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A 33-year-old man presents to a surgical clinic in Saudi Arabia, following referral from another facility due to concerns about a painless swelling in his upper right thigh. He explains that he initially noticed the swelling about a year earlier, but it had remained stable in size until about 1 month ago, when it began increasing in size.

His medical history includes multiple sclerosis, for which he is receiving treatment, but he has no history of any other masses elsewhere in his body and is not suffering from lower limb weakness or any constitutional symptoms; he also has no past surgical history.

At the referring facility, the patient had undergone ultrasound-guided Tru-cut biopsy, which identified an atypical lipomatous tumor that raised concerns of potential liposarcoma. Given the risk of malignancy, the patient was referred to the surgical clinic for further workup and management.

Clinicians perform a thorough physical examination when the patient presents to their clinic. They observe a 10×13 cm soft, non-tender, non-fluctuating mass with a smooth surface and defined edges on the anterior midline of his upper right thigh. The neurovascular bundle of whole right lower limb is intact; there is no evidence of local inflammation, and skin coloration is normal.

Clinicians perform magnetic resonance imaging (MRI) of the right lower limb, which reveals a 10 × 13 × 14 cm oval mass with a bright signal in T1, and to a lesser extent T2, located between the pectineus, adductor brevis, and obturator externus muscles medially and between the sartorius, iliopsoas, and rectus femoris muscles laterally with the femoral neurovascular bundle running lateral to the lesion.

The findings are suggestive of a lipomatous lesion, such as atypical lipoma, and thus potential liposarcoma cannot be ruled out.

The team then performs an ultrasound-guided biopsy. Based on a histopathology analysis finding of atypical lipomatous cells with hibernomatous features, the team arrives at a provisional diagnosis of benign hibernoma, and proceeds with a wide local surgical excision, with a drain left in place on a negative pres­sure.

The final histopathology report identifies a fatty lobulated tumor on cross section composed of a mix of univacuolated and multivacuolated adipocytes alongside spindly fibroblastic cells with negative margins. Diagnosis of a benign hibernoma is confirmed.

The patient is discharged home on the third day after the operation, and he attends regular follow-up visits for the next 3 years with no evidence of local recurrence or any ­other similar lesions.

Discussion

Clinicians presenting this of a patient with a hibernoma note that this rare subtype of benign lipomatous tumor presents a diagnostic challenge in that it is radiologically indistinguishable from certain malignant tumors.

While lipomatous lesions account for 20% of all soft tissue tumors, hibernomas represent just 1% of all types of both benign and malignant lesions; fewer than 250 cases have been reported since 2016. Accurate diagnosis -- and hence appropriate preoperative care -- is based on differentiation of hibernomas from atypical lipomatous lesions and liposarcomas, which can present challenges even in terms of histopathology.

This case -- like up to 15% of all hibernomas -- appeared on a computed tomography scan as a well-circumscribed, hyper-dense lesion in the sub­cutaneous tissue; these are often deeply embedded intramuscularly. Thus, the case authors note that investigation of any soft tissue mass larger than 5 cm or located deep to the fascia should include MRI.

Because of their benign origin and slow growth, hibernomas tend to be asymptomatic, except when they become large enough to compress nearby structures. As in this patient, hibernomas are most commonly en­countered in the thigh during adulthood, although other reported cases have involved the neck, axilla, shoulder, thorax, breast, stomach, retroperitoneum, and bone.

Regarding the radiological findings, a plain MRI of a hibernoma would be isointense or relatively hypointense to the surrounding subcutaneous fat and relatively hyperintense in comparison to the surrounding muscles on both T1 and T2. Use of contrast typically reveals a diffused heterogeneous enhancement, secondary to the increased vascularity. However, there is no single radiological pathognomonic sign of hibernomas.

Hibernomas are often identified incidentally in patients with other indications for imaging; positron emission tomography scans are particularly sensitive to hibernomas because their brown fat tissue content gives them increased metabolic activity. Hibernomas show uptake of 8F-fluorodeoxyglucose, similar to or higher than that of a liposarcoma, add to the complexity and importance of obtaining an accurate preoperative diagnosis.

The case authors caution that a hibernoma might even be mistaken as a metastatic lesion in patients with a history of malignancy, or in some cases as a primary malignancy.

A of the accuracy of magnetic resonance imaging (MRI) in distinguishing between benign and malignant lipomatous tumors found that of MRI findings of size, localization, septa, nodules, and signal homogeneity, only septa and signal homogeneity were significantly associated with malignancy (P<0.05). The authors conclude that MRI could be helpful in distinguishing lipomatous tumors, allowing biopsy to be avoided in some cases (negative predictive value=100%).

Given that imaging rarely offers a definitive diagnosis, clinicians generally perform an incisional or a fine needle aspiration (FNA) biopsy, so that diagnosis can be confirmed through histopathology and unplanned excision of lipomatous malignant lesions can be avoided.

Although the question of malignancy may be resolved with an incisional biopsy, hibernomas have a rich blood supply and can bleed heavily, which makes FNA a safer option if a hibernoma is suspected.

Regardless of the type of biopsy used, the biopsy tract must be marked to be included during the excision; this ensures complete oncological resection in case of malignancy. On the other hand, given the variable histopathological characteristics of hibernomas, obtaining a small specimen from FNA would make it difficult to determine if it is a hibernoma or another lipomatous lesion.

Histologically, typical hibernoma cells consist of a solid pattern of large multivacuolated brown fat cells, single small eccentric nuclei, and a large amount of granular cytoplasm. These brown fat cells have been divided into four histological subtypes based on the degree of cytoplasmic eosinophilia, the presence of myxoid stroma, and spindle cell configuration.

The prevalence of hibernoma subcategories varies depending on multiple demographic factors. About 82% are categorized as typical hibernomas, while the second most common subtype, the myxoid variant, accounts for 9% of all cases; it is "so-called" due to the presence of myxoid stroma separating the multivacuolated cells.

The lipoma-like subtype, characterized by scattered hibernoma cells within univacuolated mature adipocytes, accounts for 7% of all cases. These latter two subtypes are often mistaken for liposarcoma. Finally, the spindle-cell variant ac­counts for 2% of all cases, and is regarded as a combination of the features of hibernoma and spindle-cell lipoma. However, since the clinical prognosis does not vary among these histologic subtypes, most surgical pathologists do not subtype hibernoma cases.

Using a wide local excision with negative margins helps differentiate the hibernoma from other lipomatous lesions, allowing diagnostic confidence and avoiding any future recurrence.

The case authors also cite a 2018 of 64 cases diagnosed as hibernoma mimicking typical lipomatous tumor between 2000 and 2017 in which all except four cases did not develop any recurrence or metastatic spread, and recurrences were a result of positive resection margins rather than an actual recurrence.

Conclusion

The case authors conclude that the dilemma regarding the diagnosis of a hibernoma can be resolved by performing a biopsy, with the next step -- or in cases where biopsy is not a viable option -- being wide local excision with negative mar­gins, including the site of biopsy when performed; this is recommended to prevent any future recurrence.

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