Lung Cancer Flashcards
Hamartoma
“coin lesion” and consists of mature cartilage admixed with fat, fibrous tissue, and blood vessels
Inactivation of what gene is a common early event? What gene inactivation are late events?
Inactivation of the tumor suppressor genes located on the short arm of chromosome 3 (3p) is a very common early event. Mutations of the TP53 tumor suppressor gene and the KRAS oncogene occur relatively late.
Loss of chromosomal material on 3p, are found even in benign bronchial epithelium of smokers without lung cancer.
Adenocarcinomas in non-smoking women contain mutations that activate what?
Activate the EGFR receptor. EGFR stimulates downstream pro-growth pathways involving RAS, PI3K, and other signaling molecules.
Commonly seen in non-smoking Asian women.
How are chemicals converted into carcinogens?
Chemicals require metabolic activation via the P-450 monooxygenase enzyme for conversion into carcinogens. Individuals with P-450 polymorphisms have an increased capacity to activate procarcinogens.
What are BASCs?
Bronchioalveolar stem cells (BASCs) facilitate epithelial regeneration. After lung injury, multipotent BASCs proliferate and replenish the normal cell types (bronchiolar Clara cells and alveolar cells).
Postulated that BASCs incur the initiating hit that enables these cells to escape normal “checkpoints”
Pattern of epithelial changes:
Basal cell hyperplasia and squamous metaplasia –> squamous dysplasia and carcinoma in situ –> invasive cancer
What is the precursor to adenocarcinoma?
AAH (atypical adenomatous hyperplasia) = epithelial proliferation composed of cuboidal to low-columnar cells that demonstrate nuclear hyperchromasia, pleomorphism, and prominent nucleoli.
Progression to adenocarcinoma:
AAH –> adenocarcinoma in situ –> minimally invasive adenocarcinoma (<3 cm in diameter with an invasive component of <5 mm) –> invasive adenocarcinoma (a tumor of any size with an area of invasion >5 mm)
What serves as a scaffold for adenocarcinoma in situ growth?
Alveolar septa
Where does squamous cell carcinoma arise? Where does it spread?
Arise centrally in major bronchi and eventually spread to local hilar nodes.
What proceeds squamous cell carcinoma?
Squamous metaplasia or dysplasia in the bronchial epithelium, which then transforms to carcinoma in situ, a phase that may last for several years.
What are the two neuroendocrine cell lung cancers? What do they stain positive for?
Small cell (poor differentiated)
Carcinoid (well differentiated)
Stain positive for chromogranin.
“Crush artifact”
Small cell carcinoma
Nuclear molding
SCC: resulting from close apposition of tumor cells that have scant cytoplasm
Typical patterns of syndromes for cancer types:
Squamous cell neoplasms = Hypercalcemia
Adenocarcinomas = Hematologic syndromes
Small cell carcinomas = Neurologic syndromes
Bronchial carcinoids normally occur in what population? Where do most of them occur?
Young adults. They occur in the main bronchi.
SCC stains positive for what?
Chromogranin A
Neuron-specific Enolase
Synaptophysin
Bronchial carcinoid cancers also stain positive for these.
Hypertrophic osteoarthropathy is associated with which type of lung cancer?
Adenocarcinoma. Digital clubbing and sudden-onset symmetrical arthropathy, usually involving the wrist and hands.
Adenocarcinomas stain positive for mucin. In order to demonstrate intracellular mucin what stains must be used?
PAS or Mucicarmine
Lambert-Eaton Syndrome is most associated with?
Small cell lung cancer
What type of cancer can secrete beta-HCG?
Large cell carcinoma. Can lead to very high levels of estrogen and painful gynecomastia (breast enlargement) in males as paraneoplastic signs
What genetics are associated with adenocarcinoma?
EGFR, ALK, KRAS mutations
EGFR & ALK = receptor tyrosine kinases
KRAS = GTPase
What is associated with migratory thrombophlebitis, Trousseau’s sign, and murantic endocarditis, and DIC?
Adenocarcinoma.
What is associated with hypertrophic pulmonary osteoarthropathy?
Adenocarcinoma and other NSCLC.
Medical condition combining clubbing and periostitis of the small hand joints, especially the distal interphalangeal joints and the metacarpophalangeal joints. Distal expansion of the long bones as well as painful, swollen joints and synovial villous proliferation are often seen.
Clubbing and increased bone deposition on long bones. Do a bone scan and radiograph.
Adenocarcinomas will have either of what three structures?
Mucin, Glands, or Papillary structures.
Large Cell Carcinoma: Large _____ undifferentiated carcinoma cells with _______ _________.
Large undifferentiated carcinoma cells with prominent nucleoli. Also have abundant cytoplasm.
Mutations associated with SCC?
TP53, RB, MYC, 3p deletion.
Which lung cancer has cells without nucleoli?
SCC. They also have scant cytoplasm.
SVC vs. Pancoast Tumor
SVC = usually SCLC
Pancoast = usually NSCLC
Most carcinogenic asbestos fiber and less carcinogenic fiber?
Crocidolite (amphibole) most carcinogenic.
Chrysotile (serpentile) less carcinogenic.
Inactivation of what tumor suppressor genes are associated with mesothelioma?
BAP1 and CDKN2/INK4a.
What two lung carcinomas have microvilli?
Mesothelioma = long microvilli
Adenocarcinoma = short microvilli
