L9 - Pulmonary Pathology ( Dr Muhammed Sohail) Flashcards
- to understand the pathology of lung and pleural cancers
What is the rank of lung cancer in terms of common malignancies?
Lung cancer is the third most common cancer after prostate cancer ( predominantly in males) and breast cancer ( predominantly in females - good screening and prognosis programme).
Number of prostate, breast, lung and colorectal cancer registrations (2018)
Prostate = ~ 50,000
Breast = ~ 49,000
Lung = ~ 41,000
Colorectal = ~37,00
(each year, lung cancer kills more peoplan than colon, breast and prostate cancer combined)
Why is lung cancer considered highly fatal compared to other cancers?
Despite being the third most common, lung cancer has the highest mortality rate due to:
- Late diagnosis
- Poor prognosis
- Limited effectiveness of treatments compared to breast and prostate cancer
What percentage of cancer deaths in males are due to lung cancer?
One-third (33%) of all cancer-related deaths in males are due to lung cancer.
At what age is lung cancer most commonly diagnosed?
It occurs between ages 55-84, with peak incidence at 65-74 years.
What is the overall survival rate for lung cancer in England (2013 - 2017) ?
16% overall survival rate.
what is the 5 year survival rate for metastatic lung cancer
7%
what is the 5 year survival rate for men and women with lung cancer
men is 18% whilst women is 25%
How does lung cancer survival compare to breast cancer?
Stage 1 breast cancer has an 85% five-year survival rate, whereas lung cancer survival is significantly lower.
How do survival rates compare between small cell and non-small cell lung cancer?
Non-small cell lung cancer (NSCLC): 26% five-year survival after treatment.
Small cell lung cancer (SCLC): Only 7% five-year survival rate.
What happens if small cell lung cancer (SCLC) is left untreated?
Survival is usually measured in weeks. Without treatment, patients rarely survive beyond months.
How is lung cancer classified?
Lung cancer is divided into:
- In situ carcinoma (doesn’t invade the basement membrane)
- Adenocarcinoma in situ
- Squamous cell carcinoma in situ - Invasive carcinoma (invades basement membrane so it can spread to distant sites. the prognosis is worse and requires the draining lymph nodes to be removed)
- Squamous cell carcinoma
- Adenocarcinoma
- Large cell undifferentiated carcinoma
- Sarcomatoid Carcinoma
- Neuroendocrine tumours e.g. Carcinoid, atypical carcinoid, small cell carcinoma and large cell neuroendocrine carcinoma
how was cancer tranditionally classified
- small cell carcinoma ( a highly aggressive form of lung cancer, often referred to as “oat cell carcinoma” due to the shape of the cells. typically neuroendocrine, meaning the tumor cells have characteristics similar to those of nerve and hormone-producing cells. primarily treated with chemotherapy and radiotherapy)
- large cell carcinoma ( a type of non-small cell lung cancer (NSCLC). It is characterized by large, abnormal cells that lack the specific features seen in other types of NSCLC, like adenocarcinoma or squamous cell carcinoma. primarily treated with surgery)
What is Large Cell Undifferentiated Carcinoma?
A lung cancer type where cells appear large but lack specific features of other NSCLC subtypes.
What is Sarcomatoid Carcinoma?
A rare NSCLC subtype where cancer cells resemble sarcoma-like (spindle-shaped) cells.
How does treatment differ between NSCLC and SCLC?
NSCLC → Surgery if operable
SCLC → Chemotherapy or radiotherapy (sensitive to chemotherapy)
Why was lung cancer previously only classified as small cell vs. non-small cell?
It was a quick method for clinicians to determine treatment - there are specific targeted treatments for different types of lung cancer:
Small cell → Chemotherapy
Non-small cell → Surgery if operable
Why is lung cancer now further classified into subtypes?
Due to advancements in targeted therapies, clinicians need to know specific subtypes e.g.,quamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, large cell undifferentiated carcinoma, sarcomatoid carcinoma, and neuroendocrine tumors for better treatment selection.
What is the key characteristic of Small Cell Lung Cancer (SCLC)?
It is a neuroendocrine tumor with rapid growth, early metastasis, and poor prognosis.
What is the most significant risk factor for lung cancer?
Smoking – It is the leading cause, significantly increasing the risk.
Besides lung cancer, which other organs can develop cancer due to smoking?
Smoking is linked to cancers in:
- Pancreas
- Bladder
- Esophagus
- Kidney
- Larynx
How many harmful substances have been identified in cigarette smoke?
Over 1,200 different substances, including potent carcinogens
What are some key carcinogens found in cigarette smoke?
- Polycyclic aromatic hydrocarbons (PAHs) – Direct carcinogens
- Phenol derivatives – Harmful chemicals
- Radioactive elements – Damage DNA and promote mutations
What are the 4 risk factors for lung cancer ( including smoking)
- Smoking
- Asbestos exposure
- Radiation
- Molecular genetics
What is the role of genetic variations in lung cancer risk from smoking?
- Individuals with certain genetic variants have a heightened ability to activate procarcinogens found in cigarette smoke, making them more susceptible to lung cancer.
- People with defective DNA repair genes are unable to effectively correct the genetic damage caused by smoking. Specifically, individuals whose peripheral blood lymphocytes exhibit numerous chromosomal breakages after exposure to tobacco-related carcinogens—often referred to as having a “mutagen-sensitive genotype”—have over a ten-fold increased risk of developing lung cancer compared to those without this genetic vulnerability. This heightened risk is likely due to genetic variations in the genes responsible for DNA repair.
How does asbestos exposure increase lung cancer risk?
Although asbestos is commonly associated with mesothelioma, it more frequently leads to lung cancer because:
- Asbestos fibers pass through the lungs, causing more damage.
- Alveolar macrophages engulf asbestos, triggering chronic inflammation.
- Inflammation damages lung epithelium, leading to uncontrolled cell proliferation and mutation → cancer development.
What is the process of asbestos-induced lung cancer formation?
Asbestos fibers → Alveolar macrophage activation and release of inflammatory mediators → Chronic inflammation → damage to the epithelium lining → DNA damage & mutations in the epithelium lining when they start to proliferate → Hyperplasia → Lung carcinoma.
What environmental factor besides smoking and asbestos increases lung cancer risk?
Radiation exposure (e.g., radon gas, occupational radiation).
How much does smoking increase the risk of lung cancer if you are an average vs heavy smoker?
Average smoker → 10x risk
Heavy smoker → 24x risk
How much does asbestos exposure alone increase the risk of lung cancer?
5x (fivefold) increased risk in asbestos workers who do not smoke.
How does the risk change if a person is both a smoker and exposed to asbestos?
The risk becomes 50x higher due to the combined effects of smoking (10x) and asbestos (5x) (that is if they are an average smoker ut this goes up to 120 if they are a heavy smoker)
How does asbestos exposure compare to mesothelioma in terms of lung cancer deaths?
Lung cancer is more common than mesothelioma in asbestos workers:
1 in 5 deaths due to lung cancer.
1 in 10 deaths due to mesothelioma.
What is mesothelioma.
Mesothelioma is a cancer that develops in the mesothelium, the tissue that lines the lungs, abdomen, heart, and sometimes testicles. It’s usually caused by exposure to asbestos.
What is the latent period between asbestos exposure and lung cancer development?
Approximately 20 years ( need to have a long history to find out what caused it)
How is radiation both a cause and a treatment for cancer?
It depends pm the dose and effects on DNA :
High radiation dose → Causes irreparable DNA damage, leading to cell death (used in cancer treatment).
Low radiation dose → Causes partial DNA damage, which can lead to mutations and cancer instead of cell death
How does targeted radiation therapy work?
- High-dose radiation is focused on the tumor (concentrated) to ensure cancer cells receive lethal damage.
- Minimal exposure to surrounding healthy tissue to allow normal cells to recover.
- Fractionated doses are given with gaps to allow normal cells to repair, while cancer cells (with faulty repair mechanisms) die.
how is raditaion a carcinogen
due to its damaging effects on DNA : If the cell survives after the DNA damage (mutation) then it may transform into cancer
how is radiation used as a treatment
a lethal dose of radiation is given which causes DNA damage that is too severe for the the cell to survive, so it dies ( this is the desired outcome in cases of radiotherapy)
What historical evidence links radiation exposure to lung cancer?
- Hiroshima & Nagasaki survivors → Increased lung cancer rates decades after atomic bomb exposure.
- Uranium miners (especially in Europe) → Higher risk of lung cancer due to prolonged radiation exposure.
- Radon gas exposure → Possible link to lung cancer (not definitively proven).
What are the two main types of genes involved in cancer development?
Proto-oncogenes (Accelerators) → Promote cell proliferation.
Tumor suppressor genes (Brakes) → Prevent uncontrolled cell division.q
What happens when proto-oncogenes mutate?
Gain-of-function mutation → They become oncogenes, leading to continuous cell proliferation.
What happens when tumor suppressor genes mutate?
Loss-of-function mutation → They fail to regulate cell growth, allowing cancer to develop.
Give an example of a tumor suppressor gene mutation linked to lung cancer.
P53 mutation → Prevents apoptosis (cell death), allowing damaged cells to become cancerous.
Which tumor suppressor genes are involved in lung cancer?
P53 (most common in all types)
RB1 (Retinoblastoma gene)
p16
and multiple loci on chromosome p3
What are the major proto-oncogene mutations seen in lung cancer?
EGFR (Epidermal Growth Factor Receptor) – Seen in both adenocarcinoma & squamous cell carcinoma.
KRAS – Common in adenocarcinoma.
ALK gene rearrangement – Seen in non-smokers with adenocarcinoma.
c-MYC
c-KIT
Why is lung cancer difficult to fully understand at the genetic level?
Because multiple different mutations contribute to lung cancer, and these mutations vary between individuals.
What are the most common genetic mutations in adenocarcinoma of the lung?
KRAS ( 25.5%)
EGFR (Epidermal Growth Factor Receptor) mutation (16.1%)
ALK (3-5%)
ROS1 (1%)
MET (2 - 5%)
RET (1-2%)
BRAF (2%)
PI3K (2%)
Her2 (2-5%)
In which patient population is EGFR mutation more common?
10-15% of adenocarcinomas in Caucasians
45% in non-smoking Asian women
Where do EGFR mutations typically occur?
It can occur in different areas - particularly in Exon 18-24 (Tyrosine Kinase Domain)
Why is EGFR mutation significant for treatment?
depending on where the mutation is they can be sensitive to tyrosine kinase inhibitors (TKIs) for target these mutations for precision therapy.
Which EGFR mutations lead to resistance?
T790M mutation (Exon 20) → Causes resistance to first-line TKIs and chemotherapy
What happens when lung cancer develops resistance to EGFR-targeted therapy?
Cancer cells evolve alternative mutations (bypass mechanisms), or the selection of cells which aren’t sensitive leading to treatment failure and recurrence.
Other mutations seen in adenocarcinoma?
KRAS, ALK, MET, ROS1, BRAF, PIK3CA
Which genetic mutation is most frequently seen in squamous cell carcinoma of the lung?
TP53 mutation (found in most tumors).
What is the function of TP53, and why is its mutation important?
TP53 = “Guardian of the Genome” → It prevents DNA damage from leading to uncontrolled cell growth.
Mutation leads to loss of tumor suppression and early cancer development.
What is a common histological marker for TP53 mutation in lung cancer?
Immunohistochemistry shows strong P53 protein overexpression in squamous cell carcinoma.
How is squamous cell carcinoma genetically different from adenocarcinoma?
Squamous cell carcinoma is more strongly linked to smoking exposure and has mutations (many of which are chromosome deletions) in tumor suppressor genes (TP53, RB1, FGFR2), rather than oncogenes like EGFR.
definition of an adenocarcinoma vs squamous cell carcinoma
adenocarcinoma - malignant epithelial tumour showing gland like structures
Squamous cell carcinoma - shows keratin or intracellular bridges
What are the stages of lung cancer development?
- Dysplasia → 2. Carcinoma in situ → 3. Invasive carcinoma
How early can TP53 mutations be detected in squamous cell carcinoma?
10-50% of squamous dysplasia already show TP53 mutations.
60-90% of carcinoma in situ have TP53 mutations.
Which receptor mutation is sometimes seen in SCC?
FGFR1 (Fibroblast Growth Factor Receptor 1) – found in a small proportion of SCC.
Histological features of SCC?
Keratin formation or intercellular bridges
Which two tumor suppressor genes are almost always inactivated in SCLC?
RB1 (Retinoblastoma gene)
TP53 (~90% of cases)
What happens when RB1 is mutated?
RB1 normally prevents uncontrolled cell proliferation by stopping E2F transcription factors (so it proliferation in the nucleus is not prevented )
Mutation → Uncontrolled cell cycle progression → Cancer growth
Can non-small cell lung carcinoma (NSCLC) transform into SCLC?
Yes, especially if TP53 and RB1 inactivation occurs.
What are the common symptoms of lung cancer?
Weight loss, cough, hemoptysis (coughing blood)
What are the two most likely diagnoses if a patient presents with weight loss, coughing blood and loss of appetite?
- Cancer
- Tuberculosis (TB)
Which lymph nodes can be involved in lung cancer?
Supraclavicular and neck lymph nodes
Can squamous cell carcinoma (SCC) metastasize to lymph nodes?
Yes, SCC can present with lymph node metastasis.
What is a common clinical presentation of lung cancer?
- Cough, hemoptysis (coughing blood), and weight loss
- Metastasis to other organs like the brain (delirium, falls), lymph node, bone, brain, liver and adrenals
How does lung cancer sometimes present with brain metastasis?
Brain metastasis can cause neurological symptoms (delirium, loss of balance, falls).
CT scan may reveal a tumor in both the brain and lungs.
What is a paraneoplastic syndrome?
A paraneoplastic syndrome is when lung cancer secretes hormones, leading to symptoms of diseases affecting other organs, even though the lung is not typically an endocrine organ.
what are examples of endocrine organs
the thyroid, pancreas or adrenal gland (secrete hormones)
what are example hormone that the lung can secrete ( making it similar to an adrenal gland)
- Adnocoticotropic hormone (ACTH) is a hormone produced by the anterior pituitary gland but can also be produced in some lung tumors (like small cell lung carcinoma). It stimulates the adrenal glands to produce cortisol, a hormone important for stress response, metabolism, immune function, and other vital processes. this is a feature of Cushing syndrome
What is one example of paraneoplastic syndrome in lung cancer?
Cushing Syndrome due to excessive ACTH secretion:
Symptoms: Obesity, moon face, high blood sugar.
Investigation: Adrenal glands are normal, but ACTH levels are high.
Chest X-ray can help identify the lung cancer causing this.
What hormone can be secreted by lung cancer, causing hyponatremia?
Antidiuretic hormone (ADH) leading to hyponatremia.
What other endocrine disorders are linked to lung cancer?
Hypercalcemia due to excess secretion of parathyroid hormone (PTH).
What physical signs may indicate lung cancer?
Finger clubbing and hypertrophic pulmonary osteoarthropathy.
What are some local effects of spread of lung tumours
- Pneumonia, lobar collapse : airway obstruction by tumour
- Pleural effusion : Tumour spread into pleura
- Pericarditis and cardiac tamponade: tumour spread to pericardium
- Paralysis of diaphragm: invasion of phrenic nerve
- Hoarseness of voice: Invasion into recurrent laryngeal nerve
- Horner syndrome : Invasion into sympathetic ganglia (miosis, ptosis, anhidrosis and enophthalmos)
- Rib destruction: Invasion into chest wall
- SVC syndrome: Compression of superior vena cava by tumour
How can lung cancer present as pneumonia?
- In older adults (50s-60s), if pneumonia does not improve with antibiotics, lung cancer may be the underlying cause.
- Chest X-ray may show a mass, which might mimic pneumonia.
- CT scan can help differentiate the two conditions.
How can lung cancer cause pleural effusion?
Pleural effusion can occur in lung cancer, along with other conditions like heart failure, pneumonia, or renal failure.
How can fluid analysis help diagnose lung cancer?
- Pleural effusion (fluid buildup around the lungs) is often analyzed in the cytology department to check for cancer cells.
- Cancer cells can sometimes be detected in pleural fluid, indicating metastasis or primary lung cancer.
- Fluid can come from different sources like the lung, bowel, breast, or GI tract.
What are some presenting features of lung cancer?
- Pleural effusion and fluid buildup are common, sometimes as the initial presenting symptom.
- In rare cases, pericarditis (inflammation of the heart lining) and cardiac tamponade (pressure around the heart) can occur due to tumor spread.
- Diaphragmatic paralysis may occur if the phrenic nerve is involved.
How can lung cancer affect the nervous system?
Brachial plexus involvement (nerves controlling the arms) or sympathetic ganglia can cause Horner’s syndrome, which presents as:
- Narrowing of the pupil (miosis)
- Drooping eyelid (ptosis)
- Dryness of the eye
- Sunken eye (enophthalmos)
- Sweating loss on the face (anhidrosis)
What happens if lung cancer invades the chest wall?
It can lead to rib fractures and pain or pressure on the chest wall.
What is superior vena cava syndrome?
Tumor pressure on the superior vena cava (large vein returning blood to the heart) can cause swelling in the upper body and congestion, often seen as a sign of advanced cancer.
What is adenocarcinoma in situ
a localised, small (< 30mm) growth restricted to neoplastic cells along pre existing alveolar structures ( lepidic growth) lacking stromal, vascular, alveolar space or pleural invasion or necrosis). they are non invasive tumours (don’t metastasis) and there are mucinous (rare)and non mucinous sub types
what is the cause for concern when you see a mucinous adenocarcinoma in situ
there is a chance that it could have come from another organ where mucnous epithelium / mucinous adenocarcinomas are
what are minimally invasive adenocarcinomas
a small ( less than or equal to 30mm in size), solitary adenocarcinoma with a predominantly lepidic growth pattern and less or equal to 5mm invasion (good prognosis). patients with tumours that meet this criteria for MIA should have 100% disease free and recurrence free survival if the tumour is completely resected
what should be absent in minimally invasive adenocarcinomas
- invasion of lymphatics, blood vessels or pleura
- tumour necrosis or
- spread through airspaces
What are the common patterns of adenocarcinoma?
Adenocarcinoma can present in various patterns, including:
Papillary structures
Lining of structures
Gland-forming patterns
Mucinous or non-mucinous features
Few or many glands, depending on the individual tumor and person
Where is adenocarcinoma typically found in the lungs?
Adenocarcinoma is typically found in the periphery of the lungs (and most common type of lung cancer in women and non smokers)
what is the adenocarcinoma charcterised by
acinar, papillary or lepidic growth patterns and or mucin production by tumour cells.
Where is squamous cell carcinoma typically found in the lungs?
Squamous cell carcinoma is typically seen towards the center of the lung.
How have trends in lung cancer types changed over the past 20 years?
Squamous cell carcinoma used to be more common, but with decreasing smoking rates, adenocarcinoma is now the more common type of lung cancer.
What genetic mutations are commonly associated with adenocarcinoma?
Adenocarcinoma is commonly associated with EGFR gene mutations. These mutations contribute to the development of the cancer.
How does an EGFR mutation impact adenocarcinoma treatment and prognosis
Patients with EGFR mutations have improved survival when treated with EGFR tyrosine kinase inhibitors.
How can squamous cell carcinoma be identified under the microscope
Squamous cell carcinoma is characterized by:
Keratin (appears pink under the microscope).
Intracellular bridges between cells.
Keratinization of the tumor cells.
What is the relationship between smoking and squamous cell carcinoma?
Squamous cell carcinoma is closely related to a history of smoking (most commonly found in men)
How is EGFR overexpression different from EGFR mutation in lung cancer?
In lung cancer, EGFR overexpression (not a mutation) can occur, particularly through amplification of the EGFR gene. This happens in about 80% of cases, as opposed to specific mutations seen in exons 19, 20, or tyrosine kinase inhibitor mutations.
What is the role of PD-1 monoclonal antibody in lung cancer treatment?
PD-1 monoclonal antibodies act as checkpoint inhibitors in second-line treatment. They block a signal that would normally prevent activated T-cells from attacking cancer cells, helping the immune system target and destroy neoplastic cells.
what is anti PD-1 monoclonal antibody also known as
Nivolumab
How do cancer cells evade the immune system, and how do checkpoint inhibitors help?
Cancer cells often block T-cells from targeting them through immune evasion mechanisms. Checkpoint inhibitors like PD-1 monoclonal antibodies block the signal that would prevent activated T cells, therefore allowing T-cells to become activated and target cancer cells effectively and clear them
what are large cell (undifferentiated carcinomas)
LCC is a diagnosis of exclusion in a surgically resected NSCC with no clear cut small cell carcinoma, SCC or adenocarcinoma in addition to giant cell, spindle cell or pleomorphic carcinoma on morphology or after immunohistochemistry and/or mucin stains.
what do large cell undifferentiated carcinomas comprise of
sheets / nests of large polygonal cells with vascular nuclei, prominent nuclei and moderate amounts of cytoplasm ( clear cell and / or rhabdoid cytological features may be present.
What are the challenges in diagnosing large cell undifferentiated carcinoma?
Large cell undifferentiated carcinoma is a diagnosis of exclusion. Pathologists previously used markers like TTF-1 (positive in adenocarcinomas) and CK 56/P63 (positive in squamous cell carcinoma) to differentiate, but now genetic testing helps to ensure correct diagnosis and treatment.
How can small cell carcinoma be differentiated from lymphocytes under the microscope?
Small cell carcinoma cells are larger than lymphocytes (three times larger), and have scanty or no visible cytoplasm. The cells may show moulding, where they overlap or mold into each other, a key feature of small cell carcinoma.
How aggressive is small cell carcinoma, and what is its typical clinical presentation?
Small cell carcinoma is a very aggressive tumor that often presents as metastasis (has the highest mutational burden among lung cancers) It constitutes about 20-25% of all lung cancers and has a strong association with smoking, similar to squamous cell carcinoma.
What is the relationship between small cell carcinoma and smoking?
Small cell carcinoma has a strong relationship with smoking, similar to squamous cell carcinoma. Smoking is a major risk factor for the development of this aggressive form of lung cancer.
What percentage of small cell carcinoma patients are smokers ?
99% of patients with small cell carcinoma are smokers. Only 1% of small cell carcinoma cases occur in non-smokers.
how do small cell carcinomas arise
It can arise either centrally in the bronchi or peripherally in the lungs.
what are the positive markers for small cell carcinomas
for neuro endocrine markers
How is small cell carcinoma treated, and what is its prognosis?
small cell carcinoma is not treated with surgery. It is treated with radiation or chemotherapy based on tumor size and patient condition.
Untreated survival: 6-17 weeks
Five-year survival after treatment: 5-10% due to resistance to treatment in later stages
Chemotherapy : Over time, small cell carcinoma may develop resistance to treatment, making it difficult to control. although it is typically sensitive to radiation and chemotherapy
What is the difference between carcinoid and atypical carcinoid tumors?
Carcinoid tumors: Low malignant potential, rarely metastasize, <3 mitoses, no necrosis.
Atypical carcinoid tumors: Show 3-11 mitoses, may have necrosis, and have a higher malignant potential.
Survival rates:
Carcinoid: 87% survival at 5-10 years
Atypical carcinoid: 56-35% survival at 5-10 years
What do carcinoid and atypical carcinoid tumors look like under the microscope?
Carcinoid tumors have granular, eosinophilic cytoplasm with round, pepper-like nuclei.
Atypical carcinoid tumors show more mitotic activity and may show necrosis.
What is the most common source of lung metastases, and how do they appear radiologically?
- The most common source of lung metastases is colorectal cancer but both carcinomas and sarcomas arising anywhere in the body may spread to the lung via blood or lymohatics
- Lung metastases typically appear as rounded, opaque, multiple nodules with irregular borders and a ground-glass appearance. These are often distinct from primary lung cancers, which may have different characteristics.
- often treated with surgery with visection of the tumour
nodules in the lung tumours
usually there are multiple discrete nodules (cannon ball lesions) scattered throughout all lobes, more commonly at the periphery
What are the treatment options for lung cancer?
Treatment depends on various factors, such as tumor type, size, location, stage, and the patient’s condition. The main treatment modalities include:
Surgery (if operable)
Chemotherapy
Radiotherapy
Immunotherapy
Targeted therapy
How does the treatment for small cell carcinoma differ from non-small cell carcinoma?
Small cell carcinoma is primarily treated with chemotherapy and radiation.
Non-small cell carcinoma may be treated with surgery (if operable) in addition to chemotherapy, depending on tumor size, location, and the patient’s condition.
What are the challenges in surgery for advanced lung cancer?
In cases of advanced lung cancer, especially with tumor involvement in the chest wall or other organs, surgery can be complex. Some surgeons, despite the aggressiveness of the cancer, might opt for radical surgery, including the removal of the chest wall, depending on the patient’s overall health and the feasibility of the procedure.
What factors determine the treatment approach for lung cancer?
Treatment depends on several factors, including:
Tumor type (small cell vs non-small cell)
Size and location of the tumor
Stage of cancer (how advanced it is)
Patient condition (health and fitness to undergo treatment, ability to afford therapies)
what are the different stages of lung cancer
T1 tumour : less or equal to 3cm, surrounded by lung or pleura. no tumour more proximal than lobe bronchus
T2 tumour : larger than 3cm, involving main bronchus. 2 or more cm distal to carina, invading pleura, atelectasis or pneumonitis extending to hilum but not entire lung
N1L Involvement of ipsilateral peribronchial or hilar nodes and intra, pulmonary nodes by direct extension
T3 tumour: invasion of chest wall, diaphragm mediastinal pleura, pericardium, main bronchus and less than 2cm distal to carina, atelectasis or pneumonitis of entire lung
N2 involvement ipsilateral mediastinal or subcarinal nodes
N3: Involvement of contralateral (lung) nodes or any supraclavicular node
T4 tumour: Invasion of mediastinum, heart great vessels, tracheam esophagus, vertebral body, carina ..
Who is involved in a multidisciplinary meeting to decide the treatment for lung cancer patients?
The team includes radiologists, pathologists, oncologists, surgeons, physicians, and nurses, all of whom contribute to deciding the best treatment based on patient needs and circumstances.
What is the treatment for localized non-small cell lung cancer (NSCLC)?
Surgery followed by chemotherapy.
If the patient is not surgical:
Radiotherapy to the affected area, sometimes combined with chemotherapy (called chemoradiotherapy).
What is the treatment for metastatic non-small cell lung cancer?
For metastatic NSCLC, the treatment includes:
Chemotherapy
Immunotherapy
Additionally, genetic studies may help identify specific mutations and allow for targeted treatment.
How is small cell lung cancer treated?
Small cell lung cancer is treated with chemotherapy, either alone or in combination with radiotherapy or immunotherapy.
What is pleural mesothelioma, and how common is it?
Pleural mesothelioma is a rare cancer that accounts for less than 2% of malignancies. Abdominal mesothelioma is even rarer.
- It has a poor prognosis, with 50% of patients dying within 12 months of diagnosis. Only a few survive beyond two years.
- There are specialized centers that attempt to treat it, but success is limited, particularly in well-differentiated mesothelioma cases.
Risk Factors for Mesothelioma
- Asbestos exposure: Common in industries like shipping, especially in coastal areas. 90% of mesotheliomas are related to asbestos.
- Unite fiber exposure: Found in areas like the Cappadocia region of Turkey and rural parts of Mexico.
- Genetic mutations: Specific mutations in CDKN2A, BAP1, and TP53 tumor suppressor genes increase the risk.
How is mesothelioma diagnosed?
Cytology: Shows malignant mesothelial cells (positive for EMS staining in malignant cells).
Genetic markers: BAP1 and MTP markers help confirm the diagnosis.
Asbestos exposure and genetic mutations together increase the likelihood of mesothelioma.
What are the common symptoms of mesothelioma?
Patients typically present with:
- Dyspnea (difficulty breathing)
- Unilateral chest pain or discomfort
- Cough
- Unexplained weight loss
- Low-grade fever and night sweats (similar to tuberculosis symptoms).
- On chest X-ray, diffuse thickening of the pleura surrounding the lung is often seen.
How does mesothelioma appear on an X-ray?
On X-ray, mesothelioma typically shows extensive pleural thickening that encircles the lung, often involving the chest wall, diaphragm, and even skin. It may follow the fissure between the lungs. This is an extreme form and almost certainly indicates mesothelioma.
What are the stages of development of mesothelioma?
- Initial Stage: Fibrous plaques form.
- Atypical Mesothelial Proliferation: Abnormal mesothelial cells appear.
- Mesothelioma Formation: The cancer develops and gradually enlarges, encircling the lung and spreading to surrounding tissues like the chest wall and diaphragm.
What are the different types of mesotheliomas?
Mesotheliomas can be classified into:
- Epithelioid
- Sarcomatoid
- Biphasic (containing both epithelial and sarcomatous components).
Biphasic is easier to identify as it is rare and distinct from other tumors like anovial sarcoma or mixed Müllerian tumors.
What are the challenges in diagnosing mesothelioma, especially in biphasic forms?
- Epithelioid mesothelioma can be confused with carcinoma.
- Spindle cell elements can be mistaken for sarcoma.
- Diagnosis is challenging, but certain markers help, such as:
- Positive: CK 56, WT1, and BIP4 (mesothelioma).
- Negative: BIP4 and TTF1 (indicates carcinoma).
- If BIP4 or TTF1 is positive, it’s carcinoma; if CK 56, WT1 are positive, it’s mesothelioma.
How was electron microscopy used to diagnose mesothelioma in the past?
Electron microscopy showed long, slender villi in mesotheliomas, compared to the short villi found in adenocarcinomas. This method was used for diagnosis before the advent of immunohistochemistry.
What is the prognosis for mesothelioma?
- 50% of mesothelioma patients die within 12 months of diagnosis.
- Very few survive beyond two years despite treatment advancements.
How has lung cancer classification evolved, and what impact does targeted treatment have?
- Historically, lung cancer was classified as small cell vs non-small cell.
- Now, genetic analysis and specific subtyping (especially in adenocarcinoma) are used for treatment, leading to personalized medicine.
- This has improved the prognosis, especially in adenocarcinoma cases, offering hope for better outcomes in the future.
How does the prognosis of lung cancer compare to mesothelioma?
- Lung cancer has better treatment options, and patients have a chance of improved survival with personalized medicine.
- In contrast, mesothelioma has a poor prognosis, with a high mortality rate within 12 months and very few surviving longer than two years, despite treatment advancements.
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