Mazabraud-Syndrom
Mazabraud syndrome is a rare syndrome characterized by skeletal fibrous dysplasia and intramuscular myxomas .
Epidemiology
Only 107 cases have been reported in the global literature (as of 2019) . The prevalence is ~ 1 in 1,000,000 with a strong female predilection (68-84%) . The age at diagnosis ranges from 35-60 years with a mean age of approximately 40 years . Childhood-onset has been reported in four cases .
Recently, in a cohort of 372 patients with fibrous dysplasia and a multicenter cohort study of 1446 patients with fibrous dysplasia , Mazabraud syndrome was reported with a prevalence of 2.4 and 2.2% respectively.
Associations
- McCune-Albright syndrome: café-au-lait skin pigmentations and endocrine dysfunction, such as precocious puberty, diabetes mellitus, goiter and breast fibroadenomatosis
Clinical presentation
There is a highly variable clinical presentation. Patients may be asymptomatic, may describe painless mass(es), or may describe painful mass(es), deformities, and/or pathological fractures .
Intramuscular myxomas are typically located in the vicinity of the bone lesions with both fibrous dysplasia and intramuscular myxomas most commonly affecting the pelvic girdle and lower limbs (75%). The upper limbs are affected in less than a quarter of reported cases. Interestingly, the right side is most commonly affected (60%). The fibrous dysplasia generally occurs between 6.5-10 years prior to the identification of intramuscular myxomas .
Pathology
There is a strong link with post-zygotic mutations of the GNAS1 gene located on chromosome 20q13.2-q13.3, which encodes the alpha subunit of G-protein (GSa) involved in cell proliferation . When this occurs, bone is replaced and distorted by poorly organized, structurally unsound, fibrous tissue . This mutation affects the mesenchymal precursor cells at the early stages of commitment . This may account for the wide range of clinical patterns with earlier mutations proving a more complex clinical phenotype and partly explaining why patients clinically vary from asymptomatic to painful forms with fractures and deformities .
Microscopic appearance
- fibrous dysplasia
- rimming of osteoblasts is not present around the bone spicules although this change may be focally encountered around areas of adjacent fracture
- there are bland fibrous tissue and irregular spicules of woven bone
- intramuscular myxomas
- lesions are generally hypocellular and hypovascular although areas of increased vascularity and cellularity may be present
- there are abundant mucoid material and loose reticulin fibers
- the cells have a stellate shape with small hyperchromatic pyknotic nuclei and scanty cytoplasm
- there is the absence of nuclear atypia, mitotic figures or necrosis
Radiographic features
Plain radiograph
Polyostotic (or monostotic) fibrous dysplasia display radiolucency with ground glass matrix appearance surrounded by condensed bone. This is usually smooth and homogenous with endosteal scalloping and cortical thinning usually present. Borders are well defined and the cortex is usually intact but thinned due to the expansive nature of the lesion.
CT
CT is a superior modality to plain radiographs. Osseous expansion with ground glass appearance usually attenuates at from 60-140 HU . Intramuscular myxomas appear as well-demarcated hypodense ovoid lesions close to areas of fibrous dysplasia and usually show mild diffuse enhancement or peripheral and septal enhancement seen in approximately 50% of cases .
MRI
Fibrous dysplasia shows sharply demarcated borders of intermediate to low T1 signal and intermediate to high T2 signal. The higher the number of bony trabeculae, the lower the T2 signal and vice versa - the fewer bony trabeculae, the higher the T2 signal .
Active lesions show post-contrast enhancement which may be patchy central, rim, homogenous or a combination . Diffusion-weighted imaging may help in differentiating benign from malignant lesions and ADC values particularly in the skull lesions correlate with cell density and may narrow differential diagnosis .
Intramuscular myxomas demonstrate hypointense T1 and hyperintense T2 signal. Four different contrast patterns have been described :
- peripheral enhancement
- peripheral and patchy internal enhancement
- peripheral and linear internal enhancement
- heterogeneous internal enhancement
Nuclear medicine
Technetium 99m-methyldiphosphonate can be used to detect disease extent in the young . Rapid increase in 18-FDG uptake may suggest the possibility of sarcomatous change . Fibrous dysplasia lesions are found positive on In-111 pentriotide (octreoscan), Ga-67 citrate and Tc-99m MIBI scintigraphy as well as 68-Ga-DOTATATE and 11-c choline PET/CT.
Intramuscular myxomas may show 18-FDG avidity on PET/CT however nuclear medicine plays no role in the identification of intramuscular myxomas in Mazabraud syndrome .
Treatment and prognosis
Treatment is variable and dependent on the extent of the disease. Fibrous dysplasia causing persistent pain, skeletal deformities, and danger of fracture or pathological fracture require surgical intervention. Medical therapy with anti-resorptive medication may be helpful in relieving pain and possibly reconstituting lesions with normal bone . A recent case study described the use of bisphosphonate therapy providing a clear reduction in the diameter of intramuscular myxoma after the use of zolendronic acid for 4 years .
As myxomas are benign, conservative treatment is recommended . Myxomas should be excised if they cause pain, pressure symptoms, and neurological symptoms or interfere with functionality.
Complications
The most common complication of myxomatous surgical excision is recurrence which occurs in ~ 30% of cases at a median of 8.5 years (range: 2-16 years) . Highly cellular lesions have higher recurrence rates however size, increased number and younger age at diagnosis are not significantly associated with recurrence .
Rarely, there may be malignant transformation of the fibrous dysplasia . Malignant transformation of fibrous dysplasia may be to osteosarcoma, fibrosarcoma, chondrosarcoma, and malignant fibrohistiocytoma . Seven reported cases of malignant transformation of fibrous dysplasia into osteogenic sarcoma have been reported in patients with Mazabraud syndrome justifying clinical and radiological follow-up .
No reported cases of malignant transformation in intramuscular myxomas have been identified.
History and etymology
The first case was described in the literature in 1926 but it was the French physician Mazabraud in 1967 who first recognized the association between the intramuscular myxomas and fibrous dysplasia .
Siehe auch:
Assoziationen und Differentialdiagnosen zu Mazabraud-Syndrom:
