Department of Pathology, University of California at San Francisco, San Francisco, CA, USA.
Am J Surg Pathol. 2011 Sep;35(9):1413-8. doi: 10.1097/PAS.0b013e31822280d8.
We report on the highly unusual case of a 75-year-old woman who developed a biphasic right axillary mass of apparent melanoma and adenocarcinoma 13 years after a diagnosis of primary melanoma on her right upper back. The differential diagnosis included a collision tumor and metastatic melanoma with adenocarcinomatous transdifferentiation. We utilized immunohistochemical staining, DNA sequencing, and comparative genomic hybridization (CGH) to characterize this unusual tumor. By immunohistochemistry, the melanomatous component was positive for S100 and Melan-A, and had patchy positivity for cytokeratin. The adenocarcinomatous component was negative for melanoma markers, but was strongly positive for cytokeratin. In addition, the glandular component was positive for CDX-2 and Ber-EP4, giving the distinct histologic and immunohistochemical impression of a gastrointestinal metastasis nested within a deposit of metastatic melanoma. Clinical and radiologic workup failed to reveal a primary gastrointestinal malignancy. Molecular genetic analysis, including DNA sequencing and CGH, revealed that both areas contained an identical NRAS Q61K mutation and had highly similar CGH profiles, including gains of chromosome 1q and losses of 1p, 4, 9, and 10, which are archetypical of melanoma. The NRAS mutation was also identified in a deposit of metastatic melanoma resected 12 years earlier, but was not seen in the patient's nontumorous tissue, indicating that it was somatically acquired. Genetic analyses demonstrate that 2 morphologically distinct tumors arose from a common ancestor melanoma cell that harbored an NRAS mutation and subsequently divergently evolved by the acquisition of additional genomic alterations. Our findings illustrate the ability of molecular analyses to resolve lineage in complex neoplasms and illustrate the phenotypic plasticity of cancer cells.
我们报告了一例非常不寻常的病例，一名 75 岁女性在右上背部原发性黑色素瘤诊断 13 年后，出现了明显黑色素瘤和腺癌的双相右侧腋窝肿块。鉴别诊断包括碰撞瘤和转移性黑色素瘤伴腺癌转化。我们利用免疫组织化学染色、DNA 测序和比较基因组杂交（CGH）来描述这种不寻常的肿瘤。通过免疫组织化学，黑色素瘤成分对 S100 和 Melan-A 呈阳性，对细胞角蛋白呈斑驳阳性。腺癌成分对黑色素瘤标志物呈阴性，但对细胞角蛋白呈强阳性。此外，腺体成分对 CDX-2 和 Ber-EP4 呈阳性，这给人一种明显的组织学和免疫组织化学印象，即胃肠道转移位于转移性黑色素瘤沉积内。临床和影像学检查未能发现原发性胃肠道恶性肿瘤。分子遗传学分析，包括 DNA 测序和 CGH，显示两个区域都含有相同的 NRAS Q61K 突变，并且具有高度相似的 CGH 图谱，包括 1q 染色体的增益和 1p、4、9 和 10 染色体的缺失，这是黑色素瘤的典型特征。该 NRAS 突变也在 12 年前切除的转移性黑色素瘤沉积物中被发现，但在患者的非肿瘤组织中未被发现，这表明它是体细胞获得的。遗传分析表明，2 个形态上不同的肿瘤起源于一个共同的黑色素瘤母细胞，该母细胞携带 NRAS 突变，并随后通过获得额外的基因组改变而进行不同的进化。我们的研究结果表明，分子分析能够解决复杂肿瘤中的谱系问题，并阐明癌细胞的表型可塑性。
