Path: lung CA Flashcards
1
Q
Squamous cell CA 1
A
- Arises from cigarette smoking, squamous metaplasia-> dysplasia-> CIS-> malignant squamous CA
- Grossly the lung is firm white/gray w/ central masses that involve the bronchial wall or protrude into the bronchial lumen
- Usually masses are surrounded by zone of yellow parenchyma which can produce obstructive (cholesterol) pneumonia
- Micro characteristics: keratinization and intracellular bridges
2
Q
Squamous cell CA 2
A
- Large eosinophilic cells w/ keratin pearls and intracellular bridges (desmosomal junctions btwn tumor cells)
- Pathogenesis: smoke, arsenic exposure, HPV all considered risk factors
- Usually found in large airways (central), pts present w/ cough, hemoptysis, obstructive PNA, lung abscesses, and bronchiectasis
- Cavitation of tumors can occur, and tumors tend to stay in chest cavity
3
Q
Adenocarcinoma 1
A
- Glandular differentiation or mucin production, characterized by acini, papillary, and/or solid (w/ mucin production) growth patterns
- Grossly the tumors are usually peripheral, w/ puckering of the overlying pleura (fibrotic retraction)
- Tumors are white/gray and show anthracitic pigment and gray fibrosis in center
- Micro: can be one or a mixture of acini (glands/tubules w/ mucus producing clara cells), papillae (growing stalks), or solid (sheets of cells and mucin containing vacuoles)
4
Q
Adenocarcinoma 2
A
- Mucin production is common and must be present in solid tumors for the Dx
- Most common primary lung CA, usually in periphery of lung
- Relation to smoking not as great as other lung CA
- Distant metastases are common, poor prognosis (stage most important prognostic factor)
5
Q
Adenocarcinoma in situ
A
- Well-differentiated adenoCA arising in periphery of lung and grows upon the surface of alveolar walls (lepidic growth)
- By definition the tumor is <3cm and non invading
- Can either by non-mucinous or mucinous (most are non-mucinous)
- Neoplastic cells are clara and type 2 cells
6
Q
Adenocarcinoma lepidic predominant
A
- Looks the same as adenocarcinoma in situ but are >3cm
- More likely to be invasive
- Can be glandular, acinic, tubulo-papillary, or solid nests
- Typically accompanied by desmoplastic rxn as well as cytologic atypia
7
Q
Small cell CA
A
- Very aggressive w/ lots of necrosis and mitotic figures
- May form nests and ribbons, cells have scant cytoplasm and hyper chromatic nuclei
- Nuclear molding can be found: one nucleus indents the nucleus of a neighboring cell
- Basically a sea of nuclei (looks like oats)
- 100% of these tumors will show keratin w/in tumor cells and e- microscopy shows dense core granules in cytoplasm
8
Q
Clinical presentation of small cell CA
A
- Strongly associated w/ smoking, usually located proximally and in large airways
- Tumors grow rapidly and metastases are common
- Some can cause paraneoplastic syndromes, including SIADH, ectopic cushiness, and eaton-lambert myasthenic-like syndrome
9
Q
Large cell CA
A
- Undifferentiated large cell CA that fails to show squamous or glandular differentiation or extensive mucin secretion
- Tumor cells grow in sheets and have abundant cytoplasm and large lucent nuclei w/ prominent nucleolus
- Most tumors are peripheral and can invade pleura and chest wall
10
Q
Carcinoid tumor
A
- Characterized by nests, trabecular, palisading, and ribbon arrangements w/ highly vascularized stroma
- Can be typical carcinoid (better prognosis, 2 mitoses/10HPF)
- Cells display abundant chromogranin and synaptophysin
- Tumors can be central or peripheral, are prone to bleeding (hemoptysis) especially during bronchial biopsy
- Precursor to small cell CA
11
Q
Molecular alterations of adenocarcinomas
A
- Can be EGFR, ALK, or Ras
- EGFR mutations are responsive to certain tyrosine kinase inhibitors (gefitinib, erlotinib)
- These tumors show a lepidic pattern and usually occur in never-smoking asian women
- Ras mutations common in smokers and usually related to differentiated mutinous adenoCA
- ALK associated w/ anapestic large cell lymphoma, which occur in younger pts who never have smoked and have higher stage of solid tumors
- ALK mutated tumors also can respond to TKIs
- These tumors often show signet ring cells w/ abundant intracellular mucin
12
Q
Lung CA epidemiology
A
- # 2 CA incidence for both sexes, #1 CA killer for both sexes
- Risk factors: smoking (synergistic w/ other risk factors), radon (basement cracks), silicosis (coal miners), COPD, HIV
13
Q
Lung CA classification
A
- 20% are small cell CA (SCLC), either limited stage (fits w/in one radiation port) or extensive stage (doesn’t fit in one radiation port)
- 80% are non small cell (NSCLC): mostly adenoCA and squamous CA
- Rx for SCLC is non surgical (chemo, radiation) and has poor prognosis
- Rx for NSCLC is surgic from stages 1-2, then non surgical from stages 3-4
- Staging is most important factor for prognosis
14
Q
Rx for SCLC
A
- Limited stage SCLC: tries to cure using radiation and chemo
- Extensive stage: cannot cure, palliative radiation and chemo
15
Q
Rx for NSCLC
A
- Stage 1: curative surgery only
- Stage 2: curative surgery + chemo
- Stage 3: curative chemo and radiation
- Stage 4: will not cure, palliative radiation and chemo
16
Q
Determining stage
A
- Look for complete resectibility: stage 1 when solitary tumor that is <3cm
- Look for end stage metastasis: stage 4 when there is metastases outside of chest, malignant pleural or pericardial effusion, contralateral lobe satellite nodules
- Look for stage 3: either anywhere on contralateral side, ipsilateral LN involvement that is bulky/large, or severe invasion (hearth, great vessels, carina, spine)
17
Q
Clinical presentation of squamous cell
A
- Mostly smokers, lesions likely to cavitate, located centrally
- Often endobronchial: atelectasis/lobar collapse, wheezing, hemoptysis
- DOES cause hypercalcemia as paraneoplastic syndrome, due to PTHrp excess (small cell doesn’t cause hypercalcemia as a paraneoplastic syndrome)
18
Q
Clinical presentation of adenocarcinoma
A
- Often found in NON smokers, associated w/ EGFR, ALK mutations
- Starts off peripherally and no central obstructive Sx, can lead to pleural effusions (spreads to chest wall)
- More likely than squamous cell to have metastasized on presentation
- More likely to have copious sputum production (bronchorrhea)
19
Q
Clinical presentation of small cell CA
A
- Mostly in smokers, central location often involving airways (wheezing, hemoptysis, obstructive Sx)
- Extensive mediastinal LAD, 70% already widely metastasized
- Associated w/ many paraneoplastic syndromes (cushiness, SIADH, eaton-lambert)
- Highest response to chemo/radiation due to high metabolic rate but poorest prognosis
20
Q
Clinical presentation of carcinoid tumors
A
- On endobronchioscopy the tumor looks round, polypoid, and friable
- Typical carcinoid lacks mitotic figure, but there are many in atypical
- Surgery is 1st line Rx
21
Q
Paraneoplastic syndromes 1
A
- SIADH (hyponatremia, concentrated urine), cushings (HTN, hypokalemia), dermatomyositis (weakness, skin changes, heliotropic rash, Gotran’s papules), eaton-lambert (proximal muscle weakness that gets stronger w/ exercise) all associated w/ SCLC
- Note: carcinoid tumors can do “anything SCLC can do”
- Difference btwn myasthenia gravis and eaton-lambert: MG is autoAb against nicotinic receptors (pts get weaker w/ exercise), EL is autoAb against Ca channels (pts get stronger w/ exercise
22
Q
Paraneoplastic syndromes 2
A
- Paraneoplastic syndromes NOT seen in SCLC:
- Hypercalcemia:seen in squamous cell due to PTHrp production
- Hypertrophic pulmonary osteoarthropathy (HPO) which is painful swollen joints/bone from endocrine effect (NOT metastases) is seen in adenoCA
- Gynecomastia (large breasts) seen in large cell CA
23
Q
Compression syndromes
A
- SVC compression (SCLC, NHL): mostly seen on upper R lobe tumors, pt has arm, neck and head swelling due to SVC compression
- May be ASx if tumor is slow growing and collaterals have formed (in this case not an emergency)
- Pancoast tumor syndrome (NSCLC, often squamous): superior sulcus (apical) tumors can compress surrounding nerves and cause flushing and hornet’s syndrome, shoulder pain, ulnar nerve compression, upper lobe collapse
- Nerve compression: phrenic nerve compression leads to dyspnea and elevated hemidiaphragm, hoarseness usually from L sided tumors compressing recurrent laryngeal nerve
24
Q
Single pulmonary nodule
A
- Single nodule <3cm in size surrounded by aerated lung and absence of other pathologies
- Now the definition includes sub centimeter nodules and non-solid or semi-solid nodules
25
Q
Role of PET in NSCLC
A
- PET scans are imperfect for detecting primary tumors and mediastinal LAD mets
- They are great for detecting extra thoracic mets (bone, liver, adrenal)
- PET cannot rule in or rule out cancer b/c of poor specificity (high false positive rate)
- Thus PET will not change course of Rx in a high-risk pt, they will still undergo surgery and resection anyway
- PET will only be helpful in the intermediate-risk pt, to help guide management
- Do NOT order PET when: high risk or low risk pt, or when there is suspected infection/inflammation
26
Q
Basics of NSCLC Rx
A
- Surgery is curative, but surgery only done in stage 1 and 2 pts
- Stage 2 pts need adjunctive radiation/chemo
- Stage 3 chemo + radiation aims to cure, where as stage 4 Rx is palliative
- If genetic mutant (EGFR, ALK) tyr kinase inhibitors (TKIs) are fist line Rx when stage 4 and adjunctive when stage 3
- TKI for EGFR is Tarceva, TKI for ALK is Crizotinib
27
Q
Poster child for EGFR mutant
A
- Asian female, non smoker, gets adenocarcinoma
- Stage 1-2: surgery
- Stage 3-4: TKI
