Lung malignancy Flashcards
Most common cancer and cancer death in both males and female
LUNG cancer
Risk Factors of Lung cancer
SMOKING
one gentic mutation is induced for every 15 cigarettes smoked
The best known risk factor in developing ANY cancer
AGE
High associated with lung cancer and mesothelioma
Asbestos
Cancer development
Genetic and Environmental factors
Polymorphic variations in the genes…
p53 and retinoblastoma suppressor gene expression
The process when carcinogen confers a genetic change on the normal cell
Initiation
Happens when those genetic changes confers a growth advantage on the cell over its neighboriing cells
Promotion
Lung cancer gene mutations
EGFR - cancer susceptibility to never smokers
P450 enzyme system specifically CYP1A1
RB
p53 *Li-Fraumeni syndrome) - 1st degree relatives of lung CA
Hallmarks of Cancer
Self sufficiency in growth signals
Insensitivity to antigrowth signals
Tissue invasion and metastasis
Limitless replicative potential
Sustained angiogenesis
Evading apoptosis
Avoidance of host immune system
Tumor promoting inflammation involved
Develop ability to deregulate cellular energetics
Develop genomic instability
Epithelial tumors of the lung counts for 90% of epithelial tumors of the lung counts for 90% of epithelial tumors
Bronchogenic carcinoma
NSCLC type
Adenocarcinoma
SQCCA
Large cell CA
Account for 90% of all epithelial cancers
Squamous cell lung CA
Typically central and close to carina
Frequently presenting with bronchial obstruction and hemoptysis
Highly associated with cigarette smoking
More common in men than in women
areas of squamous metaplasia
MOST frequent histologic subtype of NSCLC
Adenocarcinoma
Contains sheet of cells rather than 3D group of cells as with the case of adenocarcinoma
Squamous cell carcinoma
Possess a glandular differentiation or mucin production
Typically peripheral, sometimes originating in areas of pre-existing lung scarring
Adenocarcinoma
Most common histology found in never smokers, and also in women
Adenocarcinoma
Adenocarcinoma may manifest as:
Adenocarcinoma in situ
Minimally invasive
Invasive
Main histological patterns of adenocarcinoma
Acinar - gland like spaces
Papillary - leaf like thin septa
Solid carcinoma with mucin production - Poorly differentiated
Lepidic mixed subtype tumors with non-mucinous bronchioalveolar CA
Micropapillary
Marker for adenocarcinoma
TTF 1 or napsin A
marker for squamous CA
p40 or p63 and/or mucin stains
Lung adenocarcinomas can arise when tumorrs express this mutant gene
EGFR
What type of cells have the capacity to give rise to adenocarcinoma
Type II epithelial cells
LArge malignant cells without evidence of squamous of glandular differentiation
Large cell CA
Macroscopic features of large ccell CA
Peripheral
maybe central
Histological features of large CA
Large malignant cells that lack the cytologic and architectural features of small cell CA and glandular or squamous differentiation
Undifferentiated/oat cell Carcinoma
Squamous cell CA
Histological characteristic of small cell CA
salt and pepper pattern (Very scant cytoplasm, small, hyperchromatic nuclei with a fine chromatin pattern and absent/inconspicuous nucleoli
Cell of origin for small cell carcinoma
Kulchitsky cells
Type of cancer that secrets a lot of polypeptide hormones such as ACTH, AVP, ANF, and GRP
Small cell Carcinoma
Lung cancer associated with a lot of paraneoplastic syndromes
small cell CA
Clinical signs of lung malignancy
Cough (80%) Hemoptysis (70%) Dyspnea (60%) Chest pain (40%) Recurrent or slowly resolving pneumonia Constitutional signs Cachexia Supraclavicular or axillary LAD Tender ribs
Signs of Mediastinal compression
SVC syndrome
- facial edema, NVE, plethora, dysphagia, dyspnea
Facial edema Telagiectasia Hypotension latter part Flushing Neck vein engorgement
A tumor that occupies the apex of the lung might affect the nerve specifically ulnar nerve which can result to arm pain
Pancoast Tumor
C8, T1 and T2
Metastatic signs and symptoms
Bone Pain and tenderness
hepatomegaly and jaundice
Confsuion and neurologic signs
Nausea, vomiting, headache
Hypertrophic Pulmonary Osteoarthropathy
Clubbing
Periostitis
commonly found in small cell lung CA
swelling pain
Hypercalcemia (PNPS)
most common oncologic emergency
Increase PTH
Paraneoplastic syndrome
hypercalcemia Cushing's syndrome Carcinoid syndrome Gynecomastia Hypoglycemia
Carcinoid syndrome (serotonin)
Irregular mottled blushing Flat angiomas of the skin Acquired tricuspid and pulmonary stenosis Diarrhea Bronchial Spasm Mental aberratiion Excretion of large quantities of 5-HIAA
Neurological syndrome found in small lung CA
Eaton-lambert syndrome
Progressive proximal muscle weakness in the absence of dermatomyositis
Eaton-Lambert Syndrome
Migrating venous thrombophlebitis
Trousseau syndrome
Establishes a cytologic and/or histologic diagnosis in 80-85% of centrally located lesions
Bronchoscopy
Four types of specimens
Bronchial brush
Bronchial washing
Bronchoalveolar lavage
transbronchial FNAB - most sensitive
May diagnose up to 90% of peripheral lung cancers
CT guided transthoracic needle biopsy
Provides not only histologic dx but also important staging information
Mediastinoscopy
Scan good for staging
PET Scan
Checks for the level of glucose metabolism by cells
PET
- uses FDG 18
- uses scorring called standardized Uptake Values
Tumor component (2018)
< = 1 cm =T1a >1-2 cm = T1b >2-3cm = T1c >3-4 cm = T2a >4-5cm = T2b >5-7 cm = T3 >7 cm = T4
M component (2018)
Within the thoracic = M1a
Single extrathoracic = M1b
Multiple extrathoracic = M1c
Node invovlement
N0 = no nodes N1 = ipisilateral bronchopulmonary N2 = Ipsilateral or subcarinal N3 = contralateral hilar/mediatinal and ipsilateral
Treatment for Lung CA
I - Cure
II - Cure
III and IV - Control of local disease and increase length of survival
Surgical treatment
Wedge resection - not form small cell CA
Lobectomy - small tumors
Pneumonectomy - large tumors
Backbone of CRx treatment
Cisplatin/Carboplatin
Anti EGFR
Gefitiib - forst approved tyrosine kinase inhibitor
Erlotinib - 1st-3rd line tx of metastatic NSCLC
Afatinib - 2nd generation tyrosine kinase inhibitor
Ceftuximab
ALK inhibitors
Crizotinib - targets EML4/ALK fusion protein
Ceritinib
Alectinib
Bevacizumab
VEGF inhibitor
Immunotherapy
PD-1/PD-L1 interaction
-mediates inhibition of T cell mediated tumor cell killing and inhibition of T cell activation
nivolumab, pembrolizumab
