Cancers Staged Using This Staging System
Mucosal melanoma (MM) arising in the nasal cavity, paranasal sinuses, oral cavity, oropharynx, nasopharynx, larynx, and hypopharynx are addressed in this chapter.
Cancers Not Staged Using This Staging System
| These histopathologic types of cancer… | Are staged according to the classification for… | and can be found in chapter… |
|---|---|---|
| Melanoma arising in external lip and commissure of lip | Melanoma of the skin | 47 |
Summary of Changes
| Change | Details of Change | Level of Evidence |
|---|---|---|
| ICD-O-3 Topography Codes | C00.0 external upper lip, C00.1 external lower lip, C00.2 external lip, NOS, and C00.6 commissure of lip have been removed from this classification. | IV |
ICD-O-3 Topography Codes
| Code | Description |
|---|---|
| C00.3 | Mucosa of upper lip |
| C00.4 | Mucosa of lower lip |
| C00.5 | Mucosa of lip, NOS |
| C00.8 | Overlapping lesion of lip |
| C00.9 | Lip, NOS |
| C01.9 | Base of tongue, NOS |
| C02.0 | Dorsal surface of tongue, NOS |
| C02.1 | Border of tongue |
| C02.2 | Ventral surface of tongue, NOS |
| C02.3 | Anterior two-thirds of tongue, NOS |
| C02.4 | Lingual tonsil |
| C02.8 | Overlapping lesion of tongue |
| C02.9 | Tongue, NOS |
| C03.0 | Upper gum |
| C03.1 | Lower gum |
| C03.9 | Gum, NOS |
| C04.0 | Anterior floor of mouth |
| C04.1 | Lateral floor of mouth |
| C04.8 | Overlapping lesion of floor of mouth |
| C04.9 | Floor of mouth, NOS |
| C05.0 | Hard palate |
| C05.1 | Soft palate, NOS |
| C05.2 | Uvula |
| C05.8 | Overlapping lesion of palate |
| C05.9 | Palate, NOS |
| C06.0 | Cheek mucosa |
| C06.1 | Vestibule of mouth |
| C06.2 | Retromolar area |
| C06.8 | Overlapping lesion of other and unspecified parts of mouth |
| C06.9 | Mouth, NOS |
| C09.0 | Tonsillar fossa |
| C09.1 | Tonsillar pillar |
| C09.8 | Overlapping lesion of tonsil |
| C09.9 | Tonsil, NOS |
| C10.0 | Vallecula |
| C10.1 | Anterior (lingual) surface of epiglottis |
| C10.2 | Lateral wall of oropharynx |
| C10.3 | Posterior pharyngeal wall |
| C10.8 | Overlapping lesion of oropharynx |
| C10.9 | Oropharynx, NOS |
| C11.0 | Superior wall of nasopharynx |
| C11.1 | Posterior wall of nasopharynx |
| C11.2 | Lateral wall of nasopharynx |
| C11.3 | Anterior wall of nasopharynx |
| C11.8 | Overlapping lesion of nasopharynx |
| C11.9 | Nasopharynx, NOS |
| C12.9 | Pyriform sinus |
| C13.0 | Postcricoid region |
| C13.1 | Hypopharyngeal aspect of aryepiglottic fold |
| C13.2 | Posterior wall of hypopharynx |
| C13.8 | Overlapping lesion of hypopharynx |
| C13.9 | Hypopharynx, NOS |
| C14.0 | Pharynx, NOS |
| C14.2 | Waldeyer ring |
| C14.8 | Overlapping lesion of lip, oral cavity, and pharynx |
| C30.0 | Nasal cavity |
| C31.0 | Maxillary sinus |
| C31.1 | Ethmoid sinus |
| C32.0 | Glottis |
| C32.1 | Supraglottis (laryngeal surface) |
| C32.2 | Subglottis |
| C32.8 | Overlapping lesion of larynx |
| C32.9 | Larynx, NOS |
This list includes histology codes and preferred terms from the WHO Classification of Tumors and the International Classification of Diseases for Oncology (ICD-O). Most of the terms in this list represent malignant behavior. For cancer reporting purposes, behavior codes /3 (denoting malignant neoplasms), /2 (denoting in situ neoplasms), and in some cases /1 (denoting neoplasms with uncertain and unknown behavior) may be appended to the 4-digit histology codes to create a complete morphology code.
| Code | Description |
|---|---|
| 8720 | Mucosal melanoma |
| 8721 | Nodular melanoma |
| 8722 | Balloon cell melanoma |
| 8730 | Amelanotic melanoma |
| 8745 | Desmoplastic melanoma, malignant |
| 8746 | Mucosal lentiginous melanoma |
| 8770 | Mixed epithelioid and spindle cell melanoma |
| 8771 | Epithelioid cell melanoma |
| 8772 | Spindle cell melanoma, NOS |
Histology is not ideal for clinical care, as the staging system was not developed using these cases. Data collectors may use this code only if there is not enough information in the medical record to document a more specific diagnosis.
El-Naggar AK, Chan JKC, Grand is JR, Takata T, Slootweg PJ, eds. World Health Organization Classification of Head and Neck Tumours. Lyon: IARC; 2017. Used with permission.
International Agency for Research on Cancer, World Health Organization. International Classification of Diseases for Oncology. ICD-O-3-Online.http://codes.iarc.fr/home. Accessed September 29, 2017. Used with permission.
Approximately 55% of all mucosal melanomas (MMs) arise in the head and neck region. This disease represents less than 1% of all melanomas.1 MM is an aggressive neoplasm that exhibits unique features relative to other paranasal sinus and head and neck malignancies, as well as features distinct from cutaneous melanoma. Approximately two thirds of these lesions arise in the nasal cavity and paranasal sinuses, one quarter are found in the oral cavity, and the remainder occur sporadically in other mucosal sites of the head and neck.
MM is an aggressive neoplasm with staging introduced in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th Edition for separate consideration from other mucosal-based lesions. The utility of this new system has been confirmed.2-5
The staging system of Ballantyne showed its utility and emerged as the first staging system utilized specifically for MM.6 The TNM system for paranasal sinus cancer was not designed for and did not discriminate differences in prognosis between the various stages in MM. It also did not provide a staging system for MMs of the other potential sites where disease arose in the head and neck. Therefore, in the 7th Edition, AJCC and the Union for International Cancer Control (UICC) adopted a novel system for MM using only T3, T4a, and T4b categories to characterize the local extent of disease. The lack of clear discrimination in outcomes based on the number and size of nodal metastases resulted in adopting a dichotomous categorization of N0 versus N+. Thus, the four stages of disease for MM are represented by III, IVA, IVB, and IVC. The system omits T1 and T2 categories, justified by the overall poor prognosis for even small superficial lesions. Stratification into these stages assists the clinician in treatment decision making. In Stage III disease, the role of radiation still is not completely certain, but should be strongly considered according to National Comprehensive Cancer Network (NCCN) recommendations; in Stage IVA, local radiation is important and confers a survival benefit.7
Stage IVB denotes extensive local invasion for which treatment often is a nonsurgical approach for local palliation. Stage IVC denotes distant metastatic disease.7 This stage designation allows patients to understand their prognosis. Furthermore, it provides a starting point for worldwide data collection and analysis. At this time, key genetic mutations such as BRAF are rarely seen in MM, thus making systemic treatment with targeted agents problematic.1
Primary Site(s)
MMs occur throughout the mucosa of the upper aerodigestive tract. For a description of anatomy, refer to the appropriate anatomic site chapter based on the location of the mucosal melanoma (e.g., paranasal sinus and oral cavity).
MM originates from benign intramucosal melanocytes that reside in the mucosa of the upper aerodigestive tract (paranasal sinuses, oral cavity, pharynx, and larynx).
There is no T0 category for MM, because melanoma of unknown primary is unlikely to arise from the mucosal surfaces and far more likely to arise from skin.
The cervical nodes are the primary lymphatic drainage, and those at risk are in the basin that corresponds to the anatomic site where the tumor arises. Due to the rarity of the disease, the role of nodal metastasis is confined to either present (N+) or absent (N0). At this time, the role of extranodal extension (ENE) is unknown and this modifier is not incorporated into the system for MM.
MM tends to occur in older patients, as compared with cutaneous melanoma. MM can occur in any mucosal surface of the head and neck. The majority arise, however, in the paranasal sinuses and nasal cavity, with the remainder primarily in the oral cavity. Presenting symptoms depend on the tumor site of origin. Nasal obstruction, bleeding, and a polypoid mass are the most common symptoms. In the oral cavity, a painless pigmented mass, often on the hard palate or alveolus is the typical presenting finding.1 Up to 40% of head and neck MMs may be amelanotic. Nodal disease occurs in up to 15% of patients with oral cavity MM.
Clinical staging of MM is done through clinical examination, appropriate imaging, and histological confirmation of disease. Pathological staging is done after surgical resection. Even small MMs behave aggressively, with high rates of recurrence and death. Because even superficial MMs exhibit this aggressive behavior, there is no T1 or T2 category in the MM staging system. Thus, primary cancers limited to the mucosa and underlying soft tissue are considered T3 lesions. Advanced MMs are classified as T4a and T4b. The anatomic extent criteria to define moderately advanced (T4a) and very advanced (T4b) disease are given below. In situ MMs are extremely rare and are excluded from staging.
Imaging
Imaging recommendations for MM differ from those for other head and neck cancers. T3 disease is defined as mucosa and immediately adjacent soft tissue. Mucosal lesions often are superficial and may be evaluated easily by direct visualization and palpation or endoscopy. Superficial mucosal lesions that are assessed easily and confidently may not require any imaging. Computed tomography (CT) and magnetic resonance (MR) imaging studies can be performed or reconstructed in planes that are orthogonal to the tumor and can potentially assess the depth of tumor invasion.
Imaging can be helpful for lesions that cannot be fully assessed on clinical examination and for locally advanced disease or symptomatic patients. Either CT or MR imaging may be performed for determining soft tissue involvement (T4a). CT is superior to MR imaging to identify early cortical involvement, but MR imaging is superior to CT for bone marrow invasion. Both CT and MR imaging may be used to evaluate for spread to the masticator, carotid, or pre-vertebral space (T4b).MR imaging, however, is superior to CT for identifying involvement of the skull base, dura, or other types of intracranial extension (T4b). MR imaging also is superior to CT to evaluate for perineural spread of “named” nerves, which should be distinguished from microscopic “perineural invasion.” Positron emission tomography (PET) using 2-deoxy-2[F]-fluoro-D-glucose (FDG) is not very useful to evaluate the primary site or locoregional spread. However, PET-FDG may be helpful to screen for distant metastases in patients with local advanced disease. The role of imaging in evaluating nodal metastases is discussed in Chapter 6, Cervical Lymph Nodes and Unknown Primary Tumors of the Head and Neck.
Radiology reports should include information on the following:
Pathological staging is assigned after surgical resection. Margin status and invasion of bone, cartilage, dura, and other resected tissue should be documented. If a lymph node dissection is performed, the number of lymph nodes resected, the size and number of positive lymph nodes, and the presence of soft tissue invasion should be noted.
Prognostic Factors Required for Stage Grouping
Beyond the factors used to assign T, N, or M categories, no additional prognostic factors are required for stage grouping.
Additional Factors Recommended for Clinical Care
As with all cancers, the overall frailty and comorbidities of the patient are important determinants of prognosis. MM has few defined disease-specific prognostic factors. The site of origin in the head and neck is one of the only clear prognostic factors. Disease in the oral cavity has a higher rate of cervical nodal metastasis than those arising in the paranasal sinuses. Overall 5-year survival is 15-30% for nasal cavity, 12% for oral cavity, and 0-5% for paranasal sinus disease.9-11 Other series have demonstrated slightly better outcomes, but the relative proportion of survival remains best for nasal cavity and worst for paranasal sinus.
Prasad and colleagues proposed a microstaging system for MM. They reported that findings of vascular invasion, polymorphous tumor population, and necrosis conferred a worse prognosis.12 Others, however, have not confirmed these findings and suggest high mitotic index and other findings are more salient. At this time, it appears that no clear prognostic factors exist for MM, although many promising cand idates exist; collection of these data for future editions is advantageous.
In addition to the importance of the TNM factors, the overall health of these patients clearly influences outcome. An ongoing effort to better assess prognosis using both tumor and nontumor-related factors is underway. Chart abstraction will continue to be performed by cancer registrars to obtain important information regarding specific factors related to prognosis. These data then will be used to further hone the predictive power of the staging system in future revisions.
| Zubrod/ECOG Performance Scale | |||
|---|---|---|---|
| 0 | Fully active, able to carry out all predisease activities without restriction (Karnofsky 90-100) | ||
| 1 | Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; for example, light housework, office work (Karnofsky 70-80) | ||
| 2 | Ambulatory and capable of all self-care, but unable to carry out any work activities; up and about more than 50% of waking hours (Karnofsky 50-60) | ||
| 3 | Capable of only limited self-care; confined to bed or chair 50% or more of waking hours (Karnofsky 30-40) | ||
| 4 | Completely disabled; cannot carry on self-care; totally confined to bed (Karnofsky 10-20) | ||
| 5 | Death (Karnofsky 0) | ||
The AJCC recently established guidelines that will be used to evaluate published statistical prediction models for the purpose of granting endorsement for clinical use.16 Although this is a monumental step toward the goal of precision medicine, this work was published only very recently. Therefore, the existing models that have been published or may be in clinical use have not yet been evaluated for this cancer site by the Precision Medicine Core of the AJCC. In the future, the statistical prediction models for this cancer site will be evaluated, and those that meet all AJCC criteria will be endorsed.
MM is a rare disease and difficult to address in clinical trials. Research should first focus on molecular signatures that predict outcome and response to therapy, presence of nodal disease, and multifocality. Additional features to be considered in stratification are vascular invasion, polymorphous tumor population, and necrosis.
Definition of Primary Tumor (T)
| T Category | T Criteria |
|---|---|
| T3 | Tumors limited to the mucosa and immediately underlying soft tissue, regardless of thickness or greatest dimension; for example, polypoid nasal disease, pigmented or nonpigmented lesions of the oral cavity, pharynx, or larynx |
| T4 | Moderately advanced or very advanced disease |
| T4a | Moderately advanced disease. Tumor involving deep soft tissue, cartilage, bone, or overlying skin. |
| T4b | Very advanced disease. Tumor involving brain, dura, skull base, lower cranial nerves (IX, X, XI, XII), masticator space, carotid artery, prevertebral space, or mediastinal structures. |
Definition of Regional Lymph Node (N)
| N Category | N Criteria |
|---|---|
| NX | Regional lymph nodes cannot be assessed |
| N0 | No regional lymph node metastases |
| N1 | Regional lymph node metastases present |
Definition of Distant Metastasis (M)
| M Category | M Criteria |
|---|---|
| M0 | No distant metastasis |
| M1 | Distant metastasis present |
Registry Data Collection Variables
There is no recommended histologic grading system at this time.
Figure 14.1 shows 24-month follow-up of patients older than 18 years of age, diagnosed with MM of the head and neck, lip and oral cavity, pharynx, larynx, and nasal cavity and paranasal sinuses using the AJCC Cancer Staging Manual, 7th Edition. The cases were diagnosed in 2010-12. The curves indicate a reasonable hazard discrimination and distribution. They also suggest good prognostic discrimination.
