Basaloid squamous cell carcinoma of the mandible: Report oftwo casesEiji Hirai, DDS,a Kozo Yamamoto, DDS, PhD,a Noriaki Yamamoto, DDS, PhD,b

Yoshihiro Yamashita, DDS, PhD,b Toshiaki Kounoe, DDS,a Yoshihide Kondo, DDS,a

Hirotoshi Yonemasu, MD, PhD,c Tetsu Takahashi, DDS, PhD,b andHideo Kurokawa, DDS, PhD,a Oita and Kitakyusyu, JapanOITA RED CROSS HOSPITAL AND KYUSHU DENTAL COLLEGE

Basaloid squamous cell carcinoma is a rare aggressive malignancy that is a distinct variant of squamouscell carcinoma. This report presents 2 cases of basaloid squamous cell carcinoma in the gingiva. Case 1 is a 55-year-old Japanese man who presented with a painful, red, and irregular mass on the left mandibular gingiva. Case2 is a 65-year-old Japanese man who presented with a painless mass on the right mandibular gingiva. Bothtumors were diagnosed histopathologically as basaloid squamous cell carcinoma. In case 1, the patientunderwent wide resection of the gingival tumor with a partial mandibulectomy and ipsilateral functional neckdissection. The mandible was reconstructed with a titanium plate and forearm flap. In case 2, the patientunderwent wide resection of the gingival tumor after local irradiation (60 Gy). At the time of writing, bothpatients remained in good health and free of disease. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;

108:e54-e58)

Wain et al.1 first proposed that basaloid squamous cellcarcinoma (BSCC) was a distinct variant of squamouscell carcinoma (SCC). In 1991, the World Health Or-ganization included this tumor in the revised classifi-cation for the upper respiratory tract and ear.2 The mostfrequent sites of occurrence in the upper aerodigestivetract are the base of the tongue, the larynx, and thepyriform sinus.3 Ide et al.4 reported 46 cases of BSCCin the oral mucosa, with a single case of BSCC in thegingiva. Here, we present 2 cases of BSCC in themandibular gingiva.

CASE REPORTSCase 1

A 55-year-old Japanese man complained of pain in his leftmandibular gingiva that he first noticed 1 month before ad-mission. His medical history was noncontributory. The pa-tient was a nonsmoker and denied excessive alcohol consump-tion. The physical examination showed a well developed, wellnourished man in no apparent distress. The oral examinationrevealed a red, irregular, 37 � 21 mm mass in the leftmandibular posterior lingual gingiva (Fig. 1, A). There were

aDepartment of Oral and Maxillofacial Surgery, Oita Red CrossHospital.bDivision of Oral and Maxillofacial Reconstructive Surgery, Depart-ment of Oral and Maxillofacial Surgery, Kyushu Dental College.cDepartment of Pathology, Oita Red Cross Hospital.Received for publication Jan 15, 2009; returned for revision Jul 9,2009; accepted for publication Jul 10, 2009.1079-2104/$ - see front matter© 2009 Mosby, Inc. All rights reserved.

doi:10.1016/j.tripleo.2009.07.011

e54

no other oral mucosal anomalies and no cervical lymphade-nopathy. Neck and chest computerized tomography was neg-ative for metastatic lesion.

An incisional biopsy was performed and was reported asBSCC histopathologically. The lesion was staged as T2 N0M0. The patient underwent wide resection of the gingivaltumor with a partial mandibulectomy and ipsilateral func-tional neck dissection. The mandible was reconstructed witha titanium plate and forearm flap.

Microscopy showed epithelial-like and basaloid tumor cells.Nests of conventional SCC with keratinization were scarce. Thebasaloid cells constituted the primary invasive component andwere arranged in cords, trabeculae, and lobules that occasionallyshowed pseudoglandular formation. These cells showed periph-eral palisading with hyperchromatic nuclei of high N/C ratio(Fig. 2). The tumor had infiltrated the mandible.

Immunohistochemically, basaloid carcinoma cells were pos-itive for AE1/AE3 (ready for use; Dako, Copenhagen, Denmark)and p63 (1:50; Dako; Fig. 3, A) and focally positive for CK14(1:50; Novocastra, Newcastle, U.K.; Fig. 4, A) and laminin(1:100; Chemicon, Temecula, CA, USA), but negative for S-100protein (1:20; Dako), type IV collagen (1:1,000; Fuji MedicalInd, Takaoka, Japan), CK7 (ready for use; Dako), and vimentin(1:25; Dako). Based on the histologic and immunohistochemicalfindings, the tumor was diagnosed as BSCC.

Six years after surgery, the patient are alive with no evi-dence of disease.

Case 2A 65-year-old Japanese man complained of a painless

swelling in his right mandibular gingiva that he first noticed3 months before admission. His medical history was noncon-tributory. The patient was a nonsmoker and denied excessive

alcohol consumption. The physical examination showed a

tumor

OOOOEVolume 108, Number 5 Hirai et al. e55

well developed, well nourished man in no apparent distress.The oral examination revealed a red, irregular, 15 � 10 mmmass in the right mandibular posterior gingiva (Fig. 1, B).There were no other oral mucosal anomalies and no cervicallymphadenopathy. Neck and chest computerized tomographywas negative for metastatic lesion.

An incisional biopsy was performed and was reported asadenoid cystic carcinoma histopathologically. The lesion wasstaged as T1 N0 M0. The patient underwent wide resection ofthe gingival tumor with marginal resection of the mandible,after local irradiation (60 Gy). Microscopy showed epithelial-like and basaloid tumor cells. The basaloid cells constituted the

Fig. 1. Intraoral appearance of the tumor. A, Clinical view olingual gingiva. B, Clinical view of case 2 shows exophytic

Fig. 2. A, Keratinization is observed (arrow) (hematoxylin-Epithelial cells and basaloid cells are observed. There are pecation �40).

primary invasive component and were arranged in cords, trabec-

ulae, and lobules that occasionally showed pseudoglandular for-mation. These cells were hyperchromatic nuclei of high N/Cratio. Mitotic figures were observed throughout the nests, andkeratinization and intercellular bridges were observed in thestroma. However, the tumor had not infiltrated the mandible.Some of the nests showed comedonecrosis (Fig. 5).

Immunohistochemically basaloid carcinoma cells werepositive for p63 (Fig. 3, B) and S-100 protein and focallypositive for CK14 ((Fig. 4, B) and laminin, but negative fortype IV collagen, CK7, AE1/AE3, and vimentin. Based on thehistologic and immunohistochemical findings, the tumor wasdiagnosed as BSCC. Four years after surgery, the patient was

1 shows a red irregular mass in the left mandibular posteriorin the right gingiva.

original magnification �10). B, Case 1 histologic findings.al palisadings (arrow) (hematoxylin-eosin, original magnifi-

f case

eosin,ripher

alive with no evidence of disease.

ase 2.

e 2. In

OOOOEe56 Hirai et al. November 2009

DISCUSSIONBasaloid squamous cell carcinoma is a rare high-

grade variant of SCC.5,6 In the head and neck, it occursmost commonly in the pyriform sinus, larynx, and baseof the tongue.3,7,8 BSCC of the oral mucosa is rare.According to Ide et al.,4 46 cases of BSCC in the oralmucosa have been reported in the English-languageliterature, with a single case of BSCC in the gingiva.

Our review of the literature revealed 5 cases ofBSCC (including the present 2 cases) occurring in thegingiva.8-10 These cases provided histopathologic de-tails. The clinical features of these patients are summa-rized in Table I. Three cases were men and 2 cases werewomen, the male-to-female ratio was 3:2, and the ageranged in age from 55 to 79 years (average 65.2 years).

Fig. 3. Immunohistochemical findings (p63). A, Case 1. B, C

Fig. 4. Immunohistochemical findings (CK14). A, Case 1. B, Cas

The most frequent site of origin was the mandible (n �

4), followed by the maxilla (n � 1). Three patientspresented at stage I, and 1 patient each at stage II andstage III. One patient had regional lymph node metas-tases. All of the patients were treated with radicalsurgery, 2 underwent neck dissection, and 2 receivedadjuvant radiotherapy. All patients were alive with noevidence of disease (at 36 months’ median follow-up).

The histologic features of BSCC have been describedin many reports.1,3,4,7-9,11-13 The neoplasm is composedchiefly of basaloid cells with the typical finding of foci ofsquamous differentiation, and the basaloid cells have darkhyperchromatic nuclei and a scant cytoplasm. The neo-plasm has squamous differentiation ranging from focalsquamous differentiation to Carcinoma in situ (CIS) toinvasive SCC. The neoplasm occasionally shows palisad-

In both cases, basaloid carcinoma cells are positive for p63.

both cases, basaloid carcinoma cells are focally positive for CK14.

ing of the peripheral tumor cells, comedonecrosis, and

-eosin

radioth

OOOOEVolume 108, Number 5 Hirai et al. e57

intratumoral cystic spaces. To confirm the epithelial dif-ferentiation, earlier investigators used AE1/AE3 stains,although the percentage of positive varies greatly amongdifferent reports.3,6,14-17 In the present cases, case 1 waspositive and case 2 was negative for AE1/AE3.

The differential diagnosis of BSCC includes adenoidcystic carcinoma (ACC), small cell undifferentiated car-cinoma, basal cell adenocarcinoma (BCAC), adeno-squamous carcinoma, and basosquamous carcinoma.4,18-20

Both the cytologic and histomorphologic characteristics ofthe solid type of ACC are quite similar to those ofBSCC.21 Klijanienko et al.22 indicated that distinguishingbetween BSCC and ACC may be difficult or impossible,especially when only a small diagnostic biopsy sample isavailable. In fact, we misdiagnosed case 2 as ACC basedon the initial biopsy specimen. Although one paper statedthat immunohistochemistry was not particularly helpful indistinguishing between ACC and BSCC,23 several authorsfound that immunohistochemistry was helpful in distin-guishing between the two.18,24,25 Coletta et al.18 foundthat the cells of ACC expressed CK7, signaling a ductalpattern possibly of salivary gland origin, whereas thebasaloid cells in BSCC were positive only for CK14.

Fig. 5. Case 2 histologic findings. A, Keratinization is obB, Central comedonecrosis is observed (arrow) (hematoxylin

Table I. Published cases of basaloid squamous cell ca

Author Year Age/gender Site of les

Abiko et al.8 1998 79/F MandibWedenberg et al.9 1997 55/M MaxillaSubramanian et al.10 2009 72/F MandibHirai et al. (present cases) 2009 55/M Mandib

65/M Mandib

NED, No evidence of disease; FND, functional neck dissection; RT,

Furthermore, the presence of basement membrane–like

material positive for laminin and type IV collagen in themicrocystic spaces is a feature of BSCC but not of ACC.Madur et al.25 found that BSCC were negative for vimen-tin and S-100. Emanuel et al.24 found that the p63 stainingpattern of BSCC differed strikingly from the stainingpattern in ACC. BSCC consistently displayed diffuse p63positively, with staining of nearly 100% of tumor cells. Incontrast, ACC displayed a consistently compartmental-ized pattern within tumor nests. Both of the present caseswere positive for laminin, CK14, and p63 and negative forvimentin, type IV collagen, CK7. For S-100 protein, case1 was negative and case 2 was positive. Banks et al.3

found that 39% of BSCC were positive for S-100 protein.Regarding type IV collagen, Ferlito et al.26 found that 5out of 15 BSCC cases were positive for type IV collagen.

Andreadis et al.20 found that BSCC and BCAC sharedsome similar microscopic features, such as basaloid epi-thelial cell aggregations in solid, membranous, trabecular,and tubular nests separated from each other by thin septaor thick bands of collagenous stroma, a characteristicperipheral palisading of nuclei, foci of necrosis, and stro-mal hyalinization, and immunohistchemical findings arecritically helpful in the differential diagnosis of these

(arrow) (hematoxylin-eosin, original magnification �10)., original magnification �40).

a in the gingiva

Clinical stage TreatmentClinical outcome

(follow-up)

I (T1N0M0) Excision NED (24 mo)I (T1N0M0) Excision NED (5 mo)

III (T3N1M0) Excision � FND � RT NED (12 mo)II (T2M0N0) Excision � FND NED (79 mo)I (T1N0M0) Excision � RT NED (60 mo)

erapy.

served

rcinom

ion

le

lelele

tumors. Immunohistochemically, CK7, vimentin, and

OOOOEe58 Hirai et al. November 2009

S100 are positive in BCAC but not in BSCC. In thepresent cases CK7 and vimentin were negative, and S-100protein was positive in case 1.

Cadier et al.27 stated that it was worthwhile to notethat basaloid squamous carcinoma is quite distinct frombasosquamous carcinoma, which is an atypical basalcell carcinoma of the skin, has squamous elements, isan aggressive tumor, and not uncommonly metasta-sizes, unlike normal basal cell carcinoma.

The clinical course and prognosis of BSCC are thoughtto be worse than those of typical SCC, based on the highrecurrence rates, regional and distant metastases, andlower survival rates.3,8,9,15,22 However, few studies haveevaluated the clinical course of BSCC located exclusivelywithin the mouth, and the sample sizes are too small to berepresentative or to determine a prognosis.8,14,18 Sampaio-Goes et al.28 compared 17 BSCCs in the oral cavity withtypical SCCs in the oral cavity and concluded that theprognosis of BSCC does not differ from that of typicalSCC when matched for clinical stage. Because we couldnot find any English-language literature summarizingBSCC in the gingiva, we summarized the reported cases,including the present 2 cases. Unfortunately, the samplesize is too small to establish prognosis. The present caseswill require long-term follow-up, despite local tumor con-trol and no evidence of metastasis.

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Reprint requests:

Eiji HiraiOral and Maxillofacial SurgeryOita Red Cross Hospital870-0033, Chiyomachi 3-2-37Oita-city, OitaJapan

sika4@oita-rc-hp.jp