Nasal Cavity/Paranasal Sinuses

Ying J. Hitchcock, MD

(T) Primary Tumor		Adapted from 7th edition AJCC Staging Forms.
TNM		Definitions
TX		Primary tumor cannot be assessed
T0		No evidence of primary tumor
Tis		Carcinoma in situ
Maxillary Sinus
T1		Tumor limited to maxillary sinus mucosa with no erosion or destruction of bone
T2		Tumor causing bone erosion or destruction including extension into hard palate &/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates
T3		Tumor invades any of the following: Bone of posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses
T4a		Moderately advanced local disease: Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses
T4b		Very advanced local disease: Tumor invades any of the following: Orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve (V2), nasopharynx, or clivus
Nasal Cavity and Ethmoid Sinus
T1		Tumor restricted to any 1 subsite, ± bony invasion
T2		Tumor invading 2 subsites in a single region or extending to involve an adjacent region within nasoethmoidal complex, with or without bony invasion
T3		Tumor extends to invade medial wall or floor of orbit, maxillary sinus, palate, or cribriform plate
T4a		Moderately advanced local disease: Tumor invades any of the following: Anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses
T4b		Very advanced local disease: Tumor invades any of the following: Orbital apex, dura, brain, middle cranial fossa, cranial nerves other than (V2), nasopharynx, or clivus
(N) Regional Lymph Nodes
NX		Regional lymph nodes cannot be assessed
N0		No regional lymph node metastasis
N1		Metastasis in a single ipsilateral lymph node, ≤ 3 cm in greatest dimension
N2		Metastasis in a single ipsilateral lymph node, > 3 cm but ≤ 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none > 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none > 6 cm in greatest dimension
	N2a	Metastasis in a single ipsilateral lymph node, > 3 cm but ≤ 6 cm in greatest dimension
	N2b	Metastasis in multiple ipsilateral lymph nodes, none > 6 cm in greatest dimension
	N2c	Metastasis in bilateral or contralateral lymph nodes, none > 6 cm in greatest dimension
N3		Metastasis in a lymph node, > 6 cm in greatest dimension
(M) Distant Metastasis
M0		No distant metastasis
M1		Distant metastasis

(G) Histologic Grade		Adapted from 7th edition AJCC Staging Forms.
TNM	Definitions
GX	Grade cannot be assessed
G1	Well differentiated
G2	Moderately differentiated
G3	Poorly differentiated
G4	Undifferentiated

AJCC Stages/Prognostic Groups			Adapted from 7th edition AJCC Staging Forms.
Stage	T	N	M
0	Tis	N0	M0
I	T1	N0	M0
II	T2	N0	M0
III	T3	N0	M0
	T1	N1	M0
	T2	N1	M0
	T3	N1	M0
IVA	T4a	N0	M0
	T4a	N1	M0
	T1	N2	M0
	T2	N2	M0
	T3	N2	M0
	T4a	N2	M0
IVB	T4b	Any N	M0
	Any T	N3	M0
IVC	Any T	Any N	M1

Kadish Staging System for Esthesioneuroblastoma
Group A	Tumor localized to nasal cavity
Group B	Tumor localized to nasal cavity and sinuses
Group C	Tumor extends beyond nasal cavity and sinuses to skull base, anterior cranial fossa, orbit, or neck nodes, with or without distant metastases

Hyams Histologic Grading System for Esthesioneuroblastoma
Microscopic Features	Grade 1	Grade 2	Grade 3	Grade 4
Architecture	Lobular	Lobular	± lobular	± lobular
Pleomorphism	Absent to slight	Present	Prominent	Marked
Neurofibrillary matrix	Prominent	Present	May be present	Absent
Rosettes	Present¹	Present¹	May be present²	May be present²
Mitoses	Absent	Present	Prominent	Marked
Necrosis	Absent	Absent	Present	Prominent
Glands	May be present	May be present	May be present	May be present
Calcification	Variable	Variable	Absent	Absent
Adapted from Barnes L et al: World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours. Lyon: IARC Press, 2005. ¹Homer Wright rosettes (pseudorosettes). ²Flexner-Wintersteiner rosettes (true neural rosettes).

Coronal graphic shows a small T1 tumor

confined to the maxillary mucosa without bone destruction. On the right, there is a larger tumor that destroys bone and also extends to the hard palate

and middle meatus

. Any of these features designate this as a T2 tumor.

Graphic shows a T3 carcinoma invading the posterior bony wall of the maxillary sinus

. T3 disease is also determined by invasion of the floor or medial wall of the orbit &/or involvement of the ethmoid sinus, pterygoid fossa, or subcutaneous tissues.

Coronal graphic shows a T4a maxillary sinus carcinoma

, which is invading the anterior orbit

as well as extending out to the skin of the cheek

. T4a disease is also determined by invasion of pterygoid plates, infratemporal fossa, cribriform plate, and sphenoid or frontal sinuses.

Graphic demonstrates very advanced local disease with maxillary sinus tumor

invading posteriorly and superiorly to the orbital apex

. T4b disease is also designated when there is invasion of dura, brain, middle cranial fossa, nasopharynx, clivus, or cranial nerves other than maxillary division of trigeminal nerve.

Coronal graphic (left) shows a small tumor confined to the left ethmoid air cells

, which is a T1 tumor. On the right, there is a small tumor involving the nasal septum

and nasal floor

. Involvement of two subsites in the nasal cavity makes this a T2 tumor.

Coronal graphic shows an ethmoid tumor

, which extends to the medial orbital wall

and orbital floor

. Maxillary sinus, palate, or cribriform plate invasion also constitute T3 disease.

Coronal graphic illustrates a T4a ethmoid sinus carcinoma

invading the anterior orbit

. T4a disease is also determined by invasion of the skin of the nose or cheek, minimal extension to the anterior cranial fossa, pterygoid plates, or sphenoid or frontal sinuses.

Coronal graphic shows a very advanced local ethmoid tumor

with extensive intracranial invasion

in addition to orbital and maxillary sinus invasion. T4b disease is also evident when there is orbital apex, middle cranial fossa, clivus, nasopharynx, or cranial nerve (other than CN V2) involvement.

Coronal graphic (left) demonstrates a small tumor confined to the nasal cavity

, which is Kadish A and the least common form. On the right, there is extension of tumor from the nasal cavity to the paranasal sinuses

, which is Kadish B.

Coronal graphic illustrates a Kadish C tumor with extension beyond the nasal cavity and sinuses, into both the orbit

and anterior cranial fossa

. Kadish D was not in the original staging system, but indicates nodal &/or distant metastases.

OVERVIEW

General Comments

Rare malignancies arising from nasal cavity and paranasal sinus
Incidence of 1 per 100,000 or 3% of upper respiratory cancers
Maxillary sinus is the most common site of sinonasal malignancies
60-80% of paranasal sinus tumors arise from maxillary antrum
Squamous cell carcinoma is the most common histology
Adenocarcinomas tend to occur in ethmoid sinuses or upper nasal cavity
Esthesioneuroblastoma (ENB) originates from neuroectoderm; rare (2% of nasal malignancies)
- Referred to as olfactory neuroblastoma
- Arises from olfactory mucosa of superior 1/3 of nasal septum, cribriform plate, and superior turbinates
Subsites anatomy
- Nasal cavity
  - Nasal vestibule
  - Nasal fossa: Septum, floor, lateral wall
- Paranasal sinuses
  - Maxillary sinuses
  - Ethmoid sinuses
  - Sphenoid sinuses
  - Frontal sinuses
Late clinical presentation often results in advanced stage of disease
Regional LN spread is relatively uncommon, can occur in advanced T stage tumors
- Involvement of nodal sites: Buccinator,
  
  submandibular, upper jugular, and retropharyngeal nodes
- Bilateral spread may occur when primary extends beyond midline

Classification

Primary malignant tumors (WHO classification)
- Carcinomas
  - Squamous cell carcinomas
    - Verrucous carcinoma
    - Papillary squamous cell carcinoma
    - Basaloid squamous cell carcinoma
    - Spindle cell carcinoma
    - Adenosquamous carcinoma
    - Acantholytic squamous cell carcinoma
  - Lymphoepithelial carcinoma
  - Sinonasal undifferentiated carcinoma
  - Adenocarcinoma
    - Intestinal-type adenocarcinoma
    - Non-intestinal-type adenocarcinoma
- Neuroendocrine tumors
  - Typical carcinoid
  - Atypical carcinoid
  - Small cell carcinoma, neuroendocrine type
- Soft tissue tumors
  - Malignant tumors
    - Fibrosarcoma
    - Malignant fibrous histiocytoma
    - Leiomyosarcoma
    - Rhabdomyosarcoma
    - Angiosarcoma
    - Malignant peripheral nerve sheath tumor
  - Tumors with low malignant potential/borderline tumors
    - Desmoid-type fibromatosis
    - Inflammatory myofibroblastic tumor
    - Glomangiopericytoma (sinonasal-type hemangiopericytoma)
    - Extrapleural solitary fibrous tumor
- Tumors of bone and cartilage (malignant subtype)
  - Chondrosarcoma
  - Mesenchymal chondrosarcoma
  - Osteosarcoma
  - Chordoma
- Hematolymphoid tumors
  - Extranodal NK-/T-cell lymphoma
  - Diffuse large B-cell lymphoma
  - Extramedullary plasmacytoma
  - Extramedullary myeloid sarcoma
  - Histiocytic sarcoma
  - Langerhans cell histiocytosis
- Neuroectodermal tumors
  - Ewing sarcoma
  - Primitive neuroectodermal tumor
  - Olfactory neuroblastoma (ENB)
  - Melanotic neuroectodermal tumor of infancy
  - Mucosal malignant melanoma
- Germ cell tumors
  - Immature teratoma
  - Teratoma with malignant transformation
  - Sinonasal yolk sac tumor (endodermal sinus tumor)
  - Sinonasal teratocarcinosarcoma
  - Mature teratoma
  - Dermoid cyst
- Mucosal melanoma
- Secondary tumors

NATURAL HISTORY

General Features

Comments
- Sinonasal carcinoma
  - Most patients older than 40 years of age
  - Minor salivary gland tumors and ENB tend to appear before age 20
  - Early symptoms are vague
    - Nasal cavity: Unilateral nasal obstruction, epistaxis
    - Maxillary sinus: Most often do not present early
  - Advanced stage
    - Aggressively spreads to adjacent structures, facial pain, intranasal/intraoral mass, ocular symptoms

Epidemiology & Cancer Incidence

Sinonasal carcinoma
- Generally a relatively rare cancer, although more prevalent in Japan, South Africa
- Demographics
  - Age: 95% of patients > 45 years of age
  - Gender: M:F =2:1
- Approximately 2,000 new cases per year in USA
- Approximately 3% of head and neck cancers
- European data show incidence < 2 per 100,000 men and 1 per 100,000 women
- Risk factors
  - Tobacco use
  - Alcohol use
  - Viruses
    - Associations with HPV and EBV have been postulated
    - HPV is especially important in carcinomas arising from inverted papillomas
  - Occupational exposures (e.g., textile, leather, formaldehyde, and wood dust)
  - Age
ENB
- Age
  - Broad range: 3-88 years
  - Bimodal distribution centered in 2nd and 6th decades of life
- Gender: Slightly more common in females

Genetics

Sinonasal carcinoma
- Possible link to abnormal expression of p53
ENB
- Cytogenetic abnormalities (e.g., translocations)

Gross Pathology & Surgical Features

Sinonasal carcinoma
- Polypoid morphology
- Papillary or fungating growth
- Tan-white or pinkish red color
ENB
- Broad-based, pedunculated, lobulated, soft, glistening mass covered in mucosa
- Red-gray, red-brown color