Term
| Immune Thrombocytopenia Purpura |
|
Definition
| Autoimmune IgG made against platelet GPIIb/IIIa, Mo consume Ab-coated platelets in spleen = thrombocytopenia (low platelets); acute in kids follows viral infn. or immunization, chronic adults often secondary to SLE/AIDS; PT/PTT unchanged, increase in megakaryocytes |
|
|
Term
| Thrombotic Thrombocytopenia Purpura |
|
Definition
| = unusually high molecular weight VWF multimers made due to lack of processing → Ib-IX on platelets binds better → platelet aggregation → coagulation in small blood vessels → platelet-fibrin complexes get lodged = RBC lysis (microangiopathic hemolytic anemia); Abs against ADAMTS13 (normally degrades VWF multimers) |
|
|
Term
| Hemolytic Uremic Syndrome |
|
Definition
Normal levels of ADAMTS13; Epidemic form = infection (E. coli gastroenteritis)
stimulates production of large VWF leading to same patho as TTP; can also be familial |
|
|
Term
| Disseminated Intravascular Coagulopathy |
|
Definition
| Two causes: TF released into circulation (OB complication) or widespread endothelial damage (sepsis, neoplasm, trauma); = widespread clotting, factors used up, then mucosal bleeding, hemorrhagic bullae; acute or chronic (cancer); platelets↓, PT/PTT↑, Protein C↑, D-dimer↑, FSPs↑ |
|
|
Term
| Hereditary Hemorrhagic Telangectasia |
|
Definition
| = AD arteriovenous malformation; epistaxis (nosebleeds), GI bleeding, Intracerebral hemorrhage (vascular disorder) |
|
|
Term
|
Definition
| = collagen disorder; joint hypermobility, fragile blood vessels (vascular disorder) |
|
|
Term
|
Definition
| = Ib-IX defect → platelet adhesion defect (inherited platelet disorder) |
|
|
Term
| Glanzmann’s Thrombasthenia |
|
Definition
| = GPIIb-IIIa defect → platelet aggregation defect (inherited platelet disorder) |
|
|
Term
|
Definition
| = FVIII deficiency, 85% of hemophiliacs; X-linked (large gene, mostly inversions); musculoskeletal bleeds (hemarthrosis, iliopsoas, circumcisions); PTT↑, PT unchanged |
|
|
Term
|
Definition
| = FIX deficiency, 15% of hemophiliacs, X-linked (smaller gene, mostly missense mutations) musculoskeletal bleeds (hemarthrosis, iliopsoas, circumcisions); PTT↑, PT unchanged |
|
|
Term
|
Definition
| = defect in VWF (qualitative or quantitative; AD); most common bleeding disease; mucocutaneous bleeds; Ristocetin cofactor assay; Type I = most common, mild, VWF low quant; Type II = VWF doesn’t function right, 2M doesn’t bind platelets, 2N doesn’t bind FVIII; Type III = no VWF+ very low FVIII, severe bleeds |
|
|
Term
|
Definition
| = inherited defect in membrane proteins such that less membrane/cytoplasm → forces cells to become sphereoid shaped → less deformable → more likely to be destroyed in spleen; anemia, splenomegaly, jaundice |
|
|
Term
|
Definition
| Results in less GSSH = more oxidative damage; X-recessive; triggered by infections, drugs, and fava beans; globin denatures and forms Heinz bodies (toxic inclucions); Blacks, middle east, Mediteranea |
|
|
Term
|
Definition
| AR point mutation in β-globin gene; Precipitated by infection, dehydration, and acidosis; prominent cheekc, autosplenectomy; susceptible to encapsulated bugs; hyperbilirubinemia; growth impairment; target cells on smear; normocytic |
|
|
Term
|
Definition
Gene deletions (4 genes present)
-1 deletion = silent; 2 deletions = carrier state (“Thalassemia trait”)
-3 deletions = HbH disease = severe anemia (excess β chains form toxic tetramers); Asians
-4 deletions = hydrops fatalis |
|
|
Term
|
Definition
Gene mutations (two genes); β/β+ = β-Thalassemia minor = asymptomatic;
βoβo = β-Thalassemia major = severe form
-α tetramers, massive erythroid hyperplasia, need transfusions secondary hemochromatosis
-smear has microcytic hypochromic RBCs, targets, nucleated RBCs; HbA↓, HbA2↑, HbF↑ |
|
|
Term
| Paroxysmal Nocturnal Hemoglobinuria |
|
Definition
Acquired mutations in gene for GPI protein (anchors C’ mediator DAF) → C’ destroys
-mutations in pluripotent stem cells (affects RBCs, WBCs, platelets); intravascular hemolysis during sleep → hemoglobinemia, hemoglobinuria, hemosiderinuria; sucrose test |
|
|
Term
| Immunohemolytic Anemia: Warm Ab Type |
|
Definition
| =Most common; Auto IgG binds RBCs which then bind FcR on Mo in spleen = partial phagocytosis |
|
|
Term
| Immunohemolytic Anemia: Cold Agglutinin Type |
|
Definition
| IgM binds RBCs at cold temps and fixates C’; Ab production follows infection |
|
|
Term
|
Definition
| Inhibits ALAD and ferrochelatase = no protoporphyrin; hypochromic microcytic (normally normocytic, though); no anemia until Pb exposure high; basophilic stippling = dots in immature RBCs (not polychromasia) |
|
|
Term
| Anemia of Chronic Disease |
|
Definition
| Especially due to chronic infections or autoimmune disease; MCV normal, TIBC low, Ferritin high; Hepcidin keeps iron bound to ferritin in Mo |
|
|
Term
|
Definition
| Hypercellular marrow; macrocytes, anisocytosis + poikilocytosis; hypersegmented neutrophils; pancytopenia; pernicious anemia causes (autoimmune destruction of parietal cells = no intrinsic factor); removal of ileum can cause (where B12 absorbed); Homocystein and methylmalonic acid ↑↑ |
|
|
Term
|
Definition
| Usually dietary deficiency; have ~4 mo folate stores; Homocystein ↑, MMA normal |
|
|
Term
|
Definition
| B19 infects erythroid precursors = no erythropoiesis; pancytopenia, normal MCV but no retics or nucleated RBCs in peripheral blood (indicates marrow not working) |
|
|
Term
| Autoimmune Hemolytic Anemia |
|
Definition
| Abs aimed at RBC’s = can’t crossmatch; idiopathic or secondary to SLE, leukemia, infection |
|
|
Term
|
Definition
| Iron fails to combine w/ protoporphyrin = no heme; iron accumulates in mito around nuclei = ringed sideroblasts; hypochromic microcytic; Caused by myelodysplasia, alcohol, lead, Isoniazid |
|
|
Term
|
Definition
| = inheritance of one mutant p53; predisposes to malignancy because of two-hit hypothesis; Breast cancer |
|
|
Term
| Ataxia Telengectasia (mutated and RAD3 related) |
|
Definition
| = p53 related inability to repair certain kinds of DNA damage; are both proteins which phosphorylate p53 |
|
|
Term
|
Definition
| -Defect in dsDNA break repair (BRCA-1/2 associated) |
|
|
Term
|
Definition
| = Defect in nucleotide excision repair; UVB-induced cancers; multiple genes involved; Thymidine dimers |
|
|
Term
| Hereditary Nonpolyposis Cancer Syndrome |
|
Definition
| = Defect in mismatch repair resulting in microsatelite instability; 80% lifetime risk for cancer (most common hereditary),; ~15% sporadic colon cancers |
|
|
Term
|
Definition
| = unilateral erythematous nipple with scaly crust; is an extension of ductal carcinoma in-situ (DCIS) to nipple |
|
|
Term
|
Definition
| Mutation in helicase involved in homologous recombination; developmental defects |
|
|
Term
| Chronic Myelogenous Leukemia (CML) |
|
Definition
| t(9;22) Philadelphia creates BRC-ABL TK fusion product in HSC; granulocyte proliferation, left shift, h Philadelphia creates BRC-ABL TK fusion product; granulocyte proliferation,basophilia, left shift, hypercellular marrow; Transforms to AML (70%) and ALL (30%); BRC-ABL promotes JAK/STAT, AKT paths |
|
|
Term
| Acute Myelocytic Leukemia |
|
Definition
| Undifferentiated myeloblasts accumulate in marrow (>20%); get anemia, fatigue, thrombocytopenia, |
|
|
Term
| Acute Promyelocytic Leukemia |
|
Definition
| WHO I, t(15;17) creates PML-RAR fusion product that suppresses differentiation; Tx = ATRA; hypergranular promyelocytes can cause DIC; Auer rods |
|
|
Term
|
Definition
| WHO I, disrupts CBF-α gene for hematopeiesis, good prognosis |
|
|
Term
|
Definition
| WHO I, disrupts CBF-β, good prognosis |
|
|
Term
|
Definition
| = marrow replaced w/ fibrous tissue; pancytopenia, huge spleen, too much TGF-β, teardrop RBCs, JAK-2 mutation |
|
|
Term
|
Definition
| Proliferation of mature RBCs; leukocytosis and thrombocytosis; Thromboisis, blurry vision, H/A; Jak-2 mutation; Tx = phlebotomies |
|
|
Term
|
Definition
| = Increased platelet production; normocellular marrow w/big megakaryocytes; DVT, hemorrhage, burning in hands/feet; Jak-2 mutation |
|
|
Term
|
Definition
| = myeloid SC mutation causing reduced RBCs, platelets, and white cells; Pseudo-Pelger-Huet cells (hyposegmented neutrophils); Ringed sideroblasts; 5q, 7q, 20q |
|
|
Term
|
Definition
| Reed Sternberg cells (owl-eyed nuclei) secrete cytokines = inflammatory mass; painless lymphadenopathy in young females; enlarding cervical/mediastinal mass; node has band of sclerosis w/RS cells in lake-like spaces (= nodular sclerosis); sometimes have B-symptoms |
|
|
Term
| Acute Lymphoblastic Leukemia |
|
Definition
| T(12;21) = good t(9;22) = bad; abrupt onset anemia, thrombocytopenia, severe bone pain; CNS invasion; see lymphoblasts (CD10+/TDT+) in blood; B-ALL = most (kids), T-ALL = teens, thymus |
|
|
Term
|
Definition
| t(11;14) increases cyclin D1 production; generalized painless lymphadenopathy, CD5+ |
|
|
Term
|
Definition
| = most common leukemia; hypogammaglobulinemia, lymphocytosis, smudge cells; Richter trans (to DLBCL), RAI Staging system; 13q deletion = loss miRNA; 17p deletion = p53 |
|
|
Term
| Diffuse Large B-Cell Lymphoma |
|
Definition
| Large malignant B-cells grow diffusely in node; EBV and Kaposis, malignant effusions, median age 60; rapidly fatal if untreated, very treatable |
|
|
Term
|
Definition
| t(8;14) = overexpression of C-MYC; “starry sky,” surface IgM, BCL6+, African = EBV, mandibular mass, kids; Sporadic = abdominal mass invading ileocecum, adults, bad prognosis |
|
|
Term
|
Definition
| t(14;18) = BCL2 overexpression; Ann Arbor staging; Rickter trans; centroblasts and centrocytes |
|
|
Term
|
Definition
| t(1;14) = MALT, t(11;18), trisomy 18; extranodal sites; |
|
|
Term
|
Definition
| No chromosomal abnormality; CD103+, older men, pancytopenia, splenomegaly |
|
|
Term
|
Definition
| = plasma cells; t(4;14) and t(14;16) = bad prognosis, t(11;14) = good; ISS staging with beta-2 microglobulin concentration; IL-6 = lytic bone lesions = hypercalcemia; Rouleaux formation; IgG and IgA,, macroglossia; amyloidosis = renal failure |
|
|
Term
| Lymphoplasmacytic Leukemia |
|
Definition
| Tumor cells secrete so much IgM that get hyperviscosity syndrome (Walderstrom); BM = primary site; visual problems, neuro probs, bleeding; progressive and incurable |
|
|
Term
| Anaplastic Large Cell Lymphoma |
|
Definition
| = CD8+/CD30+ T cells; B-symptoms; can be confined to skin = cutaneous ALCL; horseshoe-shaped nuclei, AKL rearrangement = better prognosis |
|
|
Term
|
Definition
| = CD4+ T-Cells; HTLV-1; Cloverleaf nuclei; Japan, West Africa, Carribb; skin lesions, hypercalcemia, lymphadenopathy, hepatosplenomegaly; Fatal within one year even with treatment |
|
|
Term
| Extranodal NK/T-cell Lymphoma |
|
Definition
| Mass that obstructs nasal/sinus/palate; Hong Kong and Peru; B symptoms uncommon; Tx = radiation |
|
|
Term
|
Definition
E6 -> inactivates p53
E7 -> inactivates pRB
Types 16 & 18 = High risk for genital cancers. |
|
|
Term
|
Definition
| Bladder-like transitional epithelium; benign. |
|
|
Term
|
Definition
| Useful serum marker for monitoring treatment and recurrence of ovarian cancers. Not useful for screening. |
|
|
Term
|
Definition
| Mimics fetal tissue; derived from all 3 embryonic layers (skin, hair, fat, bone); most common germ cell tumor; benign, but can become malignant (more neural tissue = more malignant potential) |
|
|
Term
|
Definition
| Mimics oocytes, most common malignant germ cell tumor; called seminoma in testis; High LDH, PLAP; Normal AFP; Fried egg appearance; good prognosis: responds to chemotherapy |
|
|
Term
| Yolk Sac Tumor/ Endodermal Sinus Tumor |
|
Definition
| Mimics yolk sac; most common germ cell tumor in children; High AFP; Schiller-Duval Bodies |
|
|
Term
|
Definition
| Malignant tumor composed of trophoblasts and syncytiotrophoblasts; mimics placental tissue; High B-hCG; Poor chemo response |
|
|
Term
| Adult Granulosa Cell Tumors |
|
Definition
| Estrogenic; induce early puberty/ abnormal uterine bleeding; inhibin (serum levels used to monitor); Histo: Coffee bean, nuclear grooves, bland cytology, Call Exner bodies. |
|
|
Term
| Juvenile Granulosa Cell Tumor |
|
Definition
| Uncommon; Assoc. w/ Ollier syndrome (Enchrondromatosis) and Maffucci syndrome (Enchondromatosis + Hemangiomatosis) |
|
|
Term
|
Definition
| Most common sex cord stromal tumor (benign); Elevated CA125; Meigs syndrome (Fibroma ascites, right sided pleural effusion); Gorlin syndrome (Hereditary basal cell nevus syndrome, bilat. ovarian fibromas) |
|
|
Term
| Sertoli-Leydig Cell Tumors |
|
Definition
| Crystal of Reinki in Leydig cells; Sertoli = form tubules; Leydig = b/w tubules; androgenic (defeminization) |
|
|
Term
|
Definition
| Metastatic mucinous tumor that involves both ovaries; Signet ring; poor prognosis; often of gastric origin; bilaterality helps distinguish from metastasis from primary mucinous ovarian cystadenocarcinoma (which is unilateral) |
|
|
Term
|
Definition
| Mucinous tumor of appendix w/ usual metastasis to ovary; Extensive mucinous ascites; peritoneal mucinous carcinomatosis = gelatinous ascites |
|
|
Term
|
Definition
| Lines fallopian tubes (serous), endometrium, endocervix (mucinous) |
|
|
Term
|
Definition
| Single cyst w/ simple, flat lining: premenopause |
|
|
Term
| Malignant cystadenocarcinoma |
|
Definition
| Complex cyst w/ thick, shaggy lining: postmenopause |
|
|
Term
|
Definition
| CD10, CD19, CD20, CD21, CD23, CD79 |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Ag indicative of lymphocyte immaturity |
|
Definition
|
|
Term
|
Definition
1. Female + vague abdominal complaints = think ovarian cancer; do pelvic exam
2. The significance of a psammoma body is the company it keeps (context)
3. The difference between a borderline tumor and a malignant tumor is destructive stromal invasion
4. You only see what you know to look for
5. Ovarian cyst + frozen with mucinous neoplast = think appendix + appendectomy
6. Listen to patients, think, consider differential |
|
|
Term
|
Definition
| Silent hindgut or appendix tumor; slow growing; may cause carcinoid syndrome; Cholecystectomy if octreotide therapy contemplated. |
|
|
Term
| Adenoma -> Carcinoma sequence |
|
Definition
Benign -> Dysplastic -> CA
APC at 5q21-> APC/Beta-catenin -> KRAS -> p53, LOH, SMAD 2 & 4 -> Carcinoma
85% of colon/ rectal CA; early CA may be dx'd within polyps. |
|
|
Term
| Left-Sided colorectal carcinomas |
|
Definition
| May produce occult bleeding, changes in bowel habits, or cramping of the left lower quadrant |
|
|
Term
| Right Sided colorectal carcinomas |
|
Definition
| More often called to attention by the appearance of fatigue and weakness due to iron deficiency anemia |
|
|
Term
|
Definition
| Often grow as polypoid, exophytic masses that extend along one wall of the cecum and ascending colon; rarely result in obstruction |
|
|
Term
|
Definition
| Tend to be annular lesions that produce "napkin ring" constrictions and luminal narrowing, sometimes to the point of bowel obstruction |
|
|
Term
| Microsatellite Instability Sequence |
|
Definition
| Mutations in microsatellite sequences located in coding or promoter regions of genes involved in regulation of cell growth, such as those encoding the Type II TGF-Beta receptor and pro-apoptotic BAX genes, result in genomic instability that hinders DNA mismatch repair; leads to faster mutation accumulation and progression to cancer; CpG hypermethylation silencing; BRAF oncogene mutation |
|
|
Term
| Distribution of colorectal cancers |
|
Definition
|
|
Term
| Transcriptional activators; nuclear regulatory proteins |
|
Definition
C-MYC -> Burkitt Lymphoma
N-MYC -> Neuroblastoma, small cell lung CA
L-MYC -> Small cell lung CA |
|
|
Term
| GTP-binging proteins involved in signal transduction |
|
Definition
K-RAS -> Colon, lung, pancreatic tumors
H-RAS -> Bladder and kidney tumors
N-RAS -> Melanomas, hematologic malignancy |
|
|
Term
| Nonreceptor tyrosine kinase |
|
Definition
| BCR-ABL -> Chronic myeloid leukemia |
|
|
Term
|
Definition
|
|
Term
| What is RAS and its role in cancer? |
|
Definition
| GTPase; Binds GTP, recruits kinases to transmit stim. signals from growth factor receptors. Point mutations can occur, which prevent GTP hydrolysis, so RAS become constitutively active. Stimulatory signals are provided despite absence of growth factor binding. |
|
|
Term
| What is ErbB2/Her2/Neu and its role in cancer? |
|
Definition
| Encodes a TK growth factor receptor. Overexpression causes slow ligand dissociation, prolonged firing, and increased cell proliferation |
|
|
Term
| What is Myc and its role in cancer? |
|
Definition
| Transcription factor normally made after stim. from growth factors. Activates genes that cause the cell to grow. If MYC is amplified, cell becomes sensitive to growth factors. Translocation may insert MYC near the Ig gene to increase its expression. |
|
|
Term
| What is BCR-ABL and its role in cancer? |
|
Definition
| ABL normally codes an intracellular TK. Not normally activated. t(9;22) results in BCR-ABL, a constitutively active TK that increases white cell proliferation in CML and ALL |
|
|
Term
| What is PDGF and its role in cancer? |
|
Definition
| Platelet derived growth factor. Over production results in proliferation of neighboring cells. |
|
|
Term
| What is Cyclin D1 and its role in cancer? |
|
Definition
| Initiates entrance past restriction point of G1 to S phase. Normally associates with Cdks to phosphorylate (inactivate) pRB (a growth inhibitory molecule), releasing the breaking effect of pRB. Overexpression of Cyclin D1 leads to repeated proliferation of cells via excessive production of proteins needed to progress through cell cycle. Mantle cell lymphoma. |
|
|
Term
| What is p53 and its role in cancer? |
|
Definition
| "Guardian of the genome." Senses DNA damage and halts cell division so damage can be repaired or induces apoptosis. Loss of inhibition -> cell cycle dysregulation -> loss of DNA repair mechanisms and increased mutation rate -> abnormal growth |
|
|
Term
| What is pRB and its role in cancer? |
|
Definition
| Master brake of the cell cycle. When unphosphorylated it blocks cycling by sequestering transcription factors. Releases transcription factors when phosphorylated by the cyclin-Cdk complexes. Retinoblastoma |
|
|
Term
| What is BRCA and its role in cancer? |
|
Definition
| Involved in DNA repair. Interacts with proteins involved in dsDNA breaks. Mutations = incorrect DNA repair and genomic instability. Involved in 80% of familial breast cancer. |
|
|
Term
| What is APC and its role in cancer? |
|
Definition
| Anaphase promoting complex. Works during M-phase. Encodes proteins that inhibit beta-catenin in the cell cytoplasm. A tumor suppressor. |
|
|
Term
| What is NF-1 and its role in cancer? |
|
Definition
| Encodes a protein that inactivates RAS (converts RAS from GTP bound to GDP); inhibits stimulation. Loss of APC = lack of RAS regulation = uncontrolled proliferation |
|
|
Term
| What is p16 and its role in cancer? |
|
Definition
| Blocks the activity of Cdks that bind to Cyclin D1. Prevents advance of cell from G1 to S phase. Mutation = dysregulation of cell cycle and excessive proliferation. |
|
|
Term
| What is BAX and its function? |
|
Definition
| Protein which is upregulated by p52. Forms channels in the mitochondria to release cytochrome c, which activates caspases leading to apoptosis. |
|
|
Term
| What is BCL-2 and its role in cancer? |
|
Definition
| Normally inhibits apoptosis. Overexpression of BCL-2 leads to widespread binding and inactivation of BAX, preventing caspase activation and apoptosis (contributes to cell immortality) |
|
|
Term
|
Definition
| Proteases involved in apoptosis. Clip endonucleases to activate then, resulting in internucleosomal fragmentation and intracellular degradation of DNA. |
|
|
Term
| Phenotypic characteristics of all cancers |
|
Definition
1. Evasion of programmed cell death
2. Insensitivity to anti-growth signals
3. Self-sufficiency in growth signals
4. Sustained angiogenesis
5. Limitless growth potential
6. Tissue invasion and metastasis |
|
|
Term
| What is PTEN and its normal function? |
|
Definition
| Phosphatase and Tensin homologue. Normally prevents interactions with extracellular matrix. |
|
|
Term
|
Definition
| Type of DCIS. Solid sheet of high-grade malignant cells with central necrosis. Necrosis often calcified, seen as linear branching microcalcifications on mammogram. |
|
|
Term
|
Definition
Comedocarcinoma
Solid
Cribiform
Papillary
Micropapillary |
|
|
Term
|
Definition
| Grade ranges from high to low. Calcifications seen with central necrosis, but more commonly seen when there are intraluminal inclusions. Cells are monomorphic |
|
|
Term
|
Definition
| Intraepithelial spaces evenly distributed and regular in shape |
|
|
Term
|
Definition
| Lacks myoepithelial cell layer |
|
|
Term
|
Definition
| Recognized by bulbous protrusion without a fibrovascular core, often forming complex intraductal patterns |
|
|
Term
|
Definition
| Proliferatin of a monomorphic population of cells that are loosely cohesive and larger than normal w/ oval/ round nuclei and small nucleoli; Signet ring w/ mucin; Found in terminal ducts or ductules; Rarely distorts underlying tissue; Calcifications are rare; NEVER FORMS A MASS (incidentally found) |
|
|
Term
| Invasive ductal carcinoma of "no special type" |
|
Definition
| Increased dense, fibrous tissue stroma; hard consistency; malignant cells in cords, solid cell nests, tubules, or combinations which invade stroma; chalky white streaks and calcifications |
|
|
Term
| Invasive lobular carcinoma (ILC) |
|
Definition
| Strands of infiltrating cells, often only one cell in width (single file) loosely dispersed throughout fibrous matrix. Cells may form solid, irregular nests. Appear same as LCIS (lack cohesion). Signet cells common. |
|
|
Term
|
Definition
| No desmoplasia (hyperplasia of fibroblasts with excessive fibrous connective tissue elaboration) normally seen in cancer. Appears as solid, syncytium-like sheets w/ pleomorphic nuclei. Mitotic figures frequent. |
|
|
Term
| Colloid (mucinous) carcinoma |
|
Definition
| "Lakes" of infiltrating, lightly staining, amorphous mucin. Neoplastic cells within the mucin. |
|
|
Term
|
Definition
| Well-formed tubules; absent myoepithelial layer; cribiform spaces may be present; calcifications may be present in lumens |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Tetrahydrofolate reductase |
|
|
