Multiple familial cutaneous glomangioma: A pedigree of 4 generations and critical analysis of histologic and genetic differences of glomus tumors

Background Glomangiomas are benign tumors arising from neuromyoarterial cel ls surrounding cutaneous arteriovenous anastomoses that serve as temperatur e regulators. They exist as solitary or multiple types, occurring sporadica lly or in a familial pattern, the latter of which is rare. Objective: We describe a 4-generation pedigree of familial cutaneous gloman gioma, in addition to the 3 other well-documented pedigrees reported in the literature to date, and we clarify ways in which to distinguish the differ ent types of glomus tumors. Methods: Nodular skin lesions of 4 affected family members were analyzed by histologic, immunohistologic, and electron microscopic methods. To elucida te the gene defect in this family, we searched for a linkage to a candidate locus on chromosome 11q23 previously identified in paragangliomas, one for m of glomus tumor, in 16 family members of 4 generations by using polymorph ic markers. Results: The diagnosis of disseminated cutaneous glomangiomas was confirmed histologically in 4 family members of 3 different generations. Glomangioma s were transmitted in an autosomal dominant pattern via the paternal line. Genetic linkage analysis of the affected family members excluded linkage to chromosome 11q23. Conclusion: An autosomal dominant pattern of inheritance has been described for glomus tumors of the paraganglioma type originating from the APUD cell system, the underlying genetic defect of which has been mapped to chromoso me 11q23. In contrast, we show that the genetic defect in disseminated cuta neous glomus tumors of the glomangioma type deriving from smooth muscle cel ls or pericytes is not linked to chromosome 11. Thus we suggest that the co mmon term glomus tumor, used for both paragangliomas and glomangiomas in th e current literature, is misleading and should be avoided because these tum ors have different histologic derivation and genetic origin.