Materiały źródłowe

• #1 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. […] Accurate diagnosis can be challenging and requires several diagnostic markers, especially for some subtypes. They typically present during the 50th to 60th decade of life, with a higher prevalence in males. Occupational exposure, genetic mutations, and viral infections can be considered etiological agents in several sinonasal tumors. Overall poor survival is largely due to the biology of the different cancer types, frequent presentation at an advanced stage and limited treatment options for advanced disease, especially when surgery and radiotherapy are not a curative option anymore. Recent developments have been driven by advances in immunohistochemistry and molecular analysis. Better understanding of the pathogenesis, along with the possibility to differentiate distinct subtypes, has important implications for clinical practice, especially in the development and delivery of targeted treatment.

• #2 Rare nasosinusal tumors: Case series and literature review | Brazilian Journal of Otorhinolaryngology

  https://www.elsevier.es/en-revista-brazilian-journal-otorhinolaryngology-english-edition–497-articulo-rare-nasosinusal-tumors-case-series-S180886941531106X

  Tumors of the nasal cavity and paranasal sinuses are unusual pathologies found in clinical practice. Approximately 0.8% of all human cancers are located in this area. Despite being rare, nasosinusal neoplasms usually manifest through nonspecific symptoms that are common to numerous inflammatory pathologies. The aim of this study is to describe a series of rare nasosinusal tumors, including esthesioneuroblastomas, central giant cell granulomas, extramedullary plasmocytomas, nasosinusal hemangiopericytomas, neurofibromas and cemento-ossifying fibromas, diagnosed at the Fortaleza General Hospital. We, hereby, briefly review each of the aforementioned pathologies, stressing the need for a precise histological diagnosis for proper treatment in each case. […] Nasosinusal malignant tumors are rare, representing less than 3% of head and neck cancers and 0.8% of all human cancers. Approximately 55% originate in the maxillary sinuses, 35% in the nasal cavity, 9% in the ethmoid and 1% in the frontal and sphenoid sinuses. In the USA, the incidence of nasal cavity tumors is less than 1 case in 100 thousand persons per year. With the exception of non-epithelial tumors, nasosinusal cancer is a disease that affects adults, being more frequent in men above 50 years of age.

• #3 Mayo Clinic Health Library – Nasal and paranasal tumors | Swiss Medical Network

  https://www.swissmedical.net/fr/healtcare-library/con-20198269

  Nasal and paranasal tumors happen when cells in the nasal cavity or chambers around the nose develop changes in their DNA. A cell’s DNA holds the instructions that tell a cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions also tell the cells to die at a set time. In tumor cells, the changes give different instructions. The changes tell the tumor cells to make many more cells quickly. Tumor cells can keep living when healthy cells would die. This causes too many cells. […] Sometimes the changes in the DNA turn the cells into cancer cells. Cancer cells can invade and destroy healthy body tissue. In time, cancer cells can break away and spread to other parts of the body. When cancer spreads, it’s called metastatic cancer.

• #4 Mayo Clinic Health Library – Nasal and paranasal tumors | Swiss Medical Network

  https://www.swissmedical.net/fr/healtcare-library/con-20198269

  Nasal and paranasal tumors happen when cells in the nasal cavity or chambers around the nose develop changes in their DNA. A cell’s DNA holds the instructions that tell a cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions also tell the cells to die at a set time. In tumor cells, the changes give different instructions. The changes tell the tumor cells to make many more cells quickly. Tumor cells can keep living when healthy cells would die. This causes too many cells. […] Sometimes the changes in the DNA turn the cells into cancer cells. Cancer cells can invade and destroy healthy body tissue. In time, cancer cells can break away and spread to other parts of the body. When cancer spreads, it’s called metastatic cancer.

• #5 What Causes Nasal Cancer? | What Causes Paranasal Sinus Cancer? | American Cancer Society

  https://www.cancer.org/cancer/types/nasal-cavity-and-paranasal-sinus-cancer/causes-risks-prevention/what-causes.html

  We dont know what causes each case of nasal cavity or paranasal sinus cancer. But we do know some of the risk factors for these cancers and how some of them cause normal cells to become cancer. For example, some risk factors, such as workplace exposure to certain chemicals, may cause these cancers by damaging the DNA of cells that line the inside of the nose and sinuses. […] Cancers can be caused by DNA changes that turn on proto-oncogenes or turn off tumor suppressor genes. This leads to cells growing out of control. Changes in many different genes are usually needed to cause nasal cavity or paranasal sinus cancer. […] Scientists believe that some risk factors, such as workplace exposures to certain chemicals and tobacco use, cause these cancers by damaging the DNA of the cells that line the inside of the nasal cavity and paranasal sinuses.

• #6 Nasal & Paranasal Tumors: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/24927-nasal-tumors

  Nose tumors occur when the genes that control cell growth become damaged or abnormal. Experts still arent sure exactly why these gene changes occur. […] There are, however, certain risk factors that can increase your risk for developing nose tumors, including exposure to tobacco smoke (both primary and secondary), wood or leather dust, and vapors from certain chemicals and substances, including glue, radium, solvents and formaldehyde. […] For cancerous nasal tumors, the most common approach includes surgery in combination with radiation therapy. […] Chemotherapy involves medications that kill cancer cells. It may be given orally (in pill form) or intravenously (through a vein). Chemotherapy isnt used as often as surgery or radiation therapy in the treatment of nose tumors. But in some cases, your provider may recommend chemotherapy or chemoradiation (a combination of chemotherapy and radiation therapy). […] Many cancerous nose tumors are curable, especially if detected early. Like most types of cancer, the longer a nasal tumor goes undetected, the more likely it is to grow and spread.

• #7 Paranasal Sinus Cancer – Ear, Nose, and Throat Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/ear-nose-and-throat-disorders/mouth-nose-and-throat-cancers/paranasal-sinus-cancer

  Doctors are not sure what causes these cancers, but they are more common among people who smoke tobacco or regularly inhale certain types of wood and metal dust. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) may sometimes play a role. […] Doctors treat paranasal sinus cancer with a combination of surgery and radiation therapy. […] Radiation therapy is given following surgery if the tumor is likely to recur.

• #8 Malignant Tumors of the Sinuses: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/847189-overview

  Risk factors for sinonasal malignancies (SNMs) have been extensively investigated. They are complicated, multifactorial, and somewhat controversial. The idea that squamous cell carcinoma (SCC) and adenocarcinoma in this area are associated with exposure to nickel dust, mustard gas, thorotrast, isopropyl oil, chromium, or dichlorodiethyl sulfide is well established. Wood dust exposure, in particular, is found to increase the risk of SCC 21 times and the risk of adenocarcinoma 874 times. […] Viral infections and their relationship to malignancy is an interesting area that has not received sufficient investigation. […] Preliminary studies show that epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) in elevated levels of expression may be associated with early events in inverting papilloma (IP) carcinogenesis. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) infection may also be an early event in a multistep process of malignant transformation of inverting papilloma (IP).

• #9 Malignant Tumors of the Sinuses: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/847189-overview

  Risk factors for sinonasal malignancies (SNMs) have been extensively investigated. They are complicated, multifactorial, and somewhat controversial. The idea that squamous cell carcinoma (SCC) and adenocarcinoma in this area are associated with exposure to nickel dust, mustard gas, thorotrast, isopropyl oil, chromium, or dichlorodiethyl sulfide is well established. Wood dust exposure, in particular, is found to increase the risk of SCC 21 times and the risk of adenocarcinoma 874 times. […] Viral infections and their relationship to malignancy is an interesting area that has not received sufficient investigation. […] Preliminary studies show that epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) in elevated levels of expression may be associated with early events in inverting papilloma (IP) carcinogenesis. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) infection may also be an early event in a multistep process of malignant transformation of inverting papilloma (IP).

• #10 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  Research has heavily focused on HPV infection as a potential driver of IP malignant transformation, this agent being well known for its pathogenic role in oropharyngeal lesions. […] However, the prevalence of HPV infection in IP and SNSCC, either IP-derived or primary, greatly varies among studies, as does the HPV genotype putatively involved (low-risk vs. high-risk). […] ITAC, however, may develop even after short exposure: 9.6% of patients had less than 5 years of exposure and in 13.2% of patients, the interval between exposure and diagnosis exceeded 40 years. […] Several studies suggested that ITAC develops by chronic inflammation caused by prolonged exposure and irritation by WD particles, stimulating cellular turnover. […] The key-gene in the regulation of intestinal differentiation is CDX2, that is, the pre-requisite of intestinal metaplasia, of which the overexpression within ITAC cells is almost systematic.

• #11 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. […] Accurate diagnosis can be challenging and requires several diagnostic markers, especially for some subtypes. They typically present during the 50th to 60th decade of life, with a higher prevalence in males. Occupational exposure, genetic mutations, and viral infections can be considered etiological agents in several sinonasal tumors. Overall poor survival is largely due to the biology of the different cancer types, frequent presentation at an advanced stage and limited treatment options for advanced disease, especially when surgery and radiotherapy are not a curative option anymore. Recent developments have been driven by advances in immunohistochemistry and molecular analysis. Better understanding of the pathogenesis, along with the possibility to differentiate distinct subtypes, has important implications for clinical practice, especially in the development and delivery of targeted treatment.

• #12 What Causes Nasal Cancer? | What Causes Paranasal Sinus Cancer? | American Cancer Society

  https://www.cancer.org/cancer/types/nasal-cavity-and-paranasal-sinus-cancer/causes-risks-prevention/what-causes.html

  We dont know what causes each case of nasal cavity or paranasal sinus cancer. But we do know some of the risk factors for these cancers and how some of them cause normal cells to become cancer. For example, some risk factors, such as workplace exposure to certain chemicals, may cause these cancers by damaging the DNA of cells that line the inside of the nose and sinuses. […] Cancers can be caused by DNA changes that turn on proto-oncogenes or turn off tumor suppressor genes. This leads to cells growing out of control. Changes in many different genes are usually needed to cause nasal cavity or paranasal sinus cancer. […] Scientists believe that some risk factors, such as workplace exposures to certain chemicals and tobacco use, cause these cancers by damaging the DNA of the cells that line the inside of the nasal cavity and paranasal sinuses.

• #13 What Causes Nasal Cancer? | What Causes Paranasal Sinus Cancer? | American Cancer Society

  https://www.cancer.org/cancer/types/nasal-cavity-and-paranasal-sinus-cancer/causes-risks-prevention/what-causes.html

  Gene changes related to these cancers usually develop during life rather than being inherited. These acquired mutations are often the result of exposure to cancer-causing chemicals like those found in the workplace or in tobacco smoke. Acquired mutations probably cause most nasal cavity and paranasal sinus cancers, but sometimes they happen for no apparent reason.

• #14 Sinonasal Squamous Cell Carcinoma: Etiology, Pathogenesis, and the Role of Human Papilloma Virus

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7314379/

  1. Currently, there is a poor understanding of the etiology and pathogenesis of SNSCC. […] 2. High risk HPV appears to play a role in the pathogenesis of a subset of SNSCCs. […] 3. While not definitively proven, evidence supports a role for high-risk HPV in a subset of SNSCC, and low-risk HPV in a subset of inverted papillomas which transform to SNSCC. […] 4. The pathogenesis and genomic underpinnings of SNSCC remains poorly defined. […] 5. The genomic landscape of SNSCC is poorly defined. […] 6. Somatic mutations: TP53 mutations have been described in a significant portion of SNSCCs, particularly in those tumors associated with exposure to wood dust. […] 7. Similar to other HNSCCs, patients with TP53 altered SNSCC appears to have worse OS. […] 8. The presence of transcriptionally active HR-HPV varies for the various SCC subtypes in the sinonasal tract and is more frequently detected in nonkeratinizing SCC compared with keratinizing.

• #15 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  In favor of this hypothesis, next-generation sequencing studies have reported loss of function TP53 mutation as a frequent event in IP-derived SNSCC. […] In light of this evidence, it can be hypothesized that p53 and p21 mutations may be two independent mechanisms which both result in anti-apoptotic activity in cancer cells. […] Going along the line of cell cycle regulatory molecules, expression of cyclooxygenase-2 (COX-2), an inflammation-inducible factor with proliferative and anti-apoptotic activity, was found to be progressively higher as IP progresses to SNSCC, and it also seems to be higher in primary SNSCC compared to IP alone. […] Higher COX-2 expression may be due to p53 mutation, as wild-type p53 normally suppresses COX-2 transcription. […] Overall, it seems that IP-derived SNSCC is characterized by aberrant angiogenesis, as demonstrated by higher vascular density and increased Vascular Endothelial Growth Factor (VEGF) expression in IP-derived SNSCC than in IP alone.

• #16 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  TP53 mutations and p53 overexpression seem to be related to WD exposure and have been identified not only in metaplastic foci, but even in normal epithelial mucosa and stromal glands of woodworkers. […] ONB is characterized by a heterogenous biological behavior. A few recurrent genomic aberrations or somatic mutations have been consistently reported by some authors, which may pave a way for new tailored treatment approaches. […] Aberrant Shh pathway seems to be also involved in the pathogenesis of ONB and the expression levels of Patched1, Gli1, and Gli2 appear to be correlated with its pathological degrees. […] Pathogenesis of the three most common sinonasal malignancies is currently ill defined, largely due to the rarity of these entities. A better understanding of pathogenic mechanisms behind sinonasal malignancies may pave the way towards tailored treatment approaches, and therefore, improve their prognosis.

• #17 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  Research has heavily focused on HPV infection as a potential driver of IP malignant transformation, this agent being well known for its pathogenic role in oropharyngeal lesions. […] However, the prevalence of HPV infection in IP and SNSCC, either IP-derived or primary, greatly varies among studies, as does the HPV genotype putatively involved (low-risk vs. high-risk). […] ITAC, however, may develop even after short exposure: 9.6% of patients had less than 5 years of exposure and in 13.2% of patients, the interval between exposure and diagnosis exceeded 40 years. […] Several studies suggested that ITAC develops by chronic inflammation caused by prolonged exposure and irritation by WD particles, stimulating cellular turnover. […] The key-gene in the regulation of intestinal differentiation is CDX2, that is, the pre-requisite of intestinal metaplasia, of which the overexpression within ITAC cells is almost systematic.

• #18 Pathology Outlines – Sinonasal carcinoma-general

  https://www.pathologyoutlines.com/topic/nasalcarcinomageneral.html

  Rare and heterogenous group of malignancies that originate in the nasal cavity and paranasal sinuses and present with different histologic features and clinical behavior. […] Sinonasal carcinomas are a rare and heterogeneous group of malignancies that develop in the nasal cavity and the paranasal sinuses with diverse histology. […] Persistent exposure to wood and leather dust, textiles and organic solvents over a period of time is a strong risk factor for developing sinonasal carcinomas and is thought to be the result of chronic inflammation. […] Organic dust and occupational exposures associated with tumor development are not considered directly mutagenic. […] These substances may cause chronic inflammation due to continuous mucosal irritation. […] Chronic inflammation is a recognized mechanism of malignancy in several cancer types.

• #19 Pathology Outlines – Sinonasal carcinoma-general

  https://www.pathologyoutlines.com/topic/nasalcarcinomageneral.html

  Phagocytosis of inhaled organic dust, mineral fibers or fungal spores induce alveolar macrophages to secrete cytokines and chemokines involved in the inflammatory response. […] Stimulation by wood dust results in the release of reactive oxygen species and reactive nitrogen species by alveolar macrophages. […] Wnt / beta catenin pathway is also frequently affected. […] Metaplasia of the normal respiratory or olfactory epithelium is thought to occur in early stages of development. […] Histopathologic change that represents cellular and tissue response to chronic inflammation. […] These metaplastic tissues have been observed adjacent to these tumors and in people with exposure to environmental or occupational risk factors.

• #20 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  In favor of this hypothesis, next-generation sequencing studies have reported loss of function TP53 mutation as a frequent event in IP-derived SNSCC. […] In light of this evidence, it can be hypothesized that p53 and p21 mutations may be two independent mechanisms which both result in anti-apoptotic activity in cancer cells. […] Going along the line of cell cycle regulatory molecules, expression of cyclooxygenase-2 (COX-2), an inflammation-inducible factor with proliferative and anti-apoptotic activity, was found to be progressively higher as IP progresses to SNSCC, and it also seems to be higher in primary SNSCC compared to IP alone. […] Higher COX-2 expression may be due to p53 mutation, as wild-type p53 normally suppresses COX-2 transcription. […] Overall, it seems that IP-derived SNSCC is characterized by aberrant angiogenesis, as demonstrated by higher vascular density and increased Vascular Endothelial Growth Factor (VEGF) expression in IP-derived SNSCC than in IP alone.

• #21 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  In favor of this hypothesis, next-generation sequencing studies have reported loss of function TP53 mutation as a frequent event in IP-derived SNSCC. […] In light of this evidence, it can be hypothesized that p53 and p21 mutations may be two independent mechanisms which both result in anti-apoptotic activity in cancer cells. […] Going along the line of cell cycle regulatory molecules, expression of cyclooxygenase-2 (COX-2), an inflammation-inducible factor with proliferative and anti-apoptotic activity, was found to be progressively higher as IP progresses to SNSCC, and it also seems to be higher in primary SNSCC compared to IP alone. […] Higher COX-2 expression may be due to p53 mutation, as wild-type p53 normally suppresses COX-2 transcription. […] Overall, it seems that IP-derived SNSCC is characterized by aberrant angiogenesis, as demonstrated by higher vascular density and increased Vascular Endothelial Growth Factor (VEGF) expression in IP-derived SNSCC than in IP alone.

• #22 Sinonasal Squamous Cell Carcinoma: Etiology, Pathogenesis, and the Role of Human Papilloma Virus

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7314379/

  1. Currently, there is a poor understanding of the etiology and pathogenesis of SNSCC. […] 2. High risk HPV appears to play a role in the pathogenesis of a subset of SNSCCs. […] 3. While not definitively proven, evidence supports a role for high-risk HPV in a subset of SNSCC, and low-risk HPV in a subset of inverted papillomas which transform to SNSCC. […] 4. The pathogenesis and genomic underpinnings of SNSCC remains poorly defined. […] 5. The genomic landscape of SNSCC is poorly defined. […] 6. Somatic mutations: TP53 mutations have been described in a significant portion of SNSCCs, particularly in those tumors associated with exposure to wood dust. […] 7. Similar to other HNSCCs, patients with TP53 altered SNSCC appears to have worse OS. […] 8. The presence of transcriptionally active HR-HPV varies for the various SCC subtypes in the sinonasal tract and is more frequently detected in nonkeratinizing SCC compared with keratinizing.

• #23 Sinonasal Squamous Cell Carcinoma: Etiology, Pathogenesis, and the Role of Human Papilloma Virus

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7314379/

  9. HPV in ISPs has been detected by different methods with Low-risk HPV being 2.8 times as frequent as HR-HPV in ISP and ISP-associated SCC. […] 10. However, HR-HPV is more frequent in cases with high-grade dysplasia and carcinoma. […] 11. A recent meta-analysis suggests that HPV-18 may be specifically associated with ISPSCC. […] 12. HPV-related multiphenotypic sinonasal carcinoma with adenoid cystic-like features is a newly described entity under the category of NKSCC in the latest WHO classification. […] 13. HMSC is associated with strong and diffuse p16 staining in all cases and Ki-67 staining in 40-90%. […] 14. HMSC is by definition associated with high-risk HPV infection, with HPV-33 and HPV-35 being the most common genotypes. […] 15. Unlike the remainder of mucosal HNSCCs, the pathogenesis and genomic underpinnings of SNSCC remains poorly defined.

• #24 Sinonasal Squamous Cell Carcinoma: Etiology, Pathogenesis, and the Role of Human Papilloma Virus

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7314379/

  9. HPV in ISPs has been detected by different methods with Low-risk HPV being 2.8 times as frequent as HR-HPV in ISP and ISP-associated SCC. […] 10. However, HR-HPV is more frequent in cases with high-grade dysplasia and carcinoma. […] 11. A recent meta-analysis suggests that HPV-18 may be specifically associated with ISPSCC. […] 12. HPV-related multiphenotypic sinonasal carcinoma with adenoid cystic-like features is a newly described entity under the category of NKSCC in the latest WHO classification. […] 13. HMSC is associated with strong and diffuse p16 staining in all cases and Ki-67 staining in 40-90%. […] 14. HMSC is by definition associated with high-risk HPV infection, with HPV-33 and HPV-35 being the most common genotypes. […] 15. Unlike the remainder of mucosal HNSCCs, the pathogenesis and genomic underpinnings of SNSCC remains poorly defined.

• #25 Malignant Tumors of the Sinuses: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/847189-overview

  Squamous cell carcinoma (SCC) constitutes over 80% of all malignancies that arise in the nasal cavity and paranasal sinuses. […] Prognosis is improved in those patients presenting with ethmoid primaries and early lesions treated with both radiation and surgery, as well as with a history of IP. […] A study that compared overall survival in association with HPV status in sinonasal SCC found that 3-year overall survival was 18.5% higher for HPV-positive tumors when compared with HPV-negative lesions. […] Adenoid cystic carcinoma (ACC) is of salivary origin and is the second most common sinonasal malignancy, accounting for 10% of cases. […] Adenocarcinoma of the nasal cavity and paranasal sinuses is historically important and is associated with specific risk factors including exposure to wood dust, lacquers, and other organic compounds.

• #26 Malignant Tumors of the Sinuses: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/847189-overview

  Risk factors for sinonasal malignancies (SNMs) have been extensively investigated. They are complicated, multifactorial, and somewhat controversial. The idea that squamous cell carcinoma (SCC) and adenocarcinoma in this area are associated with exposure to nickel dust, mustard gas, thorotrast, isopropyl oil, chromium, or dichlorodiethyl sulfide is well established. Wood dust exposure, in particular, is found to increase the risk of SCC 21 times and the risk of adenocarcinoma 874 times. […] Viral infections and their relationship to malignancy is an interesting area that has not received sufficient investigation. […] Preliminary studies show that epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) in elevated levels of expression may be associated with early events in inverting papilloma (IP) carcinogenesis. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) infection may also be an early event in a multistep process of malignant transformation of inverting papilloma (IP).

• #27 Sinus Cancer: Causes, Symptoms & Treatments

  https://www.cancercenter.com/cancer-types/sinus-cancer

  Sinus cancer occurs in the nasal cavity and paranasal sinus spaces behind the nose through which air passes on its way to the throat. Cancer that occurs in the sinus is categorized as head and neck cancer. Cancer occurs when malignant (cancerous) cells form. The most common type of sinus cancer is squamous cell carcinoma, likely because squamous cells are the most common cell type in the head and neck. […] Certain lifestyle behaviors and environmental factors, such as smoking and exposure to carcinogens, may increase the risk of developing sinus cancer. Risk factors for sinus cancer also depend on the location as with nasal cavity cancer or paranasal sinus cancer and the types of cancer involved. […] Factors that increase the risk of sinus cancer may include: Workplace exposure to certain chemicals and substances, including woodworking (exposure to wood dust) and working with nickel and other heavy metals, Epstein-Barr virus (EBV), known for causing mono (mononucleosis) in young adults, smoking and tobacco use, alcohol abuse, human papillomavirus (HPV), exposure to high doses of radiation therapy, particularly in the head or neck region, including radiation for retinoblastoma.

• #28 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  The aim of the present review was to summarize the scientific evidence regarding molecular mechanisms behind the most common sinonasal malignant tumors. […] In total, our search yielded 1450 articles. […] Finally, 246 articles were included in the qualitative analysis. The details of the systematic search are shown in Figure 1. Since the large majority of the retrieved articles examined SNSCC, ITAC, and ONB, the discussion was focused on these three pathological entities. […] As known, SNSCC may arise from benign lesions with malignant transformation potential. Even though a rare event, SNSCC progression from inverted papilloma (IP) provides the perfect model to understand molecular changes associated with SNSCC pathogenesis. […] Increased cell proliferation unopposed by programmed cell death, as seen in many other malignancies, is one proposed mechanism behind IP transformation.

• #29 Malignant Tumors of the Sinuses: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/847189-overview

  Squamous cell carcinoma (SCC) constitutes over 80% of all malignancies that arise in the nasal cavity and paranasal sinuses. […] Prognosis is improved in those patients presenting with ethmoid primaries and early lesions treated with both radiation and surgery, as well as with a history of IP. […] A study that compared overall survival in association with HPV status in sinonasal SCC found that 3-year overall survival was 18.5% higher for HPV-positive tumors when compared with HPV-negative lesions. […] Adenoid cystic carcinoma (ACC) is of salivary origin and is the second most common sinonasal malignancy, accounting for 10% of cases. […] Adenocarcinoma of the nasal cavity and paranasal sinuses is historically important and is associated with specific risk factors including exposure to wood dust, lacquers, and other organic compounds.

• #30 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  The aim of the present review was to summarize the scientific evidence regarding molecular mechanisms behind the most common sinonasal malignant tumors. […] In total, our search yielded 1450 articles. […] Finally, 246 articles were included in the qualitative analysis. The details of the systematic search are shown in Figure 1. Since the large majority of the retrieved articles examined SNSCC, ITAC, and ONB, the discussion was focused on these three pathological entities. […] As known, SNSCC may arise from benign lesions with malignant transformation potential. Even though a rare event, SNSCC progression from inverted papilloma (IP) provides the perfect model to understand molecular changes associated with SNSCC pathogenesis. […] Increased cell proliferation unopposed by programmed cell death, as seen in many other malignancies, is one proposed mechanism behind IP transformation.

• #31 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  In favor of this hypothesis, next-generation sequencing studies have reported loss of function TP53 mutation as a frequent event in IP-derived SNSCC. […] In light of this evidence, it can be hypothesized that p53 and p21 mutations may be two independent mechanisms which both result in anti-apoptotic activity in cancer cells. […] Going along the line of cell cycle regulatory molecules, expression of cyclooxygenase-2 (COX-2), an inflammation-inducible factor with proliferative and anti-apoptotic activity, was found to be progressively higher as IP progresses to SNSCC, and it also seems to be higher in primary SNSCC compared to IP alone. […] Higher COX-2 expression may be due to p53 mutation, as wild-type p53 normally suppresses COX-2 transcription. […] Overall, it seems that IP-derived SNSCC is characterized by aberrant angiogenesis, as demonstrated by higher vascular density and increased Vascular Endothelial Growth Factor (VEGF) expression in IP-derived SNSCC than in IP alone.

• #32 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  In favor of this hypothesis, next-generation sequencing studies have reported loss of function TP53 mutation as a frequent event in IP-derived SNSCC. […] In light of this evidence, it can be hypothesized that p53 and p21 mutations may be two independent mechanisms which both result in anti-apoptotic activity in cancer cells. […] Going along the line of cell cycle regulatory molecules, expression of cyclooxygenase-2 (COX-2), an inflammation-inducible factor with proliferative and anti-apoptotic activity, was found to be progressively higher as IP progresses to SNSCC, and it also seems to be higher in primary SNSCC compared to IP alone. […] Higher COX-2 expression may be due to p53 mutation, as wild-type p53 normally suppresses COX-2 transcription. […] Overall, it seems that IP-derived SNSCC is characterized by aberrant angiogenesis, as demonstrated by higher vascular density and increased Vascular Endothelial Growth Factor (VEGF) expression in IP-derived SNSCC than in IP alone.

• #33 Malignant Tumors of the Sinuses: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/847189-overview

  The most common types of SNM are squamous cell carcinoma (50-55%) and adenocarcinoma (10-15%). Other types include esthesioneuroblastoma (6%), adenoid cystic carcinoma (6%), mucosal melanoma (7%), undifferentiated carcinoma (3%), and other neoplasias (14%). […] Although rare, SNMs can be lesions of immense importance. They produce few, if any, signs while the tumor is in its early stages. This problem is exacerbated by the fact that the initial manifestations (eg, unilateral epistaxis, nasal obstruction) mimic signs and symptoms of many common but less serious conditions. Therefore, the patient and clinician often disregard or minimize the initial presentation of these tumors and treat early-stage malignancy as a benign sinonasal disorder. […] The anatomy of the nasal cavity and paranasal sinuses causes these tumors to manifest in advanced stages and complicate their treatment. They are located adjacent to important structures such as the skull base, orbits, cranial nerves, and vital vascular structures.

• #34 Malignant Tumors of the Sinuses: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/847189-overview

  Squamous cell carcinoma (SCC) constitutes over 80% of all malignancies that arise in the nasal cavity and paranasal sinuses. […] Prognosis is improved in those patients presenting with ethmoid primaries and early lesions treated with both radiation and surgery, as well as with a history of IP. […] A study that compared overall survival in association with HPV status in sinonasal SCC found that 3-year overall survival was 18.5% higher for HPV-positive tumors when compared with HPV-negative lesions. […] Adenoid cystic carcinoma (ACC) is of salivary origin and is the second most common sinonasal malignancy, accounting for 10% of cases. […] Adenocarcinoma of the nasal cavity and paranasal sinuses is historically important and is associated with specific risk factors including exposure to wood dust, lacquers, and other organic compounds.

• #35 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  Research has heavily focused on HPV infection as a potential driver of IP malignant transformation, this agent being well known for its pathogenic role in oropharyngeal lesions. […] However, the prevalence of HPV infection in IP and SNSCC, either IP-derived or primary, greatly varies among studies, as does the HPV genotype putatively involved (low-risk vs. high-risk). […] ITAC, however, may develop even after short exposure: 9.6% of patients had less than 5 years of exposure and in 13.2% of patients, the interval between exposure and diagnosis exceeded 40 years. […] Several studies suggested that ITAC develops by chronic inflammation caused by prolonged exposure and irritation by WD particles, stimulating cellular turnover. […] The key-gene in the regulation of intestinal differentiation is CDX2, that is, the pre-requisite of intestinal metaplasia, of which the overexpression within ITAC cells is almost systematic.

• #36 Pathology Outlines – Sinonasal carcinoma-general

  https://www.pathologyoutlines.com/topic/nasalcarcinomageneral.html

  Phagocytosis of inhaled organic dust, mineral fibers or fungal spores induce alveolar macrophages to secrete cytokines and chemokines involved in the inflammatory response. […] Stimulation by wood dust results in the release of reactive oxygen species and reactive nitrogen species by alveolar macrophages. […] Wnt / beta catenin pathway is also frequently affected. […] Metaplasia of the normal respiratory or olfactory epithelium is thought to occur in early stages of development. […] Histopathologic change that represents cellular and tissue response to chronic inflammation. […] These metaplastic tissues have been observed adjacent to these tumors and in people with exposure to environmental or occupational risk factors.

• #37 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  TP53 mutations and p53 overexpression seem to be related to WD exposure and have been identified not only in metaplastic foci, but even in normal epithelial mucosa and stromal glands of woodworkers. […] ONB is characterized by a heterogenous biological behavior. A few recurrent genomic aberrations or somatic mutations have been consistently reported by some authors, which may pave a way for new tailored treatment approaches. […] Aberrant Shh pathway seems to be also involved in the pathogenesis of ONB and the expression levels of Patched1, Gli1, and Gli2 appear to be correlated with its pathological degrees. […] Pathogenesis of the three most common sinonasal malignancies is currently ill defined, largely due to the rarity of these entities. A better understanding of pathogenic mechanisms behind sinonasal malignancies may pave the way towards tailored treatment approaches, and therefore, improve their prognosis.

• #38 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  TP53 mutations and p53 overexpression seem to be related to WD exposure and have been identified not only in metaplastic foci, but even in normal epithelial mucosa and stromal glands of woodworkers. […] ONB is characterized by a heterogenous biological behavior. A few recurrent genomic aberrations or somatic mutations have been consistently reported by some authors, which may pave a way for new tailored treatment approaches. […] Aberrant Shh pathway seems to be also involved in the pathogenesis of ONB and the expression levels of Patched1, Gli1, and Gli2 appear to be correlated with its pathological degrees. […] Pathogenesis of the three most common sinonasal malignancies is currently ill defined, largely due to the rarity of these entities. A better understanding of pathogenic mechanisms behind sinonasal malignancies may pave the way towards tailored treatment approaches, and therefore, improve their prognosis.

• #39 Malignant Tumors of the Sinuses: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/847189-overview

  Squamous cell carcinoma (SCC) constitutes over 80% of all malignancies that arise in the nasal cavity and paranasal sinuses. […] Prognosis is improved in those patients presenting with ethmoid primaries and early lesions treated with both radiation and surgery, as well as with a history of IP. […] A study that compared overall survival in association with HPV status in sinonasal SCC found that 3-year overall survival was 18.5% higher for HPV-positive tumors when compared with HPV-negative lesions. […] Adenoid cystic carcinoma (ACC) is of salivary origin and is the second most common sinonasal malignancy, accounting for 10% of cases. […] Adenocarcinoma of the nasal cavity and paranasal sinuses is historically important and is associated with specific risk factors including exposure to wood dust, lacquers, and other organic compounds.

• #40 Malignant Tumors of the Sinuses: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/847189-overview

  Treatment is surgical excision with wide margins and postoperative radiotherapy for advanced disease or positive margins. […] Malignant melanoma is a rare disorder of the nasal cavity and paranasal sinus mucosa. […] Sinonasal neuroendocrine tumors are a unique and often confusing group of sinonasal malignancies (SNMs) including esthesioneuroblastoma (ENB), sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and small cell carcinoma (SmCC). […] Sinonasal undifferentiated carcinoma (SNUC) is an uncommon, rapidly growing neoplasm of the sinonasal region. […] Small cell neuroendocrine carcinoma (SmCC), similar to oat-cell carcinoma of the lungs, is reported to arise in the nasal cavity and paranasal sinuses of patients aged 26-77 years.

• #41 Sinus Cancer: Causes, Symptoms & Treatments

  https://www.cancercenter.com/cancer-types/sinus-cancer

  Sinus cancers are classified according to the type of cancer cells involved. Those types include: Squamous cell carcinoma, which originates in the thin, flat cells lining the sinuses, with carcinoma in situ confined to this cellular layer and invasive squamous cell carcinoma spreading more deeply into the tissue, Mucosa cell carcinoma, which occurs in the mucous membrane, Adenoid cystic cell carcinoma, which is a rare form of sinus cancer that occurs in the minor salivary glands of the paranasal sinuses, Acinic cell carcinoma, which develops in the salivary glands, particularly in the parotid gland near the base of each ear, Sinonasal undifferentiated carcinoma, which is a rare neoplasm that develops in the epithelium of the nose or sinuses. […] The nasal cavity and paranasal sinuses are the most common areas affected by sinus cancers. Symptoms vary depending on where the cancer develops, the size of the tumor and how significantly it spreads.

• #42 Update from the 5th Edition of the WHO Classification of Nasal, Paranasal, and Skull Base Tumors: Imaging Overview with Histopathologic and Genetic Correlation | American Journal of Neuroradiology

  http://www.ajnr.org/content/early/2023/08/17/ajnr.A7960

  SUMMARY: Sinonasal and skull base tumors are a heterogeneous group of neoplasms with considerable histologic variation and overlapping imaging features. […] The 5th edition of the World Health Organization (WHO) classification of head and neck tumors was released online in 2022 with a focus on distinctive molecular and genetic characteristics of tumors including in the sinonasal tract (SNT). […] The new classification allows a more logical and stratified approach, with successive entities showing progression from benign to malignant and higher-grade tumors. […] Histopathologic analysis remains a vital part of the pathologic work-up of SNTs, despite the challenging morphologic overlap. […] Genetic profiling has caused an explosion in the subclassification of sinonasal malignancies, particularly focused on subtyping for improved prognostication and treatment, though profiling is still lagging for head and neck tumors, compared with other systems like CNS tumors.

• #43 Update from the 5th Edition of the WHO Classification of Nasal, Paranasal, and Skull Base Tumors: Imaging Overview with Histopathologic and Genetic Correlation | American Journal of Neuroradiology

  http://www.ajnr.org/content/early/2023/08/17/ajnr.A7960

  SUMMARY: Sinonasal and skull base tumors are a heterogeneous group of neoplasms with considerable histologic variation and overlapping imaging features. […] The 5th edition of the World Health Organization (WHO) classification of head and neck tumors was released online in 2022 with a focus on distinctive molecular and genetic characteristics of tumors including in the sinonasal tract (SNT). […] The new classification allows a more logical and stratified approach, with successive entities showing progression from benign to malignant and higher-grade tumors. […] Histopathologic analysis remains a vital part of the pathologic work-up of SNTs, despite the challenging morphologic overlap. […] Genetic profiling has caused an explosion in the subclassification of sinonasal malignancies, particularly focused on subtyping for improved prognostication and treatment, though profiling is still lagging for head and neck tumors, compared with other systems like CNS tumors.

• #44 Update from the 5th Edition of the WHO Classification of Nasal, Paranasal, and Skull Base Tumors: Imaging Overview with Histopathologic and Genetic Correlation | American Journal of Neuroradiology

  http://www.ajnr.org/content/early/2023/08/17/ajnr.A7960

  The histologic grading of SNTs is an important independent predictor of tumor behavior. […] The propensity for grade transformation, progression, and recurrence is also dependent on the molecular subtypes, underlining their importance not just for the surgeons and oncologists but also for radiologists. […] In the past decade, molecular markers and genetics have revolutionized the taxonomy of sinonasal and skull base tumors, leading to recognition of new entities and more accurate understanding of the underlying pathogenesis.

• #45 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  TP53 mutations and p53 overexpression seem to be related to WD exposure and have been identified not only in metaplastic foci, but even in normal epithelial mucosa and stromal glands of woodworkers. […] ONB is characterized by a heterogenous biological behavior. A few recurrent genomic aberrations or somatic mutations have been consistently reported by some authors, which may pave a way for new tailored treatment approaches. […] Aberrant Shh pathway seems to be also involved in the pathogenesis of ONB and the expression levels of Patched1, Gli1, and Gli2 appear to be correlated with its pathological degrees. […] Pathogenesis of the three most common sinonasal malignancies is currently ill defined, largely due to the rarity of these entities. A better understanding of pathogenic mechanisms behind sinonasal malignancies may pave the way towards tailored treatment approaches, and therefore, improve their prognosis.

• #46 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review

  https://www.mdpi.com/1422-0067/24/3/2670

  Research has heavily focused on HPV infection as a potential driver of IP malignant transformation, this agent being well known for its pathogenic role in oropharyngeal lesions. […] However, the prevalence of HPV infection in IP and SNSCC, either IP-derived or primary, greatly varies among studies, as does the HPV genotype putatively involved (low-risk vs. high-risk). […] ITAC, however, may develop even after short exposure: 9.6% of patients had less than 5 years of exposure and in 13.2% of patients, the interval between exposure and diagnosis exceeded 40 years. […] Several studies suggested that ITAC develops by chronic inflammation caused by prolonged exposure and irritation by WD particles, stimulating cellular turnover. […] The key-gene in the regulation of intestinal differentiation is CDX2, that is, the pre-requisite of intestinal metaplasia, of which the overexpression within ITAC cells is almost systematic.

• #47 Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms-A Systematic Review – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36768990/

  Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. […] The genetic and epigenetic changes underlying the oncogenic process were discussed, through a qualitative synthesis of the included studies. The identification of a comprehensive model of carcinogenesis for each sinonasal cancer subtype is needed, in order to pave the way toward tailored treatment approaches and improve survival for this rare and challenging group of cancers.

Zobacz więcej