TY - JOUR
T1 - The histopathology of fibrous dysplasia of bone in patients with activating mutations of the Gsα gene
T2 - Site-specific patterns and recurrent histological hallmarks
AU - Riminucci, Mara
AU - Liu, Bin
AU - Corsi, Alessandro
AU - Shenker, Andrew
AU - Spiegel, Allen M.
AU - Robey, Pamela Gehron
AU - Bianco, Paolo
PY - 1999
Y1 - 1999
N2 - Gsα mutations and histopathology have been analysed in a series of 13 patients with fibrous dysplasia (FD) of bone, including 12 patients with the McCune-Albright syndrome (MAS) and one patient with monostotic FD. Activating mutations (either R201C or R201H) of the gene encoding the α subunit of 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- specific oligonucleotide hybridization, and DNA sequencing]. A spectrum of bone lesions associated with such mutations was identified and it was possible to recognize three primary, but distinct, histological patterns, defined here as Chinese writing type, sclerotic/Pagetoid type, and sclerotic/hypercellular type, which are characteristically associated with the axial/appendicular 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 characteristics of the different subtypes, two of which diverge from standard descriptions of FD and have never been characterized before, were dependent on the amount and structure of bone tissue within the FD lesion. These data emphasize the non-random (site- specific) variability of FD histopathology in patients carrying activating mutations of the Gsα gene and provide additional evidence for the occurrence of GSα mutations in cases of FD other than typical MAS.
AB - Gsα mutations and histopathology have been analysed in a series of 13 patients with fibrous dysplasia (FD) of bone, including 12 patients with the McCune-Albright syndrome (MAS) and one patient with monostotic FD. Activating mutations (either R201C or R201H) of the gene encoding the α subunit of 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- specific oligonucleotide hybridization, and DNA sequencing]. A spectrum of bone lesions associated with such mutations was identified and it was possible to recognize three primary, but distinct, histological patterns, defined here as Chinese writing type, sclerotic/Pagetoid type, and sclerotic/hypercellular type, which are characteristically associated with the axial/appendicular 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 characteristics of the different subtypes, two of which diverge from standard descriptions of FD and have never been characterized before, were dependent on the amount and structure of bone tissue within the FD lesion. These data emphasize the non-random (site- specific) variability of FD histopathology in patients carrying activating mutations of the Gsα gene and provide additional evidence for the occurrence of GSα mutations in cases of FD other than typical MAS.
KW - Bone
KW - Confocal microscopy
KW - Fibrous dysplasia
KW - G protein
KW - Gsα mutation
KW - McCune-Albright syndrome
KW - Pathology
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U2 - 10.1002/(SICI)1096-9896(199901)187:2<249::AID-PATH222>3.0.CO;2-J
DO - 10.1002/(SICI)1096-9896(199901)187:2<249::AID-PATH222>3.0.CO;2-J
M3 - Article
C2 - 10365102
AN - SCOPUS:0032902792
SN - 0022-3417
VL - 187
SP - 249
EP - 258
JO - Journal of Pathology
JF - Journal of Pathology
IS - 2
ER -