness was 3.2 mm. D, June 1998. B-scan ultrasonogram demonstrates the untreated, regressed choroidal melanoma.
In April 1998, a strikingly smaller choroidal mass measuring 5.3 mm in thickness was noted. In May 1998, the mass continued to decrease to 3.5 mm in thickness and on referral to us in June 1998, it was 3.2 mm thick. Evidence of prior subretinal fluid with retinal pigment epithelium mottling of the inferonasal fundus was found. Our diagnosis was choroidal melanoma with partial spontaneous regression. Options for treatment included continued observation, radiotherapy, or enucleation. The tumor was treated with a notched radioactive plaque and supplemental thermotherapy.
A 78-year-old woman with Alzheimer disease developed ocular redness, swelling, and extreme pain in her right eye in June 1998. Funduscopy revealed a total bullous serosanguineous retinal detachment with shifting subretinal fluid. A large pigmented choroidal mass measuring 20.0 mm at the base and 11.7 mm in thickness was seen. Ocular ultrasonography confirmed a mushroom-shaped ciliochoroidal mass with intrinsic vascular pulsations, consistent with melanoma. Enucleation was advised. At the time of enucleation, 8 days later, the inflammatory symptoms had completely resolved leaving the patient comfortable, without eyelid or conjunctival edema. On ophthalmoscopy, the tumor was dramatically smaller, measuring 8.5 mm in thickness. We suspected that the melanoma had undergone partial spontaneous regression.
Histopathologically, the enucleated globe demonstrated a highly necrotic ciliochoroidal malignant melanoma. The necrotic cells were rimmed by macrophages, and the viable cells demonstrated features of spindle and epithelioid malignant melanoma cells.
Spontaneous regression of cancer is a remarkable but rarely observed phenomenon, estimated to occur in 1 in 80,000 to 100,000 cases of cancer.1 It is defined as the complete or partial disappearance of a neoplasm in the absence of treatment. Spontaneous regression can occur with many systemic cancers, but it has not been correlated with complete tumor cure as most will ultimately recur.1 In a major review of all of the literature on 504 cases of spontaneously regressed cancer from 1966 to 1987, Challis and Stam1 found the primary cancer sites to be cutaneous malignant melanoma in 14%, renal cell carcinoma in 13%, lymphoma in 13%, leukemia in 11%, neuroblastoma in 8%, retinoblastoma in 6%, and breast cancer in 4%.
From the standpoint of cutaneous melanoma, it is believed that some degree of spontaneous regression is detected in 10% to 30% of cases.2,3 The clinical features suggesting regression are the development of depigmented areas and inflammation. The histopathologic appearance of cutaneous melanoma regression includes degeneration of tumor cells, lymphohistiocytic infiltrate, pigment-laden macrophages, dermal fibrosis, and epidermal atrophy.2 The prognostic significance of spontaneous regression with cutaneous melanoma is unclear, but some investigators feel it is associated with a worse prognosis.3 Sondergaard and Hou-Jensen3 found that stage I cutaneous melanoma has a 95% 10-year survival rate in those without regression and a 79% 10-year survival rate in those with spontaneous regression. In unusual circumstances, the primary site of cutaneous melanoma completely regresses leaving no clinical trace of tumor, but these patients are still at risk for metastatic melanoma.
Spontaneous regression of choroidal melanoma has been recognized, often masquerading as scleritis.4 Unfortunately, the regressed tumor often relapses.4 In this report we document photographically the clinical features of 3 patients, all of whom had ocular inflammation. The rate of tumor regression varied from a 45% decrease in thickness in 2 months to a 27% decrease in thickness in 1 week.
The mechanisms of spontaneous regression of cancer remain unclear. It is speculated that regression may occur from multiple mechanisms that include immunologic forces, hormonal influence, carcinogen elimination, tumor cell differentiation or necrosis, angiogenesis inhibition, and others.1,2 Knisely and Niederkorn5 demonstrated in the murine melanoma model that spontaneous regression can occur in immunologically intact hosts, using cytotoxic T-lymphocyte and delayed-type hypersensitivity responses directed against melanoma cells.
In conclusion, choroidal melanoma can show partial spontaneous necrosis with regression. The tumor often demonstrates inflammatory findings during the process of necrosis. A better understanding of the mechanisms of spontaneous regression of cancer, and uveal melanoma in particular, may provide insight into alternative treatments.
Reprints: Carol L. Shields, MD, Ocular Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19107.
This study was supported by the Paul Kayser International Award of Merit in Retina Research, Houston, Tex (Dr J. A. Shields), the Macula Foundation, New York, NY (Dr C. L. Shields), and the Eye Tumor Research Foundation, Philadelphia, Pa.
Shields CL, Shields JA, Santos MCM, Gündüz K, Singh AD, Othmane I. Incomplete Spontaneous Regression of Choroidal Melanoma Associated With Inflammation. Arch Ophthalmol. 1999;117(9):1245–1247. doi:
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