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Print version ISSN 0365-0596
An. Bras. Dermatol. vol.86 no.4 Rio de Janeiro July/Aug. 2011
Inverted papilloma (Schneiderian papilloma) with involvement of the oral cavity: report of an unusual case*
Marta Rabello PivaI; Thiago de Santana SantosII; Paulo Ricardo Saquete Martins FilhoIII; Paulo Nand KumarIV; Liane Maciel Almeida SouzaV; Luiz Carlos Ferreira da SilvaVI
IPhD in Oral Pathology from the Federal University of Rio Grande do Norte (Universidade Federal do Rio Grande do Norte - UFRN) - Professor of Oral Pathology at the Federal University of Sergipe (Universidade Federal de Sergipe - UFS) - São Cristovao (SE), Brazil
IIMaster's degree in Buccomaxillofacial Surgery and Traumatology from the School of Dentistry of Pernambuco, University of Pernambuco (Faculdade de Odontologia de Pernambuco, Universidade de Pernambuco - FOP - UPE) - PhD program student in Buccomaxillofacial Surgery at the School of Dentistry of Ribeirao Preto, São Paulo University (Faculdade de Odontologia de Ribeirao Preto, Universidade de São Paulo - FORP - USP) - Ribeirao Preto (SP), Brazil
IIIMaster's degree in Health Sciences from the Graduate Medical Studies Nucleus, Federal University of Sergipe (Nucleo de Pos- graduagao em Medicina, Universidade Federal de Sergipe - UFS) - Substitute Professor of Oral Diagnosis at the Federal University of Sergipe (Universidade Federal de Sergipe - UFS) - São Cristovao (SE), Brazil
IVDental surgeon graduated from the Federal University of Sergipe (Universidade Federal de Sergipe - UFS) - Dental surgeon at the Hospital Dentistry Unit, Emergency Hospital of Sergipe (Unidade de Odontologia Hospitalar, Hospital de Urgencia de Sergipe (HUSE) - Aracaju (SE), Brazil
VPhD in Implant dentistry from the School of Dentistry São Leopoldo Mandic (Faculdade de Odontologia São Leopoldo Mandic - SLMANDIC) - Professor of Oral Surgery I at the Federal University of Sergipe (Universidade Federal de Sergipe (UFS) - São Cristovao (SE), Brazil
VIPhD in Buccomaxillofacial Surgery and Traumatology from the School of Dentistry of Pernambuco, University of Pernambuco (Faculdade de Odontologia de Pernambuco, Universidade de Pernambuco - FOP - UPE) - Professor of Oral Surgery II at the State University of Sergipe (Universidade Federal de Sergipe (UFS) - São Cristovao (SE), Brazil
Inverted Schneiderian papilloma (ISP) is a neoplasm of epithelial lining origin which arises in the respiratory mucosa that lines the nasal cavity and paranasal sinuses. The inverted Schneiderian papilloma frequently appears as a unilateral lesion in the nasal septum and extends secondarily to the nasal and paranasal sinuses. This paper reports an unusual case of this pathology with involvement of the oral cavity in a 61-year-old white man. Clinical evaluation revealed a vegetating mass in the alveolar ridge of the right maxilla that had been present for approximately 4 months. After radiographic evaluation, involvement of the maxillary sinus was detected. Microscopic evaluation, in situ hybridization and immunohistochemical analysis of the specimen led to a diagnosis of ISP moderate dysplasia associated with HPV infection.
Keywords: Immunohistochemistry; In Situ Hybridization; Papilloma, inverted; Pathology, oral
Inverted Schneiderian papilloma (ISP) is a neoplasm of epithelial lining origin, with onset on the respiratory mucosa that lines the nasal cavity and paranasal sinuses, also known as Schneiderian membrane.1 Three morphologically distinct forms of Schneiderian papilloma may be detected: inverted papilloma, oncocytic papilloma and exophytic papilloma. The oncocytic papilloma has not been associated with the human papillomavirus (HPV), in contrast with the inverted papilloma and the exophytic papilloma, which may undergo squamous metaplasia and verrucous proliferation. Approximately 20% of the ISP may present several degrees of epithelial dysplasia, which confers a malignant potential to this type of tumor.2 The ISP frequently appears as a unil ateral lesion on the nasal septum that extends secondarily to the nasal cavity and paranasal sinuses.3 The present study reports an unusual ISP case with oral cavity involvement. Furthermore, the immunohistochemical profile of this type of tumor and its association with HPV were evaluated.
A 61-year old white man, with no signs of nasal obstruction, presented an exophytic mass on the right alveolar border of maxilla for approximately 4 months, with two recurrence episodes after surgical removal (Figure 1). The lesion was white-reddish and of vegetating aspect, bleeding after palpation. The patient reported history of dental extraction from the site that had taken place 5 months before. The panoramic X-ray reveated a radiodense image that occut pied the entire right maxillary sinus (Figure 2). Surgery was performed through the oral cavity, under general anesthesia. A reddish mas was removed, measuring around 6 cm in diameter, which apparently was not adhered to the sinus cavity walls. The sample was sent to the oral pathology laboratory and analyzed by routine procedure, with slides stained using the hematoxylin-eosin technique. The histopathological analysis revealed papilliferous projections lined by keratinized and nonkeratinized squamous epithelium, with invagination areas directed to the stroma (Figure 3A) and koilocytes in the superficial layers (Figure 3B). In some of the basal and parabasal layer areas, hyperchromatic cells could be observed, with voluminous nuclei and scarce cytoplasm and mitotic figures. The connective tissue was edematous. Vascular con gestion and discreet mononuclear inflammatory infiltrate were also observed (Figures 3 and 4A). On this occasion, the mass was diagnosed as moderate epithelial dysplasia associated with infection by HPV. The case was analyzed and diagnosed as ISP.
An in situ hybridization was requested to obtain additional data for discussion and positive results were obtained for HPV of the types that present low (6/11) and high risk (16/18) for malignancy (Figure 4B). In addition, an immunohistochemical study was carried out for detection of p53, p21, Ki-67 and CD44v6. Ki-67 is a cell proliferation marker, p53 and p21 verify if cell transformation is taking place and CD44v6 verifies whether there is cell adhesion alteration.
Positive staining was classified as weak, moderate and strong, according to the positive cells rate (<20%, 20-40% and > 40%, respectively. Immunohistochemistry was negative for p53, weakly positive for p21, moderately positive for Ki-67 in the several layers in the lower third of the epithelium (Figure 5) and strongly positive for CD44v6 in nondysplastic epithelial areas (Figure 6A). The dysplastic areas of the neoplasm presented reduced CD44v6 exprest sion (Figure 6B). The patient had not shown any signs of recidivism in two years after surgery.
The ISP case here described had its onset in the paranasal sinuses and grew toward the oral cavity, possibly due to buccosinusal communication resulting from dental extraction in the region. The X-ray image of the maxillary sinus lesion, as well as the histological analysis of the sample removed defined the ISP diagnosis.
The dysplastic areas in the epithelium lining the lesion and the confirmation of presence of high-risk HPV through in situ hybridization corroborate its malignization potential. According to Depprich et al.4, ISP may evolve into a verrucous carcinoma or a squamous-cell carcinoma, with possible involvement of HPV in the malignant transformation process.
According to the WHO, the malignization potential of ISP may also be related to keratinization of lesions, since in most cases its lining epithelium is keratin-free.5 The keratinized squamous epithelium areas found in our case may result from communication of the lesion with the oral cavity. According to Nair et al.6, the squamous metaplasia undergone by ISP in some situations and the clinical acquisition of a verrucous aspect may be reasons for diagnostic error, as the lesions are easily mistaken for verrucous carcinoma.
Thus, it is important to emphasize that the term epithelial dysplasia is employed when there are morphological and architectural alterations that may involve some layers or the entire epithelium, characterizing the lesion as potentially malignant. In accordance with the findings in this case, we may consider ISP as an epithelial hyperplasia induced by HPV, that may present alterations ranging from dysplasia to carcinoma. The epithelial dysplasia was evidenced by epithelium disorganization, as well as by immune reactions of the markers utilized.
It is a fact that HPV has oncogenic potent ial, since benign hyperplastic lesions induced by the virus may undergo neoplastic transformation. Moreover, the difficulty for histopathological and clinical delimitation of these lesions is well known, as there may be the beginning of incipient neoplasia in the borderline region of the hyperplasia. 7 Thus, we point out to the importance of utilization of immunohistochemical markers in supplementation of morphological findings for verification of potential for cellular proliferation and lesion prognosis.8, 9
The removal of papill oma lesions by invas ive methods, such as electrodissection, cryosurgery and/or laser therapy may be successful and could be combined with topical application of podophyll otoxin, trichloroacetic acid, 5-fluorouracil gel, epinephrine, topical chemotherapy, cidofovir or interferon.1 0 In the pres ent study, surgery was cons ervative and no sign of relapse was observed during two years of proservation. It should be emphasized that the nasal septum was not involved.
The absence of staining for p53 and the weak markings for p21 may be related to a possible inactivation of E6 and E7 viral proteins respectively, which would make the tissue more susceptible to malignant transformation, as it occurs in the presence of highrisk HPV, leaving the tissue susceptible to malignant transformation by additional mutations.1 1 However, the tumors associated with HPV infection usually have bett er prognosis, since they rarely overexpress p53 and p21.1 2 The moderate Ki-67 expression, involving the two lower thirds of the epithelium, mainly in nonkeratinized areas, is corroborated by report of Saegusa et al.9, who attributed a better prognosis to keratinized tumors, as Ki-67 expression is higher in nonkeratinized tumors and in little differentiated areas. Dysplastic epithelium areas showed reduced CD44v6 expression, while nondysplastic areas presented strong immunomarking. According to Ogawa et al.13, CD44 expression suggests a lower risk for metastasis, with indication of conservative treatment in cases of squamous-cell carcinoma.
These results suggest that HPV may be involved in the IPS malignant transformation process and it is an early event in tumor progression. The immunohistochemical panel presented in this report was adequate to verify the occurtence of cell protiferation and transformation in the affected tissue, as well as to study the prognosis for the case.
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Mailing address: Received on 08.02.2010. * Study carried out at the Federal University of Sergipe (Universidade Federal de Sergipe - UFS) and at the School of Dentistry of Pernambuco, University of Pernambuco (Faculdade de Odontologia de Pernambuco, Universidade de Pernambuco - FOP - UPE) - Camaragibe (PE), Brazil.
Thiago de Santana Santos
Universidade Federal de Sergipe - Departamento de Odontologia
Rua Cláudio Batista s/n, - Sanatório
CEP: 49000-000 Aracaju - Sergipe, Brazil
Approved by the Advisory Board and accepted for publication on 06.07.2010.
Conflict of interest: None
Financial funding: None
Received on 08.02.2010.
* Study carried out at the Federal University of Sergipe (Universidade Federal de Sergipe - UFS) and at the School of Dentistry of Pernambuco, University of Pernambuco (Faculdade de Odontologia de Pernambuco, Universidade de Pernambuco - FOP - UPE) - Camaragibe (PE), Brazil.