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\begin{document}

\title{Surgical management of recurred hibernoma of the neck}



\author[1]{Young Chul Kim}%
\author[1]{Jiwon Koh}%
\author[1]{Seong Keun Kwon}%
\affil[1]{Seoul National University Hospital}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\selectlanguage{english}
\begin{abstract}
Cervical hibernoma is a rare, benign lipogenic tumor. Surgical removal
of cervical hibernoma is needed when it causes symptoms such as dyspnea
or dysphagia due to its mass effect, or when malignancy cannot be
excluded. During surgery, en bloc resection is crucial to prevent
hemorrhage and recurrence.%
\end{abstract}%



\sloppy


\textbf{Surgical management of recurred hibernoma of the neck}

Running title: Management of recurred hibernoma of the neck

Young Chul Kim, MD\textsuperscript{1}, Jiwon Koh, MD,
PhD\textsuperscript{3}, Seong Keun Kwon, MD, PhD\textsuperscript{1,2}

\textsuperscript{1}Department of Otorhinolaryngology-Head and Neck
Surgery, Seoul National University Hospital, Seoul National University
College of medicine, Seoul, Republic of Korea

\textsuperscript{2}Department of Otorhinolaryngology-Head and Neck
Surgery, Seoul National University College of medicine, Seoul, Republic
of Korea

\textsuperscript{3}Department of Pathology, Seoul National University
Hospital, Seoul National University College of medicine, Seoul, Republic
of Korea

Co-author

Jiwon Koh

Professor

Department of Pathology, Seoul National University Hospital

Address: 101, Daehak-ro, Jongno-gu, Seoul, 03080, The Republic of Korea

Tel: +82-2-2072-0028; +82-10-7284-5447

E-mail: jwskoh@snu.ac.kr

Corresponding author

Seong Keun Kwon, M.D., Ph.D.

Professor

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National
University Hospital

Address: 101, Daehak-ro, Jongno-gu, Seoul, 03080, The Republic of Korea

Tel: +82-2-2072-2286; fax: +82-2-745-2387

E-mail: otolarynx@snuh.org

Keywords: hibernoma, lipoma, brown fat, lipogenic tumor, cervical mass

Key Clinical Message: This case review shows a successful removal of
recurred hibernoma in neck. En bloc resection is important to prevent
recurrence and bleeding.

\textbf{Introduction}

Hibernoma is a rare, benign lipogenic tumor that mostly occurs in thigh.
It occurs even more rarely in head and neck area, and there are only few
case reports of head and neck hibernoma. This article is a retrospective
review of a successful removal of recurred hibernoma in neck.

While managing patients with lipogenic tumor, clinical suspicion should
be primarily needed and histological, imaging work-ups should be
followed to exclude lipomatous malignancy. Surgical removal of cervical
hibernoma is needed when it causes symptoms such as dyspnea or dysphagia
due to its mass effect, or when malignancy cannot be excluded. During
surgery, en bloc resection is crucial to prevent hemorrhage and
recurrence.

\textbf{Case report}

A 16 year old female was incidentally found to have mediastinal widening
in plain chest X-ray took at medical check-up and referred to thoracic
surgery department of Seoul National University Hospital (SNUH) at
2019-04-10. She denied any underlying diseases or family history of
malignancy, and she had never experienced smoking or alcohol. She had
dysphagia, weight loss and exertional dyspnea at the time of the first
visit, but her symptom was not severe and neglected until plain chest
X-ray was taken. Her initial height was 160cm and body weight was
42.5kg.

Chest CT taken at outside hospital showed about 9.5x6.1cm sized fat
containing mass lesion without calcification in the lower neck to
posterior upper mediastinum, and tracheal compression was observed. The
differential diagnosis made by radiologist was well differentiated
liposarcoma or immature teratoma. F-18 FDG PET/CT was taken and it
showed mild uptake (\textasciitilde{}1.9) at aforementioned mass, with
metabolic defect in fat portion (Figure 1). The core needle biopsy of
the mass was done, and the pathologic report confirmed lipogenic tumor
with some brown fat cells, suggestive of hibernoma.

Mediastinal mass excision via full sternotomy under V-V ECMO support was
done by thoracic surgery team. Anesthesiologist recommended V-V ECMO
support because there was mid tracheal compression more than 50\%, with
diameter lower than 5mm, through which plain E-tube ID 3.0mm could
barely pass. Before the anesthesia induction, fiberoptic, rigid
bronchoscope was prepared and high flow nasal cannula was applied for
the possibility of emergent airway collapse. Under MAC anesthesia, the
V-V ECMO was inserted with 17Fr catheter at right and left femoral vein,
then the general anesthesia with endotracheal intubation with plain ID
6.5mm tube was followed. There was no difficulty during the intubation
process, and the intubation depth was 22cm. Airway patency was checked
with fiberoptic bronschoscope.

During the main procedure, approach through full median sternotomy was
made, and large mass through superior aspect of anterior mediastinum to
anterior neck was identified. The mass was well circumscribed and
lobulated, and the adhesion to nearby tissues was minimal. There was no
evidence of vessel, nerve, pleural invasion, and delicate dissection
with complete removal was performed. Bilateral recurrent laryngeal
nerves were identified and preserved. The patient was transferred to
pediatric intensive care unit after the surgery, and was discharged at
postoperative day 5 without any complication.

The size of the mediastinal mass was 9.6 x 7.9 x 3.8cm, and the final
pathology confirmed mediastinal hibernoma. On gross examination,
resected mediastinal lesion contained fatty tissue-like yellowish mass
measuring 5.3 cm. The mass was composed of polygonal cells resembling
brown fat with multivacuolated cytoplasm, admixed with mature
adipocytes. The lesion was also characterized by fibrous septae and
myxoid stroma, suggestive of myxoid variant. Small, delicate, branching
capillaries were noted. Nuclei were small with no significant atypia,
and necrosis was not observed. Immunohistochemistry for CD31 showed
staining in hibernoma cells as well as capillary endothelial cells
(Figure 2).

Regular follow up at outpatient clinic was done with chest PA, and there
was no evidence of recurrence. Initial symptoms such as dysphagia and
dyspnea were also disappeared, and she had no complaint. She also gained
weight, and her body weight was 47.4kg at 2022-01-10. However, the chest
CT taken at 2020-08-26 showed small attenuating lesion at left
supraclavicular area. The size of the mass was increased to about 2.2cm,
which was suspicious for residual mass or recurrence of hibernoma. Due
to its location, the patient was referred to Otolaryngology department
at SNUH.

2022-01-10 neck CT was taken, and the size of the left level VI mass was
increased (2.2 -\textgreater{} 2.6cm) (Figure 3). In addition, 1.6cm
mass was incidentally identified at right submandibular gland posterior
aspect, and followed ultrasound gun biopsy confirmed pleomorphic
adenoma.

Eventually, left level VI neck dissection with right submandibular gland
mass excision was done at 2022-01-25. Electromyography tube was
intubated for intraoperative recurrent laryngeal nerve monitoring. About
5cm midline horizontal incision was made along the skin crease at the
level of thyroid gland. During the removal process, the mass was well
circumscribed with capsule and pinpoint capsule violation was observed,
but there was no definite spillage of tumor content. Delicate dissection
was performed to save nearby structures (Figure 4). Eventually, complete
removal was achieved, and left vagus nerve, carotid vessels, thyroid
gland were saved. Left recurrent laryngeal nerve was not identified due
to severe adhesion, but the patient's vocal fold movement was intact
postoperatively. Suspicious fat tissue nearby main mass was also
removed. The right submandibular gland mass was also removed in a
routine manner.

The recurred tumor at left level VI was also confirmed as hibernoma,
which had similar histologic features with more pronounced myxoid stroma
compared to mediastinal mass (Figure 2). Removed fat tissue adjacent to
main mass was diagnosed as mature adipose tissue. The right
submandibular gland was confirmed as pleomorphic adenoma with clear
resection margin.

The patient was discharged at postoperative day 2 without any
complications, including vocal fold palsy, hematoma, wound infection,
etc. There was no evidence of recurrence at 6 month follow up neck CT.

\textbf{Discussion}

Hibernoma is a rare, benign tumor which consists of cells that
histologically resemble brown fat cells. It was first reported by Merkel
in 1906 and then named by Grey as ``hibernoma'' in 1914, because of its
histological similarity to the brown fat of hibernating animals {[}2{]}.
Unlike typical adipose tissue, brown fat has abundant vascularity to
generate heat {[}3{]}. Brown fat usually disappears after 8 weeks of
life, and it is slowly replaced by white fat {[}4{]}.

Hibernoma accounts for only 1\% of all benign lipomatous tumors and are
usually asymptomatic unless it compresses nearby structures with bulky
mass. It is most commonly identified in the thigh, but it can also occur
anywhere with scattered brown fat, such as bone, retroperitoneum, scalp,
neck, axilla, shoulder, thorax, breast, stomach, etc. {[}2{]}. Its
prevalence peaks in the fourth and fifth decades of life, and gender
predominance is controversial among articles {[}3, 4{]}.

Due to its low incidence, it is sometimes misdiagnosed as
well-differentiated liposarcomas, or myxoid liposarcomas. On computed
tomography (CT) scans, hibernomas sometimes present as well
circumscribed, hypodense lesions with linear septations, which indicates
high vascularity {[}3{]}. On MRI, hibernomas can be isointense or
relatively hypointense to the surrounding fat on both T1 and T2, and
diffuse heterogenous enhancement can be identified due to
hypervascularity of the mass. On F-18 FDG PET/CT scan, hibernomas show
uptake because of metabolically active brown fat tissue. However, none
of images listed above are pathognomic, and this also hinders the
differentiation of hibernoma with sarcomas {[}2{]}.

Therefore, the pathologic diagnosis should be performed before initial
treatment to exclude malignancy. Fine needle aspiration is suggested
rather than core needle biopsy because there is a possibility of
hemorrhage due to high vascularity. On the other hand, some prefer core
needle biopsy because sufficient tissue can increase diagnostic yield
{[}2{]}.

As described in this case, large multivaculolated brown fat cells,
single central or small eccentric nuclei, large amount of granular
cytoplasm, fibrous septae, branching capillaries can be seen in
microscopic examination of hibernoma {[}2{]}.

Furlong et al. suggested four main histological variants of hibernoma:
typical, spindle, lipoma-like, and myxoid type. Typical hibernoma and
lipoma-like variant are most commonly occurred in thigh, whereas the
myxoid and spindle cell type are frequently found in the head and neck
region {[}1{]}. Typical hibernomas, which is characterized with
eosinophilic, pale, and myxoid cells, accounts for about 82\% for all
cases. The second most common type is the myxoid variant, which has a
loose basophilic matrix, accounting for 9\% for total cases. Lipoma-like
type and spindle cell type are followed, each accounting for 7\% and 2\%
of all cases. Most surgical pathologists do not subclassify
aforementioned subtypes because all of them have similar prognosis
{[}2{]}.

Because of its multiple pathological variants and the remaining
possibility of misdiagnosis regardless of using clinical, imaging, and
pathologic information, some researchers suggested additional
chromosomal evaluation to differentiate hibernoma {[}1{]}.

To date, there is no reported case of malignant transformation or
metastasis of hibernoma, so theoretically asymptomatic hibernoma doesn't
need treatment {[}5{]}. However, due to diagnostic uncertainty of
modalities as mentioned above, the treatment of choice is en bloc
resection of the mass. En bloc removal is important to prevent
recurrence, and also bleeding due to its high vascularity. According to
previous articles, almost none of hibernoma patients had recurrence of
disease and none died due to the complications of hibernoma with en bloc
resection. Some exceptions with recurrences were possibly due to
positive resection margins rather than a true recurrence {[}2{]}.

Since hibernoma is well known for no recurrence after complete removal,
the recurrence after the thoracic surgery in this case is also likely to
be a result of remnant tumor after the first surgery. Considering the
mass extension from thoracic cage into infra-thyroid level at the
initial CT, the recurrence might have not been occurred if the primary
surgery was planned as co-operation with thoracic surgeon and head and
neck surgeon. In addition, even though vocal fold palsy did not occur in
this patient, since it was difficult to identify recurrent laryngeal
nerve at the second surgery due to the adhesion caused by the first
surgery, co-operation should have been preferred as the initial plan for
this patient. Even though hibernoma is a benign tumor, this case
emphasizes the importance of complete removal of mass to prevent
recurrence.

\textbf{Conclusion}

We present~a successful removal of recurred hibernoma in neck without
any complication. This is a first case report of cervical hibernoma and
its management in Korea.

\textbf{Acknowledgements}

None



\textbf{Funding and Conflicts of Interest}

The authors have no other funding, financial relationships, or conflicts
of interest to disclose.

\textbf{Author contributions}

Professor Seong Keun Kwon performed surgery, and Young Chul Kim assisted
the surgery and took care of the patient during the admission period.
Professor Jiwon Koh examined the specimen and pathologically confirmed
the diagnosis. Young Chul Kim summarized the case and Jiwon Koh, Seong
Keun Kwon read and approved the final manuscript.

\textbf{Ethical approval}

Consent: The study was published with the written consent of the
patient's legal guardians.

\textbf{References}

1. Turaga, K. K., Silva-Lopez, E., Sanger, W. G., Nelson, M., Hunter, W.
J., Miettinen, M., \& Gatalica, Z. (2006). A (9;11)(q34;q13)
translocation in a hibernoma.~\emph{Cancer genetics and cytogenetics}
,~\emph{170} (2), 163--166.

2. AlQattan, A. S., Al Abdrabalnabi, A. A., Al Duhileb, M. A., Ewies,
T., Mashhour, M., \& Abbas, A. (2020). A Diagnostic Dilemma of a
Subcutaneous Hibernoma: Case Report.~\emph{The American journal of case
reports} ,~\emph{21} , e921447.

3. Prendes, B. L., Kohli, C., Brooks, J. S., \& Newman, J. G. (2011).
Cervical hibernoma, a rare, benign tumor: case report.~\emph{Ear, nose,
\& throat journal} ,~\emph{90} (1), E19--E21.

4. Prakash A, Singh S, Dhull K, Sharma S, Vyas T, Jain A. (2020).
Cervical hibernoma: A very rare tumor of childhood -- Case report with
review of literature. \emph{Indian J Med Paediatr Oncol} , 41(1), 72-4.

5. Furlong, M. A., Fanburg-Smith, J. C., \& Miettinen, M. (2001). The
morphologic spectrum of hibernoma: a clinicopathologic study of 170
cases.~\emph{The American journal of surgical pathology} ,~\emph{25}
(6), 809--814.

\textbf{Figure~Legends}

\textbf{Figure~1:} Initial imaging,~(A) axial chest CT, (B) coronal
chest CT, (C) F-18 FDG PET/CT, (D) ultrasound showing mass from lower
neck to posterior upper mediastinum

\textbf{Figure 2:} (A) The lesion was fatty tissue-like yellowsish mass
on gross examination. (B) Polygonal cells resembling brown fat with
multivacuolated cytoplasm were admixed with mature adipocytes in the
background of myxoid stroma. (C) Small, delicate, branching capillaries
were noted. (D) No significant nuclear atypism was seen. (E) CD31
immunostaining highlighted hibernoma cells and capillary endothelial
cells. (F) The recurred tumor at supraclavicular area had similar
histologic features with more pronounced myxoid stroma.

\textbf{Figure 3:} neck CT showing recurred tumor at left
supraclavicular area (red arrow), (A) axial view, (B) coronal view

\textbf{Figure 4:} Intraoperational photo of left supraclavicular
recurred hibernoma, (A) hibernoma was well circumscribed with capsule,
and delicate dissection was performed to save nearby structures, (B)
anterior plane of removed hibernoma, (C) posterior plane of removed
hibernoma\selectlanguage{english}
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