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Purpose: To describe a clinical case of biopsy-proven Merkel cell carcinoma of the eyelid following golimumab therapy for rheumatoid arthritis (RA)., Methods: Interventional case report., Results: A 73-year-old woman with a history of chronic RA presented with a right upper eyelid mass. She had been treated with golimumab (tumor necrosis factor (TNF) inhibitors) injection therapy for the past 6 months. A biopsy showed findings suggestive of a Merkel cell carcinoma of the eyelid., Conclusions: Merkel cell carcinoma may be associated with anti-TNF treatment and should be included in the differential diagnosis of an eyelid tumor in patients treated with TNF inhibitors.

The discovery of BRAF mutation in ~50% of melanomas led to the development of small molecule BRAF inhibitors, including sorafenib, debrafenib, and vemurafenib. Clinical trials have shown these agents to be effective in treatment of metastatic and locally advanced melanoma, increasing overall and progression-free survival. However, some of the most common toxicities associated with BRAF inhibitor therapy include adverse skin events such as rashes, photosensitivity, hyperkeratosis, papillomas, keratoacanthomas, and squamous cell carcinomas. Here, the authors describe 3 patients who developed keratinocytic neoplasms on the eyelid, including invasive squamous carcinoma secondary to vemurafenib. Vigilant screening and a high index of suspicion for eyelid carcinomas are recommended in patients treated with vemurafenib.

Purpose: To evaluate the effect of cyclopamine, an inhibitor of the Sonic hedgehog (Shh) signal, on the growth of an epithelial neoplasm., Methods: Chemically induced eyelid tumors in XPC-null mice (n=40) were treated daily with a subcutaneous injection of cyclopamine (1 mg/animal) for 7 days. The animals were killed after bromodeoxyuridine (BrdU) labeling, and the tumors were histologically examined. An in vitro study was conducted by using a squamous cell carcinoma (SCC) cell line. The SCC cells were treated with 0, 12.5, or 25.0 microg/ml recombinant Shh (rShh) and either 0 or 100 microM cyclopamine, and cell proliferation was evaluated by using an MTT assay. Cells from this cell line were also implanted subcutaneously in nude mice (n=8) to develop tumors, and the effect of cyclopamine administration was examined in the developed tumors., Results: Histology showed that cyclopamine treatment suppressed BrdU incorporation and induced apoptosis in the majority of cells in tumors chemically induced in the eyelid of the XPC-null mice. Cell proliferation of the SCC cell line was enhanced by adding rShh, and this effect was abolished by adding cyclopamine. Proliferation of the SCC cell line was not affected by adding cyclopamine in the absence of rShh. On the other hand, the SCC cells expressed Shh in vivo in tumors developed in nude mice, but cyclopamine suppressed cell proliferation in the tumors, and the Shh-signaling pathway was inhibited by cyclopamine-induced apoptosis., Conclusions: Cyclopamine inhibits proliferation and induces apoptosis in epithelial tumor cells in vivo. The Shh-signaling pathway may be a potential therapeutic target for patients with eyelid tumors., (Copyright (c) Japanese Ophthalmological Society 2006.)

Spontaneous amelanotic melanomas in the eyelids of F344 rats were found in one of 1/926 (0.11%) male and 5/925 (0.54%) female F344 rats that were used as control and treated animals in five different carcinogenicity studies conducted by the National Toxicology Program (Research Triangle Park, NC). These melanomas were grossly recognized as single, tan or white, well-circumscribed masses of the right or left eyelid. These melanomas primarily occurred in the dermis of the skin of the eyelids and consisted of poorly differentiated spindle cells characteristically arranged in interlacing fascicles. Rarely, epithelioid tumor cells were also observed, and these tumor cells showed a negative histochemical reaction for melanin. The epidermis and dermal-epidermal junction were usually uninvolved. The diagnosis of amelanotic melanoma could only be established by electron microscopic examination. The most striking ultrastructural feature of the tumor cells was a large number of intracytoplasmic premelanosomes (stage II melanosomes without melanin), which nearly filled the cytoplasm of most tumor cells. Giant premelanosomes and melanophagosomes were also seen. The tumor cells did not possess the ultrastructural features characteristics of Schwann cells (thin, long cell processes and pericytoplasmic basal laminae). The histologic and ultrastructural features of these palpebral tumors were similar to those of cutaneous amelanotic melanomas of the pinna in F344 rats.

This is a case report of a patient with parkinsonism on levodopa therapy who developed a lid margin melanoma. The possible association is discussed.

A 40-year-old woman had documented mycosis fungoides of the skin. Over a period of five years, she had undergone intermittent treatment with psoralen long-wave ultraviolet light (PUVA) therapy. Despite regression of the skin lesions, tumor plaques developed in her eyelid and conjunctiva within the area shielded by dark glasses. Light and electron microscopic examination of a biopsy from the conjunctival plaque confirmed that the lesion was a deposit of mycosis fungoides. Local radiotherapy resulted in complete regression of these ocular lesions. The conjunctiva may well be an iatrogenic "sanctuary site" when this disease is treated with PUVA therapy.

Twenty-two cases of intra-epidermal carcinoma of the ciliary margin have been diagnosed in a 15-year survey. The clinical appearance is variable, resembling in some instances a benign warty lesion, and in others a fully developed squamous cell carcinoma. As the lesion grows it produces keratotic plugging of the lash follicles and nodules on the lid margin; in due course this results in loss of the related cilia. When dermal invasion occurs the resultant squamous cell carcinoma is potentially dangerous because of the involvement of the adnexal structures, which on the ciliary margins are particularly large and penetrate deeply into the lid substance. Adequate biopsy which includes at least one lash follicle is essential for accurate diagnosis, and treatment requires complete excision with a reasonable margin for safety. Of the twenty-two patients, nineteen were male and three female; fourteen of the men involved had handled oils and greases for prolonged periods.