Updated Protocol for the Examination of Specimens From Patients With Carcinoma 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” section 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 has 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 the document. 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.This protocol applies to all invasive carcinomas of the lung. It is based on the 6th edition of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) TNM classification system for the staging of carcinomas of the lung. Sarcomas and other rare tumors are not included.For consistency in reporting, the histologic classification published by the World Health Organization for carcinomas of the lung is recommended.1 This protocol does not preclude the use of other systems of classification of histologic types.2Epithelial tumorsSoft tissue tumorsMesothelial tumorsMiscellaneous tumorsLymphoproliferative diseasesSecondary tumors (metastatic)Unclassified tumorsTumor-like lesionsEach category of lung neoplasms includes a variety of benign and malignant tumors. A detailed list of all these neoplasms is beyond the scope of this protocol. Most lung neoplasms are malignant epithelial tumors.Preinvasive lesions include:Squamous dysplasiaCarcinoma in situAtypical adenomatous hyperplasiaDiffuse idiopathic pulmonary neuroendocrine cell hyperplasiaMalignant epithelial tumors of the lung include:Squamous cell carcinomaPapillaryClear cellSmall cellBasaloidSmall cell carcinomaVariantCombined small cell carcinoma (small cell carcinoma and non–small cell component)AdenocarcinomaAcinarPapillaryBronchioloalveolar carcinomaNonmucinousMucinousMixed mucinous and nonmucinous typeSolid adenocarcinoma with mucinAdenocarcinoma with mixed subtypesVariantsWell-differentiated fetal adenocarcinomaMucinous (“colloid”) adenocarcinomaMucinous cystadenocarcinomaSignet-ring adenocarcinomaClear cell adenocarcinomaLarge cell carcinomaVariantsLarge cell neuroendocrine carcinomaCombined large cell neuroendocrine carcinomaBasaloid carcinomaLymphoepithelioma-like carcinomaClear cell carcinomaLarge cell carcinoma with rhabdoid phenotypeAdenosquamous carcinomaCarcinomas with pleomorphic, sarcomatoid, or sarcomatous elementsCarcinomas with spindle and/or giant cellsSpindle cell carcinomaGiant cell carcinomaCarcinosarcomaPulmonary blastomaCarcinoid tumorTypical carcinoidAtypical carcinoidCarcinomas of salivary gland typeMucoepidermoid carcinomaAdenoid cystic carcinomaOthersUnclassified carcinomaTo standardize histologic grading, the following grading system is recommended3:Grade X (GX): Cannot be assessedGrade 1 (G1): Well differentiatedGrade 2 (G2): Moderately differentiatedGrade 3 (G3): Poorly differentiatedGrade 4 (G4): UndifferentiatedUndifferentiated (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, since 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, as they are high-grade tumors with poor prognosis.The presence of visceral pleural invasion in tumors smaller than 3 cm will change the stage from T1 to T2 and increase stage IA to IB or stage IIA to IIB.4 There are situations in which pleural invasion is difficult to assess, and evaluation of elastic stains may provide useful information.45 Visceral pleural invasion may not, by itself, be an independent prognostic factor.6Although the presence or absence of venous/lymphatic vessel invasion by the tumor78 and extracapsular extension of a positive mediastinal lymph node9–12 may represent unfavorable prognostic findings, they do not change the pT and pN classifications, respectively, or the TNM stage grouping (see note E).13 Nonetheless, this information is considered important by some clinicians and may influence their selection of therapy.The AJCC/UICC TNM Staging System for carcinoma of the lung is recommended and is shown below.314By 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 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. Pathologic staging depends on pathologic documentation of the anatomic extent of disease, regardless of whether 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.orTumor of any size in the main bronchus less than 2 cm distal to the carina but without involvement of the carinaorTumor of any size associated with atelectasis or obstructive pneumonitis of the entire lungorTumor of any size with separate tumor nodule(s) in same lobeorTumor of any size with a malignant pleural effusion†* 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 also classified as T1.† Most pleural effusions with lung cancer are due to tumor. However, in a few patients multiple cytopathologic examinations of pleural fluid are negative for tumor, and 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.For identification of special cases of TNM or pTNM classifications, the “m” suffix and “y,” “r,” and “a” prefixes are used. Although they do not affect the stage grouping, they indicate cases needing separate analysis.The “m” suffix indicates the presence of multiple primary tumors in a single site and is recorded in parentheses: pT(m)NM.The “y” prefix indicates those cases in which classification is performed during or following initial multimodality therapy (ie, neoadjuvant chemotherapy, radiation therapy, or both chemotherapy and radiation therapy). The cTNM or pTNM category is identified by a “y” prefix. The ycTNM or ypTNM categorizes the extent of tumor actually present at the time of that examination. The “y” categorization is not an estimate of tumor prior to multimodality therapy (ie, before initiation of neoadjuvant therapy).The “r” prefix indicates a recurrent tumor when staged after a documented disease-free interval and is identified by the “r” prefix (rTNM).The “a” prefix designates the stage determined at autopsy (aTNM).Residual Tumor (R)Tumor remaining in a patient after therapy with curative intent (eg, surgical resection for cure) is categorized by a system known as the R classification, as shown below.For the surgeon, the R classification may be useful to indicate the known or assumed status of the completeness of a surgical excision. For the pathologist, the R classification is relevant to the status of the margins of a surgical resection specimen. That is, tumor involving the resection margin on pathologic examination may be assumed to correspond to residual tumor in the patient and may be classified as macroscopic or microscopic according to the findings at the specimen margin(s).Vessel InvasionBy AJCC/UICC convention, vessel invasion (lymphatic or venous) does not affect the T category indicating local extent of tumor unless specifically included in the definition of a T category. In all other cases, lymphatic and venous invasion by tumor are coded separately as follows.Lymphatic Vessel Invasion (L)Venous Invasion (V)Synchronous primary carcinomas of the lung of different histologic types are generally considered separate primaries, and they are staged independently.15–18 Recommendations for staging of multiple pulmonary tumor masses of similar histology are provided in note E (such as in tumor of any size with separate tumor nodule[s] in same lobe and would be considered as T4).The anatomic classification of regional lymph nodes adopted by the AJCC and UICC18 is shown below.All N2 nodes lie within the mediastinal pleural envelope.Superior Mediastinal NodesAortic NodesInferior Mediastinal NodesAll N1 nodes lie distal to the mediastinal pleural reflection and within the visceral pleura.