Oral Oncology 117 (2021) 105215

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Oral Oncology
journal homepage: www.elsevier.com/locate/oraloncology

Letter to the editor

Fat-free pleomorphic lipoma of the buccal mucosa: An immunohistochemical study and

literature review

A R T I C L E I N F O A B S T R A C T

Keywords Pleomorphic lipomas are extremely rare in the oral cavity. Due to the significant overlap of morphological
Lipoma findings with several benign and malignant soft tissue tumors, especially in the absence of adipocytes, the
Floret giant cells diagnosis is challenging. We reported the clinicopathological and immunohistochemical features of an uncom­
Soft tissue neoplasm
mon case of a fat-free variant of pleomorphic lipoma in a 48-year-old female presenting clinically as a painless
nodule on the buccal mucosa. Microscopically, the lesion showed atypical spindle cells, numerous floret-like
giant multinucleated cells, and abundant ropey collagen fibers bundles. Immunohistochemistry showed strong
positivity for vimentin and CD34. Mast cell tryptase highlighted numerous mast cells distributed throughout all
tumor stroma. S-100 protein, pan-cytokeratin, desmin, α-SMA, EMA, CD68, STAT6, Bcl-2, MDM2, and CDK4
were negative. Conservative surgical excision was carried out, and no recurrence was observed after 13 months
of follow-up. Careful histopathological and immunohistochemistry analysis of these lesions is recommended to
ensure the correct diagnosis and provide adequate management through a conservative surgical approach. To the
best of our knowledge, this is the second case of fat-free pleomorphic lipoma in the oral cavity.

Introduction well-circumscribed lesion containing atypical spindle cells, floret-like

Spindle cell lipoma (SCL) is an uncommon subtype of lipoma first
described in 1975 by Enzinger and Harvey [1], which often occurs in the
head and neck region and upper trunk of older male patients [2]. Since
then, approximately 45 cases involving the oral cavity had been re­
ported in the English-language literature [3]. The pleomorphic subtype
described less than a decade later by Shmookler and Enzinger [4] is even
more unusual, with only 5 cases reported in the oral cavity until to date,
including the current case [5–8].
Interestingly, an extremely unusual fat-free variant of pleomorphic
lipoma (PL) [5], as well as low-fat/fat-free variant of spindle cell lipoma
these lesions have been reported in the oral cavity [3,9]. The absence or
small amount of the lipogenic component makes these lesions frequently
confused histologically with several benign and malignant entities
because the diagnosis depends on its non-adipose component analysis
[9].
Herein, we report an additional rare case of a PL affecting the buccal
mucosa. To the best of our knowledge, the present case is the second
report of fat-free PL in the oral cavity to date.
Case report
A 48-year-old female patient was referred to an oral medicine service
to evaluate swelling in the mouth lasting four months. On intraoral
examination, an asymptomatic nodule measuring about 2.0 cm in
diameter was observed in the right buccal mucosa. The lesion was mo­
bile and firm in consistency with no hardening of surrounding tissues
and covered by normal-colored mucosa. The clinical differential diag­
nosis included fibrous hyperplasia and benign soft tissue tumors. An
excisional biopsy was carried out. Microscopic examination revealed a
giant multinucleated cells, and numerous mast cells in a stroma pre­
senting ropey collagen (Fig. 1A-F). By immunohistochemistry, the tumor
cells were strongly and diffusely positive for vimentin and CD34.
Numerous mast cells were also observed and showed positivity for mast
cell tryptase (Fig. 1G-I). The Ki-67 labeling index was <1%. Desmin, S-
100 protein, AE1/AE3, EMA, α-SMA, CD68, STAT6, Bcl-2, MDM2, and
CDK4 were negative. The diagnosis was a fat-free PL. Currently, the
patient remains without evidence of recurrence after 13 months of
follow-up.
Discussion
In the past, SCL and PL were considered different clinicopathological
entities [2]. However, it is currently believed that these lesions are part
of the same spectrum because both share clinicopathological, immu­
nohistochemical, and cytogenetic characteristics, specifically the loss of
16q and 13q [2,10,11]. Also, the existence of hybrid lesions, presenting
intermediate histopathological characteristics between SCLs and PLs,
emphasize a possibly histogenetic relation and providing further evi­
dence that both types represent morphologic variations of the same
entity [2]. Based on this evidence, the term unifying spindle cell/pleo­
morphic lipoma was proposed for cases showing overlapping features.
Although some cases are entirely spindled or totally pleomorphic, both
components can predominate [2].
To the best of our knowledge, only five cases of PLs affecting the oral
cavity have been reported in the English-language literature, including
the current case (Table 1) [5–8]. Most oral PLs clinically presented as
slow-growing asymptomatic submucosal nodules, mainly affecting the
buccal mucosa and tongue of adult women (1.5:1 female-to-male ratio),
with a mean age of 54 years [5–8].

https://doi.org/10.1016/j.oraloncology.2021.105215
Received 26 January 2021; Received in revised form 26 January 2021; Accepted 29 January 2021
Available online 16 February 2021
1368-8375/© 2021 Elsevier Ltd. All rights reserved.
Letter to the editor Oral Oncology 117 (2021) 105215

Morphologically, at one end of the spectrum, classical SCLs show
similar amounts of spindle cells and mature adipose tissue. In contrast,
at the other end of the spectrum, PL exhibits few spindle cells, numerous
floret-like multinucleated giant cells, and variable amounts of adipose
tissue [2]. However, both variants share some features such as charac­
teristic wiry to ropey collagen, numerous mast cells, and connective
tissue of myxoid or mucoid appearance [2]. Lipoblasts may also be
observed in both SCLs and PLs; however, infiltrative growth pattern,
pleomorphic lipoblasts, necrosis, and significant mitotic activity are
usually not observed [2]. Rarely, similar to the present case, no fatty
tissue is observed. In these circumstances, the histopathological diag­
nosis is challenging because the adipose component of the tumor is not
apparent, and the diagnosis is based on the non-lipomatous component
of the lesion [9,12]. Another complicating factor is the immunohisto­
chemical positivity for CD34 observed in most lesions in the differential
diagnosis. Although the differential morphological diagnosis of spindle
cell/pleomorphic lipoma depends on which elements predominate, in
general, includes atypical lipomatous tumors/well-differentiated lip­
osarcoma (ALT/WDLS), myxofibrosarcoma , fat-forming solitary fibrous
tumor , neurofibroma, schwannoma, mammary-type myofibroblastoma,
and cellular angiofibroma [2,5,9]. However, it is important to empha­
size that among the differential diagnoses, the distinction between lip­
osarcoma and LPs is the most important and essential to avoid
unnecessary treatments.
The distinction between PL and ALT/WDLS can be challenging
because both lesions may contain floret-like multinucleated giant cells,
lipoblasts, mature adipocytes, and myxoid areas [2]. However, unlike
our case, ALT/WDLS contains fat cells of different sizes and shapes,
lipoblasts, and tends to exhibit an infiltrative growth pattern. In addi­
tion, the ropey collagen bundles, as noted in the present case, are
characteristic of the PLs and are a useful distinguishing feature because
this collagen pattern is usually not seen in ALT/WDLS [2]. Ultimately,
ALT/WDLS exhibits nuclear immunoreactivity for MDM2 and CDK4
[13,14], in contrast to our case, which was negative for all of them.
Pleomorphic liposarcoma should also be considered in the differential
diagnosis. However, it contains markedly atypical spindled and
epithelioid cells, pleomorphic lipoblasts, and easily identifiable mitotic
figures [2]. It is important to emphasize that the distinction between
these variants of liposarcoma and PLs is essential to avoid unnecessary
treatment.
In summary, careful morphological analysis of spindle cell/pleo­
morphic lipomas, supported by immunohistochemistry, is recom­
mended to avoid misdiagnosis because of the potential morphological
pitfalls. Low-fat and fat-free variants of PL have no prognostic relevance.
However, the morphological diagnosis can be challenging, even for
experienced pathologists. The treatment of choice is conservative sur­
gical excision, and recurrence is uncommon.

Fig. 1. Histopathological and immunohistochemical features of pleomorphic lipoma. A-B, Low power view of the lesion shows a mixture of pleomorphic spindle cells
and thick ropey collagen. C, Note the presence of numerous floret-like multinucleated giant cells in the surrounding connective tissue. D, Photomicrography showing
an area of loose connective tissue containing multinucleated giant cells, numerous mast cells (arrows), and the delicate blood vessels. E-F, High-power photomi­
crograph showing detail of floret-like multinucleated giant cell with radially arranged hyperchromatic nuclei and central eosinophilic cytoplasm (arrowhead) and
bizarre pleomorphic multinucleated cells (arrows) (hematoxylin and eosin stain; A, ×50; B, ×100; C and D, ×200; E and F, ×400). G, Tumor cells showing strong
positivity for vimentin. H, Positive immunohistochemical staining for CD34. I, Numerous mast cells showing strong positivity for mast cell tryptase (Immunohis­
tochemistry; G, H, and I × 200).

2
Letter to the editor Oral Oncology 117 (2021) 105215

Table 1
Summary of previous cases of pleomorphic lipomas affecting the oral cavity (1986–2020).
Case Author Age Sex Location Size Duration Symptoms Treatment Follow up time Recurrence
(cm) (months) (months)

1 Guillou et al., 60 F Tongue – – – – – –

1986a
2 Atik et al., 2002 45 M Tongue 2.0 × 24 Difficulty in chewing Total 12 No
1.5 × 1.0 and swallowing resection
3 Perrotti et al., 59 M Upper right maxillary 2.0 14 No Surgical 60 No
2006 buccal vestibule excision
4 Ranganathan 22 F Buccal mucosa 2.0 12 No Surgical 6 No
et al., 2017b excision
5 Present caseb 48 F Buccal mucosa 2.0 4 No Surgical 13 No
excision

NR not reported, F female, M male.

a
The full text was not available.
b
Fat-free variant of pleomorphic lipoma.

Financial support
This study was financed in part by the Coordenação de Aperfeiçoa­
mento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001.
The authors John Lennon Silva Cunha and Saygo Tomo received,
respectively, a MSc scholarship and a PhD scholarship by the Coor­
denação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil
(CAPES).
Chromosomes and Morphology (CHAMP) Collaborative Study Group. Am J Pathol
1996;148(2):623–30.
[12] Jäger M, Winkelmann R, Eichler K, Valesky E, Kaufmann R, Meissner M. Pleo­
morphic lipoma. J Dtsch Dermatol Ges 2018;16(2):208–10.
[13] Stojanov IJ, Mariño-Enriquez A, Bahri N, Jo VY, Woo SB. Lipomas of the oral
cavity: utility of MDM2 and CDK4 in avoiding overdiagnosis as atypical lipomatous
tumor. Head Neck Pathol 2019;13(2):169–76.
[14] Thway K, Flora R, Shah C, Olmos D, Fisher C. Diagnostic utility of p16, CDK4, and
MDM2 as an immunohistochemical panel in distinguishing well-differentiated and
dedifferentiated liposarcomas from other adipocytic tumors. Am J Surg Pathol
2012;36(3):462–9.

Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
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John Lennon Silva Cunhaa,*, Saygo Tomob, Carolina Peres Motac, Ivan
José Correia Netod, Sílvia Ferreira de Sousac,*, Jorge Esquiche Leóne,
Ricardo Luiz Cavalcanti de Albuquerque-Júniorf
a
Oral Pathology Section, Department of Oral Diagnosis, Piracicaba Dental
School, University of Campinas (UNICAMP), Piracicaba, SP, Brazil
b
Oral Oncology Center, São Paulo State University (UNESP), School of
Dentistry, Araçatuba, SP, Brazil
c
Department of Oral Surgery and Pathology, School of Dentistry,
Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
d
Department of Oral and Maxillofacial Pathology, School of Dentistry,
University of São Paulo (USP), São Paulo, SP, Brazil
e
Oral Pathology, Department of Stomatology, Public Oral Health, and
Forensic Dentistry, School of Dentistry of Ribeirão Preto, University of São
Paulo (USP), Ribeirão Preto, SP, Brazil
f
Laboratory of Morphology and Experimental Pathology, Institute of
Technology and Research, Tiradentes University (UNIT), Aracaju, SE,
Brazil
*
Corresponding authors at: Oral Pathology Section, Department of Oral
Diagnosis, Piracicaba Dental School, University of Campinas
(UNICAMP), Av. Limeira 901, Piracicaba, São Paulo 1314-903, Brazil
(J.L.S. Cunha). Department of Oral Surgery and Pathology, School of
Dentistry, Universidade Federal de Minas Gerais (UFMG), Av.
Presidente Antônio Carlos, 6627 Pampulha, Belo Horizonte, MG, Brazil
(S.F. de Sousa).
E-mail addresses: lennon.patologia@outlook.com (J.L.S. Cunha),
silviafsousa@ufmg.br (S.F. de Sousa).