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86 Cards in this Set
- Front
- Back
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PATHOLOGY OF DIFFUSE ENDOCRINE (APUD) SYSTEM - CIBULL - WEDNESDAY FEB 21
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what do cells in the APUD system (distributed throughout body) have in common (4)?
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1) biochemical characteristics; 2) morphology; 3) function; 4) embryogenesis
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what does APUD stand for?
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amine precursor uptake and decarboxylation
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what does this system use as biochemical precursor substrates (2)?
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1) dopa; 2) 5-HT
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what does this system secrete (2 types of molecules)?
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1) LMW polypeptides; 2) bioactive amines
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how is the morphology of APUD cells similar in LM?
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similar cytology and pattern of growth
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what stains can all APUD cells take up (2)?
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10 silver; 2) chromogranin
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how are APUD cells similar on EM?
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all have cytoplasmic dense core (neurosecretory) granules
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how are many APUD tumors identified?
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due to excess secretion of biologically active substances, with resultant clinical syndromes (many APUD cells have endocrine function)
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what cells do all APUD cells arise from embryologically (2)?
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1) neuroectodermal; 2) gut-related endodermal
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what is the incidence of carcinoid tumors?
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1-2 / 10^5
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what is the M:F ratio?
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2 to 3
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what is the most common age?
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50, although any age is possible
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77% of what tumor site are carcinoid tumors?
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appendiceal
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what is the most common site of carcinoid tumors, and what % come from this site?
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lungs, bronchi, and trachea - 32.7 %
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what is the next most common site?
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ileum - 17.6 (followed by rectum - 10.1%, and appendix - 7.6%) - overall, more occur in the GIT than the respiratory system - other sites are the stomach, duodenum, jejunum, cecum, and colon
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what does metastatic potential of carcinoid tumors correllate best with?
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size and location (rather than histologic appearance)
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what location has the highest % localized at diagnosis?
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appendix - 98%
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what % are localized in the small intestine, colon, rectum & sigmoid, and lungs?
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SI - 40%, colon - 30%, rectum and sigmoid - 85%, lungs - 80%
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what is the rate of metastasis if the tumor is <2cm, and >2cm?
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if <2cm, mets unusual (<10%), if >2cm mets common (>80%)
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what % of carcinoids are multiple?
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up to 20%
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what is the growth pattern of carcinoids?
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slow growing - even with liver metastases, 5 year survival is >20%
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what blood tests can be used to follow disease status (2)?
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1) serum chromogranin levels; 2) urine 5-H1AA
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what % of patients are positive for urine 5-H1AA?
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75%
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what % of carcinoid tumors are associated with non-carcinoid tumors?
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roughly 10%
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what are carcinoid syndromes related to?
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secretion of active substances (serotonin, etc.)
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what substances were mentioned to be involved in carcinoid syndromes of midgut (2)?
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1) serotonin; 2) kaliikrein
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what problems were said to occur in carcinoid syndromes (4)?
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1) flushing; 2) cramping abdominal pain/diarrhea; 3) asthma; 4) endocardial fibrosis
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what % get asthma?
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10-20%
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what % get endocardial fibrosis, and what is it (2 problems)?
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2/3 of patients with carcinoid syndromes develop carcinoid heart disease: 1) right sided endocardial fibrosis; 2) tricuspid insufficiency
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what GI origin was said to cause an atypical carcinoid syndrome?
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foregut origin
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what may effects of these foregut tumors be related to and why?
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many effects may be histamine ralted, because these tumor cells lack decarboxylase activity, and they don't make serotonin, and patients don’t excrete 5-H1AA
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what effects may be seen from histamine (4)?
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1) prolonged dark flush; 2) facial edema and tearing; 3) profound vasodilation; 4) shock
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what must tumors in the gut get past for carcinoid syndrome to take place?
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bioactive substances must get past the liver - if the tumor is in the portal circulation, liver metastases must exist
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when may carcinoid syndromes not be related to metastatic disease?
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when they occur outside the portal circulation
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what type of carcinoid was said not to cause carcinoid syndrome, and why?
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hindgut carcinoid, because it does not secrete bioactive substances
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ISLET CELL TUMORS
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what % of autopsies turn up islet cell tumors?
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1.5% (but clinical syndromes are much less common)
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why are most malignant and benign islet cell tumors found?
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because of symptoms related to the secretion of bioactive substances (80% of malignant tumors and all benign tumors/hyperplasias are found this way)
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what are four things that favor malignancy in islet cell tumors?
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1) not an insulinoma; 2) >2cm; 3) angioinvasion; 4) Ki-67 more than 2%
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what is the most common islet cell tumor?
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insulinoma
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what % are benign, what % are multiple or hyperplasia, and what % are malignant?
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80% benign, 10% multiple or hyperplasia, 10% malignant
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what is diagnosis of insulinoma related to (2)?
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1) hypoglycemia; 2) resultant sympathetic stimulation
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what is the name of the triad that helps diagnose insulinoma, and what are the three things this triad consists of?
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Whipple's Triad - 1) attacks precipitated by fasting with; 2) blood sugards < 50mg/100ml; 3) relieved by glucose
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what is the second most common islet cell tumor, and where do most occur?
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gastrinoma - most (85%) are pancreatic, 13% are duodenal
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what % are benign, what % are multiple or hyperplasia, and what % are malignant?
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20% benign, 20% multiple or hyperplasia, 60% malignant
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what syndrome is involved with gastrinomas?
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Zollinger-Ellison syndrome
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how can Z-E syndrome cause diarrhea, and what % get it?
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damages intestinal mucosa by hypersecretion of gastric acid - 33%
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what % of Z-E sufferers get peptic ulcer disease and what are ulcers like (severity, location)?
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25% - fulminant, recurrent, resistant peptic ulceration - ulceration may be more distal than usual
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what other problems occur in Z-E syndrome, in order of frequency (4)?
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1) pain (95%); 2) G.I. bleeding (40%); 3) vomiting (26%); 4) perforation (18%)
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what things are used to diagnose gastrinoma?
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1) elevated serum gastrin (3-30x / nl); 2) elevated gastric secretion (both acid and volume) not affected by stimulation
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what is the treatment for gastrinoma (4)?
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1) remove tumors (if possible); 2) H2 blocker or related drugs; 3) antineoplastic drugs; 4) total gastrectomy
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what is the mortality of gastrinoma, if untreated?
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78%
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what % of patients died of neoplastic progression, in the past?
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only 20%
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what is the prognosis with aggressive medical/surgical management?
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10-year survival may be greater than 90%
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what are two rare types of islet cell tumors?
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1) glucagonomas; 2) diarrheogenic
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what problems can glucagonomas cause in the GIT (3)?
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1) constipation; 2) ileus; 3) ascites
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what other problems can glucagonomas cause (2)?
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1) diabetes mellitus (usually not severe); 2) dermatitis (necrolytic migratory erythema)
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what are diarrheogenic islet cell tumors?
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non-B islet cell tumors
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what syndrome is associated with diarrheogenic carcinoid tumors, and what else is it known as?
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Verner-Morrison syndrome - WDHA
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what does WDHA stand for?
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Watery Diarrhea, Hypokalemia, Achlorhydria
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what other tumors are there rare reports of?
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islet cell tumors secreting other peptides such as CCK and somatostatin with resultant clinical manifestations
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MULTIPLE ENDOCRINE NEOPLASIA SYNDROMES
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how are all MEN syndromes inherited?
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autosomal dominant inheritence
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what are alternate names for MEN I (2)?
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1) pluriglandular; 2) Wermer's
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what are alternate names for MEN II (2)?
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1) Sipples; 2) IIA
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what is an alternate name for MEN III?
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IIB
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what are the most common tumor sites of involvement in MEN-I (3)?
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1) pituitary (65%); 2) parathyroid (88%); 3) pancreas (islet cell tumor - 81%)
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what are the most common tumor sites of involvement in MEN-II (3)?
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1) parathyroid (45%); 2) medullary CA (75-100%); 3) pheochromocytoma (40-75%)
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what are the most common tumor sites of involvement of MEN-III?
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1) medullary CA (94%); 2) pheochromocytoma (41%); 3) ganglioneuromatosis
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what is the most common islet cell tumor in MEN-I?
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gastrinoma
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what is parathyroid disease like in MEN-I (90 % of the time)?
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four gland hyperplasia
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what % of patients with Z-E syndrome have MEN-I?
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20-50%
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where is the MEN-I gene located (chromosome)?
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chromosome 11
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what should be remembered about tumors in both II and III (2)?
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1) pheochromocytoma often bilatera/extra-adrenal; 2) medullary carcinoma usually multifocal
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what area is never involved in MEN-III?
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parathyroid
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what should be remembered about tumors that occur in III?
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1) medullary carcinoma is very aggressive (more so than in sporadic or II); 2)
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what else is common in MEN-III (not a tumor)?
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skeletal anomalies are common (81%)
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what gene is responsible for MEN II, II, and familial medullary carcinoma of the thyroid, and what chromosome is it located on?
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RET proto-oncogene, located on chromosome 10
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so, what tumors do II and III involve, that MEN-I does not (2)?
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1) medullary CA; 2) adrenal medulla (pheochromocytoma)
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what do MEN I and II involve, but not III?
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parathyroid glands
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