背景:病理学家面临着区分良性和恶性黑色素细胞肿瘤的挑战。PRAME(黑色素瘤中的PReferential表达的抗原)具有在这些类型的病变之间进行区分的证明价值。然而,单一免疫组织化学的敏感性是可变的。HMB-45是另一个有价值的标记,但靠它自己,在设置原发性黑素细胞肿瘤的能力有限。本研究旨在评估PRAME和HMB-45双重组合在原发性黑素细胞肿瘤评估中的诊断潜力。
方法:259个肿瘤,其中141例为良性痣,31发育不良痣(低度或高度发育不良),还有87例恶性黑色素瘤,从部门的档案中检索,并由两名经验丰富的皮肤病理学家进行评估。新切片分别用PRAME和HMB-45染色。对于PRAME,一个核,对于HMB-45,细胞质染色,被认为是阳性的,并按照文献中的描述在0到4+的量表上评分。仅在HMB-45染色上评估真皮组分。
结果:PRAME仅在1例良性痣中弥漫性表达,与弥漫性22例和局灶性HMB-45阳性良性痣103例相比,局灶性表达在28例。5高级别发育不良痣表现为表皮成分中弥漫性PRAME表达,在邻近的真皮隔室中具有不同程度的阳性,8例发育不良痣仅表现为局灶性表达。HMB-45仅在2个中弥漫性表达,在23个中局灶性表达,其余6个发育不良痣无明显阳性。在侵袭性黑色素瘤组中,在64/87肿瘤中PRAME染色>75%细胞,然而,10/87黑色素瘤完全阴性。HMB-45在49/87黑色素瘤中被弥漫性捕获,32显示斑片状表达,6例肿瘤均为空白阴性。弥漫性4+PRAME阳性显示出73.6%和96.5%的高敏感性和特异性,分别,与HMB-45、56,3%和86,0%相比,分别。没有痣表现出双重4+阳性,然而,双阳性的敏感性仅为49,4%。
结论:我们的结果证实了PRAME优于HMB-45在黑素细胞肿瘤的鉴别诊断中的优越性。然而,联合染色可以显着提高特异性,在双4+弥漫性阳性设置中呈现良性诊断更不可能。
BACKGROUND: Pathologists face ongoing challenges distinguishing between benign and malignant melanocytic tumors. PRAME (PReferentially expressed Antigen in Melanoma) has a demonstrated value distinguishing between these types of lesions. However, the sensitivity of single immunohistochemistry is variable. HMB-45 is another valuable marker, but on its own, has a limited ability in setting of primary melanocytic tumors. This study sought to evaluate the diagnostic potential of a dual panel combining PRAME and HMB-45 in the assessment of primary melanocytic tumors.
METHODS: 259 tumors, of which 141 were benign nevi, 31 dysplastic nevi (either low- or high grade dysplasia), and further 87 malignant melanomas, were retrieved from the department\'s archives and assessed by two experienced dermatopathologists. New sections were stained with PRAME and HMB-45, respectively. For PRAME, a nuclear, and for HMB-45, a cytoplasmic staining, was considered positive and scored as described in the literature on a scale from 0 to 4+. Only dermal component was assessed on HMB-45 stain.
RESULTS: PRAME was diffusely expressed in only 1 benign nevus, with focal expression in further 28 compared to 22 diffusely and 103 focally HMB-45-positive benign nevi. 5 high-grade dysplastic nevi showed diffuse PRAME expression in epidermal component, with varying degree of positivity in adjacent dermal compartment, and further 8 dysplastic nevi showed only focal expression. HMB-45 was diffusely expressed in only 2, with focal expression in 23, and no apparent positivity in remaining 6 dysplastic nevi. In invasive melanoma group, PRAME stained >75 % cells in 64/87 tumors, however, 10/87 melanomas were completely negative. HMB-45 was captured diffusely in 49/87 melanomas, 32 showed patchy expression, and 6 tumors were blank negative. Diffuse 4+ PRAME positivity showed superior sensitivity and specificity of 73,6 % and 96,5 %, respectively, compared to HMB-45, 56,3 % and 86,0 %, respectively. No nevi showed double 4+ positivity, however, the sensitivity for double positivity was only 49,4 %.
CONCLUSIONS: Our results confirm the superiority of PRAME over HMB-45 in the differential diagnosis of melanocytic tumors. However, combined staining can significantly increase specificity, rendering a benign diagnosis more unlikely in a double 4+ diffuse positivity setting.