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Cancers of the nose, and especially the nose vestibule, represent a significant challenge for clinicians due to their rarity, the intricate nature of surrounding vital structures, the nonspecific early symptoms, and the etiological factors that are not completely understood. Emerging research suggests that alterations in the nasal microbiome, also known as microbial dysbiosis, may contribute to the pathogenesis of those malignancies through mechanisms involving chronic inflammation, immune modulation, and cellular changes. The aims of this paper are to review the current literature covering the nasal microbiome's role in carcinogenesis, particularly in the context of squamous cell carcinoma, and to explore how microbial dysbiosis might foster a pro-tumorigenic environment. It further discusses potential future directions for research and therapeutic approaches.

Objective: Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare, malignant tumor of neuroectodermal origin that arises from the olfactory neuroepithelium. In this study the authors present the first series in the literature on distant brain metastases (BMs) secondary to ENB that were treated with stereotactic radiosurgery (SRS), to evaluate the safety and effectiveness of SRS for this indication., Methods: A retrospective analysis of clinical and radiological outcomes of patients with ENB who underwent CyberKnife (CK) SRS at a single center was conducted. The clinical and radiological outcomes of patients, including progression-free survival, overall survival, and local tumor control (LTC) were reported., Results: Between 2003 and 2022, 32 distant BMs in 8 patients were treated with CK SRS at Stanford University. The median patient age at BM diagnosis was 62 years (range 47-75 years). Among 32 lesions, 2 (6%) had previously been treated with surgery, whereas for all other lesions (30 [94%]), CK SRS was used as their primary treatment modality. The median target volume was 1.5 cm3 (range 0.09-21.54 cm3). CK SRS was delivered by a median marginal dose of 23 Gy (range 15-30 Gy) and a median of 3 fractions (range 1-5 fractions) to a median isodose line of 77% (range 70%-88%). The median biologically effective dose was 48 Gy (range 21-99.9 Gy) and the median follow-up was 30 months (range 3-95 months). The LTC at 1-, 2-, and 3-year follow-up was 86%, 65%, and 50%, respectively. The median progression-free survival and overall survival were 29 months (range 11-79 months) and 51 months (range 15-79 months), respectively. None of the patients presented adverse radiation effects., Conclusions: In the authors' experience, SRS provided excellent LTC without any adverse radiation effects for BMs secondary to ENB.

Objectives: To assess the site and histopathology of polyps at the first revision surgery for recurrent nasal polyposis (NP) after radical ethmoidectomy (nasalization)., Study Design: Retrospective study., Methods: Between January 2008 and December 2015, a total of 62 patients having undergone revision surgery for recurrent NP after nasalization were included. The site and histology of the recurrence of polyps were analyzed according to operative and pathological reports., Results: Histology showed classical inflammatory nasal polyps (CINP) in 91% of nasal cavities at primary surgery versus respiratory epithelial adenomatoid hamartoma (REAH) or REAH associated to CINP in 54.8% at revision surgery (P < .0001). Polyps were principally observed in the ethmoidal complex in 70% of nasal cavities during primary surgery and in the olfactory clefts in 88.7% during revision surgery (P < .0001). The mean interval between nasalization and first revision surgery was 8.8 ± 4.4 years (0.4-21.7 years). This interval was significantly shorter for grade 3 polyps, polyps removed from both ethmoidal complex and olfactory cleft at primary surgery, association of CINP and REAH at primary surgery, and when primary surgery had preserved the middle turbinates., Conclusion: Polyp recurrences after nasalization were mainly observed in the olfactory clefts and can be different histological features: inflammatory polyps, respiratory epithelial adenomatoid hamartoma, or a combination of both., Level of Evidence: 4 Laryngoscope, 130:2098-2104, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

BACKGROUND Carcinosarcoma of the sinonasal tract is an extremely rare malignant neoplasm; it is often designated as carcinoma with spindle cell or sarcomatoid features. We report a case of carcinosarcoma arising in a pre-existing inverted Schneiderian papilloma in the left maxillary antrum and nasal cavity of a 72-year old male patient. CASE REPORT The patient had a significant history of radiotherapy for squamous cell carcinoma in the sinonasal area, 3 decades ago. The patient presented with chief complaints of left nasal blockage, nasal discharge, anosmia, and occasional epistaxis. Computed tomography scan displayed a lobular soft tissue mass resulting in narrowing of the nasopharyngeal airway with massive destruction of palatal tissue. The lesion was resected via endoscopic surgery. Macroscopically, a white fleshy appearance with necrosis was noted in the submitted specimen. Microscopically, the tumor was composed of pleomorphic epithelial and spindle cells with numerous mitoses and remarkable tissue necrosis. Residual inverted papilloma (IP) with high-grade dysplasia, and minimal foci of moderately differentiated squamous cell carcinoma (SCC) component was present at the tumor margin. A distinct zone of transition of SCC to spindle cell carcinoma (SpSCC) was noted and confirmed by focal positivity of p63 in epithelial and sacromatoid components. The pleomorphic sarcomatoid tumor was positive for vimentin with Ki67 highlighting 70% of tumor cells. A final diagnosis of sinonasal spindle cell carcinoma associated with residual inverted papilloma was rendered. CONCLUSIONS Due to the rarity of such cases, the prognosis and response to treatment is unclear. No effective directed treatment has been developed. Unfortunately, the patient refused any further treatment and died of persistent disease. To the best of our knowledge, only one case of sinonasal carcinosarcoma arising from dysplastic inverted papilloma has been reported. The distinct possibility of previous radiotherapy contributing to development of sarcomatoid features in this neoplasm should also be considered.

Respiratory epithelial adenomatoid hamartoma (REAH) is a rare lesion in nasal cavity first reported by Wenig and Heffner in 1995. Most commonly seen in men in third to ninth decade of life. Majority of cases presents as a polypoidal mass in one or both nasal cavities. We experienced such a case of REAH originating from the nasal septum, in posterior aspect, treated by endoscopic approach. It is important to differentiate REAH from other sinonasal pathologies like inverted papilloma and low grade sinonasal adenocarcinoma. Complete surgical resection is the treatment of choice., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Different risk factors are suspected to be involved in malignant transformation of sinonasal papillomas and include HPV infection, tobacco smoking, occupational exposure, EGFR/KRAS mutations and DNA methylation alterations. In our study, 25 inverted sinonasal papillomas (ISPs), 5 oncocytic sinonasal papillomas (OSP) and 35 squamous cell carcinomas (SCCs) from 54 patients were genotyped for 10 genes involved in EGFR signalling. HPV-DNA detection was performed by in-situ hybridisation and LINE-1 methylation was quantitatively determined by bisulphite-pyrosequencing. High-risk HPV was observed only in 13% of ISP-associated SCC and in 8% of de novo-SCC patients. EGFR mutations occurred in 72% of ISPs, 30% of ISP-associated SCCs and 17% of de novo-SCCs. At 5-year follow-up, SCC arose in only 30% (6/20) of patients with EGFR-mutated ISPs compared to 76% (13/17) of patients with EGFR-wild-type ISP (p = 0.0044). LINE-1 hypomethylation significantly increased from papilloma/early stage SCC to advanced stage SCC (p = 0.03) and was associated with occupational exposure (p = 0.01) and worse prognosis (p = 0.09). In conclusion, our results suggest that a small subset of these tumours could be related to HPV infection; EGFR mutations characterise those ISPs with a lower risk of developing into SCC; LINE-1 hypomethylation is associated with occupational exposure and could identify more aggressive nasal SCC., (© 2018 UICC.)

Rationale: Tumor-induced osteomalacia (TIO) is a rare, paraneoplastic syndrome featured with fibroblast growth factor 23 (FGF23) secretion primarily by benign mesenchymal tumors and sometimes by malignancies. TIO diagnosis and treatment is often delayed because TIO usually has nonspecific generalized bone pain and weakness, and location of TIO tumor is quite challenging. Very few TIO caused by sinonasal hemangiopericytoma have been reported in the literature., Patient Concerns: A 40-year-old Chinese woman presented with diffuse bone pain for more than 1 year. Laboratory examination showed hypophosphatemia, hyperphosphaturia, hypocalcemia, an elevated serum alkaline phosphatase (ALP) level and bone-specific ALP level. Imaging studies revealed low bone mineral density (BMD) and multiple pseudofractures at the ribs. F-18 fluorodeoxyglucose positron emission tomography was negative in searching for tumors. Because no tumor was located, the patient was treated with oral phosphate, calcium, and alfacalcidol, and achieved great relief in her symptoms and improvement in BMD. Six years later, the patient had breast cancer surgery and received chemotherapy, and still had hypophosphatemia. During this time, nasopharyngo-fiberscope showed nasal mass in her left nasal cavity. Then she had her nasal polyps removed and surprisingly the serum phosphate became normal., Diagnoses and Interventions: The patient had the nasal mass resected, and pathological diagnosis of the nasal mass was sinonasal hemangiopericytoma. Immunohistochemical analysis was positive for FGF23. Thus the final diagnosis was osteomalacia induced by sinonasal hemangiopericytoma. Phosphate supplementation and alfacalcidol were discontinued., Outcomes: The patient had normal serum phosphate after 6-month follow-up., Lessons: By presenting this case, we hope to remind clinicians that in patients with osteomalacia with undetermined reason and intranasal polypoid mass, sinonasal hemangiopericytoma should be suspected.

Backgrounds: Clinical manifestations and molecular basis of Taiwanese patients with Peutz-Jeghers syndrome (PJS) were investigated to add the knowledge of phenotype and genotype of the disease., Methods: Based on the Pathology Data Bank and the Colorectal Cancer Register, we collected their clinical data. The entire coding sequence of the STK11 gene was amplified and analyzed by sequencing using the genomic DNA., Results: Fifteen patients diagnosed with PJS from 11 unrelated families were collected until 2015. The median age at the onset of symptoms was 19 years with intussusception as the most frequent presenting symptom. Ten patients developing 11 cancers at various anatomical sites, including two cases of sinonasal cancer, two lung cancers, two breast cancers, two rectal cancers, two gynecological cancers and one small bowel cancer. Five of the deceased patients had died of cancers. The median age of diagnosis of first cancer in the probands was 32 years. Seventy patients (7 of 10) diagnosed before age of 40. Mutations found in eight families included five novel mutations (exon 6, c.843 ins G; exon 8, c.2065 delete A; exon 8, c.G923A, nonsense; exon 6, c.748dupA; and mTOR c.5107dupA) and three previously reported mutations. The other three PJS families without detectable STK11 mutations did not develop malignancies so far., Conclusion: This is the first comprehensive study of patients with Peutz-Jeghers syndrome in the Taiwanese. We have demonstrated that the phenotype of Peutz-Jeghers syndrome varies greatly among the patients. Patients with detectable STK11 mutations have very high risk of developing cancers., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

We report a rare case of squamous cell carcinoma (SCC) of the nasal cavity arising in a patient with granulomatosis with polyangiitis (GPA). The patient was a 35-year-old man who had been diagnosed 15 years earlier with GPA and treated medically for sinonasal, pulmonary, and renal involvement. He presented to us with left-sided orbital and cheek pain and nasal obstruction. Endoscopy detected a friable, exophytic mass that involved the left lateral nasal wall and septum. Biopsy analysis identified the mass as an SCC. A definitive endoscopic resection was performed, followed by chemoradiation, but the patient exhibited progression of disease 2 months after the cessation of therapy. He then underwent an open craniofacial resection and a second round of chemoradiation. At 7 months of follow-up, he remained disease-free. Sinonasal symptoms in GPA are consistent with those in chronic rhinosinusitis, but the presence of unilateral symptoms may suggest a neoplastic process. Immunosuppressants are implicated in the pathophysiology of this malignancy, but equally plausible is the oncogenic role of chronic inflammation.

Nasal and sinonasal inverted papilloma (NSIP) is a benign tumor in which surface epithelial cells grow downward into the underlying supportive tissue with varying degrees of metaplasia. Human papillomavirus (HPV) has been proposed as the causal agent in the pathogenesis of this disease. Many studies have shown that HPV can activate the Akt/mechanistic target of rapamycin (mTOR) signaling pathway, but the role of this pathway in HPV-associated NSIP is largely unknown. In this study, we enrolled 40 control tissue samples and 80 NSIP tissue samples. HPV genotyping showed that 47 of the 80 examined cases of NSIP were HPV-positive (58.8%), and the most common subtype was HPV11 (20/53, 37.7%). The immunohistochemistry showed statistically significant differences in phosphorylated Akt and phosphorylated S6 ribosomal protein staining among control samples, HPV-positive NSIP and HPV-negative NSIP. The HPV11 L1-L2 plasmid increased the proliferation of normal human nasopharyngeal epithelial NP69-SV40T cells and human nasopharyngeal cancer CNE1 cells. Meanwhile, rapamycin, an mTOR inhibitor, reversed the increased cell proliferation induced by the HPV11 L1-L2 plasmid. Western blot analysis showed that Akt/mTOR/S6 were overexpressed in NP69-SV40T cells and CNE1 cells infected with the HPV11 L1-L2 plasmid. These data demonstrate that HPV promotes cell proliferation through the Akt/mTOR signaling pathway in NSIP., (© The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder characterized by hamartomatous polyps in both of the gastrointestinal tract and mucosal pigmentation. It could increase in risk of intestinal and extra-intestinal neoplasms. We here described three cases of sinonasal polyposis in a PJS family and two developed sinonasal type adenocarcinoma. Genetic study revealed a germline STK11/LKB1 mutation on codon 179 (c.C536G, p.P179R) of exon 4. LOH analysis of the LKB1 locus confirms this to be a deleterious mutation. Sinonasal polyposis with malignant transformation could be encountered in PJS patients. Regular follow-up was recommended for the risk of malignant changes in nasal polyps.

RUNX3, runt-domain transcription factor, is a master regulator of gene expression in major developmental pathways. It acts as a tumor suppressor in many cancers but is oncogenic in certain tumors. We observed upregulation of RUNX3 mRNA and protein expression in nasal-type extranodal natural killer (NK)/T-cell lymphoma (NKTL) patient samples and NKTL cell lines compared to normal NK cells. RUNX3 silenced NKTL cells showed increased apoptosis and reduced cell proliferation. Potential binding sites for MYC were identified in the RUNX3 enhancer region. Chromatin immunoprecipitation-quantitative PCR revealed binding activity between MYC and RUNX3. Co-transfection of the MYC expression vector with RUNX3 enhancer reporter plasmid resulted in activation of RUNX3 enhancer indicating that MYC positively regulates RUNX3 transcription in NKTL cell lines. Treatment with a small-molecule MYC inhibitor (JQ1) caused significant downregulation of MYC and RUNX3, leading to apoptosis in NKTL cells. The growth inhibition resulting from depletion of MYC by JQ1 was rescued by ectopic MYC expression. In summary, our study identified RUNX3 overexpression in NKTL with functional oncogenic properties. We further delineate that MYC may be an important upstream driver of RUNX3 upregulation and since MYC is upregulated in NKTL, further study on the employment of MYC inhibition as a therapeutic strategy is warranted.

The risk of cancer is significantly increased in patients undergoing renal transplant surgery than in the general population. In particular, skin cancer is the most commonly occurring cancer in these patients.A 34-year-old man underwent living renal transplantation for focal segmental glomerulosclerosis. After 18 months, he developed a lesion on the nasal dorsum, approximately 1 cm in size, and the lesion rapidly expanded to cover the entire dorsum.Owing to its rapid expansion, the lesion was suspected to be a malignant tumor and wide excision was planned.We removed the lesion with a 6-mm margin. Squamous cell carcinoma was diagnosed through intraoperative rapid pathological examination. The nasal bone and septum were invaded by the tumor and, as a result, the entire external nose was removed. The patient's nose was subsequently reconstructed using a free forearm flap for lining, iliac bone graft for the nasal frame, and a scalping forehead flap for skin coverage.Selective target radiotherapy was administered at the closest margin around the lesion, and the dosage of immunosuppressants was reduced.At >2 years postoperatively, the patient showed good cosmetic results with no relapse or metastasis of the tumor.We report the unusual case of a young man who developed a rapidly progressing squamous cell carcinoma on his nasal dorsum after 18 months of immunosuppression. Squamous cell carcinoma in organ transplant recipients may be more aggressive and may progress differently than in regular patients. Therefore, special attention is required for patients who take immunosuppressive drugs after renal transplant surgery.

Papillomas are uncommon tumors of the sinonasal tract histologically derived from the Schneiderian membrane. Three distinctive variants are described, the exophytic, the inverting and the oncocytic types. On physical examination, their appearance varies from exophytic-fungiform seen in the exophytic variant, to polypoid-papillary in both the inverting and oncocytic variant. The presence of an asymptomatic mass or epistaxis and unilateral nasal obstruction are the typical presenting symptoms. Clinically they tend to recur and, although benign, they may erode the bone laminas by pressure, especially the inverting type, causing proptosis and other co-morbidities. Malignant transformation is seen both synchronously, on a pre-existing papilloma, and metachronously after several recurrences of papilloma. Schneiderian papillomas are at a date a topic of controversy regarding their etiology, pathogenesis and biological behavior. Furthermore, histologic criteria to assess dysplasia and malignant transformation are ill-defined. The present study aims to comparatively review the histologic types of papillomas, their etiology, the currently available criteria for malignant transformation, their treatment and prognosis., (© Copyright Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Inverted papilloma is a rare sinonasal tumor that mainly occurs in adults during the 5th decade. Three characteristics make this tumor very different from other sinonasal tumors: a relatively strong potential for local destruction, high rate of recurrence, and a risk of carcinomatous evolution. Etiology remains little understood, but an association with human papilloma virus has been reported in up to 40% of cases, raising the suspicions of implication in the pathogenesis of inverted papilloma. Treatment of choice is surgery, by endonasal endoscopic or external approach, depending on extension and tumoral characteristics. Follow-up is critical, to diagnose local relapse, which is often early but may also be late. The seriousness of this pathology lies in its association with carcinoma, which may be diagnosed at the outset or at recurrence during follow-up. It is important to diagnose recurrence to enable early treatment, especially in case of associated carcinoma or malignancy. A comprehensive review of the international literature was performed on PubMed and Embase, using the following search-terms: "sinonasal" [All Fields] AND ("papilloma, inverted" [MeSH Terms] OR ("papilloma" [All Fields] AND "inverted" [All Fields]) OR "inverted papilloma" [All Fields] OR ("inverted" [All Fields] AND "papilloma" [All Fields])). We reviewed all articles referring to sinonasal inverted papilloma published up to January 2015. The present article updates the state of knowledge regarding sinonasal inverted papilloma., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Sinonasal intestinal-type adenocarcinomas (ITACs) are epithelial tumors of the nasal cavity and the paranasal sinuses, often related to professional exposure to organic dust, mainly wood or leather. It is a rare cancer. If resectable, surgery is the treatment of choice. Postoperative radiotherapy is often indicated to increase local control. Systemic treatment (chemotherapy, targeted agents, or immunotherapy) of irresectable ITACs and/or metastasized disease is less standardized., Methods: Articles on ITAC histopathology, molecular profile, and current treatment options of this specific tumor were identified and reviewed, using the electronic databases Pubmed, Medline, Cochrane, and Web of Science., Results: This article reviews what is currently known on the histopathology, tumorigenesis, molecular characteristics, and standardized treatment options of ITAC., Conclusion: More translational research is needed to identify druggable targets that may lead to a personalized treatment plan in order to improve long-term outcome in patients with locally advanced and/or metastasized ITAC. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1570, 2016., (© 2016 Wiley Periodicals, Inc.)

A 5-year-old spayed female Shih Tzu was referred for evaluation of a nasal transitional carcinoma. A total lifetime dose of 117 Gy was delivered to the intranasal mass in three courses over nearly 2 years using fractionated intensity modulated radiation therapy (IMRT) to spare normal tissues. Clinically significant late normal tissue side effects were limited to bilaterally diminished tear production. The patient died of metastatic disease progression 694 days after completion of radiation therapy course 1. This case demonstrates that retreatment with radiation therapy to high lifetime doses for recurrent local disease may be well tolerated with IMRT., (© 2016 American College of Veterinary Radiology.)

We report a case of radiation-induced mucosal melanoma in a 41-year-old woman with a history of childhood rhabdomyosarcoma of the nasal cavity that had been treated with radiotherapy. During the workup for the melanoma, the patient was found to be negative for S-100 protein on immunostaining. While many melanotic markers for the histologic confirmation of melanoma exist, they can be negative in some cases, such as ours. To the best of our knowledge, only 1 case of radiation-induced melanoma has been previously reported in the English-language literature, and in that case the patient was S-100-positive. Although our case is rare, it suggests another possible long-term adverse effect of radiotherapy. We also describe the morphologies and histology associated with diagnosing melanoma in an S-100-negative patient.

A growing number of molecular epidemiological studies have been conducted to evaluate the association between human papillomavirus (HPV) infection and the malignancy of sinonasal inverted papilloma (SNIP). However, the results remain inconclusive. Here, a meta-analysis was conducted to quantitatively assess this association. Case-control studies investigating SNIP tissues for presence of HPV DNA were identified. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Mantel-Haenszel method. An assessment of publication bias and sensitivity analysis were also performed. We calculated a pooled OR of 2.16 (95% CI=1.46-3.21, P<0.001) without statistically significant heterogeneity or publication bias. Stratification by HPV type showed a stronger association for patients with high-risk HPV (hrHPV) types, HPV-16, HPV-18, and HPV-16/18 infection (OR=8.8 [95% CI: 4.73-16.38], 8.04 [95% CI: 3.34-19.39], 18.57 [95% CI: 4.56-75.70], and 26.24 [4.35-158.47], respectively). When only using PCR studies, pooled ORs for patients with hrHPV, HPV-16, and HPV18 infection still reached statistical significance. However, Egger's test reflected significant publication bias in the HPV-16 sub-analysis (P=0.06), and the adjusted OR was no longer statistically significant (OR=1.65, 95%CI: 0.58-4.63). These results suggest that HPV infection, especially hrHPV (HPV-18), is significantly associated with malignant SNIP., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To perform a systematic review to analyze the association between occupational exposure to wood dust and cancer., Methods: A systematic literature search of entries made in the MEDLINE-PubMed database between 1957 and 2013 was conducted to identify studies that had assessed the relationship between occupational exposure to wood dust and different types of cancer. A meta-analysis of selected case-control and cohort studies was subsequently performed., Results: A total of 114 studies were identified and 70 were selected for review. Of these, 42 studies focused on the relationship between wood dust and nasal cancer (n = 22), lung cancer (n = 11), and other types of cancer (n = 9). Low-to-moderate quality evidence that wood dust acts as a carcinogen was obtained, and a stronger association between wood dust and nasal adenocarcinoma was observed. A lesser association between wood dust exposure and lung cancer was also observed. Several studies suggested that there is a relationship between wood dust and the onset of other cancers, although there was no evidence to establish an association. A meta-analysis that included four case-controls studies showed that workers exposed to wood dust exhibited higher rates of nasal adenocarcinoma than other workers (odds ratio = 10.28; 95% confidence interval: 5.92 and 17.85; P<0,0001), although a large degree of heterogeneity was found., Conclusions: Low-to-moderate quality evidence supports a causal association between cancer and occupational exposure to wood dust, and this association was stronger for nasal adenocarcinoma than for lung cancer. There was no evidence of an association between wood dust exposure and the other cancers examined.

Nasal gliomas (nasal glial heterotopia) are rare benign congenital frontonasal lesions occurring in approximately 1:20.000-40,000 live births. The diagnosis is rarely reported prenatally. Nasal gliomas are typically isolated lesions, with syndromic association being exceedingly rare. Metopic craniosynostosis can occur as an isolated abnormality or in association with multiple syndromes. This case is the first reported case of nasal glioma in association with craniosynostosis in the published literature.

Most amniotes are the hosts of many, distantly related papillomaviruses (PVs). Infection by PVs can be asymptomatic, or lead instead to benign or malignant lesions. However, PVs infecting animals and associated with malignancies are still largely understudied. In the present study, we communicate the complete genome of a novel PV found in a nasal neoplasia of a free-ranging alpine chamois (Rupicapra r. rupicapra) in an Italian national park. Long-PCR and cloning approaches followed for Sanger sequencing were used to identify the first PV found in chamois. The genome of the novel virus - RrupPV1 - of 7256 bp in length, presents the classical PV structure, and lacks the interE2-L2 region that hosts the E5 gene in AlphaPVs and in DeltaPVs. The nucleotide identity percentage of the L1 ORF, places RrupPV1 together with OaPV3 in the same genus. The latter is a PV isolated from a squamous cell carcinoma in sheep in Sardinia. Full-genome phylogenetic reconstructions suggest that these two viruses are sister taxa, and that both of them are very distantly related to any other known PV. Many cetartiodactyl species are infected by non-monophyletic PVs. Our results exemplify further the multiple links between the infection by certain, distantly related PVs and the development of diverse cancers in animals and highlight the need of a systematic search of oncogenic and non-oncogenic animal PVs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Oral cavity and pharyngeal cancers account for 75% of head and neck cancers and are the fourth most spread cancer in men. Their incidence has decreased since 1980 in men (incidence from 2011 gives 13,930 for lip, oral cavity, pharyngeal and laryngeal carcinomas) but has increased in women, linked to the more recent smoking or alcohol intoxication in women. In addition to the smoking or alcohol consumption risk factors, the EBV role in nasopharyngeal carcinomas, HPV in the oropharyngeal carcinomas and professional exposures in paranasal sinuses cancers are recognized. Head and neck cancers are the fifth most common cancer in men mortality in France. Extended anatomical sites reflect the diagnostic's complexity specific to some locations (sinuses, nasopharynx), possible therapies and prognosis depending on the affected site.

Wood dust is recognised as a human carcinogen, based on the strong association of wood dust exposure and the elevated risk of malignant tumours of the nasal cavity and paranasal sinuses [sino-nasal cancer (SNC)]. The study aimed to assess genetic damage in workers exposed to wood dust using biomarkers in both buccal and nasal cells that reflect genome instability events, cellular proliferation and cell death frequencies. Nasal and buccal epithelial cells were collected from 31 parquet layers, installers, carpenters and furniture workers (exposed group) and 19 non-exposed workers located in Switzerland. Micronucleus (MN) frequencies were scored in nasal and buccal cells collected among woodworkers. Other nuclear anomalies in buccal cells were measured through the use of the buccal micronucleus cytome assay. MN frequencies in nasal and buccal cells were significantly higher in the exposed group compared to the non-exposed group; odds ratio for nasal cells 3.1 [95% confidence interval (CI) 1.8-5.1] and buccal cells 1.8 (95% CI 1.3-2.4). The exposed group had higher frequencies of cells with nuclear buds, karyorrhectic, pyknotic, karyolytic cells and a decrease in the frequency of basal, binucleated and condensed cells compared to the non-exposed group. Our study confirms that woodworkers have an elevated risk for chromosomal instability in cells of the aerodigestive tract. The MN assay in nasal cells may become a relevant biomonitoring tool in the future for early detection of SNC risk. Future studies should seek to standardise the protocol for MN frequency in nasal cells similar to that for MN in buccal cells.

Esthesioneuroblatoma (Olfactory neuroblastoma) is a rare malignant neoplasm arising from the olfactory epithelium with bimodal age distribution between with first peak in second decades and second peak in sixth decade. Proptosis due to esthesioneuroblastoma is one of the rare causes. They have a long natural history characterized by frequent local or regional recurrence. Computed tomography and magnetic resonance imaging are the imaging modalities for diagnosing these tumors. A multidisciplinary approach with surgery and radiation therapy is an excellent treatment options for these tumors with chemotherapy being used to treat advanced or recurrent disease.

Angiofibroma is a benign vascular tumor that usually occurs in the nasopharynx, and extranasopharyngeal angiofibromas are rarely reported. We report the first case of an angiofibroma arising from the inferior turbinate after CO2 laser turbinoplasty. Endoscopic excisional biopsy was performed, but the tumor recurred after 2 months of surgery. The mass was excised by endoscopic approach including surrounding normal mucosal tissue. Histologic examination suggested the diagnosis of angiofibroma. The patient was asymptomatic, and there was no evidence of recurrence after 1 year of the second surgery.

Background: There are few studies of the effects of nasal snuff and environmental factors on the risk of nasal cancer. This study aimed to investigate the impact of using nasal snuff and of other risk factors on the risk of nasal cancer in German men., Methods: A population-based case-control study was conducted in the German Federal States of Bavaria and Baden-Württemberg. Tumor registries and ear, nose and throat departments provided access to patients born in 1926 or later., Results: Telephone interviews were conducted with 427 cases (mean age 62.1 years) and 2.401 population-based controls (mean age 60.8 years). Ever-use of nasal snuff was associated with an odds ratio (OR) for nasal cancer of 1.45 (95% confidence interval [CI] 0.88-2.38) in the total study population, whereas OR in smokers was 2.01 (95% CI 1.00-4.02) and in never smokers was 1.10 (95% CI 0.43-2.80). The OR in ever-smokers vs. never-smokers was 1.60 (95% CI 1.24-2.07), with an OR of 1.06 (95% CI 1.05-1.07) per pack-year smoked, and the risk was significantly decreased after quitting smoking. Exposure to hardwood dust for at least 1 year resulted in an OR of 2.33 (95% CI 1.40-3.91) in the total population, which was further increased in never-smokers (OR 4.89, 95% CI 1.92-12.49) in analyses stratified by smoking status. The OR for nasal cancer after exposure to organic solvents for at least 1 year was 1.53 (1.17-2.01). Ever-use of nasal sprays/nasal lavage for at least 1 month rendered an OR of 1.59 (1.04-2.44). The OR after use of insecticides in homes was 1.48 (95% CI 1.04-2.11)., Conclusions: Smoking and exposure to hardwood dust were confirmed as risk factors for nasal carcinoma. There is evidence that exposure to organic solvents, and in-house use of insecticides could represent novel risk factors. Exposure to asbestos and use of nasal snuff were risk factors in smokers only.

Extranodal NK/T-cell lymphoma, nasal type, is a rare type of non-Hodgkin lymphoma that is most common in Asia and is driven by Epstein-Barr virus infection. These tumors usually arise in the nasal region; in rare cases they can involve extranasal sites, most often skin, with involvement of the breast being rare. Lymphomas arising adjacent to breast implants are rare, and most cases reported to date have been anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Here we report a 41-year-old white woman with bilateral saline breast implants placed for cosmetic reasons who almost 9 years later developed painful swelling at the right-breast implant site. Excisional biopsy revealed lymphoma composed of monomorphic large cells associated with necrosis and angioinvasion. Immunohistochemical analysis showed an aberrant, NK/T-cell immunophenotype with the lymphoma cells being CD2+, CD3+, CD56+, partial CD30+, granzyme B, TIA-1+, CD4+, CD5+, CD7+, and CD8+. In situ hybridization analysis showed Epstein-Barr virus-encoded RNA within the neoplastic cells. Polymerase chain reaction analysis showed monoclonal T-cell receptor-γ chain gene rearrangement. These findings support the diagnosis of extranodal NK/T-cell lymphoma, nasal type. On the basis of our review of the literature, this case is unique. In addition, we believe this case is important to report, because it expands the spectrum of T-cell lymphomas that can be associated with breast implants and may be a forerunner of additional cases to follow.

Sinonasal cancers are rare and are often associated with occupational exposure that should be researched. Their diagnosis is often delayed. Carcinomas are the most common histological variety. The aim of the present report is to review the main scientific literature about sinonasal cancer to identify their clinicopathological features, and their main causes and treatment modalities. The treatment of these tumors is surgical, usually followed by radiotherapy.

Management of malignant neoplasms of the sinonasal tract and skull base is hampered by the relative low incidence and pathologic diversity of patient presentations. Many studies have reported successful outcomes in the endoscopic management of malignancy since 1996, and these are summarized in this article. Nonsurgical adjuvant therapies are important for locoregional control because surgery occurs in a restricted anatomic space with close margins to critical structures, and distant disease is an ongoing concern in these disorders. There remains a need for collaborative consistent multicenter reporting, and international registries have been established to assist in such efforts., (Copyright © 2011 Elsevier Inc. All rights reserved.)

National surveillance systems of occupational diseases may contribute to evaluate the work-related component of diseases investigated in SENTIERI Project. For a description of SENTIERI, refer to the 2010 Supplement of Epidemiology & Prevention devoted to SENTIERI Project. The National Workers Compensation Authority (INAIL) archives all occupational diseases claims (more than 230 000 in the period 2000-2007) and is in charge of their compensation. The Italian National Mesothelioma Register (ReNaM) and the Sinonasal Cancer Register (ReNaTuNS) record high occupational etiological fraction neoplasms (i.e. mesothelioma and sinonasal cancers). The former has identified more than 10 000 mesothelioma cases until now, and covers almost the whole country; the latter is active only in three Italian regions, Piemonte, Lombardia and Toscana. The monitoring of cancer sites at lower occupational etiological fraction is based on a record-linkage procedure between population-based cancer registries and employment history data, available at the Italian National Institute for Social Security (INPS). Finally, the informative system Mal.Prof collects and classifies all the diseases possibly related to the work environment reported by the Prevention Services of the Local Health Units.

Sinonasal carcinomas are rare tumors with an aggressive clinical behaviour which frequently pose a number of problems regarding the interpretation of diagnostic findings and the treatment. In addition, in comparison with other malignancies of the head and neck region, an elevated fraction of sinonasal carcinomas can be attributed to occupational exposure. This review is focused on the recent advances in the molecular and phenotypic characterization of sinonasal carcinomas, and their possible implications for the interpretation of epidemiological data, as well as for the diagnosis and treatment of these rare malignancies. The increasing knowledge on their phenotypic and genotypic features is progressively leading to a refinement in diagnosis, especially for poorly differentiated and undifferentiated lesions, as well as to the identification of markers which can be potentially useful to identify the early phases of carcinogenesis, to detect subclinical disease, to predict the response to therapy, and finally, that may represent potential targets for alternative treatments., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

It is well known that patients with rheumatoid arthritis (RA) have a higher risk of developing malignant lymphoma (ML) than the general population. Most of these lymphomas occur in patients receiving immunosuppressive (IS) agents such as methotrexate (MTX). Spontaneous regression of tumors is often observed after the discontinuation of IS drugs, especially in patients with Epstein-Barr virus-positive lymphoma. Here we encountered an RA patient who developed extranodal NK/T-cell lymphoma, nasal type during treatment of RA with MTX and etanercept. Despite the discontinuation of MTX and etanercept, the tumor did not show any regression. Complete response was achieved after treatment with concurrent chemoradiotherapy. ML of NK-cell origin is extremely rare, while the majority of ML cases associated with RA are of B-cell origin. This report describes extranodal NK/T-cell lymphoma, nasal type case associated with RA. Such cases should be accumulated to evaluate the mechanism of onset and clinical characteristics of NK/T-cell lymphoma associated with RA.

Purpose: Radiation-induced olfactory neuroblastoma (ONB) is an uncommon neoplasm that is generally associated with a poor prognosis. We describe a new case of olfactory neuroblastoma in a patient previously treated for astrocytoma with holocranial radiotherapy 9 years ago., Materials and Methods: We reviewed the medical records of four patients with radiation-induced olfactory neuroblastoma between 2001 and 2009., Results: This work supports the idea that ONB can be induced by radiation., Conclusions: As radiotherapy is a standard treatment in other tumors, clinicians must be aware of the possibility of a second tumor induced by radiation.

Nasal NK/T-cell lymphoma (NKTCL) frequently presents with necrotic, granulomatous lesions in the upper respiratory tract, and usually shows a highly aggressive clinical course. Thus, it was initially included in the clinical condition of lethal midline granuloma. Recently, the disease has been recognized as a neoplastic proliferation of NK/T cells. The disease is much more frequent in Asian and Latin American countries than in Western countries, and is universally associated with Epstein-Barr virus (EBV) infection. Analyses of gene mutations, especially p53 and c-kit, revealed the different frequencies by district. Abnormalities of other genes have also been reported. Case-control studies showed that the exposure to pesticides and chemical solvents could be causative of NKTCL. Further studies including HLA antigen typing of patients is necessary to further clarify the disease mechanism.

Objectives: We compared histologic findings on light microscopy of viscid secretions found in association with nasal polyps with those found in patients with chronic sinusitis without polyposis (CSWP). The differences might further understanding of nasal polyp pathogenesis., Methods: In a prospective controlled study, viscid secretions found in association with nasal polyps were collected at endoscopic sinus surgery. Retained secretions in patients with CSWP acted as a control group. Both were fixed in 10% formalin, processed, and examined with a light microscope., Results: Viscid secretions were encountered among nasal polyps in 25 of 132 patients (18.9%). Polyps containing multiloculated cysts filled with viscid secretions were found in 2 of them. Histologic examination of viscid secretions showed variable histologic pictures, ranging from a homogeneous material infiltrated with inflammatory cells, newly formed blood vessels, and bundles of collagen fibers to a well-developed connective tissue core covered with a respiratory epithelium in some areas. Histologic examination of retained secretions in patients with CSWP revealed amorphous material infiltrated with inflammatory cells with no further maturation or epithelial coverage., Conclusions: Viscid secretions, originating from ruptured mucosal cysts, might represent the initial step in nasal polyp pathogenesis. The variable histologic pictures detected possibly reflect different stages in nasal polyp formation from these secretions. Factors postulated in nasal polyp etiopathogenesis might trigger maturation and changes in the morphological structure of these secretions.

The causal role of work-related exposure to wood dust in the development of sinonasal cancer has long been established by numerous epidemiologic studies. To study molecular changes in these tumors, we analyzed TP53 gene mutations in 358 sinonasal cancer cases with or without occupational exposure to wood dust, using capillary electrophoresis single-strand conformation polymorphism analysis and direct sequencing. A significant association between wood-dust exposure and adenocarcinoma histology was observed [adjusted odds ratio (OR) 12.6, 95% confidence interval (CI), 5.0-31.6]. TP53 mutations occurred in all histologies, with an overall frequency of 77%. TP53 mutation positive status was most common in adenocarcinoma (OR 2.0, 95% CI, 1.1-3.7; compared with squamous cell carcinoma), and mutation positivity showed an overall, nonsignificant association with wood-dust exposure (OR 1.6, 95% CI, 0.8-3.1). Risk of TP53 mutation was significantly increased in association with duration (> or =24 years, OR 5.1, 95% CI, 1.5-17.1), average level (>2 mg/m(3); OR 3.6, 95% CI, 1.2-10.8) and cumulative level (> or =30 mg/m(3) x years; OR 3.5, 95% CI, 1.2-10.7) of wood-dust exposure; adjustment for formaldehyde affected the ORs only slightly. Smoking did not influence the occurrence of TP53 mutation; however, it was associated with multiple mutations (p = 0.03). As far as we are aware, this is the first study to demonstrate a high prevalence of TP53 mutation-positive cases in a large collection of sinonasal cancers with data on occupational exposure. Our results indicate that mutational mechanisms, in particular TP53 mutations, are associated with work-related exposure to wood dust in sinonasal cancer.

Objective: Patients with a genetic history of retinoblastoma have an increased risk of developing a second neoplasm. When these secondary malignancies occur in the previously irradiated field of the primary tumor they are most commonly osteosarcomas, fibrosarcomas, and squamous cell carcinomas. We present the first case of a radiation induced adenocarcinoma in a patient after treatment for retinoblastoma., Study Design: A case report of one patient., Methods: This case study underwent a chart review, comprehensive history, physical exam, rigid nasal endoscopy, and radiographic imaging. A literature review of the MEDLINE database 1966-2009 using key words, retinoblastoma, radiation, and second malignancy was performed., Results: Our case is a 29 year old man with a past medical history significant for surgical resection followed by irradiation at age 1 for retinoblastoma who presented with right sided epistaxis and nasal obstruction. Endoscopy revealed a mass in the right nasal cavity. MRI and CT revealed a mass filling the right nasal cavity and ethmoids with erosion through the cribriform plate. The patient underwent surgical resection and pathology revealed an adenocarcinoma., Conclusions: Second malignancies in patients with retinoblastoma tend to occur in the previously irradiated field of the primary tumour and contribute significantly to long term morbidity and mortality rates. This is the first case of a sinonasal adenocarcinoma occurring in the previously irradiated field. The endoscopic skull base surgeon plays a vital role as patient survival depends on the diagnosis and surgical management.

Background: Sinonasal cancer (SNC) includes uncommon tumours that are characterized by a high occupational etiologic component. For this reason they are an easy target for systematic surveillance by setting up a specific disease registry. The National Registry of these tumours is located at the Italian Institute for Occupational Safety and Prevention (ISPESL) and is based on data from Regional Operating Centres (ROCs). In the Lombardy Region a ROC was established in 2008 at the Clinica del Lavoro "Luigi Devoto" in Milan aimed at making surveillance systematic and thus provide adequate support for scientific research and prevention measures in the high risk work sectors., Objectives: To estimate the incidence of SNC, to define different sources of occupational exposure both known (wood, leather, nickel, chromium) and unknown., Methods: The Registry collects all the new incident cases of epithelial SNC occurring among residents ofthe Lombardy Region. The Regional Registry is managed in accordance with the specific National Guidelines and uses the experience already acquired with the organizational and operational management of the Regional Mesothelioma Registry., Results: During the first period of activity (1.1.2008-30.9.2009) 556 cases of suspected SNC were reported to the Registry; only 62 (11.2%) of these actually complied with the inclusion criteria of the Registry and were mainly adenocarcinoma and squamous carcinoma. Occupational exposure to wood or leather dust was ascertained in 50% of cases., Conclusion: Data collected up to now confirm that occupational exposure to wood and leather dusts are the most significant risk factors for SNC. The study of occupational sectors and job tasks in cases with as yet undefined exposure might suggest new etiologic hypotheses.

Extranodal NK/T-cell lymphoma, nasal type (ENKT), is a distinct clinicopathologic disease, common among East Asia and Latin America population. Clinically, it frequently occurs in middle-aged men. It predominantly occurs in the nasal or paranasal areas and less frequently in the skin. The main clinical features are nasal congestion, sore throat, dysphagia and epistaxis, due to a destructive mass involving the midline facial tissues. The pathogenesis of ENKT remains uncertain. It is thought that Epstein-Barr virus (EBV) may play a role in the development of this entity. Pathologically, lymphoma cells exhibit angioinvasion, angiodestruction and coagulative necrosis. It has unique characteristics including the expression of cytoplasmic CD3, CD56 and cytotoxic molecules such as TIA-1, and is positive for EBV in situ hybridization. The overall prognosis of this disease is poor because of frequent relapse or resistance to treatment. Although several studies have explored the treatment of ENKL in recent years, the optimal therapy has still not been found. Due to the highly aggressive features of tumors, every endeavor has been made to investigate factors associated with poor outcome. In this review, the recent advances on cause and pathogenesis, clinical manifestations and staging, pathologic characteristics, diagnosis and differential diagnosis, therapy and prognosis of ENKL are summarized.

Chronic nasal disease is a common problem in dogs. To determine the aetiology, a retrospective study in 75 dogs with persistent and chronic nasal disease was done. All dogs were evaluated by means of survey nasal radiographs, antegrade and retrograde rhinoscopy, bacterial and fungal cultures, and histopathology. A definitive diagnosis was made in 74/75 cases (98.6%). Nasal neoplasia was the most common diagnosis (46.7%), median age 108 months, followed by lympho-plasmacytic rhinitis (20%), median age 112 months, and fungal rhinitis (10.7%), median age 53.5 months. Other diagnoses included nasal foreign body (5.3%), median age 51 months, and primary bacterial rhinitis (6.7%), median age 116.5 months. Rare aetiologies identified were nasal polyps, granulomatous rhinitis, oro-nasal fistula and naso-pharyngeal stenosis. This study showed that by using a structured combination of survey radiography, rhinoscopy, cultures and histopathology, a diagnosis could be made in dogs with chronic nasal disease.