Guo Ruifeng, Franco-Palacios Maria, Russell Madison, Goddard Lindsey, Hassell Lewis, Gillies Elizabeth, Fung Kar-Ming
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma city, Oklahoma 73104, USA.
Int J Clin Exp Pathol. 2013 Jul 15;6(8):1658-64. Print 2013.
Metastatic malignant melanoma has a wide spectrum of histopathologic patterns and often lacks melanin pigment. Without a known primary tumor, the diagnosis of metastatic malignant melanoma relies on a combination of morphology and immunohistochemical profile. Infrequently, commonly used markers for melanoma (S100, HMB45, Melan-A and Tyrosinase A) are negative. These cases pose critical diagnostic challenges. Recent studies show that Microphthalmia Transcription Factor (MITF) has high sensitivity (88-100%) and specificity for metastatic melanoma. We are reporting here three cases of high grade tumors that were studied by a comprehensive immunohistochemical panel including cytokeratins, S100, HMB-45, Melan A, Tyrosinase, and MITF. All three tumors were also analyzed for the presence of BRAF mutations. All three metastatic tumors were negative for S100, Melan A, HMB-45 and Tyrosinase but positive for MITF. Subsequent to the diagnoses, previously existing or concurrent primary melanomas were identified in 2 of the 3 cases. Interestingly, S100, Melan A, and HMB-45 were positive in the primary tumors. No BRAF (V600E) mutations were identified in the three metastatic melanomas and CD 117 (c-kit) was positive in one of the cases. In summary, our experience shows that MITF can be a valuable adjunct in the diagnosis of metastatic tumors that are suspicious for melanoma but negative for other melanoma markers.
转移性恶性黑色素瘤具有广泛的组织病理学模式，且常常缺乏黑色素。在没有已知原发肿瘤的情况下，转移性恶性黑色素瘤的诊断依赖于形态学和免疫组化特征的综合判断。偶尔，黑色素瘤常用标志物（S100、HMB45、Melan-A和酪氨酸酶A）呈阴性。这些病例带来了严峻的诊断挑战。最近的研究表明，小眼畸形转录因子（MITF）对转移性黑色素瘤具有高敏感性（88 - 100%）和特异性。我们在此报告三例高级别肿瘤，通过包括细胞角蛋白、S100、HMB - 45、Melan A、酪氨酸酶和MITF在内的综合免疫组化检测进行研究。所有三个肿瘤还分析了BRAF突变的存在情况。所有三个转移性肿瘤的S100、Melan A、HMB - 45和酪氨酸酶均为阴性，但MITF为阳性。诊断后，3例中有2例发现了先前存在或同时存在的原发性黑色素瘤。有趣的是，原发性肿瘤中的S100、Melan A和HMB - 45呈阳性。在三个转移性黑色素瘤中未发现BRAF（V600E）突变，其中1例CD 117（c - kit）呈阳性。总之，我们的经验表明，对于怀疑为黑色素瘤但其他黑色素瘤标志物为阴性的转移性肿瘤，MITF可作为一种有价值的辅助诊断指标。
