Pathology Flashcards
Vimentin stains for…
connective tissue intermediate filaments
desmin stains for…
muscle intermediate filaments
cytokeratin stains for…
epithelial cell intermediate filaments
GFAP stains for…
neuroglia intermediate filaments
Neurofilaments stain for…
neuron intermediate filaments
Post-strep glomerulonephritis IF and EM findings
IF = C3 granular staining along GBM EM = subepithelial humps
Anti-GBM disease LM and IF findings
LM - glomerular crescents
IF = linear staining (IgG) along GBM
Rapidly progressive glomerulonephritis LM and IF findings
LM = glomerular crescents IF = fibrinogen in crescent
IgA nephropathy LM and IF findings
LM = mesangial hypercellularity IF = IgA in mesangium
Alport syndrome EM findings
EM = lamellated appearanced of GBM
Granulomatous Diseases
M. TB Fungal infections (e.g. histo, coccidioid) Treponema pallidum (syphilis) M. leprae (leprosy) Bartonella Henslae Sarcoidosis Crohn's Granulomatosis with polyangiitis Churg-Strauss syndrome Berylliosis, silicosis
Th1 releases IFN gamma –> macros activated –> release TNF alpha –> induces and maintains granuloma
anti-TNF drugs –> granuloma breakdown –> system disease
Transudate
hypocellular
protein poor
specific gravity
Exudate
cellular
protein rich
specific gravity >1.020
c/b:
lymphatic obstruction
inflammation
eg cancer, infection, PE
Iron poisoning
cell death 2/2 peroxidation of membrane lipid
acute - gastric bleeding
chronic - metabolic acidosis, scarring leading to GI obstruction
Amyloidosis
abrnomal aggregation of proteins or their fragments into beta pleated sheet structures –> cell damage and apoptosis
affected tissue = waxy appearance
AL amyloidosis = primary
deposition of Ig Light chains
c/b plasma cell d/o or MM
multi organ impact = renal, cardiac, hematologic, hepatomegaly, neuropathy
AA (secondary) amyloidosis
fibrils composed of serum Amyloid A –> multisystem
RA, IBD, spondyloarthropathy, chronic infections
Dialysis-related amyloidosis
fibrils composed of beta2-microglobulin in pts with ESRD and long-term dialysis
p/w carpal tunnel syndrome and other joint issues
heritable amyloidosis
eg ATTR neurologic/cardiac amyloidosis c/b transthyretin (TTR or prealbumin) gene mutation
transthyretin = protein that make amyloid fibrils
senile systemic amyloidosis
deposition of wild-type TTR in myocardium and other sites
slower progression of cardiac dysfunction than AL type
organ-specific amyloidosis
single organ
Alzheimer’s 2/2 deposition of amyloid-beta protein cleaved from amyloid precursor protein (APP)
what cytokines is cachexia mediated by?
TNF-alpha
IFN-gamma
IL-6
what neoplasms are associated with Down Syndrome?
ALL (“we ALL fall DOWN”)
AML
what neoplasms are associated with Xeroderma pigmentosum, albinism?
squamous cell carcinomas of the skin
melanoma
basal cell carcinoma
what neoplasms are associated with tuberous sclerosis (facial angiofibroma, seizures, mental retardation)?
Giant cell astrocytoma
renal angiomyolipoma
cardiac rhabdomyoma
what neoplasm is associated with actinic keratosis?
squamous cell carcinoma of the skin
what neoplasm is associated with Plummer-Vinson syndrome (dec Fe)?
squamous cell carcinoma of the esophagus
what neoplasms are associated with Paget’s disease of bone?
secondary osteosarcoma and fibrosarcoma
what neoplasm is associated with autoimmune disease (eg Hashimoto’s thyroiditis, myasthenia gravis)?
Lymphoma
what neoplasms are associated with acanthosis nigricans?
visceral malignancy (stomach, lung, uterus)
what neoplasms are associated with radiation exposure?
Leukemia
sarcoma
papillary thyroid cancer
breast cancer
abl associated tumor and gene product
CML
Tyrosine kinase
c-myc associated tumor and gene product
Burkitt’s lymphoma
Transcription factor
bcl-2 associated tumor and gene product
follicular and undifferentiated lymphomas (inhibits apoptosis)
anti-apoptotic molecule
ras associated tumor and gene product
colon carcinomas
GTPase
L-myc associated tumor and gene product
Lung tumor
Transcription factor
N-myc associated tumor and gene product
Neuroblastoma
Transcription factor
ret associated tumor and gene product
MEN2A and 2B
Tyrosine kinase
c-kit associated tumor and gene product
Gastrointestinal stromal tumor (GIST)
cytokine receptor
Rb associated tumor and gene product
retinoblastoma, osteosarcoma
inhibits E2F; blocks G1 –> S phase
p53 associated tumor and gene product
most human cancers, Li-Fraumeni syndrome
Transcription factor for p21, blocks G1 –> S phase
p16 and BRAF associated tumor
melanoma
APC associated tumor
colorectal cancer (associated with FAP)
WT1 associated tumor
Wilm’s Tumor (nephroblastoma)
NF1 associated tumor and gene product
NeuroFibromatosis 1
RAS GTPase activating protein (RAS-GAP)
NF2 associated tumor and gene product
NeuroFibromatosis 2
Merlin (schwannomin) protein
DPC4 associated tumor and gene product
Pancreatic cancer
DPC - Deleted in Pancreatic Cancer
DCC associated tumor and gene product
Colon cancer
DCC - Deleted in Colon Cancer
alpha-fetoprotein tumor marker
HCC
Nonseminomatous germ cell tumors (eg testis, ovary)
S-100 tumor marker
melanoma, neural tumors, schwannomas
alkaline phosphatase tumor marker
metastases to bone, liver, Paget’s disease of bone
bombesin tumor marker
neuroblastoma, lung, gastric cancer
TRAP tumor marker
Tartrate-Resistant Acid Phosphatase (TRAP)
Hairy cell leukemia - BC neoplasm
“TRAP the Hairy animal”
asbestos leads to…
lung bronchogenic carcinoma > mesothelioma
Psammoma bodies
laminated concentric calcific spherules:
Papillary adenocarcinoma of thyroid
Serous papillary cystadenocarcinoma of ovary
Meningioma
Malignant mesothelioma
PSaMMoma: Papillary (thyroid) Serous (ovary) Meningioma Mesothelioma
Brain mets from where?
Lung > breast > GU > osteosarcoma > melanoma > GI
acanthocyte (spur cell)
liver disease, abetalipoproteinemia (states of cholesterol dysregulation)
acantho = spiny
basophilic stippling
“BASte the ox TAiL”
Thalassemia
Anemia of chronic disease
Lead poisoning
Bite cell
G6PD deficiency
Elliptocyte
hereditary elliptocytosis
macro-ovalocyte
megaloblastic anemia (also hypersegmented PMNs) BM failure
ringed sideroblasts
sideroblastic anemia
excess iron in mitochondria = pathologic
sideroblastic anemia
there are available iron stores in body but can’t incorporate it into Hb due to x-linked defect in DELTA-ALA SYNTHASE
reversible etiologies: EtOH, lead, isoniazid
- labs: inc iron, normal TIBC, inc ferritin (vs. Fe deficiency anemia where you have dec Fe, inc TIBC, dec ferritin)
- tx: pryidoxine (cofactor for ALA synthase)
schistocyte, helmet cells
DIC, TTP/HUS, traumatic hemolysis (i.e. metal heart valve prosthesis)
Teardrop cell
BM infiltration e.g. myelofibrosis
RBC “sheds a tear” bc it’s been forced out of its home in the BM.
Target cell
HbC disease, Asplenia, Liver disease, Thalassemia
“HALT” said the hunter to his target.”
Heinz bodies
oxidation of Fe from ferrous (2+) to ferric (3+) –> denatured Hb precipitation and damage to RBC membrane –> bite cells
seen in G6PD deficiency
Heinz body-like inclusions seen in alpha thalasemia
Howell-Jolly bodies
basophilic nuclear remnants found in RBCs (remember RBC shouldn’t have nucleus)
normally removed from RBCs by splenic macrophages –> therefore seen in pts with functional hyposplenia, asplenia, or mothball (naphthalene) ingestion
Plummer-Vinson syndrome
triad of Fe deficiency anemia (microcytosis and hypochromia), esophageal webs, atrophic glossitis
alpha thalassemia: 4 gene deletion
- no alpha-globin
- Excess gamma-globin –> incompatible with life, Hydrops fetalis
alpha thalassemia: 3 gene deletion
HbH disease
- very little alpha-globin
- excess beta-globin forms beta4 (HbH)
alpha thalassemia: 1-2 gene deletion
no clinically significant anemia
beta-thalassemia
point mx in splice sites and promoter sequences –> dec beta globin synthesis
MEDITERRANEAN POPULATIONS
beta-thal minor
heterozygote
- beta chain underproduced
- asx usually
- dx = inc HbA2 (>3.5%) on electrophoresis
beta-thal major
homozygote
- beta chain is absent causing severe anemia
- requires blood transfusion (can get secondary hemochromatosis)
- marrow expansion (“crew cut” on skull x-ray) –> skeletal deformities. “Chipmunk” facies
- inc HbF (alpha2, gamma2)
HbS/beta-thal heterozygote
mild to mod sickle cell disease depending on amount of beta globin production
lead poisoning causes problems by…
inhibits ferrochelatase and ALA dehydratase –> dec heme synthesis
inhibits rRNA degradation –> RBCs retain aggregates of rRNA (see basophilic stippling)
Lead poisoning sx and tx
LEAD:
- Lead Lines on gingivae (burton’s lines) and on metaphyses of long bones on x-ray.
- Encephalopathy and Erythrocyte stippling.
- Abdominal colic and sideroblastic Anemia.
- Drops - write and foot drop.
Tx;
Dimercaprol
eDta
Succimer = chelation for kids
Giant cell tumor (osteoclastoma)
“double bubble” or “soap bubble” appearance on x-ray
benign
epiphysis of long bones (distal femur, proximal tibia)
osteochondroma (exostosis)
most common benign tumor, males
osteosarcoma (osteogenic sarcoma)
2nd most common primary malignant bone tumor (after MM)
10-20 years of age
RFs: Paget’s, bone infarcts, radiation, familial retinoblastoma
Codman’s triangle or sunburst pattern. Metaphysis of long bones.
Ewing’s
boys extremely aggressive with early mets but responsive to chemo
“onion skin”
t(11;22)
chondrosarcoma
men 30-60 yo
pelvis, spine, scapula, humerus, tibia, femur
medullary cavity
sensitive but not specific for SLE
ANA
Ab very specific for SLE and indicative of poor prognosis
anti-dsDNA
very specific but not prognostic Ab for SLE
anti-Smith
sensitive for drug-induced lupus Ab
antihistone
Polymyositis and Dermatopolymyositis Ab
anti-Jo-1 Ab
Myasthenia gravis Ab
postsynaptic ACh receptor
Lambert-Eaton myasthenic syndrome Ab and association
presynaptic Ca channel –> dec ACh release
small cell lung cancer
Diffuse scleroderma Ab
anti-Scl-70 Ab (anti-DNA topoisomerase I Ab)
CREST syndrome Ab
antiCentromere Ab