Department of Dermatology, Fundación Jiménez Diaz, Universidad Autónoma, Madrid, Spain.
Department of Pathology, Fundación Jiménez Diaz, Universidad Autónoma, Madrid, Spain.
JAMA Dermatol. 2017 Dec 1;153(12):1298-1301. doi: 10.1001/jamadermatol.2017.3959.
Multiple endocrine neoplasia type 2 (MEN 2) syndrome is an autosomal dominant, hereditary cancer disorder caused by germline mutations in the RET (formerly MEN2A, MEN2B) proto-oncogene located on chromosomal band 10q11.21. Two distinct clinical forms have been described as the following phenotypes: multiple endocrine neoplasia type 2A (MEN 2A) and multiple endocrine neoplasia type 2B (MEN 2B) syndromes. The common and necessary nexus that defines these 2 phenotypes is the presence of medullary thyroid carcinoma (MTC). The familial MTC type of MEN 2 syndrome was included within the spectrum of MEN 2A syndrome. Cutaneous manifestations of MEN 2A syndrome include macular amyloidosis, whereas MEN 2B syndrome is traditionally linked to multiple mucosal neuromas.
To describe a family with cutaneous manifestations not previously described in patients with MEN 2A syndrome and to discuss the association of this disorder with Cowden syndrome.
DESIGN, SETTING, AND PARTICIPANTS: Clinicopathologic correlation of cutaneous lesions and genetic studies in 11 members of a family with familial MTC.
Cutaneous lesions were histopathologically and immunohistochemically studied. Genetic screening for a germline mutation at the RET gene was performed in 11 family members.
Identification of cutaneous lesions not previously described in patients with MEN 2A syndrome.
This family of 11 individuals with familial MTC type of MEN 2A syndrome demonstrated the moderate risk RET p.Val804Met (protein valine at residue 804 replaced by methionine) genetic mutation, with 2 of the relatives presenting with dermal hyperneury, cutaneous lesions classically described in MEN 2B syndrome, and 1 relative also showing multiple sclerotic fibromas, a cutaneous manifestation of PTEN (phosphatase and tensin homologue) hamartoma-tumor syndrome.
Dermal hyperneury and multiple sclerotic fibromas should be added to the list of cutaneous manifestations of patients with the familial MTC type of MEN 2A syndrome.
多发性内分泌肿瘤 2 型（MEN 2）综合征是一种常染色体显性遗传性癌症疾病，由位于染色体 10q11.21 带的 RET（原 MEN2A、MEN2B）原癌基因突变引起。已经描述了两种不同的临床形式，如下表型：多发性内分泌肿瘤 2A（MEN 2A）和多发性内分泌肿瘤 2B（MEN 2B）综合征。定义这两种表型的共同必要联系是存在甲状腺髓样癌（MTC）。家族性 MTC 型 MEN 2 综合征被纳入 MEN 2A 综合征的范围。MEN 2A 综合征的皮肤表现包括斑状淀粉样变，而 MEN 2B 综合征传统上与多发性黏膜神经瘤相关。
描述一组以前在 MEN 2A 综合征患者中未描述的皮肤表现，并讨论该疾病与考登综合征的关联。
设计、地点和参与者：对一个家族性 MTC 患者的皮肤病变进行临床病理相关性研究，并对 11 名家族成员进行遗传筛查。
对皮肤病变进行组织病理学和免疫组织化学研究。对 11 名家族成员的 RET 基因的胚系突变进行基因筛查。
鉴定以前未在 MEN 2A 综合征患者中描述的皮肤病变。
这个家族的 11 名个体患有家族性 MTC 型 MEN 2A 综合征，表现为中度风险的 RET p.Val804Met（第 804 位氨基酸缬氨酸被蛋氨酸取代）基因突变，其中 2 名亲属患有皮肤神经纤维瘤，这是 MEN 2B 综合征中经典描述的皮肤病变，1 名亲属还表现出多发性硬化性纤维瘤，这是一种 PTEN（磷酸酶和张力蛋白同源物）错构瘤-肿瘤综合征的皮肤表现。
皮肤神经纤维瘤和多发性硬化性纤维瘤应添加到家族性 MTC 型 MEN 2A 综合征患者的皮肤表现列表中。
