Mazabraud syndrome associated with McCune-Albright syndrome: a case report and review of the literature.

Mazabraud syndrome is a very rare benign disorder characterized by the association of monostotic or polyostotic fibrous dysplasia and one or multiple intramuscular myxomas. McCune -Albright syndrome is a rare benign disorder characterized by the association of polyostotic fibrous dysplasia, cafè-au-lait skin pigmentations and endocrine dysfunction, such as precocious puberty, diabetes mellitus, goiter and breast fibroadenomatosis. The association of Mazabraud syndrome and McCune-Albright in the same patient is an anecdotal event. We report the case of a 28-year-old girl with Mazabraud syndrome associated with McCune-Albright syndrome. Our literature review shows that in these patients there is a higher risk of malignant transformation of fibrous dysplasia into osteosarcoma, confirming previous reports. Conversely, no malignant transformation has been reported for myxomas in isolated Mazabraud syndrome or in the association with McCune-Albright syndrome. We conclude that these patients should be scheduled to a close and long-term follow-up.

Dear Editor, we report the case of a 2 8-year-old girl with the association of Mazabraud syndrome (MS) and McCune-Albright syndrome (MAS). Since birth she had cafè-au-lait spot on the right buttock and tight (figure 1). When she was 4-year-old she developed precocious puberty and fibrous dysplasia (FD) at the right upper limb and left chest wall. Hypothyroidism, polycystic ovary and breast fibroadenomatosis accompanied the extraskeletal manifestations. She was admitted at our Institute because of an intramuscular myxoma on the right leg (figure 2) that was biopsied and later excised.

Figure 1

A typical cafè-au-lait lesion on the right buttock and thigh which demostrates jagged “coast of Maine” borders and the tendency to respect the midline

Figure 2

Non-contrast axial STIR-weighted image displaying an intramuscular mass within the medial gastrocnemius which is homogeneous and higher signal intensity compared to the muscle.

MS is a rare benign condition characterized by the association of one or multiple myxomas with FD, which can be monostotic or polyostotic. The syndrome was first described by Henschen in 1926 (1) and later by Mazabraud in 1957 (2) and 1967 (3). Today, approximately 80 cases of MS have been reported in the English literature. According one of the most recent reviews (4), MS is characterized by female prevalence with odds-ratio female/male of 2:1. The average age of diagnosis is 32 years, with FD usually diagnosed 12 years before myxomas. FD is polyostotic in 80%, myxomas are multiple in 70%. Only four cases of malignant transformation of FD in MS are reported in the literature. Conversely, no malignant transformation has been described for myxomas.

MAS was originally described by McCune and Albright in 1936 (5) and 1937 (6) as the association of polyostotic FD, cafè-au-lait skin pigmentation and precocious puberty. It was later recognized that other endocrinopaties, including hyperparathyroidism, growth hormone excess, renal phosphate wasting, Cushing syndrome, polycystic ovary and breast fibroadenomatosis could be found in association with the original triad (7). Malignant transformation of FD into osteosarcoma is the most common and best described malignancy that occurs in MAS (8). The frequency of malignant transformation of FD in MS is higher than that in isolated FD or MAS; we found 4 cases reported by Zoccali et al. (4) in a cohort of 67 MS, and a recent case reported by Crawford et al. (9). A greater tendency for malignant transformation in patients who have concomitant growth-hormone excess has been described (10).

The association of MS and MAS in the same patient is a very rare event, with few reports in the English literature. Only 26 cases have been reported of which only 10 with the typical triad of MAS, such as polyostotic FD, cafè-au-lait spots and endocrine dysfunction (Table 1). All these patients were female with an average age of 18 years at the FD diagnosis and 40 years at the myxoma diagnosis, confirming the later onset of myxomas respect to FD reported by Zoccali et al. (4). Myxomas were multiple in 8 cases. Precocious puberty was the most common endocrine dysfunction, present in 9 cases. Our review shows a higher risk of malignant transformation of FD in patients with MS associated with the classical triad of MAS (2 cases out of 10). Probably the percentage is overestimated because a malignant transformation is more probably object of publication rather than the association of two syndromes that are often misdiagnosed because of the lack of symptoms.

Table 1

Ten cases (except the current case) showed the association of Mazabraud syndrome with the typical triad of McCune-Albright syndrome (polyostotic fibrous dysplasia, cafè-au-lait skin pigmentation and endocrine dysfunction)

Authors	Sex	FD onset	Myxoma onset	Fibrous dysplasia	Myxoma	Endocrine dysfunction	Malignancy
Heinemann and Worth (11)	f	18	82	poly	mul	goiter	no
Laporte (12)	f	12	24	poly	single	p.p. hyperthyroidism	no
Mazabraud (3)	f	infant	n.r.	poly	mul	p.p.	osteo
Roze (13)	f	20	38	poly	mul	p.p.	no
Logel (14)	f	child	41	poly	mul	p.p., dibetes mellitus, goiter	no
Lopez-Ben (15)	f	5	40	poly	mul	p.p.	osteo
Faivre (16)	f	35	35	poly	mul	goiter	no
Tsitouridis (17)	f	5	28	poly	single	p.p.	no
Fertikh (18)	f	59	59	poly	mul	p.p. hyperthyroidism	no
Kitagawa (19)	f	35	30	poly	mul	p.p., goiter, adrenal adenoma	no
Current case	f	5	28	poly	single	p.p., hypothyroidism, polycystic ovary	no

Abbreviations f: female, poly: polyostotic, mul: multiple, p.p.: precocious puberty, osteo: osteosarcoma, n.r.: not reported

Our case report represents probably the 11th case of MS associated with the classical triad of MAS. Our review shows that in MS associated with MAS there is a higher risk of malignant transformation of FD into osteosarcoma, confirming previous reports. Conversely, no malignant transformation has been reported for myxomas in MS or in the association with MAS. We conclude that these patients, especially female, should be scheduled to a close and long-term follow-up.