Paranasal and Nasal Malignancies

Paranasal and Nasal Malignancies

Module Summary

Paranasal sinus malignancies comprise a diverse group of histologies, accounting for approximately 3% of upper aerodigestive tract malignancies. Most malignancies are diagnosed within the 5th and 6th decades of life, are more prominent in Caucasians, and disproportionally affect men twice as often as women. Malignancies of the paranasal sinuses frequently present at more advanced stages, as compared to cancers of the nasal cavity. This has been attributed to the fact that lesions in these cavities, particularly the maxillary sinuses, can grow inconsequentially for longer periods of time before producing symptoms. Overall five-year relative survival for all types of sinonasal malignancies is poor at approximately 50%, although this greatly depends on the histology involved and the primary site of origination.

Squamous cell carcinoma is the most commonly involved epithelial malignancy, followed by adenocarcinoma, mucosal melanoma, esthesioneuroblastoma, adenoid cystic carcinoma, and sinonasal undifferentiated carcinoma (SNUC).  For lymphomas, diffuse large cell B cell lymphoma is most common, followed by nasal NK/T cell lymphoma.  Leather, nickel, and wood dust have been associated with the development of adenocarcinoma, whereas squamous cell carcinoma is more frequently associated with tobacco and alcohol abusers. In general, the maxillary sinus cavities are the most commonly involved paranasal subsite, followed by the ethmoid, sphenoid, and frontal sinuses. 

Epithelial malignancies of the nasal cavity, maxillary and ethmoid sinuses are staged by the TNM staging criteria as outlined by the American Joint Committee on Cancer (AJCC).  Malignancies of the sphenoid and frontal sinuses are so rare that no set staging system is currently in place for these primary sites.  Lymph node involvement and distant metastasis are generally rare in sinonasal tumors, but portend poorer prognoses when present.  Some differences in staging are notable for particular histologies. As per the AJCC 7th edition, mucosal melanomas are all considered advanced stage, regardless of regional or distant metastasis. Esthesioneuroblastomas and SNUC tumors are typically staged by Hyams or Kadish staging systems.  Staging for lymphomas are classified with the Lugano system (based on the Ann Arbor system).  Treatment for paranasal sinus malignancies (non-lymphomas) consists of primary surgical therapy, with or without radiotherapy.  Treatment for lymphomas primarily consists of chemotherapy and radiation therapy.

Module Learning Objectives 
  1. Describe the incidence and epidemiologic factors associated with paranasal sinus malignancies      
  2. Explain the evaluation and workup of paranasal sinus malignancies
  3. Understand the various types of malignancies that present in the paranasal sinuses
  4. Describe the AJCC staging systems
  5. Appreciate management strategies based on stage and primary site

Anatomy

Learning Objectives 
  1. Understand which sinonasal sites are most commonly associated with the development of cancer
  2. Appreciate how primary site location can impact prognosis and survival
References 
  1. Dutta R, Dubal PM, Svider PF, Liu JK, Baredes S, Eloy JA. Sinonasal malignancies: A population-based analysis of site-specific incidence and survival. Laryngoscope. 2015; 125:2491-2497.

Pathogenesis

Learning Objectives 

Know the most common types of paranasal sinus malignancies, and appreciate their survival outcomes

  • Squamous cell carcinoma
  • Adenocarcinoma
  • Adenoid cystic carcinoma
  • Sinonasal undifferentiated carcinoma 
  • Olfactory neuroblastoma 
  • Mucosal melanoma
  • Lymphomas
References 
  1. Ansa B, Goodman M, Ward Ket al. Paranasal sinus squamous cell carcinoma incidence and survival based on Surveillance, Epidemiology, and End Results data, 1973 to 2009. Cancer. 2013; 119:2602-2610.
  2. Kilic S, Samarrai R, Kilic SS, Mikhael M, Baredes S, Eloy JA. Incidence and survival of sinonasal adenocarcinoma by site and histologic subtype. Acta Otolaryngol. 2018; 138:415-421.
  3. Sanghvi S, Patel NR, Patel CR, Kalyoussef E, Baredes S, Eloy JA. Sinonasal adenoid cystic carcinoma: comprehensive analysis of incidence and survival from 1973 to 2009. Laryngoscope. 2013; 123:1592-1597.
  4. Chambers KJ, Lehmann AE, Remenschneider Aet al. Incidence and survival patterns of sinonasal undifferentiated carcinoma in the United States. J Neurol Surg B Skull Base. 2015; 76:94-100.
  5. Jethanamest D, Morris LG, Sikora AG, Kutler DI. Esthesioneuroblastoma: a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg. 2007; 133:276-280.
  6. Moreno MA, Roberts DB, Kupferman MEet al. Mucosal melanoma of the nose and paranasal sinuses, a contemporary experience from the M. D. Anderson Cancer Center. Cancer. 2010; 116:2215-2223.
  7. Peng KA, Kita AE, Suh JD, Bhuta SM, Wang MB. Sinonasal lymphoma: case series and review of the literature. Int Forum Allergy Rhinol. 2014; 4:670-674.

Basic Science

Learning Objectives 

Appreciate the association of occupational and environmental factors with the development of adenocarcinoma versus squamous cell carcinoma.

References 
  1. t Mannetje A, Kogevinas M, Luce Det al. Sinonasal cancer, occupation, and tobacco smoking in European women and men. Am J Ind Med. 1999; 36:101-107.
  2. Acheson ED, Cowdell RH, Hadfield EH, Macbeth RG. Nasal cancer in woodworkers in the furniture industry. BMJ. 1968;2(5605): 587–596 
  3. Holmila R, Cyr D, Luce Det al. COX-2 and p53 in human sinonasal cancer: COX-2 expression is associated with adenocarcinoma histology and wood-dust exposure. Int J Cancer. 2008; 122:2154-2159.

Incidence

Learning Objectives 
  1. Describe the overall trends in incidence rates of paranasal sinus malignancies.
  2. Appreciate the disparities of these trends by gender and race.

 

Patient Evaluation

Learning Objectives 

Describe the evaluation of a patient with a paranasal malignancy.

References 
  1. Harvey RJ, Dalgorf DM. Chapter 10: Sinonasal malignancies. Am J Rhinol Allergy. 2013; 27:35-38.

Imaging

Learning Objectives 

Explain the role that CT, MRI, and PET imaging play in the workup of paranasal cancer.

References 
  1. Fatterpekar GM, Delman BN, Som PM. Imaging the paranasal sinuses: where we are and where we are going. Anat Rec (Hoboken). Nov 2008;291(11):1564-1572.
  2. Gomaa MA, Hammad MS, Abdelmoghny A, Elsherif AM, Tawfik HM. Magnetic resonance imaging versus computed tomography and different imaging modalities in evaluation of sinonasal neoplasms diagnosed by histopathology. Clin Med Insights Ear Nose Throat. 2013;6:9-15.
  3. Lloyd G, Lund VJ, Howard D, Savy L. Optimum imaging for sinonasal malignancy. J Laryngol Otol. Jul 2000;114(7):557-562.
  4. Wild D, Eyrich GK, Ciernik IF, Stoeckli SJ, Schuknecht B, Goerres GW. In-line (18)F-fluorodeoxyglucose positron emission tomography with computed tomography (PET/CT) in patients with carcinoma of the sinus/nasal area and orbit. J Craniomaxillofac Surg. Jan 2006;34(1):9-1

Pathology

Learning Objectives 

Appreciate the potential role of EGFR mutations in the pathogenesis of squamous cell carcinoma.

References 
  1. Lopez F, Llorente JL, Oviedo CMet al. Gene amplification and protein overexpression of EGFR and ERBB2 in sinonasal squamous cell carcinoma. Cancer. 2012; 118:1818-1826.
  2. Takahashi Y, Bell D, Agarwal Get al. Comprehensive assessment of prognostic markers for sinonasal squamous cell carcinoma. Head Neck. 2014; 36:1094-1102.
     

Treatment

Learning Objectives 
  1. Understand the general management methodologies for paranasal sinus malignancies.
  2. Appreciate the role of radiation and chemotherapy in treatment.
  3. Discuss the management of the clinically N0.
  4. Understand appropriate follow-up and surveillance following treatment.
References 
  1. Byrd JK, Clair JM, El-Sayed I. AHNS Series: Do you know your guidelines? Principles for treatment of cancer of the paranasal sinuses: A review of the National Comprehensive Cancer Network Guidelines. Head Neck. Jun 2018.
  2. Robin TP, Jones BL, Gordon OMet al. A comprehensive comparative analysis of treatment modalities for sinonasal malignancies. Cancer. 2017; 123:3040-3049.
  3. Robbins KT, Ferlito A, Silver CE, et al. Contemporary management of sinonasal cancer. Head Neck. Sep 2011;33(9):1352-1365.
  4. Abu-Ghanem S, Horowitz G, Abergel A, et al. Elective neck irradiation versus observation in squamous cell carcinoma of the maxillary sinus with N0 neck: A meta-analysis and review of the literature. Head Neck. Dec 2015;37(12):1823-1828.
  5. Logsdon MD, Ha CS, Kavadi VS, Cabanillas F, Hess MA, Cox JD. Lymphoma of the nasal cavity and paranasal sinuses: improved outcome and altered prognostic factors with combined modality therapy. Cancer. 1997;80(3):477–488. 
  6. Parasher AK, Kuan EC, John MAS, Tajudeen BA, Adappa ND. What is the appropriate timing for endoscopic and radiographic surveillance following treatment for sinonasal malignancies? Laryngoscope. 2018; 128:1511-1512.
  7. Cantù G, Bimbi G, Miceli R, et al. Lymph node metastases in malignant tumors of the paranasal sinuses: prognostic value and treatment. Arch Otolaryngol Head Neck Surg. 2008;134(2):170–177.
     

Surgical Therapies

Learning Objectives 
  1. Discuss the variety of surgical techniques utilized in the management of paranasal sinus cancer.
  2. Appreciate when endoscopic, open, or combined approaches are appropriate.
  3. Understand when orbital preservation surgery is indicated.
References 
  1. Farag A, Rosen M, Evans J. Surgical Techniques for Sinonasal Malignancies. Neurosurg Clin N Am. 2015; 26:403-412.
  2. Higgins TS, Thorp B, Rawlings BA, Han JK. Outcome results of endoscopic vs craniofacial resection of sinonasal malignancies: a systematic review and pooled-data analysis. Int Forum Allergy Rhinol. 2011; 1:255-261.
  3. Harvey RJ, Nalavenkata S, Sacks Ret al. Survival outcomes for stage-matched endoscopic and open resection of olfactory neuroblastoma. Head Neck. 2017; 39:2425-2432.
  4. Howard DJ, Lund VJ, Wei WI. Craniofacial resection for tumors of the nasal cavity and paranasal sinuses: a 25-year experience. Head Neck. 2006;28(10):867–873
  5. Lisan Q, Kolb F, Temam S, Tao Y, Janot F, Moya-Plana A. Management of orbital invasion in sinonasal malignancies. Head Neck. 2016; 38:1650-1656.
     

Staging

Learning Objectives 
  1. Describe the AJCC TNM staging system for maxillary and ethmoid sinus cancer.
  2. Describe the Hyams and Kadish staging system for olfactory neuroblastoma and sinonasal undifferentiated carcinoma.
References 
  1. Edge S, Byrd D, Compton C, Fritz A, Greene F, Trotti A, eds. American Joint Committee on Cancer Staging Manual. 7th ed. New York: Springer; 2010. 
  2. Desai DD, Brandon BM, Perkins EL, Ebert CS, Zanation AM, Thorp BD. Staging of Sinonasal and Ventral Skull Base Malignancies. Otolaryngol Clin North Am. 2017; 50:257-271.
  3. Miyamoto RC, Gleich LL, Biddinger PW, Gluckman JL. Esthesioneuroblastoma and sinonasal undifferentiated carcinoma: impact of histological grading and clinical staging on survival and prognosis. Laryngoscope. 2000; 110:1262-1265.

Complications

Learning Objectives 

Be aware of the potential complications from surgical and radiation therapies.

References 
  1. Suh JD, Ramakrishnan VR, Chi JJ, Palmer JN, Chiu AG. Outcomes and complications of endoscopic approaches for malignancies of the paranasal sinuses and anterior skull base. Ann Otol Rhinol Laryngol. 2013; 122:54-59.
  2. Nakissa N, Rubin P, Strohl R, Keys H. Ocular and orbital complications following radiation therapy of paranasal sinus malignancies and review of literature. Cancer. 1983; 51:980-986.
  3. Teshima M, Shinomiya H, Otsuki Net al. Complications in Salvage Surgery for Nasal and Paranasal Malignant Tumors Involving the Skull Base. J Neurol Surg B Skull Base. 2018; 79:224-228.

Review

Review Questions 
  1. What histologies are the most common paranasal sinus malignancies?
  2. What is the general workup for paranasal malignancies?
  3. How are maxillary and ethmoid sinus cancers staged? How does staging differ by histology?
  4. What are the most common prognostic factors influencing outcomes?
  5. How are these malignancies typically treated? How does management change by histology or primary site location?