The Clinical Spectrum of Multiple Endocrine Neoplasia Type 2A with Cutaneous Lichen Amyloidosis in Ethnic Han Chinese

Abstract

This study systematically reviewed previous literatures and analyzed the genotype-phenotype relationship between the multiple endocrine neoplasia type 2A (MEN 2A)-cutaneous lichen amyloidosis (CLA) and RET/OSMR/IL31RA mutations. RET/OSMR/IL31RA screening was performed on 8 RET-carriers from 3 independent Chinese MEN 2A families. Besides, 51 MEN 2A-CLA patients in 116 RET carriers from literatures were clustered and analyzed. Our results indicated that almost all MEN 2A-CLA patients exhibited CLA which was located in the scapular region and carried RET mutation at codon 634. Meanwhile, we firstly described MEN 2A-CLA here in Chinese Han patient with RET p.C634F mutation.

The RET C611Y mutation causes MEN 2A and associated cutaneous lichen amyloidosis

“…The genotype–phenotype relationship between CLA and the RET mutation has been discussed previously ( 1 , 2 , 4 , 5 , 6 , 7 , 8 , 23 , 24 , 25 , 26 ). Eng et al ( 2 ) reported that CLA was detected in approximately 9% (18/199) of patients with MEN 2A, and all 18 families carried RET codon 634 mutations.…”

“…We extracted the genomic DNA from the peripheral blood per the manufacturer’s instructions (Qiagen, Hilden, Germany). In addition, the PCR amplification of each entire exon of the RET proto-oncogene was performed, followed by direct bidirectional DNA sequencing with the ABI Prism 3700 automatic sequencer (Perkin-Elmer) ( 7 , 9 ).…”

“…The skin biopsy specimen was obtained from the cutaneous lesions of one subject (III:12), fixed in 10% buffered formalin and embedded in paraffin wax. Furthermore, we used haematoxylin–eosin, Congo red and crystal violet (Solaibao, Beijing, China) staining to 4 µm thick sections ( 1 , 6 , 7 , 22 , 23 , 24 ).…”

“…Initially, the presence of CLA was observed in patients with MEN 2A, who were explicitly related to codon 634 germline mutations in exon 11 of RET proto-oncogene; this mutation locates in the extracellular cysteine-rich region of the RET protein. CLA in MEN 2A is exclusively located in the scapular region of the upper back, corresponding to dermatomes T2–T6 ( 1 , 2 , 3 , 4 , 5 , 6 , 7 ). Reportedly, the following two germline mutations exist in intracellular tyrosine kinase domains: the RET V804M mutation within exon 14 in an American female with medullary thyroid carcinoma (MTC) and CLA on the upper back ( 8 ) and the RET S891A mutation within exon 15 binding OSMR variant G513D in a Chinese familial MTC (FMTC) family with cutaneous biphasic amyloidosis comprising the lower legs to thighs, upper back, shoulders, arms and forearms ( 9 ).…”

Elevated basal serum levels of calcitonin and simultaneous surgery of MEN2A-specific tumors

“…presented a high dominance in female patients with CLA. Moreover, the proportion of CLA in the RET mutation carriers was 45.1% (55/122) in 20 MEN2 families with CLA, and data from 51 individuals with CLA displayed prevalence for MTC, PHEO and HPTH of 96.1% (49/51), 47.1% (24/51) and 13.7% (7/51), respectively [7], despite the diverse evidence in a few speci c families with CLA [7,8,28,29]. These ndings suggest that CLA might represent a common, early and 'premonitory' clinical symptom of MEN2A-related CLA families, which may imply that improving early recognition of CLA in MEN2A-related CLA facilitate timely screening of RET, diagnosis of MEN2A-speci c tumors, and subsequent resection of MTC or/and PHEO to improve outcomes [7,8,14,28,29].…”