Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases
Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases
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DOI：
10.1038/modpathol.2015.62
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发表时间：
2015-08-01
期刊：
影响因子：
7.5
通讯作者：
Folpe, Andrew L.
中科院分区：
文献类型：
--
作者：
Romano, Ryan C.;Carter, Jodi M.;Folpe, Andrew L.
已知恶性黑素瘤表达波形蛋白以及其他中间丝。虽然恶性黑色素瘤的异常角蛋白表达已有报道，但其发生率并不确定，这种现象也不为人所知。我们曾在会诊中看到一些恶性黑色素瘤伴有角蛋白、其他中间丝或突触素的异常表达，因此研究了一大组原发性和转移性黑色素瘤，以确定这些事件的发生频率。从我们的档案中检索到来自71名患者（51名男性，20名女性;平均59岁，范围17-87岁）的约73例恶性黑色素瘤（22例原发瘤和51例转移瘤）。通过重新审查苏木精和伊红切片和相关（例如，S100蛋白、HMB 45、Melan-A和酪氨酸酶）免疫组织化学研究。对可用切片进行角蛋白（OSCAR和AE 1/AE 3抗体）、结蛋白、神经丝蛋白、胶质细胞酸性蛋白、突触素和嗜铬粒蛋白A免疫染色。并非所有病例都可以检测所有标记物。主要为上皮样增生（48/73，66%）或梭形细胞/促结缔组织增生（25/73，34%）。S100蛋白、Melan-A、HMB 45和酪氨酸酶的阳性率分别为60/65（92%）、34/64（53%）、30/60（50%）和25/48（52%）。所有5例S100蛋白阴性病例均表达至少一种其他黑素细胞标志物：Melan-A（4例中的2例，50%）、HMB 45（3例中的2例，67%）和酪氨酸酶（2例中的1例，50%）。所有病例均表达至少一种黑素细胞标志物。角蛋白（OSCAR，17/61，28%; AE 1/AE 3，16/40，40%）、结蛋白（11/47，24%）、神经丝蛋白（5/31，16%）、胶质细胞酸性蛋白（3/32，9%）和突触素（10/34，29%）阳性，通常仅在少数细胞中阳性。嗜铬粒蛋白阴性（0/32，0%）。共9/73例（12%）显示>1个中间丝的表达。所有S100蛋白阴性的黑色素瘤显示异常的中间丝表达（角蛋白-1例，结蛋白-3例，神经丝蛋白-1例）。与梭形细胞/促结缔组织增生性黑色素瘤（中间丝，8/25，32%;突触素，3/12，25%）相比，上皮样黑色素瘤（中间丝，27/48，56%;突触素，7/22，32%）中异常中间丝或突触素表达更常见。总体而言，48%（35/73）的病例显示至少一种中间丝的异常表达。所有中间丝和突触素的异常表达被发现在恶性黑色素瘤的重要子集，代表潜在的严重的诊断陷阱。虽然纳入咨询案例可能会增加这些调查结果在这一系列中的频率，但在机构案例中也发现了类似的结果。恶性黑色素瘤表现出异常的中间丝和突触素表达，很容易被误认为癌、横纹肌肉瘤和神经内分泌肿瘤。意识到这一现象，仔细的组织病理学评价，并适当的黑素细胞免疫组化面板应有助于诊断恶性黑色素瘤与不寻常的免疫表型。
Malignant melanomas are known to express vimentin, among other intermediate filaments. Though anomalous keratin expression by malignant melanoma has been reported, its frequency is not well-established and this phenomenon is not well-known. We have seen in consultation a number of malignant melanomas with anomalous expression of keratin, other intermediate filaments, or synaptophysin, and therefore studied a large group of primary and metastatic melanomas to determine the frequency of these events. About 73 cases of malignant melanoma (22 primaries and 51 metastases) from 71 patients (51 male, 20 female; mean 59 years, range 17-87 years) were retrieved from our archives. Prior diagnoses were confirmed by re-review of hematoxylin and eosin sections and relevant (e.g., S100 protein, HMB45, Melan-A, and tyrosinase) immunohistochemical studies. Available sections were immunostained for keratin (OSCAR and AE1/AE3 antibodies), desmin, neurofilament protein, glial fibrillary acidic protein, synaptophysin, and chromogranin A. Not all cases could be tested for all markers. Cases were predominantly epithelioid (48/73, 66%) or spindle cell/desmoplastic (25/73, 34%). S100 protein, Melan-A, HMB45, and tyrosinase were positive in 60/65 (92%), 34/64 (53%), 30/60 (50%), 25/48 (52%) of cases, respectively. All five S100-protein-negative cases expressed at least one of the other melanocytic markers: Melan-A (two of four, 50%), HMB45 (two of three, 67%), and tyrosinase (one of two, 50%). All cases expressed at least one melanocytic marker. Cases were positive for keratin (OSCAR, 17/61, 28%; AE1/AE3, 16/40, 40%), desmin (11/47, 24%), neurofilament protein (5/31, 16%), glial fibrillary acidic protein (3/32, 9%), and synaptophysin (10/34, 29%), typically only in a minority of cells. Chromogranin was negative (0/32, 0%). Altogether 9/73 cases (12%) showed expression of >1 intermediate filament. All S100-protein-negative melanomas showed anomalous intermediate filament expression (keratin-one case, desmin-three cases, neurofilament protein-one case). Anomalous intermediate filament or synaptophysin expression was more common in epithelioid (intermediate filament, 27/48, 56%; synaptophysin, 7/22, 32%) as compared with spindle cell/desmoplastic (intermediate filament, 8/25, 32%; synaptophysin, 3/12, 25%) melanomas. Overall, 48% (35/73) of cases showed anomalous expression of at least one intermediate filament. Anomalous expression of all intermediate filaments and synaptophysin was found in significant subsets of malignant melanoma, representing potentially serious diagnostic pitfalls. While the inclusion of consultation cases may inflate the frequency of these findings in this series, similar findings were also seen in institutional cases. Malignant melanoma showing anomalous intermediate filament and synaptophysin expression may easily be mistaken for carcinomas, rhabdomyosarcomas, and neuroendocrine tumors. Awareness of this phenomenon, careful histopathological evaluation, and an appropriate melanocytic immunohistochemical panel should facilitate the diagnosis of malignant melanoma with unusual immunophenotypes.