Intramuscular Myxoma Associated with Fibrous Dysplasia

Mazabraud’s Syndrome: Intramuscular Myxoma Associated with Fibrous Dysplasia

Authors: Dr Fevziye Kabukcuoglu and Dr Yavuz Kabukcuoglu Creation date: January 2005

Scientific Editor: Prof Loic Guillevin

Department of Pathology and Department of Orthopedics and Traumatology. Sisli Etfal Training and Research Hospital, Istanbul Turkey. [email protected]

Abstract Key words Definition and disease name Differential Diagnosis Incidence Etiology Clinical Description Radiologic findings Histopathology Treatment Unresolved Questions References

Abstract Mazabraud’s syndrome is a rare disease known as the association of intramuscular myxoma with fibrous dysplasia. The number of reported cases in 2004 is 55. Myxomas generally occur as multiple masses and fibrous dysplasia most commonly appear with its polyostotic form. Both lesions tend to involve the same anatomical region. Patients usually present with a painless mass with a history of long duration due top lack of symptoms. Most fibrous dysplasias are asymptomatic while some may appear with pain, skeletal deformities or fractures. Generally fibrous dysplasias occur during the growth period and the myxomas appear during adult life. The relationship between fibrous dysplasia and myxoma remains unclear, where an underlying localized error in tissue metabolism has been proposed. Molecular genetic analysis has shown activating mutations in GNAS1 gene. Several benign lesions as well as richly myxoid malignant lesions may be confused with myxoma. Histopathologic examination should be carried out to exclude malignancy. Treatment is dependent on the extent of the lesions. Malignant transformation of myxoma is not reported, although local recurrence may be expected if incompletely resected. While sarcomatous transformation is uncommon for fibrous dysplasia, greater risk has been reported for Mazabraud’s syndrome. In a patient with soft tissue mass and multiple bone lesions, it is important to recognize Mazabraud’s syndrome for appropriate management of the patient.

Key words Mazabraud’s syndrome, intramuscular myxoma, fibrous dysplasia

Definition and disease name Mazabraud’s syndrome is a rare disease Differential Diagnosis described as the association of single or multiple Many different lesions like enchondroma, intramuscular myxomas with monostotic or aneurysmal bone cyst, chondrosarcoma, simple polyostotic form of fibrous dysplasia. This bone cyst, low grade central osteosarcoma, relationship was first noted in a case of osteitis nonossifying fibroma, osteofibrous dysplasia and fibrosa and multiple myxomas (Henschen, medullary bone infarct are considered in 1926). Mazabraud et al. reviewed the literature radiographic differential diagnosis of fibrous of and proposed the existence of a syndrome dysplasia especially if the lesion is monostotic. characterized by intramuscular myxoma and Although in most cases fibrous dysplasia fibrous dysplasia of bone (Mazabraud,1967). exhibits a very characteristic histologic picture,

Kabukcuoglu F, Kabukcuoglu Y. Mazabraud’s Syndrome: Intramuscular Myxoma Associated with Fibrous Dysplasia, Orphanet encyclopedia. January 2005: http://www.orpha.net/data/patho/GB/uk-Mazabraud.pdf 1 sometimes it may be necessary to distinguish it common, yet, undetermined denominator has from lesions like desmoplastic fibroma, been proposed to explain the origin. ostefibrous dysplasia, nonossifying fibroma, and Molecular genetic analysis has shown point low grade central osteosarcoma. Osteofibrous mutations in the GNAS-1 gene encoding a signal dysplasia and fibrous dysplasia exhibit similar transduction protein that regulates the cellular radiologic and histopathologic features. The cyclic adenosine monophosphate level in former lesion has a predilection for the cortex of intramuscular myxoma. (Okomato, 2000) the tibia. Osteofibrous dysplasia has immature Mutations in codon 211 were detected in five of nonlamellar bone rimmed by osteoblasts. When six intramuscular myxoma cases with the bone formation is limited there may be a Mazabraud’s syndrome (Faivre, 2001) The same problem in distinguishing from non ossifying Gsα mutations also have been detected in fibroma. Osteosarcoma has pleomorphic cells McCune Albright syndrome as well as in with frequent mitosis. The distinctive trabecular sporadic intramuscular myxoma (Schwindinger, pattern is not present. 1992, Cohen, 2002). Benign and malignant myxoid lesions may be confused with intramuscular myxoma. Benign Clinical Description tumors like myxolipoma, myxoid neurofibroma, Intramuscular myxoma is a tumor of adult life. neurothecoma, myxochondroma and nodular About two thirds of the patients are female fasciitis may show areas resembling (Iwasko, 2002). Most patients present with a intramuscular myxoma. It is important to painless mass usually with a history of long recognize richly myxoid malignant tumours like duration due to relative lack of symptoms. myxoid malignant fibrous histiocytoma, myxoid (Gianoutsos, 1990) The lesions involve the lower liposarcoma, low grade fibromyxoid sarcoma extremities more commonly. While intramuscular and myxoid chondrosarcoma in differential myxomas are solitary, 81% of patients with diagnosis. While low-grade malignant fibrous Mazabraud’s syndrome have multiple myxomas histiocytoma (myxofibrosarcoma) is a (Prayson, 1993). They tend to be multiple and hypocellular lesion with abundant myxoid appear in close proximity to the region of the stroma, there is always nuclear hyperchromasia most severely affected bone. However a and cytologic atypia leading to a malignant contiguous connection between a myxoma and a tumour. Myxoid liposarcoma has a regular fibrous dysplasia has never been established. plexiform vasculature, stellate cells with mild The number and size of myxoma and dysplasia cytologic atypia and lipoblasts. Low grade lesions occur irrespective of each other. fibromyxoid sarcoma is another entity Most fibrous dysplasia are asymptomatic. characterized by uniform spindle shaped cells, Symptoms occur many years after the presence myxoid matrix, and swirling arrangement of of the lesion. Some patients present with pain, tumour cells around thin walled capillaries. skeletal deformities, and pathologic fractures Myxoid chondrosarcoma is identified by nests particularly for lesions of the lower extremities and chords of cells with dense eosinophilic when not accompanying myxomas, fibrous stroma in a chondroitin sulfate rich stroma dysplasia tends to be monostotic. Most patients (Enzinger, 2001). Awareness of Mazabraud’s with Mazabraud’s syndrome present with the syndrome, especially when the myxoma is polyostotic form of the disease but monostotic solitary, can prevent misdiagnosing a malignant involvement has been reported as well mesenchymal tumour. (Sundaram,1989). The lower extremities are

most commonly affected. There is predilection Incidence for one side of the body in polyostotic form of the Mazabraud’s syndrome is rare. Individual disease. In most cases fibrous dysplasia is noted sporadic cases have been reported. The number during the growth period while myxomas of reported cases in 2004 is 55. become apparent during adult life. (Wirth, 1971, Blazier, 1986) Rarely multiple intramuscular Etiology myxomas are detected before the osseous The relationship between the two lesions lesions (Court-Payen,1997). remains unclear. A basic error in tissue metabolism persistent years beyond initial Radiologic findings growth and restricted to the regions of bony Radiographic appearance of fibrous dysplasia involvement has been proposed. (Wirth, 1971) varies with the proportion of osseous and fibrous Also higher incidences of minor bone tissue. The more fibrous lesions show greater abnormalities like cortical thickening, cystic lucency exhibiting a ground glass appearance, translucencies, exostoses or supernumerary while the osseous lesions are dense and bones have been detected accompanying sclerotic. Besides secondary calcifications or intramuscular mxyoma (Miettinen, 1985). A ossification patterns may be observed. The

Kabukcuoglu F, Kabukcuoglu Y. Mazabraud’s Syndrome: Intramuscular Myxoma Associated with Fibrous Dysplasia, Orphanet encyclopedia. January 2005: http://www.orpha.net/data/patho/GB/uk-Mazabraud.pdf 2 borders are well defined. The cortex is usually is possible with incomplete resection of the intact, but it may be thinned due to expansive lesion (Miettinen, 1985. Silver, 2002). nature of the lesion. Bone scintigraphy is useful Clinical course of fibrous dysplasia is variable. in showing the activity and multicentricity of the When the lesions are extensive the fibrous lesions (Hoshi,1990). Computed tomography dysplasia may progress to marked deformities helps to point out the extent of bone involvement and fractures. The disease progresses slowly (Daffner 1982) . Magnetic resonance image and has a favorable prognosis if the involvement show homogenous moderately low signal is local. intensity on T1 weighted images. On T2 weighted Patients with multiple intramuscular myxomas images the signal may be mixed or high. Signal should be preoperatively examined for osseous intensity on T1 and T2 weighted images depend lesions. A proper histopathologic examination is on the degree of bone trabeculae, fibrous tissue, necessary to exclude malignancy or metastatic cystic and hemorrhagic changes. The sclerotic tumor in an elderly patient (Kabukcuoglu, 2004). rim is seen as a band of signal intensity on both A post-operative follow up is also needed to T1 and T2 sequences (Jee,1996). detect other soft tissue myxomas. In a patient Plain radiographs of myxomas show nonspecific, with multiple intramuscular tumours associated poorly defined soft tissue masses. MRI with bone lesions, recognition of Mazabraud’s demonstrates a well-circumscribed mass with syndrome is important for appropriate homogenous signal intensity. T1 weighted management to avoid unnecessary wide sequences demonstrate low signal intensity excision and radiotherapy. mass and T2 weighted images show a high The lesions of fibrous dysplasia tend to stabilize signal intensity mass. With contrast as skeletal maturity is reached. Treatment is enhancement is proportional to the amount of usually conservative and aims to prevent solid myxoid tissue and fibrous septa. (Iwasko, deformity. Bisphosphonates may be helpful in 2002, Cabral, 1998). relieving pain and possibly in reconstituting lesions with normal bone (Lane, 2001). Surgical Histopathology treatment is indicated for severe and progressive Fibrous dysplasia is characterized by disease, nonunion, persistent pain or fracture of replacement of normal bone and marrow by a weight bearing bone. Surgery is not necessary tissue composed of bland fibrous tissue and for an asymptomatic lesion unless there is a risk irregular spicules of woven bone. Rimming of of pathological fracture. Curettage and grafting osteoblasts is not present around the bone of the bone defect with autograft or allograft may spicules although this change may be focally result in resorption of the graft into fibrous encountered in areas adjacent to fracture. dysplasia causing high rates of local recurrence. Myxomas have a glistening gray-white Curettage and bone grafting alone is best suited appearance depending on the amount of myxoid to lesions in non-weight bearing bones. Painful material. Although they may seem well long bone lesions can be stabilized by cortical circumscribed, they infiltrate the adjacent grafting or implant fixation. Expendable bones muscles. The tumor is relatively hypocellular with can be treated by excision. Deformity may abundant mucoid material and loose reticulin require corrective osteotomy and internal fixation fibers. Vascular structures are sparse. The cells (Ippolito, 2003). have a stellate shape with small hyperchromatic While sarcomatous transformation is uncommon pyknotic nuclei and scanty cytoplasm (Enzinger, in fibrous dysplasia alone, a greater risk is 2001). Some myxomas may show focal areas of present for patients with Mazabraud’s syndrome. hypercellularity. However absence of nuclear Sporadic cases have been reported calling for atypia, mitotic figures or necrosis help to rule out the necessity of clinical follow up. (Witkin, 1986, malignancy (Nielsen, 1998). Mucoid material Lopez-Ben,1999, Jhala, 2003). stain positively for alcian blue, mucicarmine and colloidal iron. Immunohistochemical studies have Unresolved Questions shown staining for vimentin and no reaction for Involvement of the same anatomical region by S100. dissimilar lesions remains to be a anonymity. In

addition, the relationship between fibrous Treatment dysplasia and myxoma remains unclear. Myxomas are benign. No report has been Bisphosphonates have been proven to be encountered describing malignant degeneration effective in decreasing pain in fibrous dysplasia, of a myxoma. Treatment is dependent on the but their effect on the course of the disease and extent of the lesions. They should be excised if fracture rate is not clear. Further investigations pain or pressure symptoms develop. Simple are needed for effective treatment of fibrous local excision is sufficient. Rare local recurrence dysplasia.

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