PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
The ethmoid sinuses and nasal passages are the appropriate introduction to the upper respiratory tract oncoanatomy since the malignant gradient of the ethmoid sinus is its access and invasion into all of the other paranasal sinuses.
Also included in this chapter is a new site, mucosal melanoma of the head and neck, and its staging criteria. It has been included in this chapter because of the similarity in histopathology of these sites.
PERSPECTIVE AND PATTERNS OF SPREAD
Ethmoid sinus cancer, although rare, is more common than cancers of the sphenoid or frontal sinus. Because of their deep-seated location, these neoplasms are even more difficult to diagnos than maxillary antral cancers. The cancer is insidious in onset, but each manifestation is explicable by the pattern of invasion of the surrounding anatomy. A deep-seated headache around or posterior to the eyes suggests invasion into the surrounding sinuses—the frontal anteriorly, the sphenoid posteriorly, or the contralateral ethmoid or the maxillary sinus inferiorly (Fig. 2.2). With lateral extension, orbital invasion and globe displacement can occur. The clinical triad of symptoms and signs of ethmoid sinus cancer are diplopia, a bloody nasal discharge, and loss of sensation in the upper lip (Fig. 2.2). Patterns of Spread are presented as a cancer crab that can invade in six basic directions Superior-Inferior, Medial-Lateral, Anterior-Posterior (SIMLAP) of adjacent anatomic sites (Fig. 2.2; Table 2.2).
PATHOLOGY
These mucoperiosteum spaces have ciliated, thin pseudo-stratified columnar epithelium that sweeps mucus to the nasal cavity. Ethmoid cancers arise from these mucosal linings of the sinus and tend to be adenocarcinomas as well as squamous cell cancers. They have been associated with the shavings and dust of furniture and cabinetmakers (Table 2.1; Fig. 2.1).
Figure 2.1 | Cytologic grading of squamous cell carcinoma. Well-differentiated (grade 1) squamous cell carcinoma. The tumor cells bear a strong resemblance to normal squamous cells and synthesize keratin, as evidenced by epithelial pearls.
Figure 2.2 | Patterns of spread. A. Coronal. B. Sagittal. The primary cancer (paranasal ethmoid sinus) invades in various directions, which are color-coded vectors (arrows) representing stage of progression: Tis, yellow; T1, green; T2, blue; T3, purple; T4a, red; T4b, black. Three vectors of invasion are into orbit, into nasal passage, and paranasal sinuses and intracranially. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six directional patterns, i.e. SIMLAP Table 2.2.
TNM STAGING CRITERIA
TNM STAGING CRITERIA
The ethmoid paranasal sinus cancer progression is not by size of cancer but invasion into subsites as it advances (Fig. 2.3). T1, ethmoid sinus; T2, paranasal and other ethmoid sinus; T3, maxillary sinus; T4, sphenoid and/or frontal sinus.
SUMMARY OF CHANGES SEVENTH EDITION AMERICAN JOINT COMMITTEE ON CANCER (AJCC)
The TNM stages according to the 7th Edition of AJCC are illustrated in color code of advancement (Fig. 2.3A). T4 lesions have been divided into T4a (moderately advanced local disease) and T4b (very advanced local disease), leading to the stratification of Stage IV into Stage IVA (moderately advanced local/regional disease), Stage IVB (very advanced local/regional disease), and Stage IVC (distant metastatic disease). For an overview of the evolution of cancer staging of the head & neck, see Chapter 1. The TNM Staging Matrix is color coded for identification of Stage Group once T and N stage are determined (Table 2.3A).
Figure 2.3A | TNM stage grouping. Ethmoid cancers invade other paranasal sinuses and the orbit. Vertical presentations of stage groupings, which follow the same color code for cancer stage advancement, are organized in horizontal lanes: stage 0, yellow; I, green; II, blue; III, purple; IVA, red; IVB, black. Definitions of TN on left and stage grouping on right
TNM STAGING CRITERIA
MUCOSAL MELANOMAS
Mucosal melanomas of the head and neck are highly malignant tumors and fortunately are rare. Of the different categories, the mucosal melanomas that occur in the sinuses are the most lethal, followed in the oral cavity, pharynx, and intranasal lesions. These mucosal melanomas represent a small percentage of all melanomas (i.e., 1% to 2% in most large series as compared to cutaneous melanomas) (Fig. 2.3B).
• Mucosal melanomas are derived from mucosa of neuroectodermal origin–derived mucosa whereas nonectodermally derived mucosa such as mucosa of nasopharynx, larynx, and tracheobronchial, which are of endodermal origin, are therefore more free of mucosal melanomas.
• Sinonasal mucosal melanomas, primarily a disease of adults and the elderly, have an onset characteristically two decades later than skin melanomas; 60% are older than 55 years of age.
• Most common sites are palate (34%) and paranasal sinuses (20%) then oral cavity; floor of mouth and tongue constitute only 2% to 10%.
• Advanced stage presentation is common, thus the current TNM system starts at T3, T4a, T4b, since often the exact site of origin can be obscured. Unilateral nasal or sinus obstruction and epistaxis accounted for 85% to 90% of symptoms encountered, often persisting for months. In the oral cavity approximately 35% have preexisting benign mucosal melanotosis because the primary is obscured; they more often present as a metastatic neck node clinically (Fig. 2.3C).
• Pathologic diagnosis requires identification of intracellula melanin, which occurs in 50% to 70% of cases. Enzyme immunochemistry improves accuracy as does the finding o premelanosomes.
• Histologic cellular composition is composed of three types of cells: spindle cell, polygonal cell, and mixed cell.
• Depth of invasion is a key prognostic factor (i.e., 0.5 cm survival is 30%, 0.6 cm to 1 cm is 18%, and >1 cm is only 10%). Size of lesion is less useful for prognosis.
• Angioinvasiveness is another feature and it predicts for early metastatic spread.
• Staging of mucosal melanomas in the literature generally indicates 75% are localized, 18% have regional nodes, and 6% to 10% present as metastases.
• Local failure despite treatment is common and salvage is approximately 25% or less. Distant metastases increase overtime: 51% after treatment but rises to 75% with local failure.
• Survival from pooled series (approximately 1,000 patients), mean survival is 39%, at 5 years 17%; 10 years mean survival drops to 5%, and over 10 years survival is 1% to 2%.
• Treatment is mostly surgical, survival is better for nasal (31%) or oral cavity (12%) and poorest for paranasal sinus (0%).
• Radiation, when used as the primary treatment, is given in a hypofractionation schedule, and local control has been reported to vary from 44% to 61%. Neutron therapy has also had some success.
• Chemotherapy and immunotherapy (BCG) has been used as an adjuvant with little success.
Figure 2.3B | Histopathology Microsection. Malignant melanoma, vertical growth phase. The host response consists of lymphocytes infiltrating amid the melanocytes (“tumo infiltrating lymphocytes”).
Figure 2.3C | TNM stage grouping. Mucosal melanomas of the head and neck are highly malignant tumors and fortunately are rare. Of the different categories, the mucosal melanomas that occur in the sinuses are the most lethal, followed in the oral cavity, pharynx, and intranasal lesions. These mucosal melanomas represent a small percentage of all melanomas i.e. 1%–2% in most large series as compared to cutaneous melanomas. Vertical presentations of stage groupings, which follow the same color code for cancer stage advancement, are organized in horizontal lanes: stage 0, yellow; I, green; II, blue; III, purple; IVA, red; IVB, black. Definitions of TN on left and stage grouping on right
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR T-ONCOANATOMY
The ethmoid sinus is the anatomic isocenter of all paranasal sinuses. The anatomic isocenter is at the level of the floor o the orbit and extends to the sphenoid at the skull base. The anterior surface bullet enters to the right or left of the mid-sagittal plane at or below the medial canthus of the eye (Fig. 2.4A). The lateral bullet is at or below the lateral canthus of the eye (Fig. 2.4B).
T-oncoanatomy
The ethmoid sinuses and nasal passages are the appropriate introduction to the upper respiratory tract. The four paired sinuses are the maxillary, ethmoid, frontal sinuses, and the sphenoid. Although the sphenoid appears as a single midline sinus, it is a paired sinus. A three-dimensional reconstruction, focusing on bony anatomy, allows for an understanding of the interrelationships. The anatomy may be divided by drawing three parallel lines across the frontal view of the skull, one line passing above and another below the orbits, the third passing through the floor of the antra or hard palate. The two vertical lines separate the ethmoid and nasal fossa from the maxillary antra. The nasal septum separates the ethmoid and nasal fossa into right and left sides. In a comparison with anteroposterior and lateral projections or coronal and sagittal sections, three important planes become evident: (i) The floor of the anterior fossa of the skull is th roof of the nasal cavity and ethmoid; (ii) The hard palate is the floor of the maxillary antra; and (iii) An imaginary plane below the orbits divides the paranasal sinuses into a suprastructure and an infrastructure. The suprastructure contains the ethmoids, superomedial to which is the apex of the nasal cavity and cribriform (olfactory region). Posterior to this are the sphenoid sinuses, lateral are the orbits, and inferior are the nasal fossa and turbinates. The infrastructure contains the maxillary antra and the major portion of the nasal cavity or vestibule. These planes are helpful in relating the surface anatomy to the radiographic anatomy. The three-dimensional planar views are crucial to understanding the malignant gradient:
• Coronal plane (Fig. 2.5A): In the coronal view, the lateral anterior wall separates the ethmoid sinus from the orbit and inferiorly drains into the nasal cavity.
• Sagittal plane (Fig. 2.5B): The relationship to the maxillary antrum is readily seen as well as to the sphenoid sinus. Superior to the ethmoid is the cribriform plate and cranial nerve I (olfactory).
• Axial plane (Fig. 2.5C): The orbit and its relation to the ethmoid sinus is shown and illustrates the fineness of the wall separating the two cavities. The sphenoid sinus has the most complex anatomic location in contrast to the frontal sinus, which has the simplest. To understand cranial nerve anatomy, one must relate the course of the first six nerves t the walls of the sphenoid sinuses. The various divisions and branches of the cranial nerve V and its trigeminal ganglion are in its vicinity. This is detailed when studying the nasopharynx, which is directly below the sphenoid sinuses and cavernous sinus.
Figure 2.4 | Orientation of Three-planar T-oncoanatomy. The anatomic isocenter is at the axial level of the sphenoid sinus. A. Coronal. B. Sagittal. Landmarks: Coronal, Right/Left of midline orbit; Sagittal, Zygomatic arch; Transverse, Sphenoid Sinus.
Figure 2.5 | T-oncoanatomy. The Color Code for the anatomic sites correlates with the color code for the stage group (Figure 2.3) and patterns of spread (Figure 2.2) and SIMLAP table (Table 2.2). Connecting the dots in similar colors will provide an appreciation for the 3D Oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
The sentinel nodes are the high retroparapharyngeal and parapharyngeal nodes along the carotid sheath. When they are involved and extend into the retrostyloid compartment (Fig. 2.6), this leads to entrapment of the cranial nerves emerging alongside the jugular foramen. The nodes in this region are named after Rouviere, famous for his treatise on lymphoid anatomy. Again, numerous neurologic syndromes can occur. Retroparotidian syndrome, or the jugular foramen syndrome, is characterized by loss of the gag reflex (cranial nerve IX), vocal cord paralysis (crania nerve X), atrophy of the trapezius muscle (cranial nerve XI), and deviation of the uvula (cranial nerve X) and tongue on protrusion (cranial nerve XII) (Table 2.4).
M-ONCOANATOMY
The lateral pterygoid buccal venous plexus drains into the jugular vein and then into the brachiocephalic veins and to the superior vena cava. Hematogenous spread, although uncommon, can include lung and bone as favored sites of involvement; distant metastases occur infrequently (Fig. 2.7A,B).
Figure 2.6 | N-oncoanatomy. The red node highlights the sentinel node, which is the highest retropharyngeal node. A. Anterior view. B. Lateral view. Once the sentinel node is involved, all of the neck nodes are at risk for metastases. The regional nodes include: (1) retropharyngeal; (2) submandibular; (3) submental; (4) superior deep cervical; (5) jugulodigastric; and (6) midjugular. The juxtaregional nodes are: (7) prelaryngeal; (8) jugulo-omohyoid; (9) inferior deep cervical; (10) supraclavicular; (11) paratracheal; (12) pretracheal; and (13) spinal accessory. M-oncoanatomy is determined by the jugular vein, which joins with the subclavian vein to form the right brachiocephalic vein on the right, and the left brachiocephalic vein on the left; both brachiocephalic veins form the superior vena cava, which drains into the right side of the heart and then into lung.
Figure 2.7 | M-oncoanatomy. A. Carotid artery with major branches shown. B. Pterygoid plexus of veins drains most of head and neck sites into internal deep jugular. The jugular vein drains into the superior vena cava and then into the right heart, making jung the target organ.
Perineural invasion and compression of Ethmoid Cancers is V2 external nasal branch as the cancer invades into Nasal Cavity. The infraorbital perineural invasion occurs with erosion of the lateral wall and floor of the orbit resulting in round spot of hypoesthesia below the lower eyelid (Fig. 2.7C).
Figure 2.7 C | Cranial Nerve Oncoanatomy.
STAGING WORKUP
TABLE 2.5 Ethmoid Sinus
RULES OF CLASSIFICATION AND STAGING
Clinical Staging and Imaging
Inspection and palpation of paranasal sinuses is limited in early localized stages. For ethmoid cancers, orbital invasion may displace the globe and trap the anterior ethmoid branch of cranial nerve V1, leading to altered sensation in the upper lip. Maxillary antral cancers, when advanced, fill the gingival buccal gutte, loosen molar teeth, and invade the cheek and hard palate. Infection and inflammatory sinusitis obscures cancers. Bot magnetic resonance imaging (MRI) and computed tomography enhancement (CTe) are recommended to distinguish tumor from fluid. CTe is best for determining bone erosion of the paper-thin lamina bones of sinus walls. For evaluation of retropharyngeal nodes imaging is essential (Table 2.5 and Figure 2.8).
Pathologic Staging
The gross specimen should be evaluated for margins. Unresected gross residual tumor must be included and marked with clips. All resected lymph node specimens should describe the size, number, and level of involved nodes and whether there is extracapsular spread. Specimens taken after radiation or chemotherapy need to be noted as such; specimen shrinkages may occur up to 30% after resection itself. Designations pT and pN should be used after histopathologic evaluation. Perineural invasion deserves special notation.
Oncoimaging Annotations
• MRI and CT play complementary roles in the assessment and staging process for these tumors.
• MRI is best at detecting tumor extension outside the sinonasal cavity. CT is most sensitive in assessing anatomy and bone invasion with these tumors. The hallmark of sinonasal malignancy is bone destruction, seen in approximately 80% of all CT scans in these patients.
• MRI aids in separating complex sinonasal secretions/infections from tumor. Combined T1- and T2-weighted, contrast medium-enhanced images are needed for this evaluation.
• Orbital extension is manifest on CT and MRI by bone erosion and changes in the orbital fat. MRI tends to underestimate orbital invasions.
• Sinonasal bony sclerosis caused by tumor is rare; its presence is normally related to coexistent chronic inflammator changes.
PROGNOSIS AND CANCER SURVIVAL
PROGNOSTIC FACTORS
The seventh edition of the AJCC Cancer Staging Manual lists the following prognostic factors for nasal ethmoid sinus cancers:
• Size of lymph nodes
• Extracapsular extension from lymph nodes for head and neck
• Head and neck lymph nodes levels I-III
• Head and neck lymph nodes levels IV-V
• Head and neck lymph nodes levels VI-VII
• Other lymph node group
• Clinical location of cervical nodes
• Extracapsular spread (ECS) clinical
• Extracapsular spread (ECS) pathologic
• Human papillomavirus (HPV) status
• Tumor thickness*
*The foregoing passage is from Edge SB, Byrd DR, and Compton CC, et al, AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010, p. 99.
Figure 2.8 | MRI Scan. The ethmoid sinuses are located between or orbits and demonstrates why lateral invasion into orbit is a common pattern of invasion. The CT/MRI transverse section can be correlated with the anatomy in Fig. 2.5C as an assist to staging.
CANCER STATISTICS AND SURVIVAL
Generally, cancers of the oral cavity and pharynx (the upper digestive passage) account for 36,540 new cases. In addition, cancer of the larynx affects another 12,720 patients and thyroid cancers, 44,670. Approximately 25% of head and neck cancer patients die annually, often owing to other causes. Long-term survival rates in patients with thyroid cancer, with only 1,500 deaths (5%), is the exception. The improvement in survival rates in patients with oral cavity and pharyngeal tumors from 1950 to 2000 was modest at 14% and matches that for patients with tumors of the larynx at 15%. A multi-disciplinary approach is vital, and normal tissue conservation and reconstructive techniques have both added greatly to quality of life. Unfortunately, this patient population contains ethanol and nicotine abusers, and it is difficult to change thes habits. Persistence of smoking and drinking contributes to their demise, often from second malignant tumors in adjacent sites.
Specificall, paranasal sinus cancers are detected late due to being mistaken for sinusitis. Both ethmoid and maxillary central cancers remain well below 50% 5-year survival. If diagnosed early survival rates are above 50% 5-year survival (Fig. 2.9).
Figure 2.9 | Five-year survival rates by stage at diagnosis. (Data from Edge SB, Byrd DR, and Compton CC, et al., AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010.)