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Background
This is a group of carcinomas that arise within the nose and paranasal sinuses. The majority of these tumor are keratinizing squamous cell carcinomas. The rest of the tumors are undifferentiated carcinomas and adenocarcinomas. Although earlier classifications positioned this tumor as a variant of a squamous cell carcinoma, modern classifications favor a distinct entity.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS INCIDENCE/
PREVALENCEAGE SEX GEOGRAPHY EPIDEMIOLOGIC ASSOCIATIONS
DISEASE ASSOCIATIONS CHARACTERIZATION
PATHOGENESIS CHARACTERIZATION EPSTEIN-BARR VIRUS
Anticancer Res. 1998 Nov-Dec;18(6B):4581-4. Abstract quote
Epstein-Barr virus (EBV) has a well-established association with nasopharyngeal carcinoma (NPC), while its association with sinonasal carcinoma is still controversial. The role of EBV in sinonasal carcinoma and the potential value of EBER is situ hybridization in differentiating carcinomas originating from these anatomically neighboring regions were investigated. EBER in situ hybridization was applied to detect EBV in the specimens of surgically proved sinonasal carcinoma and the biopsies of carcinoma of the nasopharynx. EBER in situ hybridization was performed on paraffin embedded tissues by using PCR-derived, digoxigenin-labeled EBER-1 DNA probes.
EBV was detected in 2 of 31 (6.5%) surgical specimens of sinonasal carcinoma, including 1 keratinizing squamous cell carcinoma and 1 adenocarcinoma. EBV was detected in all of 31 (100%) biopsies of carcinomas of the nasopharynx, including 1 keratining squamous cell carcinoma, 15 nonkeratinizing carcinomas, 14 undifferentiated carcinomas, and 1 adenocarcinoma.
The present study does not support the role of EBV in the development of sinonasal carcinoma as does in carcinoma of the nasopharynx. EBER in situ hybridization is a useful adjunct for differentiating carcinomas originating from the sinonasal region and the nasopharynx.
Am J Surg Pathol. 1995 Sep;19(9):994-1001. Abstract quote
Nasopharyngeal carcinomas, a common occurrence in Southern Chinese people, shows a strong association with Epstein-Barr virus (EBV); in the same population, sinonasal carcinomas are distinctly rare. Although most nasopharyngeal carcinomas are lymphoepitheliomas, sinonasal carcinomas have a wide morphological spectrum.
We studied the clinicopathological features and EBV status of 29 sinonasal carcinomas from Hong Kong Chinese patients. By in situ hybridization using antisense Epstein-Barr virus early RNA (EBER) probe, seven tumors were shown to be strongly positive for the EBV RNA. They displayed a wide morphological spectrum, including one cylindric cell carcinoma, one intestinal type adenocarcinoma, four nonkeratinizing squamous cell carcinomas, and one undifferentiated carcinoma. All were from elderly subjects (mean age, 67), including six men and one woman. Three of these seven patients had complete remission after radiotherapy with a median follow-up period of 29 months. In two cases, EBV latent membrane protein-1 was expressed.
Detection of the virus in a number of histological subtypes, including cylindric cell carcinoma and adenocarcinoma, suggests that EBV may play a role in the pathogenesis of a diverse spectrum of carcinomas.
HUMAN PAPILLOMA VIRUS
- Prevalence of High-Risk Human Papillomavirus DNA in Nonkeratinizing (Cylindrical Cell) Carcinoma of the Sinonasal Tract: A Distinct Clinicopathologic and Molecular Disease Entity.
El-Mofty SK, Lu DW.
From the *Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO; and daggerDepartment of Pathology, Huntington Memorial Hospital, Pasadena, CA.
Am J Surg Pathol. 2005 Oct;29(10):1367-1372. Abstract quote
Carcinomas of the nose and paranasal sinuses are a heterogeneous group of neoplasms that differ histologically, biologically, and clinically. Some of these tumors are known to harbor high-risk human papillomavirus (HPV) DNA.
In an attempt to identify specific phenotypes associated with HPV infection, 39 cases of sinonasal carcinomas were evaluated by PCR for the presence of HPV DNA. The tumors were also studied with a panel of immunohistochemical stains, including p16, p53, and Ki-67 antibodies. Twenty-one cases were identified as keratinizing squamous cell carcinoma (KSCC) with a male-to-female ratio of 3:1. Eight cases were nonkeratinizing (cylindrical cell) carcinoma (NKCa) with a male-to-female ratio of 1:1. Ten cases were sinonasal undifferentiated carcinoma (SNUC), and 9 of these patients were men. HPV DNA, particularly type 16, was detected in 9 cases: 4 of 21 (19%) of KSCC, 4 of 8 (50%) of NKCa, and 1 of 10 (10%) of SNUC. In addition to a higher prevalence of HPV DNA in NKCa, the tumors also showed a distinct immunophenotype characterized by strong and diffuse staining for p16, high labeling scores for Ki-67, and negative or low reactivity to p53. On the other hand, KSCC and SNUC were either negative or weakly reactive to p16 antibodies. KSCC cases were more likely to be positive and more strongly reactive to p53 stain. Unlike KSCC, SNUC had high Ki-67 labeling scores.
These observations suggest that NKCa of the sinonasal tract is a distinct histopathologic and molecular disease entity, which should be added to the list of upper aerodigestive tract tumors with strong etiologic relationship to high risk HPV.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC LABORATORY MARKERS
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Invaginating epithelial growth with ribbons and garland-like pattern
Sharp demarcation between epithelium-stroma
High mitotic count
Extensive necrosis
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE CYTOKERATINS
- Sinonasal undifferentiated carcinoma, nasopharyngeal-type undifferentiated carcinoma, and keratinizing and nonkeratinizing squamous cell carcinoma express different cytokeratin patterns.
Franchi A, Moroni M, Massi D, Paglierani M, Santucci M.
Department of Human Pathology and Oncology, Medical School, University of Florence, Viale G.B. Morgagni 85, 50134 Florence, Italy.
Am J Surg Pathol. 2002 Dec;26(12):1597-604. Abstract quote
Sinonasal undifferentiated carcinoma (SNUC) is a highly aggressive malignant neoplasm that is often difficult to distinguish from other poorly differentiated carcinomas arising in the sinonasal tract.
To search for a differential cytokeratin (CK) expression that could be useful for diagnostic purposes, we compared the expression of a large panel of CKs in a series of 6 SNUCs, 10 poorly differentiated squamous cell carcinomas (SCCs), 10 nonkeratinizing squamous cell carcinomas (NKSCCs), and 5 nasopharyngeal-type undifferentiated carcinomas (NPTCs). SCC, NKSCC, and NPTC frequently showed immunoreactivity for CK5/CK6, CK8, CK13, and CK19. In addition, SCC and NKSCC expressed CK14, which was not detected in NPTC, and SCC expressed CK7 (60% of cases) and CK4 (30% of cases), which were absent in NKSCC and NPTC.
Three NKSCCs were associated with a Schneiderian papilloma, and the results of the immunostaining were similar in the two components, with the exception of CK4 and CK7, which were expressed by the papilloma and not by the carcinoma. In contrast to other carcinomas, SNUC was characterized by the exclusive expression of CKs of simple epithelia, such as CK8 (100% of cases), CK7 (50% of cases), and CK19 (50% of cases).
Thus, there are significant differences in the pattern of CK expression between SNUC, SCC, NKSCC, and NPTC, which could be of diagnostic aid. Moreover, these findings support the hypothesis that SNUC is a separate entity from SCC and NPTC of the sinonasal tract.ELECTRON MICROSCOPY
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES BASALOID SQUAMOUS CELL CARCINOMA
- Basaloid squamous cell carcinoma of the sinonasal tract.
Wieneke JA, Thompson LD, Wenig BM.
Department of Endocrine and Otorhinolaryngic--Head and Neck Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
Cancer. 1999 Feb 15;85(4):841-54 Abstract quote.
BACKGROUND: Basaloid squamous cell carcinoma (BSCC) is a high grade, aggressive variant of squamous cell carcinoma with a predilection for the larynx, hypopharynx, tonsils, and base of the tongue. To the authors' knowledge, BSCC originating in the nasal cavity and paranasal sinuses rarely has been reported.
METHODS: Fourteen cases of BSCC involving the nasal cavity and paranasal sinuses were identified in the files of the Otolaryngic-Head and Neck Pathology Tumor Registry of the Armed Forces Institute of Pathology from 1975-1997. Clinical records and follow-up were available in all cases. Paraffin blocks were available for histochemical and immunohistochemical studies in all cases.
RESULTS: There were 7 females and 7 males, ages 32-86 years (median, 66.5 years; mean, 62 years). The patients presented primarily with a mass lesion and unilateral nasal obstruction. In nine patients the tumor was confined to the nasal cavity. In three patients the tumor involved the sinuses alone and in two patients the tumor involved the nasal cavity and paranasal sinuses. Histologically, the tumors were widely invasive with a variety of growth patterns, including lobular, solid, trabecular, cribriform, and fascicular. The neoplastic infiltrate included predominantly pleomorphic, basaloid-appearing cells with hyperchromatic nuclei, inconspicuous to prominent nucleoli, and a variable amount of eosinophilic to clear-appearing cytoplasm. Mitotic figures, including atypical forms, were readily apparent as was necrosis (individual cell and comedo-type). Foci of squamous differentiation were limited in extent but were found in all cases and included squamous whorls, individual cell keratinization, and intercellular bridges. Intraepithelial dysplasia, carcinoma in situ, or invasive squamous carcinoma was present in all cases. Other histologic features included intercellular stromal hyalinization and peripheral nuclear palisading. In two cases, neural-type rosettes were found. Immunoreactivity for a variety of epithelial markers including cytokeratin (AE1/AE3/LP34), CAM 5.2, 34betaE12, CK7, and epithelial membrane antigen was present in all cases. Variable reactivity was present with vimentin, actins (smooth muscle and muscle specific), neuron specific enolase, S-100 protein, glial fibrillary acidic protein, CK20, carcinoembryonic antigen, Leu7, and Ewing's marker. Chromogranin, synaptophysin, neurofibrillary protein, leukocyte common antigen, HMB-45, desmin, and Epstein-Barr virus latent membrane protein were absent. Surgical resection was the treatment of choice. Eight patients had recurrent or persistent tumor and metastatic disease occurred in five patients. At last follow-up, 7 patients (50%) had died of disease with a median survival of 12 months from the time of diagnosis and 3 patients were alive with disease over periods ranging from 8 months-5 years. Of the 4 remaining patients, 2 were alive without disease at 1 month and 5 years, respectively, 1 patient was lost to follow-up with no evidence of tumor at 3 years, and 1 patient had died of unrelated causes with no evidence of disease.
CONCLUSIONS: Sinonasal BSCC is a histologically distinct variant of squamous cell carcinoma with pathologic features and aggressive biologic behavior similar to BSCC localized to more common mucosal sites of the upper aerodigestive tract.
PROGNOSIS CHARACTERIZATION VASCULAR ENDOTHELIAL GROWTH FACTOR
- Prognostic significance of microvessel density and vascular endothelial growth factor expression in sinonasal carcinomas.
Valente G, Mamo C, Bena A, Prudente E, Cavaliere C, Kerim S, Nicotra G, Comino A, Palestro G, Isidoro C, Beatrice F.
Pathology Section, Department of Medical Sciences, Amedeo Avogadro University Medical School, Novara, Italy.
Hum Pathol. 2006 Apr;37(4):391-400. Epub 2006 Feb 8. Abstract quote
The prognostic significance of microvessel density and proliferative activity of the neoplastic cells, evaluated respectively by CD31 and Ki-67 positivity, and immunohistochemical expression of vascular endothelial growth factor (VEGF) was retrospectively investigated in 105 cases of sinonasal carcinoma (80 surgical specimens and 25 biopsies).
The most represented histologic types were intestinal-type adenocarcinoma found in 36 patients (34.3%), squamous cell carcinoma (SCC) in 34 (32.4%), mucinous adenocarcinoma (mainly made up of signet-ring cell patterns) in 15 (14.3%), and adenoid cystic carcinoma in 7 (6.7%). Microvessel density values (in vessels per square millimeter), VEGF, and Ki-67 were not dependent on histologic type but were rather correlated to the histologic grading in SCC. Clinical data were available for 92 (87.6%) of 105 patients, with minimum follow-up of 48 months. Most of the patients (81.5%) were at an advanced stage (T3-T4) at diagnosis. The values of all markers were correlated to tumor stage (P = .03).
Multivariate analysis showed that both microvessel density and proliferative activity of the neoplastic cells were independent prognostic parameters (mortality hazard ratio, 1.33 and 1.60, respectively). Although VEGF expression was not correlated to prognosis on the whole series (P = .06), it was a powerful prognostic marker when the analysis was restricted to the group of SCCs (hazard ratio, 3.02; 90% confidence interval, 1.58-5.80).
These results show that tumor neoangiogenesis, expressed by microvessel density, together with proliferative activity, is a pathologic marker with a strong prognostic impact in sinonasal carcinomas. Therefore, it may be a useful tool in this field so as to carry out therapeutic protocol planning, which may be further enhanced by the adoption of the more recent antiangiogenic molecules.
TREATMENT CHARACTERIZATION GENERAL Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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