sinonasal malignancies

1. Sinonasal Malignancies Todd Weiss M.D. SIU School of Medicine Division of Otolaryngology Grand Rounds Presentation

2. Epidemiology Rare and heterogeneous diseases of the head and neck 3% of all head and neck malignancies Reported in all races Mean age at diagnosis is in sixth decade Environmental exposures: Adenocarcinoma Wood dust, leather dust Squamous cell carcinoma Aflatoxin, chromium, asbestos, nickel, mustard gas, polycyclic hydrocarbons

3. Epidemiology 80% of sinonasal tumors involve the maxillary sinus Isolated sinonasal involvement: Maxillary � 25% Ethmoid � 5 - 25% Nasal > sphenoid > frontal 70 � 90% display invasion through at least one wall of the presenting sinus 5-year overall survival rates of 27-53%

4. Sites of Tumor Origin

5. Sinus Anatomy Maxillary antrum Significance Superior � orbit, ethmoids Posterior � pterygoids, infratemporal fossa Ethmoid sinus Significance Superior � fovea, cribiform Medial � lamina papyracea Sphenoid sinus Significance Superior � optic nerve, pituitary Lateral � ICA, cavernous sinus Lateral wall < 0.5mm Inferior � NP, vidian nerve Frontal sinus Significance Inferior � orbit Posterior � anterior cranial fossa

6. Paranasal Sinus Lymphatics Retropharyngeal Jugulodigastric

7. Presentation Symptoms Initial Facial pain Nasal obstruction Epistaxis Advanced disease Diploplia Epiphora Facial edema Trismus, malocclusion Hearing loss Facial numbness Neck mass Signs Nasal/facial/intraoral mass Facial edema Nonvital teeth Proptosis Periorbita compression vs. invasion Cranial nerve deficits II, III, IV, V1, V2, VI

8. Case Presentation HPI: 55 y/o M 6 month hx of facial pain, nasal congestion (R > L) Mild hyposmia PMH: Hypertension, asthma SH/FH: No tobacco, ETOH No H&N CA PE: Nasal polypoid mass with exudate Maxillary antrum not visible

9. Case Presentation - MRI

10. Case Presentation Underwent nasal bx in OR DX: Esthesioneuroblastoma (low grade) Underwent surgical excision with post-op XRT Margins (+) Symptoms resolved with normal F/U

11. Squamous Cell Carcinoma Most common histologic type within sinonasal cavity (50-90%) Moderately differentiated Maxillary > ethmoid > sphenoid / frontal (<2%) Regional spread through anterior or posterior lymphatics Synchronous: 10-20% Metachronous: 20-35%

12. Squamous Cell Carcinoma Distant metastatic disease in 18% Majority of treatment failures reported are local

13. Adenocarcinoma 10 � 20% of sinonasal malignancies Epidemiologic association Ethmoids > nasal cavity > other sinuses Locally aggressive with low incidence of distant mets Varied histogenesis of non-salivary type: Enteric Non-enteric (seromucinous) Metastatic colonic adenocarcinoma

14. Adenocarcinoma

15. Adenocarcinoma Both enteric and nonenteric types are ectodermally derived Primary enteric-type adenocarcinoma evolves from metaplasia of respiratory surface mucosa Clinical outcome: Higher local recurrence with enteric-type tumors regardless of margin status and adjuvant radiotherapy Improved disease free survival with nonenteric tumors

16. Adenoid Cystic Carcinoma Arise from minor salivary glands within the head and neck Most abundant in sinonasal compartment Common antral involvement 5 � 15% of carcinoma in sinonasal cavity Propensity to recur locally Soft tissue infiltration Perineural spread Distant skip lesions Neck nodal metastasis extremely rare Distant metastasis mostly to lung

17. Adenoid Cystic Carcinoma 63% histologically positive margins

18. Neuroendocrine Tumors Uncommon neoplasms of sinonasal cavity Locally aggressive Potential to metastasize

19. Neuroendocrine Tumors Clinically: independent entities Clinical manifestations, aggressiveness Response to therapy Histopathologically: similar entities High degree of overlap Single tumor with regions of differing morphology Differential diagnosis: Immunohistochemical Ultrastructural studies Interpretation/classification remains highly debated

20. Esthesioneuroblastoma(olfactory neuroblastoma) Derived from specialized olfactory neuroepithelium Most common of the group 945 cases reported in world literature Largest single institutional series average 31 cases (range, 11-49) Metastasis reported in 10 � 30% of cases Cervical LN > (brain, bone, viscera, lung, trachea) Locoregional recurrence as late as 10 years Modern series local control rates 86 � 96%

21. Sinonasal Neuroendocrine CA Exact site of origin unknown Common: nasal cavity, ethmoid, maxillary Uncommon: sphenoid, frontal Clinical symptoms identical to ENB and SNUC Requires histopathologic differentiation Small clinical series 40% cervical node mets 10% distant mets 5-year overall survival 74 � 100%

22. Sinonasal Undifferentiated CA Initially described in 1986 by Frierson and colleagues Rare, no prospective trials Tumor origin diffuse among sinonasal tract Symptoms often less than expected given CT findings Highly aggressive local progression Early series report dismal outcomes Lack of effective chemo Inclusion of small cell histology

23. Sinonasal Undifferentiated CA Review between 1986 � 2001 68 patients from 15 papers Overall median survival time 24 months (range, 1 � 195)

24. Sinonasal Small Cell CA Least prevalent type Current literature extremely limited Highest rate of locoregional failure and distant mets Equated with anaplastic small cell lung carcinoma

25. Other Less Common Carcinomas Lymphoma Bimodal presentation Non-Hodgkin�s type B-cell > T-cell 50 - 70% T4 at presentation Mucosal melanoma 0.5 - 1.5% of all melanoma arise from nose and paranasal sinuses 5th to 8th decades Nasal cavity (anterior septum) Maxillary sinus (antrum) 5 and 20 yr survival 11% and 0.5% (mean 2.3 yrs)

26. Other Less Common Carcinomas Mucoepidermoid CA Acinic cell CA Osteogenic sarcoma Fibrosarcoma Chondrosarcoma Rhabdomyosarcoma Extramedullary plasmacytoma Distant mets Kidney (renal cell CA) Lung Breast Colon Inverted pappilloma (intermediate)

27. Hemangiopericytoma Vascular tumor formed by the proliferation of vascular pericytes of Zimmerman Mesenchymal origin �Spiral� around capillaries Primary occurrence site is extremities (lower) 15 � 30% occur in H&N Sinonasal presentation is rare Benign or malignant nature determined clinically, not histologically Lack of reliable histopathologic criteria Recurrence rate 25 � 50% Metastasis rate is 11 � 65% (Sabini, 1998) Lifelong follow-up

28. Evaluation of Sinonasal Mass Physical exam Endoscopic endonasal exam Anosmia, unilateral epistaxis or nasal congestion Unilateral proptosis, lateral globe displacement Imaging Low threshold for CT with IV contrast MRI for skull base, cavernous sinus, orbital extension Resectability Biopsy Office based: Informed decision as to appropriateness OR: hemostasis, fresh tissue specimen

29. Tumor Staging TNM system relatively new concept Epithelial malignancies Maxillary and nasoethmoid tumors Ohngren�s line (1933): Imaginary line from medial canthus to mandible angle dividing maxillary antrum into anterior inferior and posterior superior portions

30. Staging Maxillary Sinus CA AJCC 6th edition

31. Staging Nasoethmoid CA AJCC 6th edition

32. Staging Neuroendocrine CA Kadish system (1976) Provides acceptable prognostic information

33. Case Continuation Patient returned to clinic 8 years post-op 1 month hx of recurrent unilateral epistaxis No other symptoms PE R nasal polypoid mass, 2x3 cm No cervical LAD

34. Case Continuation - Imaging

35. Sinonasal CA Management Literature difficult to interpret Low incidence Wide variety of treatments Absence of uniform staging system Selection bias Non-accurate histology

37. Tumor Management 125 pts, 1974-1995 Majority early stage Multi-modality Tx Did not include CFR Prognostic value: Nodal stage Tumor stage Locoregional failure

38. NE Tumor Management 72 pts, 1982 � 2002 Mean follow-up 81.5 mos (6-266)

39. Rosenthal et al.

40. Rosenthal et al. Although common origin, natural histories diverge ENB - surgery + post-op local RT Non-ENB - systemic therapy + RT

41. Tumor Management Surgical options: 1) Assess bony and soft tissue structures to be included for en bloc resection 2) Approach must provide adequate exposure while preserving function and cosmetic integrity whenever possible 3) Repair should include planned prosthetics or free tissue transfer when necessary Lower maxilla � fibula oseocutaneous Orbitozygomatic support � scapula osteocutaneous Iliac crest osteomyocutaneous flap for additional bone/bulk �Covering recurrent disease�

42. Surgical Options - Maxillectomy

43. Surgical Options - CFR

44. Combined Surgery and Irradiation Improved locoregional control over radiotherapy alone T3 vs. T4 tumors Preop vs. post-op Resectability Tumor-free margins improve survival Toronto � preop XRT 5500 rad followed by radical resection 5-year survival (-) margins: 77% (+) margins: 23%

45. Chemoradiation Improved locoregional control and survival over radiation therapy alone Less morbidity than CFR Sakai et al., Japan > 780 patients with since 1957 5000 cGy, continuous IA 5-FU, Caldwell-Luc 5- year survival improved from 20% - 54% Nibu et al, SCCA maxillary sinus 3000 � 4000 cGy preop, concomitant IA chemo 3000 � 4000 cGy post-op 5-year survival rates: T3 86%, T4 67%

46. RADPLAT

47. Samant, Robbins et al.

48. RADPLAT 11 patients, 1996 � 2003 Avg. f/u 57.2 mos (12-95) All underwent CFR 9 pt�s T4N0M0 2 pt�s T3N0M0

49. Management of the Neck Cervical node mets on average seen in 20% Relatively low incidence Bias toward more aggressive cases Rinaldo et al., Acta Otolaryngol 2002; Elective neck treatment in patients with SCCA of maxillary sinus When cervical node disease present, neck dissection IS indicated Diagnostic and therapeutic Individual consideration for radiating retropharyngeal and parapharyngeal LN

50. Conclusions Most tumors present at an advanced stage Require aggressive multimodality therapy Survival and local disease control are better when the orbit is included in the treatment Consider primary and secondary nodal mets in advanced disease Be aware of comparative literature when determining evidence based treatment plan