Human Papillomavirus-related Carcinomas of the Sinonasal Tract.
ABSTRACT High-risk human papillomavirus (HPV) is an established cause of head and neck carcinomas arising in the oropharynx. The presence of HPV has also been reported in some carcinomas arising in the sinonasal tract, but little is known about their overall incidence or their clinicopathologic profile. The surgical pathology archives of The Johns Hopkins Hospital were searched for all carcinomas arising in the sinonasal tract from 1995 to 2011, and tissue microarrays were constructed. p16 immunohistochemical analysis and DNA in situ hybridization for high-risk types of HPV were performed. Demographic and clinical outcome data were extracted from patient medical records. Of 161 sinonasal carcinomas, 34 (21%) were positive for high-risk HPV DNA, including type 16 (82%), type 31/33 (12%), and type 18 (6%). HPV-positive carcinomas consisted of 28 squamous cell carcinomas and variants (15 nonkeratinizing or partially keratinizing, 4 papillary, 5 adenosquamous, 4 basaloid), 1 small cell carcinoma, 1 sinonasal undifferentiated carcinoma, and 4 carcinomas that were difficult to classify but exhibited adenoid cystic carcinoma-like features. Immunohistochemistry for p16 was positive in 59/161 (37%) cases, and p16 expression strongly correlated with the presence of HPV DNA: 33 of 34 (97%) HPV-positive tumors exhibited high p16 expression, whereas only 26 of 127 (20%) HPV-negative tumors were p16 positive (P<0.0001). The HPV-related carcinomas occurred in 19 men and 15 women ranging in age from 33 to 87 years (mean, 54 y). A trend toward improved survival was observed in the HPV-positive group (hazard ratio=0.58, 95% confidence interval [0.26, 1.28]). The presence of high-risk HPV in 21% of sinonasal carcinomas confirms HPV as an important oncologic agent of carcinomas arising in the sinonasal tract. Although nonkeratinizing squamous cell carcinoma is the most common histologic type, there is a wide morphologic spectrum of HPV-related disease that includes a variant that resembles adenoid cystic carcinoma. The distinctiveness of these HPV-related carcinomas of the sinonasal tract with respect to risk factors, clinical behavior, and response to therapy remains to be clarified.
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ABSTRACT: The sinonasal cavities represent an anatomical region affected by a variety of tumours with clinical, aetiological, pathological, and genetic features distinct from tumours at the main head and neck cancer localizations. Together, squamous-cell carcinoma and adenocarcinoma account for 80% of all sinonasal tumours, and are aetiologically associated with professional exposure to wood and leather dust particles and other industrial compounds, and therefore, are officially recognized as an occupational disease. Owing to their distinctive characteristics, sinonasal tumours should be considered as separate entities, not to be included in the miscellany of head and neck cancers. Sinonasal tumours are rare, with an annual incidence of approximately 1 case per 100,000 inhabitants worldwide, a fact that has hampered molecular-genetic studies of the tumorigenic pathways and the testing of alternative treatment strategies. Nevertheless, the clinical management of sinonasal cancer has improved owing to advances in imaging techniques, endoscopic surgical approaches, and radiotherapy. Genetic profiling and the development of in vitro cell lines and animal models currently form the basis for future targeted anticancer therapies. We review these advances in our understanding and treatment of sinonasal tumours.Nature Reviews Clinical Oncology 06/2014; · 15.03 Impact Factor
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ABSTRACT: SMARCB1 (INI-1) is a tumor-suppressor gene located on chromosome 22q11.2. Its gene product is ubiquitously expressed in nuclei of all normal tissues. SMARCB1 gene inactivation has been implicated in the pathogenesis of a diverse group of malignant neoplasms that tend to share "rhabdoid" cytomorphology. This group of SMARCB1-deficient tumors is now further expanded by a subset of carcinomas arising in the sinonasal tract. SMARCB1 immunostaining was performed on 142 sinonasal carcinomas. Tumors that showed loss of expression were further characterized for SMARCB1 deletions by fluorescence in situ hybridization. Nine of 142 (6%) primary sinonasal carcinomas showed loss of SMARCB1 expression by immunohistochemistry. Five patients were women, and patients ranged in age from 33 to 78 years (mean 59 y). The SMARCB1-deficient tumors were characterized by nests, sheets, and cords of cells without any histologic evidence of specific (eg, squamous or glandular) differentiation. The tumors comprised varying proportions of basaloid and rhabdoid cells. The SMARCB1-deficient carcinomas had been diagnosed as nonkeratinizing squamous cell carcinomas (n=3), sinonasal undifferentiated carcinomas (n=2), myoepithelial carcinoma (n=2), nonintestinal adenocarcinoma (n=1), and carcinoma, not otherwise specified (n=1). Fluorescence in situ hybridization analysis revealed SMARCB1 deletions in 6 of 8 (75%) carcinomas. The SMARCB1-deficient carcinomas did not harbor human papillomavirus or NUT-1 alterations. Six patients presented with T4 disease, 5 patients developed local recurrences and/or distant metastases, and 4 died of their disease. Inactivation of the SMARCB1 tumor-suppressor gene appears to be involved in the pathogenesis of a subset of sinonasal carcinomas, further expanding the family of SMARCB1-deficient neoplasms and further delineating a bewildering group of poorly/undifferentiated, aggressive carcinomas arising at this site. The ability to detect SMARCB1 loss by immunohistochemistry, particularly when dealing with poorly differentiated carcinomas with basaloid or rhabdoid features, should facilitate a more comprehensive understanding of these sinonasal carcinomas including clinical behavior and response to targeted therapies.American Journal of Surgical Pathology 07/2014; · 4.59 Impact Factor
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ABSTRACT: Small cell neuroendocrine carcinoma of the paranasal sinuses is an extremely rare and aggressive neoplasm. Despite aggressive management, the tumor carries a poor prognosis, with a high risk of local recurrence or distant metastases. The management strategy is based on that for pulmonary small cell cancer and includes platinum-based chemotherapy combined with radiotherapy. We are reporting a case of an 89-year-old female patient diagnosed with small cell carcinoma of right-sided ethmoid and sphenoid sinuses. The tumor was found to have invaded the right orbit and anterior cranial fossa. Metastases to cervical lymph nodes and bone were also found. Due to the extended stage and poor prognosis of the patient, the management plan is palliative chemoradiotherapy.Case Reports in Medicine 01/2014; 2014:874719.