Term
| what is the most frequently diagnosed CA in the world and what is it due to? |
|
Definition
| lung CA which is due to cigarette smoke |
|
|
Term
| what is the peak age of lung CA incidence? |
|
Definition
|
|
Term
| what is the general prognosis for lung CA pts? |
|
Definition
| poor, a 15% five year survival for most pts |
|
|
Term
| what is the etiology of lung CA? |
|
Definition
| lung CA arises in a stepwise fashion w/accumulations of genetic abnormalities along with the fact that the duration and amount of cigarette smoking determines greater risks |
|
|
Term
| what are some of the carcinogenic components of cigarette smoke? |
|
Definition
| polycyclic aromatic hydrocarbons and phenol derivatives |
|
|
Term
| what are industrial hazards incurring greater lung CA risk? |
|
Definition
| high dose ionizing radiation, uranium, and asbestos |
|
|
Term
| what an indoor pollutant that can increase risk of air pollution? |
|
Definition
|
|
Term
| how many genetic mutations are likely to occur before a lung tumor becomes clinically apparent? |
|
Definition
| 10-20 - some of which are seen in both small cell and non-small cell CA, but others are more specific |
|
|
Term
| what are common oncogenes associated with lung CA? |
|
Definition
| c-MYC, K-RAS, EGFR, and HER-2/neu |
|
|
Term
| what are commonly deleted tumor suppressor genes associated with lung CA? |
|
Definition
| *p53, RB, p16, and multiple loci on chr 3p |
|
|
Term
| is are deletions of p53 seen in both small and non small cell CA? |
|
Definition
|
|
Term
| what general kind of CA has alteration in c-MYC and RB? |
|
Definition
|
|
Term
| what general kind of CA has alteration in RAS and p16? |
|
Definition
|
|
Term
| what is a possible predisposition associated with CYP1A1? |
|
Definition
| people with certain alleles of CYP1A1 (cytochrome p450 gene) have increased capacity to metabolize procarcinogens derived from cigarette smoke and may incur a greater risk of developing lung CA |
|
|
Term
| what are some lung CA prescursor lesions? |
|
Definition
| 1) squamous dysplasia & CA in situ 2) atypical adenomatuous hyperplasia 3)diffuse idiopathic pulmonary neuroendocrine cell neoplasia |
|
|
Term
| what are the general lung CA classifications? |
|
Definition
| squamous cell carcinoma, adenocarcinoma, and small cell carcinoma |
|
|
Term
| what characterizes small cell carcinoma? |
|
Definition
| small cell carcinomas are most often metastatic w/a high initial response to chemotherapy |
|
|
Term
| what characterizes non-small cell carcinoma? |
|
Definition
| non-small cell carcinomas are less often metastatic and less responsive to chemotherapy |
|
|
Term
| where does lung CA commonly arise from? less commonly? |
|
Definition
| lung CA arises in the hilus of the lung commonly and most originate from the bronchi. a small number of primary tumors arise in the periphery from the alveolar septal cells or terminal bronchioles - these are typically adenocarcinomas, w/one type being the bronchioalveolar type |
|
|
Term
| how does squamous cell CA begin? how can it progress? |
|
Definition
| as an area of in situ cytologic dysplasia which eventually develops into a small area of thickening bronchial mucosa. this then progresses to a warty excrescence that elevates or erodes the epithelium which can fungate through the bronchial lumen (can cause obstructive atelectasis). |
|
|
Term
| what characterizes the continual spread of lung CA? |
|
Definition
| lung CA may penetrate the bronchus to infiltrate the peribronchial tissue or mediastinum. it may extend to the pleura, pericardium, mediastinal, tracheal, and bronchial nodes. the mass is always firm and gray-white with foci of hemorrhage and necrosis |
|
|
Term
| what sex has a higher predilection for squamous cell lung carcinomas? what is the process that happens to the squamous cells? what characterizes the mitotic activity of the tumors? where do most arise? |
|
Definition
| squamous cell lung CA is more common in men who smoke. the squamous cells undergo keratinization, and mitotic activity if greater in the poorly differentiated tumors. most of the squamous cell carcinomas arise centrally (hilum) - but the incidence in the periphery is increasing |
|
|
Term
| what kind of mutations do squamous cell lung CA have a high frequency of? what is the rate of association between squamous cell lung CA and EGF, CDK-inhibitor, and RB? |
|
Definition
| squamous cell lung CA has *the highest frequency of p53 mutations. overexpression of epidermal growth factor has been detected in 80% of cases. the CDK-inhibitor is inactivated and its protein product is lost in 65% of tumors. they may lack protein expression of the tumor suppression gene RB in about 15% of cases. |
|
|
Term
| how does squamous cell lung CA appear histologically? |
|
Definition
| a ball of squamous cells with prominent nuclei and a keratin pearl |
|
|
Term
| what is the most common type of lung CA in women and nonsmokers? what kind of differentiation do they have? what kind of growth patterns? where are they located in the lung? |
|
Definition
| adenocarcinomas, which are epithelial tumors of *glandular differentiation or mucin production. they have *multiple growth patterns; acinar, papillary, bronchioalveolar, and solid. adeoncarcinomas are *more peripherally located and smaller than squamous cell CA |
|
|
Term
| how does the growth of adenocarcinomas in the lung compare to SCCs? are they associated with scarring? are there any genetic mutations primarily seen in adenocarcinomas? |
|
Definition
| adenocarcinomas grow more slowly than SCCs, but metastasize more widely and earlier. they are associated w/scarring and KRAS mutations are primarily seen in adenocarcinomas, while p53, RB, and p16 mutations/inactivation are seen with the same frequency as those in SCC |
|
|
Term
| how do adenocarcinomas appear histologically? |
|
Definition
| they may appear to be "trying" to form primitive glands - by circling |
|
|
Term
| how does adenocarcinoma appear in terms of differentiation? |
|
Definition
| they can have moderate differentiation - w/some appearance of gland formation, though the cells still have abnormalities (high N/C ratios, poorly shaped lumens, mitotic figures, *nuclei of various heights) |
|
|
Term
| where do bronchioloalveolar carcinomas typically form? how do they form? can they cause atelectasis/emphysema? |
|
Definition
| in the terminal bronchioalveolar regions - usually occurring in the *peripheral region, either as a nodule or multiple diffuse nodules which may coalesce to form *pneumonia-like consolidation. these nodules have a mucinous, gray secretion or a solid white area. major bronchi are not involved - so atelectasis and emphysema are *uncommon. they may mimic some granulomatous formations. |
|
|
Term
| do broncioloalveolar carcinomas destroy the structures they grow along? |
|
Definition
|
|
Term
| what are the 2 types of broncioloalveolar carcinomas? |
|
Definition
|
|
Term
| what defines a mucinous broncioloalveolar carcinoma? |
|
Definition
| mucinous broncioloalveolar carcinomas have *tall, columnar cells w/cytoplasmic and alveolar mucin that spread and form satellite tumors. they may present as a single nodule, multiple nodules, or a consolidation of an entire lobe resembling lobar pneumonia - less likely to be cured by sx |
|
|
Term
| what defines the non-mucinous type of broncioloalveolar carcinomas? |
|
Definition
| non-mucinous broncioloalveolar carcinomas have columnar *or cuboidal-shaped cells which consist of a *peripheral lung nodule w/rare spread and is more amenable to sx. |
|
|
Term
| may there be a connection between atypical adenomatous hyperplasia, non-mucinous type of broncioloalveolar carcinomas and invasive adenocarcinomas? |
|
Definition
|
|
Term
| what defines the cells of small cell lung CA? how malignant is this CA generally? |
|
Definition
| small cell carcinomas have cells with *scant cytoplasm, *ill defined cell borders, *finely granular nuclear chromatin and *absent or inconspicuous nucleoli. the cells are round to oval **w/nuclear molding (mold around each other like in a puzzle)** and grow in clusters *w/o glandular or squamous organization. the *mitotic count is high and all cells are *high grade |
|
|
Term
| what is a a combined small cell carcinoma? |
|
Definition
| a small cell carcinoma which includes large cells and neuroendocrine carcinomas |
|
|
Term
| how would a small cell carcinoma appear on EM? |
|
Definition
| a dense core of *neurosecretory granules |
|
|
Term
| what do small cell carcinomas secrete? |
|
Definition
| *polypeptide hormones and *neuroendocrine markers |
|
|
Term
| do small cell carcinomas have a strong link to cigarette smoking? |
|
Definition
|
|
Term
| where do small cell carcinomas occur? |
|
Definition
| in the major bronchi and in the periphery of the lung |
|
|
Term
| what is the most aggressive of all the lung tumors? |
|
Definition
| small cell carcinomas which metastasize widely and are virtually incurable by sx |
|
|
Term
| is there a known preinvasive phase or carcinoma insitu for small cell carcinoma? |
|
Definition
|
|
Term
| what genes are frequently mutated with small cell carcinoma? |
|
Definition
| p53 and RB tumor suppressor genes are frequently mutated, while the **anti-apoptotic gene BCL2 is seen in 90% of tumors w/a **low frequency of the pro-apoptotic gene BAX |
|
|
Term
| how do small cell carcinomas appear histologically? |
|
Definition
| a lot of small dark cells molded together, very little cytoplasm |
|
|
Term
| what is a large cell carcinoma? |
|
Definition
| a bit of a misnomer, but this refers to an undifferentiated epithelial tumor which lacks the cytologic feature of a small cell cacinoma and glandular or squamous differentiation. |
|
|
Term
| how do large cell carcinomas appear histologically? |
|
Definition
| large nuclei, *prominent nucleoli, and a *moderate amount of cytoplasm |
|
|
Term
| what might a large cell carcinoma represent? |
|
Definition
| an undifferentiated adenocarcinoma or SCC |
|
|
Term
| what is one variant of large cell carcinoma? |
|
Definition
| the large cell *neuroendocrine carcinoma |
|
|
Term
| what is some secondary pathology that lung CA can lead to ? |
|
Definition
| partial obstruction causing *focal emphysema, total obstruction leading to (resorption) atelectasis, impaired drainage of the airway leading to suppurative or ulcerative bronchitis/bronchiectasis, pulmonary abscesses, *superior vena cava syndrome (compression of the SVC leads to venous congestion & dusky head+arm edema), and extension to pericardial or pleural may cause pericarditis/pleuritis (sharp pain upon inhalation) |
|
|
Term
|
Definition
| adenomas may secrete cellular lipid to the point of lung obstruction due to macrophages engulfing the lipid and accumulating (foamy macrophages) |
|
|
Term
| can lung CA cause hoarseness? |
|
Definition
| yes, if the recurrent laryngeal nerve is invaded |
|
|
Term
| can lung CA cause dysphagia? |
|
Definition
| yes due to esophageal impingement/invasion |
|
|
Term
| can lung invade and destroy ribs? |
|
Definition
|
|
Term
|
Definition
| when lung CA invades the sympathetic ganglia |
|
|
Term
| what is the clinical course of lung CA? |
|
Definition
| cough, *weight loss, chest pain, dyspnea. most lung CA pts have a poor prognosis and the overall survival rate is about 15%. some pts may be cured by lobeectomy or pneumonectomy |
|
|
Term
| what are paraneoplastic syndromes? |
|
Definition
| paraneoplastic syndromes occur when tumors begin to secrete their own hormones for example: ADH (inducing hypoatremia - test for electrolytes) and ACTH (adrenocorticotropic hormone = cushing syndrome, truncal obesity/abdominal striae/buffalo hump/muscle wasting in the extremities), PTH/prostaglandin E (hypercalcemia, potentially associated w/metastatic bone lesions), calcitonin (gynecomastia), and serotonin/bradykinin (carcinoid syndrome - skin flushing) |
|
|
Term
| what kind of lung CA is associated with paraneoplastic secretion of ACTH and ADH? |
|
Definition
|
|
Term
| what kind of lung CA is associated with hypercalcemia? |
|
Definition
|
|
Term
| what is lambert-eaton myasthenic syndrome? |
|
Definition
| muscle weakness caused by auto-antibodies directed to the neuronal Ca++ channel |
|
|
Term
| can lung CA cause peripheral neuropathy? |
|
Definition
| yes - most likely due to Ca++ or electrolyte abnormalities |
|
|
Term
| what is *acanthosis nigricans? |
|
Definition
| thickened hyperpigmented areas of skin often seen in flexural areas such as the axillae, groin and anogenital regions - linked w/lung CA |
|
|
Term
| can lung CA lead to leukomoid rxns? |
|
Definition
| yes, there may be abnormal levels of WBCs in peripheral circulation |
|
|
Term
| can lung CA lead to hypertrophic pulmonary osteoarthropathy? what is this? |
|
Definition
| yes, hypertrophic pulmonary osteoarthropathy is *clubbing of the fingers due to an abnormality of the connective tissue |
|
|
Term
| what is horner syndrome, which is associated with lung CA? |
|
Definition
| enophthalmos, ptosis, miosis, anhidrosis on the same side as the lesions due to *apical lung tumors* in the superior pulmonary sulcus which invade the neural structures around the trachea - including the *cervical sympathetic plexus* these tumors are referred to as *pancoast tumors* |
|
|
Term
| what % of lung tumors are carcinoid? who do they affect? incidence associated w/smoking? |
|
Definition
| 1-5% most pts affected are younger than 40 yrs and can be either sex. about 20-40% are non-smokers? |
|
|
Term
| what are carcinoid tumors? |
|
Definition
| low grade malignant tumors. typical carcinoids have no p53 mutations or BCL2/BAX imbalance, but atypical carcinoids will. some carcinoids show loss of heterozygosity at 3p, RB, 9p and 5q22 |
|
|
Term
| how do carcinoid tumors grow? |
|
Definition
| carcinoid lung tumors may arise centrally or peripherally and grow as *finger-like or *spherical polyploid masses* (button-like) that project into the lumen of the bronchus and are covered by intact mucosa. they rarely exceed 3-4 cm in diameter |
|
|
Term
| how do carcinoid tumors appear histologically? |
|
Definition
| carcinoid tumors are composed of trabecular (bridge-like), palisading, ribbon, or rosette-like arrangements of cells separated by delicate *fibrovascular stroma. they have uniform, round nuclei and a moderate amount of *eosinophilic cytoplasm |
|
|
Term
| how do carcinoid tumors appear on EM? |
|
Definition
| dense core granules characteristic of *neuroendocrine tumors |
|
|
Term
| what are differences between typical and atypical carcinoid tumors? |
|
Definition
| typical carcinoids: few mitoses/no necrosis, atypical carcinoids: more frequent mitoses, may have necrosis, increased cellularity, nucleoli, lymphatic invasion and disorganized architecture. |
|
|
Term
| what is carcinoid syndrome? |
|
Definition
| attacks of diarrhea, flusching and cyanosis |
|
|
Term
| do carcinoid tumors metastasize? what is their clinical course like? |
|
Definition
| most carcinoid tumors do not metastasize to distant sites and are amenable to sx and follow a relatively benign course for long periods |
|
|
Term
| what are other symptoms of carcinoid tumors? |
|
Definition
| cough, hemoptysis, infections, bronchiectasis, atelectasis, and emphysema |
|
|
