高分化甲状腺癌皮肤转移灶的临床病理特征及BRAF(V600E)突变分析
Clinicopathologic features and BRAF(V600E) mutation analysis in cutaneous metastases from well-differentiated thyroid carcinomas.
作者信息
Erickson Lori A, Jin Long, Nakamura Nobuki, Bridges Alina G, Markovic Svetomir N, Lloyd Ricardo V
机构信息
Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
出版信息
Cancer. 2007 May 15;109(10):1965-71. doi: 10.1002/cncr.22641.
BACKGROUND
Cutaneous metastases from well-differentiated thyroid carcinomas are rare and are usually identified in patients with widely disseminated disease. Occasionally, thyroid carcinomas can present as cutaneous metastases for which the primary site needs to be determined. Papillary thyroid carcinomas (PTCs) commonly have BRAF(V600E) mutation. A series of 16 cutaneous metastases were analyzed from well-differentiated thyroid carcinomas to learn more about the clinicopathologic features and BRAF(V600E) mutation status.
METHODS
Eleven cases of PTC and 5 of follicular thyroid carcinoma (FTC) metastatic to the skin were evaluated. All cutaneous metastases were studied histologically and with thyroglobulin and thyroid transcription factor immunostains. All tumor samples were analyzed for mutations at nucleotide 1799 in exon 15 of the BRAF gene.
RESULTS
Two patients with FTC presented with cutaneous metastases. Fourteen of 16 patients died of disease and 2 were alive with disease at follow-up. The histologic features of the cutaneous metastases were generally characteristic of the primary tumor; however, 2 of the 11 PTC metastases demonstrated cytoplasmic clearing not typical of classic PTC. BRAF(V600E) mutation (T1799A) was detected in 5 of 11 cases of PTC and in none of the 5 FTCs.
CONCLUSIONS
Cutaneous metastases from PTC may show prominent clear cell change requiring differentiation from clear cell hidradenoma, clear cell dermatofibroma, malignant melanoma with prominent clear cell change, and cutaneous metastasis from renal cell carcinoma. BRAF(V600E) mutation is identified in a subset of cutaneous metastases from PTC. Cutaneous metastases from PTC and FTC are associated with a very poor prognosis.
背景
高分化甲状腺癌的皮肤转移罕见,通常在疾病广泛播散的患者中发现。偶尔,甲状腺癌可表现为皮肤转移,此时需要确定原发部位。乳头状甲状腺癌(PTC)通常存在BRAF(V600E)突变。分析了16例高分化甲状腺癌的皮肤转移病例,以进一步了解其临床病理特征和BRAF(V600E)突变状态。
方法
评估了11例转移至皮肤的PTC和5例滤泡状甲状腺癌(FTC)。所有皮肤转移灶均进行了组织学检查,并进行了甲状腺球蛋白和甲状腺转录因子免疫染色。对所有肿瘤样本进行BRAF基因第15外显子1799位核苷酸的突变分析。
结果
2例FTC患者出现皮肤转移。16例患者中有14例死于疾病,2例在随访时仍有疾病存活。皮肤转移灶的组织学特征通常与原发肿瘤相似;然而,11例PTC转移灶中有2例表现出不典型的经典PTC的胞质透明。11例PTC中有5例检测到BRAF(V600E)突变(T1799A),5例FTC均未检测到。
结论
PTC的皮肤转移可能表现出显著的透明细胞改变,需要与透明细胞汗腺瘤、透明细胞皮肤纤维瘤、具有显著透明细胞改变的恶性黑色素瘤以及肾细胞癌的皮肤转移相鉴别。BRAF(V600E)突变在PTC的一部分皮肤转移中被发现。PTC和FTC的皮肤转移预后很差。