Protocol for the Examination of Specimens From Patients With Primary Non–Small Cell Carcinoma, Small Cell Carcinoma, or Carcinoid Tumor of the Lung

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the "Surgical Pathology Cancer Case Summary (Checklist)" portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice.The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of this document.The seventh edition TNM staging system for lung of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) is recommended.Select a Single Response Unless Otherwise Indicated* Data elements with asterisks are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management.Specimen__ Lung__ Lobe(s) of lung (specify): ______ Bronchus (specify): ______ Other (specify): ______ Not specifiedProcedure__ Major airway resection__ Wedge resection__ Segmentectomy__ Lobectomy__ Bilobectomy__ Pneumonectomy__ Other (specify): ______ Not specifiedSpecimen Integrity__ Intact__ Disrupted__ IndeterminateSpecimen Laterality__ Right__ Left__ Not specifiedTumor Site (select all that apply)__ Upper lobe__ Middle lobe__ Lower lobe__ Other(s) (specify): ______ Not specifiedTumor SizeGreatest dimension: __ cm*Additional dimensions: __ × __ cm__ Cannot be determinedTumor Focality (note A)__ Unifocal__ Separate tumor nodules in same lobe__ Separate tumor nodules in different lobes (specify sites): ______ Synchronous carcinomas (specify sites): ______ Cannot be determinedHistologic Type (note B)__ Carcinoma, type cannot be determined__ Non–small cell carcinoma, subtype cannot be determined__ Small cell carcinoma__ Combined small cell carcinoma (small cell carcinoma and non–small cell component) (specify type of non–small cell carcinoma component: ____)__ Squamous cell carcinoma__ Squamous cell carcinoma, papillary variant__ Squamous cell carcinoma, clear cell variant__ Squamous cell carcinoma, small cell variant__ Squamous cell carcinoma, basaloid variant__ Adenocarcinoma__ Adenocarcinoma, mixed subtype__ Acinar adenocarcinoma__ Papillary adenocarcinoma__ Bronchioloalveolar carcinoma__ Bronchioloalveolar carcinoma, nonmucinous__ Bronchioloalveolar carcinoma, mucinous__ Bronchioloalveolar carcinoma, mixed nonmucinous and mucinous__ Solid adenocarcinoma__ Fetal adenocarcinoma__ Mucinous (colloid) adenocarcinoma__ Mucinous cystadenocarcinoma__ Signet ring adenocarcinoma__ Clear cell adenocarcinoma__ Large cell carcinoma__ Large cell neuroendocrine carcinoma__ Combined large cell neuroendocrine carcinoma (specify type of other non–small cell carcinoma component: ____)__ Basaloid carcinoma__ Lymphoepithelioma-like carcinoma__ Clear cell carcinoma__ Large cell carcinoma with rhabdoid phenotype__ Adenosquamous carcinoma__ Sarcomatoid carcinoma__ Pleomorphic carcinoma__ Spindle cell carcinoma__ Giant cell carcinoma__ Carcinosarcoma__ Pulmonary blastoma__ Typical carcinoid tumor__ Atypical carcinoid tumor__ Mucoepidermoid carcinoma__ Adenoid cystic carcinoma__ Epithelial-myoepithelial carcinoma__ Other (specify): ____Histologic Grade (note C)__ Not applicable__ GX: Cannot be assessed__ G1: Well differentiated__ G2: Moderately differentiated__ G3: Poorly differentiated__ G4: Undifferentiated__ Other (specify): ____Visceral Pleura Invasion (note D)__ Not identified__ Present__ IndeterminateTumor Extension (select all that apply) (note E)__ Not applicable__ Not identified__ Superficial spreading tumor with invasive component limited to bronchial wall__ Tumor involves main bronchus 2 cm or more distal to the carina__ Parietal pleura__ Chest wall* Specify involved structure(s): ______ Diaphragm__ Mediastinal pleura__ Phrenic nerve__ Parietal pericardium__ Tumor in the main bronchus less than 2 cm distal to the carina but does not involve the carina__ Mediastinum* Specify involved structure(s): ______ Heart__ Great vessels__ Trachea__ Esophagus__ Vertebral body__ Carina__ Other (specify): ____Margins (select all that apply) (note F)Bronchial Margin__ Not applicable__ Cannot be assessed__ Uninvolved by invasive carcinoma__ Involved by invasive carcinoma__ Squamous cell carcinoma in situ (CIS) present at bronchial margin__ Squamous cell carcinoma in situ (CIS) not identified at bronchial marginVascular Margin__ Not applicable__ Cannot be assessed__ Uninvolved by invasive carcinoma__ Involved by invasive carcinomaParenchymal Margin__ Not applicable__ Cannot be assessed__ Uninvolved by invasive carcinoma__ Involved by invasive carcinomaParietal Pleural Margin__ Not applicable__ Cannot be assessed__ Uninvolved by invasive carcinoma__ Involved by invasive carcinomaChest Wall Margin__ Not applicable__ Cannot be assessed__ Uninvolved by invasive carcinoma__ Involved by invasive carcinomaOther Attached Tissue Margin (specify): ______ Not applicable__ Cannot be assessed__ Uninvolved by invasive carcinoma__ Involved by invasive carcinomaIf all margins uninvolved by invasive carcinoma:Distance of invasive carcinoma from closest margin: __ mmSpecify margin: ____Treatment Effect (note G)__ Not applicable__ Cannot be determined__ Greater than 10% residual viable tumor__ Less than 10% residual viable tumor* Tumor-Associated Atelectasis or Obstructive Pneumonitis (note H)*__ Extends to the hilar region but does not involve entire lung*__ Involves entire lungLymph-Vascular Invasion (note I)__ Not identified__ Present__ Indeterminate* Lymph Nodes (note J)* Extranodal extension*__ Not identified*__ PresentPathologic Staging (pTNM) (note J)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, or tumor proven by presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy__ pT0: No evidence of primary tumor__ pTis: Carcinoma in situ__ pT1a: Tumor 2 cm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (ie, not in the main bronchus); orSuperficial spreading tumor of any size with its invasive component limited to the bronchial wall, which may extend proximally to the main bronchus__ pT1b: Tumor greater than 2 cm, but 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (ie, not in the main bronchus)__ pT2a: Tumor greater than 3 cm, but 5 cm or less in greatest dimension surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (ie, not in the main bronchus); orTumor 5 cm or less in greatest dimension with any of the following features of extent: involves main bronchus, 2 cm or more distal to the carina; invades the visceral pleura; associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung__ pT2b: Tumor greater than 5 cm, but 7 cm or less in greatest dimension__ pT3: Tumor greater than 7 cm in greatest dimension; orTumor of any size that directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, or parietal pericardium; orTumor of any size in the main bronchus less than 2 cm distal to the carina but without involvement of the carina; orTumor of any size associated with atelectasis or obstructive pneumonitis of the entire lung; orTumors of any size with separate tumor nodule(s) in same lobe__ pT4: Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; orTumor of any size with separate tumor nodule(s) in a different lobe of ipsilateral lung (note A)Regional Lymph Nodes (pN)__ pNX: Cannot be assessed__ pN0: No regional lymph node metastasis__ pN1: Metastasis in ipsilateral peribronchial and/ or ipsilateral hilar lymph nodes, and intrapulmonary nodes, including involvement by direct extension__ pN2: Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)__ pN3: Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s)Specify:Number examined __Number involved __Number cannot be determined (note J)If lymph node(s) involved, specify involved nodal station(s): ____Distant Metastasis (pM)__ Not applicable__ pM1a: Separate tumor nodule(s) in contralateral lung; tumor with pleural nodules or malignant pleural (or pericardial) effusion (note A)__ pM1b: Distant metastases outside the lung/pleura* Specify site(s), if known: ____* Additional Pathologic Findings (select all that apply)*__ None identified*__ Atypical adenomatous hyperplasia*__ Squamous dysplasia*__ Metaplasia (specify type): ____*__ Diffuse neuroendocrine hyperplasia*__ Inflammation (specify type): ____*__ Emphysema*__ Other (specify): ____* Ancillary Studies (note K)*__ Epidermal growth factor receptor (EGFR) analysis results (specify method): ____*__ K-ras mutational analysis results: ____*__ Other (specify): ____* Comment(s): ____There is evidence that patients with multiple tumor nodules of similar histology in the same lobe have markedly better survival than patients with tumors that meet the AJCC, 7th edition, TNM classification criteria for T4 (ie, invasion of mediastinal structures), and, in fact, their survival is similar to patients categorized as T3 in the AJCC, 6th edition. For this reason, the presence of grossly recognizable, multiple tumor nodules of similar histology in the same lobe are to be categorized as T3.1 Survival among patients with multiple tumor nodule(s) of similar histology in ipsilateral separate lobes is similar to patients classified as T4, and, therefore, such tumors are to be categorized as T4.12 However, if separate tumors of similar histology in different segments, lobes, or lungs show an origin from CIS, no carcinoma in lymphatics common to both tumors, and no extrapulmonary metastases at the time of diagnosis, they should be categorized as synchronous primary carcinomas and staged independently.3 Physically distinct and separate tumors of different histologic types are generally considered separate, synchronous primaries and are staged separately.1–3 In such cases, the highest T category is reported, followed in parentheses by multiplicity or number of tumors (eg, T2(m) or T2(5)).For consistency in reporting, the histologic classification published by the World Health Organization (WHO) for tumors of the lung, including carcinoids, is recommended.45 The histologic types are listed in this protocol in the order in which they appear in the WHO classification. This protocol does not preclude the use of other systems of classification of histologic types.6The diagnosis of bronchioloalveolar carcinoma requires exclusion of stromal, vascular, and pleural invasion—a requirement that demands that the tumor be evaluated histologically in its entirety.4 It is, therefore, recommended that a definitive diagnosis of bronchioloalveolar adenocarcinoma not be made on specimens in which the tumor is incompletely represented.To standardize histologic grading, the following grading system is recommended4:Undifferentiated (grade 4) is reserved for carcinomas that show minimal or no specific differentiation in routine histologic preparations. According to the definition of grading, a squamous cell carcinoma or an adenocarcinoma arising in the lung can be classified only as grade 1, grade 2, or grade 3 because, by definition, these tumors show squamous or glandular differentiation, respectively. If there are variations in the differentiation of a tumor, the least favorable variation is recorded as the grade, using grades 1 through 3. By definition, small cell and large cell carcinomas of the lung are assigned grade 4 because they are high-grade tumors with poor prognosis.The presence of visceral pleural invasion by tumors smaller than 3 cm changes the T category from pT1 to pT2 and increases the stage from IA to IB in patients with N0, M0 disease, or from stage IIA to IIB in patients with N1, M0 disease (M0 is defined as no distant metastasis).1 Studies have shown that tumors smaller than 3 cm that penetrate beyond the elastic layer of the visceral pleura behave similarly to similar-sized tumors that extend to the visceral pleural surface.78 Visceral pleural invasion should, therefore, be considered present not only in tumors that extend to the visceral pleural surface, but also in tumors that penetrate beyond the elastic layer of the visceral pleura (Figure).7–9 Elastic stains may aid in the assessment of visceral pleural invasion.710Based on available data, a tumor with local invasion of another ipsilateral lobe without tumor on the visceral pleural surface should be classified as T2.10Pleural tumor foci that are separate from direct pleural invasion should be categorized as M1a.2According to the AJCC, direct invasion of the parietal pleura is categorized as T3, as is direct invasion of the chest wall.11 Although not required, specifying the chest wall structures directly invaded by tumor (eg, intercostal muscle[s], rib[s], pectoralis muscle, latissimus muscle, serratus muscle) may facilitate patient management.In addition to containing the heart and great vessels, the mediastinum includes the thymus and other structures between the lungs; direct invasion of any of which is considered T4.Occasionally, lung cancer specimens consist of en bloc resections that incorporate other structures directly invaded by tumor that are not referred to in AJCC pathologic staging but are discussed under the clinical staging section of the AJCC manual.11 The T categories that correspond to direct invasion of these structures are summarized in the collaborative staging manual.12 These should be reported under the "Other" designation and include the following:Surgical margins represent sites that have either been cut or bluntly dissected by the surgeon to resect the specimen. The presence of tumor at a surgical margin is an important finding because there is the potential for residual tumor remaining in the patient in the area surrounding a positive margin. Peripheral wedge resections contain a parenchymal margin, which is represented by the tissue at the staple line(s). Lobectomy and pneumonectomy specimens contain bronchial and vascular margins, and depending on the completeness of the interlobar fissures and other anatomic factors, may also contain parenchymal margins in the form of staple lines. En bloc resections in which extrapulmonary structures are part of the specimen contain additional margins (eg, parietal pleura, chest wall) that should be designated by the surgeon for appropriate handling. This includes cases in which the visceral pleura is adherent to the parietal pleura. Note that the visceral pleura is not a surgical margin.For patients who have received neoadjuvant chemotherapy and/or radiation therapy before surgical resection, quantifying the extent of therapy-induced tumor regression provides prognostically relevant information.13 A "y" prefix is applied to the TNM classification in such cases (see note J).Although the presence and extent of obstructive pneumonitis associated with tumor can sometimes be determined in pneumonectomy specimens, accurate assessment of tumor-associated atelectasis or obstructive pneumonitis typically requires integration of radiographic information.14There are data showing that lymphovascular invasion by a tumor may represent an unfavorable prognostic finding.15 Angiolymphatic invasion does not change the pT and pN classifications or the TNM stage grouping.The TNM staging system of the AJCC and the UICC is recommended for non– small cell lung cancer.1116 Small cell lung cancer has been more commonly classified according to a separate staging system as either "limited" or "extensive" disease, but based on analysis of the International Association for the Study of Lung Cancer (IASLC) database, TNM staging is also recommended for small cell lung cancer.1718 Carcinoid and atypical carcinoid tumors should also be classified according to the TNM staging system.By AJCC/UICC convention, the designation "T" refers to a primary tumor that has not been previously treated. The symbol "p" refers to the pathologic classification of the TNM, as opposed to the clinical classification, and is based on gross and microscopic examination. pT entails a resection of the primary tumor or a biopsy adequate to evaluate the highest pT category, pN entails removal of nodes adequate to validate lymph node metastasis, and pM implies microscopic examination of distant lesions. Clinical classification (cTNM) is usually carried out by the referring physician before treatment during initial evaluation of the patient or when pathologic classification is not possible.Pathologic staging is usually performed after surgical resection of the primary tumor and depends on pathologic documentation of the anatomic extent of disease, whether or not the primary tumor has been completely removed. If a biopsied tumor is not resected for any reason (eg, when technically unfeasible) and if the highest T and N categories or the M1 category of the tumor can be confirmed microscopically, the criteria for pathologic classification and staging have been satisfied without total removal of the primary cancer.The uncommon, superficial spreading tumor, of any size, with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is classified as T1.11Most pleural effusions with lung cancer are due to tumor. However, in a few patients, multiple cytopathologic examinations of pleural fluid are negative for tumor; the fluid is nonbloody and is not an exudate. Where these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element, and the tumor should be classified as T1, T2, or T3.11Although pneumonectomy specimens allow assessment of tumor involvement of a main bronchus, determining the distance to the carina, which is necessary to accurately assign a T category for centrally located tumors, typically requires consultation with the surgeon, bronchoscopist, or radiologist.19A number of other T category considerations are addressed above (see notes A, D, E, and G).Although extranodal extension of a positive mediastinal lymph node may represent an unfavorable prognostic finding, it does not change the pN classification or the TNM stage grouping.20–23 Extranodal extension refers to the extension of metastatic intranodal tumor beyond the lymph node capsule into the surrounding tissue. Direct extension of a primary tumor into a nearby lymph node does not qualify as extranodal extension.In certain situations, in particular, when lymph nodes are obtained by mediastinoscopy, it may not be possible to ascertain the actual number of nodes submitted for evaluation (unless it is specified by the surgeon) because the pieces of tissue submitted may represent multiple discrete nodes or multiple fragments of a single node. If nodal involvement is identified in this setting, the lymph node station(s) (see below) involved, if known, should be reported.The anatomic classification of regional lymph nodes proposed by the IASLC is shown below, which reconciles differences between the Naruke11 and Mountain/Dresler2425 lymph node maps.Lower cervical, supraclavicular, and sternal notch nodesUpper border—Lower margin of cricoid cartilageLower border—Clavicles bilaterally and, in the midline, the upper border of the manubrium; 1R designates right-sided nodes; 1L, left-sided nodes in this regionUpper paratracheal nodes2R: Upper border—Apex of lung and pleural space2R: Lower border—Intersection of caudal margin of the innominate vein with the trachea2L: Upper border—Apex of the lung and pleural space2L: Lower border—Superior border of the aortic archPrevascular and retrotracheal nodes: 3A, prevascular; 3P, retrotrachealLower paratracheal nodes:4R: Includes right paratracheal nodes and pretracheal nodes extending to the left lateral border of tracheaUpper border—Lower border of origin of innominate arteryLower border—Lower border of azygos vein4L: Includes nodes to the left of the left lateral border of the trachea, medial to the ligamentum arteriosumUpper border—Upper margin of the aortic archLower border—Upper rim of the left main pulmonary arterySubaortic nodes (aortopulmonary window): Subaortic nodes are lateral to the ligamentum arteriosumUpper border—The lower border of the aortic archLower border—Upper rim of the left main pulmonary arteryPara-aortic nodes (ascending aorta or phrenic): Nodes lying anterior and lateral to the ascending aorta and the aortic archUpper border—A line tangential to the upper border of the aortic archLower border—The lower border of the aortic archSubcarinal nodesUpper border—The carina of the tracheaLower border—The upper border of the lower lobe bronchus on the left; the lower border of the bronchus intermedius on the rightParaesophageal nodes (below carina): Nodes lying adjacent to the wall of the esophagus and to the right or left of the midline, excluding subcarinal nodesUpper border—The upper border of the lower lobe bronchus on the left; the lower border of the bronchus intermedius on the rightLower border—The diaphragmPulmonary ligament nodes: Nodes lying within the pulmonary ligamentUpper border—The inferior pulmonary veinLower border—The diaphragmHilar nodes: Nodes immediately adjacent to the mainstem bronchus and hilar vessels including the proximal portions of the pulmonary veins and main pulmonary arteryUpper border—The lower rim of the azygos vein on the right; upper rim of the pulmonary artery on the leftLower border—Interlobar region nodes: Nodes lying between the of the lobar for of the upper lobe bronchus and bronchus intermedius on the the and lower lobe on the nodes: Nodes adjacent to the lobar nodes: Nodes adjacent to the nodes: Nodes the tumor cells are single tumor cells or small of not more than in greatest dimension, on routine more by or tumor cells in lymph nodes or at distant sites should be classified as or following classification of may be No regional lymph node negative for No regional lymph node positive for No regional lymph node negative for No regional lymph node positive for of cases of TNM or the and the "y" and are Although they not the stage they cases separate the presence of multiple primary tumors in a single and is recorded in (see note "y" prefix cases in which classification is performed during or following initial therapy (ie, neoadjuvant radiation or both chemotherapy and radiation The or category is identified by a "y" The or the extent of tumor present at the time of that examination. The "y" is not an of tumor before therapy (ie, before of neoadjuvant (see note prefix a recurrent tumor when staged after a and in non– small cell lung to from these include of patients with and tumors show and/or in the of to of non–small cell carcinomas contain these and to of patients with such to that have been to to treatment with include mutational analysis and in situ The is to the and which account for to of reported is from either or and through of the of the are and to are confirmed by of the tumor by in situ both of as with a 7 and of in of of is with or with the presence of on data, not to have a in the of patients to to to in the K-ras are with a an poor and a of to patients who have non–small cell lung cancer with in fact, be which are commonly and less are present in of lung with for is, at considered an for treatment