Bilateral multiple spindle cell lipomas of the tongueTomoaki Imai, DDS, PhD,a Masahiro Michizawa, DDS, PhD,b Hidetaka Shimizu, DDS, PhD,c

Takumi Imai, DDS, PhD,d Naonori Yamamoto, DDS,e and Yoshiaki Yura, DDS, PhD,f Osakaand Nara, JapanSAISEIKAI SENRI HOSPITAL, OSAKA UNIVERSITY GRADUATE SCHOOL OF DENTISTRY, AND TENRIHOSPITAL

Spindle cell lipoma (SCL) typically occurs in elderly men as a solitary lesion in the posterior neck and back, butless commonly also involves the oral cavity. Here, we describe a rare case of bilateral multiple SCLs of the tongue. Thepatient was a 72-year-old Japanese man with multiple painless soft nodules in the bilateral margins of the tongue. Thepatient was not obese, and had used alcohol moderately for more than 40 years. A clinical diagnosis of multiple tonguelipomas was made. The tumors were resected surgically, and they exhibited the histopathological features of SCL,composed of mature fat cells, collagen-forming CD34-positive spindle cells, and sparse mast cells. This suggests thatdifferential diagnosis of intraoral multiple lipomatous nodules should include not only lipomatosis but also multiple SCLs,

notwithstanding the rare incidence of the latter. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:264-9)

Lipomas are the most frequent benign soft tissue tu-mors, occurring as a slowly enlarging, painless massformation. They commonly affect the upper back andshoulder, but also occur in the oral cavity in lower rates,predominantly the buccal mucosa, followed by the lipand the tongue.1,2 Multiple involvement is known asbenign symmetrical lipomatosis (BSL; Madelung’s dis-ease), and characterized by the diffuse growth of non-encapsulated lipomas.3,4 Multiple tongue lipomas,5

particularly symmetric tumor formation, is called sym-metric lipomatosis of the tongue (SLT).6-10

Histologically, lipomas are classified into varioussubtypes, including simple lipoma, fibrolipoma, angio-lipoma, myxoid lipoma, pleomorphic lipoma, and spin-dle cell lipoma. Spindle cell lipoma (SCL), an uncom-mon variant first reported by Enzinger and Harvey in1975,11 is composed of mature fat cells, collagen-form-ing spindle cells, and sparse mast cells. SCL typicallyoccurs in elderly men as a solitary lesion in the poste-

aClinical Fellow, Department of Oral and Maxillofacial Surgery,Saiseikai Senri Hospital, Suita, Osaka, Japan.bHead, Department of Oral and Maxillofacial Surgery, SaiseikaiSenri Hospital, Suita, Osaka, Japan.cAssistant Professor, Department of Oral and Maxillofacial Surgery II,Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.dClinical Fellow, Department of Oral and Maxillofacial Surgery,Tenri Hospital, Tennri, Nara, Japan.eGraduate Fellow, Department of Oral and Maxillofacial Surgery II,Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.fProfessor, Department of Oral and Maxillofacial Surgery II, OsakaUniversity Graduate School of Dentistry, Suita, Osaka, Japan.Received for publication Dec 18, 2007; returned for revision Feb 18,2008; accepted for publication Feb 18, 2008.1079-2104/$ - see front matter© 2008 Mosby, Inc. All rights reserved.

doi:10.1016/j.tripleo.2008.02.026

264

rior neck and back,11,12 but may less commonly alsoinvolve the oral cavity.13,14 Because the occurrence ofmultiple intraoral SCLs is extremely rare15 and theirclinical appearance is similar to that of conventionallipoma, multiple lipomatous nodules of the tonguewould be clinically diagnosed as multiple tongue lipo-mas or SLT. Here we describe a case of bilateralmultiple SCLs of the tongue.

A CASE REPORTA 72-year-old Japanese man attended Saiseikai Senri

Hospital complaining of painless soft nodules in the leftmargin of the tongue, first noticed 2 weeks previously.Clinical examination revealed 2 tumors with maximaldiameters of 12 mm and 15 mm in the left margin of thetongue. The covering mucosa appeared normal (Fig. 1).Further examination showed 3 smaller submucosal nod-ules ranging from 3 mm to 5 mm in the right margin.Palpation revealed elastic soft nodules of the tongue andno lymphatic node enlargement in the neck. No tumormasses were identified on the trunk, head and neck, orextremities. There was no family history of similar tu-mors. The patient had a history of angina pectoris, was notobese, had no allergies to foods or medications, did notsmoke, and had used alcohol moderately for more than 40years. Laboratory data were within normal limits. Com-puted tomography (CT) and magnetic resonance imaging(MRI) failed to delineate the tumor masses because ofmetal artifacts from full-cast crowns on neighboring teeth,but detected no enlarged lymphatic nodes in the neck. Onthe basis of these findings, a clinical diagnosis of multipletongue lipomas was made.

The 2 large lesions in the left side were resectedunder general anesthesia, followed 3 months later by

those on the right under local anesthesia. Macroscopi-

OOOOEVolume 106, Number 2 Imai et al. 265

cally, the lesions consisted of encapsulated, easily enu-cleated whitish-yellow nodules (Fig. 2). Histopatho-logic examination revealed that all lesions werecomposed of mature adipocytes with a clear cytoplasm,well-aligned fibroblastic spindle cells, and wiry colla-gen bundles (Fig. 3), with no evidence of cellular atypiaor pleomorphism. A histopathological diagnosis ofSCL was made. The relative proportions of adipocytesand spindle cells varied markedly in different areaswithin the large lesions of the left tongue (Fig. 3, A),particularly with the appearance of the spindle cellcomponent (Fig. 3, B). Furthermore, fat cells dominatedthe area neighboring this component in the same lesion(Fig. 3, C). In contrast, this intratumor variation wasalmost completely absent in all small lesions of theright tongue(Fig. 3, D), which were essentially devoidof a large spindle cell component and showed a largelyhomogeneous appearance with approximately equalproportions of adipocytes and spindle cells. The myx-oid area was localized in the spindle cell componentand homogeneously positive-stained with alcian blue,

Fig. 1. Clinical appearance. Submucosal lipomatous nodulesare seen in the left (A) and right (B) side of the tongue(arrows).

indicating the existence of abundant acid mucopolysac-

charides (Fig. 4). Immunohistochemical staining forCD34 demonstrated intracytoplasmic reactivity in spin-dle cells but not adipocytes, which had immunoreac-tivity for S-100 antibody (Fig. 5). Further, mast cellsimmunoreactive for tryptase, a mast cell marker, werepredominantly scattered among the spindle cells andcollagen bundles (Fig. 6).

No sign of recurrence has been observed at 1 yearafter the second operation.

DISCUSSIONSCL is a relatively uncommon benign tumor that

accounts for approximately 1.5% of all adipocytic neo-plasms.16 Although usually occurring as a solitary le-sion, about 0.5% to 3.0% of cases are of multipletumors.17 Previous reports of oral lipomas also de-scribed a low occurrence of 1.36% (2 SCL cases of 146oral lipomas)13 or 2.2% (1 case of 46 lipomas).1 Fur-long et al.,2 however, recently reported 59 SCL cases(47%) of 125 lipomas in the oral and maxillofacialregion, indicating that oral SCL may be more common

Fig. 2. Excised tumors. A, Encapsulated whitish-yellow tu-mor on the left side. B, Smaller tumor nodules on the rightside.

than previously estimated. Although review of the lit-

sion w

OOOOE266 Imai et al. August 2008

erature reveals more than 50 cases of intraoral SCL,2,14

SCL of the tongue is relatively uncommon,18-20 andonly one of these was of multiple SCLs,15 in that case

Fig. 3. Micrographic appearance. The tumors consist of a m(hematoxylin and eosin stain). A, A low-magnification photointerface between the adipocytic component and collagenousSpindle cell–rich area of the anterior lipoma of the left tonguof the same tumor nodule (�100). D, The central lipoma of tof fat cell and spindle cell areas, compared with the large le

Fig. 4. Alcian blue-staining for myxoid matrix. High-magnifi-cation photomicrograph of the myxoid area in the spindle cellcomponent of the anterior lipoma of the left tongue (�200). Theintracellular matrix varies from collagenous to myxoid. A typicalmyxoid matrix stained homogeneously is shown (arrows).

occurring bilaterally in the margin of the tongue.

Histologically, SCL displays an admixture of maturefat cells and well-aligned uniform spindle cells withstrong immunoreactivity for CD34 in a fibrocollag-enous and myxoid background.11 CD34 was originallyidentified on the surface of hematopoietic progenitorcells of the lymphoid and myeloid lineage,21 and is alsoexpressed in nonhematopoietic tissues and their neo-plasms, including dermal dendritic cells, endoneurialcells, solitary fibrous tumors, and interstitial dendriticspindle cell components of lipomatous neoplasms.22,23

Spindle cells are believed to be nonlipoblastic stellatemesenchymal cells of the primitive fat lobules that havelost their ability to differentiate to lipocytes but arenevertheless capable of collagen synthesis.24

With regard to the clinical and histological differen-tial diagnosis of solitary SCL, consideration should begiven to the possibility of well-differentiated liposar-coma, which requires more radical treatment.12 SCLcan be differentiated from the liposarcoma by its well-circumscribed form, superficial location, slow growth,few or no lipoblasts, the uniformity and association ofthe spindle cells with collagen bundles, sparse vascu-larity, and the absence of atypical cells.12,25-27 How-ever, well-differentiated liposarcoma can also arise inthe tongue as a slow-growing and circumscribed sub-

of mature lipocytes and spindle cells in varying proportionsgraph of the anterior lipoma of the left tongue, showing the

cell component. The tumor is thinly encapsulated (�40). B,the thick wiry collagen bundles (�100). C, Adipocytic areat. This small mass lesion displays homogeneous distributionith intratumor variation (�100).

ixturemicro

spindlee. Notehe righ

mucosal mass.26 Pleomorphic lipoma exhibits features

OOOOEVolume 106, Number 2 Imai et al. 267

similar to SCL, but can be differentiated by the pres-ence of floret-type giant cells.24

With regard to the histological features of myxoidinterstitial material in SCL, some cases contain anabundant myxoid matrix,28 while others display collag-enous interstitium with small amount of myxoid.20 Thepresent case might be considered a combination ofthese types. The highly myxoid pattern with few spin-dle cells simulates myxoma or myxolipoma. Further-more, SCL is occasionally indistinguishable from den-dritic fibromyxolipoma,29 which is characterized byspindle or stellate fibroblastic cells admixed with adi-pose tissue in an abundant myxoid and collagenizedstroma. Although a vascular pattern is usually incon-spicuous in SCL, prominent vascularization in certainsegments might lead to a misdiagnosis of angiolipoma

Fig. 5. Immunohistochemistry of CD34 and S-100. A, Spin-dle cells are strongly immunopositive for CD34 (�200). B,Mature lipocytes stain positive for S-100 protein, while thespindle cell area is negative for S-100 protein (�200).

or angiomyxolipoma.30

The proportion of spindle cells in SCL varies in differ-ent areas within the same lesion.11,31 In multiple SCLs ofthe trunk and extremities, the lesions became increasinglymore cellular as they develop over time.17 The previousreport of intraoral multiple SCLs15 presented 2 uniformtumors of 30 mm and 24 mm, but did not describe thedistribution of spindle cell areas. The finding in ourpresent case that collagen-forming spindle cell areas werepredominant in the large but not small lesions indicatesthat the increasing cellularity with development occursindependently of tumorigenesis region. This characteristicmay be associated with mast cell infiltration, on the basisthat mast cells have biological effects on mesenchymalcell proliferation and collagen production.32,33 On his-topathological diagnosis, the predominant collagen andspindle cell area in SCL may cause the tumor to berecognized as a nonlipomatous lesion,31 such as a solitaryfibrous tumor, but in contrast as a conventional lipoma ifthe localized spindle cells are overlooked. The possibilityof misdiagnosis on incisional biopsy of a large lesion isthus increased.

In the present case, the clinical presentation of multipleinvolvement suggested little potential for malignant lipo-matous neoplasm. A clinical diagnosis of multiple tonguelipomas that might develop to SLT was thus made, buthistopathological examination confirmed a diagnosis ofmultiple SCLs. Moreover, a review of tongue liposarco-mas in 32 cases described 2 cases of submucosal multi-nodular lesions.27 These findings suggest that differentialdiagnosis of intraoral multiple lipomatous nodules, partic-

Fig. 6. Immunohistochemistry of tryptase, a mast cellmarker. Mast cells are predominantly sparse among spindlecells and collagen bundles in the spindle cell-rich area (bar)(�200).

ularly of the tongue, should include not only lipomatosis

the ton

OOOOE268 Imai et al. August 2008

but also multiple lesions of SCL or liposarcoma, notwith-standing the rare incidence of the latter.

The term SLT has been clinically used to describelipomatosis involving only the tongue (Table I).6-10 Incontrast, BSL initially appears predominantly on theposterior neck and spreads sequentially in a caudaldirection,3,4,17 with only rare involvement of thetongue.34-36 Although SLT and BSL share the samehistopathological features, recent reports have sug-gested different etiologies. SLT has a different ethnicbackground to BSL, and is less relevant than BSL tomedical conditions such as alcoholism and obesity.6-10

A recent study suggested that BSL was associated withbrown fat mitochondrial dysfunction,37 but the etiologyof SLT has not be clearly elucidated.

In terms of the most common initial site and direc-tion of progress, multiple SCLs resemble BSL (TableI).17 In contrast to this similarity in clinical appearance,multiple SCL patients share no common medical con-dition or environmental exposure.17 However, the factthat the present patient had used alcohol moderatelysuggests that an etiological mechanism involving alco-hol remains a possibility, as occurs with lipomatosis.The small number of cases means that the etiologicaldifferences between the conventional widespread pat-tern of multiple SCLs in Caucasian men and the local-ized lingual pattern in Japanese men cannot yet beclarified. Further differentiation awaits the accumula-tion of additional cases.

With regard to treatment, the gold standard for symp-tomatic SCL is complete surgical resection, but this can

Table I. Clinical features of lipomatosis and multiple

Lipomatosis

BSL

Predominant locations Posterior neck and uppertrunk; �rareinvolvement of thetongue

Tongue on

Number of cases Over 200 7Sex (male:female) M:F � 15:1 All M

Average age, y 52 68Predominant ethnic

backgroundMediterranean descent Asian men

Associated medicalconditions

Alcoholism (60%-90%),liver disease, obesity

Weaker as1 alcoho5 nondr

References 3, 4, �34-36 6-10

BSL, benign symmetric lipomatosis; SLT, symmetric lipomatosis of

lead to postexcisional cosmetic or functional disorders in

the case of multiple SCLs or a large solitary lesion. For-tunately, our present patient did not develop a postopera-tive feeding disorder or disturbance of pronunciation. Be-chara et al.38 recently reported the use of injectionlipolysis with phosphatidylcholine to reduce tumor vol-umes, and this will likely become an effective therapeuticoption for patients with multiple conventional lipomas.Injection lipolysis may also be valuable as preoperativetherapy in progressive multiple SCLs.

No clear case of malignant transformation of SCLhas been reported to date. However, Harvell39 recentlydescribed a 48-year-old man with multiple SCLs of theneck who suffered a fibrosarcomatous transformationof the chest into dermatofibrosarcoma protuberans(DFSP), a CD34-positive neoplasm of intermediate ma-lignancy derived from interstitial dendritic cells. Thesemesenchymal cells are considered to have the ability todifferentiate into CD34-positive spindle cells.23 Thiscase may suggest the potential for malignant neoplasticconversion of spindle cells in patients with multipleSCLs.

Generally, solitary SCL shows no features of localrecurrence after total excision,17 with only 1 case reportedto date.16 In the case of multiple involvement, consider-ation should be given to the possibility of sequential andmulticentric development of lesions over several years,and the postoperative area should be carefully monitored.

The authors thank Dr. Aki Kakutani, Department of Pathol-ogy and Laboratory Medicine, Saisekai Senri Hospital, foradvice and for confirmation of the histopathological diagno-

mSCLs

mSCLs

mSCLs of thetongue (previous

and present cases)

Posterior neck and uppertrunk

Tongue only

19 2Familial: both sexes

(male predominant)Non-familial: all M

all M

55.2 73.5Caucasian men Japanese men

n than BSL;ild drinker,

No particular Previous case: NDPresent case:moderatedrinker

17, 39 15

gue; mSCLs, multiple spindle cell lipomas; ND, not described

SCLs

SLT

ly

sociatiolic, 1 m

inker

sis.

OOOOEVolume 106, Number 2 Imai et al. 269

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Reprint requests:

Tomoaki Imai, DDS, PhDDepartment of Oral and Maxillofacial SurgerySaiseikai Senri Hospital1-1-6 Tsukumodai, SuitaOsaka 565-0862, Japan

hsc12@hotmail.com