Frequent association between MEN 2A and cutaneous lichen amyloidosis.
OBJECTIVE
Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are genetic diseases due to activating mutations of the RET proto-oncogene. Affected patients develop medullary thyroid carcinoma (100%), in an isolated form (FMTC) or in association with phaeochromocytoma (30-50%), and primary hyperparathyroidism (10-20%) (MEN 2A). The presence of cutaneous lichen amyloidosis (CLA) has been anecdotally described in few families harbouring RET proto-oncogene mutation in codon 634. The aim of the study was to evaluate the incidence of CLA in MEN 2A/FMTC families.


METHODS
Ten MEN 2A/FMTC families were studied and RET gene mutations identified in all. Complete dermatological assessment was carried out in each family member. Skin biopsy for histological studies was performed in patients with CLA.


RESULTS
Among 10 MEN 2A/FMTC families, the presence of CLA was found only in patients belonging to the three families with MEN 2A and RET mutation in codon 634. Nine of 25 patients (36%) with codon 634 mutation presented CLA, though two of them did not show CLA skin lesions but the typical neurological pruritus in the upper back. In all patients, neurological pruritus was present since infancy as a precocious marker of the disorder. The dermatological study of patients with CLA skin lesions added further evidence that pruritus has a pivotal role in the development of CLA, the amyloid deposition being the consequence of repeated scratching. Light microscopy revealed orthokeratotic hyperkeratosis, with elongation of the rete ridges, rare intramalpighian apoptic keratinocytes and deposits of amorphous material in the superficial dermis. Examination under ultraviolet light showed thioflavin T-positive staining, confirming the presence of amyloid in the papillary dermis. The use of Capsaicin at the dilution of 0.025% had a mild efficacy on the cutaneous symptoms.


CONCLUSIONS
Among the members of the three families with MEN 2A and RET 634 mutation, the incidence of CLA was 36%, a figure similar to that reported in the literature for phaeochromocytoma (30-50%) and even higher than that for hyperparathyroidism (10-20%). The present data confirm that CLA is linked to codon 634 RET mutations and is a precocious marker of the disorder.
Verga
Uberta
U
University of Milan, Ospedale Maggiore IRCCS, Italy.
Fugazzola
Laura
L
Cambiaghi
Stefano
S
Pritelli
Chiara
C
Alessi
Elvio
E
Cortelazzi
Donatella
D
Gangi
Emanuela
E
Beck-Peccoz
Paolo
P
D000293:Adolescent; D000328:Adult; D028226:Amyloidosis, Familial / Q000150:complications* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000150:complications* / Q000235:genetics; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D010375:Pedigree; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; D011537:Pruritus / Q000150:complications / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012875:Skin Diseases, Metabolic / Q000150:complications* / Q000235:genetics
C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases