PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
Squamous cell cancers are true bronchogenic carcinomas arising in major bronchi, which are extrapleural in location with an oxygenated arterial blood supply.
PERSPECTIVE AND PATTERNS OF SPREAD
Squamous cell lung cancers (SQC) are often extrapulmonary cancers arising in the major bronchi—located in the mediastinum rather than lung parenchyma. The normal pseudo-stratified ciliated columnar epithelium with its different cell types undergoes metaplastic changes, losing its ciliation, secretory goblets, brush cells, and serous cells due to smoking and its pollutants, leading to a dry hacking “smoker's cough.” As the patient's mucous thickens, his or her lungs and cough produce plugs of phlegm. The metaplastic changes in the columnar and cuboidal basal cells lead to stratified squamous dysplasia and, over time, to squamous cell neoplasia with malignant transformation. The epithelial surface breaks down with fine ulcerations and then rust-streaked sputum appears. The triad of coarse rhonchial breathing over a major bronchus, hemoptysis, and a long history of smoking virtually ensures a diagnosis of SQC, which can be readily confirmed with a chest film. Although SQCs at one time were the most common lung cancers (50%), they have been surpassed by adenocarcinomas, which now constitute the majority of histopathologic types. The patterns of cancer invasion in major bronchi can result in dramatic obstruction, that is, complete atelectasis and collapse of one lung (Fig. 17.2; Table 17.2).
PATHOLOGY
Squamous cell cancers tend to arise in the main bronchi, and the distance from the carina determines whether it is T2 greater than 2 cm or T3 less than 2 cm. Unlike other more peripheral locations, they are supplied by the bronchial artery (oxygenated blood) versus pulmonary artery (unoxygenated blood). This may explain their tendency to necroses once their blood supply is invaded. An irregular, shaggy walled abscess, with wall thickness exceeding 15 mm strongly suggests a diagnosis of squamous cell cancer (Table 17.1; Fig. 17.1).
Figure 17.1 | Squamous cell carcinoma of the lung. A photomicrograph shows well-differentiated squamous cell carcinoma with a keratin pearl composed of cells with brightly eosinophilic cytoplasm.
Figure 17.2 | Patterns of spread. Squamous cell cancers that arise in the major bronchi of lung are color coded for primary tumor spread to carina: Tis, yellow; T1, green (>2 cm); T2, blue (>2 cm) without obstruction of bronchus; T3, purple (>2 cm of carina with obstruction leading to complete lung collapse); T4, red (invading carina); M1, black (invading mediastinal structures). The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six directional pattern i.e. SIMLAP Table 17.2.
TNM STAGING CRITERIA
TNM STAGING CRITERIA
SQCs arise from metaplastic bronchial epithelium in major bronchi, which is specifically addressed in the staging system in relationship to the carina. T1 is an early intraluminal lesion less than 3 cm in diameter and greater than 2 cm from the carina. T2 is of larger size (greater than 3 cm in diameter) and is less than 2 cm from the carina without bronchial obstruction. Cavitation may occur due to the necrosis and most often occurs in SQC. T3 tumors may occlude major stem bronchi, which may cause unilateral atelectasis or pneumonitis with complete collapse of an entire lung. When the cancer involves the carina or trachea, it becomes T4 and invariably invades paracarinal mediastinal nodes directly or subcarinal or contralateral nodes. The resectability of an entire lung depends on producing a well-healed stump and also providing a reasonable margin when SQC of the major bronchi approach the carina.
SUMMARY OF CHANGES SEVENTH EDITION AJCC
• This staging system is now recommended for the classification of both non–small cell and small cell lung carcinomas and for carcinoid tumors of the lung.
• The T classifications have been redefined:
• T1 has been subclassified into T1a (≤2 cm in size) and T1b (>2–3 cm in size)
• T2 has been subclassified into T2a (>3–5 cm in size) and T2b (>5–7 cm in size)
• T2 (>7 cm in size) has been reclassified as T3
• Multiple tumor nodules in the same lobe have been reclassified from T4 to T3
• Multiple tumor nodules in the same lung but a different lobe have been reclassified from M1 to T4
• No changes have been made to the N classification. However, a new international lymph node map defining the anatomical boundaries for lymph node stations has been developed.
• The M classifications have been redefined:
• The M1 has been subdivided into M1a and M1b
• Malignant pleural and pericardial effusions have been reclassified from T4 to M1a
• Separate tumor nodules in the contralateral lung are considered M1a
• M1b designates distant metastases
Because of the magnitude of the T category changes with shifts in both directions, that is both downstaging and upstaging, it is important to review the stage groupings of the sixth and seventh editions. The TNM Staging Matrix is color coded for identification of Stage Group once T and N stages are determined (Table 17.3).
SQUAMOUS CELL CANCER
Figure 17.3 | TNM staging diagram. Squamous cell cancers arise in main and lobar bronchi in dysplastic epithelia that becomes neoplastic. Vertical presentation of stage groupings, which follow the same color code for cancer advancement, are organized in horizontal lanes: Stage 0, yellow; I, green; II, blue; IIIA, purple; IIIB, red; metastatic stage IV, black. Definitions of TN are on the left and stage grouping is on the right. Major stage group progression is dominated by the N stage progression.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR ONCOANATOMY
The isocenter of the respiratory system is at the carina of the trachea and the origin of the main stem bronchi. The isocenter of the main stem bronchi is inferior to the manubriosternal angle anteriorly, and posteriorly the plane is at the thoracic vertebral level T5-6. The carina and 2 cm of the major bronchi are within the mediastinal pleural. The relationships of the bifurcation of the trachea to other mediastinal structures, which are from the midline to superficial, are super imposed (Fig. 17.4).
T-oncoanatomy
The T-oncoanatomy is displayed in three planar views. A. Coronal, B. Sagittal, C. Traverse Axial (Fig. 17.5). SQC are often bronchogenic cancers involving the major bronchi, which are at the T5 level positioned inferior to the manubriosternal angle. A unique feature of this location is that the SQC are unlike other lung cancers, because they are supplied by oxygenated blood. The blood supply for SQCs is derived from the bronchial artery directly arising from the thoracic aorta. Cavitation may be more common in SQCs because its vascular attenuation may lead to severe hypoxia and necrosis. Other lung cancers, such as adenocarcinoma, are supplied with unoxygenated pulmonary arterial blood and may be more accustomed to hypoxic conditions.
• Coronal view: The extrapulmonary portion of the bronchial tree is seen arising from the trachea at the carina. The left major bronchi is longer than the right, which immediately divides into right middle lobe, the bronchus intermedius, and right lower lobe with its own bronchi.
• Sagittal view: The hilus is highly trafficked with pulmonary vessels anterior to the bronchi.
• Axial view: Pulmonary arteries dominate the middle mediastinum at the T5-6 level along with the ascending aorta in the midline and the thoracic duct in the midline. The azygos vein enters the superior vena cava posteriorly. The descending aorta is the most posterior structure and on the left side in mediastinum.
Figure 17.4 | Orientation of T-oncoanatomy. The isocenter of the major bronchi are mid-mediastinum and at the T5-6 thoracic level. A. Coronal. B. Sagittal.
Figure 17.5 | T-oncoanatomy. The Color Code for the anatomic sites correlates with the color code for the stage group (Fig. 17.3) and patterns of spread (Fig. 17.2) and SIMLAP tables (Table 17.2). Connecting the dots in similar colors will provide an appreciation for the 3D Oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
Mediastinal supracarinal and subcarinal nodes rather than hilar nodes may be the first sentinel nodes because these cancers tend to be extrapulmonary and mediastinal in location. The three-planar views depict the mediastinal lymph nodes in the region of the major bronchi and carina are depicted in Figure 17.6 and Table 17.4).
REGIONAL LYMPH NODES
The regional lymph nodes extend from the supraclavicular region to the diaphragm. During the past three decades, three different lymph node maps have been used to describe the regional lymph node potentially involved by lung cancers. The first map was endorsed by the Japan Lung Cancer Society. The second map, the Mountain Dresler modification of the American Thoracic Society (MDATS) lymph node map, is used in North America and Europe. The nomenclature for the anatomical locations of lymph nodes differs between these two maps. Recently the International Association for the Study of Lung Cancer (IASLC) proposed a lymph node map (Figure 17.6B) that reconciles the discrepancies between these two previous maps. The IASLC lymph node map is now the recommended means of describing regional lymph node involvement for lung cancers.
There are no evidence-based guidelines regarding the number of lymph nodes to be removed at surgery for adequate staging. However, adequate N staging is generally considered to include sampling or dissection of lymph nodes from stations 2R, 4R, 7, 10R, and 11R for right-sided tumors, and stations 5, 6, 7, 10, L, and 11L for left-sided tumors. Station 9 lymph nodes should also be evaluated for lower lobe tumors. The more peripheral lymph nodes at stations 12–14 are usually evaluated by the pathologist in lobectomy or pneumonectomy specimens but may be separately removed when sublobar resections (e.g., segmentectomy) are performed. There is evidence to support the recommendation that histological examination of hilar and mediastinal lymphenectomy specimen(s) will ordinarily include 6 or more lymph nodes/stations. Three of these nodes/stations should be mediastinal, including the subcarinal nodes and three from N1 nodes/stations.*
M-ONCOANATOMY
The venous drainage is into the azygos system by bronchial veins with entry of circulating metastatic cells to the lung. The anatomic distribution of distant metastases is shown in Figure 17.7.
Drainage into the subclavian vein, if invaded, then via the superior vena cava and pulmonary artery drain into the lung. Cancer invasion of chest wall drains into intercostal veins, then the azygos vein, and then the superior vena cava, which leads to lung dissemination. Adenocarcinoma dissemination of metastases is the most common lung cancer and is presented as the prototype for metastases into other organs.
*Preceding passage from Edge SB, Byrd DR, and Compton CC, et al. AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010, pp. 254–255.
Figure 17.6 | A: N-oncoanatomy. Paracarinal and subcarinal nodes as well as hilar nodes are sentinel nodes. B: M-oncoanatomy. International Association for the Study of Lung Cancer (IASLC). Labels correlate with Table 17.4.
Figure 17.7 | Incidence and Distribution of Distant Metastases of Squamous Cell lung correlate with Table 12.6.
STAGING WORKUP
RULES FOR CLASSIFICATION AND STAGING
Clinical Staging and Imaging
The TNM classification system is primarily for staging non–small cell lung cancers. The most important change dates back to the fourth edition of the American Joint Committee on Cancer where T3, resectable disease, was distinguished from T4, unresectable disease. Simultaneously, a greater reliance on more sophisticated imaging has occurred. It is with the sixth edition that computed tomography (CT) and positron emission tomography (PET) are allowed. The imaging modalities for detection and diagnosis apply to staging (see Table 17.5). Chest films and CT (preferably spiral) are essential steps in both the diagnosis and staging. PET combined with CT is utilized to overcome motion artifacts. Magnetic resonance imaging (MRI) is useful for mediastinal evaluation. Another advantage of CT over MRI for staging is that it allows for metastatic workup of lung, liver, adrenal, ribs, and vertebrae (Fig. 17.8).
Pathologic Staging
All pathologic specimens from clinical invasive procedures—bronchoscopy, mediastinoscopy, mediastinotomy, thoracentesis, and thorascopy—are applicable to pathologic stage. Thoracotomy and resection of primary and lymph nodes are the mainstay of pathologic staging. Margin status and any residual cancer need to be noted. Preferably, six nodes should be examined.
Oncoimaging Annotations
• Chest radiographs seldom detect primary lung cancers in their early stages.
• Spiral CT is useful in high-risk patients to detect nodules and infiltrates.
• PET imaging with18 FDG (fluorodeoxyglucose) appears to be of value in discriminating malignant versus benign nodules.
• CT can detect mediastinal adenopathy, but histologic verification is essential to ascertain if it is malignant.
• Determining N2 versus N3 mediastinal nodes is important; it establishes resectability.
• MRI can be of value in assessing mediastinal invasion, chest wall and rib erosion, and compromised large vein involvement.
• Coronal cuts on CT or MRI can be useful in determining distance from major bronchi cancer's edge to the carina.
• Cavitation with irregular thick wall occurs (often greater than 5 mm) and can reach 30% in some series.
• Cavity walls greater than 15 mm are 90% malignant.
• Bronchi can be occluded, resulting in a shifted fissure, a primary sign of lobar collapse.
Also of interest are biological and genetic markers that are of prognostic value based on meta-analysis data of the International Association for Study of Lung Cancer (IASLC).
PROGNOSIS AND CANCER SURVIVAL
PROGNOSIS
The limited number of prognostic factors are listed in Table 17.6
Figure 17.8 | Axial CTs of T5 and T6 level correlate with the T-oncoanatomy transverse section (Figure 17.5C). Oncoimaging with CT is commonly applied to staging lung cancers, often combined with PET to determine true extent of primary cancer and involved lymph nodes. A. Mediastinal window. 1, ascending aorta; 2, descending aorta; 3, main pulmonary artery; 4, right pulmonary artery; 5, superior vena cava; 6, interlobar pulmonary artery; 7, superior pulmonary vein; 8, LUL bronchus; 9, left main bronchus; 10, bronchus intermedius; 11, azygos vein. B. Lung window. 1, left main bronchus; 2, LUL bronchus; 3, bronchus intermedius; 4, esophagus; 5, interlobar pulmonary artery.
CANCER STATISTICS AND SURVIVAL
According to American Cancer Society facts and figures 2010, the age adjusted Cancer Death Rates for the more common cancers is striking in that cancer of lung and bronchus is the only cancer site that increases over the last 2 decades where as others decrease or plateau. (ACS Figure P3)
The number of new cases in the USA, exceed 220,000 new cases and result in approximately 157,000 deaths almost equally divided between genders with males exceeding females in incidence and mortality rates. Lung cancer constitutes of 15% of all cancer in males and is the second most common cancer, exceeded only by prostate cancer. Similarly in females, it constitutes 14% of all cancer cases and second only to breast cancer.
• Lung cancer remains the most lethal of all cancers accounting for 29% of male cancer deaths vs. 26% for female deaths.
• Smoking cigarettes remains the major risk factor and increases with quantity and duration. Other risk factors are second hand smoke, occupational or environmental exposure to radon, asbestos, and certain metals (chromium, cadmium, and arsenic).
• The value of CT screening in detecting early stage cancer in high risk patients is encouraging and is still undergoing clinical trial investigation.
• The 1 year survival for lung cancer increased from 35% in the seventies to 42% in 2000–2005.
• Generally the 5 year survival for NSCLC is 13% vs. 6% SCLC.
• Survival, according to stage: localized is 53%, regional nodes is 24% and for metastatic distant disease is 4%.
• According to the IASLC lung database, a series of survival curves, plotted by stage group demonstrates the median survival for combination of clinical and pathologic staging, and illustrates the decrement of survival with stage (F25.5). Histopathology is a major factor and (F25.4) NSCLC vs. SCLC demonstrates the increasing mortality as anticipated.
The impact of both stage and histopathology is well demonstrated in T14.7 illustrating the 5 year relative survival rates for different lung cancers. Although 5 year survival rates have improved with early detection and surgery in localized stages and current radiation chemotherapy regimens, the outcome for each subset is presented in the graph.
Figure 17.9 | Survival in all NSCLC by TNM stage (according to “best” based on a combination of clinical and pathologic staging). From Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging manual. 7th ed. New York: Springer, 2010:261, with permission.