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Hibernoma
Brown Fat Tumor

Hibernoma is an infrequent type of benign soft tissue tumor composed of brown adipocytes that may present in a similar manner to liposarcoma, despite the fact that it has no malignant or metastatic potential.

Images

WIKIDATA, CC BY-SA 3.0
WIKIDATA, CC BY-SA 3.0

Presentation

Hibernomas are usually located in the interscapular region, but may also be encountered in the cervical, thigh or axillary areas. Intra thoracic, intramuscular, abdominal and retroperitoneal lesions have also been described, as well as exceptional locations such as the uterus, breast, popliteal area, cranium, pericardium [1] or mediastinum. Lesions may be multiple or bilateral, are painless, but may cause symptoms related to their mass effect [2] or to their secretory activity, as they are known to sometimes produce steroid hormones. They are usually described as slow growing (but fast growth is also possible) and firm or rubbery and are mostly encountered in adults in their thirties, and differential diagnosis with lipomas and liposarcomas must be taken into consideration, given that clinical presentations of the three pathological entities often overlap [3] [4]. Once the diagnosis of hibernoma is established, the physician does not need to be concerned about malignant transformation or metastasis [5]. However, recurrence is possible, although very rare.

Entire Body System

  • Swelling

    A 68-year-old man with no notable medical history presented with left cervical swelling that had been slowly increasing in size for 3 years. The patient was afebrile. [nejm.org]

    Clinical History This patient noticed a swelling on the medial aspect of left knee after blunt trauma. On examination, a soft lobulated painless swelling was noted on the medial aspect of left knee. [eurorad.org]

    An unusual case of congenital benign hibernoma, in the submandibular region, in a 2.5 years old girl, is reported, who presented with a progressively increasing neck swelling. A CAT scan of neck revealed a superficial and deep low density mass. [ncbi.nlm.nih.gov]

  • Lymphadenopathy

    There was no surrounding lymphadenopathy, and there were no signs of compression. Computed tomography revealed that the mass was heterogeneous and measured 27 cm by 16 cm by 17 cm (Panel B). [nejm.org]

    No pathologic cervical lymphadenopathy was seen. Download figure Open in new tab Download powerpoint Fig. 1. [ajnr.org]

    No pathological lymphadenopathy was noted. [academic.oup.com]

    There was no associated inguinal lymphadenopathy. After preoperative evaluation, the lesion was excised with the clinical diagnosis of a lipoma and the patient remained free of symptoms following the excision. [ijpmonline.org]

    No cervical lymphadenopathy or other well-defined aerodigestive masses were identified ( Fig. 1 ). Fig. 1 Coronal CT scan of the neck with contrast showing a right sided level Va well circumscribed mass in the supraclavicular fossa. [entokey.com]

  • Surgical Procedure

    Detailed preoperative imaging allowed to plan a single surgical procedure in which an extrathoracic axillary approach was combined with intrathoracic video-assisted thoracic surgery. [rug.nl]

    The patient underwent surgical resection of the mass and neurolysis of the nerves in the vicinity. Following the surgical procedure, the patient had improvement in the pain and paresthesia that he was suffering from. [neurologyindia.com]

    All variants have benign features.[8] Histopathological variant of a hibernoma does not affect the surgical procedure. Complete surgical resection is the curative treatment for these tumors. [tgkdc.dergisi.org]

    The final diagnosis is made after a fine needle aspiration procedure or after the surgical excision [6]. [bmcearnosethroatdisord.biomedcentral.com]

    Marginal excision is a sufficient and curative surgical procedure. However, preoperative biopsy is recommended because this tumor is clinically indistinguishable from malignant lesions. [healio.com]

  • Short Stature

    Untreated children may exhibit seizures, spasticity, short stature and intellectual disability. Most affected infants are now identified at birth through newborn screening. [rarediseases.org]

    Short stature in two patients, mongoloid eyes in one patient, hallux valgus in one patient, microcephaly in five patients, facial dysmorphism in four patients, and bony abnormalities in one patient (scoliosis) were the common associations [Figure 3]. [pediatricneurosciences.com]

Gastrointestinal

  • Diarrhea

    Emesis, diarrhea, anorexia, and abdominal pain have been described in patients with mesenteric or retroperitoneal lipoblastomas (, 79 ). The natural history of lipoblastomas is to evolve into mature lipomas. [pubs.rsna.org]

Skin

  • Erythema

    No overlying warmth or erythema was noted, and no lymphadenopathy was found. The patient had no neurological deficit. CT scan demonstrated a well defined large mass in the back of the neck (Figure 2). [ispub.com]

    No overlying warmth or erythema was noted, and no lymphadenopathy was found. The patient had no neurological deficit but reported experiencing a painful sensation along the dorsum of his lower left arm. [mdmag.com]

    No overlying warmth or erythema was noted. The neurovascular status was intact, and no lymphadenopathy was found. [journals.lww.com]

    No erythema or overlying skin changes were appreciated. His abdominal exam was normal. A non-contrast Computed Tomography (CT) scan revealed a left upper quadrant mass in the area correlating with the physical exam. [ncbi.nlm.nih.gov]

  • Blister

    HSV-1 is exceedingly common, typically causing oral lesions (i.e., fever blisters), and is most commonly associated with HSE in adult patients (95%). [casemed.case.edu]

    It is marked by small fluid-filled blisters appearing on the lips or genitals often accompanied by fever. Herpes simplex encephalitis rarely occurs in conjunction with oral or genital lesions. [rarediseases.org]

    Both HSV type 1 — associated with cold sores and fever blisters around your mouth — and HSV type 2 — associated with genital herpes — can cause encephalitis. [mayoclinic.org]

    HSV-1 causes oral lesions (so-called fever blisters); these are common and may respond to antiviral medications, though they spontaneously remit in most cases. HSV-2 causes genital lesions. [emedicine.medscape.com]

    […] in the trigeminal ganglia of 85–90% of people at unselected necropsy.8 Latent HSV-1 periodically is reactivated, either spontaneously or following various triggering events such as trauma, sunlight, immunosuppression, and x-ray irradiation, to cause blisters [jnnp.bmj.com]

Face, Head & Neck

  • Neck Mass

    The physical examination was unremarkable except for large swelling of the left side of the neck (Panel A), which caused limited mobility of the neck. The neck mass was firm, mobile, and nontender. [nejm.org]

    A CT of the neck with contrast and demonstrated a round, well-defined, low-density mass measuring 4.5 × 3.0 cm in the right neck. [entokey.com]

    We report a case of a patient with an asymptomatic neck mass that initially presented for evaluation of hoarseness. Imaging and complete surgical excision of the mass were performed and revealed hibernoma. [ncbi.nlm.nih.gov]

Workup

The first step in diagnosing a hibernoma after the clinical suspicion is raised is to perform imaging procedures. A radiography of the affected region will show no bone erosion or calcification. Echography describes hyperechoic tissue, while Doppler imaging highlights the presence of enlarged vessels. Computer tomography scanning describes well vascularized, well circumscribed, heterogeneous, diffusely septated lesions with a possibly incomplete peripheral capsule. Hibernoma signal intensity in magnetic resonance imaging is variable [6], usually high, but slightly inferior to that of subcutaneous tissue [5]. The degree of homogeneity is variable [7]. This method shows diffuse gadolinium enhancement of an otherwise isointense or mildly hypointense tissue formation. Myxoid hibernomas, being richer in water have higher signal intensity on magnetic resonance imaging scans [8]. Fluorodeoxyglucose positron emission tomography shows important radiotracer capture [9] due to the fact that hibernomas contain numerous mitochondria and are metabolically very active. Scintigraphy also reveals high radiotracer uptake with 99mTc-tetrofosmin, 123I-meta-iodobenzylguanidine and 99mTc-methoxyisobutylisonitrile administration. If an angiography is considered to be necessary, it may reveal, besides intense vascularization, the presence of internal arterio-venous shunting [10] which is important information prior to excision.

If clinical and imaging differential diagnosis cannot exclude a malignancy, excision is imperative. Analysis of the surgical specimen reveals a light brown to gray mass of tissue surrounded by a thin capsule [11]. Microscopic examination reveals high -number of mature, multivacuolated or uni vacuolar adipocytes intersecting with brown fat, intense vascularization, and few adipocyte atypia. Tumors may, however, be more or less well differentiated. Immunohistochemical analysis shows a positive cluster of differentiation (CD) 68 and negative CD 34.

In cases where cytogenic analysis reveals the presence of a 11q13 translocation, liposarcoma is improbable [12]. Rearrangements in the 11q13-21 region can be detected using metaphase fluorescent in situ hybridization.

Treatment

The literature provides only a few treatment details regarding this variant. [ncbi.nlm.nih.gov]

[…] and prognosis The treatment of hibernomas consists of complete surgical excision. [radiopaedia.org]

Complete surgical excision is the treatment of choice, and is considered curative. Cite this Apa Standard Harvard Vancouver BIBTEX RIS Klevos, G., Jose, J., Pretell, J. A. A., & Conway, S. A. (2015). Hibernoma. [miami.pure.elsevier.com]

Prognosis

This review discusses the clinical features, radiologic and histopathologic characteristics, ancillary studies, suggested pathogenesis, differential diagnosis, and treatment of and prognosis for these uncommon lesions. [ncbi.nlm.nih.gov]

There are multivacuolated cells and a cell with a central nucleus IMMUNOHISTOCHEMISTRY Positive • S100 • Oil red O • Sudan black Negative • CD 34 • P53 PROGNOSIS BIOLOGICAL BEHAVIOR • Hibernoma is benign and does not metastasize or convert to a malignancy [tumorsurgery.org]

[…] to help differentiate from malignancy The radiological report should include a description of the following: form, location and size tumor margins and transition zone relations to the muscular fascia relation to neurovascular structures Treatment and prognosis [radiopaedia.org]

[…] typically prominent; cytoplasm multivacuolated, oval, eosinophilic, granular LM DDx reaction to silicone implant Gross lobulated lesion, light-brown, usually extremities Site soft tissue - adipocytic lesions Clinical history young adults Prevalence uncommon Prognosis [librepathology.org]

Etiology

TERMINOLOGY Synonyms Fetal lipoma, lipoma of embryonic fat Definitions Benign tumor most frequently occurring in younger adults, with differentiation toward brown fat Tumor has characteristic cytogenetic aberrations, mainly involving 11q13-21 ETIOLOGY [basicmedicalkey.com]

He subsequently underwent dual time point FDG PET/CT imaging which revealed a significant rise in standard uptake value (SUV) within the lesion over time, favoring a malignant etiology. [ncbi.nlm.nih.gov]

Etiology The etiology involves clinically significant persistence of remnants of or accumulation of brown fat in regions where small amounts of brown fat normally persist as vestigial remnants. [dermatologyadvisor.com]

Epidemiology

[…] brown fat Tumor has characteristic cytogenetic aberrations, mainly involving 11q13-21 ETIOLOGY/PATHOGENESIS Developmental Anomaly Etiology unknown Many occur at sites of normal brown fat in fetuses and newborns Genetic changes in some CLINICAL ISSUES Epidemiology [basicmedicalkey.com]

Usually asymptomatic.[3] Epidemiology: Young adults. Gross Well-circumscribed. Lobulated and light-brown on sectioning. [librepathology.org]

Definition / general Lipoma containing prominent brown adipocytes that resembles normal brown fat as classic lipoma resembles white fat Epidemiology Rare (2% of lipomas) Mean age 26 - 38 years; 60% male Sites Most commonly in axilla, back, mediastinum [pathologyoutlines.com]

Neurology and Neurosurgery Czech and Slovak Ophthalmology Czech and Slovak Psychiatry Czech Geriatric Review Czech Gynaecology Czech Rheumatology Czech Dental Journal Czech Urology Czech-Slovak Dermatology Czecho-Slovak Pathology Czech-Slovak Pediatrics Epidemiology [prolekare.cz]

Epidemiology[edit] The tumor is rare, affecting adults in the 4th decade most commonly. Patients are usually younger than those who present with a lipoma. There is a slight male predominance. [en.wikipedia.org]

Pathophysiology

Pathophysiology Pathophysiology involves cytogenic abnormalities of chromosomes 11q13-21 and 10q22, which can cause a deletion in the MEN-1 gene. Structural rearrangements involving the long arm of chromosome 11 are characteristic. [dermatologyadvisor.com]

We describe the case of an intramuscular hibernoma and illustrate the pathophysiology of the observed hibernoma in relation to recent insights on physiological BAT. [ncbi.nlm.nih.gov]

Prevention

These tumors are by definition benign entities but, given their propensity for growth over time, they require complete extirpation to prevent recurrence. [ncbi.nlm.nih.gov]

Prevention Can you prevent a hibernoma? Hibernomas are rare. There isn’t any way to prevent the gene change that causes them. Outlook / Prognosis What is the outlook for someone with a hibernoma? Surgery to remove a hibernoma cures the condition. [my.clevelandclinic.org]

References

  1. Ucak A, Inan K, Onan B, et al. Resection of intrapericardial hibernoma associated with constrictive pericarditis. Interact Cardiovasc Thorac Surg. 2009;9(4):717-719.
  2. Furlong M, Fanburg-Smith J, Miettinem M. The morphologic spectrum of hibernoma: a clinicopathologic study of 170 cases. Am J Surg Pathol. 2001;25(6):809–814.
  3. Lee J, Gupta A, Saifuddin A, et al. Hibernoma: MRI features in eight consecutive cases. Clin Radiol. 2006;61(12):1029–1034.
  4. Dursun M, Agayev A, Bakir B, et al. CT and MR characteristics of hibernoma: six cases. Clin Imaging. 2008;32(1):42–47.
  5. Murphey M, Carroll J, Flemming D, et al. From the archives of the AFIP: benign musculoskeletal lipomatous lesions. Radiographics. 2004;24(5):1433-1466.
  6. Cypess A, Lehman S, Williams G, et al. Identification and Importance of Brown Adipose Tissue in Adult Humans. N Engl J Med. 2009;360:1509–1517.
  7. Drevelegas A, Pilavaki M, Chourmouzi D. Lipomatous tumors of soft tissue: MR appearance with histological correlation. Eur J Radiol. 2004;50(3):257–267.
  8. Ritchie D, Aniq H, Davies A, et al. Hibernoma—correlation of histopathology and magnetic-resonance-imaging features in 10 cases. Skeletal Radiol. 2006;35(8):579-589.
  9. Chatterton B, Mensforth D, Coventry B, et al. Hibernoma: intense upstake seen on Tc-99m tetrofosmin and FDG positron emission tomographic scanning. Clin Nucl Med. 2002;27(5):369–370.
  10. Angervall L, Nilsson L, Stener B. Microangiographic and histological studies in 2 cases of hibernoma. Cancer. 1964;17:685-692.
  11. Lele M, Chundru S, Chaljub G, et al. Hibernoma. Arch Pathol Lab Med. 2002;126(8):975-978.
  12. Mrózek K, Karakousis C, Bloomfield C. Band 11q13 is nonrandomly rearranged in hibernomas. Gen Chrom Cancer. 1994;9(2):145-147.
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