Lung cancer is the second most frequent cancer, but it causes the most cancer-related deaths worldwide.
Smoking is famously the biggest risk factor, and also the reason that lung cancer incidence increased dramatically during the 1900s.
We can compare smoking habits with a measure called “pack-year”. If you have smoked 1 pack of cigarettes (20 pcs) every day for one year have you accumulated 1 pack-year. If you smoke one half pack every day for four years have you accumulated 2 pack-years.
Other risk factors include:
- Genetic susceptibility
- Ionising radiation
- Uranium miners
- Indoor radon gas
- Polycyclic hydrocarbons
Around 95% of all primary lung tumors are carcinomas (epithelial origin), and these four types are most important:
- Squamous cell carcinoma
- Neuroendocrine carcinomas
- Small cell carcinoma
- Large cell carcinoma
Lung cancer localization
The different types of lung tumors have a preference to where they prefer to originate in the lung, either centrally or peripherally.
Centrally in this case means around the hilum and main bronchi. Squamous cell carcinomas and small-cell lung carcinomas usually originate here. Central cancers usually cause symptoms earlier than peripheral cancers, because the cancers are closer to the airways. Central cancers also more frequently spread to surfaces like the mediastinum. It’s much harder to remove cancers surgically that are close to the bronchi without damaging the bronchi, so these cancers are much harder to treat surgically.
Peripherally in this case means anywhere else in the lung, often further away from the airways, often just beneath the pleural surface, subpleurally. Adenocarcinomas and large-cell lung carcinomas usually originate here. These cancers will show symptoms at a much later stage than the central cancers, but they are also much easier to remove surgically.
Squamous cell carcinoma
SCC are usually found centrally, where they originate from major bronchi. Well-differentiated tumors will show keratinization, poorly-differentiated tumors won’t. It’s highly associated with smoking, but not with HPV, like laryngeal SCC is.
It follows the following process of development:
- Normal bronchial epithelium
- Basal cell hyperplasia
- Squamous metaplasia
- Squamous dysplasia
- Carcinoma in situ
- Invasive carcinoma
This development takes many years. The pathohistology slide shows this progression.
These tumors usually form cavities because of central necrosis.
Adenocarcinomas are the most common type and are found peripherally. They’re the most common type in women and is not associated with smoking, but rather with several genetic mutations, like:
- EGFR (epidermal growth factor receptor)
- PD-L1 (a checkpoint protein)
TTF-1 is a transcription factor that is expressed in lung adenocarcinomas and small cell carcinomas that is commonly used to distinguish between these types and squamous cell carcinoma, which doesn’t express TTF-1.
Five subtypes exist. They are, from best to worst prognosis:
- Lepidic type
- Acinar type
- Papillary type
- Solid type
- Micropapillary type
The lepidic type is technically an adenocarcinoma in situ, because the tumor cells only line the alveolar spaces and don’t invade past the basement membrane (yet. They can mutate further and become invasive).
These cancers are thought to originate from neuroendocrine cells in the lung, cells that respond to nerve signals by producing endocrine hormones. They are also related to smoking. The grading system for neuroendocrine carcinomas is special; it’s dependent on the rate of mitosis in the tumor. The stages go like this:
|Stage||Rate of mitosis||Name||Prognosis|
|III||Fast||Large-cell lung carcinoma|
|III||Fast||Small-cell lung carcinoma||Worst prognosis|
Small cell lung carcinomas (SCLC) are found centrally. They grow very quickly and metastasize early. Because of this is surgery very rarely possible, however it responds well to chemotherapy. Because they grow so quickly mitotic bodies are usually aplenty.
Large cell lung carcinoma is actually an umbrella term for a group of very poorly differentiated carcinomas, however one type, large cell neuroendocrine carcinoma, is neuroendocrine in origin. Large cell carcinomas are found peripherally.
Lung cancer usually spreads to:
- Hilar lymph nodes
- Pleura (pleural carcinosis)
- Adrenal gland
Lymphangitis carcinomatosa is common in the lung. It’s caused by the lymph vessels being filled up with invading malignant tumor cells. This causes the lymph vessels to dilate and become visible.
Symptoms of lung cancer include:
- Progressive dyspnoea
- Weight loss
Any lung tumor, regardless of subtype (but mostly non-small cell), is called a Pancoast tumor if it occurs in the apex of the lung. There are many structures in that area which the tumor can compress or invade, and so Pancoast tumors therefore have multiple extra consequences:
- Shoulder pain – due to compression of local nerve roots
- Pain in upper extremities – due to compression of the brachial plexus
- Horner syndrome – due to compression of the stellate ganglion
- Facial anhidrosis
- Superior vena cava syndrome – due to compression of the SVC
- Oedema of the face
- Hoarse voice – due to compression of the recurrent laryngeal nerve
Paraneoplastic syndromes are common in lung cancer. Common occurrences include:
- ACTH secretion, leading to Cushing syndrome
- ADH secretion – leading to syndrome of inappropriate ADH (SIADH)
- Parathyroid hormone-related protein (PTHrP) secretion, leading to hypercalcaemia. Occurs especially in SCC
81. Vascular diseases of the lung
83. Pleural and mediastinal disorders