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McCune-Albright Syndrome: Differential Diagnoses & Workup
Updated: Dec 18, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
In a typical case, the diagnosis of McCune-Albright syndrome (MAS) usually is not in doubt. However, in atypical cases, the combination of cutaneous pigmentation, bony lesions, and soft-tissue masses may suggest systemic mastocytosis and neurofibromatosis.
Particularly when associated with a great degree of deformity, other important diagnostic considerations include the following:
- Ossifying fibromas of the bone
- Paget disease of bone - This typically has onset in adulthood, unlike MAS, which more typically begins in childhood.
- Proteus syndrome
- Stein-Leventhal syndrome
- Thyrotoxicosis
- Various congenital syndromes associated with hydrocephalus
If multiple bony fractures and deformity predominate, MAS may be mistaken for a milder form of osteogenesis imperfecta.
If precocious puberty predominates, the differential diagnosis becomes even wider and includes congenital adrenal hyperplasia.
Vaginal bleeding in neonates and infants is one of the typical presentations of MAS. In this setting, rhabdomyosarcoma of the vaginal tract is an important differential. This typically appears as a "bunch of grapes" (hence the name sarcoma botryoides).
Workup
Laboratory Studies
- In patients with sexual precocity, baseline gonadotropin (ie, luteinizing hormone and follicle-stimulating hormone) and gonadotropin levels stimulated by gonadotropin-releasing hormone (GnRH) are below normal limits.
- In females who are affected, estrogen levels are elevated above the age-adjusted expected level. Similarly, males who are affected have elevated serum-free and total testosterone levels. These findings can be of a transitory nature, particularly in female patients.
- Androgen levels in female patients remain within normal limits.
- Blood and urinary chemistries show evidence of excessive bone turnover and elevated indicators for bone formation and resorption (eg, urinary N-telopeptide, pyridinolines, deoxypyridinolines). Serum alkaline phosphatase levels (total and bone-specific fractions), osteocalcin, and serum adenosine 3,'5'-cyclic monophosphate (cAMP)12 levels are elevated.
- Urinary excretion of hydroxyproline, N-telopeptides, pyridinium X-links, and cAMP is elevated. Depending on the extent of coexisting osteomalacia, serum calcium may be normal or slightly reduced. Typically, the rickets/osteomalacia associated with McCune-Albright syndrome is hypophosphatemic and hyperphosphaturic.
Imaging Studies
- In McCune-Albright syndrome (MAS), plain bone radiographs typically show multiple patchy areas of bony lysis (see image below) and sclerosis. The findings are consistent with bone dystrophy (ie, areas of hypertrophy, geodes bounded by fine sclerotic rims).
Fibrous dysplasia of a long bone characterized by focal bony expansion, patchy areas of sclerosis, and bony cyst formation.
- Mixed radiopaque and radiolucent areas with thin or hypertrophic cortices are present.
- Virtually any bone in the body may be affected. Monostotic fibrous dysplasia (MFD) is more common than the polyostotic form. MFD is not associated with other findings that are typical of MAS.
- Commonly affected bones include the femur, tibia, ribs, and facial bones. Involvement of the small bones of the hands and feet account for 50% of cases.
- Long-bone lesions are more frequent in the metaphyseal and diaphyseal regions. The individual lesions may be trabeculated, with thin cortices and ground-glass appearance.
- Formal bone-age estimations may be higher in patients with sexual precocity.
- Ultrasonography may be a useful diagnostic adjunct to evaluate patients with historical or examination evidence of soft-tissue swelling. Myxomas in the context of MS can be seen as sharply defined hypoechoic masses with a few central, fluid-filled cavities. However, an abdominal ultrasonogram that reveals multiple hypoechoic cystic lesions within the uterus and upper vaginal vault is characteristic of embryonal rhabdomyosarcoma.
- Computed tomography (CT) scans and magnetic resonance imaging (MRI) also show hypoechoic areas in the setting of myxomas. These are hypointense or isointense on T1-weighted imaging with gadolinium enhancement or on T2-weighted imaging.
- Reports suggest that the MRI may be useful to define the extent of bony disease, similar to bone scanning.13
- Radionuclide bone scans (technetium-99m [99m Tc]–labeled methylene diphosphonate scans) in patients with polyostotic fibrous dysplasia appear as areas of increased activity. This is helpful in defining the extent of disease activity after the diagnosis is made. The poor specificity of increased patchy bone activity on bone scans precludes use for screening/exact diagnosis.
Procedures
- Bone biopsy may be necessary to rule out malignancy in a patient with a rapidly expanding lesion. It can be used clinically to aid in the diagnosis of osteomalacia and has been used for research purposes in an academic setting.
- Similarly, a rapidly expanding myxoma may require a muscle or soft-tissue biopsy.
- Enlarging thyroid nodules or hypofunctioning solitary thyroid nodules warrant a fine-needle aspiration biopsy.
Histologic Findings
The bone affected by polyostotic fibrous dysplasia has areas of fibrous metaplasia within flat and tubular bones. The basic anomaly in fibrous dysplasia lesions is a progressively expanding fibrous lesion of bone-forming mesenchyme. The lesions typically expand concentrically from the medullary cavity outwards (ie, towards the cortex). The bony lesions are well defined, although invariably, they are not encapsulated. The lesions are rich in spindle-shaped fibroblasts, with a swirled appearance within the marrow space and erratically arranged "tongues" of woven bone. Islands of cartilaginous tissue also may be interspersed within the lesions. Some parts of the affected bones may have cystic lesions lined by multinucleated giant cells, akin to osteitis fibrosa cystica (of severe hyperparathyroidism) but with a paucity of osteoblasts.
More on McCune-Albright Syndrome |
| Overview: McCune-Albright Syndrome |
 Differential Diagnoses & Workup: McCune-Albright Syndrome |
| Treatment & Medication: McCune-Albright Syndrome |
| Follow-up: McCune-Albright Syndrome |
| Multimedia: McCune-Albright Syndrome |
| References |
| Further Reading |
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Keywords
McCune-Albright syndrome, hyperthyroidism, gynecomastia, thyroid gland, hyperparathyroidism, acromegaly, dysplasia, endocrine glands, Cushing syndrome, Cushing's syndrome, precocious puberty, fibrous dysplasia, endocrine gland, thyroid glands, cafe au lait spots, café au lait spots, endocrinopathy, McCune Albright syndrome, hyperprolactinemia, polyostotic fibrous dysplasia, Mazabraud syndrome
