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Nivolumab for adjuvant treatment of desmoplastic malignant melanoma: A case report

Dear Editor, Desmoplastic malignant melanoma (DM) is a rare variant of malignant melanoma (MM), and immune checkpoint inhibitors are effective in treating this condition. We report a case of DM treated with nivolumab. A 74-year-old Japanese woman presented to our department with a 7-month history of a nodule on her upper left arm (Fig. 1a). A skin biopsy was performed at another hospital; however, no definitive diagnosis was made. After 5 months, the nodule had gradually increased in size, becoming painful, so the patient was referred to our hospital. Physical examination revealed a clear red nodule of 50 mm 9 50 mm diameter on her upper left arm. A brown macular lesion was also observed adjacent to the red nodule. A biopsy specimen obtained from the red nodule revealed spindle-shaped tumor cells with bundle-like proliferation in the deep dermis and the subcutaneous adipose tissue. There was collagenous fiber hyperplasia in the interstitium, along with relatively small and elongated ellipsoidal nuclei (Fig. 1b). Immunohistochemical analysis showed that the tumor cells were positive for S100 and SOX10, but negative for MDM2, CDK4 and p53; these findings were indicative of DM. A biopsy specimen from the brown macule showed nests of atypical melanocytes in the upper dermis and epidermis (Fig. 1c). Melanophages were observed in the upper dermis infiltration, possibly due to some regression of the atypical melanocytes. We diagnosed the macule as lentigo maligna melanoma (LMM). The tumor was excised under general anesthesia; deep excision included the deltoid muscle with a margin of 20 mm from the area of the erythema and 10 mm from the macular area. In spite of this, tumor cells were detected at the bottom of the lesion. The patient refused reoperation, due to the invasive nature of the surgery. The patient tested negative for BRAF mutations. Radiotherapy (50 Gy/20 fx) was administrated. Ten weeks after surgery, positron emission tomography/computed tomography showed lymph node metastasis in the left axilla, and dissection of the left axillary lymph nodes was performed. Four months after surgery, the patient started a treatment with nivolumab (3 mg/kg, every 2 weeks), and 11 months after surgery there was no sign of recurrence. Desmoplastic malignant melanoma is a variant of MM, which was first reported by Conley et al. in 1971, and it is often found over sun-damaged areas of the skin. Although DM may occur de novo, it is also known to occur concurrently with common MM. Our patient had a 20-year history of LMM prior to the occurrence of DM. We speculated that the DM in our patient occurred as a satellite lesion of the adjacent LMM. Treatment with nivolumab was very effective in the described case. Recently, Zeynep et al. reported that antiprogrammed death 1 (PD-1) inhibitors showed a high response rate in DM. In their study, 60 patients with advanced DM were treated with anti-PD-1 or PD ligand 1 antibodies. Objective tumor responses were observed in 42 of the 60 patients, including 19 patients who showed complete response. The mechanisms of action of the PD-1 antibody involved in the effective treatment of DM require further study.