Flashcards in PATH: Pulmonary Neoplasia Deck (104):
What types of neoplasms RARELY originate in the lung, and are not included in the definition of lung cancer?
Lymphomas and sarcomas
True or False: lung cancer is the most common cause o f cancer death and the US world-wide.
What is the major risk factor for lung cancer?
SMOKING (80% in active or former smokers)
What occupational hazard increases the risk of lung cancer 5 fold?
What are KRAS, BRAF and PIK3CA ?
cytoplasmic signal transducer oncogenes that can be mutated in lung cancers
What are NKX2-1 (which codes for TTF1) and MYC?
nuclear DNA transcription oncogenes that are amplified in some lung cancers
What are CDKN2A (which codes for p16(INK4A), RB, TP53 and LKB1?
tumor suppressor genes mutated or deleted in some lung cancers
What is TTF1?
Thyroid transcription factor 1 (controls the expression of surfactant proteins and part of embryonic lung morphogenesis)--but has anti-oncogenic AND pro-oncoenic effects
What are the 3 major types of lung cancers?
1) Adenocarcinoma (40%)
2) Squamous cell carcinoma (20%)
3) Small cell lung cancer (15%)
In what epidemiological groups are adenocarcinomas becoming more comon?
Women, Young Patients (under 40), Asians, and never smokers
Where are adenocarcinomas most commonly found?
What type of lung cancer is becoming less common?
squamous cell carcinomas
What are features of squamous cell carcinoma in the lung?
commonly metastatic to local lymph nodes at presentation
cause post-obstructive pneumonia and hypercalcemia
True or false: small cell lung cancer is more commonly benign at presentation.
FALSE: >67% metastatic at presentation
What are some features of small cell lung cancer?
associated with paraneoplastic syndrome of inappropriate antidiuretic hormone, Cushing syndrome, or Eaton-Lambert syndrome
What is the average age for lung cancer symptoms to present?
What are the most common symptoms of lung neoplasms?
Cough (less common with adenocarcinoma because it is peripheral)
How do you diagnose lung cancer?
STEP 1: Discovery via radiology (should screen 55-80 year olds with 30+ pack years of smoking with low dose CT)
STEP2: Actionable diagnosis with biopsy
What is the treatment for lung cancer?
-Surgery if low stage
-Adjuvant 2-agent chemo (1 plat based) if higher stage, large, or if lymph nodes involved
If lung cancer is limited to chest and mediastinal lymph nodes, what is the treatment?
chemo and radiation
What is erlotinib?
targeted drug therapy for mutated EGFR
What is crizotinib?
targeted therapy for translocated ALK
What is the prognosis for lung cancer?
BAD: 5 year survival is 17%
What is a lung primary adenocarcinoma?
malignant epithelial tumor of lung with glandular features such as making glands or mucin
Why has the incidence of filter cigarettes increased the amount of adenocarcinomas?
filter removes large particles but forces smoker to inhale deeper, so small particles get deposited in small airways
Which type of adenocarcinoma has an EFGR-dependent pathway?
adenocarcinoma in never-smokers
Which type of adenocarcinoma has an KRAS-dependent signaling pathway?
adenocarcinoma in smokers
(this is way less common than the EFGR mutation!)
True or false: the only way to become resistant to erlotinib is to have a mutation to EGRF?
FALSE: if KRAS is mutated (downstream), you will also get resistance (KRAS mutation is slightly more common than EGFR mutation)
What is the consequence of an EML4-ALK translocation fusion oncogene?
has potent oncogenic activity and confers resistance to crizotinib
Which tumor suppressor gene is mutated in 60-70% of adenocarcinomas?
True or false: adenocarcinomas are the most likely lung cancer to respond to targeted therapy.
Describe the gross pathology of adenocarcinomas.
< 4 cm
Solitary and solid
may have demoplastic reaction (scar)
What are the 5 microscopic patterns of adenocarcinoma?
Which is the most common microscopic pattern of adenocarcinoma? What are its features?
acinar (makes glands and has demoplastic rxn)
Which microscopic pattern of adenocarcinoma has a good prognosis?
lepidic- spreads within alveoli (commonly a single cellular layer) without invading (adenocarcinoma in situ)
What two patterns of adenocarcinoma have bad prognoses?
What are the most common symptoms of adenocarcnoma?
cough (50%), weight loss (40%), hemoptysis (25%), dyspnea (25%), chest pain (20%, usually dull and persistent)
Which pulmonary neoplasms are typically Napsin A, CK7, and TTF1 positive, but RARELY CK5/6 or p40 positive?
Which pulmonary neoplasms are typically p40, p63, and CK5/6 positive but rarely TTF1 or Napsin A positive?
squamous cell carcinoma
What is the treatment for adenocarcinoma?
surgical resection (option only for low stage)
erlotinib (if have EGFR mutation)
crizotinib (if have ALK translocation)
IF INOPERABLE: radiation and double-agent cytotoxic chemotherapy
What is the first agent used in chemotherapy of adenocarcinomas?
DNA-cross-linking platinum salt (cisplatin or carboplatin)
What is typically the second agent used in chemotherapy of adenocarcinomas?
a antimicrotubule agent mitotic inhibitor like Taxol
What is a third agent that can improve survival if added to carboplatin and paclitaxel?
Bevacizumab (mAb to VEGF)
What is pemetrexed?
antifolate metabolite inhibitor of thymidylate synthetase (prevents formation of purine and pyrimidine nucleotides for formatio of DNA and RNA)
What is etoposide?
topoisomerase inhibitor that forms a complex iwth DNA and the enzyme and prevents re-ligation of DNA strands
What is adenocarcinoma in situ?
non-invasive adenocarcinoma of lung characterized by non-destructive growth along intact alveolar septa (called lepidic growth)
Is adenocarcinoma in situ common?
NO <5% of lung cancers (mostly in women, older, and smokers)
What are the two types of adenocarcinoma in situ of the lung?
From what cells is mucinous adenocarcinoma in situ of the lung derived?
Metaplasia of bronchiolar epithelium
What are some features of mucinous adenocarcinoma in situ of the lung?
-pneumonia type radiologic infiltrate
-rarely demonstrating EGFR mutations
more frequently harboring and driven by a KRAS mutation
From what cells is non-mucinous adenocarcinoma in situ of the lung derived?
terminal respiratory unit cells (type II pneumocytes, goblet cells, Clara cells)
What are some features of non-mucinous adenocarcinoma in situ of the lung?
-Predominates in smokers
-Radiologic ground-glass opacity often at presentation
What is aerogenous spread?
tumor spread via airways (tumor cells carried up by mucociliary ladder and then aspirated into other bronchi )
True or false: multifocal nodular cases are more common in the non-mucinous type.
FALSE: Single nodules are more commonly non-mucinous and multifocal nodular cases are mucinous type
What type of pulmonary neoplasm is CK20 positive and TTF1 negative, and usually KRAS positive and EGFR negative?
mucinous adenocarcinoma in situ
What type of pulmonary neoplasm is , usually TTF1 positive and CK20 negative, usually KRAS negative and “commonly” EGFR positive?
non-mucinous adenocarcinoma in situ
What is a way to remember the expression of markers between the two type of adenocarcinoma in situ?
MaCK NET (sounds like magnet)
Mucinous is CK20 positive and KRAS positive
Non-mucinous is positive for ERFR and TTF1
If a patient has bronchorrhea (rare) what is the most likely adenocarcinoma in situ that they have?
advanced mucinous (produce up to 100 mL of watery sputum)
What is squamous cell carcinoma of the lung?
lung primary malignant epithelial neoplasm with keratinization and/or intercellular bridges
Who gets squamous cell carcinoma of the lung?
What is the pathogenesis of squamous cell carcinoma of the lung?
squamous metaplasia of bronchial mucosa and cumulative mutations in genes controlling cell proliferation caused by carcinogens in cigarette smoke
Why is squamous cell carcinoma of the lung most likely to cause hypercalcemia?
the production of a substance resembling parathyroid hormone by the cancer
In which pat of the lungs do squamous cell carcinoma of the lungs arise?
2/3 arising from main, lobar, segmental or subsegmental bronchi, 1/3 arising from smaller peripheral bronchi
What is the microscopic pathology of squamous cell carcinoma of the lung?
cohesive sheets, nests or cords of large cells with moderate smooth eosinophilic cytoplasm
intercellular bridges and/or keratinization (may form keratin pearls)
What drugs should you not treat squamous cell carcinoma of the lung with? Why?
Pemetrexed (does not work)
Bevacizumab (associated with hemorrhages--some fatal)
What is small cell carcinoma of the lung?
lung primary malignant epithelial neuroendocrine neoplasm composed of “small” cells (most aggressive type of lung cancer and most likely to cause paraneoplastic syndrome)
Who gets small cell carcinoma of the lung?
What is the pathogenesis of small cell carcinoma of the lung?
cumulative genetic alterations in genes controlling cell proliferation caused by carcinogens in cigarette smoke
What are the top 6 most common mutations in small cell carcinoma of the lung?
What is RASSF1?
gene that codes for a tumor supressor protein that inhibits RAS (promoter is commonly shut down by hypermethylation in small cell carcinomas)
What is FHIT?
gene that fragile histidine triad tumor suppressor protein involved in purine metabolism.
What is the microscopic pathology of small cell lung carcinoma?
"small” cells with round-to-oval shape, scant cytoplasm, finely granular (“salt and pepper”) nuclear chromatin, absent or inconspicuous nucleoli, frequent nuclear molding, many mitoses
What are some signs of small cell lung carcinoma?
Cervical and arm edema
Pemberton's sign (facial flushing, Inspiratory stridor, and elevation of JVP when you raise you arms above head)
What is the prognosis for small cell lung carcinoma?
responsive to chemotherapy but rapidly fatal despite being responsive
What are pulmonary metastases?
malignant neoplasms in the lungs originating from primary tumors in other organs
True or false: pulmonary metastases are much more common than primary lung tumors.
What are 5 reasons why the lung is the organ that gets most metastases?
1) Lungs receive entire right heart blood flow
2) Lungs have densest capillary bed in the body
3) lungs have first capillary bed met by venous return from every other organ
4) lungs have first capillary bed met by lymphatic drainage after dumpted into SVC from thoracic duct
5) lung capillary bed offers uniquely high O2 levels
What types of neoplasia spread hematogenously (veins)?
*more commonly spread to lung
What types of neoplasms spread via lymphatic channels?
How do you differentiate metastases from lung primary tumors?
-multiple and frequently numerous
-tend to be smaller than lung primary tumors, usually <3 cm,
-tend to be rounder than primary tumors
-more commonly peripheral,
-less commonly endobronchial
-more rapidly growing
What is Lymphangitic carcinomatosis?
metastatic disease that can fill lymphatics and infiltrate interstitium without creating mass lesions
What are the immunohistochemical tests you use to differentiate between primary adenocarcinoma and metastasis?
FIRST: CK7 and CK20
SECOND: CDX2 and TTF1
THIRD: tons fo immunostains
What organ's primary adenocarcinoma is commonly CK7 and TTF1 positive, CK20 and CDX2 negative?
lung primary adenocarcinoma
What organ's primary adenocarcinoma is commonly CK20 and CDX1 positive and CK7 and TTF1 negative?
colon primary adenocarcinoma
What organ's primary adenocarcinoma is commonly CK1 and CK20 positive and CDX2 and TTF1 negative?
breast primary adenocarcinoma
What organ's primary adenocarcinoma is commonly negative for CK1, CK20, CDX2, and TTF1?
kidney primary adenocarcinoma
What are the top 3 organs that metastasize to the lung?
What is a carcinoid tumor?
low-grade malignant neuroendocrine epithelial neoplasms.
Describe the gross pathology of carcinoid tumors?
central small soft tan endobronchial polypoid mass or peripheral nodule.
Describe the microscopic pathology of typical carcinoid tumors.
arrangements of medium size cells with uniform round nuclei and a moderate amount of eosinophilic cytoplasm, fewer than two mitoses per 10 high-power fields and no necrosis
Describe the microscopic pathology of atypical carcinoid tumors.
2-10 mitoses per 10 high-power fields and/or foci of necrosis, increased pleomorphism, more prominent nucleoli, more disorganized architecture and sometimes lymphatic invasion
How can you differentiate between utterly benign to viciously malignant neuroendocrine tumors?
-High % of cells expressing Ki67 (nuclear protein expressed in proliferating cells)
How do you treat carcinoid tumors?
What is the prognosis for carcinoid tumors?
good for typical carcinoid and okay for atypical carcinoids
What is mesothelioma?
malignant neoplasm of pleura (rarely pericardium or peritoneum).
Who gets mesothelioma?
uncommon but present in elderly white mails exposed to asbestosis (25-45 year latent period)
What is the most common genetic alteration in mesothelioma?
homozygous deletion of tumor supressor gene: CDKN2A/INK4a
What is the gross pathology of mesothelioma?
typically a thick layer of soft, gelatinous, grayish tumor arising either from visceral or parietal pleura, diffusely involving the pleura and associated with a large pleural effusion.
What are the 3 microscopic types of mesothelioma?
What is the microscopic pathology of epitheloid mesothelioma?
cuboidal, columnar, or flattened cells forming tubular or papillary structures resembling an adenocarcinoma
What is the microscopic pathology of sarcomatoid mesothelioma?
Which form of mesothelioma will immunostain strong positive for keratins, calretinin, Wilms tumor 1 (WT-1), cytokeratin 5/6, and D2-40?
Which form of mesothelioma will sometimes immunostain strong for only keratin?