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Natalizumab is a monoclonal antibody licensed for the treatment of relapsing-remitting multiple sclerosis (RRMS). It is known to increase the potential risk of developing progressive multifocal leukoencephalopathy (PML). There is current debate in the literature regarding its association with malignant melanoma. Herein, we report a case of a 55-year old lady with RRMS for whom natalizumab therapy was being considered by her neurologist. Her medical history included a choroidal melanoma which had undergone successful treatment. Additionally, in this case study we discuss the issues regarding malignant melanoma risk and recurrence with natalizumab treatment., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Objective: To report the third known and documented occurrence of malignant disease as a complication of immunosuppression associated with low-dose methotrexate therapy for rheumatoid arthritis., Material and Methods: We present a case report of a 64-year-old woman with rheumatoid arthritis who had received low-dose methotrexate therapy for 16 months in whom blurred vision occurred. An ophthalmologic examination was performed, and prednisone was administered. Subsequently, she complained of sore throat, weakness, and fever. An axillary lymph node biopsy and immunologic studies were done., Results: Funduscopic examination revealed severe bilateral choroidal thickening. Findings on the biopsy disclosed a large cell, B-cell phenotype non-Hodgkin's lymphoma. Immunologic studies performed on frozen and paraffin-embedded tissue samples showed that the neoplastic cells were positive for CD20 and CD22 and without definite immunoglobulin light chain expression., Conclusion: Although the occurrence of lymphoma may be associated with autoimmune diseases, low-dose methotrexate therapy has also been implicated. Because of the increasing use of low-dose methotrexate therapy for classic and juvenile rheumatoid arthritis, an increased risk of lymphoproliferative disease is possible.

Background: Currently, there are no animal models of primary uveal melanoma in an eye large enough to allow documentation of the clinical evolution of the lesion by either funduscopy or fundus photography., Methods: The authors induced primary uveal melanocytic lesions in the eyes of Dutch (pigmented) rabbits using a two-stage carcinogenesis protocol involving initiation with 4 weekly topical applications of 10 microliters of a 1% solution of 7,12-dimethyl-benz[a]anthracene (DMBA) in acetone (21 eyes) followed by 12 weekly topical applications of a 10 microliters solution of either 0.25% or 0.5% croton oil in acetone. They also investigated the effect of initiation with DMBA without promotion and the effects of chronic topical exposure to acetone and proparacaine., Results: Exposure to DMBA followed by promotion with croton oil in either concentration was the most effective means of inducing clinically detectable fundus lesions. Histologically, a spectrum of melanocytic proliferations developed including benign nevi, nevi with varying grades of cytologic atypia, and clusters of confluent atypical melanocytes that may represent early melanomas. Although clinical regression of fundus lesions was noted in eight eyes after promotion had been stopped, five of these eyes showed unequivocal histologic evidence of a residual uveal melanocytic lesion. Chronic ocular irritation is capable of inducing cytologically benign subclinical uveal melanocytic proliferations., Conclusions: The conventional classification of human uveal melanocytic lesions includes only nevi and melanomas, but a comparison of the results of this study with descriptions of human uveal melanocytic nevi suggests the existence of a spectrum of intermediate atypical precursor lesions in humans.

This 5-year prospective study of ophthalmologic findings in 1299 patients treated with oral 8-methoxypsoralen photochemotherapy (PUVA) for psoriasis failed to demonstrate a significant dose-dependent increase in the risk of developing symptomatic cataracts. These patients were instructed to wear UVA-blocking eyeglasses when exposed to sunlight and during treatment for a 12-h period beginning from the time of 8-methoxypsoralen ingestion. However, we did observe a small increase in the risk for development of nuclear sclerosis and posterior subcapsular opacities among patients who received at least 100 PUVA treatments, compared to patients with fewer than 100 treatments (relative risk = 2.3 and 3.0, respectively; p less than .05 both comparisons). We compared our results to those of a large, population-based study and found, after adjusting for differences in methods, that the prevalence of cataracts in our study patients, aged 52-75 years, was not significantly different. Since the latency period for development of symptomatic ocular abnormalities may be longer than 5 years, continued surveillance of our cohort and continued use of appropriate ocular protection by all patients treated with PUVA is indicated.

The most abundant carcinogen in tobacco smoke or its condensate has been identified as N-nitrosonornicotine. This is formed predominantly from nicotine in tobacco during curing and smoking but may also be generated within the body. Intravenous injection of 14C NNN appears highly concentrated in the choroid of pigmented mice. Like nicotine, it crosses the placental barrier and appears in the choroid of the embryonic eye in pregnant female mice. Other studies of the male melanoma population show a trend toward earlier life appearance of malignant melanoma in smokers and significantly less of disease-free melanoma-bearing males at five years among smokers. Immunoglobulin G and natural killer leukocyte activities appear to be reduced in male smokers with or without melanomas. Although species and strain differences in susceptibility to carcinogenic agents are well known, these findings led us to a retrospective analysis of 126 white adults undergoing enucleation as immediate therapy for unilateral malignant melanoma of the choroid between 1958 and 1978. Histologic verification and adequate follow-ups were obtained in 105 patients. Minimum follow-up in 65 survivors was 3 years and maximum was 24 years. In 40 patients with metastatic melanomas, death occurred at 3 months to 13 years or at an average of 44 months following surgery. An adequate history of tobacco use was obtained in 94 patients, 44 of which were positive for tobacco use (32 male; 12 female) and 50 were denials (16 male; 34 female). Questions to female patients or families of deceased women evoked more prompt and uncompromising denial than was experienced in questioning of male patients. Straight (non-actuarial) five year tumor mortality in white males with choroidal malignant melanoma showed 12 of 32 or 37% dead among male smokers and 1 of 13 or 8% dead among male non-smokers. Actuarial calculation of five year survival showed only 62% in tobacco using males and 85% in non-tobacco using males. The distribution of cytology was essentially similar in groups both by sex and other subgroupings. There were, however, more large tumors (greater than 10 mm in diameter) in the tobacco group (61%) vs the non-smokers (31%). These preliminary findings merit further analysis by prospective tobacco histories in malignant melanoma patients, particularly among the male population.

In five patients with choroidal melanoma occurring among present or former workers of the duPont Belle, West Virginia, plant the involved eye was enucleated and histopathologic confirmation of the diagnosis was made. This represents a statistically significantly greater than expected occurrence of choroidal melanomas in the white male study population.