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Case history

image A 62-year-old man was diagnosed with a 2.4 mm ulcerated acral lentiginous malignant melanoma of the right great toe nail bed in May 2014. His medical history included essential hypertension, although he was not on any regular medication. He was active and had a performance status of 0. The melanoma was surgically resected by amputation of his right great toe. Sentinel lymph node biopsy was positive: two out of two nodes sampled contained melanoma. He underwent right groin completion lymph node dissection; 12 nodes were removed, one of which contained malignant melanoma. Overall his disease was staged as IIIC malignant melanoma (T3bN2M0). BRAF mutation testing was negative. Following multidisciplinary team review he began high-risk follow-up with both oncology and plastic surgery teams.

Two years later a PET-CT scan demonstrated asymptomatic recurrent disease in his right internal and external iliac nodes. These were resected laparoscopically; histological examination showed that 13 out of 19 lymph nodes contained metastatic melanoma.

Three months later he presented with left-sided inguinal lymphadenopathy. A staging CT scan showed a 2 × 1.5 cm left inguinal lymph node but no other areas of metastatic disease. He agreed to start combination immunotherapy with nivolumab and ipilimumab in September 2016. By November 2016 he had completed four cycles, complicated by hypopituitarism treated with hydrocortisone replacement.

A restaging CT scan after four cycles of treatment demonstrated progressive disease with left inguinal lymphadenopathy measuring 3.6 × 2.3 cm, a new pulmonary nodule measuring 5 mm and new mediastinal lymphadenopathy measuring up to 1.9 cm. He remained well, with a performance status of 0, and was referred for consideration of participation in a clinical trial. While going through clinical trial screening it was discovered that his tumour was KIT wild-type, prompting further reassessment scans.

A restaging CT scan 8 weeks after stopping treatment showed a delayed response to immunotherapy with a marked regression in the mediastinal lymph nodes but an increase in size of the left inguinal lymph node to 5.4 × 3.4 cm. Several weeks later he observed a spontaneous clinical regression of his left inguinal lymph node. He began maintenance nivolumab therapy. Recent scans show an ongoing response to treatment; on clinical review there was no palpable lymphadenopathy. He remains on nivolumab immunotherapy and hormone replacement therapy; no further toxicities have been observed.

What is the evidence for the treatment of acral melanoma with immunotherapy?

Are there other cases displaying a delayed response to immunotherapy described in the literature?

What are the immune-related response criteria?

What is the evidence for the treatment of acral melanoma with immunotherapy?

Acral lentiginous melanoma occurs on non-hair-containing surfaces of the body such as the palms, soles and under the nails. It is less common in people with lighter skin types. Acral melanomas are morphologically and epidemiologically distinct from non-acral cutaneous melanoma (CM).1 A small subset of patients with acral melanoma have activating mutations in the KIT...

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