PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
The parotid gland has its malignant gradient from superficial to deep by virtue of its anatomic location and bilobed configuration, which surrounds the ramus of the mandible and houses cranial nerve VII.
PERSPECTIVE AND PATTERNS OF SPREAD
Salivary gland tumors are uncommon, accounting for 5% to 7% of all head and neck malignancies; this constitutes 2,000 to 2,500 cases in the United States, mainly in the parotid gland (85%). Fortunately, the majority are relatively benign, and are most often mixed salivary gland tumors or pleomorphic adenomas. Tumors in the submaxillary and sublingual glands tend more toward being malignant.
The parotid gland, by virtue of its anatomic location and bilobed configuration surrounding the ramus of the mandible, presents therapeutic challenges. Foremost is the preservation of the facial nerve (cranial nerve VII), which traverses through its isocenter. The malignant gradient is from anterior to posterior, from lateral to medial, that is, the superficial to deep lobe. The major salivary glands are branched tubuloalveolar exocrine glands whose connective tissue septa subdivide the gland into lobes and lobules. Embedded in the gland are lymph nodes and neural components that can affect survival outcomes.
Alterations in salivary gland flow can be discerned as dryness or abnormal taste in the subclinical phase of tumor growth. It is usually swelling that alerts the patient; once facial paresis appears, medical care is actively sought. Tumors arising in the superficial lobe involve skin and facial nerve and its various branches when aggressive and resection demands sacrificing the facial nerve (T4a). Of greater concern is the deep lobe, where the cancer can enter into the parapharyngeal area by way of the retroparotidian space. The carotid artery, jugular vein, and cranial nerves IX, X, XI, and XII can be involved. 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. 6.2; Table 6.2).
PATHOLOGY
The histopathology can be highly varied, reflecting the cellular components of the acinar glands, which tend to be serous or mucous with an elaborate ductal system. The histopathology of cancers is long and varied reflecting the range of cell types in glands and ducts (Table 6.1). One of the more common salivary gland malignancies is adenoid cystic carcinoma (Figure 6.1).
Figure 6.1| Adenoid cystic carcinoma showing cribriform growth in which cystlike spaces are filled with basophilic material. The cyst spaces are really pseudocysts surrounded by myoepithelial cells.
Figure 6.2 | Patterns of spread. A. In the Sagittal view, the proximity to the facial nerve (CN VII) and its branching to the parotid gland is noted. B. Coronal view: the spread into soft tissues, such as the retroparotidean space and mandible are noteworthy. The primary cancer (parotid gland) invades in various directions, which are color-coded vectors (arrows) representing stage of progression: T0, yellow; T1, green; T2, blue; T3, purple; T4a, red; and T4b, black. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six directional pattern i.e. SIMLAP Table 6.2.
TNM STAGING CRITERIA
TNM STAGING CRITERIA
The staging system for salivary glands appeared in the fourth edition of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) guidelines (1992), and was based on an extensive retrospective study of malignant tumors of the major salivary glands collected from 11 participating American and Canadian institutions. Although statistical analysis of the data revealed that numerous factors affected patient survival, the classification proposed involved only four clinical variables: Tumor size, local extension of the tumor, palpability and suspicion of nodes, and presence or absence of distant metastasis. The anatomic configuration and location predetermines the staging features of the parotid gland. Involvement of the pterygoid plates or skull base renders tumors unresectable (T4b).
SUMMARY OF CHANGES SEVENTH EDITION AJCC
The TNM stages according to the 7th Edition of AJCC are illustrated in color code of advancement (Fig. 6.3). 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). The TNM Staging Matrix is color coded for identification of Stage Group once T and N stages are determined (Table 6.3).
PAROTID GLAND
Figure 6.3 | TNM stage grouping. Parotid gland cancers are highly varied histopathologically and perineural invasion of the VIIth and Vth cranial nerves are the major concern. 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; and IVB, black. Definitions of TN on left and stage grouping on right.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR ONCOANATOMY
The parotid is a superficial gland above the angle of the mandible and wraps around the ramus. The anatomic isocenter is axially at the level of the bodies of C2 and C3. The anterior bullet skims the cheek at the level of the lobule of the external ear (Fig. 6.4A) and the lateral bullet is through the body of the ramus of the mandible superior to the angle of the jaw (Fig. 6.4B).
T-oncoanatomy
The parotid, submaxillary, and sublingual glands are the major salivary glands in contradistinction to the many minor salivary glands, each and all providing digestive enzymes, lubrication, or both for the lumen of the upper digestive passage. The major salivary glands are best oriented (Fig. 6.4AB) to the oral cavity because their major ducts empty into this region. Stensen's duct opens into the buccal cavity opposite the 2nd maxillary molar and Wharton's duct empties into the floor of mouth along the frenulum of the tongue. The three-dimensional planar views (Fig. 6.5A–C) are essential to appreciate the oncoanatomy.
• Sagittal plane (Fig. 6.5A): The sagittal view is the most informative; the cranial nerve VII (facial nerve) enters and exits through the parotid gland between the superficial lobe and the mandible, innervating multiple muscles of the face. Equally important are branches of cranial nerve V3 and the lingual nerve, both of which can be involved with deep lobe cancers. Perineural invasion can occur, particularly with cylindromas. Such cancers can travel retrograde along the nerve and penetrate into the middle fossa of the skull and the Gasserian ganglion of cranial nerve V.
• Coronal plane (Fig. 6.5B): The coronal view demonstrates the relationship of the parotid and submaxillary gland to the mandible.
• Transverse plane (Fig. 6.5C): This view is essential to define the retroparotidian space through which the carotid artery, jugular vein, parapharyngeal nodes, and cranial nerves IX, X, XI, and XII pass along the posterior pharyngeal wall.
Figure 6.4 | Orientation of three-planar T-oncoanatomy. The anatomic isocenter is at the axial level at C2/C3. A. Coronal. B. Sagittal.
Figure 6.5 | T-oncoanatomy. The Color Code for the anatomic sites correlates with the color code for the stage group (Fig. 6.3) and patterns of spread (Fig. 6.2) and SIMLAP table (Table 6.2). Connecting the dots in similar colors will provide an appreciation for the 3D Oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
M-ONCOANATOMY
The rich network of superficial lymphatics of the face, including the scalp and eyelids, drains into the preauricular and parotid lymph nodes (Fig. 6.6; Table 6.4). The jugulodigastric lymph node is just inferior to the parotid gland. The deep lobe of the parotid drains into the retropharyngeal lymph nodes. The submaxillary gland drains into submandibular nodes (Fig. 6.6). The risk estimation for percent positive neck nodes is based on T score/stage and histopathology (Table 6.5A).
N-ONCOANATOMY
The parotid gland drains to the pterygoid venous plexus, facial vein, internal jugular vein, brachiocephalic vein and superior vena cava, and into the right side of the heart. The target metastatic organ is lung, but the pulmonary vascular bed acts as a sanctuary housing metastases that often do not produce any severe or life-threatening loss of pulmonary function (see Fig. 6.7A).
Figure 6.6 | N-oncoanatomy. The red node highlights the sentinel node, which are the parotid node and submandibular node. A. Anterior view. B. Lateral view. M-oncoanatomy is determined by the jugular vein, which joins with the subclavian vein to form the superior vena cava on the right, and the innominate vein, which drains into the right side of the heart and then into lung.
Figure 6.7 | A. The Incidence and Distribution of Distant Metastases. The Oropharyngeal cancers can serve as a prototype for head and neck cancers. Lung (58%) is the target organ with liver metastases next (29%) and bone metastases third (22%) followed by distant lymph nodes (17%), mediastinum (14%). The remainder of sites are 11% (kidney) or less than 10%. B. Cranial nerve for Parotid Gland CN IX.
CRANIAL NERVES AND NEUROVASCULAR BUNDLE
The importance of appreciating the complex anatomy of cranial nerves lies in the patterns of cancer spread at the primary cancer site as well as nodal spread patterns. Perineural invasion or compression by metastatic lymph nodes often is manifested by specific neurologic symptoms and signs. The overview of cranial nerves provides an intricate roadmap as to points of vulnerability (Fig. 6.7B; Table 6.5B).
Cranial nerve invasion can produce specific syndromes and neurologic evaluation is a vital part of physical diagnosis in all head and neck cancers.
A tabulation of potential neurologic syndromes either due to perineural invasion at the primary site or nodal compression will alert the astute clinician to extent of cancer advancement anatomically.
Salivary gland or parotid gland cancers tend to invade the facial nerve CN VII as it exists from the stylohyoid foramen and result in impairment of facial musculature depending on its invasion of branches vs. the main nerve. Sensory taste in the anterior 2/3 of tongue and soft palate can be altered. Cylindromas are notorious for perineural invasion and if branches of V3 mandibular nerve are involved, it can penetrate into the bassercan ganglion into the middle fossa.
Retroparotidean nodes can compress IX, X, XI, XII, especially if the primary involves the deep lobe.
STAGING WORKUP
RULES OF CLASSIFICATION AND STAGING
Clinical Staging and Imaging
Careful history, physical examination, inspection, and palpation are essential. Full assessment of cranial nerves should be fully evaluated, especially for cylindromas. Computed tomography (CT) and magnetic resonance imaging (MRI) are complementary for assessing deep extraglandular tumor spread and perineural and bone invasion (see Table 6.6 and Fig. 6.8).
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 size, number, and level of involved nodes and whether there is extracapsular spread. Specimens taken after radiation, chemotherapy, or both need to be so noted, but 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
• Perineural invasion of cranial nerve VII is best appreciated on MRI.
• Perineural invasion of cranial nerve V3 with extension in a retrograde fashion to the middle fossa of the skull is best seen on MRI.
• Lung CT should be performed in advanced stage cancer because the lung is most often the metastatic target site.
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 6.8 | The MRI axial view at C2/C3 indicates relationship of superficial and deep lobes of parotid gland and proximity of retroparotidian space to carotid artery, jugular vein in parapharyngeal space with cranial nerves. The muscular oropharynx is continuity with intrinsic and extrinsic musculature of tongue. The CT/MRI transverse section can be correlated with the anatomy in Figure 6.5C as an assist to staging.
CANCER STATISTICS AND SURVIVAL
Generally, cancers of the oral cavity, pharynx, and upper digestive passage account for 36,640 new cases per year. 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 due to other causes. Long-term survival is exceptional in thyroid cancer (1,500 deaths [5%]). The improvement in oral cavity and pharyngeal tumors from 1950 to 2000 was modest at 14% and matches larynx at 15%. (See Fig. 1.10). A multidisciplinary approach is vital and normal tissue conservation and reconstructive techniques have both added greatly to quality of life.
Specifically, improvements in salivary gland tumors dramatically occurred with fast neutron therapy, in which more than 50% of advanced stages responded and were locally controlled. As surgical techniques improved, and when combined with postoperative megavoltage photon and electron therapy, 55% 5-year survival rose to 75% in the assessment of many series in the literature. According to the latest AJCC survival data (Fig. 6.9) Stage I salivary gland cancers are 90% survival with Stage II and Stage III cancers survival at 5 years is better than 50%.
Figure 6.9 | 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.)