Article

Hibernoma

Am J Orthop. 2015 June;44(6):284-287

Hibernomas are rare benign soft-tissue tumors containing brown fat. Clinically, they present as slow-growing, painless soft-tissue masses. Physical examination usually reveals a palpable, solitary, soft, and rubbery mass within the subcutaneous fat, which is freely mobile and not attached to deep layers.

Conventional radiography may show a radiolucent mass without internal mineralization or associated osseous abnormalities. Sonographically, hibernomas are well-circumscribed, solid, hyperechoic masses with increased internal vascular flow. Computed tomography shows internal septations and low attenuation values, between those of fat and muscle. Hibernomas are usually hyperintense to skeletal muscle on T1-weighted magnetic resonance imaging (MRI) but slightly hypointense to subcutaneous fat. On T2-weighted images, high signal intensity similar to that of subcutaneous fat is typical. Hibernomas demonstrate intense fluorine-18 fluorodeoxyglucose uptake on positron emission tomography, because, unlike other adipogenic tumors, they contain abundant mitochondria and are highly metabolically active.

Complete surgical excision is the treatment of choice, and is considered curative.

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References

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Hibernomas are rare benign soft-tissue tumors originally described as pseudolipomas by Merkel¹ in 1906. Gery coined the term hibernoma in 1914, after noting the multivacuolated cytoplasm of the tumor cells and its resemblance to normal brown fat found in hibernating animals.²

Hibernomas represent 2% of all benign fat-containing tumors and are composed of brown adipocytes, which are histologically different from the white fat of lipomas. Hibernomas usually develop between ages 20 and 40 years, and their incidence is slightly higher in males.

Diffusely present in human newborns, brown fat usually regresses by 8 weeks of age.³ Residual brown fat deposits may remain in the neck, axilla, shoulder, thorax, thigh, retroperitoneum, and periscapular/interscapular regions.⁴ All these vestigial areas are therefore common locations of hibernomas, with the thigh accounting for up to 30% of cases.⁵ These tumors are seldom identified in the abdomen, popliteal fossa, or even intracranially. Injury to brown fat cells in these locations, either by infection, inflammation, or trauma, is considered a predisposing risk factor for development of hibernomas.⁶

Clinical Presentation

Clinically, hibernomas present as slow-growing, painless soft-tissue masses. Physical examination usually reveals a palpable, solitary, soft, and rubbery mass within the subcutaneous fat, which is freely mobile and not attached to deep layers. These tumors may rarely produce steroid hormones and result in a paraneoplastic syndrome. Even though these tumors are usually large at presentation, compression of adjacent structures seldom occurs.

Histology and Differential Diagnosis

The characteristic hibernoma cell is a multivacuolated adipocyte with centrally located nucleus, indistinct nucleolus, and coarsely granular eosinophilic (or pale) cytoplasm (Figure 1). Cytoplasmic vacuoles are uniform, round, regular, and small and stain for neutral fat. Nuclei are usually small with no or rare atypia. These multivacuolated brown fat–like tumor cells usually stain positive for S100 and CD31, usually stain negative for CD34 and p53, and can show 11q13-21 rearrangements, also seen in lipomas and liposarcomas. Hibernomas have 4 histologic variants: typical (classic), myxoid, lipoma-like, and spindle-cell.⁵ The typical hibernoma, the most common, contains a varying mixture of brown and white fat cells. The myxoid type, second most common, is composed of hibernoma cells floating in a loose acellular myxoid stroma. The lipoma-like variant consists of a few scattered hibernoma cells in a predominance of white fat cells. The spindle-cell variant, the rarest, has features of typical hibernoma and spindle-cell lipoma.⁷

Grossly, hibernomas are well encapsulated, soft, and lobular with prominent feeding vessels.⁸ They typically are tan or brown because of their hypervascularity and abundant mitochondria. Tumor size ranges from 1 to 24 cm (mean, 9.4 cm).⁹ These tumors are well-defined intermuscular/intramuscular, subcutaneous, or retroperitoneal lesions that tend to grow along fascial planes and displace surrounding structures rather than invade them. Delicate branching capillaries are usually seen within the tumor.

Although rare, hibernoma should be included in the differential diagnosis of lipomatous soft-tissue tumors.¹⁰ Imaging findings of hibernoma are not specific; other differential diagnostic considerations for a mass with a signal similar to that of fat or containing large intratumoral vessels include angiolipoma, intramuscular hemangioma with fat, spindle-cell lipoma, pleomorphic lipoma, lipoblastoma, hemangiopericytoma, and hemangioblastoma,^11-15 as well as malignant processes, including lipoma-like well-differentiated liposarcoma and myxoid liposarcoma.¹⁶ Other entities that should be considered include residual brown fat and rhabdomyoma.

Hibernomas are histologically distinguished from well-differentiated liposarcomas by location (liposarcomas tend to be deep), atypia, presence of a prominent “plexiform” capillary pattern, and specific molecular translocations, including t (12;16). Lipomas have lipocytes that are not multivacuolated, and residual brown fat does not present as a distinct mass. Rhabdomyomas are distinguished by an absence of cytoplasmic lipid vacuoles.

Imaging

Conventional radiography may show a radiolucent mass without internal mineralization or associated osseous abnormalities⁴ (Figure 2). Calcifications are notably absent.¹⁷ Sonographically, hibernomas are well-circumscribed, solid, hyperechoic masses with increased internal vascular flow on both grayscale and color Doppler sampling; however their appearance is not pathognomonic (Figure 3). Angiography reveals a hypervascular tumor that may have internal arteriovenous shunting.¹⁸ Hibernomas have a heterogeneous appearance on computed tomography (CT) and magnetic resonance imaging (MRI) because of the variable distribution of brown fat cells, white fat cells, myxoid material, and spindle cells within the individual tumor subtypes.⁵ CT of these tumors shows internal septations and low attenuation values, between those of fat and muscle¹⁹ (Figure 4). Intravenous contrast enhances internal septa, but enhancement varies from none to intense, and from generalized to focal, depending on internal tumor composition.^3,17,20-22

Hibernomas are usually hyperintense to skeletal muscle on T1-weighted MRI but slightly hypointense to subcutaneous fat because of the different gyromagnetic ratios and precessional frequencies of protons in white fat versus those in brown fat¹⁷ (Figure 5). Rarely, lesions are isointense to skeletal muscle on T1-weighted images.²³ On T2-weighted images, high signal intensity similar to that of subcutaneous fat is typical.²⁴ Flow voids can be readily identified.²⁵ Short tau inversion recovery (STIR) MRI shows some areas with signal intensity higher than that of subcutaneous fat, and other areas of fat suppression.⁹ Ritchie and colleagues²¹ reported that hibernomas histologically composed of more than 70% multivacuolated adipocytes tended to have MRI signal characteristics different from those of subcutaneous fat, and those with less than 70% multivacuolated adipocytes tended to have signal characteristics paralleling those of subcutaneous fat. Myxoid hibernomas have higher signal intensity on T2-weighted and STIR MRI because of high water content.^17,21,26,27