Hematology / Oncology - Diseases Flashcards
Hemolytic-Uremic Syndrome (HUS)
Caused by Shiga-like toxin produced by EHEC O157:H7
Clinical triad of anemia + thrombocytopenia + acute renal failure
Toxin damages vessel endothelium allowing formation of microthrombi; microthrombi consume platelets (causing thrombocytopenia), cause mechanical shearing of RBCs (hemolytic uremia) which reduces renal blood flow (renal failure)
Treatment: Supportive care
Disseminated Intravascular Coagulation (DIC)
Widespread activation of clotting causes consumption of clotting factors and platelets, leading to a bleeding state; caused by sepsis (gram negative), malignancy, trauma, obstetric complications, acute pancreatitis, nephrotic syndrome, transfusion
Treated with fresh frozen plasma to replace clotting factors
Hodgkin Lymphoma
B-cell origin lymphoma confined to a single group of lymph nodes; characterized by Reed-Sternberg cells
Primarily affects young adults and adults > 55; affects men > women (except for nodular sclerosing type); 50% associated with EBV
Commonly presents with B symptoms - fever, weight loss, night sweats
4 Types: Nodular sclerosing (most common, affects men and women equally), lymphocyte-rich (best prognosis), mixed cellularity, lymphocyte-depleted
Better prognosis than non-Hodgkin lymphomas
Burkitt Lymphoma
Neoplasm of mature B cells, most commonly seen in adolescents / young adults and highly associated with EBV
Sporadic form presents with abdominal/pelvic lesions; endemic form (Africa) presents with jaw lesions
t(8;14) - c-myc oncogene / Ig heavy chain
“Starry sky” appearance - sheets of lymphocytes interspersed with macrophages
Diffuse, large B cell lymphoma
Most common type of non-Hodgkin lymphoma in adults
t(14,18) - Ig heavy chain / BCL-2 (same as Follicular lymphoma)
Mantle Cell Lymphoma
Usually seen in older males
B cells are CD5+
t(11;14) - cyclin D1 / Ig heavy chain
Follicular Cell Lymphoma
Primarily affects adults with indolent course; presents as waxing/waning painless lymphadenopathy
t(14;18) - BCL2 / Ig heavy chain
Adult T Cell Lymphoma
Caused by HTLV-1 virus; associated with IV drug use
Presents with cutaneous skin lesions, lytic bone lesions, and hypercalcemia
Mycosis Fungoides / Sezary Syndrome
Lymphoma of mature T cells primarily affecting adults
Presents with cutaneous patches / tumors with potential spread to lymph nodes and viscera; indolent course
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Caused by an acquired mutation of GPI membrane-anchored protein in a hematopoietic stem cell; GPI is present on the RBC membrane where it prevents complement-mediated lysis; complement attaches preferentially at low pH, i.e. overnight when decreased RR causes respiratory acidosis
Presents with anemia, morning hemoglobinuria, pancytopenia, and thrombosis; thrombosis (DVT, PE) is leading cause of early mortality
Treated with Eculizumab
Lead Poisoning
Pb inhibits aminolevulinic acid (ALA) dehydrogenase and ferrochelatase enzymes in the heme synthesis pathway; Pb also inhibits ribonucleases in RBCs
Presents with fatigue, abdominal discomfort, peripheral neuropathy (wrist/foot drop); increased risk in children who live in old houses, adult ceramic painters
Findings: Elevated serum ALA, microcytic anemia, elevated ferritin, decreased transferrin, decreased TIBC, basophilic stippling of RBCs, Burton Lines on metaphyses of long bones on X ray
Trx: Chelating agents - EDTA, dimercaprol
Factor V Leiden
Autosomal dominantly inherited mutation of Factor V clotting protein, making it resistant to proteolytic cleavage by protein C
Increased risk of DVT, especially in the setting of venous stasis
Monoclonal Gammopathy of Undetermined Significance (MGUS)
Asymptomatic precursor to multiple myeloma, characterized by monoclonal expansion of plasma cells
Defined by serum monoclonal Ig light chain (M spike) < 3g/dL and <10% monoclonal plasma cells in the bone marrow
Progresses to multiple myeloma at 1-2% per year
Multiple Myeloma
Neoplastic proliferation of monoclonal plasma cells with production of large amounts of IgG or IgA
Clinical syndrome: CRAB = hypercalcemia, renal insufficiency, anemia, lytic bone lesions/back pain; also increased susceptibility to infection, primary amyloidosis
Findings: “Punched out” lytic bone lesions on X-ray, M-spike on serum protein electrophoresis, Bence-Jones protein in the urine, Rouleaux formation on peripheral blood smear
Hereditary Spherocytosis
Caused by a genetic mutation in one of the proteins which functions to anchor the RBC cytoskeleton to the plasma membrane (spectrin, ankyrin); less membrane surface area results in small, round RBCs without central pallor which are prematurely cleared by the spleen
Labs: Elevated MHCH, normal/low MCV, high retic count
Physical findings: Splenomegaly
Treatment: Splenectomy
Antiphospholipid antibody syndrome
Can occur as a primary disorder or secondary to another autoimmune condition (as in “Lupus anticoagulant” seen in SLE)
Causes a hyper-coagulable state with increased risk of arterial and venous thrombosis, and lost pregnancy
Findings: Paradoxical prolongation of PTT that is NOT correctable with 1:1 mixing of patient serum and fresh frozen plasma
Waldenstrom’s Macroglobulinemia
Neoplastic proliferation of B cells producing IgM
Presents with anemia, hyperviscosity syndrome; no lytic bone lesions or hypercalcemia (vs. multiple myeloma)
Labs show high IgM
Methemoglobinemia
High level of methemoglobin in the blood characterized by heme iron in the Fe3+ state; methemoglobin does not transport O2 well and so peripheral tissues undergo hypoxia
Presents with peripheral cyanosis + headache, dizziness, nausea, SOB, confusion, coma
Labs: Normal PO2 and PCO2; blood appears dark brown/”muddy”
Treated with methylene blue or ascorbic acid (Vitamin C), which reduces Fe3+ back to Fe2+
Osteosarcoma
Primary malignant tumor of bone; mostly seen in males < 20 years old
Primarily affects long bones near the metaphyses
X-ray shows “sunburst” pattern
Associated with Rb mutation (Retinoblastoma)
Alpha thalassemia trait
Due to inherited defect of 2/3 alpha globin genes
alpha-thal-1 trait (aa/–) is more common in Asian populations
alpha-thal-2 trait (a-/a-) is more common in African populations
HbH Disease
Caused by genetic defect of 3/4 alpha globin genes
Excess beta globins form unstable tetramers B4 (HbH) with poor O2 delivery to tissues
Presents as microcytic, hypochromic anemia with hepatosplenomegaly; target cells and Heinz bodies can be seen on peripheral smear
Hydrops fetalis
Fatal condition caused by deletion of all 4 alpha globin genes, leading to over-production of y4 hemoglobin (Hb Barts)
Incompatible with life, often resulting in stillbirth
Beta thalassemia minor
Caused by genetic defect of one beta globin gene
May be asymptomatic or present with mild microcytic, hypochromic anemia with > 3.5% HbA2 (a2d2)
Beta thalassemia intermedia
Caused by genetic inheritance of two partially non-functional beta globin genes
Affected individuals may require occasional transfusion during periods of increased physiologic stress (pregnancy, serious illness)
Beta thalassemia major
Caused by deletion/defect of both beta globin genes, resulting in lack of beta globin protein
Presents as severe microcytic, hypochromic anemia with hepatosplenomegaly and skeletal abnormalities due to excessive extra-medullary hematopoiesis
Affected individuals usually present after 6 months age (HbF is protective <6 months) and require serial blood transfusion
Gout
Acute, inflammatory, monoarthritis caused by precipitation of monosodium urate crystals in joint fluid; 90% due to under-excretion, 10% due to over-production (Lesch-Nyhan, tumor lysis syndrome)
Presents as an acutely red, swollen painful joint (most commonly MTP of the big toe) + tophi (olecranon bursa, ear, Achilles tendon)
Diagnosed by presence of needle-shaped, negatively bi-refringent crystals
Treated acutely with NSAIDS (Indomethacin), Gluccocorticoids, and Colchicene
Chronically with Allopurinol (for over-producers) or Probenecid (for under-excretors)
Seronegative spondyloarthropathies
Arthritis not associated with Rheumatoid Factor; strongly associated with HLA-B27, more commonly seen in men:
Ankylosing Spondylitis
Reactive arthritis (Reiter’s Syndrome)
Psoriatic Arthritis
Ankylosing Spondylitis
Chronic inflammatory disease of the vertebral column and SI joints leading to joint fusion
Also associated with ulcerative colitis, uveitis
X-ray shows “bamboo spine”
Reactive Arthritis (Reiter’s Syndrome)
Post-infectious, inflammatory arthritis; most commonly seen after GI infections (Shigella, Yersinia, Salmonella, Campylobacter) or Chlamydia urethritis
Classic triad = conjunctivitis / uveitis + urethritis + arthritis (“can’t see, can’t pee, can’t climb a tree”)
Psoriatic Arthritis
Seronegative arthritis strongly associated with HLA-B27
Seen in fewer than 1/3 of patients with Psorias
Fidnings: Dactylitis (“Sausage Fingers”), “pencil-in-cup” deformity of fingers on X-ray
Chronic Myeloid Leukemia (CML)
Associated with the “Philadelphia Chromosome” - t[9;22] BRC-ABL translocation which codes for a constitutively active tyroskine kinase leading to unregulated stem cell growth
Characterized by leukocytosis with decreased leukocyte alk phos and with transformation to AML
Acute Promyelocytic Leukemia (APL)
A subtype of acute myelocytic leukemia (AML) characterized by t[15;17] with creation of a PML-RARA fusion protein
Characterized by leukocytosis with > 20% circulating myeloid blasts; + Auer rods on peripheral smear
Treated with all-trans retinoic acid
Risk of DIC
Lambert-Eaton myasthenic syndrome
Paraneoplastic syndrome characterized by production of auto-antibodies against the pre-synaptic Ca2+ channels at the NMJ
Presents as muscle weakness, especially of the facial muscles
Commonly seen in small cell lung carcinoma
Retinoblastoma
Inherited mutation of the Rb tumor suppressor gene followed by sporadic mutation of the second copy - “two hit” mechanism
Rb binds and inactivates transcription factor EF2 involved in progression of the cell cycle; lack of functional Rb results in unregulated EF2 activity and progression from G1 to S phase of the cell cycle
Associated with eye tumors, osteosarcoma
Juvenile Idiopathic Arthritis
Systemic autoimmune condition characterized by relapsing/remitting fevers, macular “salmon pink” rash, polyarticular arthralgias, chronic uveitis, and hemophagocytic syndrome (digestion of RBCs by macrophages, causing anemia)
Findings: Usually Rheumatoid Factor negative
Treatment: NSAIDs, corticosteroids, MTX, IVG
Sarcoidosis
Idiopathic, widespread, non-caseating granulomas; often seen in AA females
Labs: Elevated serum ACE levels, Elevated CD4 / CD8 ratio, hypercalcemia
CXR shows bilateral hilar lymphadenopathy and coarse reticular opacities
Also associated with restrictive lung disease, erythema nodosum, uveitis, Bell’s palsy
Treated with corticosteroids
Thrombotic thrombocytopenic purpura
Caused by a deficiency in the enzyme ADAMTS13 which normally functions to degrade vWF; presence of large vWF multimers in circulation promotes platelet adhesion
Presents with fevers, thrombocytopenia, microangiopathic hemolysis, neurological symptoms, and renal insufficiency
Labs show thrombocytopenia, elevated lactate dehydrogenase and indirect bilirubin, elevated Creatinine
Smear shows schisocytes
