The histopathology of fibrous dysplasia of bone in patients with activating mutations of the Gs alpha gene: Site-specific patterns and recurrent histological hallmarks

Gs alpha mutations and histopathology have been analysed in a series of 13 patients with fibrous dysplasia (FD) of bone, including 12 patients with th e McCune-Albright syndrome (MAS) and one patient with monostotic FD, Activa ting mutations (either R201C or R201H) of the gene encoding the a subunit o f the stimulatory G protein, Gs, were detected in all cases, including the case of monostotic FD, using a variety of techniques [reverse transcription -polymerase chain reaction (RT-PCR) with allele-specific primers, allele-sp ecific oligonucleotide hybridization, and DNA sequencing], A spectrum of bo ne lesions associated with such mutations was identified and it was possibl e to recognize three primary, but distinct, histological patterns, defined here as Chinese writing type, sclerotic/Pagetoid type, and sclerotic/hyperc ellular type, which are characteristically associated with the axial/append icular skeleton, cranial bones, or gnathic bones, respectively, Features of FD histopathology were characterized by confocal fluorescence microscopy, which allowed the definition of osteogenic cell shape changes and 'Sharpey fibre bone' as common denominators of all histological subtypes. Defining c haracteristics of the different subtypes, two of which diverge from standar d descriptions of FD and have never been characterized before, were depende nt on the amount and structure of bone tissue within the FD lesion. These d ata emphasize the non-random (site-specific) variability of FD histopatholo gy in patients carrying activating mutations of the Gsa gene and provide ad ditional evidence for the occurrence of Gs alpha mutations in cases of FD o ther than typical MAS. Copyright (C)1999 John Wiley & Sons, Ltd.