PERSPECTIVE AND PATTERNS OF SPREAD
The TNM lung cancer staging system reflects the oncoanatomy of the bronchial tree and its numerous divisions into pulmonary segments and functioning respiratory units, with variations in lining epithelial cell phenotypes.
PERSPECTIVE AND PATTERNS OF SPREAD
The thorax is associated with two major malignancies: pulmonary and breast cancers. To paraphrase Dickens as to the survival outcomes of these two highly prevalent cancers, one is the worst of our times and the other among the best of our times. Both organs consist of an elaborate branching ductile systems ending in a vast fine network of functioning acini. In the lung, its extensive bronchial labyrinth terminates in a huge alveolar micromesh for aeration. In the breast, its more pliable, but fine ductwork terminates in myriad compound tubuloalveolar acini that, under the stimulus of pregnancy and elevated levels of estrogens and progesterones, can expand rapidly for lactation.
Lung cancer, one of the most malignant cancers, generally strikes active men and women in the prime of their lives and is associated consistently with a 20- to 30-year history of smoking. Even the earliest signs, unfortunately, are indicative of advanced spread. A patient who presents with unresolved and recurrent pneumonia or persistent cough that leads to mild or severe chest pain often has unresectable disease. Cancers of the lung are highly invasive, rapidly metastasizing tumors. The term lung cancer is used in reference to many different histopathologic types, which can masquerade in the form of a large number of benign pulmonary conditions. A collage of patterns of cancer spread presents the basis for the large diversification on clinical presentations (Fig. 12.1 and Table 12.1).
Cancers of the bronchi and lung are highly lethal tumors. More than 90% of lung cancer patients do not survive this disease, and more than 50% have distant metastases at the time of diagnosis. In women, the death rate associated with lung cancer began to exceed that of breast cancer by 1987. Two million people in the United States died from lung cancer by 2000 before better diagnostic and therapeutic methods were developed. Breast cancer strikes one of every seven women in the United States, and accounts for more than 25% of all cancers in women. With advances in diagnosis and treatment, survival rates have improved by 25% over the past five decades, ranging as high as a 97% 5-year survival for early stage node-negative disease.
If one views normal lung and lung cancers as derived from a pluripotential stem cell, then it is possible to understand its capability of expressing different features of the complex pulmonary anatomy as well as a variety of malignant phenotypes. The highly varied characteristics of each lung cancer's biologic behavior reflect their normal cell histogenic counterpart. These cells include pseudostratified epithelial reserve cells, type II pneumocytes, ciliated columnar cells, goblet cells, and neuroendocrine cells, each giving rise to a specific type of cancer. Utilizing this construct, the microscopic and macroscopic behavior of the various lung cancers and their spread patterns provides a logical basis for understanding the various staging notations and clarifications that have gradually evolved over time, while maintaining a consistently defined set of criteria for its staging. The current classification and staging was agreed to by the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) in the third edition (1978); however, in subsequent editions annotations have been added to provide detailed explanations of modifications to the basic staging system, again recognizing that lung cancer is more than one disease.
Lung cancer spreads in different patterns depending on its inherent biopathology and anatomic location in the bronchial tree. Briefly, centrally located bronchial tumors tend to be squamous cell cancers (SQCC), whereas tumors arising in peripheral bronchi more often are adenocarcinomas. Bronchioloalveolar cancers arise in alveoli and appear in a peripheral scar or as a patchy, diffuse pneumonitis and can be bilateral in distribution. Adenocarcinomastend to arise in the segmental bronchi and are associated with lobar pneumonitis and atelectasis. SQCCs are true bronchogenic cancers arising in the major bronchi. Small cell anaplastic cancers tend to be central masses, whereas large cell anaplastic carcinomas are more peripheral and extensively infiltrating. No structure in the thorax or mediastinum is spared. Compression of mediastinal structures is associated invariably with advanced lymph node involvement, which can lead either to esophageal compression and difficulty in swallowing, venous compression and congestion associated with collateral circulation, or tracheal compression. Signs of metastatic disease involving such remote sites as the liver, brain, or bone are seen before any knowledge of a primary lung lesion.
Figure 12.1 | Cancer spread patterns. A. Lung cancer can arise in many different sites in the bronchial tree and therefore presenting symptoms and signs are highly variable depending on its anatomic location. The cancer crabs are color-coded for T stage: Tis, yellow; T1, green; T2, blue; T3, purple; T4, red; and metastatic, black. B. Breast cancer spreads into the ductal system, stroma and ultimately invades lymphatics, skin and chest wall. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six-directional pattern i.e. SIMLAP Table 12.1.
TNM STAGING CRITERIA
TNM STAGING CRITERIA: LUNG
Lung cancer classification and staging has been stable since the first AJCC edition 1977. A major change in T categories occurred in the third edition (1988), when T3 resectable advanced disease was distinguished from T4 unresectable advanced disease. Also, N2 mediastinal nodes were divided into N2 ipsilateral and N3 contralateral nodes. Specific clarifications as to special presentations and histopathologic types were added in subsequent editions. In the third edition (1988), the AJCC introduced an elaborate numbering system for intrapulmonary and mediastinal nodes. The nodal status determines the stage grouping rather than the primary cancer status. Stage I is N0; stage II is N1; and stages IIIA and IIIB are determined by anatomic node location in the mediastinum, namely, ipsilateral or contralateral. In the fifth edition (1997), T3N0 was downstaged to stage IIB due to better survival for node-negative advanced disease patients. Then, nodal status is unresectable and assignment to stage IV would have been just as logical. Prognostic factors, including molecular, biologic, and genetic markers, are noted but are considered investigational and have not been incorporated into the staging system.
The origin of breast cancer is mainly within its glandular or ductal structure that infiltrates the lobule of its origin, then its quadrant that invades in one of two directions, toward skin or chest wall. The chest wall, for both breast and lung cancer, when involved is a sign of advancement. It is essential to understand the oncologic anatomy of the mammary gland to appreciate breast cancer's clinical manifestations and patterns of spread. Detection requires knowledge of the cancer's pathologic behavior, the surrounding structures that are commonly invaded, the location of the regional lymph nodes, and how the cancer can spread to remote sites through the breast's rich vascular network. Knowing this anatomy is a fundamental step toward the diagnosis and staging of this cancer.
With the seventh edition of the AJCC manual, dramatic changes in lung cancer staging and classification occurred. The database for the fifth and sixth editions were based on M. D. Anderson Cancer Center experience totaling 5,319 cases. The revisions currently are based on the International Association for Study of Lung Cancer (IASLC), which has amassed more than 100,000 patients of which 80,000 were used for analysis based on data from 46 centers in 19 countries, diagnosed and followed between 1990 and 2000. Summary of TNM stages are recommended for both non–small cell and small cell cancers plus carcinoid tumors.
SUMMARY OF CHANGES SEVENTH EDITION AJCC
The current 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 (Fig. 12.2).
• 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 Separate tumor nodules in the contralateral lung are considered 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 12.2).
Figure 12.2 | The T criteria are varied for each histopathologic type of lung cancer in their manifestation due to their anatomic location and origin, the bronchial tree. Pancoast cancer arises in superior sulcus and advances by local invasion into juxta-opposed structures. Bronchioloalveolar cancer (BAC) arises in the acini peripherally and advances by lepidic spread via alveolar pores of Kohn. Adenocarcinomas (AdenoCA) arise in lobar bronchi and advance by producing lobar atelectasis and pneumonitis. Squamous cell cancers (SQC) tend to arise in main bronchi and advance to the carina. All lung cancer types can become multifocal in the lobe, they arise in T3, or spread into lung of origin T4, or spread to contralateral lung M1.
OVERVIEW OF HISTOGENESIS
In the thorax, there are three major sectors and four major cancer sites that are staged (Fig. 12.3A–D). The first sector is the lung, major bronchi, and its visceral pleura. The second sector is the chest wall, which includes the parietal pleura and breast. The third sector is anatomically the most diverse, namely, the mediastinum and its contents: the heart and great vessels, thymus gland, major intrathoracic lymph node chains, thoracic duct, and esophagus. A cancer arising in one of the sectors tends to remain localized within that sector until it spreads into regional nodes or invades hematogenously. The bony thorax and intercostal musculature are anatomic structures that surround the lung and mediastinum (Table 12.3).
• The bronchial tree (Fig. 12.3A) originates at the tracheal carina starting with the main bronchi; then it divides within the visceral pleura into the pulmonary parenchyma as lobar bronchi (secondary bronchi). The left lung is divided into two lobes and further divides into 10 bronchopulmonary segments. The right lung divides into three lobes and also into 10 bronchopulmonary segments. The segmental bronchus and its associated lung parenchyma constitute a bronchopulmonary segment. Each segment of each lobe has its own blood supply (bronchial, pulmonary arteries, and veins) and can be resected along their connective tissue septa. The bronchi undergo another five to six orders of divisions, down-sizing into terminal bronchioles that finally end in respiratory bronchioles. The smallest functional unit of pulmonary structure consists of a single respiratory bronchiole, which allows for gas exchange via its acini and their multiple alveolar sacs.
• The subdivisions of the bronchial tree and summary of its histologic features are shown in Figure 12.3B. An anatomic relationship is postulated between lining epithelial cells and specific pulmonary cancers. Relating these different anatomic divisions of the bronchi to the origin of each histopathologic cancer type provides a rationale for many of the notations and clarifications for specific lung cancers and their staging features. The mesothelial pleural surfaces are barriers to cancer penetration. The lungs are encased in membranes called visceral pleura; the chest cavity is lined with a similar, although more fibrous, membrane called the parietal pleura. The potential space between these two membranes is the pleural cavity that allows for the smooth movement of lungs with respiration. Pleural mesotheliomas represent a new category that has been staged and classified for the first time in the sixth edition of the AJCC/UICC.
• The mammary gland consists of 15 to 20 lobes of glandular tissue with varying amounts of fat, in a dense fibroareolar stroma, and is attached to the anterior chest wall (Fig. 12.3C). In cross-sections starting from the nipple, there are openings of the lactiferous ducts and their lactiferous sinuses, which are the conduits for the secretions of the hormonally stimulated breast glands. These ducts are distinct and individual for each lobule; they first run dorsally from the nipple and then spread radially into the glandular tissue. The breast can be viewed three-dimensionally in terms of its anatomic relationship to other structures. As a superficial gland, it is covered by skin. Posteriorly, it is bounded by the underlying muscles of the chest. Deep to the glandular tissue there is usually a small amount of fat, which, along with the breast proper, is bounded by a deeper layer of superficial fascia. This layer can usually be dissected free from the deep fascia, investing the pectoralis major muscle. Connective tissue septa called the suspensory ligaments (of Cooper) form subdivisions of the breast, dividing the breast into lobes. The pectoralis major, the muscle underlying the breast, consists of two heads that arise from the clavicle, sternum, cartilages of the true ribs, and the sixth rib. The schematic of the breast dramatizes the largely ductal branched tubuloalveolar glands contained within a dense connective tissue stroma and variable amounts of adipose tissue. Each of the 15 to 20 lobes of the breast radiates from the mammary papilla (nipple), and each is connected by a specific lactiferous duct with its own lacuna or dilated sinus (Fig. 12.3F,G).
• The esophagus consists of three principal regions (cervical, thoracic, cardiac) and it bridges the head and neck, thoracic, and abdominal oncoanatomies. Its mediastinal course allows for a rapid overview of the various organs and structures in the mediastinum, especially those contained in the posterior compartment, which include the sympathetic and parasympathetic nerves and ganglia, the spinal cord and thoracic vertebrae, the thoracic duct and the aorta, which has the longest contact with the esophagus as both of these structures descend in the chest and exit via their own diaphragmatic stoma into the abdomen. In summary, the thorax oncoanatomy is presented to encompass all the potential primary sites and their malignant gradient.
• The lung oncoanatomy rests on its bronchial tree and its order of 10 subdivisions, lung lobes, and segments and the variation in cell lining phenotypes. The malignant gradient tends to worsen as cancers in the periphery arise in more central locations (Fig. 12.3D).
• The breast oncoanatomy rests on its more pliable 15 to 20 lobules, their extensive ductal arrays with the malignant gradient tends to worsen as cancers arise in the periphery and invade into the chest wall and more rapidly into lymphatics (Fig. 12.3D).
• The esophagus is a thin-walled structure that courses through the mediastinum with a high malignant gradient throughout; cancers penetrate vital structures and viscera in the different mediastinal compartments.
Figure 12.3 | Overview of histogenesis. A. Lung: Divisions of the Bronchial Tree. B. The lobar bronchi on the right and left divide into ten segmental bronchi. C. All ducts and their branches in an autopsy breast, viewed “en face”. Each roman numerical refers to different independent duct systems for the fifteen lobules that constitute the duct system. D. Comparison of breast ductile system and lung bronchial tree.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR T-ONCOANATOMY OF PRIMARY SITES
The three-planar anatomy to overcome the physiologic changes with respiratory and cardiac motion are correlated with anatomic views in dissection atlases, highlighting selected coronal and sagittal planes. The transverse planes are assigned to different lung cancers to provide a basis to encompass the complexities of thoracic anatomy. The assigned axial level is provided at 10 different levels to act as a scaffold for correlative computed tomography (CT) and cross-sectional magnetic resonance imaging (MRI).
The multiplanar diagrams in anterior (Fig. 12.4A) and lateral (Fig. 12.4B) views present the different thoracic malignancies, as variations of lung cancer histopathology and its intrinsic anatomy. Again, the biologic behavior and invasions of pulmonary cancer are determined in large part by the anatomy. To encompass the thoracic and pulmonary anatomy, the presentation of the 10 different primary site isocenters is utilized. Therefore, in Table 12.4 a specific anatomic aspect of the normal lung will be correlated with each cancer type, reinforcing concepts as to classification, staging, primary anatomy, lymph node drainage, and vascular drainage. A cephalad to caudad odyssey follows.
1. Pancoast cancers arise in the neck rather than the chest, emphasizing the apex of the lung which extends above and behind the clavicle. The symptom complex or syndrome caused by the apical cancer is readily apparent clinically since the superior sulcus of the lung is in direct contact with the inferior portion of the brachial plexus (C8 and T1). Also the stellate ganglion of the sympathetic chain is often compressed against the T1 transverse process as the cancer invades perineurally.
2. Bronchioloalveolar cancers (BACs) arise from the peripheral and most terminal part of the bronchoalveolar segment, at which point respiratory bronchioles (without cartilage) branch into an acinus consisting of alveolar sacs. BACs typically consist of large, mucus-containing cells, reminiscent of the type II pneumocytes and appear as parenchymal nodules. With their lepidic, scale-like growth pattern, they often appear in association with peripheral scars. BACs account for 5% to 9% of all lung cancers but in recent studies have increased to 20% to 24% of all lung cancers.
3. Adenocarcinomas (ADC) are the most common histopathology type of lung cancer and arise from the intrapulmonary bronchi that branch like limbs of a tree in each lung then divide into segmental and subsegmental bronchi, characterized by cartilage in their walls. They tend to be intra-pulmonary in location, arising from glandular forming epithelial lining cells of bronchi. Four subtypes or variants exist and range from abundant mucus production in well-differentiated cancers and to a cancer that becomes more undifferentiated, losing the glandular arrangement. The lobar anatomy is stressed because atelectasis and obstructive pneumonitis are common and extend to the hilar area.
4. Small cell carcinoma (SCC) are the most dedifferentiated cancers and tend to be more central in location close to the mediastinum. Such cancers arise from or revert to anlage pluripotential epithelial stem cells, and one may draw an appropriate analogy to the endoderm forming cells at the time in embryogenesis when the epithelia of the future lung airways appear as right and left lung buds, giving rise to lobar and segmental airways. SCCs are extremely aggressive cancers and in the majority of presentations (80%) are central mediastinal tumors, disseminating rapidly into submucosal lymphatic vessels and regional lymph nodes, and almost always present without bronchial invasion. This pattern of spread is to hilar and mediastinal nodes with no evident primary bronchial lesion.
5. Squamous cell cancers (SQC) are true bronchogenic cancers arising in major bronchi, which are often extrapleural in location with a different blood supply, namely, bronchial arteries instead of pulmonary arteries. SQCs are common cancers, although they comprise less than 50% incidence, more in the 30% to 35% range. Smoking is invariably part of the history and, when hemoptysis is associated with a coarse hilar rhonchial wheeze, this triad is diagnostic of bronchogenic carcinoma.
6. Large cell anaplastic cancers (LCAC) are a histologic diagnosis of exclusion and behave similarly to small cell anaplastic cancers. The large cell anaplastic cancers are more proximal in location and locally tend to invade the mediastinum and its structures early. Pericardial effusion is currently categorized as T4 if malignant cells are present. The most common cardiac involvement is a pericardial malignancy secondary to pulmonary cancer, or to a lesser degree, breast cancer. If pericardial cytology is negative, an incidental viral pericarditis needs to be ruled out. Although metastatic hematogenous spread places malignant cells in direct contact with the endocardial surface of the heart, metastatic myocardial nodules are a terminal event and are most often found postmortem. Large cell anaplastic cancers behave similar to small cell cancers and are known for their rapid fatal spread.
Figure 12.4 | Orientation of three-planar T-oncoanatomy of nine primary sites in the thorax. A. Anterior coronal. B. Lateral sagittal. Because of the angulation of the vertebrae to the convex curvature of the thoracic spine, the reference levels are between the vertebrae. (T-oncoanatomy) C. Respiratory system pleura/pleural cavity. D. Breast on chest wall and contour is shaped by ligaments of Cooper. E. Mediastinum is divided into four compartments. F.Esophagus can invade different mediastinal structures depending on location.
Anatomic Isocenters of Primary Cancer Sites TABLE 12.4
7. Mesotheliomas are pleural-based malignancies derived from the cell lining of the pleuroperitoneal membranes of the diaphragm that separate the pleural and peritoneal cavities from each other during their embryonal development. The mesenchyme lining of these cavities differentiates into a simple single layer of squamous epithelium or mesothelium. The mesothelium of the lung is the visceral pleura. In contrast, the parietal pleura lines the diaphragm, thoracic wall, and mediastinum. Pleural-based malignancies are designated as mesotheliomas and most often are due to asbestos exposure years earlier (Fig. 12.4C).
8. Breast cancers arise in the mammary glands, an appendage on the chest wall. Cancers of the mammary gland predominate among tumors of the chest wall, which are both benign and malignant. Breast cancers can invade their rich lymphatic plexus and drain into the axillary and internal thoracic nodes (mammary or parasternal), which are essential features of its anatomic spread. As the most common female cancer, it has been thoroughly studied and analyzed. The anatomic origin is most often either intraductal or the terminal lobule. It gradually invades the lobar segments and their suspensory ligaments with dimpling of the skin due to the loss of elasticity. Extensive invasion of dermal lymphatics leads to a peau d'orange pitting, which is caused by the pull of multiple Cooper ligament insertions in the edematous dermal layer. Invasion into the pectoral muscle and chest wall leads to fixation of the cancer (Fig. 12.4D).
9. Mediastinal tumors can arise from any structure, encompassed between the anterior manubrial sternal boney plate and the posterior spine, which are invested in the mediastinal pleura. A multitude of malignancies arise in the different compartments of the mediastinum, which is divided into superior, anterior, middle, and posterior segments. The superior mediastinum is defined by a plane intersecting T4 with the manubriosternal junction, and the other compartments are located below with the heart in the middle mediastinum separating the anterior and posterior compartments (Fig. 12.4E).
10. Esophageal cancers arise in different anatomic regions ranging from its cervical origin to the longer longitudinal intrathoracic portion terminating at the cardia of the stomach. Although the esophagus is thought of as a thoracic organ, esophageal cancers can present in the neck and abdomen as well as in the chest. The TNM staging for esophageal cancer is presented as an introduction to gastrointestinal malignancies. Its thin muscular walls, once invaded, rapidly disseminate epithelial cancers, mistaking them for a bolus of food. The peristaltic milking activity allows for its rapid dissemination through its submucosal lymphatics and its drainage into regional lymph nodes (Fig. 12.4F).
11. The heart occupies the middle mediastinum and primary neoplasms are extremely uncommon. The most common pattern of metastatic spread is direct extension into the pericardial sac from lung, breast, and esophagus cancers, resulting in pericardial effusions and tamponage. Multiple military metastases to heart as part of diffuse metastatic spread is more often discovered at autopsy rather than clinically (Fig. 12.4F).
N-ONCOANATOMY
N-ONCOANATOMY OF REGIONAL NODES
The lymph node anatomy of the thorax follows the orientation of the three sectors of primary site anatomy and its complexity is a result of their interconnectivity.
• The lung and its bronchial tree reflects the pulmonary lobar and segmental anatomy, which drains into hilar and mediastinal nodes.
• The breast or mammary gland is a chest wall appendage that drains into axillary, interpectoral, and internal (mammary or parasternal) thoracic lymph nodes.
• The esophagus has paraesophageal lymph nodes that drain into the posterior mediastinal nodes.
Another important aspect that needs to be appreciated is that as cancer infiltrates and replaces a node, lymph flow alters its prograde direction into collateral or retrograde channels, reaching lymph nodes that are not normally at risk of becoming involved.
For the lung, the first stations of lymph nodes are the intra-pulmonary and bronchopulmonary lymph nodes that lie within the visceral pleura. Their designation follows the bronchial divisions: hilar, interlobar, lobar bronchi, segmental, and subsegmental (Fig. 12.5A). These drain into second station carinal and mediastinal nodes. The entire right lung drains to the right hilar nodes and ipsilateral superior mediastinal nodes. The left lower lobe lymphatics cross over from the carinal region to the contralateral right side of the superior mediastinum. The left upper lobe and lingula drain to the ipsi-lateral left superior mediastinal nodes. A right scalene node biopsy is often favored because its drainage encompasses both right and left lungs. The lymph nodes of the lower posterior mediastinum do not appear to drain the lower lobes unless lower lobe cancers invade the pleural surfaces.
For the mediastinum, lymph nodes range from the thoracic inlet to the diaphragm and the major structures such as the thymus and esophagus intermingle their para-aortic lymph nodes with those from lung.The heart has pericardial nodes at its apex and base along the diaphragm. Mediastinal lymph nodes are within the right and left parietal pleura. Most important is the thoracic duct, which runs the vertical length of the thorax, crossing from right to left at the T6 to T4 levels. When the thoracic duct is compressed and invaded, a right-sided chylothorax can result. The AJCC utilizes a numbering system from 1 to 14 to locate thoracic lymph nodes, which is helpful to thoracic surgeons resecting and labeling mediastinal nodes (Fig. 12.5B; Table 12.5). For lymphomas, again in contrast is the concept of a lymph node–bearing region wherein the entire mediastinum is one node-bearing region with each hilar region designated separately (Fig. 12.5C).
For breast, its drainage encompasses much of the axilla and chest wall via four major routes: axillary, transpectoral, internal thoracic, and parasternal or internal mammary. Depending on which quadrant the breast cancer arises in, first station nodes include axillary (low, middle), axillary apex, supraclavicular, internal thoracic, parasternal nodes, interpectoral, and subclavicular nodes. Other pathways include crossover lymphatic channels to the opposite breast and inferior drainage into diaphragmatic and subdiaphragmatic channels. Disease involvement in all other nodes—cervical, contralateral supraclavicular, and contralateral internal thoracic (mammary)—is equivalent to distant metastases. The AJCC divides the axilla into three levels: (i) low axillary, (ii) mid-axillary, beneath the pectoralis minor muscle insertion, and (iii) high axillary and apical (Fig. 12.5D).
Figure 12.5 | Orientation of N-oncoanatomy. Lymphatic drainage and regional lymph nodes. A. Lung. B. AJCC number system of lung and mediastinal nodes (see Table 12.5). C. Anatomic definition of separate lymph node regions. D. Schematic diagram of the breast and regional lymph nodes. (1) Low axillary, level I. (2) Midaxillary, level II. (3) High axillary, apical, level III. (4) Supraclavicular. (5) Internal thoracic (mammary or parasternal) nodes.
M-ONCOANATOMY
M-ONCOANATOMY OF REGIONAL VEINS AND NEUROVASCULAR BUNDLE
The major vessels of the thorax are great vessels of the mediastinum, the aorta, and its divisions into brachiocephalic and subclavian arteries (Figs. 12.6A and 12.6B). The great veins consist of the anterior located, superior vena cava and brachiocephalic vein, the midthoracic pulmonary veins, and the azygos and hemiazygos venous complex posteriorly. The major neurovascular bundle is the vagal esophageal plexus and sympathetic gangli and nerves located in posterior mediastinum. Metastatic spread to distant organs according to the histopathologic type of lung cancer is listed in Table 12.6. The anatomic distribution of distant metastases is presented as a function of histopathologic type of lung cancer.
The lung is the most common site of metastatic cancer from other cancers due to the drainage of most sites into the superior and inferior vena cava into the right side of the heart and the flow via pulmonary artery into the lung, which acts as a filter for circulating cancer cells. For this reason, pulmonary metastases are more common than primary lung cancers. Pulmonary metastases can be the size of cannon balls on imaging and often nodules are round and well defined (see Table 31.1 Clinical Oncology 8th ed., p. 845).
Lung metastases can also be solitary and when detected as single or limited, the number of oligometastases can be successfully cured by surgical resection or stereotactic radiation surgery or therapy. The incidence of lung cancer metastases far exceeds diagnosis by imaging (see Table 32.1 Rubin P, Williams JP. Clinical Oncology: A multi-Disciplinary Approach for Physicians & Students 8th edition. Philadelphia, W. B. Saunders, 2001. p. 856).
Lymphangitic spread is less common and presents as “B lines,” producing a diffuse reticular pattern from hilus to pleura, leading to shortness of breath and asphyxia.
Figure 12.6A | Orientation of M-oncoanatomy. Pulmonary anterior views are related to metastatic spread to and from lung, pulmonary artery, and pulmonary vein respectively.
Figure 12.6B | Adenocarcinoma is the most common lung cancer and is presented as a prototype for lung cancers. The incidence and distribution of distant metastases are noted as percentages and correlate with Table 12.6.
Figure 12.7 | Lung cancer imaging. The most frequent manifestation or masquerades of bronchial cancers (1) to (16). (1) Hilar lung cancer with endobronchial growth (relatively early elicitation of the cough reflex). (2) Typical round focus. (3) Tumor cavern (note the thick irregular walls). (4) Subpleural focus infiltrating the chest wall. (5) Obstructive segmental discontinuation with retention in pneumonia. (6) Atelectasis, which is hidden behind the cardiac shadow (lateral radiograph). (7) Secondary bronchiectasis due to partial stenosis. (8) Focus near to the pleura, with effusion. (9) Necrotizing tumor with draining bronchus (abscess symptom). (10) Segmental atelectasis. (11) Obstruction emphysema due to valve occlusion. (12) and (13) Outbreak of carcinoma into the mediastinum, for example, in the direction of the vena cava (upper inflow congestion) or as Pancoast tumor. (14) Lymph node involvement in the upper mediastinum and paratracheally, extending to the upper clavicular fossa. Detection by lymph node biopsy according to Daniels or by mediastinoscopy: (15) and (16) carcinoma spreading to the trachea and pericardium, respectively. Note: A bronchial carcinoma can be masked even in a normal radiograph.
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.
• Positron emission tomography (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.
RULES OF CLASSIFICATION AND STAGING
Clinical Staging and Imaging
Lung cancer masquerades as many different pulmonary diseases and their clinical presentations are radiologically. The most commonly used procedure for staging lung, mediastinal, and breast cancers is the spiral CT. This is utilized to define the extent of both lung and breast cancer when they are invasive and advanced MRI is useful for assessing the mediastinal malignancies or adenopathy related to pulmonary and breast lymphatic invasion. Metastatic spread workup, which is common to lung and breast cancer, includes bone scans when osseous metastases are suspected. MRI is often utilized for brain and CT liver metastases. The workup for metastatic disease is based on symptoms being present rather than electively (Table 12.7; Figure 12.7).
STAGING WORKUP, PROGNOSIS, AND CANCER SURVIVAL
PROGNOSIS AND CANCER STATISTICS AND SURVIVAL
Also of interest are biological and genetic markers that are of prognostic value based on meta-analysis data of the IASLC (Table 12.7).
The 5-year survival rates for thoracic cancer over five decades presents the best and worst achievements in controlling cancer deaths. Because breast cancer is slowly increasing in incidence and prevalence, it is anticipated that there will be more than 200,000 new diagnoses of invasive breast cancers annually in this country alone. In addition, there are 60,000 cases of highly curable preinvasive cancers. Breast cancer is currently found with mammography, mainly in noninvasive or early stage I cancers where survival rates are at the 95% mark. The improvement in breast cancer survival over the past five decades has been dramatic, with a doubling in the survival rate from 45% to 90%, also reflecting the advances in multimodal management. Breast cancer is the most common cancer in women (215,990), which translates to one third of all neoplasms diagnosed in the United States. Fortunately, most patients with breast cancer survive and only 40,110 deaths (15%) can be attributed to the malignancy.
Lung and bronchus cancers are the second most common cancers at almost 116,000 new male patients and a comparable 105,000 female patients, accounting for 15% and 14%, respectively, of cancer patients. However, lung and bronchus cancer is public enemy number one and is the leading cause of death for men 86,000 (29%) and 71,000 (26%) women. An estimated 222,500 new cases of lung cancer annually will be diagnosed by 2010, with a predicted 160,000 deaths in the same year (Tables 12.8 and 12.10). This is one of the most dismal cancer survival rates for NSCLC at 17% vs 6% for SCLC. Despite the progress of research, the causes of this disease and mortality rates have not been reduced.
Curability concepts can only be applied to breast cancer with 86% of all stages surviving 5 years, and with excellent results for all stages: 88% 5-year and an impressive 97% 5-year for localized disease and even 78% for regional nodes. For lung and esophageal cancers, most patients are in advanced stages with only 2% to 3% surviving 5 years. Although there have been improvements in multimodal approaches, only about 10% of such patients survive.
Whereas the 10% gain in lung cancer survival over five decades also represents a doubling in survival rates, it remains one of the most lethal of all cancers despite gains in knowledge. To end on a positive note, early stage I lung cancer can result in a better than 90% survival (Fig. 12.8). Although routine spiral CT scans of the thorax in high-risk patients have yielded a high number of early stage lung cancers, this procedure is too costly to apply routinely. However, it is recommended for the habitual heavy smoker on an annual basis. Large cohorts of patients have been screened, and early detection of small lung cancers have been found with an increase in their survival rate.
Figure 12.8 | Trajectory of Lung, Mesothelioma, Esophagus Incurability over seven decades in contrast to the high curability of breast cancer.