Lung cancer
Epidemiology
Lung cancer is the most common cause of death by cancer, accounting for 1.8 million
deaths annually (and 2 million new cases). It largely occurs after age 40; recently there
has been an increase of cases in women due to increased smoking whilst male rates have
stabilized.
Etiology and risk factors
- Smoking: 90% cases, increases risk 10-fold. Highest risk in people with chronic
inflammation (COPD) and in people with P-450 polymorphisms due to the
activation of mutagenic carcinogens in smoke. Smoking cessation decreases risk
that however never returns to baseline.
- Radon: radioactive gas in the ground (contains alpha-particles) causing DNA
damage
- Air pollution: lung inflammation
- Exposure to arsenic, metal, fibers, dusts
- Household coal combustion
- Endogenous: genetic predisposition, first degree relatives with lung cancer (2-3x
risk), female sex, age.
Classification (WHO)
Based on H&E staining, mucin assessment, radiology, IHC, Genetics.
- NSCLC (85%): diagnosed at advanced stages in 70% cases.
o Adenocarcinoma (50%): expression of TTF1, glands and mucin
o Large cell carcinoma (2%): neuroendocrine
o Squamous cell carcinoma (20%): expression of p40, keratinizing features
o NOS: in between squamous and adenocarcinoma
- SCLC (15%).
There is a need for molecular characterization of non-squamous NSCLC by testing for
predictive markers with NGS because of the new targeted therapies available.
Characteristic features
Samples are collected with EBUS FNA, to allow mediastinal lymph node staging, FNA of
primary tumor, rapid on site evaluation and generation of paraffin blocks for IHC testing.
EBUS-FNA is mainly used for central lesions, whilst percutaneous biopsy, CT or US
guided, is used to evaluate peripheral lung cancers.
1. Adenocarcinoma: most common NSCLC, malignant epithelial tumor possessing
glandular differentiation, mucin production or pneumocyte marker expression.
Most common in non-smokers and women (most common lung cancer in
Asians). Usually located in the periphery.
Microscopy: cytologically we see very large nuclei, abundant cytoplasm, and
intracytoplasmic vacuoles with mucin; histologically only a sold pattern is visible. May
, see a mucus cap in lepidic-type adenocarcinoma (bronchioalveolar). Usually develops
from precursor lesion atypical adenomatous hyperplasia that may last for many years;
eventually the tumor may penetrate the wall of the bronchus and peri-bronchial tissue,
leading to obstruction of major bronchi, becoming symptomatic with atelectasis and
pneumonia. Lesions are small in size and grow slowly even though they are highly
aggressive.
Subtypes of AD:
- Acinar: small glands infiltrate the stroma, forming a lumen. Intermediate
prognosis.
- Solid: mucin formation, cells indent the nucleus, pushing the cell membrane.
Poor prognosis.
- Papillary: fibrovascular core (finger-like projections) covered by epithelial
neoplastic cells. Intermediate prognosis.
- Micropapillary: cells attached one to another protruding into an empty space, no
fibrovascular core present. Poor prognosis.
- Lepidic: subtype of adenocarcinoma arising in the terminal bronchioalveolar
region is known as bronchioalveolar or with lepidic growth (1-9% cases): growth
resembles that of a normal alveolus due to dissemination of neoplastic cells
along the alveolar walls. Neoplastic cells grow in a scale-like pattern, filling the
alveolar space, eventually infiltrating >5mm and usually also having a mucinous
component in the invasive phase. Good prognosis if non-mucinous.
IHC: TTF1 positivity, mucin can be stained with H&E but also with mucicarmine (purple).
The tumor is characterized by mutations in KRAS, EGFR, RB1, p16 and ALK.
Metastasis occurs via both lymphatic and hematogenous spread, commonly affecting
the adrenal glands, liver, brain and bone. This cancer is associated with better
prognosis because there is no stromal, vascular or pleural invasion.
2. Squamous cell carcinoma: most common lung cancer in males, strong
correlation with smoking Usually located in the central hilar region (upper lobes).
Microscopy: cytologically and histologically we see keratinization and intercellular
bridges (diagnostic). Often arise in setting of precursor lesions like squamous
metaplasia or dysplasia in the bronchial epithelium. Tumor growth is exophytic, with
production of an intraluminal mass, eventually obstructing the bronchus causing distal
atelectasis and infection → hemoptysis may occur and sputum examination may reveal
cancer cells that were shed.
Grossly: gray-white, firm mass, with focal areas of hemorrhage and necrosis with
possible cavitations.
IHC: CK5-6 positivity (orange stain), p40 expression (truncated p63), p53 mutations
3. Small cell carcinoma: highly malignant, deadliest lung cancer with 3 month
survival if untreated, almost exclusively in smokers. Usually located centrally,
widely metastatic at presentation and surgically incurable. May be associated
with ectopic hormone production and paraneoplastic syndromes.
Epidemiology
Lung cancer is the most common cause of death by cancer, accounting for 1.8 million
deaths annually (and 2 million new cases). It largely occurs after age 40; recently there
has been an increase of cases in women due to increased smoking whilst male rates have
stabilized.
Etiology and risk factors
- Smoking: 90% cases, increases risk 10-fold. Highest risk in people with chronic
inflammation (COPD) and in people with P-450 polymorphisms due to the
activation of mutagenic carcinogens in smoke. Smoking cessation decreases risk
that however never returns to baseline.
- Radon: radioactive gas in the ground (contains alpha-particles) causing DNA
damage
- Air pollution: lung inflammation
- Exposure to arsenic, metal, fibers, dusts
- Household coal combustion
- Endogenous: genetic predisposition, first degree relatives with lung cancer (2-3x
risk), female sex, age.
Classification (WHO)
Based on H&E staining, mucin assessment, radiology, IHC, Genetics.
- NSCLC (85%): diagnosed at advanced stages in 70% cases.
o Adenocarcinoma (50%): expression of TTF1, glands and mucin
o Large cell carcinoma (2%): neuroendocrine
o Squamous cell carcinoma (20%): expression of p40, keratinizing features
o NOS: in between squamous and adenocarcinoma
- SCLC (15%).
There is a need for molecular characterization of non-squamous NSCLC by testing for
predictive markers with NGS because of the new targeted therapies available.
Characteristic features
Samples are collected with EBUS FNA, to allow mediastinal lymph node staging, FNA of
primary tumor, rapid on site evaluation and generation of paraffin blocks for IHC testing.
EBUS-FNA is mainly used for central lesions, whilst percutaneous biopsy, CT or US
guided, is used to evaluate peripheral lung cancers.
1. Adenocarcinoma: most common NSCLC, malignant epithelial tumor possessing
glandular differentiation, mucin production or pneumocyte marker expression.
Most common in non-smokers and women (most common lung cancer in
Asians). Usually located in the periphery.
Microscopy: cytologically we see very large nuclei, abundant cytoplasm, and
intracytoplasmic vacuoles with mucin; histologically only a sold pattern is visible. May
, see a mucus cap in lepidic-type adenocarcinoma (bronchioalveolar). Usually develops
from precursor lesion atypical adenomatous hyperplasia that may last for many years;
eventually the tumor may penetrate the wall of the bronchus and peri-bronchial tissue,
leading to obstruction of major bronchi, becoming symptomatic with atelectasis and
pneumonia. Lesions are small in size and grow slowly even though they are highly
aggressive.
Subtypes of AD:
- Acinar: small glands infiltrate the stroma, forming a lumen. Intermediate
prognosis.
- Solid: mucin formation, cells indent the nucleus, pushing the cell membrane.
Poor prognosis.
- Papillary: fibrovascular core (finger-like projections) covered by epithelial
neoplastic cells. Intermediate prognosis.
- Micropapillary: cells attached one to another protruding into an empty space, no
fibrovascular core present. Poor prognosis.
- Lepidic: subtype of adenocarcinoma arising in the terminal bronchioalveolar
region is known as bronchioalveolar or with lepidic growth (1-9% cases): growth
resembles that of a normal alveolus due to dissemination of neoplastic cells
along the alveolar walls. Neoplastic cells grow in a scale-like pattern, filling the
alveolar space, eventually infiltrating >5mm and usually also having a mucinous
component in the invasive phase. Good prognosis if non-mucinous.
IHC: TTF1 positivity, mucin can be stained with H&E but also with mucicarmine (purple).
The tumor is characterized by mutations in KRAS, EGFR, RB1, p16 and ALK.
Metastasis occurs via both lymphatic and hematogenous spread, commonly affecting
the adrenal glands, liver, brain and bone. This cancer is associated with better
prognosis because there is no stromal, vascular or pleural invasion.
2. Squamous cell carcinoma: most common lung cancer in males, strong
correlation with smoking Usually located in the central hilar region (upper lobes).
Microscopy: cytologically and histologically we see keratinization and intercellular
bridges (diagnostic). Often arise in setting of precursor lesions like squamous
metaplasia or dysplasia in the bronchial epithelium. Tumor growth is exophytic, with
production of an intraluminal mass, eventually obstructing the bronchus causing distal
atelectasis and infection → hemoptysis may occur and sputum examination may reveal
cancer cells that were shed.
Grossly: gray-white, firm mass, with focal areas of hemorrhage and necrosis with
possible cavitations.
IHC: CK5-6 positivity (orange stain), p40 expression (truncated p63), p53 mutations
3. Small cell carcinoma: highly malignant, deadliest lung cancer with 3 month
survival if untreated, almost exclusively in smokers. Usually located centrally,
widely metastatic at presentation and surgically incurable. May be associated
with ectopic hormone production and paraneoplastic syndromes.
