Siref Andrew B, Huynh Carissa A T, Balzer Bonnie L, Frishberg David P, Essner Richard, Shon Wonwoo
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
J Cutan Pathol. 2019 Apr;46(4):261-266. doi: 10.1111/cup.13412. Epub 2019 Jan 31.
Distinguishing benign nodal nevus from metastatic melanoma can be diagnostically challenging, with important clinical consequences. Recently, the loss of epigenetic marker, 5-hydroxymethylcytosine (5-hmC) expression by immunohistochemistry has been found in melanomas and atypical melanocytic neoplasms.
About 41 metastatic melanomas and 20 nodal nevi were retrieved. Nuclear 5-hmC (brown) and cytoplasmic Melan-A Red (red) double immunohistochemical staining was performed.
Total or partial loss of nuclear expression of 5-hmC was noted in 40/41 metastatic melanomas; these tumor cells were strongly positive for Melan-A Red, except in one case of desmoplastic melanoma. All cases of nodal nevus showed uniformly retained nuclear expression of 5-hmC accompanied by strong Melan-A Red cytoplasmic staining. In two cases containing both nodal nevus and metastatic melanoma, all tumor cells were positive for Melan-A Red, but a nuclear expression of 5-hmC was selectively absent only in the melanoma tumor cells.
Dual 5-hmC/Melan-A Red immunohistochemistry is highly specific in distinguishing nodal nevus from metastatic melanoma. Our protocol for brown and red chromogens used in this study provides excellent color contrast and is easy to interpret. Furthermore, this dual staining method allows the preservation of limited tumor tissue, which could be used for potential molecular studies.
鉴别良性结节性痣与转移性黑色素瘤在诊断上具有挑战性，且会产生重要的临床后果。最近，通过免疫组织化学发现黑色素瘤和非典型黑素细胞肿瘤中表观遗传标记5-羟甲基胞嘧啶（5-hmC）表达缺失。
收集了约41例转移性黑色素瘤和20例结节性痣。进行了细胞核5-hmC（棕色）和细胞质Melan-A Red（红色）双重免疫组织化学染色。
40/41例转移性黑色素瘤中观察到5-hmC细胞核表达全部或部分缺失；除1例促纤维增生性黑色素瘤外，这些肿瘤细胞Melan-A Red呈强阳性。所有结节性痣病例均显示5-hmC细胞核表达一致保留，同时伴有Melan-A Red细胞质强染色。在2例同时含有结节性痣和转移性黑色素瘤的病例中，所有肿瘤细胞Melan-A Red均为阳性，但仅黑色素瘤肿瘤细胞中选择性缺乏5-hmC细胞核表达。
5-hmC/Melan-A Red双重免疫组织化学在鉴别结节性痣与转移性黑色素瘤方面具有高度特异性。我们在本研究中使用的棕色和红色显色剂方案提供了出色的颜色对比度，易于解读。此外，这种双重染色方法可保留有限的肿瘤组织，可用于潜在的分子研究。
