Carcinoma of the lung is a malignant disease originating in the epithelium of the airways or respiratory alveoli, with the exact cause not known but with multiple well known high risk factors including cigarette smoking as the major contributor.
The result is a space occupying abnormality in the lung or bronchus with both mechanical and functional effects.
The patient is usually asymptomatic in the early stages, but as the disease progresses symptoms may include coughing, shortness of breath, hemoptysis, chest pain, weight loss, loss of appetite, wheezing, fever, hoarseness.
The diagnosis is initially suspected based on the patients clinical background and a suspicious CXR, and then may be confirmed by sputum cytology, computerized CT scan, bronchoscopy, positron tomography (PET) scan, lung biopsy, or mediastinoscopy.
Treatment options include surgery, radiotherapy, and chemotherapy. Stenting of occluded bronchi with metallic stents helps open obstructed bronchi. Newer techniques in therapy include endobronchial laser therapy and photodynamic therapy (PDT).
Lung cancer is treated according to the histological type and the stage of the disease. Small cell carcinoma is managed primarily by chemotherapy and sometimes radiotherapy while non small cell carcinoma has a wider variety of options including surgery, radiotherapy, and chemotherapy.
Cancer named as such by Hippocrates as “karkinos,” meaning crab, because the blood vessels surrounding malignant tumors resembled crabs. (32222)
In this section we discuss the principles of structure and then the principles of malignant growth and the structural changes that occur.
From the outset is important to understand the classification of lung cancer since the biology and approach to therapy depends significantly on this understanding.
There are two broad categories of lung cancer
Small Cell Lung Cancer (SCLC)
Non Small Cell Lung Cancer (NSCLC)
The reason for dividing them in this way is that SCLC is an aggressive non surgical disease with no curative possibility at this time, while treatment of NSCLC depends dominantly on staging where earlier stages have surgical and curative possibilities.
Non small lung cancers also are divided into
Squamous cell carcinoma
Large Cell Carcinoma
The lung cancers are structurally divided into those that have a predilection for the larger airways and are called central cancers (more commonly small cell cancer, and squamous cell cancer) and the peripheral cancers that occur in the smallest airways and alveoli (more commonly adenocarcinoma and its subtypes bronchioloalveolar carcinoma and large cell carcinoma)
There are many implications in this structural division of tumors but of great significance is the fact that the major vessels including arteries, veins, airways, and lymphatics take origin or converge at the hilum centrally so that space occupation in this region has far reaching effects on the tree like structures more peripherally. The peripheral tumors on the other hand are close to the end of the line of the branching structure and so the structural implications are not as great.
The central system in this context incorporates the main bronchi, through 16-23 divisions to, but not including the terminal bronchioles. The first division after the trachea results in the right and left main stem bronchi, and then branching follows to lobar bronchi (right upper, middle and lower, left upper, and lower) , segmental, subsegmental bronchi and then lobular bronchioles. At this point the central airways transitions into the peripheral system at the level of the terminal bronchioles.
About 75% of lung cancers originate from the first order, second order and third order bronchi. Within this group of central airways, the dominant tumors include small cell carcinomas (75-80% of SCLC occur in this region), and squamous cell carcinomas (65% of squamous cases occur in this region). The flexible bronchoscope has an external diameter that ranges between 4.9-6.2mm which will allow access to the fifth and even 6th generation bronchus. (Naidich) Ultrathin bronchoscopes that enable access to the 10th generation (outer diameter 2.7mm -3.8mm)
The peripheral system starts at the terminal bronchiole which after it divides becomes the respiratory (acinar) bronchiole, alveolar duct, and finally the termination of the system – the alveoli. It is in this region that the peripheral carcinomas commonly arise including adenocarcinoma, its variant bronchioloalveolar carcinoma (BAC) and large cell carcinomas.
The Terminal Bronchiole
The terminal bronchiole is the last airway of the tracheobronchial tree whose sole function is to transport air but without the ability to enable gas exchange. It measures about .7mm.
It terminates by dividing into sac-like protrusions, which allow gas exchange to start taking place. The first branch that is able to perform this gas exchange is called the respiratory bronchiole (acinar bronchiole) which measures about .5mm. After three divisions the respiratory bronchioles become alveolar ducts and after further division become alveolar sacs. Finally, at the terminal end of this pathway, the alveoli emerge.
The acinus is defined as the portion of lung that is distal to the terminal bronchiole (Webb) and is supplied by the respiratory bronchiole and usually measures about 6-10mms in diameter. (Osborne)
The acinus is functionally characterized by having the ability to both conduct air as well as enable gas exchange. When it is filled with fluid, it can be visualized on a CXR as a 6-7mm density called an “acinar shadow.” As a structural entity it has little diagnostic utility. We will expand on the pulmonary lobule in the next section which has greater implications for the imaging of the lung. Functionally, however, the acinus can be considered as the unit of gas exchange in the lung.
The Secondary Lobule
The secondary lobule (Webb) is the fundamental functional and structural unit that is enclosed in a membrane, measuring between 1-2.5cms in diameter, and is subtended by a small bronchiole and arteriole. There are usually between 8-12 acini per lobule, but this number varies between 3-24 . (Itoh)
The peripheral cancers either originate from the terminal bronchiole or from the airways of the acinus or from the alveolar cells as in the case of the bronchioloalveolar carcinoma.
The peripheral lesions from the terminal bronchiolar and alveolar epithelium are mostly but not universally adenocarcinomas and are distinguished by a glandular epithelium with fibrous and stromal response around tumor cell nests. Adenocarcinoma destroys the tissues and connective tissue infrastructure, incites desmoplasia and invades the lymphatics. It sometimes produces mucus
BAC arises from and grows along alveolar surfaces, spreading along the infrastructure, and uses the framework to spread without tissue destruction with resulting pneumonia like appearance on the CT scan.
Cancers arising in the periphery are mostly asymptomatic in the early stages – and therefore at the time of presentation are usually more advanced. Sputum cytology is usually negative presumably because they are so remote.
Draining Lymph Nodes
There are 4 basic group of nodes
Superior Mediastinal Nodes
1 Highest Mediastinal Nodes
2 Upper Tracheal Nodes
3 Prevascular and Retrotracheal Nodes
4 Lower Paratracheal Nodes
5 Subaortic Nodes (A-P window)
6 Paraaortic Nodes (Ascending Aorta or Phrenic)
Inferior Mediastinal Nodes
7= subcarinal nodes
9 = Pulmonary Ligament Nodes
10 Hilar Nodes
11 Interlobar Nodes
12 Lobar Nodes
Principles of Malignant Disease
Malignant cells occupy the space of normal tissue but they do not contribute to the structural nor functional welfare of the body at large. They arise in the lung more commonly in the proximal airways and either occupy the lumen or extend beyond the lumen and occupy parenchymal space, which may cause mass effect on other neighboring structures including blood vessels, lymphatics, pericardium, pleura, heart, and esophagus.
Partial or total blockage of the bronchi results in obstruction and atelectasis, which can be complicated by secondary infection, and bleeding.
Normal cells reproduce about 50 times before dying. Malignant cells, however, grow uncontrollably.
Malignant cells lack contact inhibition, meaning that they do not stop growing when they make contact with another object. The tumor may invade a neighboring tissue or organ and impede its function.
A malignant tumor may release an angiogenetic growth factor, enabling the formation of feeding blood vessels.
Invasion of the lymphatics and venous structures is inevitable though invasion of arterioles does not usually occur. Once in the mainstream of the venous or lymphatic system they can metastasize and reestablish a new colony with similarly aggressive and parasitic features. The usual “next stop” for hematogenously spread lung primaries is the brain. In the end malignant disease dominates the body and the healthy structures succumb to the unbearable burden.