{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T02:00:09Z","timestamp":1777082409160,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinics and Practice"],"abstract":"<jats:p>Background: 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\u2013phenotype correlation is described in patients who carry RET proto-oncogene pathogenic variants. Methods: Our objective was to provide an endocrine perspective of a case series diagnosed with RET-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 RET pathogenic variant at 634 codon (exon 11): c.1900T&gt;G, p.634G (TGC634CGC). Results: 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 RET 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. Conclusions: 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 RET-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 RET pathogenic variant is not associated with the same dermatologic features as shown in the vignette. The same RET mutation does not mean that all family members will present the same skin anomaly.<\/jats:p>","DOI":"10.3390\/clinpract14060179","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T08:42:09Z","timestamp":1730191329000},"page":"2284-2299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Endocrine Perspective of Cutaneous Lichen Amyloidosis: RET-C634 Pathogenic Variant in Multiple Endocrine Neoplasia Type 2"],"prefix":"10.3390","volume":"14","author":[{"given":"Alexandru-Florin","family":"Florescu","sequence":"first","affiliation":[{"name":"Endocrinology Department, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700111 Iasi, Romania"},{"name":"Endocrinology Department, \u201cSf. Spiridon\u201d Emergency County Clinical Hospital, 700111 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oana-Claudia","family":"Sima","sequence":"additional","affiliation":[{"name":"PhD Doctoral School of \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-5666","authenticated-orcid":false,"given":"Claudiu","family":"Nistor","sequence":"additional","affiliation":[{"name":"Department 4\u2013Cardio-Thoracic Pathology, Thoracic Surgery II Discipline, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Thoracic Surgery Department, \u201cDr. Carol Davila\u201d Central Emergency University Military Hospital, 010825 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4402-7194","authenticated-orcid":false,"given":"Mihai-Lucian","family":"Ciobica","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Gastroenterology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Internal Medicine I and Rheumatology, \u201cDr. Carol Davila\u201d Central Military University Emergency Hospital, 010825 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai","family":"Costachescu","sequence":"additional","affiliation":[{"name":"PhD Doctoral School of \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Thoracic Surgery Department, \u201cDr. Carol Davila\u201d Central Emergency University Military Hospital, 010825 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela","family":"Stanciu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550024 Sibiu, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denisa","family":"Tanasescu","sequence":"additional","affiliation":[{"name":"Medical Clinical Department, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florina Ligia","family":"Popa","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550024 Sibiu, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-3835","authenticated-orcid":false,"given":"Mara","family":"Carsote","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Clinical Endocrinology V, \u201cC.I. Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, D., Liang, N., Sun, H., Frattini, F., Sui, C., Yang, M., Wang, H., and Dionigi, G. (2024). Critically evaluated key points on hereditary medullary thyroid carcinoma. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1412942"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ando.2019.04.014","article-title":"Clinical utility of genetic diagnosis for sporadic and hereditary medullary thyroid carcinoma","volume":"80","author":"Elisei","year":"2019","journal-title":"Ann. 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