Experience of prophylactic thyroidectomy in multiple endocrine neoplasia type 2A kindreds with RET codon 804 mutations.

OBJECTIVE AND DESIGN: Genetic screening in multiple endocrine neoplasia type 2 (MEN 2) has led to specific management guidelines based on genotype-phenotype analysis. However, there is controversy regarding the appropriate age for prophylactic thyroidectomy in families with mutations in codon 804 in exon 14 of the RET proto-oncogene, where medullary thyroid cancer (MTC) may not develop until adulthood. We prospectively studied two MEN 2A families, one with the V804L and the other with the V804M RET mutation, to report our experience of genetic and biochemical screening and prophylactic thyroidectomy. Family 1 is one of the largest MEN 2A families in the literature, where 22 prophylactic thyroidectomies have been performed. PATIENTS AND RESULTS: C-cell hyperplasia (CCH) was found in 23 out of 25 thyroidectomy specimens from family members of ages 5 years and upwards. MTC was found in 10 out of 18 adults of age 25 years upwards, including the family 2 proband, who was found to have MTC with lymph node metastases at age 28. Phaeochromocytoma was only observed in one patient, but six cases of histologically confirmed hyperparathyroidism were seen in family 1. CONCLUSION: We suggest that prophylactic thyroidectomy should not be delayed until adulthood in MEN 2A families carrying codon 804 RET mutations, but should be performed when there is CCH, before the development of MTC, as close as possible to age 6 years, which is the age of the youngest reported case of MTC in '804' families.

Pedigree of multiple benign adnexal tumours of Brooke-Spiegler type.

A pedigree of autosomal dominant expression of multiple benign adnexal tumours is presented. Seven cases spanning three generations are discussed. The clinical manifestations of these tumours are quite variable, including multiple papules concentrated on the face, scalp nodules and a large turban tumour. One member of the family had a linear papular eruption involving one half of his body. Histopathology of all lesions demonstrated benign adnexal characteristics, including well-characterized eccrine spiradenomas, trichoepitheliomas and an eccrine cylindroma. The cutaneous tumours occurring in these patients have continued to develop during their lifetimes. The authors propose that this pedigree has phenotypic characteristics consistent with Brooke-Spiegler syndrome.