Hematology / Oncology - Diseases

Question 1

Hemolytic-Uremic Syndrome (HUS)

Answer 1

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

Question 2

Disseminated Intravascular Coagulation (DIC)

Answer 2

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

Question 3

Hodgkin Lymphoma

Answer 3

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

Question 4

Burkitt Lymphoma

Answer 4

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

Question 5

Diffuse, large B cell lymphoma

Answer 5

Most common type of non-Hodgkin lymphoma in adults

t(14,18) - Ig heavy chain / BCL-2 (same as Follicular lymphoma)

Question 6

Mantle Cell Lymphoma

Answer 6

Usually seen in older males

B cells are CD5+
t(11;14) - cyclin D1 / Ig heavy chain

Question 7

Follicular Cell Lymphoma

Answer 7

Primarily affects adults with indolent course; presents as waxing/waning painless lymphadenopathy

t(14;18) - BCL2 / Ig heavy chain

Question 8

Adult T Cell Lymphoma

Answer 8

Caused by HTLV-1 virus; associated with IV drug use

Presents with cutaneous skin lesions, lytic bone lesions, and hypercalcemia

Question 9

Mycosis Fungoides / Sezary Syndrome

Answer 9

Lymphoma of mature T cells primarily affecting adults

Presents with cutaneous patches / tumors with potential spread to lymph nodes and viscera; indolent course

Question 10

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Answer 10

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

Question 11

Lead Poisoning

Answer 11

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

Question 12

Factor V Leiden

Answer 12

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

Question 13

Monoclonal Gammopathy of Undetermined Significance (MGUS)

Answer 13

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

Question 14

Multiple Myeloma

Answer 14

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

Question 15

Hereditary Spherocytosis

Answer 15

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

Question 16

Antiphospholipid antibody syndrome

Answer 16

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

Question 17

Waldenstrom’s Macroglobulinemia

Answer 17

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

Question 18

Methemoglobinemia

Answer 18

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+

Question 19

Osteosarcoma

Answer 19

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)

Question 20

Alpha thalassemia trait

Answer 20

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

Question 21

HbH Disease

Answer 21

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

Question 22

Hydrops fetalis

Answer 22

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

Question 23

Beta thalassemia minor

Answer 23

Caused by genetic defect of one beta globin gene

May be asymptomatic or present with mild microcytic, hypochromic anemia with > 3.5% HbA2 (a2d2)

Question 24

Beta thalassemia intermedia

Answer 24

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)

Question 25

Beta thalassemia major

Answer 25

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

Question 26

Gout

Answer 26

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)

Question 27

Seronegative spondyloarthropathies

Answer 27

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

Question 28

Ankylosing Spondylitis

Answer 28

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”

Question 29

Reactive Arthritis (Reiter’s Syndrome)

Answer 29

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”)

Question 30

Psoriatic Arthritis

Answer 30

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

Question 31

Chronic Myeloid Leukemia (CML)

Answer 31

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

Question 32

Acute Promyelocytic Leukemia (APL)

Answer 32

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

Question 33

Lambert-Eaton myasthenic syndrome

Answer 33

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

Question 34

Retinoblastoma

Answer 34

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

Question 35

Juvenile Idiopathic Arthritis

Answer 35

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

Question 36

Sarcoidosis

Answer 36

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

Question 37

Thrombotic thrombocytopenic purpura

Answer 37

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