Med Mol Morphol DOI 10.1007/s00795-013-0066-4

CASE REPORT

Squamous cell carcinoma with rhabdoid features of the gingiva: a case report with unusual histology Kimihide Kusafuka • Tetsuro Onitsuka • Tomoko Miki • Chika Murai • Toshihito Suda • Tomohito Fuke • Tomoyuki Kamijo • Yoshiyuki Iida • Takashi Nakajima

Received: 25 June 2013 / Accepted: 4 December 2013 Ó The Japanese Society for Clinical Molecular Morphology 2013

Abstract Squamous cell carcinoma (SCC) with rhabdoid features (SCCRF) is extremely rare in the oral cavity. We report herein a case of oral SCCRF. The patient was a 69-year-old Japanese woman who had been suffering from a mass in the right lower gingiva. Right hemi-mandibulectomy was performed. The gingival tumor was composed of pleomorphic, non-cohesive ovoid tumor cells with abundant cytoplasm and eccentric nuclei, which were positive for both pan-cytokeratin and vimentin. In another portion, moderately differentiated SCC and carcinoma in situ were also seen. A transition zone existed between the components. Finally, we diagnosed SCCRF. Four months after the operation, multiple bone metastases, lung and skin metastases and marked hypercalcemia were found. SCCRF, therefore, might be more aggressive than the usual type of oral SCC. Keywords Squamous cell carcinoma  Rhabdoid cells  Gingiva  Acantholysis  Immunohistochemistry

Introduction Squamous cell carcinoma (SSC) is a common malignant tumor in the oral cavity, but some variations of SCC are known, including acantholytic SCC (ASCC) [1]. Such a variant of SCC is rare. ASCC usually shows duct-like structures, but SCC with rhabdoid features (SCCRF) shows non-cohesive growth of ovoid carcinoma cells without duct-like structures. SCCRF is the extreme phenotype of ASCC, which is composed of non-cohesive carcinoma cells with large ovoid or pleomorphic eosinophilic cytoplasm and eccentric nuclei. Herein, we present a case of SCC of the gingiva in which [70 % of the tumor consisted of pleomorphic, large, and non-cohesive cells that often showed rhabdoid features. The residual portion was composed of cohesive tumor cells, which showed the usual type of SCC and carcinoma in situ (CIS). We describe the clinicopathological and immunohistochemical features of oral SCCRF. To the best of our knowledge, this case is the first report of oral SCCRF.

Case report K. Kusafuka (&)  T. Miki  T. Nakajima Pathology Division, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan e-mail: [email protected] T. Onitsuka  T. Suda  T. Fuke  T. Kamijo  Y. Iida Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan C. Murai Division of Dentistry and Oral Surgery, Shizuoka Cancer Center, Shizuoka, Japan

The patient was a 69-year-old Japanese woman who had been suffering from swelling of the right anterior portion of the gingiva. Three months later, the mass enlarged rapidly, and she was admitted to a local dental clinic, where a right gingival tumor and a tumor of the right upper lip were diagnosed. She was admitted to our hospital 1 month later. A bulky and protruding tumor was found in the right anterior portion of the gingiva, which expanded to the floor of the mouth and sublingual mucosa of the tongue. MRI and CT suggested invasion to the floor of the mouth, the sublingual gland,

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the sublingual mucosa of the tongue, and the bone marrow of the mandible. A whitish lesion with lowpapillary growth was also found at the right upper lip. Under the clinical diagnosis of advanced gingival carcinoma and early lip carcinoma, right hemi-mandibulectomy and partial resection of the right side of the tongue, mucosal resection of the right lip tumor, and bilateral neck dissections were performed. Multiple metastases to the chest skin, both lungs, and systemic bones occurred with hypercalcemia 6 months later. She was alive with disease in another hospital 2 years after the operation.

Materials and methods Several step-sections were fixed in 10 % formalin and processed by routine histological techniques, including mucin stains, such as mucricarmine and Alcian blue-periodic acid Schiff (AB-PAS). Hemi-mandibrectomy specimen was decalcified with Planck-Rychlo decalcification solution (formic acid, hydrochloric acid and aluminum chloride hexahydrate) at 4 °C for approximately 2 weeks and embedded in paraffin wax. Immunohistochemistry was performed on the deparaffinized tissue sections using the primary antibodies (Table 1), EnVision (DakoCytomation, Carpinteria, CA, USA) method and an Autostainer (DakoCytomation).

Pathological findings Macroscopically, a 23 9 35 9 25 mm, protruding, dark reddish mass was observed from the right anterior portion of the gingiva to the right sublingual region (Fig. 1a, b). On the cut surface, mandibular bone invasion was found. Although the pre-operative biopsy specimen showed it was the usual type of SCC, the surgical specimen histologically showed that [70 % of the tumor consisted of alveolar- or reticular-pattern proliferation of non-coherent, pleomorphic, ovoid to polygonal tumor cells with edematous intercellular spaces (Fig. 2a). The tumor cells possessed abundant eosinophilic cytoplasm, eccentric nuclei, marked cellular atypia, and enlarged nucleoli, which showed rhabdoid features (Fig. 2b). The tumor sometimes contained elongated spindle cells with marked cellular atypia. The tumor cells were negative for mucin staining, such as mucicarmine and AB-PAS stains. The residual portion of the gingival tumor showed the typical histology of moderately differentiated SCC with focal keratinization, intercellular bridges, and tight coherence (Fig. 2c) and CIS existed at the sublingual mucosa. The components intermingled with a transitional zone between them. Venous permeation of the tumor cells was observed near the margin of the oral floor (Fig. 2d). Immunohistochemically, the non-coherent tumor cells were for positive for pan-cytokeratin (CK), CK5/6, CK14,

Table 1 Antibodies used in this study and their results Antigan

Clone

Source

Case SCCRF

MDSCC

Pan-CK

AE-1/3

Signet Laboratories (Danham, MA, USA)

??

??

HMWK

34 b El2

DakoCytomation (Carpinteria. CA, USA)

?

?

CK5/6

D5/16B4

DakoCytomation (Carpinteria. CA, USA)

p?

?

CK14

LL002

Chemicon International (Temecula, CA. USA)

p?

p?

p63

4A4

LAB Vision (Fremont CA, USA)

?

??

Vimentin

V9

S-100 protein

DakoCytomation (Carpinteria. CA, USA)

??

-

DakoCytomation (Carpinteria. CA, USA)

-

-

Melanosome

HMB45

DakoCytomation (Carpinteria. CA, USA)

-

-

Melen-A aSMA

A103 1A4

DakoCytomation (Carpinteria. CA, USA) DakoCytomation (Carpinteria. CA, USA)

-

-

Desmin

D33

DakoCytomation (Carpinteria. CA, USA)

-

-

Caldesmon

h-CD(M3557)

DakoCytomation (Carpinteria. CA, USA)

-

-

CEA

CEM10

TaKaRa Bio (Shiga, Japan)

-

p?

CA125

OC125

DakoCytomation (Carpinteria. CA, USA)

-

p?

CA19–9

116NS199

DakoCytomation (Carpinteria. CA, USA)

-

-

p53

DO-7

DakoCytomation (Carpinteria. CA, USA)

-

-

Ki-67

MJB-1

DakoCytomation (Carpinteria. CA, USA)

21.3 %

12.4 %

SCCRF squamous cell carcinoma with rhabdoid features, MDSCC moderately differentiated squamous cell carcinoma, CK cytokeratin, CEA carcinoembryonic antigen, CA carbohydrate antigen, - negative, p? partially positive, ? positive, ?? diffusely and strongly positive

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tumor showed the stratified pattern of Ki-67-labeled cells. We finally diagnosed the gingival tumor as ‘‘SCCRF’’ and the lip tumor as ‘‘verrucous carcinoma’’ The biopsy specimen from the chest skin showed pleomorphic ovoid or spindle atypical cells with intercellular myxoid spaces, which had rhabdoid features, similar to the gingival carcinoma (Fig. 5a–c); therefore, the tumor of the chest skin was a metastatic lesion from the gingival carcinoma, and not a primary metaplastic carcinoma of the breast.

Discussion

Fig. 1 a Macroscopic appearance of the resected specimen of gingival cancer. The bulky protruded tumor has a dark reddish surface, which shows erosion. b Low-power view of the cut surface of the specimen (H&E stain 94) shows a polypoid tumor with edematous stroma (black arrows) and, in its continuum, the usual histology of squamous cell carcinoma (red arrow). On this cut surface, the tumor did not invade into the mandible (asterisk) (color figure online)

high-molecular-weight keratin (HMWK), p63, and vimentin (Fig. 3a, b), whereas they were negative for carcinoembryonic antigen (CEA), CA125, CA19-9, melanocytic markers (S-100 protein, HMB45 and Melan-A), and skeletal markers such as desmin and caldesmon. The usual SCC component was positive for CKs, p63, CEA, and CA125, but negative for vimentin, CA19-9, melanocytic markers, and skeletal markers. On the other hand, the right lip tumor showed bulbous downward growth of very well-differentiated squamous cells with keratin plugs (Fig. 4a, b). Immunohistochemically, this

The present tumor showed a diffuse or alveolar pattern of non-cohesive, ovoid to spindle tumor cells in [70 % of the entire tumor, with \30 % of typical moderately differentiated SCC and CIS. This tumor was considered to have originated in the gingiva. As there was a transitional zone between the components, the non-cohesive component arose from the typical SCC component due to the biological and morphological progression of the SCC cells. This change might be from the decreased expression of E-cadherin in ASCC [11]. It was unclear, however, whether the two phenotypes were of biclonal origin or monoclonal origin, histologically and immunohistochemically. According to the current World Health Organization classification, the present tumor may be categorized as acantholytic SCC [1], because it showed morphological and immunohistochemical phenomena such as marked acantholysis of the central portion of the neoplastic squamous epithelium and was partly accompanied with typical SCC components. We considered that the present tumor might be an extreme phenotype of ASCC. As the present case mainly showed the diffuse growth of non-cohesive rhabdoid cells rather than the gland-like structures, we believe that the present case should be categorized as SCCRF rather than ASCC. Previously, we reported an early case of ASCC that showed gland-like structures of atypical squamous cells with CIS [2]. ASCC, which is an extreme rare neoplasm of the head and neck region, usually shows gland-like structures [2–4]. Although approximately 30 cases of oral ASCC have been reported [2–11], there had been not description of the rhabdoid features of this tumor. ASCC is more frequent on the skin, where it accounts for 2–4 % of all SCC [12]; however, a review of the English literature revealed 22 cases of ASCC on the vermilion border of the lips [10] and 12 cases in the oral mucosa [2, 7–9, 13–16] Nine patients were men and 4

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Med Mol Morphol Fig. 2 Histological findings of the gingival tumor. Tumor cells show diffuse proliferation with non-coherence (a H&E stain 9200). Tumor cells show marked cellular atypia, eosinophic cytoplasm, eccentric nuclei, and swelling of the nucleoli with intercellular edema (b H&E stain 9400). Another part shows moderately differentiated squamous cell carcinoma, which is composed of keratinization and tight intercellular junctions such as intercellular bridges (c H&E stain 9200). The tumor embolus is seen, which consists of less adherent tumor cells (d H&E stain 9200)

Fig. 3 Immunohistochemical findings of the gingival tumor. The gingival tumor cells are positive for both pan-cytokeratin (a immunostaining 9200) and vimentin (b immunostaining 9200)

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women. The age ranged from 50 to 86 years, with an average age of 63 years. Five lesions were located on the tongue, 4 on the floor of the mouth, 3 on the gingiva (2 maxilla, 1 mandible), and 1 on the buccal mucosa. Due to the lack of cases, the main clinical features of ASCC have not been fully elucidated. Malignant epithelial tumors with rhabdoid features have been described at various sites, including the stomach [17], colon [18], lung [19], urinary bladder [20], pancreas [21], and skin [22–24]. Carcinomas with true rhabdoid features were positive for both pan-CK and vimentin [17–24]. Although rhabdoid features were prominent in these reported cases, they frequently also had the typical components of the usual neoplasia of such organs to some extent. However, carcinomas with rhabdoid features are also extremely rare in other organs. For example, the rhabdoid gastric adenocarcinoma shows 0.1 % of the total gastric carcinomas [17], whereas only 32 cases of lung carcinomas with rhabdoid features have been reported in the English literature [19]. Skin SCCRF clinically showed the rapid growth mass with easy bleeding such as the present case [22–24]. The present case also had a typical SCC component. In general, the rhabdoid phenotype is associated with a poor prognosis [25]. We recently reported two cases of salivary duct carcinoma with rhabdoid features (Kusafuka et al. [26], accepted), and these two patients are alive with multiple metastatic diseases. Although this patient also showed

Med Mol Morphol

Fig. 4 Pathological findings of the lip tumor. Macroscopically the tumor is a whitish plate-like lesion (a) and histologically, it suggests verrucous carcinoma, which is composed of papillomatous growth of the well-differentiated neoplastic squamous epithelium with keratin plugs and elongation of the rete ridges (b H&E stain 9100)

multiple metastases subsequently, she is alive. We speculated that rhabdoid cells in SCCRF might lose the cell–cell adhesion due to decreasing the expression of E-cadherin [11] and sydecan-1 [27], and might acquire more aggressiveness or invasion ability due to intracytoplasmic accumulation of the c-2 chain of laminin and b-catenin [15], so SCCRF may be related with a worse prognosis. Some investigators have suggested that as rhabdoid features are related to apoptosis [28], such features might indicate a more aggressive type of neoplasia to some extent. SCCRF of the skin clinically showed rapid growth and poor prognosis, and the present case histologically showed the similarities with it. Verrucous carcinoma is infrequently seen in the lip mucosa. This tumor is one subtype of SCC, which shows very good differentiation of neoplastic squamous epithelium. The present case showed the typical histology of verrucous carcinoma and arose at a different site from the gingival SCCRF. These tumors were, therefore, entirely different. In conclusion, we believe that the present case is the first well-described report of SCCRF arising in the lower gingiva, accompanying verrucous carcinoma of the lip. Immunohistochemically, the rhabdoid cells expressed both CKs (epithelial markers) and vimentin (mesenchymal marker), but were negative for skeletal and neuroectodermal markers. Oral SCCRF may show a worse prognosis than the usual oral SCC.

Fig. 5 Histologically, the biopsy specimen of the chest skin shows non-adhesive growth of the spindle or ovoid tumor cells with marked acantholysis, similar to the gingival tumor (a H&E stain 9200). Immunohistochemically, tumor cells are positive for both p63 (b immunostaining 9200) and vimentin (c immunostaining 9200)

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Med Mol Morphol Acknowledgments The author thanks Mr. Isamu Hayashi, Mr. Yoichi Watanabe, Ms. Sachiyo Oono, Ms. Kaori Nagata, Mr. Hiroshi Tashiro, Mr. Koji Muramatsu, Mr. Masatake Honda, Mr. Masato Abe, Ms. Chiho Tashiro, Mr. Takuya Kawasaki, Mr. Shogo Fujii, and Ms. Kazumi Yamamoto, the staff of the Pathology Division, Shizuoka Cancer Center, Shizuoka, Japan, for excellent technical assistance. He is also grateful to Mr. Daniel Mrozek, Medical English Service, Kyoto, Japan, for his valuable help with the English editing of this manuscript. The authors received no financial support for this research, authorship, and/or publication of this article. Informed consent Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. Conflict of interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Squamous cell carcinoma with rhabdoid features of the gingiva: a case report with unusual histology.

Squamous cell carcinoma (SCC) with rhabdoid features (SCCRF) is extremely rare in the oral cavity. We report herein a case of oral SCCRF. The patient ...
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