What is hibernoma?
Hibernoma, also known as fetal lipoma or lipoma of embryonic fat, is a rare subtype of benign lipomatous tumour derived from brown fat. It was first reported as a ‘pseudolipoma’ (a ‘peculiar fat tumour’) by Merkel in 1906  and was given its name by Gery in 1914 for its resemblance to brown fat found in hibernating animals .
What causes hibernoma?
The main function of brown adipose tissue is non-shivering thermogenesis (‘burning’ fat), which it accomplishes through fatty-acid dependent uncoupling of adenosine triphosphate (ATP) production in the mitochondria via the uncoupling protein UCP1 . Brown fat deposits are typically found in infants [4,5], and were believed to disappear during adulthood [6,7]. However, several reports indicate the existence of brown fat in adults [8–10], with debate over whether these deposits constitute classical brown fat or are ‘beige’ fat [11,12]. Continuous growth of these vestiges of brown fat lead to the formation of a hibernoma.
Hibernoma is associated with chromosomal rearrangements in the long arm of chromosome 11 (11q13-21), which includes the multiple endocrine neoplasia type 1 (MEN1) region [13–15].
Loss of AIP and MEN1 genes are considered to be essential for hibernoma development . There are reports of hibernoma in patients with multiple endocrine neoplasia type 1 (MEN1) syndrome . However, the cytogenetic pattern seen in hibernoma differs from those seen in MEN1-associated tumours and it is believed they progress via different mechanisms .
Two isolated cases of hibernoma have been reported with high expression of TP53, with the authors speculating that inactivation of the protein may be important for their development .
Who gets hibernoma?
Hibernomas are rare, comprising ~1% of all adipocytic tumours . They occur in the third to fourth decade of life (the mean age of onset is 38) and they are uncommon in children. They are more common in men .
What are the clinical features of hibernomas?
Hibernoma presents as a progressive, slow-growing, painless subcutaneous mass . The most common locations for hibernoma include the thigh, shoulder, back, neck, chest, arm, and retroperitoneum . Other locations include the breast, [21,22], larynx , pleura , pelvis , vulva , and scrotum [27,28]. Approximately 10% of hibernomas are intramuscular .
What are the complications of hibernomas?
Complications of hibernoma are related to the rapid tumour growth and infiltration of neighbouring structures. Pressure on nerves can result in neuropathic pain.
- A 36-year-old patient presented with carpal tunnel syndrome due to a hibernoma in the wrist .
- A 55-year-old man had thoracic outlet syndrome from intrathoracic extension of an axillary hibernoma .
- Sciatic neuropathy has been reported in a patient with a giant (27 cm) hibernoma of the thigh .
- An intraosseous hibernoma is typically an incidental finding after a patient presents with back pain (vertebral hibernoma) or knee pain (femoral hibernoma) [32,33].
- Mediastinal hibernoma was reported as the cause of chronic cough in a 33-year-old female .
How is hibernoma diagnosed?
Radiographic imaging is used when considering a diagnosis of hibernoma [19,35].
- Computed tomography (CT) shows well-circumscribed mass with attenuation intermediate between subcutaneous fat and skeletal muscle.
- Magnetic resonance imaging (MRI) shows well-circumscribed mass slightly hypointense to fat on T1- and T2- weighted images.
- 18F-fluorodeoxyglucose (FDG) PET/CT shows high uptake due to high metabolic activity of brown adipocytes, with change in avidity on follow-up. Uptake values are often higher compared to liposarcoma.
The diagnosis of hibernoma is confirmed by histopathology on biopsy or excision.
- Hibernoma is a well-circumscribed, encapsulated, soft/rubbery mass that varies from yellow to red-brown when cut.
- Light microscopy shows typical hibernoma cells: multivacuolated brown fat cells with eosinophilic, slightly granular cytoplasm, a small central nucleus, and a single prominent nucleolus with evenly dispersed chromatin. These cells express high levels of cytoplasmic UCP1 .
There are four hibernoma variants .
Typical lobular hibernoma
The lobular hibernoma is the most common variant (82%), which appears as a mixture of pale cells, hibernoma cells, and eosinophilic cells.
- The pale cell subtype has mostly pale, multivacuolated cells mixed with univacuolated adipocytes. This type is more common on the thigh and is most commonly intramuscular.
- The mixed cell subtype has equal numbers of pale and eosinophilic multivacuolated cells. This type is more common on the trunk.
- The eosinophilic subtype has a predominance of eosinophilic multivacuolated cells. This is more common on the upper extremities.
A myxoid hibernoma contains a loose basophilic matrix and foamy histiocytes. It is more common in men and in the head and neck region (including the scalp and shoulder).
Lipoma-like hibernoma has univacuolated white adipocytes with scattered hibernoma cells. It arises most commonly in the thigh.
Spindle cell hibernoma
Spindle cell hibernoma is the least common variant, accounting for 2% of hibernomas. It has features of spindle cell lipoma and hibernoma. Histology shows hibernoma cells, CD34+ spindle cells, thick collagen bundles, mast cells, myxoid stroma, and mature adipocytes. It is found on the scalp and posterior neck.
What is the differential diagnosis for hibernoma?
The differential diagnosis for hibernoma includes benign and malignant tumours [19,35].
Benign soft tissue tumours
Benign soft tissue tumours that could be interpreted as hibernoma include:
- Lipoma — a homogenous mass with no contrast enhancement on imaging
- Haemangioma — calcifications, T2-hyperintensity, and internal vasculature forming a lump under the skin
- Angiolipoma — T2-hyperintensity and internal vasculature forming a lump under the skin.
Malignant soft tissue tumours
Malignant soft tissue tumours that could be interpreted as hibernoma include:
- Well-differentiated liposarcoma — presents with thickened septa, decreased vascularity, and areas of T2-hyperintensity
- Myxoid liposarcoma — a malignant tumour with t(12;16) translocation and characteristic branching vascularisation
- Rhabdomyosarcoma — a malignant and aggressive cancer associated with bone destruction
- Lymphoma — isoattenuated (weakened to the same degree as background tissue) CT pattern.
What is the treatment for hibernoma?
The definitive treatment for hibernoma is complete surgical resection . Since hibernomas are almost never malignant , no treatment is required if the patient is asymptomatic.
What is the outcome for hibernoma?
Hibernomas are typically benign, and recurrence is rare after complete excision .