Neoadjuvant treatment with dabrafenib of unresectable localizations from occult melanoma

Abstract

A 30-year-old woman was referred to the Veneto Institute of Oncology (Padua, Italy) for a painful and fast-growing large mass in the triceps muscle of the left arm. The patient presented with semiflexion of the forearm and flexion of the hand because this position avoided the onset of pain. At physical examination, a mass with a diameter of 5 × 5 cm, hard, painful, and fixed inside the triceps muscle was found. One of the lymph nodes of the ipsilateral axilla was enlarged. Contrast-enhanced computed tomography (CT) of the limb showed a solid hyperdense oval lesion of 45 × 32 × 42 mm without welldefined margins and vascular infiltration (Fig. 1a). A fineneedle aspiration biopsy was performed on the mass. The final diagnosis was metastasis of melanoma. An ultrasound scan of axilla identified a lymph node highly suspicious for malignancy and fine-needle aspiration cytology confirmed the presence of cells of melanoma.A full skin examination and dermoscopy were also negative. Serum protein S-100B was elevated to 3.74 μg/l (normal range 0-0.1 μg/l); serum lactate dehydrogenase was normal. Whole-body staging with brain, chest, and abdominal CT scan showed three hepatic hemangiomas.The patient was diagnosed as stage III of melanoma of unknown primary (MUP). The clinic case was discussed at the multidisciplinary melanoma meeting. The primary limbsparing surgery was not considered possible because of the massive infiltration of triceps muscle and its compression/ infiltration of the artery and radial nerve. The biopsy was then tested for the BRAF mutation. The BRAF sequencing indicated a V600E mutation; therefore, this patient was eligible for treatment with the BRAF inhibitor dabrafenib. In case of dabrafenib failure, this patient was evaluated for chemotherapy or ipilimumab plus radiotherapy. The patient was started on dabrafenib (150 mg) orally twice a day. During treatment, the metastatic triceps mass and the axillary lymph node were clinically regressed, not painful, and palpable with difficulty, and the patient had a normal position of the arm. After 3 months of dabrafenib treatment, the brain, thoracic, and abdominal CT scan were still negative. The upper limb CT scan confirmed a reduction in the metastatic mass and vascularization (about 24 × 20 × 25 vs. 45 × 32 × 42 mm) (Fig. 1b). The clinical case was discussed again and the opinion was that the patient could be eligible for conservative surgery, which consisted of partial resection of triceps muscle with clear macroscopic margins and axillary lymph node dissection ( Fig. 2a and b). The histological report showed two lymph node metastases out of 41 examined lymph nodes and a solid tumor nodule without necrosis of 20 mm diameter.This neoplastic nodule showed infiltrative margins into the skeletal muscle with foci of lymphocytic inflammation at the periphery of the lesion and few areas of necrosis, and it was not surrounded by a capsule; the margins were clear (Fig. 3). Four weeks after surgery, protein S-100 was normalized and it was decided to start adjuvant low-...

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