Section. General Principles of Management of Head and Neck Cancer

Transcription

1 Section 1 General Principles of Management of Head and Neck Cancer

2 CHAPTER 1 Bruce M. Wenig and Jean-Marc Cohen General Principles of Head and Neck Pathology The surgical pathologist is an integral member of the clinical team that administers to the head and neck cancer patient. The pathologist s role is multifactorial. In the simplest of terms, it is his/her job to render the correct diagnosis. However, that final goal is not an isolated achievement, nor is the diagnosis the sole responsibility placed on the surgical pathologist. There are numerous factors that go into the diagnosis of cancer, not the least important of which are what type of cancer is it, how invasive is the tumor, are the surgical margins free of involvement, is there metastatic disease, and are there any pathologic features that may allow for predicting the biologic behavior for a given tumor. This chapter will be an overview of the pathologic issues relative to head and neck cancer. The chapter will be divided into two sections. Section I will be an overview of the general principles of the pathology of head and neck neoplasms. Section II will focus primarily on head and neck squamous cell carcinoma (HNSCC), including the parthologic findings of precursor lesions of HNSCC, invasive squamous cell carcinoma (SCC), and variants of SCC. Due to limitations of space, the pathology of salivary gland neoplasms, neuroendocrine neoplasms, thyroid and parathyroid lesions, and mesenchymal and hematolymphoid neoplasms will not be included in this chapter. The reader is referred to other chapters in this textbook discussing these subjects. The Surgical Pathology Report and the Tissue Specimen The pathology report is the document that contains the pathologist s diagnosis for a given surgical or cytologic specimen. The pathology report not only contains the diagnosis of the tumor but may also include the type, differentiation, and histologic grade of the tumor, the extent of disease, including whether the tumor is invasive (in situ vs. submucosal invasion), whether the surgical margins are involved by tumor, whether there is neural or lymphvascular space invasion, and whether nodal metastases and extranodal extension is present. In addition, the pathology report may contain the results of any adjunct studies that assist in establishing the diagnosis. Therefore, the pathology report includes information of prognostic and therapeutic import. Further, the pathology report is a legal document that becomes a part of the patient s medical record. The College of American Pathologists (CAP) has established guidelines (referred to as checklists) for the reporting of human cancers. These guidelines include cancers of all body sites. The most recent guidelines for the reporting of cancers of the head and neck, including the thyroid gland, are detailed in Tables 1.1 through 1.6. The final histologic diagnosis is not an isolated achievement or the sole responsibility of the pathologist. In addition to the final diagnosis, the pathology report contains the gross and microscopic description of the specimen. For small specimens such as a biopsy, the gross description is relatively simple and straightforward. For larger surgical resections, like those often required for the head and neck cancer patient, the surgical specimen may be large and complex in its details. The complexity of the surgical specimen necessitates that the pathologist has a good functional understanding of the surgical anatomy of the region. It is the responsibility of the pathologist to properly evaluate the gross specimen and to describe in detail the gross characteristics of the tumor to include its relationship to the surrounding structures. Equally important is the proper sectioning of the specimen. Improper sectioning will result in erroneous evaluation of the specimen. To this end, the surgeon and pathologist must work in unison, especially in appropriately orienting a large resection specimen and determining the key aspects of the specimen (e.g., surgical margins) that require special attention. The sections that are taken by the pathologist will ultimately indicate whether the tumor involves the surgical margins or whether the surgical margins are free of tumor. The issue of surgical margin involvement will impact on the necessity for additional surgical intervention and/or the utilization of adjuvant therapy. Therefore, the proper gross evaluation of the specimen, including the sectioning for histologic evaluation, is a critical component in the overall management of the head and neck cancer patient. It should be obvious that the pathologist s role as a member of the clinical team goes beyond the histologic evaluation of a tumor and the assigning of a name (i.e., a diagnosis). Certainly, the diagnosis of the tumor is important, but there are multiple additional factors that are equally important, perhaps even more important to the overall management and prognosis of the head and neck cancer patient. These issues will be discussed in detail later in this chapter. The pathologist is entirely dependent on the tissue sampling that is received from the surgeon. Without the appropriate material, a diagnosis cannot be rendered. This is true for neoplastic, as well as nonneoplastic lesions. In general, necrotic or ulcerated tissue should be avoided as the diagnostic yield from this material, at best, is low. The viable tissue surrounding or deep to the ulcerated or necrotic tissue should be sampled. The most common types of neoplastic proliferations 2

3 CHAPTER 1 General Principles of Head and Neck Pathology 3 Table 1.1 College of American Pathologists (CAP) Check Lists for Cancers of the Larynx Surgical Pathology Cancer Case Summary (Checklist) Protocol web posting date: June 2012 LARYNX (SUPRAGLOTTIS, GLOTTIS, SUBGLOTTIS): Incisional and Excisional Biopsy, Resection Select a single response unless otherwise indicated. Specimen (select all that apply) Larynx, supraglottis Larynx, glottis Larynx, subglottis Other (specify): Not specified Received Fresh In formalin Other (specify): Procedure (select all that apply) Incisional biopsy Excisional biopsy Resection Endolaryngeal excision Transoral laser excision (glottis) Supraglottic laryngectomy Supracricoid laryngectomy Vertical hemilaryngectomy (specify side): Partial laryngectomy (specify type): Total laryngectomy Neck (lymph node) dissection (specify): Other (specify): Not specified *Specimen Integrity * Intact * Fragmented Laryngectomy (required only if applicable) Open Unopened Specimen Size Greatest dimensions: cm *Additional dimensions (if more than one part): cm Tumor Laterality (select all that apply) Right Left Bilateral Midline Not specified (continued)

4 4 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.1 College of American Pathologists (CAP) Check Lists for Cancers of the Larynx (Continued) Tumor Site (select all that apply) Larynx, supraglottis Epiglottis Lingual aspect Laryngeal aspect Aryepiglottic folds Arytenoid(s) False vocal cord Ventricle Larynx, glottis True vocal cord Anterior commissure Posterior commissure Larynx, subglottis Other (specify): Not specified Transglottic Yes No Tumor Focality Single focus Bilateral Multifocal (specify): Tumor Size Greatest dimension: cm *Additional dimensions: cm Cannot be determined (see Comment) *Tumor Description (select all that apply) *Gross subtype: * Polypoid * Exophytic * Endophytic * Ulcerated * Sessile * Other (specify): *Macroscopic Extent of Tumor *Specify: Histologic Type (select all that apply) Squamous cell carcinoma, conventional Variants of Squamous Cell Carcinoma Acantholytic squamous cell carcinoma Adenosquamous carcinoma Basaloid squamous cell carcinoma Papillary squamous cell carcinoma Spindle cell squamous cell carcinoma Verrucous carcinoma Giant cell carcinoma Lymphoepithelial carcinoma (nonnasopharyngeal)

5 CHAPTER 1 General Principles of Head and Neck Pathology 5 Table 1.1 College of American Pathologists (CAP) Check Lists for Cancers of the Larynx (Continued) Neuroendocrine Carcinoma Typical carcinoid tumor (well-differentiated neuroendocrine carcinoma) Atypical carcinoid tumor (moderately differentiated neuroendocrine carcinoma) Small cell carcinoma, neuroendocrine type (poorly differentiated neuroendocrine carcinoma) Combined (or composite) small cell carcinoma, neuroendocrine type Mucosal malignant melanoma Carcinomas of Minor Salivary Glands Adenoid cystic carcinoma Mucoepidermoid carcinoma Low grade Intermediate grade High grade Other (specify): Other carcinoma (specify): Carcinoma, type cannot be determined Histologic Grade Not applicable GX: Cannot be assessed G1: Well differentiated G2: Moderately differentiated G3: Poorly differentiated Other (specify): *Microscopic Tumor Extension Specify: Margins (select all that apply) Cannot be assessed Margins uninvolved by invasive carcinoma Distance from closest margin: mm or cm Specify margin(s), per orientation, if possible: Margins involved by invasive carcinoma Specify margin(s), per orientation, if possible: Margins uninvolved by carcinoma in situ (includes moderate and severe dysplasia # ) Distance from closest margin: mm or cm Specify margin(s), per orientation, if possible: Margins involved by carcinoma in situ (includes moderate and severe dysplasia # ) Specify margin(s), per orientation, if possible: Not applicable # Applicable only to squamous cell carcinoma and histologic variants. *Treatment Effect (applicable to carcinomas treated with neoadjuvant therapy) * Not identified * Present (specify): * Indeterminate Lymph-Vascular Invasion Not identified Present Indeterminate Perineural Invasion Not identified (continued)

6 6 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.1 College of American Pathologists (CAP) Check Lists for Cancers of the Larynx (Continued) Present Indeterminate Lymph Nodes, Extranodal Extension Not identified Present Indeterminate Pathologic Staging (ptnm) Note: The phrases in italics include clinical findings required for AJCC staging. This clinical information may not be available to the pathologist. However, if known, these findings should be incorporated into the pathologic staging. TNM Descriptors (required only if applicable) (select all that apply) m (multiple primary tumors) r (recurrent) y (posttreatment) Primary Tumor (pt) ptx: Cannot be assessed pt0: No evidence of primary tumor ptis: Carcinoma in situ For All Carcinomas Excluding Mucosal Malignant Melanoma Primary Tumor (pt): Supraglottis pt1: Tumor limited to one subsite of supraglottis with normal vocal cord mobility pt2: Tumor invades mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx pt3: Tumor limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, preepiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage pt4a: Moderately advanced local disease. Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of neck including deep extrinsic muscle of tongue, strap muscles, thyroid, or esophagus) pt4b: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures Primary Tumor (pt): Glottis pt1: Tumor limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility pt1a: Tumor limited to one vocal cord pt1b: Tumor involves both vocal cords pt2: Tumor extends to supraglottis and/or subglottis and/or with impaired vocal cord mobility pt3: Tumor limited to the larynx with vocal cord fixation and/or invades paraglottic space and/or minor thyroid cartilage erosion (eg, inner cortex) (Note H) pt4a: Moderately advanced local disease. Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus) (Note H) pt4b: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures Primary Tumor (pt): Subglottis pt1: Tumor limited to subglottis pt2: Tumor extends to vocal cord(s) with normal or impaired mobility pt3: Tumor limited to larynx with vocal cord fixation pt4a: Moderately advanced local disease. Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus) pt4b: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures Regional Lymph Nodes (pn) # pnx: Cannot be assessed pn0: No regional lymph node metastasis pn1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension

7 CHAPTER 1 General Principles of Head and Neck Pathology 7 Table 1.1 College of American Pathologists (CAP) Check Lists for Cancers of the Larynx (Continued) pn2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension pn2a: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension pn2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension pn2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension pn3: Metastasis in a lymph node more than 6 cm in greatest dimension No nodes submitted or found Number of Lymph Nodes Examined Specify: Number cannot be determined (explain): Number of Lymph Nodes Involved Specify: Number cannot be determined (explain): * Size (greatest dimension) of the largest positive lymph node: # Superior mediastinal lymph nodes are considered regional lymph nodes (level VII). Midline nodes are considered ipsilateral nodes. Distant Metastasis (pm) Not applicable pm1: Distant metastasis * Specify site(s), if known: * Source of pathologic metastatic specimen (specify): For Mucosal Malignant Melanoma Primary Tumor (pt) pt3: Mucosal disease pt4a: Moderately advanced disease. Tumor involving deep soft tissue, cartilage, bone, or overlying skin pt4b: 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 Regional Lymph Nodes (pn) pnx: Regional lymph nodes cannot be assessed pn0: No regional lymph node metastases pn1: Regional lymph node metastases present Distant Metastasis (pm) Not applicable pm1: Distant metastasis present * Specify site(s), if known: * Source of pathologic metastatic specimen (specify): * Additional Pathologic Findings (select all that apply) * None identified * Keratinizing dysplasia (Note M) * Mild * Moderate * Severe (carcinoma in situ) * Nonkeratinizing dysplasia (Note M) * Mild * Moderate * Severe (carcinoma in situ) * Inflammation (specify type): * Squamous metaplasia (continued)

8 8 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.1 College of American Pathologists (CAP) Check Lists for Cancers of the Larynx (Continued) * Epithelial hyperplasia * Colonization * Fungal * Bacterial * Other (specify): * Ancillary Studies (Note N) * Specify type(s): * Specify result(s): * Clinical History (select all that apply) * Neoadjuvant therapy * Yes (specify type): * No * Indeterminate * Other (specify): *Data elements preceded by this symbol are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. Table 1.2 College of American Pathologists (CAP) Check Lists for Cancers of the Lip and Oral Cavity Surgical Pathology Cancer Case Summary (Checklist) Protocol web posting date: June 2012 Lip and Oral Cavity: Incisional Biopsy, Excisional Biopsy, Resection Select a single response unless otherwise indicated. Specimen (select all that apply) Vermilion border upper lip Vermilion border lower lip Mucosa of upper lip Mucosa of lower lip Commissure of lip Lateral border of tongue Ventral surface of tongue, not otherwise specified (NOS) Dorsal surface of tongue, NOS Anterior two-thirds of tongue, NOS Upper gingiva (gum) Lower gingiva (gum) Anterior floor of mouth Floor of mouth, NOS Hard palate Buccal mucosa (inner cheek) Vestibule of mouth Upper Lower Alveolar process Upper Lower

9 CHAPTER 1 General Principles of Head and Neck Pathology 9 Table 1.2 College of American Pathologists (CAP) Check Lists for Cancers of the Lip and Oral Cavity (Continued) Mandible Maxilla Other (specify): Not specified Received Fresh In formalin Other (specify): Procedure (select all that apply) Incisional biopsy Excisional biopsy Resection Glossectomy (specify): Mandibulectomy (specify): Maxillectomy (specify): Palatectomy Neck (lymph node) dissection (specify): Other (specify): Not specified * Specimen Integrity * Intact * Fragmented Specimen Size Greatest dimensions: cm * Additional dimensions (if more than 1 part): cm Specimen Laterality Right Left Bilateral Midline Not specified Tumor Site (select all that apply) Vermilion border upper lip Vermilion border lower lip Mucosa of upper lip Mucosa of lower lip Commissure of lip Lateral border of tongue Ventral surface of tongue, NOS Dorsal surface of tongue, NOS Anterior two-thirds of tongue, NOS Upper gingiva (gum) Lower gingiva (gum) Anterior floor of mouth Floor of mouth, NOS Hard palate Buccal mucosa (inner cheek) (continued)

10 10 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.2 College of American Pathologists (CAP) Check Lists for Cancers of the Lip and Oral Cavity (Continued) Vestibule of mouth Upper Lower Alveolar process Upper Lower Mandible Maxilla Other (specify): Not specified Tumor Focality Single focus Multifocal (specify): Tumor Size Greatest dimension: cm * Additional dimensions: cm Cannot be determined (see Comment) * Tumor Thickness (pt1 and pt2 tumors) * Tumor thickness: mm * Intact surface mucosa: ; or ulcerated surface: * Tumor Description (select all that apply) * Gross subtype * Polypoid * Exophytic * Endophytic * Ulcerated * Sessile * Other (specify): * Macroscopic Extent of Tumor * Specify: Histologic Type (select all that apply) Squamous cell carcinoma, conventional Variants of Squamous Cell Carcinoma Acantholytic squamous cell carcinoma Adenosquamous carcinoma Basaloid squamous cell carcinoma Carcinoma cuniculatum Papillary squamous cell carcinoma Spindle cell squamous carcinoma Verrucous carcinoma Lymphoepithelial carcinoma (nonnasopharyngeal) Carcinomas of Minor Salivary Glands Acinic cell carcinoma Adenoid cystic carcinoma Adenocarcinoma, not otherwise specified (NOS) Low grade Intermediate grade

11 CHAPTER 1 General Principles of Head and Neck Pathology 11 Table 1.2 College of American Pathologists (CAP) Check Lists for Cancers of the Lip and Oral Cavity (Continued) High grade Basal cell adenocarcinoma Carcinoma ex pleomorphic adenoma (malignant mixed tumor) Low grade High grade Invasive Minimally invasive Invasive Intracapsular (noninvasive) Carcinoma, type cannot be determined Carcinosarcoma Clear cell adenocarcinoma Cystadenocarcinoma Epithelial-myoepithelial carcinoma Mucoepidermoid carcinoma Low grade Intermediate grade High grade Mucinous adenocarcinoma (colloid carcinoma) Myoepithelial carcinoma (malignant myoepithelioma) Oncocytic carcinoma Polymorphous low-grade adenocarcinoma Salivary duct carcinoma Other (specify): Adenocarcinoma, Non Salivary Gland Type Adenocarcinoma, not otherwise specified (NOS) Low grade Intermediate grade High grade Other (specify): Neuroendocrine Carcinoma Typical carcinoid tumor (well-differentiated neuroendocrine carcinoma) Atypical carcinoid tumor (moderately differentiated neuroendocrine carcinoma) Small cell carcinoma (poorly differentiated neuroendocrine carcinoma) Combined (or composite) small cell carcinoma, neuroendocrine type Other (specify): Carcinoma, type cannot be determined Mucosal malignant melanoma Histologic Grade Not applicable GX: Cannot be assessed G1: Well differentiated G2: Moderately differentiated G3: Poorly differentiated Other (specify): * Microscopic Tumor Extension * Specify: (continued)

12 12 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.2 Margins (select all that apply) Cannot be assessed Margins uninvolved by invasive carcinoma Distance from closest margin: mm or cm Specify margin(s), per orientation, if possible: Margins involved by invasive carcinoma Specify margin(s), per orientation, if possible: Margins uninvolved by carcinoma in situ (includes moderate and severe dysplasia # ) (Note E) Distance from closest margin: mm or cm Specify margin(s), per orientation, if possible: Margins involved by carcinoma in situ (includes moderate and severe dysplasia # ) (Note E) Specify margin(s), per orientation, if possible: Not applicable # Applicable only to squamous cell carcinoma and histologic variants. * Treatment Effect (applicable to carcinomas treated with neoadjuvant therapy) * Not identified * Present (specify): * Indeterminate Lymph-Vascular Invasion Not identified Present Indeterminate Perineural Invasion Not identified Present Indeterminate College of American Pathologists (CAP) Check Lists for Cancers of the Lip and Oral Cavity (Continued) Lymph Nodes, Extranodal Extension Not identified Present Indeterminate Pathologic Staging (ptnm) TNM Descriptors (required only if applicable) (select all that apply) m (multiple primary tumors) r (recurrent) y (posttreatment) For All Carcinomas Excluding Mucosal Malignant Melanoma Primary Tumor (pt) ptx: Cannot be assessed pt0: No evidence of primary tumor ptis: Carcinoma in situ pt1: Tumor 2 cm or less in greatest dimension pt2: Tumor more than 2 cm but not more than 4 cm in greatest dimension pt3: Tumor more than 4 cm in greatest dimension pt4a: Moderately advanced local disease. Lip: Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose Oral cavity: Tumor invades adjacent structures only (e.g., through cortical bone [mandible, maxilla], into deep [extrinsic] muscle of tongue [genioglossus, hyoglossus, palatoglossus, and styloglossus], maxillary sinus, skin of face)

13 CHAPTER 1 General Principles of Head and Neck Pathology 13 Table 1.2 College of American Pathologists (CAP) Check Lists for Cancers of the Lip and Oral Cavity (Continued) pt4b: Very advanced local disease. Tumor invades masticator space, pterygoid plates, or skull base, and/or encases internal carotid artery Note: Superficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify a tumor as T4. Regional Lymph Nodes (pn) # (Notes J through M) pnx: Cannot be assessed pn0: No regional lymph node metastasis pn1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension pn2a: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension pn2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension pn2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension pn3: Metastasis in a lymph node more than 6 cm in greatest dimension No nodes submitted or found Number of Lymph Nodes Examined Specify: Number cannot be determined (explain): Number of Lymph Nodes Involved Specify: Number cannot be determined (explain): * Size (greatest dimension) of the largest positive lymph node: # Superior mediastinal lymph nodes are considered regional lymph nodes (level VII). Midline nodes are considered ipsilateral nodes. Distant Metastasis (pm) Not Applicable pm1: Distant metastasis * Specify site(s), if known: * Source of pathologic metastatic specimen (specify): For Mucosal Malignant Melanoma Primary Tumor (pt) pt3: Mucosal disease pt4a: Moderately advanced disease. Tumor involving deep soft tissue, cartilage, bone, or overlying skin pt4b: 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 Regional Lymph Nodes (pn) pnx: Regional lymph nodes cannot be assessed pn0: No regional lymph node metastases pn1: Regional lymph node metastases present Distant Metastasis (pm) Not applicable pm1: Distant metastasis present * Specify site(s), if known: * Source of pathologic metastatic specimen (specify): * Additional Pathologic Findings (select all that apply) * None identified * Keratinizing dysplasia (Note N) * Mild * Moderate * Severe (carcinoma in situ) (continued)

14 14 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.2 College of American Pathologists (CAP) Check Lists for Cancers of the Lip and Oral Cavity (Continued) * Nonkeratinizing dysplasia (Note N) * Mild * Moderate * Severe (carcinoma in situ) * Inflammation (specify type): * Epithelial hyperplasia * Colonization * Fungal * Bacterial * Other (specify): * Ancillary Studies * Specify type(s): * Specify result(s): * Clinical History (select all that apply) * Neoadjuvant therapy * Yes (specify type): * No * Indeterminate * Other (specify): *Data elements preceded by this symbol are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. Table 1.3 College of American Pathologists (CAP) Check Lists for Cancers of the Nasal Cavity and Paranasal Sinuses Surgical Pathology Cancer Case Summary (Checklist) Protocol web posting date: June 2012 Nasal Cavity and Paranasal Sinuses: Incisional Biopsy, Excisional Biopsy, Resection Select a single response unless otherwise indicated. Specimen (select all that apply) Nasal cavity Septum Floor Lateral wall Vestibule Paranasal sinus(es), maxillary Paranasal sinus(es), ethmoid Paranasal sinus(es), frontal Paranasal sinus(es), sphenoid Other (specify): Not specified Received Fresh In formalin Other (specify):

15 CHAPTER 1 General Principles of Head and Neck Pathology 15 Table 1.3 College of American Pathologists (CAP) Check Lists for Cancers of the Nasal Cavity and Paranasal Sinuses (Continued) Procedure (select all that apply) Incisional Biopsy Excisional Biopsy Resection (specify type) Partial maxillectomy Radical maxillectomy Neck (lymph node) Dissection (specify): Other (specify): Not Specified * Specimen Integrity * Intact * Fragmented Specimen Size Greatest dimensions: cm * Additional dimensions (if more than one part): cm Specimen Laterality (select all that apply) Right Left Bilateral Midline Not specified Tumor Site (select all that apply) Nasal cavity Septum Floor Lateral wall Vestibule Paranasal sinus(es), maxillary Paranasal sinus(es), ethmoid Paranasal sinus(es), frontal Paranasal sinus(es), sphenoid Other (specify): Not specified Tumor Focality (select all that apply) Single focus Bilateral Multifocal (specify): Tumor Size Greatest dimension: cm * Additional dimensions: cm Cannot be determined (see Comment) * Tumor Description (select all that apply) * Gross subtype * Polypoid * Exophytic * Endophytic (continued)

16 16 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.3 College of American Pathologists (CAP) Check Lists for Cancers of the Nasal Cavity and Paranasal Sinuses (Continued) * Ulcerated * Sessile * Other (specify): * Macroscopic Extent of Tumor * Specify: Histologic Type (select all that apply) Carcinomas of the Nasal Cavity and Paranasal Sinuses Squamous cell carcinoma, conventional Keratinizing Nonkeratinizing (formerly cylindrical cell, transitional cell) Variants of Squamous Cell Carcinoma Acantholytic squamous cell carcinoma Adenosquamous carcinoma Basaloid squamous cell carcinoma Papillary squamous cell carcinoma Spindle cell squamous cell carcinoma Verrucous carcinoma Giant cell carcinoma Lymphoepithelial carcinoma (nonnasopharyngeal) Sinonasal undifferentiated carcinoma (SNUC) Adenocarcinoma, Non Salivary Gland Type Intestinal type Papillary type Colonic type Solid type Mucinous type Mixed type Nonintestinal type Low grade Intermediate grade High grade Carcinomas of Minor Salivary Glands Acinic cell carcinoma Adenoid cystic carcinoma Adenocarcinoma, not otherwise specified (NOS) Low grade Intermediate grade High grade Carcinoma ex pleomorphic adenoma (malignant mixed tumor) Clear cell adenocarcinoma Epithelial-myoepithelial carcinoma Mucoepidermoid carcinoma Low grade Intermediate grade High grade Myoepithelial carcinoma (malignant myoepithelioma) Oncocytic carcinoma Polymorphous low-grade adenocarcinoma

17 CHAPTER 1 General Principles of Head and Neck Pathology 17 Table 1.3 College of American Pathologists (CAP) Check Lists for Cancers of the Nasal Cavity and Paranasal Sinuses (Continued) Salivary duct carcinoma Other (specify): Neuroendocrine Carcinoma Typical carcinoid tumor (well-differentiated neuroendocrine carcinoma) Atypical carcinoid tumor (moderately differentiated neuroendocrine carcinoma) Small cell carcinoma (poorly differentiated neuroendocrine carcinoma) Combined (or composite) small cell carcinoma, neuroendocrine type Mucosal malignant melanoma Other (specify): Carcinoma, type cannot be determined Histologic Grade Not applicable GX: Cannot be assessed G1: Well differentiated G2: Moderately differentiated G3: Poorly differentiated Other (specify): * Microscopic Tumor Extension * Specify: Margins (select all that apply) Cannot be assessed Margins uninvolved by invasive carcinoma Distance from closest margin: mm or cm Specify margin(s), per orientation, if possible: Margins involved by invasive carcinoma Specify margin(s), per orientation, if possible: Margins uninvolved by carcinoma in situ (includes moderate and severe dysplasia # ) (Note D) Distance from closest margin: mm or cm Specify margin(s), per orientation, if possible: Margins involved by carcinoma in situ (includes moderate and severe dysplasia # ) (Note D) Specify margin(s), per orientation, if possible: Not applicable # Applicable only to squamous cell carcinoma and histologic variants. * Treatment Effect (applicable to carcinomas treated with neoadjuvant therapy) * Not identified * Present (specify): * Indeterminate Lymph-Vascular Invasion Not Identified Present Indeterminate Perineural Invasion (Note F) Not identified Present Indeterminate Lymph Nodes, Extranodal Extension (Note G) Not identified (continued)

18 18 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.3 College of American Pathologists (CAP) Check Lists for Cancers of the Nasal Cavity and Paranasal Sinuses (Continued) Present Indeterminate Pathologic Staging (ptnm) TNM Descriptors (required only if applicable) (select all that apply) m (multiple primary tumors) r (recurrent) y ( posttreatment) Primary Tumor (pt) ptx: Cannot be assessed pt0: No evidence of primary tumor ptis: Carcinoma in situ For All Carcinomas Excluding Mucosal Malignant Melanoma Primary Tumor (pt): Maxillary Sinus pt1: Tumor limited to maxillary sinus mucosa with no erosion or destruction of bone pt2: Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates pt3: Tumor invades any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses pt4a: Moderately advanced local disease. Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses pt4b: 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 (V 2 ), nasopharynx, or clivus Primary Tumor (pt): Nasal Cavity and Ethmoid Sinus pt1: Tumor restricted to any one subsite, with our without bone invasion pt2: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with our without bone invasion pt3: Tumor extends to invade the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate pt4a: 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 pt4b: 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 (V 2 ), nasopharynx, or clivus Regional Lymph Nodes (pn) # pnx: Cannot be assessed pn0: No regional lymph node metastasis pn1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension pn2: Metastasis in a single ipsilateral lymph node, more than 3cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral nodes, none more than 6 cm in greatest dimension pn2a: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension pn2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension pn2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension pn3: Metastasis in a lymph node more than 6 cm in greatest dimension No nodes submitted or found Number of Lymph Nodes Examined Specify: Number cannot be determined (explain): Number of Positive Lymph Nodes Specify:

19 CHAPTER 1 General Principles of Head and Neck Pathology 19 Table 1.3 College of American Pathologists (CAP) Check Lists for Cancers of the Nasal Cavity and Paranasal Sinuses (Continued) Number cannot be determined (explain): * Size of the largest positive lymph node: * Size of the associated metastatic focus: * Position of the involved node (level): # Metastases at level VII are considered regional lymph node metastases. Midline nodes are considered ipsilateral nodes. Distant Metastasis (pm) Not applicable pm1: Distant metastasis * Specify site(s) if known: * Source of pathologic metastatic specimen (specify): For Mucosal Malignant Melanoma Primary Tumor (pt) pt3: Mucosal disease pt4a: Moderately advanced disease. Tumor involving deep soft tissue, cartilage, bone, or overlying skin pt4b: 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 Regional Lymph Nodes (pn) pnx: Regional lymph nodes cannot be assessed pn0: No regional lymph node metastases pn1: Regional lymph node metastases present Distant Metastasis (pm) Not applicable pm1: Distant metastasis present * Specify site(s), if known: * Source of pathologic metastatic specimen (specify): * Additional Pathologic Findings (select all that apply) * None identified * Carcinoma in situ (Note M) * Epithelial dysplasia (Note M) * Specify: * Inflammation (specify type): * Squamous metaplasia * Epithelial hyperplasia * Colonization * Fungal * Bacterial * Other (specify): * Ancillary Studies (Note N) * Specify type(s): * Specify result(s): * Clinical History (select all that apply) * Neoadjuvant therapy * Yes (specify type): * No * Indeterminate * Other (specify): *Data elements preceded by this symbol are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management.

20 20 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.4 College of American Pathologists (CAP) Check Lists for Cancers of the Pharynx Surgical Pathology Cancer Case Summary (Checklist) Protocol web posting date: June 2012 Pharynx (Oropharynx, Hypopharynx, Nasopharynx): Incisional Biopsy, Excisional Biopsy, Resection Select a single response unless otherwise indicated. Specimen (select all that apply) Oropharynx Nasopharynx Hypopharynx Other (specify): Not specified Received Fresh In formalin Other (specify): Procedure (select all that apply) Incisional biopsy Excisional biopsy Resection Tonsillectomy Laryngopharyngectomy Other (specify): Neck (lymph node) dissection (specify): Other (specify): Not specified * Specimen Integrity * Intact * Fragmented Specimen Size Greatest dimensions: cm * Additional dimensions (if more than one part): cm Specimen Laterality (select all that apply) Left Right Bilateral Midline Not specified Tumor Site (select all that apply) Oropharynx Palatine tonsil Base of tongue, including lingual tonsil Soft palate Uvula Pharyngeal wall (posterior) Other Nasopharynx Nasopharyngeal tonsils (adenoids) Hypopharynx Piriform sinus Postcricoid

21 CHAPTER 1 General Principles of Head and Neck Pathology 21 Table 1.4 College of American Pathologists (CAP) Check Lists for Cancers of the Pharynx (Continued) Pharyngeal wall (posterior and/or lateral) Other Other (specify): Not specified Tumor Laterality (select all that apply) Left Right Bilateral Midline Not specified Tumor Focality Single focus Bilateral Multifocal (specify): Tumor Size Greatest dimension: cm * Additional dimensions: cm Cannot be determined (see Comment) * Tumor Description (select all that apply) * Gross subtype: * Polypoid * Exophytic * Endophytic * Ulcerated * Sessile * Other (specify): * Macroscopic Extent of Tumor * Specify: Histologic Type (select all that apply) Carcinomas of the Oropharynx and Hypopharynx Squamous cell carcinoma, conventional Variants of Squamous Cell Carcinoma Acantholytic squamous cell carcinoma Adenosquamous carcinoma Basaloid squamous cell carcinoma Papillary squamous cell carcinoma Spindle cell squamous carcinoma Verrucous carcinoma Lymphoepithelial carcinoma (nonnasopharyngeal) Carcinomas of the Nasopharynx Keratinizing squamous cell carcinoma (formerly WHO-1) Nonkeratinizing carcinoma Differentiated carcinoma (formerly WHO-2; transitional carcinoma) Undifferentiated carcinoma (formerly WHO-3; lymphoepithelioma) Basaloid squamous cell carcinoma (continued)

22 22 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.4 College of American Pathologists (CAP) Check Lists for Cancers of the Pharynx (Continued) Adenocarcinomas (Non Salivary Gland Type) Nasopharyngeal papillary adenocarcinoma Adenocarcinoma, not otherwise specified (NOS) Low grade Intermediate grade High grade Other (specify): Carcinomas of Minor Salivary Glands Acinic cell carcinoma Adenoid cystic carcinoma Adenocarcinoma, not otherwise specified (NOS) Low grade Intermediate grade High grade Basal cell adenocarcinoma Carcinoma ex pleomorphic adenoma (malignant mixed tumor) Carcinoma, type cannot be determined Clear cell adenocarcinoma Cystadenocarcinoma Epithelial-myoepithelial carcinoma Mucoepidermoid carcinoma Low grade Intermediate grade High grade Mucinous adenocarcinoma (colloid carcinoma) Myoepithelial carcinoma (malignant myoepithelioma) Oncocytic carcinoma Polymorphous low-grade adenocarcinoma Salivary duct carcinoma Other (specify): Neuroendocrine Carcinoma Typical carcinoid tumor (well-differentiated neuroendocrine carcinoma) Atypical carcinoid tumor (moderately differentiated neuroendocrine carcinoma) Small cell carcinoma (poorly differentiated neuroendocrine carcinoma) Combined (or composite) small cell carcinoma, neuroendocrine type Mucosal malignant melanoma Other carcinoma (specify): Carcinoma, type cannot be determined Histologic Grade Not applicable GX: Cannot be assessed G1: Well differentiated G2: Moderately differentiated G3: Poorly differentiated Other (specify): * Microscopic Tumor Extension * Specify:

23 CHAPTER 1 General Principles of Head and Neck Pathology 23 Table 1.4 College of American Pathologists (CAP) Check Lists for Cancers of the Pharynx (Continued) Margins (select all that apply) Cannot be assessed Margins uninvolved by invasive carcinoma Distance from closest margin: mm or cm Specify margin(s), per orientation, if possible: Margins involved by invasive carcinoma Specify margin(s), per orientation, if possible: Margins uninvolved by carcinoma in situ (includes moderate and severe dysplasia # ) (Note D) Distance from closest margin: mm or cm Specify margin(s), per orientation, if possible: Margins involved by carcinoma in situ (includes moderate and severe dysplasia # ) (Note D) Specify margin(s), per orientation, if possible: Not applicable # Applicable only to squamous cell carcinoma and histologic variants * Treatment Effect (applicable to carcinomas treated with neoadjuvant therapy) * Not identified * Present (specify): * Indeterminate Lymph-Vascular Invasion Not identified Present Indeterminate Perineural Invasion Not identified Present Indeterminate Lymph Nodes, Extranodal Extension Not identified Present Indeterminate Pathologic Staging (ptnm) Note: The phrases in italics include clinical findings required for AJCC staging. This clinical information may not be available to the pathologist. However, if known, these findings should be incorporated into the pathologic staging. TNM Descriptors (required only if applicable) (select all that apply) m (multiple primary tumors) r (recurrent) y (posttreatment) Primary Tumor (pt) ptx: Cannot be assessed pt0: No evidence of primary tumor ptis: Carcinoma in situ For All Carcinomas Excluding Mucosal Malignant Melanoma Primary Tumor (pt): Oropharynx pt1: Tumor 2 cm or less in greatest dimension pt2: Tumor more than 2 cm but not more than 4 cm in greatest dimension without fixation of hemilarynx pt3: Tumor more than 4 cm in greatest dimension or with fixation of hemilarynx or extension to lingual surface of epiglottis (continued)

24 24 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.4 College of American Pathologists (CAP) Check Lists for Cancers of the Pharynx (Continued) pt4a: Moderately advanced local disease. Tumor invades larynx, deep/extrinsic muscle of tongue, medial pterygoid muscles, hard palate, or mandible # pt4b: Very advanced local disease. Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base, or encases carotid artery # Note: Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of larynx. Primary Tumor (pt): Nasopharynx pt1: Tumor confined to nasopharynx, or tumor extends to oropharynx and/or nasal cavity without parapharyngeal extension # pt2: Tumor with parapharyngeal extension # pt3: Tumor invades bony structures of skull base and/or paranasal sinuses pt4: Tumor with intracranial extension and/or involvement of cranial nerves, hypopharynx, orbit, or with extension to the infratemporal fossa/masticator space # Parapharyngeal extension denotes posterolateral infiltration of tumor. Primary Tumor (pt): Hypopharynx pt1: Tumor limited to one subsite of hypopharynx and/or 2 cm or less in greatest dimension pt2: Tumor invades more than one subsite of hypopharynx or an adjacent site, or measures more than 2 cm but not more than 4 cm in greatest dimension without fixation of hemilarynx pt3: Tumor measures more than 4 cm in greatest dimension or with fixation of hemilarynx or extension to esophagus pt4a: Moderately advanced local disease. Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue # pt4b: Very advanced local disease. Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures # Note: Central compartment soft tissue includes prelarnygeal strap muscles and subcutaneous fat. Regional Lymph Nodes (pn) pnx: Cannot be assessed pn0: No regional lymph node metastasis Regional Lymph Nodes (pn): Oropharynx and Hypopharynx # pn1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension pn2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension pn2a: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension pn2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension pn2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension pn3: Metastasis in a lymph node more than 6 cm in greatest dimension No nodes submitted or found Number of Lymph Nodes Examined Specify: Number cannot be determined (explain): Number of Lymph Nodes Involved Specify: Number cannot be determined (explain): * Size (greatest dimension) of the largest positive lymph node: # Note: Metastases at level VII are considered regional lymph node metastases. Midline nodes are considered ipsilateral nodes. Regional Lymph Nodes (pn): Nasopharynx # pn1: Unilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa ## pn2: Bilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa ## pn3: Metastasis in a lymph node greater than 6 cm and/or to supraclavicular fossa ## pn3a: Greater than 6 cm in dimension pn3b: Extension to the supraclavicular fossa ## No nodes submitted or found

25 CHAPTER 1 General Principles of Head and Neck Pathology 25 Table 1.4 College of American Pathologists (CAP) Check Lists for Cancers of the Pharynx (Continued) Number of Lymph Nodes Examined Specify: Number cannot be determined (explain): Number of Lymph Nodes Involved Specify: Number cannot be determined (explain): * Size (greatest dimension) of the largest positive lymph node: # Metastases at level VII are considered regional lymph node metastases. Midline nodes are considered ipsilateral nodes. ## Supraclavicular zone or fossa is relevant to the staging of nasopharyngeal carcinoma and is the triangular region defined by three points: (1) the superior margin of the sternal end of the clavicle, (2) the superior margin of the lateral end of the clavicle, (3) the point where the neck meets the shoulder (see Figure 1-3, no. 2). Note that this would include caudal portions of Levels IV and VB. All cases with lymph nodes (whole or part) in the fossa are considered N3b. Distant Metastasis (pm) Not applicable pm1: Distant metastasis * Specify site(s), if known: * Source of pathologic metastatic specimen (specify): For Mucosal Malignant Melanoma Primary Tumor (pt) pt3: Mucosal disease pt4a: Moderately advanced disease. Tumor involving deep soft tissue, cartilage, bone, or overlying skin. pt4b: 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. Regional Lymph Nodes (pn) pnx: Regional lymph nodes cannot be assessed pn0: No regional lymph node metastases pn1: Regional lymph node metastases present Distant Metastasis (pm) Not applicable pm1: Distant metastasis present * Specify site(s), if known: * Source of pathologic metastatic specimen (specify): * Additional Pathologic Findings (select all that apply) * None identified * Keratinizing dysplasia * Mild * Moderate * Severe (carcinoma in situ) * Nonkeratinizing dysplasia * Mild * Moderate * Severe (carcinoma in situ) * Inflammation (specify type): * Squamous metaplasia * Epithelial hyperplasia * Colonization * Fungal * Bacterial * Other (specify): (continued)

26 26 SECTION 1 General Principles of Management of Head and Neck Cancer Table 1.4 College of American Pathologists (CAP) Check Lists for Cancers of the Pharynx (Continued) Ancillary Studies (required only for oropharynx [p16, HPV] and nasopharynx [EBV] if available at time of report completion) (select all that apply) (Notes M and O) p16 Positive Negative Human papillomavirus (HPV), in situ hybridization (ISH) Type (specify): Positive Pattern Punctate Diffuse Mixed Negative Indeterminate (explain): HPV, polymerase chain reaction (PCR) Type (specify): Positive Negative Epstein-Barr virus (Epstein-Barr virus encoded RNA [EBER], other) Positive Negative Other (specify): Not specified * Clinical History (select all that apply) * Neoadjuvant therapy * Yes (specify type): * No * Indeterminate * Other (specify): *Data elements preceded by this symbol are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. Table 1.5 College of American Pathologists (CAP) Check Lists for Cancers of the Salivary Glands Surgical Pathology Cancer Case Summary (Checklist) Protocol web posting date: June 2012 Major Salivary Glands: Incisional Biopsy, Excisional Biopsy, Resection Select a single response unless otherwise indicated. Specimen (select all that apply) Parotid gland Superficial lobe only Deep lobe only Total parotid gland Submandibular gland Sublingual gland

27 CHAPTER 1 General Principles of Head and Neck Pathology 27 Table 1.5 College of American Pathologists (CAP) Check Lists for Cancers of the Salivary Glands (Continued) Other (specify): Not specified Received Fresh In formalin Other (specify): Procedure (select all that apply) Incisional biopsy Excisional biopsy Resection, parotid gland Superficial parotidectomy Total parotidectomy Resection, submandibular gland Resection, sublingual gland Neck (lymph node) dissection (specify): Other (specify): Not specified * Specimen Integrity * Intact * Fragmented Specimen Size Greatest dimensions: cm * Additional dimensions (if more than 1 part): cm Specimen Laterality Right Left Bilateral Not specified Tumor Site (select all that apply) Parotid gland Superficial lobe Deep lobe Entire parotid gland Submandibular gland Sublingual gland Other (specify): Not specified Tumor Focality Single focus Bilateral Multifocal (specify): Tumor Size Greatest dimension: cm * Additional dimensions: cm Cannot be determined (see Comment) (continued)