Box 11.1 SELECTED NSCLC HISTOLOGIC SUBTYPES
I. Squamous cell carcinoma
A. Variants: papillary, clear cell, small cell, basaloid
II. Adenocarcinoma
Preinvasive lesions
Atypical adenomatous hyperplasia
Adenocarcinoma in situ (≤3 cm (formerly bronchioloalveolar carcinoma [BAC])
Nonmucinous
Mucinous
Mixed mucinous/nonmucinous
Minimally invasive adenocarcinoma (≤3 cm lepidic predominant tumor with ≤5mm invasion)
Nonmucinous
Mucinous
Mixed mucinous/nonmucinous
Invasive adenocarcinoma
Lepidic predominant (formerly nonmucinous BAC pattern, with >5mm invasion)
Acinar predominant
Papillary predominant
Micropapillary predominant
Solid predominant with mucin production
Variants of invasive adenocarcinoma
Invasive mucinous adenocarcinoma (formerly mucinous BAC)
Colloid
Fetal (low- and high-grade)
Enteric
III. Large cell carcinoma
Variants: large cell neuroendocrine carcinoma, combined large cell neuroendocrine carcinoma, basaloid carcinoma, lymphoepithelioma-like carcinoma, clear cell carcinoma, large cell carcinoma with rhabdoid phenotype
IV. Adenosquamous carcinoma
V. Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements
VI. Unclassified carcinoma (i.e., poorly differentiated)
SOURCES: Reproduced with permission of the European Respiratory Society © 2001. Brambilla E, Travis WD, Colby TV, et al. The new World Health Organization classification of lung tumours. Eur Respir J. 2001;18:1059–1068. II. Adenocarcimona section reprinted with permission from Travis WD, Brambilla E, Noguchi M, et al., for International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society. International multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–285.
Mutations in the tyrosine kinase domain of EGFR are seen in 10% of NSCLC in the United States and in 40% of lung cancers in Asian countries. They are more prevalent in never-smokers, women, and people of Asian descent, and they are virtually always associated with adenocarcinoma histology. These mutations cause constitutive activation of the EGFR signaling pathway, which drives tumor proliferation and prevents apoptosis. The small-molecule tyrosine kinase inhibitors gefitinib and erlotinib potently inhibit many mutant forms of EGFR, resulting in profound responses in patients with exon 19 deletions or the L858R point mutation.
STAGING OF NSCLC
Lung cancer is currently staged using the American Joint Committee on Cancer (AJCC) seventh edition staging system (see table 11.1). In the workup of patients with suspected lung cancer, the extent of the workup is determined by the patient’s presentation, performance status, and treatment preferences. The goal of the staging is to determine the extent of disease. If metastatic disease is confirmed, curative treatment is generally not possible.
Owing to the high frequency of metastatic disease in 25–30% of patients with lung cancer, even those with small tumors, most patients with suspected lung cancer should have the following workup:
Chest CT (often used during diagnosis)
PET or combined PET/CT
Head MRI with contrast or head CT with contrast if MRI is contraindicated
Bone scan if PET is not available
Pulmonary function testing (for possible operative candidates)
Laboratory workup to rule out hematologic, electrolyte, renal, or hepatic abnormalities
Many patients who are considered surgical candidates have historically undergone mediastinoscopy to rule out the possibility of mediastinal nodal involvement. PET scanning and coregistered PET/CT scanning helps to identify the extent of lymph node involvement or can identify metastatic disease, which helps patients avoid unnecessary surgery. A combined PET/CT that demonstrates neither enlarged mediastinal lymph nodes nor PET activity in the mediastinum has only a 5% false-negative rate.
Table 11.1 SEVENTH EDITION NSCLC STAGING
NOTES: * First number in range denotes survival by clinical stage, second number by pathologic stage.
Definition of TNM:
Primary Tumor (T)
• TX: Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy
• T0: No evidence of primary tumor
• Tis: Carcinoma in situ
• T1: Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). The uncommon superficial spreading tumor of any size is classified as T1 even when extending to the main bronchus, as long as the invasive component is limited to the bronchial wall.
–T1a: Tumor ≤2 cm in greatest dimension
–T1b: Tumor >2 cm but ≤3 cm in greatest dimension
–T2: Tumor >3 cm but ≤7 cm or tumor with any of the following features (T2 tumors with these features are classified T2a if ≤5 cm)
• Involves the 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
–T2a: Tumor >3 cm but ≤5 cm in greatest dimension
–T2b: Tumor >5 cm but ≤7 cm in greatest dimension
• T3: >7 cm or one that directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium; or tumor in the main bronchus <2 cm distal to the carina but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe
• A tumor of any size that directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or tumor in the main bronchus <2 cm distal to the carina but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung
• T4: Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina; separate tumor nodule(s) in a different ipsilateral lobe
Regional Lymph Nodes (N)
• NX: Regional lymph nodes cannot be assessed
• N0: No regional lymph node metastasis
• N1: Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes including involvement by direct extension of the primary tumor
• N2: Metastasis to ipsilateral mediastinal and/or subcarinal lymph node(s)
• N3: Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s)
Distant Metastasis (M)
• MX: Distant metastasis cannot be assessed
• M0: No distant metastasis
• M1a: Separate tumor nodule(s) in a contralateral lobe, tumor with pleural nodules or malignant pleural or pericardial effusion
• M1b: Distant metastasis
SOURCE: Reprinted with permission from Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: Proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of Malignant Tumours. J Thorac Oncol. 2007;2(8):706–714.
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