Module 7 Pulmonary: Lung Cancer Flashcards
What are the 4 main types of lung neoplasms?
- Adenocarcinoma
- Squamous cell carcinoma
- Large cell carcinoma
- Small cell carcinoma
The non small cell lung cancers contribute to about 70-75% of cases, what are some characteristics?
- Adenocarcinoma (periphery)(most aggressive of all and most common)
- Squamous cell carcinoma (Central)
- Large cell carcinoma (central)
- -abundant cytoplasm
- -pleomorphic nuclei with coarse chromatin
- -prominent nucleoli
- -glandular and squamous architecture
- -absent neuroendocrine markers
* *responds poorly to chemotherapy: treat with surgery because its slower growing
The small (oat) cell carcinoma is central and accounts for the last 20-25% of cases, what are some characteristics?
- scant cytoplasm
- small hyperchromatic nuclei with fine chromatin pattern
- indistinct nucleoli
- diffuse sheets of cells
- -neuroendocrine markers present
- *metastasize quickly sx not an option so chemo
Adenocarcinoma make up 30-35% of the non small cell carcinomas and it is therefore the most common primary lung tumor, what is the etiology of adenocarcinoma?
Adenocarcinoma (peripheral)
–seen in smokers mutation is KRAS
–seen in non smoker Asian women is mutation in EGFR
–seen in non smoker women is a mutation in ALK with signet rings
(remember only need one hit)
What is the cell of origin, precursor lesion and appearance on CXR for a patient with adenocarcinoma?
Cell of origin = bronchioloalveolar stem cell or clara cell
Precursor lesion = atypical adenomatous hyperplasia (AAH)
Peripherally located = coin lesion on CXR
What is the presentation for an adenocarcinoma?
SOB
cachexia (b/c of TNFalpha)
Finger clubbing (All lung cancers)
If you take a wedge resection (Excisional biopsy) of an adenocarcinoma what would you see?(note bronchoscopy wont reach this tumor because its peripheral in nature)
Malignant (dysplastic slide 15b) glands invading stroma
- –produce lots of mucin: well differentiated in function
- -positive for cytokeratin and PAS: diastase resistant because no glycogen
- -Immunohistological stains: TTF-1, cytokeratin 7 and napsin A
What are the complications of adenocarcinoma?
Location makes it easy to cause pleural effusions — compression atelectasis
Left side — pericardial effusion — pericardial tamponade (hypotension, distended jug veins and muffled heart sounds)
Also can lead to scarring or contraction atelectasis, so other name is scar carcinoma.
Cor Pulmonale
What would you see on cytology of a patient with an adenocarcinoma? (note not the best investigation for this)
On slide 15b: you see 5 cancer cells all clumped together. composed of a nucleus
- -blue space is the prominent nucleolus (fine chromatin arrangement)
- -clear cytoplasm ( because it contains mucin)
What are the paraneoplastic syndromes associated with adenocarcinoma?
Hematological – all due to Mucin
DIC
Nonbacterial thrombotic endocarditis (marentic endocarditis)
Trousseaus syndrome (recurrent migratory thrombotic phlebitis) —thrombus in superficial vein — vein in red, hot, swollen and painful –recurrent and migratory
How is adenocarcinoma in situ different from adenocarcinoma?
- Non invasive of the stroma
- –butterfly on the fence or Lepidic pattern on biopsy those are the cancer cells just chillin on the alveolar wall (slide 16)
Now adenocarcinoma in situ presents very similar to lobar pneumonia. What are the similarities and then what is the distinguishing factor of the two?
Same: –productive cough with a lot of sputum, SOB and pleuritic chest pain, no coin lesion just consolidation of the lobe on xray (ground glass and interstitial infiltrates)
Different: patient will not respond to ABX when placed on them
What is the main complication of adenocarcinoma in situ?
resp failure due to mucin overproduction — too much in alveolar space
The next non small cell lung carcinoma is squamous cell carcinoma, what is the etiology for this?
Etiology: Smoking, radon exposure and Asbestosis (Also called mesothelioma)
- –smoke + asbestosis = higher risk
- -Men greater than women
What is the origin and precursor lesion for squamous cell carcinoma?
Origin: bronchial wall (as seen on slide 17a)
Precursor lesion: squamous dysplasia (pre-malignant)
–again remember this is non small cell so sx because slow growing
What is the pathogenesis for squamous cell carcinoma?
Pseudostratified —- squamous
–again precursor lesion is squamous dysplasia
What is the presentation for squamous cell carcinoma?
SOB
Cachexia (b/c of TNFalpha)
Finger clubbing
Hemoptysis
What would you see on biopsy for a patient with squamous cell carcinoma?
Keratin Pearls: well differentiated in function and intercellular bridges
- -cytokeratin positive
- –Immunohistological stains: P63, cytokeratin 56 and cytokeratin 903
What gene mutations are associated with squamous cell carcinoma?
RB, P16, P53
–again remember all tumor suppressor genes need 2 hits
On slide 17b there is a cytology, what are the associated arrows pointing it?
Arrow at top: normal appearing squamous cell (Should not have squamous cells in the bronchus though) so good example of squamous metaplasia
Arrow at bottom: squamous dysplasia called a tadpole dysplastic cell
What are the complications of a squamous cell carcinoma?
Centrally located so it blocks bronchial lumen and no cilia
–mucus trapped – recurrent pneumonia — lung abscess –bronchiectasis
Gets bigger and compresses the esophagus (dysphagia) , trachea, recurrent laryngeal nerve (hoarseness) and bilateral hilar lymphadenopathy and compression of phrenic nerve
–Resorptive atelectasis due to obstruction of lumen by tumor
–supresses superior vena cava: edema of face and UE, distended jug veins, dusty cyanosis and compression of central structures
What is the paraneoplastic syndrome associated with squamous cell carcinoma?
PTH like syndrome so hypercalcemia and PTH goes down (neg feedback)
- metastatic calcification
- -hypercalcemia due to lytic lesions in the bone
The last non small cell carcinoma is large cell carcinoma which makes up about 10-12% of those tumors. What is involved in large cell carcinoma?
Undifferentiated epithelial malignancy
- -lacks features of small cell and no glandular or squamous differentiation
- -poor prognosis and early metastasis
What are the two different types of large cell carcinoma?
Large cell carcinoma (undifferentiated)
Large cell neuroendocrine carcinoma (neuroendocrine markers: chromogranin, synaptophysin and CD56)
What is the pathogenesis of large cell carcinoma?
3p delection
P16/CDKN2a
Small (oat) cell carcinoma is centrally located and associated strictly with smoking. What is the cell of origin and neuroendocrine marker and immunohistochemical marker?
Cell of origin: Kulchitsky (neuroendocrine cells)
neuroendocrine marker: synaptophysin, chromogranin, CD56
Immunohistochemical marker: TTF1 (thyroid transcription factor)
Again all small cell carcinomas are central (hilar) and are very aggressive and therefore the only option for treatment is chemo/or radiation. Most by the time they are caught are already metastasized, what is the order of metastasis?
From lungs:
lymph nodes — blood — adrenal glands — liver — brain — bone and kidney
What is the pathogenesis of small (oat) cell carcinoma?
Myc amplification, p53 and pRB
3p delection
What investigations would you do for small (oat) cell carcinoma? And what would you find?
Biopsy: salt and pepper appearance
Histology: Round, scant cytoplasm, finely granular chromatin, fragile, crush artifacts (Azzopardi effect) , nuclear molding and extensive necrosis (note:bronchial carcinoid looks exactly the same because the same cell of origin)(absent nucleoi, high nuclear:cytoplasmic ratio)
Cytology: nuclear molding (not in bronchial carcinoid) (only cancer you will see with this)
Keratin stain: classic rim and dot staining; rim = cytoplasm and dot = golgi apparatus
What are the associated paraneoplastic syndromes associated with small (oat) cell carcinoma?
SIADH: dilutional hyponatremia which leads to cerebral edema and papilledema
Gonadotropins: FSH=gynecomastia, LH= problems ovulating which leads to infertility, amenorrhea and hirsutism (hairy)
ACTH — Cushing syndrome (most common): buffalo hump, purple striae and moon face
Lambert Eaton — destruction of voltage gated calcium channels (waxing)
What is malignant mesothelioma?
Primary malignancy of pleura, peritoneum or pericardium
- -strong association with asbestos
- -rind-like encasement of lung
What are the three primary patterns of malignant mesothelioma?
Epithelial
Sarcomatoid
Mixed (biphasic)
What is the stain used for malignant mesothelioma?
Calretinin
As stated earlier the order of metastasis for lung cancer is lymph — blood—adrenal, liver, brain, bone and kidney in that exact order. Which are the symptomatic organs?
Brain, bone and kidney
- –need to destroy 90% of parenchyma in order to show symptoms
- -liver and adrenal glands have a lot of parenchyma so its takes awhile for these to show symptoms
Now when these lung cancers metastasis there can be hypercalcemia found, why?
Bone has lytic lesions so the bones are literally breaking and therefore releasing calcium
—fav bone is vertebra
What are the common lung cancers to metastasize in order?
Small cell lung carcinoma (makes sense because its aggressive)
Adenocarcinoma
Squamous Cell Carcinoma
Bronchial Carcinoid (Best prognosis)
Slide 19A shows a centrally located tumor on the right and remember this is all lung cancers except adenocarcinoma. so what are some affects of this tumor???
- Resorption Atelectasis: there is some sort of blockage of the bronchial lumen
- Compression of esophagus (dysphagia) and hilar lymph nodes
- Widening of mediastinum
- Compression of recurrent laryngeal nerve (horseness)
- Compression of left phrenic nerve (leading to raised hemidiaphragm)
- Tracheal deviation to right
- SVC syndrome (cant get blood back to right heart) so red face
Slide 19A shows a pancoast tumor/superior sulcus tumor, what are some affects of this tumor?
- Right cervical sympathetic syndrome - ipsilateral horner syndrome (anhydrosis, miosis, and ptosis and endopthalmos-sucken)
- Wasting of thenar eminence because compression of brachial plexus
- Recurrent laryngeal nerve paralysis and dysphagia (compression of esophagus)
- Right side- SVC syndrome
- Left side –compress thoracic duct — chylothorax and compression atelectasis
What does SPHERE mean in terms of complications for squamous cell carcinoma?
Superior vena cava syndrome Pancoast tumor Horner syndrome Endocrine: paraneoplastic (hypercalcemia) Recurrent laryngeal nerve compression Effusion
What are the 4 Cs of squamous cell carcinoma?
Central
Cavities
Cigarettes
HyperCalcemia
Review: 10% of all lung cancer have associated paraneoplastic syndromes. What are the syndrome and associated cancer?
Hypercalcemia: PTH related peptide - squamous cell
Cushings (ACTH): bilateral adrenal hyperplasia: small cell
Syndrome of inappropriate ADH secretion: hyponatremia: small cell
Gonadoptropins: gynecomastia: small cell
Review Quiz: what are the stages of tumor progression in adenocarcinoma?
- Atypical Adenomatous Hyperplasia (AAH): precursor lesion
- Adenocarcinoma in situ: less than 3cm and non invasive
- -two forms: non-mucinous type and mucinous type (tall columnar mucin producing cells lining alveoli in a lepidic fashion mucin is actually in the alveoli) - Minimally invasive adenocarcinoma: less than 3cm invasive but less then 5cm in total size
- Invasive histologic types: greater then 5cm with 5 different histological types: acinar, papillary, solid and micropapillary and lepidic
Review Quiz: what are the different types of invasive adenocarcinoma and appearance on histology?
Acinar: gland formation and mucin production
Solid: gland formation is not so clear all you have is solid sheets of cells; alot of vacuoles containing mucin
Papillary: not traditional types but glands take on a papillary appearance
Lepidic: butterfly on fence
Review Quiz: what is the grading of adenocarcinoma?
Well differentiated: well formed glands greater then 90%
Moderately differentiated: moderately well formed glands (50-90%)
Poorly differentiated: poorly formed glands (5-50%)
Review Quiz: how do you get cavity formation in a squamous cell carcinoma?
Central necrosis = cavitation
distinct feature of squamous cell carcinoma
Review Quiz: squamous cell carcinoma spreads where?
hilar lymph nodes
remember that lymph nodes are first for spread
Review Quiz: there is progression of squamous cell carcinoma in situ to invasive squamous cell carcinoma, what marks the progression?
pseudostratified columnar ciliated epithelium
Invasive: cells not confined to mucus seen in the submucosa (infiltrating sheets of squamous cells)
Review Quiz: what is the grading of squamous cell?
Well differentiated: prominent keratinization and intercellular bridges
Moderately differentiated: reduced numbers of squamous pearls, difficult to find intercellular bridges and tumor necrosis
Poorly differentiated: virtually no intercellular bridges and keratin pearls
Review Quiz: what percent of small cell cancer are associated with cigarette smoking?
99% with early mets to mediastinal lymph nodes.
Review Quiz: What pneumonia does SIADH?
Legionella
