Papillary Squamous Cell Carcinoma: A Rare Oral Variant

Headnote

Abstract

Squamous cell carcinoma is the most common malignancy ofthe oral cavity. Inmost ofthe instances, squamous cell carcinomas do not present with diagnostic difficulty. However, papillary squamous cell carcinoma, a rare variant of conventional squamous cell carcinoma can histologically mimic both benign and other malignant lesions. Therefore, an accurate diagnosis is important for prognostic and therapeutic purposes. The present article reports a rare case of papillary squamous cell carcinoma ofthe oral cavity in a female patient, which presented as an exophytic growth. In this article emphasis has also been laid on the clinical features, differential diagnoses, immunohistochemical analysis, treatment and prognosis ofthis lesion.

Keywords: Squamous cell carcinoma; papillary squamous cell carcinoma; micro-invasion.

Introduction

Papillary squamous cell carcinoma (PSCC) is a clinically rare variant of squamous cell carcinoma (SCC) ofthe upper aerodigestive tract mucosa which was first described by Parkhill in 1968.1 Crissman et ah, were the first one to propose the term papillary carcinoma to this variant of SCC.2 This lesion was included in the current WHO classification and has been described in other parts of the body including skin, uterine cervix, conjunctiva ofthe eye and thymus.' It occurs predominantly in men in the 6th and 7th decades and the most common site is the larynx, followed by the oropharynx and nasopharynx.2 3 PSCC is very rare in the oral cavity; only a few cases have been reported so far.4 Herewith, a case of PSCC of the oral cavity has been reported to focus its clinical features and histopathological pattern.

Case report

A 40-year-old female patient reported to the out patient department with a complaint of pain and growth in her lower right region of mouth since 2 months. Patient was apparently healthy with no known systemic illness and was moderately built and nourished. History revealed that a small growth was seen few months ago in the same region which has progressed to the present size. The growth was rapidly progressing and was associated with pain. Patient had the habit of paan chewing from past few years. Intraoral examination revealed a proliferative lesion on the right side of the labial mucosa measuring about 2.5X1.5cm extending to the labial sulcus in relation to 43, 44 and 45. Surface ofthe lesion was irregular giving a cauliflower like appearance with a mixture of red and white areas and the surrounding mucosa was normal in colour (Figure 1). The lesion had a rough surface texture and was tender on palpation with no signs of bleeding on touching. Extraoral examination revealed palpable right submandibular lymph node which was tender. Orthopantamograph was obtained and there was no evidence ofunderlying bone invasion.

Complete excision of the lesion was performed and sent to the Department of Oral and Maxillofacial Pathology for histopathological examination. Hematoxylin and eosin stained sections revealed a numerous exophytic papillary projections ofthe hyperkeratinized stratified squamous epithelium with thin connective tissue core consisting ofnumerous blood vessels filled with RBC's and chronic inflammatory cells (Figure 2). Epithelial cells showed basilar hyperplasia, alterednuclear/cytoplasmic ratio, nuclear hyperchromatism, cellular and nuclear pleomorphism, abnormal mitosis, and individual cell keratinization (Figure 3 ). Apoptotic bodies were also observed in the epithelium. There was also evidence of micro-invasion ofthe tumor cells into the connective tissue (Figure 4). Immunohistochemical analysis of Ki-67 was performed which exhibited moderate positivity at the basal and parabasal cell layer and at the areas of invasion (Figure 5).

Based on the clinical, histopathological and immunohistochemical study, a final diagnosis of papillary squamous cell carcinoma was rendered. Wide excision ofthe lesion was performed and no supplemental radiotherapy or chemotherapy was administered. Patient was regularly being recalled and evaluated. So far there are no signs of recurrence, and also the tender and palpable submandibular lymph node has become normal and the lesion site has healed satisfactorily.

Discussion

Papillary squamous cell carcinoma (PSCC) is an uncommon variant of squamous cell carcinoma that occurs predominantly in males in the 6a1 and 7a1 decades of life.2 3 The lesions occur most frequently in older men like nearly all variants of SCC ofthe upper aerodigestive tract.5 Although the lesions occur most frequently in the larynx, they may occur throughout the upper aerodigestive tract, especially within the sinonasal tract.2 3 5 PSCC most often presents as a soft, friable, polypoid, exophytic and papillary tumor.2

As in conventional SCC, smoking and alcohol have been assumed to be a significant etiological factor in PSCC.3 Because ofthe clinical and histopathological similarities between PSCC and squamous cell papilloma, it was postulated that HPV might be an important étiologie factor in PS CC.3 5 Latest techniques have demonstrated the frequent association of high risk HPV-16 in the sinonasal tract, oropharynx and larynx.3 6 However, there have been no studies on association of HPV in oralPSCC.7

Macroscopically, these lesions are largely exophytic and appear papillary or even warty, similar to verrucous carcinomas.5 These lesions might have a soft to firm consistency which may be arising from a broad base or from a narrow pedicle/stalk.6 Microscopically, low-power appearance is similar to sinonasal papillomas.2 These lesions typically demonstrate a papillary pattern consisting of multiple, thin, delicate filiform, fingerlike papillary projections with fibrovascular cores.1 The fibrovascular cores are covered by neoplastic, immature basaloid cells or more pleomorphic cells and shows minimal keratosis.2 The papillary proj ections are covered with a stratified squamous epithelium that shows features of malignancy like increased nuclear/cytoplasmic ratios, nuclear irregularities, and numerous mitotic figures located throughout the entire thickness of the epithelium.25

Stromal invasion can be found but may require multiple sections and re-orientation of the tissue sections in order to demonstrate definitive invasion. An associated rich chronic inflammatory response is frequently evident.6 Koilocytic atypia is frequently seen, which is seen as hyperchromatic, crenated nuclei surrounded by a clear halo of cytoplasm and an accentuated cell border. Stromal invasion usually consists of a single or multiple nests of tumor cells with dense lymphoplasmacytic inflammation at the tumor-stroma interface.2 Resection specimens should be assessed carefully for invasion because invasive lesions tend to behave in a manner more similarto conventional-type SCC.5

Two morphologic types of PSCC were identified: (1) a keratinizing (K) type, in which the dysplastic epithelium showed maturation trend with minimal surface parakeratin; and (2) a non-keratinizing (NK) type, in which the papillae were covered with immature basaloid cells.8 Terada has reported a case ofPSCC ofthe oral cavity with acantholytic and pseudovascular features.4 The growth pattern of PSCC evokes a clinical and histologic differential diagnosis ranging from solitary papilloma to verrucous carcinoma.2 The most common differential diagnosis to be considered with these lesions includes sinonasal or Schneiderian papillom2,5 as.

Takeda et al., reported that PSCC had a high Ki-67 labeling index (53.2- 59.0%), almost the same as that of SCC (56.770.4%).2 Immunohistochemical assessment of cellular proliferative activity showed a significantly high mean percentage of Ki-67 expression in comparison with verrucous carcinoma, but there was no significant difference of Ki-67 expression among PSCC, conventional squamous cell carcinoma and micro-invasive squamous cell carcinoma.2,7

Ding et al., studied 12 cases ofPSCC and found positivity for CKpan, CKhmw (high molecular weight), p53 andnegativity for CK8, vimentin, desmin, smooth muscle actin and S-100.1

It is currently recommended that non-invasive PSCC be treated by complete surgical excision.2 The treatment of an invasive PSCC, is based on the stage ofthe invasive component. PSCC has low or moderate grade malignancy. Supplemental radiotherapy and/or chemotherapy are the other treatment modalities for an invasive PSCC. It is presumed that distant metastasis of PSCC is rare and its prognosis is good.2,3,6

Conclusion

It is essential for the pathologist to differentiate PSCC from conventional SCC as PSCC has a better prognosis than the conventional SCC. Eventually, therapeutic modalities may be modified on the basis of the overall excellent prognosis ofpatients with papillary squamous cell carcinoma.

References

References

1. Ding Y, Ma L, Shi L, Feng J, Liu W, Zhou Z. Papillary squamous cell carcinoma of the oral mucosa: a clinicopathologic and immunohistochemical study of 12 cases and literature review. Ann Diagn Pathol 2013;17:18-21.

2. Singh S, Garg KN, Gupta K, Bhat P. Papillary Squamous Cell Carcinoma: A Review. J Dentofac Sei 2012; 1: 3-25.

3. Cardesa A, Nadal A. Carcinoma of the head and neck in the HPV era. Acta Dennatoven APA2011 ;20:164-65.

4. Terada T. Papillary squamous cell carcinoma of the oral cavity with acantholytic and pseudovascular features. Int J Clin Exp Pathol 2011;4:794-96.

5. Stelow EB, Mills SE. Squamous Cell Carcinoma Variants of the Upper Aerodigestive Tract. Am J Clin Pathol 2005; 124: S96-109.

6. Thompson LDR. Squamous cell carcinoma variants of the head and neck. Curr Diagn Pathol 2003 ;9:384-96.

7. Terada T. Papillary squamous cell carcinoma of the mandibular gingiva. Int J Clin Exp Pathol2012;5:707-9.

8. Samir K, El-Mofty. HPV-Related Squamous Cell Carcinoma Variants in the Head and Neck. Head and Neck Pathol 2012 ; 6:S55-62.