Florescu Alexandru-Florin, Sima Oana-Claudia, Nistor Claudiu, Ciobica Mihai-Lucian, Costachescu Mihai, Stanciu Mihaela, Tanasescu Denisa, Popa Florina Ligia, Carsote Mara
Endocrinology Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700111 Iasi, Romania.
Endocrinology Department, "Sf. Spiridon" Emergency County Clinical Hospital, 700111 Iasi, Romania.
Clin Pract. 2024 Oct 29;14(6):2284-2299. doi: 10.3390/clinpract14060179.
Medullary thyroid carcinoma (MTC), the third most frequent histological type of thyroid malignancy, may be found isolated or as part of multiple endocrine neoplasia type 2 (MEN2). One particular subtype of this autosomal dominant-transmitted syndrome includes an association with cutaneous lichen amyloidosis, although, generally, a tide genotype-phenotype correlation is described in patients who carry proto-oncogene pathogenic variants.
Our objective was to provide an endocrine perspective of a case series diagnosed with -positive familial MTC associated with cutaneous primary lichen amyloidosis amid the confirmation of MEN2. Six members of the same family had cutaneous lesion with different features (from hyperpigmented, velvety to red/pink appearance) and four of them harbored a pathogenic variant at 634 codon (exon 11): c.1900T>G, p.634G (TGC634CGC).
All six patients were females with the lesion at the interscapular region. Except for two women, four of these subjects were investigated and had MTC (three of them with postoperatory confirmation). The youngest affected individual was 6 years old. The three adult females were confirmed with pathogenic variant during their 30s, while the girl underwent the familial screening as a newborn. None of them had primary hyperparathyroidism until the present time, except for one subject, and two out of the three adults also had bilateral pheochromocytoma. Notably, all patients were rather asymptomatic from the endocrine perspective at the moment when endocrine tumor/cancer was confirmed, and the skin was progressively affected a few years before the actual MEN2 confirmation.
This case series highlights the following key message: awareness of the dermatologic findings in MTC/MEN2 patients is essential since lesions such as cutaneous lichen amyloidosis might represent the skin signature of the endocrine condition even before the actual endocrine manifestations. These data add to the limited published reports with respect to this particular presentation, noting the fact that -C634 is the most frequent pathogenic variant in MEN2-associated lichen amyloidosis; females are more often affected; the interscapular region is the preferred site; the age of diagnosis might be within the third decade of life, while we reported one of the youngest patients with the lesion. The same pathogenic variant is not associated with the same dermatologic features as shown in the vignette. The same mutation does not mean that all family members will present the same skin anomaly.
甲状腺髓样癌（MTC）是甲状腺恶性肿瘤中第三常见的组织学类型，可单独出现或作为2型多发性内分泌腺瘤病（MEN2）的一部分。这种常染色体显性遗传综合征的一种特殊亚型包括与皮肤苔藓样淀粉样变有关，不过，一般来说，携带原癌基因致病变异的患者存在基因型与表型的相关性。
我们的目的是在确诊MEN2的情况下，从内分泌学角度对一系列诊断为阳性家族性MTC并伴有皮肤原发性苔藓样淀粉样变的病例进行分析。同一家庭的六名成员有不同特征的皮肤病变（从色素沉着、天鹅绒样到红色/粉色外观），其中四人在634密码子（第11外显子）处存在致病变异：c.1900T>G，p.634G（TGC634CGC）。
所有六名患者均为女性，病变位于肩胛间区。除两名女性外，其中四名受试者接受了检查并患有MTC（其中三名经术后确诊）。最年轻的患病个体为6岁。三名成年女性在30多岁时确诊有致病变异，而该女孩在新生儿期接受了家族筛查。目前，除一名受试者外，他们均无原发性甲状旁腺功能亢进，三名成年人中有两名还患有双侧嗜铬细胞瘤。值得注意的是，在内分泌肿瘤/癌症确诊时，从内分泌学角度来看，所有患者当时都相当无症状，且在实际确诊MEN2的几年前皮肤就逐渐受到影响。
该病例系列突出了以下关键信息：认识MTC/MEN2患者的皮肤表现至关重要，因为皮肤苔藓样淀粉样变等病变甚至可能在实际内分泌表现出现之前就代表了内分泌疾病的皮肤特征。这些数据补充了关于这种特殊表现的有限已发表报告，指出-C634是MEN2相关苔藓样淀粉样变中最常见的致病变异；女性更常受累；肩胛间区是首选部位；诊断年龄可能在生命的第三个十年内，而我们报告了一名最年轻的有该病变的患者。如病例所示，相同的致病变异并不与相同的皮肤特征相关。相同的突变并不意味着所有家庭成员都会出现相同的皮肤异常。
