Clonality analysis of benign parathyroid lesions by human androgen receptor (HUMARA) gene assay

Benign conditions of the parathyroid gland have been classified as adenomas and hyperplasias. These entities however are difficult to distinguish when only a single gland is enlarged. Adenomas are defined as neoplastic clonal growths whereas hyperplasias are considered to be reactive processes of po lyclonal origin. In order to analyze the clonal pattern of these lesions, w e have studied hyperplasias and adenomas of parathyroid glands from women b y the human androgen receptor (HUMARA) assay, a recently reliable and highl y-informative technique based on the X-chromosome inactivation pattern in f emales. Samples consisted of formalin-fixed as well as frozen tissues. Info rmativeness with HUMARA marker was 87% (13/15 cases). All hyperplasias (5/5 ) and 6/8 adenomas yielded polyclonal results, since two alleles of similar intensity appeared when the lesion was HpaII-digested. Two parathyroid ade nomas had a loss of one X-allele for the HUMARA gene and they were interpre ted as monoclonal. These results show that parathyroid hyperplasias and ade nomas, considered as multigland or monogland involvement diseases respectiv ely, may be both polyclonal in origin, and that only a small subset of aden omas is found to be clonal. Consequently, clonality analysis cannot allow a clear distinction between these two entities as classically diagnosed. A d ifferent approach should be considering hyperplasia or adenoma when a polyc lonal or monoclonal result has been obtained by clonality analysis.