Lung cancer, or lung carcinoma, is the uncontrolled division of epithelial cells which line the
respiratory tract.
There are two main categories of lung cancer, small cell and non-small cell, which depend
on the type of epithelial cell that's dividing.
Both types can be fatal, especially if the cancerous cells aggressively spread and establish
secondary sites of cancer in other tissues.
The major cause of lung cancer is smoking tobacco products, and it has contributed to
the deaths of millions of people including famous individuals like Walt Disney and Claude
Monet.
Air enters the respiratory tract through either the nose or mouth and flows down the trachea,
which divides into the right and left bronchi.
Each bronchi enters its respective lung at the hilum, or root of the lung.
The bronchi then divides into lobar bronchi, which divide into segmental bronchi, then
into subsegmental bronchi, which further branch to form conducting bronchioles and then respiratory
bronchioles which end with small, sacs called alveoli that are surrounded by capillaries,
which is where gas exchange occurs.
Lining these airways are several types of epithelial cells which serve multiple functions.
These include ciliated cells that have hair-like project called cilia that work to sweep foreign
particles and pathogens back to the throat to be swallowed.
Another type, called goblet cells--which are called that because they look like goblets--secrete
mucin to moisten the airways and trap foreign pathogens.
There are also basal cells that are thought to be able to differentiate into other cells
in the epithelium, club cells that act to protect the bronchiolar epithelium, and neuroendocrine
cells, that secrete hormones into the blood in response to neuronal signals.
Cells can become mutated because of environmental or genetic factors.
A mutated cell becomes cancerous when it starts to divide uncontrollably.
As cancer cells start piling up on each other they become a small tumor mass, and they need
to induce blood vessel growth, called angiogenesis, to supply themselves with energy.
Malignant tumors are ones that are able to break through the basement membrane.
Some of these malignant tumors go a step further and detach from their basement membrane at
the primary tumor site, enter nearby blood vessels, and establish secondary sites of
tumor growth throughout the body - a process called metastasis.
A well known risk factor for small cell lung cancer and some types of non-small cell lung
cancer is smoking tobacco, and it's dose-dependent which means that smoking more cigarettes over
a longer period of time increases the risk.
Another risk factor is exposure to radon, a colorless, odorless gas which is a natural
breakdown product of uranium found in the soil.
Other environmental factors include asbestos, air pollution, and ionizing radiation, like
from medical imaging with chest X rays and CT scans.
There are also some gene mutations that are known to be associated with an increased risk
of lung cancer development.
Once it develops, lung cancer tends to metastasize quickly, rapidly establishing sites of secondary
tumors in other tissues.
Tissues particularly at risk as a secondary site are the mediastinum and hilar lymph nodes
because of their proximity to the lungs, but other sites include the lung pleura - the
lining of the lungs, heart, breasts, liver, adrenal glands, brain, and bones.
Lung cancer can be categorized as either small cell or non-small cell carcinomas.
Small cell carcinomas account for a small portion of lung cancers and originate from
small, immature neuroendocrine cells.
That means that non-small cell carcinomas account for most lung cancers, and these can
be further subdivided into four categories: adenocarcinomas which frequently form glandular
structures or have the ability to generate mucin; squamous cell carcinomas; which have
squamous, or square shaped, cells that produce keratin; carcinoid tumors from mature neuroendocrine
cells; and large cell carcinomas which lack both glandular and squamous differentiation.
Small cell carcinoma is strongly associated with smoking and usually develops centrally
in the lung, near a main bronchus.
In general, they grow the fastest and more rapidly metastasize to other organs than other
types of non-small cell lung cancers.
Because of this, by the time it's diagnosed, it's common to find large tumors in multiple
locations both within and outside the lung.
Typically when small cell carcinoma is within one lung, it's considered limited, if it
spreads beyond one lung it's considered extensive.
Small cell carcinomas can also sometimes secrete hormones and that can lead to what is called
a paraneoplastic syndrome.
One example is when the tumor releases adrenocorticotropic hormone causing an increase in production
and release of cortisol from the adrenal glands.
This causes what's known as Cushing's syndrome which causes a number of symptoms
including an elevated blood glucose and high blood pressure.
Another example is when the tumor releases antidiuretic hormone which causes water retention
leading to high blood pressure, edema and concentrated urine.
A slightly different type of paraneoplastic syndrome, is when small cell carcinoma prompts
the body to produce autoantibodies which bind and destroy neurons causing myasthenic syndrome,
which is a type II hypersensitivity reaction.
Non-small cell carcinomas are more of a mixed bag in terms of where they usually arise.
Just like small cell carcinoma, squamous cell carcinoma tends to be centrally located and
has a strong association with smoking.
In contrast, adenocarcinoma tends to develop peripherally, in a bronchiole or alveolar
wall, and doesn't have a link to smoking.
Large cell carcinomas and bronchial carcinoid tumors can be found throughout the lungs - centrally
and peripherally.
Of these two, large cell carcinoma is linked to smoking.
Both adenocarcinoma and squamous cell carcinoma can form Pancoast tumors, which are masses
in the upper region of the lung that compress the blood vessels and nerves located there.
In particular, pancoast tumors can compress and damage the thoracic inlet, brachial plexus,
and cervical sympathetic nerves leading to their dysfunction and Horner syndrome.
Clinical symptoms of Horner syndrome include a constricted pupil, a drooping upper eyelid,
and loss of ability to sweat on the same side of the body as the dysfunctional sympathetic
nerve.
A classic paraneoplastic syndrome associated with squamous cell carcinoma is the release
of parathyroid hormone which depletes calcium from the bones causing them to become brittle
and increasing calcium levels in the blood.
And, finally, a paraneoplastic syndrome specific to carcinoid tumors is carcinoid syndrome
which causes the secretion of hormones, particularly serotonin, which leads to increased peristalsis
and diarrhea, and bronchoconstriction causing asthma.
Since non-small cell carcinomas tend to be slower growing and slower to spread than small
cell, staging is more elaborate.
It's called "TNM" staging and represents three diagnostic categories: T, for tumor
size and extent of local extension; N, for spread into nearby lymph nodes in the chest,
particularly the mediastinum and hilar lymph nodes; and M, for metastasis to a secondary
site.
Within each of these categories are sub-stages, T0-T4, N0-N3, and M0-M1, where an increasing
number means increasing severity.
Finally, the combinations of these sub-stages determine thes stage group, assigned 0 to
IV.
So for example, if the diameter of the tumor is less than or equal to 3 cm and not in a
main bronchus, has invaded the hilar lymph node on the same side of the chest, but has
not spread outside the chest to other tissues, it's categorized as T1, N1, M0 and can be
considered stage group II.
But if the tumor metastasizes to a secondary site, it's considered M1 and staging group
IV regardless of it's T or N value.
Symptoms of lung cancer vary based on the size and location of the tumor, whether or
not is has spread to other organs, and whether or not it generates hormones - all of which
is often predicted by the type of cancer.
In response to the cancer cells, the body mounts an immune response which results in
the release of chemokines like TNF-alpha, IL1-beta, and IL-6 which can cause weight
loss, fevers, and night sweats.
If the primary tumor physically obstructs the airway and presses on surrounding tissue
structures it can cause a cough, shortness of breath, and leads to a pneumonia in the
lung tissue behind the obstruction.
Compression of nearby nerves can cause pain, and compression of specific nerves like the
recurrent laryngeal nerve and phrenic nerves can cause changes in voice or difficulty breathing,
respectively.
Compression of nearby vessels like the superior vena cava can cause a backup of blood in the
face leading to facial swelling and shortness of breath.
Finally, if a cancer cells invade into a blood vessel then mucus can get blood tinged or
blood clots can get coughed up.
Initially lung cancer is usually identified as a coin-shaped spot, called a coin lesion
on chest X-ray, or a non calcified nodule on chest CT.
Infections can also cause similar shaped spots, so a tissue biopsy from a bronchoscopy or
a CT-guided fine-needle aspiration is typically done to make a histopathologic diagnosis.
Though treatment will vary by category and stage of the lung cancer, often a commonality
is the use of surgery if appropriate, chemotherapy or immunotherapy, and radiation therapy when
possible.
In general, the goal of surgery is to remove as much of a tumor, ideally all of it, and
to have a small border of healthy tissue around it so that all of the cancerous cells are
gone.
Depending on the size and location of the tumor, a small wedge of tissue may be taken,
or up to an entire lung, in which case the airway is sutured shut to prevent air from
leaking into the body cavity.
In addition, it's typical to remove nearby lymph nodes which have metastasis and manage
clinical symptoms.
Since pain is a significant chronic symptom of lung cancer, it's often managed through
both nonpharmacologic approaches like yoga and guided imagery as well as pain medications.
So, a quick recap: Lung cancer is the uncontrolled growth of respiratory epithelial cells.
The minority are small cell cancers and the majority are non-small cell, which are further
categorized into adenocarcinoma, squamous cell carcinoma, bronchial carcinoid, and large
cell carcinoma.
Some common issues for all lung cancers is that they can cause airway obstruction, compression
of nearby nerves and the superior vena cava, cause paraneoplastic syndromes, and induce
an immune response which causes symptoms like weight loss, fevers, and night sweats.
Overall, lung cancers have a high rate of metastasis to other organs, and are treated
with a combination of surgery, chemotherapy, immunotherapy, and radiation depending on
the situation.
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