Term
| what % of lung cancer cases are small cell carcinomas? |
|
Definition
| 20% small cell carcinomas; 80% non-small cell (adenocarcinoma, squamous cell carcinoma) |
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|
Term
| which kind of cancer is most strongly associated with smoking? |
|
Definition
| squamous > small cell > adeno |
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Term
| what is the most frequent type of lung cancer in both males and females? and why is this? |
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Definition
| adenocarcinoma; decline in risk of lung cancer is faster for squamous cell carcinoma than for adenocarcinoma and/or changes in cig composition to low tar/nicotine --> more puffs and deeper inhalation --> greater exposure to carcinogens in peripheral lung alveoli which is where adenocarcinoma develops |
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Term
| what is the strongest determining factor in assessing a patient's risk for lung cancer? |
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Definition
| duration of smoking and the # of cigarettes smoked (pack/years) |
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Term
| 2nd hand smoke = how many cigarettes per day? |
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Definition
|
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Term
| what occupational exposures have synergism with cigarette smoking in increasing risk for lung cancer? |
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Definition
| asbestos, crystalline silica, radon, polycyclic aromatic hydrocarbons, heavy metals, welding, painting |
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Term
| what are the 4 molecular genetic changes commonly seen in all major histologic types of lung carcinomas? |
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Definition
| 1. p53 mutations 2. inactivation of the pathway controlling RB1 3. loss of heterozygosity on 3p (FHIT, RASSF1A, beta-catenin, SEMA3B) 4. other (loss of heterozygosity on other chromosomes, increased telomerase activity) |
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Term
| what is the most frequent mutation in lung carcinomas? |
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Definition
| p53 mutation (G-->T switch at sites of benzopyrene damage aka direct DNA damage from smoking) |
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|
Term
| what is the result of inactivation of the pathway controlling RB1? |
|
Definition
| loss of RB protein, inactivation of p16 and overexpression of cyclinD1 |
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Term
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Definition
| fragile histidine triad - it's a highly fragile chromosomal area where partial deletion of DNA occurs d/t direct DNA damage by smoke carcinogens. encodes for a protein with ADP hydrolase activity that regulates DNA replication and signaling stress responses (mutated in 80% of lung cancer) |
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Term
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Definition
| encodes for protein involved in control of the Ras family of oncogenes |
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Term
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Definition
| intracellular molecule, links E cadherin (transmembrane glycoprotein) to the cytoskeleton. decreased b catenin and e cadherin expression --> worse prognosis in non-small cell carcinoma |
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|
Term
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Definition
| encodes semaphorin 3B, involved in dev of neuronal and epithelial tissues |
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Term
| why are epithelial growth factor receptors important in lung cancer? |
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Definition
| they are tyrosine kinase receptors that are frequently mutated in nonsmall cell carconimas. determining their mutation status and/or if they are amplified/overexpressed determines significant response to tyrosine kinase inhibitors (gefitinib aka iressa and erlotinib are such inhibitors, useful esp in adenocarcinomas) |
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Term
| how do carcinogens translate into DNA damage? |
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Definition
| over 60 carcinogens in tobacco smoke --> converted to intermediate compounds by cytochrome p450 (adds an oxygen making it water soluble) --> glutathione s transferase makes this into an excretable form, but in the process electron deficient intermediates are formed --> highly reactive with DNA --> DNA adducts --> cells have systems to eliminate DNA adducts, but NOT ALL REPAIR SYSTEMS ARE EQUALLY ACTIVE IN ALL PEOPLE |
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Term
| what is superior vena cava syndrome and what do we do about it? |
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Definition
| superior vena cava compression by tumor --> venous distention --> backup swelling from wherever its draining --> emergency! need to tx with chemo and radiation |
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Term
| what is pancoast's syndrome and what other syndrome can it lead to? |
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Definition
| tumor in the upper lobes invade C8, T1, T2 --> neck pain down the shoulder destroying first and second ribs --> can invade sympathetic trunk in T1-T2 area and produce horner's syndrome (ptosis, miosis, anhydrosis) |
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Term
| what is the 5 year survival for all types of lung carcinoma? |
|
Definition
| 15% (if resectable, 48%, but only 15% of carcinomas are resectable) |
|
|
Term
| what % of patients experience paraneoplastic syndromes? |
|
Definition
|
|
Term
| what hormones are associated with small cell carcinoma? |
|
Definition
|
|
Term
| what hormones are associated with squamous cell carcinoma? |
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Definition
| parahormone, parathyroid hormone related peptide, prostaglandins |
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|
Term
| what hormone is associated with carcinoid tumors? |
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Definition
| seratonin and bradykinin (cause carcinoid syndrome - diarrhea, flushing, wheezing) |
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|
Term
| what is lambert-eaton myasthenia syndrome? |
|
Definition
| auto-antibodies to the neuronal calcium channels cause proximal muscle weakness (cannot walk or get up) |
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|
Term
| where in the lung does squamous cell carcinoma usually arise? |
|
Definition
| hilus of the lung (but peripheral tumors may be seen and are increasing in number) |
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|
Term
| describe the gross morphology of squamous cell carcinoma as well as the two "types" |
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Definition
| gray, white firm tumor with necrosis at the center and star like at the edge - can get quite large and possibly drain into a bronchus forming a cavity; PENETRATING type may occlude the lumen &/or invade peribronchial tissue, carina, mediastinum; CREEPING type grows laterally along bronchi with or without subepithelial invasion |
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Term
| which type of tumor stays in the thorax for a really long time? |
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Definition
| squamous cell - stays in thorax for long time being locally aggressive, with metastases late in the disease to brain, liver, adrenals, lower GI tract |
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|
Term
| what does squamous cell carcinoma look like histologically? |
|
Definition
| keratinized cells with intercellular bridges and keratin pearls |
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|
Term
| what immunohistochemical stains can we use to identify squamous cell carcinoma? |
|
Definition
| cytokeratin 7+, high molecular weight keratin + (ck5/6+ therefore do not treat with EGFR therapy bc can have life threatening hemorrhages) |
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|
Term
| what are the unique molecular genetics in squamous cell carcinoma? |
|
Definition
| overexpression of EGFR in 80%; HER-2-neu highly expressed in 30%; overexpression of met in 35%; bcl-2 overexpression is a better prognositc sign for surgically resected tumors |
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|
Term
| what is the prognosis of squamous cell carcinoma? |
|
Definition
| local recurrence after resection is common. stage for stage survival better than for adenocarcinoma |
|
|
Term
| what is the most common type of lung cancer in nonsmokers? |
|
Definition
| adenocarcinoma (esp women); 75% associated with smokers vs >98% in squamous cell |
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|
Term
| where do adenocarcinomas typically arise in the lung? |
|
Definition
| periphery (as small nodules), rarely hilar or cavitary |
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|
Term
| which type of lung cancer most frequently involves pleural/chest wall? |
|
Definition
|
|
Term
| when do adenocarcinomas metastasize (compare with squamous cell)? |
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Definition
| adenocarcinomas metastasize widely and EARLIER than squamous cell (remember: squamous cell is locally aggressive in thorax for long time and metastasizes LATE) |
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|
Term
| what are the 6 gross presentations of adenocarcinoma? |
|
Definition
| peripheral tumor (gray white with central fibrosis, pleural puckering - most common); central/endobronchial (near hilum may occlude lumen); diffuse pneumonia-like lobar consolidation (mucinous bronchoalveolar carcinoma); diffuse bilateral lung nodules or interstitial pneumonia pattern (d/t lymphatic spread of carcinoma); invasion and dissemination along visceral pleura (mimicks malignant mesothelioma); focal scar or diffuse interstitial fibrosis |
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|
Term
| what is the histologic appearance of adenocarcinoma? |
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Definition
| glandular differentiation or mucin production; histologic subtypes: acinar, papillary, solid with mucin production, bronchoalveolar carcinoma (80% of tumors = mixture of subtypes and all except BAC have central scar) |
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|
Term
| is there an immunohistochemical stain for adenocarcinoma? |
|
Definition
| TTF1+ (for adenocarcinoma of lung and also for carcinoma of thyroid) and cytokeratin 7+ |
|
|
Term
| describe the bronchioalveolar histologic subtype of adenocarcinoma |
|
Definition
| grow along preexisting alveoli (lepedic/butterfly growth) w/o evidence of invasion. NON-MUCINOUS - clara cell and/or typeII pneumocyte differentiation. well to moderately differentiated, usually solitary and easy to resect. MUCINOUS - mucous cell differentiation, low-grade tumor spreads through alveoli with satellite lesions, may consolidate entire lobe, difficult to resect, pt puts out lots of sputum |
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|
Term
| morphologic seq for squamous cell carcinoma? |
|
Definition
| squamous metaplasia, squamous dysplasia, carcinoma in situ, invasive squamous cell carcinoma |
|
|
Term
| morphologic sequence of adenocarcinoma |
|
Definition
| atypical adenomatous hyperplasia --> bronchioalveolar carcinoma --> invasive adenocarcinoma? not always invasive but still bad if it's not bc it can pop up anywhere |
|
|
Term
| what are the unique molecular genetics of adenocarcinoma? |
|
Definition
| K-ras point mutations (30%); overexpression of HER2-neu and cox-2 genes; overexpression of EGFR (anti-EGFR rx works in small % of BAC, particularly japanese females), overexpression of met in 70% |
|
|
Term
| + prognostic factors for adenocarcinoma? |
|
Definition
| more ground glass, bcl2 expression better prognostic sign for surgically resected tumors |
|
|
Term
| - prognostic factors for adenocarcinoma? |
|
Definition
| papillary pattern, loss of heterozygosity at 2q 9p 22q, kras mutations, p53 mutations, her2neu overexpression, met overexpression, rb inactivation, p16 gene inactivation (overall 5 year survival not good unless pt responds to anti-EGFR drugs) |
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|
Term
| what is the definition of large cell carcinoma? |
|
Definition
| undifferentiated epithelial cell tumor, lacks cytologic and architectural features of squamous cell carcinoma, adeno, or small cell. composed of large polygonal cells with vesicular nuclei and prominent nucleoli in sheets or nests |
|
|
Term
| where do large cell carcinomas typically arise? |
|
Definition
| peripherally, often invade visceral pleura chest wall |
|
|
Term
| what do large cell carcinomas look like grossly? |
|
Definition
| soft, pink, tan with necrosis |
|
|
Term
| what type of cellular differentiation do large cell carcinomas have? |
|
Definition
| clara cell or type II pneumocyte differentiation |
|
|
Term
| which is the most aggressive of all lung cancers? |
|
Definition
|
|
Term
| where do small cell carcinomas typically arise? |
|
Definition
| major bronchi (95%) or in lung periphery as a coin lesion (5%) |
|
|
Term
| what do small cell carcinomas arise from? |
|
Definition
| pluripotent bronchial precursor cell (kulchitsky cell!) |
|
|
Term
| why don't we use TNM staging on small cell carcinomas? |
|
Definition
| they tend to be widespread at presentation. instead we use limited vs extensive |
|
|
Term
| gross morphology of small cell carcinomas |
|
Definition
| white, tan, soft, friable with necrosis, fast growing (spreads along bronchi submucosally, circumfrentially and often quickly invades lymphatics), frequent hilar and mediastinal LN involvement |
|
|
Term
| what do small cell carcinomas look like histologically? |
|
Definition
| small (<30 mu) scant cytoplasm ill defined borders, salt and pepper chromatin, nuclear molding and necrosis, high mitotic rate, spindling, crush artifact, neurosecretory granules |
|
|
Term
| what is the azzopardi effect? |
|
Definition
| basophilic staining of vascular walls bc of tumor cell DNA (in small cell) |
|
|
Term
| what immunohistochemical stains do we use for small cell carcinoma? |
|
Definition
| (neuroendocrine markers) chromogramin, synaptophysin, CD56 |
|
|
Term
| what are the unique molecular genetics associated with small cell carcinoma? |
|
Definition
| ckit mutations (40-70%), myc (20-30%), upregulation of pro-apoptotic molcule BCL2, large segments of 3p allele loss |
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|
Term
| - prognostic factors of small cell carcinoma? |
|
Definition
| extensive stage of disease, high serum LDH or serum alkaline phosphatase, low albumin, low serum sodium |
|
|
Term
| what is large cell neuroendocrine carcinoma? |
|
Definition
| non-small cell carcinoma, has neuroendocrine granules, neuroendocrine differentiation, salt and pepper chromatin, similar cellular patterns and molecular changes as small cell carcinoma. |
|
|
Term
| histological morphology of carcinoid tumor |
|
Definition
| like small cell (salt and pepper chromatin, neuroendocrine tumor) except have uniform, polygonal cells with more cytoplasm, lack nuclear molding, lack spindling, lack a high mitotic rate |
|
|
Term
| where do carcinoid tumors typically arise in the lung? |
|
Definition
| within major bronchus, cause bronchiole obstruction |
|
|
Term
| compare typical vs atypical carcinoid tumor |
|
Definition
| TYPICAL: <2 mitotic figures per 10 hpf, no necrosis, low grade, 10-15% met to regional LN, 5-10% widespread met. ATYPICAL: 2-10 mitotic figures per 10hpf, small areas of necrosis, aggressive, 40-50% met to regional LN and beyond |
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|
Term
| what is the gross morphology of carcinoid tumors? |
|
Definition
| well demarcated, yellow-tan tumors attached to a bronchus, often endobronchial with equal distribution throughout lungs. (atypical tumors more commonly peripheral, may not be assoc with an airway) |
|
|
Term
| what are carcinoid tumors derived from? |
|
Definition
| kulchitsky cell (neuroendocrine cell), diffuse idiopathic neuroendocrine cell hyperplasia is thought to be a precursor lesion |
|
|
Term
|
Definition
| looks like typical carcinoid tumor but <5mm in diameter |
|
|
Term
| what are the immunohistochemical stains we use for carcinoid tumors? |
|
Definition
| same as those for small cell (neuroendocrine stains) chromogramin, synaptophysin, CD56 |
|
|
Term
| what are the unique molecular genetics of carcinoid tumors? |
|
Definition
| mutations of the MEN1 gene, absence of its protein product menin |
|
|
Term
| what is the 5 year survival for typical vs atypical carcinoid tumors? |
|
Definition
| TYPICAL 90-98%; ATYPICAL 61-73% |
|
|
Term
| what is the most important prognositc factor in carcinoid tumors? |
|
Definition
|
|
Term
| + prognostic factor in carcinoid tumors? |
|
Definition
| typical carcinoid with LN mets still have good prognosis |
|
|
Term
| - prognostic factor in carcinoid tumors? |
|
Definition
| aerogenous (airspace to airspace thru pores of kohn) spread in atypical carcinoid tumors. |
|
|
Term
| malignant mesotheliomas strongly associated with what 2 things? |
|
Definition
| men and prior asbestos exposure |
|
|
Term
| which form of asbestos is the most dangerous? |
|
Definition
| crocodolite > amosite > chrysolite |
|
|
Term
| what are other causes of malignant mesothelioma aside from asbestos? |
|
Definition
| therapeutic radiation, intense pleural scarring, exposure to the nonasbestos fiber (erionite) found only in cappadocia TURKEY |
|
|
Term
| when we look at lung sections for malignant mesothelioma, why dont we see asbestos itself? |
|
Definition
| asbestos fibers become encapsulated by giant cells or surrounded by protein and hemosiderin (ferruginous bodies) |
|
|
Term
| describe the gross morphology of malignant mesothelioma |
|
Definition
| multiple small firm white nodules on parietal pleura, become confluent and encase the lung ("pleural plaque" non cancerous sign of asbestos exposure, no ferruginous bodies in it, squeezes the lung, can cause collapse). loculations (collections of pleural fluid), local extension into mediastinum, pericardium, pleural cavity, lung, diaphragm and chest wall, hematologic dissemination |
|
|
Term
| what are the 4 histological morphologies of malignant mesothelioma? |
|
Definition
| epithelioid (large cells, can mimic large cell carcinoma or lymphoma), sarcomatoid (spindled cells, mistaken for sarcoma or sarcomatoid carcinoma), desmoplastic (dense collagen, atypical tumor cells in 50% of tumor), biphasic (eipthelioid and sarcomatoid patterns) |
|
|
Term
| describe the unique molecular genetics of malignant mesothelioma |
|
Definition
| DISRUPTION OF RB PATHWAY, p53 mutations UNCOMMON, mutations of NF2 GENE common, GPC3 downregulated (tumor suppressor gene) d/t aberrant promoter methylation |
|
|
Term
| + prognostic factors for malignant mesothelioma |
|
Definition
| pure epithelioid histology, stage of disease, good performance status, lack of chest pain, female <50yo |
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