Path: lung CA

Question 1

Squamous cell CA 1

Answer 1

• 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

Question 2

Squamous cell CA 2

Answer 2

• 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

Question 3

Adenocarcinoma 1

Answer 3

• 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)

Question 4

Adenocarcinoma 2

Answer 4

• 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)

Question 5

Adenocarcinoma in situ

Answer 5

• 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

Question 6

Adenocarcinoma lepidic predominant

Answer 6

• 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

Question 7

Small cell CA

Answer 7

• 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

Question 8

Clinical presentation of small cell CA

Answer 8

• 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

Question 9

Large cell CA

Answer 9

• 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

Question 10

Carcinoid tumor

Answer 10

• 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

Question 11

Molecular alterations of adenocarcinomas

Answer 11

• 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

Question 12

Lung CA epidemiology

Answer 12

• # 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

Question 13

Lung CA classification

Answer 13

• 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

Question 14

Rx for SCLC

Answer 14

• Limited stage SCLC: tries to cure using radiation and chemo
• Extensive stage: cannot cure, palliative radiation and chemo

Question 15

Rx for NSCLC

Answer 15

• 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

Question 16

Determining stage

Answer 16

• 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)

Question 17

Clinical presentation of squamous cell

Answer 17

• 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)

Question 18

Clinical presentation of adenocarcinoma

Answer 18

• 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)

Question 19

Clinical presentation of small cell CA

Answer 19

• 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

Question 20

Clinical presentation of carcinoid tumors

Answer 20

• 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

Question 21

Paraneoplastic syndromes 1

Answer 21

• 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

Question 22

Paraneoplastic syndromes 2

Answer 22

• 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

Question 23

Compression syndromes

Answer 23

• 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

Question 24

Single pulmonary nodule

Answer 24

• 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

Question 25

Role of PET in NSCLC

Answer 25

• 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

Question 26

Basics of NSCLC Rx

Answer 26

• 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

Question 27

Poster child for EGFR mutant

Answer 27

• Asian female, non smoker, gets adenocarcinoma
• Stage 1-2: surgery
• Stage 3-4: TKI