Hibernoma: An unusual tumor of adipose tissue Richard E. Hall, DDS, MS, PhD,* Jan Kooning, DMD,** Laurie Hartman, DDS,*** and Angelo DelBalso, DDS, MD,**** Bufalo, N.Y.

STATE UNIVERSITY OF NEW YORK AT BUFFALO, SCHOOL OF DENTAL MEDICINE

A case of a benign tumor of vestigial brown fat (hibernoma) is presented. The circumstances surrounding an associated odontogenic infection are discussed. The case and a review of the literature are presented to clarify a pathologic condition rarely included in the differential diagnosis of head and neck masses. (ORAL SURC ORAL MED ORAL PATHOL 1988;66:706-10)

A hibernoma is a very rare, special type of lipoma thought to arise from the vestiges of fetal brown fat. The term is derived from the microscopic similarity of this tumor to the glandular brown adipose tissue occurring in the organs of hibernation of certain animal species.* A review of the literature deter- mined that the proliferation of fetal brown fat in an adult in association with an odontogenic infec- tion has not been reported..I6 This case is pre- sented to demonstrate the signs and symptoms, diag- nostic workup, and treatment associated with this entity.

CASE REPORT

A 50-year-old black man came to the emergency depart- ment with a complaint of facial pain and left submandib- ular/submental swelling. Five weeks previously, the lower left third molar had been extracted, and two weeks before consultation, a scaling and root planing procedure was performed. The patients medical history was unremarka- ble, but laboratory studies revealed a white blood cell count of 13,000/mm3. The patient was afebrile. Clinical

*Assistant Professor, Oral and Maxillofacial Surgery, State University of New York at Buffalo, School of Dental Medicine, Buffalo, New York. **Formerly Chief Resident, Oral and Maxillofacial Surgery, State University of New York at Buffalo, School of Dental Medicine, Buffalo, New York; now in private practice in Portland, Oregon. ***Assistant Professor, Section on Oral Pathology, Department of Stomatology and Interdisciplinary Sciences, State University of New York at Buffalo, School of Dental Medicine, Buffalo, New York. ****Associate Professor, Section on Oral and Maxillofacial Radiology, Department of Stomatology and Interdisciplinary Sciences, State University of New York at Buffalo, School of Dental Medicine, Buffalo, New York.

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examination showed a patient in no acute distress with a well-circumscribed, indurated, midline submental mass (6 cm X 5 cm) that moved with motion of the tongue. Bilateral anterior cervical lymphadenopathy was noted. Intraorally, there was no purulent exudate, and none could be expressed from the major salivary gland duct orifices. There was no trismus, dysphagia, or dysphonia, and the floor of the mouth was not elevated. The site of the third molar extraction exhibited an appropriate healing response. No other pathosis was noted clinically or on routine dental radiographs.

The preliminary diagnosis of an acute odontogenic infection secondary to the previous dental treatment was made. The patient was placed on 500 mg of penicillin to be taken orally every 6 hours and was scheduled to be seen in the oral surgery clinic 48 hours later. When the patient came to the clinic, the submental mass was significantly enlarged and more edematous. His temperature was 100.6 F, and he had dysphagia and moderate respiratory distress. Intraoral examination revealed that the floor of the mouth was elevated with an area of fluctuance on the left at the junction of the floor with the alveolar process. It was thought that he had a submandibular/sublingual fascial space abscess. While the patient was under local anesthesia, an intraoral approach to the right and left submandibular and sublingual fascial spaces was used. When the incision was made, a copious amount of purulent exudate was expressed from the left submandibular region. Aerobic and anaerobic cultures were taken, and a drain was placed in each site. The penicillin dosage was increased to one gm every 6 hours and was supplemented with 600 mg of clindamycin every 6 hours.

The patients course was followed daily, and by the fourth postoperative day, he had improved greatly although the incision and drainage sites were still very productive. Culture reports at this time disclosed 2+ Neisseria, 3+ cu-hemolytic streptococci, and 1+ coagulase- positive staphylococci on aerobic culture. Anaerobic cul- ture revealed 2+ gram-positive bacilli (diphtheroids), 3+

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Fig. 1. Radiograph (CT scan) of submental mass.

gram-positive cocci (Peptococcus and Peptostreptococ- cus), and 1+ gram-negative bacilli (Bacteroides melanino- genicus) .

On the fifth postoperative day, the drains were removed but a firm, mobile, midline submental mass was still present. At this time, the differential diagnosis included an infected thyroglossal duct cyst, dermoid cyst, and hyper- plastic submental lymph node, as well as a persistent inflammatory response from the infection. Needle aspira- tion of the mass yielded negative findings. The patient was maintained on clindamycin (300 mg three times a day) and scheduled for radiographic evaluation of the soft-tissue mass.

A radioactive iodine uptake study demonstrated normal thyroid lobes in the anterior and posterior projections with no evidence of additional functioning thyroid tissue in the neck. CT scan findings, however, were quite unusual (Fig. 1). The lesion was described by the radiologist as a noncystic, soft-tissue mass occupying the subcutaneous tissues in the midline of the neck at the level of the thyroid cartilage extending upward to the inferior border of the mandible and lying between the geniohyoid muscles supe- riorly and the pretracheal fascia and subcutaneous tissue inferiorly. The mass did not seem to arise from the thyroid gland. No communication with the trachea or gastro- intestinal tract was observed. It displayed a distinct soft- tissue component in association with several fibrous strands extending out into what appeared to be normal, symmetrically surrounding subcutaneous fat. Tissue densi- ties were consistent with muscle and fat. There also appeared to be vascular elements coursing along the long axis of the mass.

The patient was scheduled for surgery so that excision of the mass could be carried out. With the patient under general anesthesia, an extraoral submental incision was made. The mass was readily visualized and noted to be well encapsulated. It easily separated from the surrounding

tissues. A brownish-yellow 5 cm X 5 cm mass was present and had the gross appearance of a lipoma. The operative site was closed in a routine fashion, and the patient recovered uneventfully.

Microscopic examination of stained preparations showed lobules and sheets of neoplastic cells infiltrating native fibrous connective tissue and striated muscle. In some portions of the tumor, the lobular arrangement was definitive, whereas in other areas it was vague (Fig 2, A). Several different cell types were viewed within the tumor mass. Neoplastic cells bearing a morphologic resemblance to brown fat and containing a multiplicity of small vacuoles surrounding a central ovoid nucleus and a some- what larger cell type with larger vacuoles, which focally indented the nucleus, were the predominant cell types (Figs. 2, B and 2, c). This latter type was associated with the presence of numerous delicate engorged capillaries. In addition, cells that resembled mature adipocytes and small cells with eosinophilic, coarsely granular cytoplasm were scattered throughout the neoplasm. A chronic inflammato- ry cell population, diffusely infiltrating the neoplasm or aggregated into focal nests, was viewed throughout the lesion. Myxoid areas were not identified within the tumor. Periodic acid-Schiff staining demonstrated a diastase- resistant glycoprotein material, indicating a high content of lipoproteins (Fig. 3, A and B).

DISCUSSION

A review of the literature disclosed few reports of brown fat tumors in the head and neck region.lm8 The first reported case was by Merke19 in 1905, but the term hibernoma was not applied to the lesion until later. The tumor most commonly occurs in young adults in the regions of the axilla, the abdominal wall, the thigh, the mediastinum, the interscapular area, and the neck, but it has been found in unusual

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Fig. 2. A, Lobular arrangement of hibernoma and lipoblasts is appreciated in this low-power photomicro- graph. A diffuse mild infiltration, as well as nests of chronic inflammatory cells and scattered mature adipocytes, is also viewed. (Hematoxylin and eosin stain. Original magnification, x40.) B, Neoplasm consists of small cells with granular cytoplasm with predominance of hibernoma cells and multivacuolated lipoblasts. Scattered lymphocytes and plasma cells infiltrate the tumor. (Hematoxylin and eosin stain, Original magnification, x250.) C, Cellular detail enhanced at higher magnification. Typical hibernoma cells with ovoid nuclei and large multivacuolated lipoblasts with indented nuclei can be discerned. (Hematoxylin and eosin stain. Original magnification, x400.)

locations.L3 This tumor grows slowly, and while it may reach dimensions of up to 20 cm, most hiberno- mas are between 5 cm and 15 cm in maximum diameter.LS~6 No gender predilection has been dis- cerned. Peak incidence by age is in the fourth decade. In most cases the patient is asymptomatic, although some patients are aware of a painless soft-tissue mass and may report a sense of fullness related to its presence.

The tumor is grossly well encapsulated and easily separable from adjacent tissues. The cut surface reveals a yellow or reddish-brown hue to the mass. Microscopically, the tumor has been reported to be either definitively or vaguely lobulated. AllenI described four cell types viewed in hibernomas and

found that the relative proportions of each may vary from case to case. These include, first, a rounded cell with eosinophilic granular cytoplasm and a central, round, bland nucleus. No lipid vacuoles are viewed within these cells. The second cell type is larger and contains numerous small, round lipid vacuoles. This cell most resembles brown fat and is termed the hibernoma or morular cell. A third cell type is larger still and contains large vacuoles that indent the nucleus, giving it the appearance of a multivacuo- lated lipoblast. Areas prolific in this cell type are also rich in fine capillaries. This rich vascular supply gives the tumor its characteristic tan-brown color* and appearance on CT scan. Last, the fourth cell type is indistinguishable from the typical mature

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Fig. 3 A, Minute magenta PAS-positive granules (arrows) visualized within foamy cells. PAS without diastase digestion. (Original magnification, x400.) B, Retention of PAS reactivity after digestion with diastase demonstrating lipoprotein content of granules (UTTOWS). (Original magnification, x400.)

adipocyte. Mitotic figures and pleomorphism are rare in hibernomas. In morphology, the tumor dis- cussed in this article consisted primarily of lobules and sheets of hibernoma cells or of multivacuolated lipoblast-like cells in a highly vascular millieu, admixed with granular cells and mature adipo- cytes.

Differential diagnosis for hibernoma includes granular cell myoblastoma, liposarcoma, lipoblasto- matosis, sebaceous adenoma, pleomorphic lipoma, and normal accumulations of brown fat. In the present case, granular cell myoblastoma could be ruled out since the myoblastoma does not display

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display a pleomorphic, bizarre, malignant histology. Lipoblastomatosis usually arises as continued post- natal growth of fetal fat and displays a unique compartmentalization of the lesion by prominent fibrous septa. Sebaceous adenomas are generally superficial in location. Normal accumulations of brown fat do not occur as mass lesions and are not encapsulated, as are hibernomas.

The treatment of hibernomas consists of surgical excision. The prognosis is excellent, and metastasis of an unequivocal hibernoma has not yet been reported.

An unusual element in this case is that the . . . _. _ .

710 Hall et al.

mass was present before the infection, but as stated previously, in most instances, this tumor is asymp- tomatic and could have been present for a long time. Another possibility is that the odontogenic infection may have provided the stimulus for the proliferation of the remnant fetal fat cells. The submandibular/ sublingual/submental space infection was probably the result of the preceding third molar extraction or vigorous scaling and root planing. Certainly, the organisms obtained from a culture of the abscess are representative of those seen in the gingival crevice. The hypothesis is that either of these procedures could have seeded organisms into the fascial space and that this produced a chronic, low-grade infec- tion, followed by an acute exacerbation. It is impor- tant to note, however, that there has been no previous report in the literature suggesting that the growth of this tumor can be induced by an infection.

SUMMARY

A case of a rare and unusual tumor of adipose tissue of the head and neck region is reported. Patient management is discussed to demonstrate an approach to the evaluation and treatment of submen- tal/midline cervical masses.

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Enterline HT, Lowry LD, Richman 4~. Does rnaligniii: hibernoma exist? Am J Surg Pathol 1979:3:265-7 1 Makino Y. A clinicopathological study on soft tissue tumor\ of the head and neck. Acta Pathol Jpn I979;29:389-408. Shafer WC, Hine MK. Levy BM. Benign and malignani tumors of the oral cavity. In: Shafer WC, Him MK, Lcv! BM, eds. A textbook of oral pathology. Philadelphia: WB Saunders Co, 1983: 153. Batsakis JG. Tumors of the head and neck, clinical and pathological considerations. Baltimore: Williams & Wilkins. 1979:363. Cox RW. Hibernoma. The lipoma of immature adipose tissue. J Pathol Bact 1954;68:511-8. Merkel H. Uber ein pseudolipom der mamma. (Eigenaitiger fettzellen tumor). Beitr Path Anat Alleg Path 1905;39:152- 7. lnglis K. The so-called interscapular gland and tumors arising therein. J Anat 1927;61:452-66. Gross S, Wood C. Hibernoma. Cancer 1953;6:159-63. Sutherland JC, Callahan WP, Campbell CL. Hibernoma: a tumor of brown fat. Cancer 1952;5:364-8. Seiber WK, Helter EL. Hibernoma: unusual location in popliteal space. Am J Clin Pathol 1952;22:977-80. Kittie CF, Boley JO, Schafer PW. Resection of an intratho- racic hibernoma. J Thorac Surg 1950;19:830-6. Stout AP, Lattes R. Lipomatoses. In: Stout AP, Lattes R, eds. Atlas of tumor pathology. Fascicle I. Tumors of the soft tissues. Washington, DC: Armed Forces Institute of Patholo- gy, 1967155-6. Allen P. Other nonmetastasizing tumors of adipose tissue. In: Allen P, ed. Tumors and proliferations of adipose tissue. New York: Masson Publishing Co. USA, Inc.. 1981:81-8.

Reprinl requests to. Richard E. Hall, D.D.S., Ph.D. State University of New York at Buffalo School of Dental Medicine Department of Oral and Maxillofacial Surgery 1 12 Squire Hall Buffalo, NY 14214