Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
Department of Dermatology, University of California, San Francisco, California.
Mod Pathol. 2024 May;37(5):100469. doi: 10.1016/j.modpat.2024.100469. Epub 2024 Mar 10.
NRAS activating mutations are prevalent in melanocytic neoplasia, occurring in a subset of common acquired melanocytic nevi and ∼30% of cutaneous melanomas. In this study, we described a cohort of 7 distinctive melanocytic tumors characterized by activating point mutations in codon 61 of NRAS with amplification of the mutant NRAS allele and shared clinicopathologic features. These tumors occurred predominantly in younger patients, with a median age of 20 years (range, 6-56 years). They presented as papules on the helix of the ear (4 cases) or extremities (3 cases). Microscopically, the tumors were cellular, relatively well-circumscribed, compound, or intradermal proliferations. The tumor cells often extended into the deep reticular dermis and involved the superficial subcutaneous fat in some cases. The melanocytes were epithelioid to spindled with moderate amounts of cytoplasm and conspicuous nucleoli. They were arranged in short plexiform fascicles, nests, and cords. Some cases had occasional pleomorphic and multinucleated melanocytes. Rare dermal mitotic figures were present in all cases. The dermis contained thick collagen bundles and minimal solar elastosis. Follow-up data were available for 5 patients, with a median period of 4.2 years (range, 1-9 years), during which no recurrences or metastases were reported. Our series highlights a clinicopathologically and molecularly distinctive subset of NRAS-mutated tumors with amplification of the mutant NRAS allele.
NRAS 激活突变在黑色素瘤肿瘤中很常见，发生在一部分常见的获得性黑色素痣和大约 30%的皮肤黑色素瘤中。在这项研究中，我们描述了一组 7 个独特的黑色素瘤肿瘤，这些肿瘤的特征是 NRAS 密码子 61 点的激活突变，突变 NRAS 等位基因扩增，并具有共同的临床病理特征。这些肿瘤主要发生在年轻患者中，中位年龄为 20 岁（范围为 6-56 岁）。它们表现为耳轮（4 例）或四肢（3 例）的丘疹。显微镜下，肿瘤为细胞性、相对界限清楚的、复合性或真皮内增殖。肿瘤细胞常延伸至深部网状真皮，并在某些情况下累及浅层皮下脂肪。黑素细胞为上皮样至梭形，细胞质中等量，有明显的核仁。它们排列成短的丛状束、巢和索。一些病例偶尔有异形性和多核性黑素细胞。所有病例均可见罕见的真皮有丝分裂象。真皮含有厚的胶原束和最小的日光弹性纤维变性。5 例患者可获得随访资料，中位随访期为 4.2 年（范围为 1-9 年），期间无复发或转移报告。我们的研究系列强调了一组具有独特临床病理和分子特征的 NRAS 突变肿瘤，其特征是突变 NRAS 等位基因扩增。
