Flashcards in Path Tricky Things Deck (124):
What does CIN stand for?
cervical intraepithelial neoplasia
Why do we classify things as CIN I-III?
because severe dysplasia looks nearly the same as early neoplasia (carcinoma in situ)
What is CIN III?
carcinoma in situ lumped with severe dysplasia
What is it called when CIN II and III are clumped together?
HSIL (high grade squamous intraepithelial lesion)
What is LSIL?
Low grade squamous intraepithelial lesion (basically CIN I)
What do LSIL cells look like on a pap smear?
What is a germline mutation in TP53 called?
What is a germline mutation in MEN1 called?
multiple endocrine neoplasia syndrome
What is the serum (mucin) marker for ovarian cancer?
An NMYC amplification causes what?
neuroblastoma (neural-crest cell derived tumor OUTSIDE the brain in small children)
An NF1 mutation (tumoral) is associated with what?
A germline NF1 mutation is associated with what?
type I neurofibromatosis
Germline CDKN1A mutations are present in 25% of what cancers?
Tumoral CDKN1A mutations are present in what cancers?
70% of glioblastomas (ONLY in adults)
75% of pancreatic carcinomas
What is the biggest hint that your patient has pancreatic cancer?
HUGE weight loss
List the 5 mutations in colon cancer in order.
1) APC mutation
2) loss of DNA methylation
3) RAS gene mutation
4) SMAD mutation on ch. 18
5) p53 mutation
What is the most common type of lung cancer? (more common in non-smokers, young patients, and women)
lung primary adenocarcinoma
Where do you find lung adenocarcinoma?
in the lung periphery (because small particles from pollution or not trapped by cigarette filter can travel further into the lung)
What is AAH?
atypical adenomatous hyperplasia (dysplasia of lung in pathway to primary adenocarcinoma)
What is BAC?
BRONCHIOLOALVEOLAR CARCINOMA (second step toward primary adenocarcinoma in lung--special type of "adenocarcinoma in situ")
What is dysplasia of the breast called?
What oncogenes are responsible for downregulation of E-cadherin expression and EMT?
SLUG and TWIST
Breast cancer has what 2 chemokines that bind to what 2 endothelial cell ligands for metastasis to other organs?
CXCR4 and CCR7 receptors bind to CXCL12 and CCL21 on target organs
What is a tumor embolus? What can it lead to?
tumor cells that have bound to platelets. Can pass though right heart and into lungs leading to pulmonary HTN and right heart failure if gets stuck in small pulmonary blood vessel
List the autosomal recessive syndromes of defective DNA repair?
What hereditary AD cancer syndrome is associated with MAH2, MLH1, and MSH6?
Hereditary non-polyposis colon cancer
(DNA mismatch repair faulty--no "proofreading"
BRCA1 and BRCA2 mutation are AD cancer syndromes caused by a cell being unable to do what?
fix dsDNA breaks
Those with Xeroderma pigmentosum are unable to do what?
remove pyramidine dimers via nucleotide excision repair
Those with Ataxia telangiectasia have what mutated?
ATM (signals p53 that there is cellular damage due to ionizing radiation)
Those with Faconi anemia are unable to do what?
fix DNA damage due to cross-linking agents like nitrogen mustards
How does p53 get involved with angiogenesis?
it induces TSP-1 from stromal fibroblasts (which is anti-angiogenic)
What is the most important etiologic factor in stomach cancer (gastric adenocarcinoma and MALT lymphomas)?
What is the oncoprotein associated with Helicobacter pylori? What does it do?
CagA (molecular syringe that activates RAS, RAF, etc. pathway that leads to proliferation)
If you see "abnormal cells floating like balloons up into the epidermis," what is your diagnosis?
What are the 4 factors associated with a mole v. melanoma?
diameter (smaller/larger than 6 mm)
What is the major cause of hepatocellular carcinoma?
What liver enzyme is slightly elevated in Hep C patients?
ALT (higher than AST slightly)
What are the top 3 symptoms of lung cancer?
What is the most common lung cancer in SMOKERS?
small cell carcinoma (basically no one who is a non-smoker will get this type)
Cachexia is mediated by what?
TNF release from macrophages
What is the most common paraneoplastic syndrome?
Hypercalcemia is seen with what types of cancer?
squamous cell carcinoma of lung
Adult T cell leukemia/lymphoma
What is the MAJOR causal agent of hypercalcemia?
parathyroid hormone-related protein
Cushing syndrome is seen with what types of cancer?
small cell carcinoma of the lung
neural tumors (PITUITARY ADENOMA)
What is the mediator of Cushing syndrome?
Carcinoid syndrome is associated with what types of cancer?
What is the causal agent of Carcinoid syndrome?
serotinin (and bradykinin)
What are the major symptoms of hypercalcemia?
NAUSEA, vomiting, constipation, polyuria, disorientation, lethargy, seizures
What is used to treat hypercalcemia?
What are the major symptoms of Cushing syndrome?
weight gain, moon face, weakness, hirsutism, HTN, glucose intolerance, depression, psychosis, buffalo hump, abdominal red striae, plethora, etc.
What are the major symptoms of Carcinoid syndrome?
flushing attacks (that may go to persistent erythema or cyanosis), diarrhea, cramps, nausea, vomiting, cough, etc.
What would you expect to find in the intestines of someone with Carcinoid syndrome?
coalescing nests of intestinal carcinoid
How many years does it typically take for smoking to cause lung cancer?
What proportion of prostate cancer patients have symptoms at the time of diagnosis?
What proportion of lung cancer patients have symptoms at the time of diagnosis?
True or false: PS is neither specific nor sensitive.
FALSE: according to Nichols, it IS sensitive (though NOT diagnostic) but lacks specificity
What proportion of breast cancer patients have symptoms at the time of diagnosis?
What are some risk factors for breast cancer? Specifically with reproductive tract?
obesity after menopause
NOT breast feeding
What word describes the anatomic extent of a tumor--including its size, extent of lymph node involvement, and distant metastases?
What word describes the qualitative assessment of the differentiation of a tumor (extent to which it resembels normal tissue at primary site)?
How does someone with RIGHT sided colon cancer differ from LEFT sided?
Right sided: bigger, more likely to be silent/advanced, because stool on right side is more liquid
Left sided: blockage more common (stool more thick on this side), patients notice watery stool
Colon cancer typically occurs in patients of what age?
What are the 3 most common symptoms of colon cancer?
change in bowel habits
hematochezia (fresh blood from anus) or melena (black, tarry stool)
What dietary component is associated with colon cancer?
True or Fasle: many colon cancers are caught late, after they have become metastatic.
FALSE: 80% are caught during colonoscopies before they are metastatic
What does cirrhosis look like?
regenerative nodules of hepatocytes completely surrounded by fibrous tissue with numerous lymphocytes
What is the most common location for an osteosarcoma?
distal femur near knee
What is the most common neoplasm in bone?
malignant neoplasm from distal area
Hamartomas are most commonly found where?
in the lung
What feature is commonly seen in ovarian carcinomas?
What type of tumor secretes PDGF and expresses PDGFR?
What type of tumor secretes TGF-alpha and expresses the TGF-alpha receptor?
What is SMAD?
a gene that is responsible for TGF-beta signal transduction
What cancer is SMAD mutation associated with?
What is the major role of TGF-beta?
to inhibit proliferation by activating CDKIs and suppressing MYC and cyclins
If you see alveoli full of foamy exudate, what should you think of?
pneumocystis jiroveci pneumonia (presenting feature in AIDS patients (CD4+ T cells less than 200)
What blood abnormality is most commonly found in those with pneumocystis jiroveci pneumonia?
hypoxemia (alveolar exudate and interstitial inflammation create an alveolar-capillary block impeding gas exchange)
If you see little RBC-shaped cysts in a bronchoalveolar lavage fluid silver-stained, what should you think of?
pneumocystis jiroveci pneumonia "pneumocystis cysts"--this is used to confirm infection!
What are the prime effector cell defenses in AIDS patients?
If you see a mass of lymphocytes and macrophages in a circle surrounded by brain tissue, what should you think of?
microglial nodule (brain equivalent of granuloma)
If you see an empty looking area with giant cells and edema surrounded by brain tissue, what should you think of?
HIV encephalitis--multinucleated giant cells formed by perivascular macrophages. HIV virus is MOST LIKELY carried to the brain by infected MONOCYTES.
If you see meninges tissue with little circular hoops within them, what should you be thinking?
cryptococcus neoformans meningitis
A HIV patient with cryptococcus neoformans meningitis would present with what complaint?
What are the two defining features of cryptococcus neoformans meningitis?
"halo" due to capsule and "narrow base budding"
True or false: only HIV patients get cryptococcus neoformans meningitis.
FALSE, 50% of people with the meningitis do NOT have HIV
If you see cells that are large, basophilic, granular, and have "owls eyes," what should you think of?
In AIDS patients, CMV is usually disseminated, but what 2 areas does it commonly locate as well?
CMV enteritis (causes diarrhea)
CMV retinitis (causes visual impairment)
If you see a clump of basophilic mess ("molded inclusions") that have large-looking nuclear areas with chromatin pushed to the margins, what should you be thinking?
Herpes simplex virus
List the viral load for the 3 phases of HIV.
Acute: peaks around 10 million/mL by 6 weeks
Chronic: decreases to around 10,000 for about 9 years
Final Crisis: increases back to 10 million/mL at about 11 years
List the CD4 Count for the 3 phases of HIV.
Acute: drops from 1000/cu mm (normal) to 500/cu mm by 6 weaks
Chronic: gradual, fluctuating decline to around 50/cu mm at 9 years
Final Crisis: falls to around 5/cu mm at 11 years
In a patient with chronic phase HIV, what can you detect first: anti-envelope antibody or anti-p24 antibody (major capsid protein)?
Anti-envelope antibody increases around 8 weeks and quickly peaks around 1 year. Major capsid protein increases around 8 weeks and more gradually peaks around 5 years.
List the 4 (immunologic) predispositions to lupus.
1) Complement C1q, C2, or C4 deficiency
2) High Interferon-alpha
3) HLA-DR2 or HLA-DR3 haplotype
4) Lymphocytes with TLR7 or TLR9
What environmental factors can predispose to lupus?
-exposure to sunlight
-sex hormones (estrogen makes it much more common in women)
If you see a glomerulus with thickened blood vessels (wire looping) and a crescent of epithelial cells, what should you think of?
diffuse lupus nephritis
What is the most common cause of lupus death?
Early scleroderma has what feature, late scleroderma has what feature?
Diffuse systemic sclerosis is associated with Abs against what? What are they called?
DNA topoisomerase I (Anti-Scl-70 antibodies)
Limited scleroderma (CREST syndrome) is associated with Abs against what?
What is the FIRST manifestation of systemic scleroderma?
(Raynauld's phenomenon, edema, etc. also occurs)
If you see skin with no pegs and lots of collagen, what should you think of?
What might you see in the renal arteries of a person with scleroderma?
"onion skinning" where concentric sclerosing of medium sized interlobar arteries (150-500) resemble onions
People with Sjogren syndrome are at increased risk of what?
non-Hodgkin B cell lymphoma (arises in setting of robust polyclonal B cell proliferation)
All transplant biopsies must be evaluated for what?
infections and post-transplant lymphoproliferative disorder (PTLD)
What type of cells are commonly seen at transplant rejection sites?
If you see diffuse lymphocytic infiltration obliterating transplanted kidney tubules, what should you think of?
acute cellular rejection
What is a rare but specific sign of amyloidosis?
peri-orbital edema and yellow-brown skin discoloration
What is typically the first site of amyloid deposition?
What are the 2 types of amyloidosis?
What are common presentations of people with amyloidosis?
What would be increased in serum of a patient with amyloidosis and hepatomegaly?
ALP (released into the blood with liver injury or hepatic space-occupying disease)
What type of amyloid gets deposited in brain of those with dementia?
a-beta amyloid makes "plaques" of loose eosinophilic material in the brain and brain's blood vessels
If you hear that "hyaline" dense eosinophilic interstitial deposits are squeezed between myocytes, what should you think of?
What is cardiac amyloidosis caused by?
deposition of transthyretin
What is the presentation of someone with cardiac amyloidosis?
elderly African-american male with sudden death (arrhthmia) or dyspnea (left heart failure)
What does gross cardiac amyloidosis look like?
abnormally pale-colored heart muscle
Describe an amyloid kidney? (microscopic)
lots of hyaline deposits are seen in the glomeruli and a little in the interstitium or walls of blood vessels
Describe an amyloid kidney? (gross)
enalrged, pale, grey and firm
What is the diagnostic test to confirm amyloidosis?
Congo red stain (apple green birefringence under polarized light)
You would only (most likely) see amyloidosis A deposits in what type of patients?
those with a history of chronic inflammatory disorders (leading to the reactive systemic amyloidosis)
What is the most common type of amyloid deposit?
AL amyloidosis (from free immunoglobulin light chains due to proliferation of plasma cells)
What is the common presentation of someone with primary amyloidosis?
peripheral edema (maybe weight gain from fluid)
Due to renal disease (nephrotic syndrome)
Preceded by nonspecific symptoms (fatigue)
If you hear of a patient with fever, abdominal pain, skin nodules, bloody stool, peripheral motor neuropathy, etc., what should you think of?
What is polyarteritis nodosa?
segmental transmural necrotizing vasculitis of small and medium arteries with fibrinoid necoriss and lesions at different stages (NOT associated with Abs)