Mazabraud syndrome

Mazabraud syndrome is defined by an association between fibrous dysplasia and intramuscular myxomas, and is thought to fall within the spectrum of protean disorders of syndromic fibrous dysplasia that includes McCune-Albright syndrome. In this article, we briefly discuss the history and evolution of the term Mazabraud syndrome, then detail the spectrum of imaging findings as they relate to the variable pathology and clinical presentations that may be encountered. Differential diagnostic considerations and potential diagnostic pitfalls are also considered.     

Transsphenoidal surgery in a patient with acromegaly and McCune-Albright syndrome: application of neuronavigation

The McCune-Albright syndrome (MAS) is characterized by a clinical triad of polyostotic fibrous dysplasia, café-au-lait hyperpigmented macules, and hypersecretory endocrinopathies. Acromegaly is an uncommon manifestation of the endocrine disturbance associated with MAS, and the role of surgery in managing these cases has been a topic of debate. The authors present the case of a 35-year-old man with MAS who was also diagnosed with acromegaly, hyperprolactinemia, and pituitary macroadenoma. The patient had an 18-year history of fibrous dysplasia involving the right frontal bone and ribs as well as multiple endocrinopathies, but no cutaneous hyperpigmented macules. An oral glucose tolerance test demonstrated partial suppression of plasma levels of growth hormone (GH). The patient underwent transsphenoidal resection of the pituitary tumor, performed with assistance of neuronavigation, and tolerated the procedure well. After the surgery, both prolactin and GH levels returned to normal. These results suggest that neuronavigation-assisted transsphenoidal surgery can safely remove pituitary adenomas associated with MAS and successfully treat the underlying endocrine abnormalities.     

A highly sensitive polymerase chain reaction method detects activating mutations of the GNAS gene in peripheral blood cells in McCune-Albright syndrome or isolated fibrous dysplasia

BACKGROUND: The somatic nature of mutations in the GNAS gene in McCune-Albright syndrome and isolated fibrous dysplasia makes their identification difficult. Conventional methods for the detection of mosaic mutations of GNAS have required polymerase chain reaction analysis of genomic DNA from affected tissues or multiple rounds of tandem polymerase chain reaction and endonuclease digestion to enrich for mutant alleles in genomic deoxyribonucleic acid (DNA) from other tissues. Peptide nucleic acid (PNA) primers specifically block synthesis from the nonmutant or wild-type allele. We therefore used PNA-clamping to detect low copy numbers of mutant GNAS alleles in DNA from peripheral blood cells from patients with McCune-Albright syndrome and fibrous dysplasia. METHODS: We applied the PNA-clamping method to the analysis of genomic DNA from peripheral blood cells of thirteen patients with McCune-Albright syndrome and three patients with isolated fibrous dysplasia. Polymerase chain reaction was performed in the presence and absence of PNA, and the polymerase chain reaction products were sequenced. In the absence of PNA, a strong 325 base-pair polymerase chain reaction band was generated from all samples; in the presence of PNA, there was an approximately 50% to 90% reduction in the intensity of this polymerase chain reaction product. RESULTS: In the absence of PNA, direct sequencing of the polymerase chain reaction products demonstrated R201 mutations in GNAS alleles of three of the thirteen patients with McCune-Albright syndrome and none of the three patients with fibrous dysplasia. In contrast, in the presence of PNA, R201 mutations were detected in eleven of the thirteen patients with McCune-Albright syndrome and in all three of the patients with fibrous dysplasia. In mixing experiments involving the use of wild-type and mutant DNA samples, we were able to determine the presence of a mutant GNAS allele in the equivalent of one cell in 1000 to 5000 cells. CONCLUSIONS: Inclusion of a specific PNA primer in the polymerase chain reaction for GNAS exon 8 allows the selective amplification of low numbers of mutant alleles, and it permits detection of activating mutations in genomic DNA from peripheral blood cells in patients with McCune-Albright syndrome and fibrous dysplasia.     

Balloon kyphoplasty for vertebral compression fractures secondary to polyostotic fibrous dysplasia. Case report

This 25-year-old woman with polyostotic fibrous dysplasia (McCune-Albright syndrome) suffered low-back pain after a minor traumatic injury. Neurological examination demonstrated normal status. Magnetic resonance imaging revealed cystic lesions in multiple thoracic and lumbar vertebral bodies, consistent with polyostotic fibrous dysplasia. Severe vertebral compression fractures (VCFs) were seen at T-8 and L-2. Balloon kyphoplasty was performed to treat the T-8 and L-2 VCFs and also prophylactically at T-9 and T-10 to forestall impending fractures at those levels. The patient tolerated the procedures very well and reported complete resolution of back pain. Balloon kyphoplasty may be an option in patients with painful VCFs caused by fibrous dysplasia.     

"Café-au-lait spots" caused by vitiligo in McCune-Albright syndrome.

Café-au-lait spots, fibrous dysplasia of bone, and endocrine gland hyperactivity are the principal features of McCune-Albright syndrome (MAS). Café-au-lait spots appear at, or soon after, birth. We illustrate "café-au-lait spots" acquired during middle age in a patient with MAS that are an illusion caused by vitiligo. This 64-year-old woman is the oldest patient reported with this disorder.     

A case of atypical McCune-Albright syndrome requiring optic nerve decompression.

McCune-Albright syndrome (MAS) is a disease of noninheritable, genetic origin defined by the triad of café-au-lait pigmentation of the skin, precocious puberty, and polyostotic fibrous dysplasia. This syndrome, which affects young girls primarily, has also been reported with other endocrinopathies, and rarely with acromegaly and hyperprolactinemia. The fibrous dysplasia in MAS is of the polyostotic type and, apart from the characteristic sites such as the proximal aspects of the femur and the pelvis, the craniofacial region is frequently involved. A male patient with MAS presented with juvenile gigantism, precocious puberty, pituitary adenoma-secreting growth hormone and prolactin, hypothalamic pituitary gonadal and thyroid dysfunction, and polyostotic fibrous dysplasia causing optic nerve compression. Visual deterioration and its surgical management are presented.     

Use of a retrograde femoral nail in a patient with McCune-Albright syndrome

McCune-Albright Syndrome is a rare condition characterized by endocrine abnormalities, precocious puberty, pigmented skin lesions and polyostotic fibrous dysplasia with consequent fractures and limb deformity. Patients with this syndrome might have had multiple operations on a limb and might also have extensive internal fixation in-situ. We review the case of a 41-year-old woman with McCune-Albright syndrome, who presented with a pathological fracture of her left femur below a long plate and screws. Our management of this challenging problem included the use of a retrograde femoral nail, which, because of the need to retain pre-existing internal fixation, had to be locked proximally through a hole in a femoral plate. This technique, combined with reaming, and thus bone grafting of the fracture, and also perioperative infusions of pamidronate, allowed an early recovery and return to premorbid function for the patient. In the present study we detail our technique and discuss its advantages over other possible methods of treatment.     

Fibrous dysplasia of the maxilla

Fibrous dysplasia is a rare disorder of the bone. It is seen in 2 main forms of presentation, monoostotic and the polyostotic form with café au lait spots and precocious puberty (McCune-Albright syndrome). Most of the cases present in the first 2 decades of life, and the lesions are rare in infants (Joseph E, Kachara R, Bhattacharya RN, et al. Fibrous dysplasia of the orbit in an infant. Pediatr Neurosurg 2000; 32: 205-208). Herein, we present a rare case of fibrous dysplasia in an infant.     

Optic Nerve Decompression for Orbitofrontal Fibrous Dysplasia

Orbitofrontal fibrous dysplasia often involves the bony orbit and the optic canal. Although fibrous dysplasia reportedly produces compression of the optic nerve leading to visual distrubances, optic nerve decompression in patients without clinical signs of optic neuropathy is still controversial. We describe two patients with orbitofrontal fibrous dysplasia without signs of visual disturbance and one patient with McCune-Albright syndrome and progressive visual impairment. Optic nerve decompression was performed prophylactically for two patients and therapeutically for one patient through the transcranial extradural route. Dystopias and craniofacial deformities induced by fibrous dysplasia also were corrected. The micropressure suction-irrigation system was especially effective for decreasing heat transfer and thereby preventing thermal injury of the optic nerve. The orbitofrontal area was reconstructed from cranial bone, iliac bone, and ribs. Postoperative follow-up revealed no disturbances in visual function and no evidence of cerebrospinal fluid leakage. These findings suggest that optic nerve decompression may be effective in preventing visual disturbances with minimal risk of other neurological sequelae. Subsequent orbital reconstruction yielded satisfactory cosmetic results.     

Activating mutations of Gs protein in monostotic fibrous lesions of bone

Activating mutations of the alpha chain of the heterotrimeric signal transducer Gs disrupt the inherent guanosine triphosphatase activity of the alpha chain, stimulate adenylyl cyclase, and can result in independent cell proliferation. Such mutations are identified in a number of endocrine disorders, including McCune-Albright syndrome, which is a triad of endocrinopathy, café au lait spots, and polyostotic fibrous dysplasia. The mutation in this syndrome is a missense point mutation in exon 8 that results in the substitution of either histidine or cysteine for arginine at position 201. Monostotic fibrous dysplasia is a nonhereditary isolated bone lesion. Other isolated bone lesions that share some cytologic and clinical similarities to fibrous dysplasia are osteofibrous dysplasia and aggressive fibromatosis involving bone. Four cases of monostotic fibrous dysplasia, four cases of aggressive fibromatosis involving bone, and one case of osteofibrous dysplasia were studied to determine if a mutation was present in exon 8 of the alpha chain of Gs. A missense mutation was present in all of the fibrous dysplasias. The other fibrous lesions and uninvolved tissue did not contain a mutation. Somatic activating mutations of Gs differentiate fibrous dysplasia from the other lesions and may be responsible for the loss of control of local proliferation and growth factor expression.     

Primary bimorphic adrenocortical disease: cause of hypercortisolism in McCune-Albright syndrome

McCune-Albright syndrome (polyostotic fibrous dysplasia, café-au-lait skin spots, and precocious puberty) is a genetically mosaic disorder with populations of mutant and normal cells in affected organs. Cushing syndrome, a rare feature of the condition, usually affects infants and is the result of corticotropin-independent primary bilateral adrenal disease, usually interpreted as nodular adrenocortical hyperplasia. In this study of 9 patients with Cushing syndrome and McCune-Albright syndrome, light microscopy revealed a characteristic bimorphic pattern of diffuse and nodular hyperplasia and a distinctive form of cortical atrophy with apparent zona glomerulosa hyperplasia in 8 patients, all very young. The pattern could be explained by the presence of a mosaic distribution of mutant and normal cells in the adrenal glands. The findings are different from those in inherited or other forms of genetically caused Cushing syndrome. The ninth patient, aged 17 years, had an adrenal adenoma and diffuse cortical hyperplasia in each adrenal gland.     

Rapidly enlarging orbital tumor in a facial fibrous dysplasia lesion

Malignant change in fibrous dysplasia (FD) is a well-described phenomenon in the literature. When rapid enlargement is observed in an FD lesion, malignant change should be considered first. We present a case with McCune-Albright syndrome in which a rapidly enlarging orbital tumor developed in a facial FD lesion, which was subsequently proven to be a metastasis from an incidental esophageal carcinoma. Although metastasis of a malignant tumor to an FD lesion is quite rare and has been neglected as a differential diagnosis in the literature, it should be included in the important differential diagnosis because hematogenous metastasis could readily occur in FD due to its abundant blood flow. The importance of systemic examinations, such as positron emission tomography, is also emphasized.     

“Banana patella”, fibrous dysplasia of patella: A rare case report

IntroductionPatella is a very uncommon site for primary bone tumours and fibrous dysplasia lesion in patella has never been reported. Fibrous dysplasia is a benign fibrosseous lesion of the bone where the fibrous connective tissue replaces the normal bone.Case reportWe report a case of 23 years female with 7 years history of progressive swelling and anterior knee pain. Radiographs showed enlarged, deformed patella like a shape of banana. The patient underwent patellectomy with extensor mechanism repair and biopsy proved to be fibrous dysplasia.ConclusionFibrous dysplasia involving patella is very rare and never been reported earlier. Although primary patellar neoplasm are not common but should be kept in mind in chronic anterior knee pain with swelling for early diagnosis and intervention with intralesional therapy otherwise patellectomy has to be done in more advanced, deformed and enlarged lesions.     

Ductal carcinoma in situ in a 27-year-old woman with McCune-Albright syndrome

McCune-Albright syndrome (MAS) is a sporadic disorder characterized by the triad of irregularly edged hyperpigmented macules (café au lait spots); a slowly progressive bone disorder, polyostotic fibrous dysplasia, usually involving the base of the skull and the long bones; and luteinizing hormone-releasing hormone (LHRH)-independent precocious puberty. This case is the first report of a 27-year-old woman with ductal carcinoma in situ (DCIS) and Paget's disease of the nipple associated with MAS. The discussion focuses on two endocrine manifestations of this syndrome including precocious puberty and excess growth hormone secretion. In our patient, both her early puberty and pituitary adenoma, in association with MAS, resulted in excess production and secretion of estrogen and growth hormone. Both of these hormones function to stimulate breast growth and development. We hypothesize they are responsible for this patient's DCIS and Paget's disease of the nipple so early in life.     

Radiographic characteristics of fibrous dysplasia of the clivus: a case report and review of the literature

Whereas fibrous dysplasia is a well-known, developmental skeletal disorder with a benign clinical course, fibrous dysplasia of the clivus is extremely rare and has seldom been reported. Differentiating this benign entity from more aggressive diseases involving the clivus is important for the proper management of lesions in this area. We here report a case of fibrous dysplasia of the clivus and discuss its radiographic features. The patient was 55-year-old male who had suffered from headache for months. Physical and neurological examinations found no abnormalities. The computed tomographic (CT) scan and magnetic resonance imaging (MRI) showed an abnormal mass lesion in the lower of the third clivus. On CT scan, the mass lesion exhibited a ground-glass appearance. The lesion was detected as hypointense and a mixture of hyperintense and isointense areas on T1-weighted and T2-weighted MRI, respectively. Heterogenous enhancement was noted after infusion of GD-DTPA. The patient underwent a transsphenoidal resection of the mass and the histopathologic diagnosis was fibrous dysplasia.     

Osteosarcoma in a pregnant patient with McCune–Albright syndrome

Malignant transformation of fibrous dysplasia is very rare and has not been previously described in patients with McCune–Albright syndrome in the absence of radiation treatment during gestation. Here, we report a 38-year-old pregnant woman with McCune–Albright syndrome and acromegaly accompanied by osteosarcoma. The patient was in the 6th week of pregnancy, when she visited our hospital. She had multiple fibrous dysplasia, skin pigmentation, and acromegaly. The markedly high bone turnover rate during pregnancy tended to decrease after a normal delivery. Fibrous dysplasia of the lower jaw rapidly increased in the 37th week of pregnancy, and the tumor was surgically resected after delivery. Pathological examination of the resected tumor revealed fibrous dysplasia admixed with osteosarcoma containing chondroblastic and osteoblastic tissue. We firstly reported a case of osteosarcoma in a patient with McCune–Albright syndrome, which rapidly progressed during pregnancy.     

A giant cranial aneurysmal bone cyst associated with fibrous dysplasia

An aneurysmal bone cyst (ABC) is a rare, benign fibro-osseous lesion, considered a vascular phenomenon secondary to fibrous dysplasia or a giant-cell tumour, and occurs mainly in long bones and vertebrae. In this case report a 16-year-old male presented with massive epistaxis. He was admitted with a 3-year history of chronic rhinitis, headaches, right ocular pain and recurrent epistaxis. CT scans showed a predominantly cystic, expansive mass obstructing both nasal cavities, extending to all paranasal sinuses and both orbits, with evidence of anterior cranial fossa skull base destruction. The patient underwent a craniofacial resection of the tumour performed with an external approach and an immediate reconstruction of the dural defect. Histology confirmed the lesion was an ABC associated with fibrous dysplasia. The patient's recovery was complete. A large facial aneurysmal bone cyst can damage the facial skeleton and skull base, and requires excision by a combined external approach.     

Bone turnover in children and adolescents with McCune-Albright syndrome treated with pamidronate for bone fibrous dysplasia

Bone fibrous dysplasia is one of the main features of McCune-Albright syndrome, a rare genetic condition caused by constitutive activating mutations of Gs-protein and defined by skin dysplasia, bone fibrous dysplasia, and autonomous multiple endocrinopathies. Raised serum alkaline phosphatase (ALP) and urinary hydroxyproline levels indicating bone metabolic hyperactivity have been reported in these patients. Encouraging therapeutic results have been achieved, mainly in adults, with pamidronate, an aminobisphosphonate. In this study we investigate newer bone metabolic indices in a cohort of 11 children and adolescents treated with pamidronate. Tenfold increases of bone ALP and urinary pyridinoline cross-links were found and osteocalcin levels were twofold higher compared with reference values. After treatment, significant decreases in bone ALP and cross-links (Wilcoxon test P < 0.06) were found. Bone mineral density (BMD) significantly increased during treatment. There were signs of radiological healing as thickening of the cortical bone was found in some cases.     

Mazabraud's syndrome: intramuscular myxoma associated with fibrous dysplasia of bone

A 53 year old male with a large swelling on the medial aspect of his right thigh was referred with a presumptive diagnosis of soft tissue sarcoma. However, biopsy revealed intramuscular myxoma and X-rays and CT scans suggested fibrous dysplasia of adjacent bone. Angiography had shown an expanded, hypervascular, intramedullary lesion in the femur, and a large avascular soft tissue mass lying medially in the distal thigh. Fibrous dysplasia of the femur was confirmed on bone biopsy. Subsequently one large and two smaller intramuscular myxomata were excised, with an uneventful postoperative course. This case illustrates Mazabraud's syndrome: the rare association between benign intramuscular myxoma and fibrous dysplasia of bone.