amyloidosis is the
abnormal aggregation of protein (or their fragments into β-sheat
amyloidosis –> …. (it causes in the cellular level)
damage and apoptosis
amyloidosis - common types
- AL (primary) 2. AA (secondary) 3. dialysis-related
- heritable 5. age related (senile) systemic
- organ specific
primary (AL) amyloidosis - mechanism
deposition of proteins from Ig Light chains (amyloid Light: AL)
primary (AL) amyloidosis is associated with
plasma cell dyscrasias (multiple myeloma)
primary (AL) amyloidosis often affects …(including, and causes)
multiple organs including renal (nephrotic syndrome), cardiac (restrictive cardiomyopathy, arrhythmia), hematologic, (easy bruising, splenomegaly), GI (hepatomegaly), neurologic (neuropathy)
secondary (AA) amyloidosis - seen with
chronic inflammatory conditions such as RA, IBD, spondyloarthropathy, protracted infection, famlilial Mediterranean fever
secondary (AA) amyloidosis - fibrils composed of
serum Amyloid A
secondary (AA) amyloidosis - affects
often multisystem like AL amyloidosis
dialysis related amylodisis - fibrils composed of
β2-microglobulin
dialysis-related amylodisis - seen in
patients with end-stage-renal-disease and/or long-term dialysis
dialysis-related amylodisis may present as
Carpal tunnel syndrome
heritable amyloidosis (including….)?
heterogenous group of disorders, including familial amyloid polyneuropathies due to transthyretin gene mutation
heritable amyloidosis is a heterogenous group of disorders, including (and due to..)
familial amyloid polyneuropathies due to transthyretin gene mutation
familial amyloid polyneuropathies are due to
transthyretin gene mutation
age-related (senile) systemic is due to
deposition of normal (wild-type) transthyretin in myocardium and other sites
age-related (senile) systemic vs primary amyloidosis according to cardiac function
cardiac dysfunction in age-related (senile) systemic has a slower progression relative to primary amyloidosis
organ specific amyloidosis?
amyloid deposition localized to a single organ
organ specific amyloidosis - Most important form is
Alzheimer disease
Alzheimer disease - mechanism of amyloidosis
deposition of β-amyloid protein cleaved from amyloid precirsor protein (APP)
islet amyloid polypeptid is commonly seen in …. (and is caused by)
diabetes mellitus type 2
deposition of amylin in pancreatic islets
Amylin is a
peptide hormone that is cosecreted with insulin from the pancreatic beta-cell
amyloidosis - appearance
- congo red stain
- congo red stain shows apple green birefringence under polarized light
- H% eosin
β2-microglobulin fibrils - amyloidosis - type?
dialysis-related amyloidosis
islet amyloid polypeptid?
deposition of amylin in pancreatic islets (DM2)
Isolated atrial amyloidosis - due to
Organ specific amyloidosis –> due to ANP (COMMON IN NORMAL AGING)
p53 - product
Transcription factor for p21–> blocks G1 to S phase
p16 - product / associated tumor
Cyclin-dependent kinase inhibitor 2A
melanoma
NF1 / NF2- product
Ras GTPase activating protein (neurofibromin)
Merlin (schwannomin protein)
PTEN - associated tumor
- breast
- prostate
- endometrial
TSC1 + TSC2 - products
Hamartin protein
Tuberin protein
VHL product
HIF1a inhibitor
BRAF - product + tumor
serine/threonine kinase
Melanoma, non-Hodgkin lymphoma
BCR-ABL - associated tumor
CML, ALL
dermatomyositis and polymyositis predispose to visceral malignancy particularly
genitourinary
immunodeficiency predisposes to (neoplasm)
- lymphoma
- melanoma
- renal cell carcinoma
- SCC of skin
neoplasm - HCV causes
neoplasm - HBV causes
hepatocellular carcinoma + LYMPHOMA
aromatic amines - examples
- benzidine
- 2- naphthylamine
carcinogens - arsenic causes
- angiosarcoma of the liver
- lung cancer
- SCC of the skin
neoplasms that produce PTHrp
- SCC of the lung
- renal cell carcinoma
- breast cancer
- bladder
- ovarian
- head and neck
tumor markers - CEA
- colorectal ca
- pancreatic ca
- gastric ca
- breast ca
- medullary thyroid ca
breast cancer tumor markers
- CEA
- CA 27-29
- CA 15-3
tumor markers - β-hCG
1. hydatidiform moles 2 .Chroriocarcinomas 3. testicular ca 4. mixed germ line tumor 5. Dysgerminoma 6. Large cell Ca of lung
tumor markers - alkaline phosphatase
- metastasis to bone
- metastasis to liver
- seminoma (placental alkaline phosphatase)
- Paget disease of the bone
tumor markers - a-fetoprotein
- hepatocellular ca
- hepatoblastoma
- yolk sac (endodermal sinus) tumor
- mixed germ cell tumor
a-fetoprotein in pregnancy
high levels –> neural tube and abdominal wall defects
low levels –> Down syndrome/Patatu (13)/Edwards (18)
Psammoma bodies are seen in
- papillary carcinoma of thyroid
- serous papillary cistadenocarcinoma of ovary
- meningioma
- malignant mesothelioma
Good syndrome? - as a paranaeoplastic syndrome - MCC
- hypogammaglobulinemia
- Thymoma
pure anemia as a paranaeoplastic syndrome - MCC
thymoma
carcinomas that spread hematogeneously
- hepatocellular
- renal cell
- follicular thyroid
- choriocarcinoma
Paraneoplastic encephalomyelitis? as a paranaeoplastic syndrome - MCC?
- Antibodies against Hu antigens in neurons
- small cell lung ca
Paraneoplastic cerebellar degeneration? as a paranaeoplastic syndrome - MCC?
- Antibodies against Hu, Yo and Tr antigens in Purkinje cells
- small cell lung ca, gynecologic and breast ca, Hodgkin
Anti-NMDA receptor encephalitis? as a paranaeoplastic syndrome - MCC?
Psychiatric disturbances, ,e,ory deficits, seizures, dyskenisias, autonomic instability, language dysfunction
ovarian teratoma
Opsoclonus myoclonus ataxia syndrome as a paranaeoplastic syndrome - MCC?
Neuroblastoma (children)
small cell lung ca (adults)
ovarian Ca - paraneoplastic
- Anti-NMDA receptor encephalitis (ovarian teratoma)
2. PTHrp
P-glycoprotein - AKA/seen in
- Multidrug resistance protein 1 (MDR1)
- Classically seen in adrenal cell ca, but also can expressed by other cacner cells (eg. colon. liver)
1ry tumors that give metastasis to liver (from the MC)
Collon»_space; stomach > pancreas
1ry tumors that give metastasis to bone (from the MC)
prostate,breast > lung,thyroid,kidnry
1ry tumors that give metastasis to brain (from the MC)
lung > breast > prostate > melanoma > GI