[The new national guidelines for the keeping of the Italian Sinonasal Cancer Registry (ReNaTuNS)]. / Il nuovo manuale operativo ReNaTuNS per la gestione dei casi di tumore naso-sinusale.

Sinonasal cancers (SNC) are rare tumours with predominant occupational aetiology associated with exposures to specific carcinogens. In Italy, SNC incidence has been under compulsory surveillance since 2008, through the National Sinonasal Cancer Registry (ReNaTuNS), a nationwide cancer registry coordinated by the National Institute for Insurance Against Accidents at Work (Inail). The ReNaTuNS has a regional structure with local registries, established at Regional Operating Centres (CORs). Currently, seven Italian Regions are active in SNC search and, together with Inail, have recently released a new version of the national guidelines for keeping the Registry (available on the Inail website). The aim of this text is to present the new guidelines, an updating version, and to underline the relevance of this tool in enforcing the role of the ReNaTuNS, considering the high occupational fraction of SNC and the unicity of the Italian Registry, which collects all the information available on occupational exposures of each SNC case registered. It is recommended that the active search for SNC cases and the analysis of exposure become a systematic and well-organized activity to prevent or reduce risks of exposure and to support and improve the efficiency of the compensation and welfare system.

Malignant Sinonasal Tumors: Update on Histological and Clinical Management.

Tumors of nasal cavity and paranasal sinuses (TuNSs) are rare and heterogeneous malignancies, presenting different histological features and clinical behavior. We reviewed the literature about etiology, biology, and clinical features of TuNSs to define pathologic features and possible treatment strategies. From a diagnostic point of view, it is mandatory to have high expertise and perform an immunohistochemical assessment to distinguish between different histotypes. Due to the extreme rarity of these neoplasms, there are no standard and evidence-based therapeutic strategies, lacking prospective and large clinical trials. In fact, most studies are retrospective analyses. Surgery represents the mainstay of treatment of TuNSs for small and localized tumors allowing complete tumor removal. Locally advanced lesions require more demolitive surgery that should be always followed by adjuvant radio- or chemo-radiotherapy. Recurrent/metastatic disease requires palliative chemo- and/or radiotherapy. Many studies emphasize the role of specific genes mutations in the development of TuNSs like mutations in the exons 4-9 of the TP53 gene, in the exon 9 of the PIK3CA gene and in the promoter of the TERT gene. In the near future, this genetic assessment will have new therapeutic implications. Future improvements in the understanding of the etiology, biology, and clinical features of TuNSs are warranted to improve their management.

A quantitative risk assessment of sinonasal cancer as a function of time in workers occupationally exposed to wood dust.

OBJECTIVES: The aim of this study is to conduct a quantitative assessment of the risk related to occupational exposure to wood dust and the occurrence of sinonasal epithelial cancer (SNEC) by histotype, depending on the duration of exposure, using mathematical models. MATERIAL AND METHODS: The relationship between the occurrence of SNEC by histotype (adenocarcinoma [AR] and tumors of other histotypes) and exposure to wood dust has been studied using the values of the odds ratios for individual periods of employment involving exposure to wood dust, and their 95% confidence intervals. The dose-response curves were constructed (more precisely, the duration of exposure-response curves). The author attempted to match the linear, quadratic or exponential models. RESULTS: In all SNEC cases, there is a relationship between the duration of occupational exposure to wood dust and the relative risk of developing cancer. The estimated relative risk of developing AR after 35 years of exposure to wood dust is about 300, and the estimated risk of developing SNEC is 50, compared to non-exposed people for whom the relative risk is equal to 1. However, the relative risk of developing other types of cancer is <20, also in comparison with non-exposed people. CONCLUSIONS: The author has identified a relationship between the duration of occupational exposure to wood dust and the relative risk of developing cancer in all SNEC cases. Int J Occup Med Environ Health. 2021;34(4):541-9.

Epithelial Squamous Metaplasia and Dysplasia in Inflammatory Nasal Polyps: An Observational Study.

Nasal polyposis (NP) is characterized by polypoid outgrowths of chronically inflamed respiratory mucosa. The presence of squamous metaplasia and dysplasia on the mucosal surface of nasal polyps (NPs) represents different manifestations of epithelial atypia. The aim of this investigation was to evaluate the presence of epithelial squamous metaplasia and dysplasia in ethmoidal NPs. This retrospective analysis of prospectively collected data involved 212 patients with NP undergoing endoscopic ethmoidectomy. To evaluate possible etiological factors for epithelial atypia, the patients in whom we histopathologically detected the presence of epithelial atypia were compared with patients with "normal" NPs in accordance with the following characteristics as found in the patients' medical records: gender, age, main symptoms, preoperative extent of sinus disease on computed tomography, atopic status, aspirin sensitivity, cigarette smoking, and occupational exposure to different noxious factors. Epithelial atypia were detected histopathologically in 44 (20.7%) NP patients, whereas features of "true" dysplasia were found in only 1 (0.5%) patient. The presence of atypia was more frequent in males than in females (P = .008). The association with aspirin-exacerbated respiratory disease and with long-term occupational exposure to different noxious chemicals, especially in workers exposed to salts of heavy metals, was more frequent in NP patients with epithelial atypia than in patients without atypia (P = .023; P = .006, respectively). Our results suggest epithelial atypia in NPs are associated with aspirin sensitivity and occupational exposure to different noxious chemicals. Although extremely rare, epithelial dysplasia may occasionally be noted in NPs, a fact potentially useful for both rhinologists and pathologists.

Clinical assessment, diagnosis and management of patients with unilateral sinonasal disease.

OBJECTIVES: Unilateral sinonasal disease is commonly encountered in practice and represents an issue of major concern since neoplasms may mimic inflammatory conditions. This paper aims to describe the demographic, clinical and radiological patterns of unilateral pathologies and, accordingly, to establish a guiding algorithm for diagnosis and management. MATERIAL AND METHODS: We conducted a retrospective review of medical records of patients with unilateral sinus opacification on CT scan who underwent endoscopic nasal surgery in our department from January 2011 to December 2017. RESULTS: Of the 150 patients included, 97(64.7%) and 53(35.3%) had inflammatory and neoplastic pathology, respectively. In the neoplastic group, malignancy was present in 35% of patients. Neoplastic conditions were more common in males (p=0.02) and older patients (56±18 years vs. 38±18, p<.01). Nasal mass or polyp was observed in 56.7% patients. Chronic sinusitis was the most prevalent inflammatory condition, whereas inverted papilloma and osteoma were the most frequent neoplasms. Facial neuralgia, paraesthesia, epistaxis and, on CT scan, superior Lund-Mackay scores, bone remodelling and erosion were significantly more common in neoplastic conditions. Excellent agreement between punch biopsy and postoperative histological results was obtained (k=.883, p<.001). CONCLUSION: A sequential and careful management of unilateral lesions is mandatory. Based on our experience, we propose that, as routine, physical examination should be complemented with nasal endoscopy, CT scan and punch biopsy, in case of visible mass. Although clinical and radiological information might raise suspicion of some conditions, final diagnosis can only be established with histological examination of the surgical specimen.

SMARC-B1 deficient sinonasal carcinoma metastasis to the brain with next generation sequencing data: a case report of perineural invasion progressing to leptomeningeal invasion.

BACKGROUND: SMARCB1-deficient sinonasal carcinoma (SDSC) is an aggressive subtype of head and neck cancers that has a poor prognosis despite multimodal therapy. We present a unique case with next generation sequencing data of a patient who had SDSC with perineural invasion to the trigeminal nerve that progressed to a brain metastasis and eventually leptomeningeal spread. CASE PRESENTATION: A 42 year old female presented with facial pain and had resection of a tumor along the V2 division of the trigeminal nerve on the right. She underwent adjuvant stereotactic radiation. She developed further neurological symptoms and imaging demonstrated the tumor had infiltrated into the cavernous sinus as well as intradurally. She had surgical resection for removal of her brain metastasis and decompression of the cavernous sinus. Following her second surgery, she had adjuvant radiation and chemotherapy. Several months later she had quadriparesis and imaging was consistent with leptomeningeal spread. She underwent palliative radiation and ultimately transitioned quickly to comfort care and expired. Overall survival from time of diagnosis was 13 months. Next generation sequencing was carried out on her primary tumor and brain metastasis. The brain metastatic tissue had an increased tumor mutational burden in comparison to the primary. CONCLUSIONS: This is the first report of SDSC with perineural invasion progressing to leptomeningeal carcinomatosis. Continued next generation sequencing of the primary and metastatic tissue by clinicians is encouraged toprovide further insights into metastatic progression of rare solid tumors.

Sinonasal cancer in The Netherlands: Follow-up of a population-based study 1989-2014 and incidence of occupation-related adenocarcinoma.

BACKGROUND: Long-term trends of sinonasal cancer in The Netherlands have been investigated with particular attention on adenocarcinoma for which wood or leather dust is a well-known risk factor. METHODS: All 4345 patients (1989-2014) registered in the Netherlands Cancer Registry were included. Standardized 3-year moving incidence rates per 1 000 000/person-years, and estimated annual percentage change (EAPC) were calculated. RESULTS: Forty-seven percent of the patients had squamous cell carcinoma (SCC), 12% had lymphoma, and 12% had adenocarcinoma. Sixty-one percent of the tumors were located in the nasal cavity, 22% in the maxillary, and 11% in the ethmoidal sinus. Male incidence decreased to 11.5/1 000 000 due to less SCC (EAPC -0.9%; 95% confidence interval [CI] -1.6 to 0.3) and adenocarcinoma (EAPC -4.3%; 95% CI -5.5 to 3.1). Female incidence increased to 7/1 000 000 (EAPC +2.0%; 95% CI +1.1 to +3.0) due to more SCC (EAPC +2.2%; 95% CI +1.0 to +3.5), whereas adenocarcinoma remained stable (0.6/1 000 000; EAPC +1.1%; 95% CI -6.0 to +8.7). Tumors of the nasal cavity increased in women (EAPC +3.3%; 95% CI +2.0 to 4.7). CONCLUSION: The decrease of male sinonasal adenocarcinoma may be the result of preventive measures combined with less workers in high-risk occupations.

Human papillomavirus (HPV) and somatic EGFR mutations are essential, mutually exclusive oncogenic mechanisms for inverted sinonasal papillomas and associated sinonasal squamous cell carcinomas.

Background: Inverted sinonasal (Schneiderian) papilloma (ISP) is a locally aggressive neoplasm often associated with sinonasal squamous cell carcinoma (SNSCC). While the etiology of ISP is not well understood, human papillomavirus (HPV) has been detected in a subset of cases. Our group recently identified activating somatic EGFR mutations in the majority of ISP and ISP-associated SNSCC. However, the relationship between EGFR mutations and HPV infection has not been explored. Patients and methods: We evaluated 58 ISP and 22 ISP-associated SNSCC (including 13 patients with matched ISP/SNSCC samples), as well as 14 SNSCC without clinical or pathologic evidence of an associated ISP. Formalin-fixed, paraffin-embedded samples were evaluated for EGFR mutations using Sanger sequencing and for HPV infection using GP5+/GP6+ PCR. HPV subtyping based on the L1 sequence was done for HPV positive cases including temporally distinct tumors for four patients. Clinicopathologic data including progression free survival was also analyzed. Results: All ISP and ISP-associated SNSCC demonstrated either an EGFR mutation or HPV infection. HPV and EGFR mutation were mutually exclusive in all cases of ISP-associated SNSCC and all but one ISP; this case was only weakly HPV positive, and analysis of a prior temporally distinct ISP specimen from this patient failed to show HPV infection, suggesting transient infection/incidental colonization. HPV subtypes in ISP and ISP-associated SNSCC were predominantly low-risk, in contrast with SNSCC without ISP association, which showed frequent high-risk HPV. All paired ISP and associated SNSCC samples demonstrated concordant HPV status and EGFR genotypes. ISP progression to SNSCC was significantly associated with the presence of HPV infection and the absence of an EGFR mutation (log-rank = 9.620, P = 0.002). Conclusions: Collectively our data show that EGFR mutations and HPV infection represent essential, alternative oncogenic mechanisms in ISP and ISP-associated SNSCC.

Chronic sinonasal tract inflammation as a precursor to nasopharyngeal carcinoma and sinonasal malignancy in the United States.

BACKGROUND: Chronic inflammatory states have been linked to the development of malignancy. Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) have been associated with nasopharyngeal carcinoma (NPC) in population-based studies in Asia. A similar association with NPC and paranasal sinus malignancy (PSM) has not been defined in a North American population. Our purpose was to investigate the impact of CRS and AR on the risk of NPC and PSM. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database was queried as a case-control study of adults ≥65 years of age. The study cohort included 2009 patients diagnosed with NPC and/or PSM diagnosed between 2003 and 2011, and 2009 propensity-score-matched controls selected from a 5% random sample of Medicare beneficiaries without cancer. CRS and AR were examined as exposures. Multivariable unconditional logistic regression was employed. RESULTS: Overall, NPC and PSM patients were more likely to have previous CRS diagnosis than the controls (9.2% vs 3.0% and 11.1% vs 2.7%, respectively). CRS was associated with greater odds of developing NPC (odds ratio [OR], 3.51; 95% confidence interval [CI], 2.12-5.79) and PSM (OR, 5.30; 95% CI, 3.55-7.92). AR was associated with greater odds of developing NPC (OR, 4.23; 95% CI, 2.96 to 6.06) and PSM (OR, 3.35; 95% CI, 2.49-4.49). The number needed to harm in the exposed population was 311. CONCLUSIONS: CRS and AR are associated with the presence of NPC and PSM in the elderly population of United States. This epidemiologic association will need to be examined for causative pathophysiologic mechanisms and utility in clinical diagnosis.

Low-Grade Sinonasal Sarcoma With Neural and Myogenic Features: A Recently Discovered Entity With Unique Features and Diagnostic Challenge.

Low-grade sinonasal sarcoma with neural and myogenic features is an entity recently described in the literature. Little is known about its etiopathogenesis, natural history, or optimal treatment. In fact, it has relatively unique findings: it has a distinctive cytogenetic signature, and it expresses both smooth muscle actin and S100 protein. However, its diagnosis is challenging on biopsies showing negative staining for these 2 markers. The differential diagnoses include fibrosarcoma, malignant peripheral nerve sheath tumors, and other benign and malignant lesions. A complete resection, with or without radiotherapy, is required because this lesion appears to be locally aggressive. However, the clinical outcome seems to be good. Low-grade sinonasal sarcoma with neural and myogenic features merits classification as an independent tumor in the next World Health Organization classification of head and neck tumors. Reports of additional cases are required to support its unique classification.

Clinical outcomes of sinonasal squamous cell carcinomas based on tumor etiology.

BACKGROUND: Squamous cell carcinoma (SCC) of the sinonasal cavity is a rare entity that arises as either de-novo tumors or from inverted papillomas (IPs). In this study we evaluate and compare oncologic outcomes of sinonasal SCCs based on their etiology and treatment strategy. METHODS: This investigation was a single-center, retrospective review comparing de-novo SCCs (n = 28) and those associated with IPs (n = 38) resected during the period from 2000 to 2015. Demographic and tumor data, surgical approach, recurrence, and clinical outcomes were analyzed. RESULTS: There was no statistical difference when comparing age, smoking history, tumor origin, or tumor stage of our patients with de-novo sinonasal SCC (DN-SCC) vs IP-transformed SCC (IP-SCC). IP-SCC tumors demonstrated better overall survival (p = 0.065) and disease-specific survival (p = 0.041) compared with DN-SCC. Early T-stage IP-SCC tumors had better disease-free survival compared with early T-stage DN-SCC tumors (p = 0.002). Distant metastasis was an independent prognostic factor of worse disease-specific survival (p = 0.002). SCC disease-specific survival was not affected by surgical resection technique. CONCLUSION: SCC tumors arising from IPs appear to have improved disease-specific survival compared with de-novo sinonasal SCC tumors. The oncologic differences between the 2 groups are found primarily among the early-stage tumors.

Intestinal-type sinonasal adenocarcinomas: The road to molecular diagnosis and personalized treatment.

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.

Sinonasal inverted papilloma: From diagnosis to treatment.

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.

Experimental Transmission of Bighorn Sheep Sinus Tumors to Bighorn Sheep (Ovis canadensis canadensis) and Domestic Sheep.

Bighorn sheep sinus tumors are a recently described disease affecting the paranasal sinuses of Rocky Mountain bighorn sheep (Ovis canadensis canadensis). Several features of this disease suggest an infectious cause, although a specific etiologic agent has not been identified. To test the hypothesis that bighorn sheep sinus tumors are caused by an infectious agent, we inoculated 4 bighorn sheep lambs and 4 domestic sheep lambs intranasally with a cell-free filtrate derived from a naturally occurring bighorn sheep sinus tumor; we held 1 individual of each species as a control. Within 18 months after inoculation, all 4 inoculated domestic sheep (100%) and 1 of the 4 inoculated bighorn sheep (25%) developed tumors within the ethmoid sinuses or nasal conchae, with features similar to naturally occurring bighorn sheep sinus tumors. Neither of the uninoculated sheep developed tumors. Histologically, the experimentally transmitted tumors were composed of stellate to spindle cells embedded within a myxoid matrix, with marked bone production. Tumor cells stained positively with vimentin, S100, alpha smooth muscle actin, and osteocalcin, suggesting origin from a multipotent mesenchymal cell. A periosteal origin for these tumors is suspected. Immunohistochemical staining for the envelope protein of JSRV (with cross-reactivity to ENTV) was equivocal, and PCR assays specific for these agents were negative.

Paranasal sinus cancer.

Paranasal sinus cancers are rare diseases, accounting for about 5% of all head and neck malignancies. The variety of histological types and the overlapping pathological features with other entities constitute difficulties in pathologic interpretation, often requiring a skilled interpretation or a second opinion. Treatment of locally advanced disease relies on surgery and radiation therapy for operable disease, with a possible role for systemic treatment in selected histologies within a multimodal approach; unresectable paranasal sinus cancers are generally treated with a combination of radiotherapy and chemotherapy. The employment of high conformal radiation techniques, such as Intensity Modulated Radiation Therapy orcharged particle therapy, proton or carbon ion therapy may improve outcome and reduce late effects. Surgical treatment has evolved due to the progressive application of transnasal endoscopic techniques for naso-ethmoidal malignancies and due to innovative reconstructive techniques after resection of cancers of the maxillary sinus. Because of the rarity and complexity of this disease, multicenter trials represent an urgent need to improve prognosis and to reduce treatment-related effects.

Occupational exposure and sinonasal cancer: a systematic review and meta-analysis.

BACKGROUND: Sinonasal cancer (SNC) has been related to occupational exposures, but the relative risk associated to specific jobs and/or carcinogen exposures other than wood and leather dust is generally based on small or inadequate sample sizes and the range of observed estimates is large. This paper is aimed at investigating such relationship through a systematic review of the literature followed by a meta-analysis of studies meeting specific inclusion criteria. METHODS: Systematic search was made with PubMed, Google Scholar and Scopus engines using related keywords. Occupational exposures include wood and leather dust, formaldehyde, nickel and chromium compounds, textile industry, farming and construction. Meta-analysis of published studies after 1985 with a case-control or cohort design was performed, firstly using the fixed-effect model. Heterogeneity was assessed with the Q statistical test and quantified by the I(2) index. When the heterogeneity hypothesis appeared relevant, the random-effect model was chosen. Sources of heterogeneity were explored using subgroup analyses. RESULTS: Out of 63 reviewed articles, 28 (11 cohort, 17 case-control) were used in the meta-analysis. Heterogeneity among studies was observed and random-effects models were used. Exposure to wood dust results associated with SNC (RRpooled = 5.91, 95% CI: 4.31-8.11 for the case-control studies and 1.61, 95% CI: 1.10-2.37 for the cohort studies), as well as to leather dust (11.89, 95% CI: 7.69-18.36). The strongest associations are with adenocarcinomas (29.43, 95% CI: 16.46-52.61 and 35.26, 95% CI: 20.62-60.28 respectively). An increased risk of SNC for exposures to formaldehyde (1.68, 95% CI: 1.37-2.06 for the case control and 1.09, 95% CI: 0.66-1.79 for the cohort studies), textile industry (2.03, 95% CI: 1.47-2.8), construction (1.62, 95% CI: 1.11-2.36) and nickel and chromium compounds (18.0, 95% CI: 14.55-22.27) was found. Subset analyses identified several sources of heterogeneity and an exposure-response relationship was suggested for wood dust (p = 0.001). CONCLUSIONS: By confirming the strength of association between occupational exposure to causal carcinogens and SNC risk, our results may provide indications to the occupational etiology of SNC (not only wood and leather dusts). Future studies could be focused on specific occupational groups to confirm causative agents and to define appropriate preventive measures.

Workers exposed to wood dust have an increased micronucleus frequency in nasal and buccal cells: results from a pilot study.

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.

Estimating the social cost of respiratory cancer cases attributable to occupational exposures in France.

PURPOSE: The objective of this article was to estimate the social cost of respiratory cancer cases attributable to occupational risk factors in France in 2010. METHODS: According to the attributable fraction method and based on available epidemiological data from the literature, we estimated the number of respiratory cancer cases due to each identified risk factor. We used the cost-of-illness method with a prevalence-based approach. We took into account the direct and indirect costs. We estimated the cost of production losses due to morbidity (absenteeism and presenteeism) and mortality costs (years of production losses) in the market and nonmarket spheres. RESULTS: The social cost of lung, larynx, sinonasal and mesothelioma cancer caused by exposure to asbestos, chromium, diesel engine exhaust, paint, crystalline silica, wood and leather dust in France in 2010 were estimated at between 917 and 2,181 million euros. Between 795 and 2,011 million euros (87-92%) of total costs were due to lung cancer alone. Asbestos was by far the risk factor representing the greatest cost to French society in 2010 at between 531 and 1,538 million euros (58-71%), ahead of diesel engine exhaust, representing an estimated social cost of between 233 and 336 million euros, and crystalline silica (119-229 million euros). Indirect costs represented about 66% of total costs. CONCLUSION: Our assessment shows the magnitude of the economic impact of occupational respiratory cancers. It allows comparisons between countries and provides valuable information for policy-makers responsible for defining public health priorities.