Lentigo maligna melanoma showing radial growth mimicking eruptive melanocytic nevi

Dear Editor, We report a case of lentigo maligna melanoma presenting an eruptive melanocytic nevi-like appearance. A 74-year-old man presented with a swollen left cervical lymph node, a 7-mm pigmented nodule, and 1-mm speckled lentiginous eruptive melanocytic nevi-like lesions on the left preauricular area [Figure 1a]. A needle biopsy of the neck found melanoma cells. From the patient's daily snapshots, the nodule had not been present at least 3 years ago. Until the first visit to our department, he had not noticed the speckled melanocytic lesions. The largest nodule seemed to be the primary lesion, with the small eruptive lesions having occurred subsequently. Dermoscopy showed atypical pigment networks and bluish-white veils in the nodule, and irregular dots and streaks in the speckled lesions [Figure 1b and c]. Metastasis to the parotid gland and the cervical lymph nodes was suspected based on preoperative contrast-enhanced computed tomography. We resected the cutaneous lesions with a 1-cm margin from the primary nodular lesion and a 5-mm margin from the outermost speckled lesions. Subtotal resection, including lymph vessels, was performed because multiple cervical lymph node metastases were suspected. The cervical lymph node dissection was performed en bloc, including from the cutaneous lesions to the sternocleidomastoid muscle. The preauricular area was reconstructed using a full-thickness skin graft from the thigh. Some of the skin graft was on the periosteum of the left temporal bone, but postsurgery engraftment was good. Subcutaneous metastasis was found during surgery (pT1bN3cM0, StageIIIC[1]). Nests of atypical melanocytes positive for S100, HMB-45, Melan A, and PRAME[2] had formed in the pigmented nodule and speckled lesions [Figure 2]. The tumor cells had invaded the dermis in the nodular lesion [Figure 2a]. Atypical melanocytes were scattered in the basal layer continuously in macroscopically normal areas [Figure 2b] between and around the nodule and the speckled lesions [Figure 2c]. Adjuvant nivolumab monotherapy (240 mg once every 2 weeks) was started 3 weeks after surgery. After three cycles, the patient had local recurrence and metastasis to the lung, liver, spleen, and multiple lymph nodes. Immunotherapy was immediately changed to a combination of nivolumab and ipilimumab. After the first cycle of combination therapy, the spleen metastasis was enlarged, although the other metastases had shrunk. After the second cycle, Grade 3 diarrhea occurred. Thus, we resumed nivolumab monotherapy. However, panuveitis and vitiligo, suggesting immune-related adverse events (irAEs), occurred after the initial administration of nivolumab monotherapy, and we abandoned further immunotherapy. Cancer multigene panel testing (Foundation One CDx) of a metastatic cervical lymph node sample identified molecular biomarkers and pathogenic variants: high tumor mutational burden (TMB) 16 mutations/megabase, NRAS Q61K, STK11 L245H, MTAP loss, and TERT promoter-124C>T. The enlargement of the multiple organ metastasis, small intestinal metastasis and invagination, and peritoneal dissemination occurred 3 months after immune checkpoint inhibitor (ICI) cessation. Palliative bowel resection of the invaginated areas was effective for only 3 months. The patient died 1 year and 2 months after primary surgery.Figure 1: (a) Clinical features of the pigmented nodule and nevus spilus-like speckled lentiginous lesions on the left preauricular area. (b and c) Dermoscopy images of the primary nodular lesion (b) and the speckled lesions (c).Figure 2: Pathological features of a resection sample, including the scattered lesions. (a) The nodular lesion, (b) the macroscopically normal area, (c) the speckled lesion (H and E, ×200).In this case, the speckled, flat lesions around the primary malignant melanoma were all malignant. It is suggested that this case was lentigo maligna melanoma because of the high cumulative sun damage profile: facial occurrence, histologically prominent solar elastosis in the dermis, high TMB, and NRAS and TERT promoter mutations.[3] There are two possible pathways of melanoma expansion from the primary lesion. One is in situ invasion from the primary nodule. This hypothesis is supported by the epidermally dominant tumor proliferation in the scattered lesions and the continuous presence of atypical melanocytes in the basal layer from the primary nodule to the scattered lesions. The other hypothesis is lymphatic metastasis. The spread was asymmetric, with a direction that appeared to follow the lymphatic channels from the periauricular lymph node. While the possibility of lymphatic metastasis cannot be completely ruled out, considering that the atypical melanocytes did not proliferate in the dermis beneath the scattered lesions, in situ invasion from the primary nodule is considered the probable pathway. Speckled lesions around a primary melanoma can be the radial growth phase of a melanoma,[4] a possibility we should consider when determining the horizontal margin. In addition, a poor prognosis was suggested by the massive lymph node metastasis, which was greater than the spreading of the cutaneous lesions. A transient tumor-free outcome was achieved after surgery, but local recurrence occurred immediately. The ICI had limited efficacy, and multiple severe irAEs occurred. After ICI cessation, he received a few intravenous courses of rehydration because of intestinal stenosis and dehydration. As general anesthesia posed a medium risk, palliative resection was a suitable choice. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Financial support and sponsorship Nil. Conflicts of interest Prof. Masashi Akiyama, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.