Questions I missed

Question 1

t(15;17) with auer rods and DIC ?

Answer 1

The patient has acute promyelocytic leukemia (APL) complicated by disseminated intravascular coagulation (DIC). The peripheral blood smear shows a hypergranular promyelocyte filled with multiple Auer rods. Auer rods are present only in variants of acute myeloblastic leukemia. Patients with APL have a characteristic t(15;17) translocation, which causes an abnormality in retinoic acid metabolism. DIC is invariably present in APL, because the release of procoagulants from the granules of the promyelocytes activates the coagulation system cascade.

Question 2

t(8;14)

Answer 2

Burkitt Lymphoma- Stary Sky with reactive histiocytes. Jaw involvement in the African Type GI involvement in the American type.

Question 3

t(9;22)

Answer 3

t(9;22) translocation is associated with chronic myelogenous leukemia (CML). In CML, Auer rods are not present in the myeloblasts, which account for <10% of the myeloid cells. The ABL-proto-oncogene on chromosome 9 is translocated to chromosome 22 where it fuses with the break cluster region to form a fusion gene. Chromosome 22 is called the Philadelphia chromosome.

Question 4

t(12;21)

Answer 4

t(12;21) translocation has prognostic significance in acute lymphoblastic leukemia. When present, the prognosis is favorable.

Question 5

t(8;14)

Answer 5

t(14;18) translocation is associated with a follicular B-cell lymphoma. The translocation causes overexpression (increased activity) of the BCL2 family of genes. The protein product of the gene prevents apoptosis of the cell by preventing cytochrome c from leaving the mitochondria. Therefore, the translocation ensures immortality of the B cells in the germinal follicles of lymph nodes.

Question 6

What could cause this ?

Answer 6

A perforated acute appendicitis produces neutrophilic leukocytosis with left shift (e.g., band neutrophils) and toxic granulation (prominent azurophilic granules), both of which are present in the photograph

Question 7

What are the clinical findings in polycytemia Vera ?

Answer 7

In polycythemia, all cell lines except lymphocytes are increased. An increase in basophils and mast cells causes the release of histamine, which produces flushing of the face (called plethora), headaches, and pruritus after bathing. All of the myeloproliferative diseases have basophilia.

Question 8

What will you find in hereditary sphereocytosis ?

Answer 8

In hereditary spherocytosis, an autosomal dominant disease with a membrane defect due to a lack of ankyrin, spherocytes are removed extravascularly by macrophages leading to an increase in unconjugated bilirubin (UCB) and a CB < 20%. AST is present in RBCs; therefore, there is a slight increase in serum AST. Urine UBG is increased due to increased production of CB by the liver and increased conversion of CB to UBG in the colon.

Question 9

Describe Alpha Thallasemia

Answer 9

α-Thalassemia is an autosomal recessive disorder that involves decreased production of α-globin chains, causing a microcytic anemia with decreased synthesis of hemoglobin A (2α2β), hemoglobin A2 (2α2δ), and hemoglobin F (2α2γ). The RBC count is usually increased in the thalassemias, and it is decreased in all the other microcytic anemias (e.g., iron deficiency anemia). Hemoglobin electrophoresis is normal, because the proportion of each of the decreased hemoglobins remains the same. Serum ferritin is normal in α-thalassemia.

Question 10

Describe CLL

Answer 10

(CLL)) is correct. The clinical and laboratory findings (age > 60 yr, fatigue, hepatosplenomegaly, generalized nontender lymphadenopathy, anemia, thrombocytopenia, and an increased leukocyte count) confirm the presence of leukemia. The peripheral blood shows numerous lymphocytes and occasional smudge cells (nuclear debris) and the absence of neutrophils, findings consistent with CLL. The lymphocytes are neoplastic virgin B cells that are unable to mature into plasma cells. This explains the hypogammaglobulinemia (flat γ-globulin peak on serum protein electrophoresis), which imposes an increased risk of infections. CLL is the most common leukemia and the most common cause of generalized lymphadenopathy in patients > 60 years of age.

Question 11

Describe AML

Answer 11

AML occurs between 15 and 60 years of age. A peripheral blood smear of patients with AML shows myeloblasts containing Auer rods (red, splinter to rod-shaped inclusions in the cytosol).

Question 12

Describe CML

Answer 12

CML usually occurs between 40 and 60 years of age. The peripheral smear shows numerous myeloid cells at different stages of development (e.g., myeloblasts, myelocytes, segmented neutrophils).

Question 13

Describe Hairy Cell Leukemia

Answer 13

Hairy cell leukemia occurs in middle-aged men. It is an uncommon chronic B-cell leukemia in which lymphadenopathy rarely occurs. In a patient with hairy cell leukemia, a peripheral blood smear shows neoplastic cells with cytoplasmic projections, which stain positive for tartrate-resistant acid phosphatase.

Question 14

What is a leukmoid Reaction ?

Answer 14

A leukemoid reaction is a benign increase in leukocytes (e.g., neutrophils, lymphocytes, eosinophils), often >50,000/mm3. It usually occurs in response to infection (e.g., tuberculosis). Anemia and thrombocytopenia usually are not present.

Question 15

Describe G-6PD

Answer 15

Deficiency of G6PD is an X-linked recessive disorder associated with a hemolytic anemia induced by infection or oxidant drugs (e.g., dapsone, primaquine). As shown in the pedigree, X-linked recessive disorders are expressed only in males, whereas females with the abnormal allele are usually asymptomatic carriers. The male transmits the abnormal allele to all of his daughters and none of his sons. The female carrier transmits the abnormal allele to 50% of her sons, which is evident in the pedigree.

Question 16

You see shistocytes in the peripheral smear and you see in the labs that the patient has microcytic anemia

You suspect Microangiopathic hemolytic anema what should you test for ?

Answer 16

Serum Ferritin

microangiopathic hemolytic anemia due to intravascular destruction of the RBCs as they hit the stenotic and dystrophically calcified valve. The damaged cells release hemoglobin directly into the blood. Haptoglobin, a protein synthesized in the liver, combines with the free hemoglobin to form complexes that are phagocytosed by macrophages in the spleen and completely degraded causing very low to absent serum haptoglobin levels. The excess hemoglobin in the plasma is then filtered into the urine producing a red color and a positive dipstick for blood. Chronic hemoglobinuria eventually causes iron deficiency and a microcytic anemia. Serum ferritin is the best screening test for iron deficiency. Since ferritin is a soluble iron-binding protein, some ferritin leaks out of bone marrow macrophages and directly reflects the ferritin stores in the bone marrow. In iron deficiency, ferritin stores are decreased; therefore, serum ferritin is also decreased. Aortic stenosis is the most common cause of a hemolytic anemia associated with schistocytes.

Question 17

Describe Burtons Agammablobinemia

Answer 17

Bruton’s agammaglobulinemia is an X-linked disorder characterized by failure of pre-B cells to develop into B cells. This produces hypogammaglobulinemia, because there are not sufficient numbers of B cells to be antigenically stimulated to become plasma cells. Deficiency of IgG produces an opsonizing defect. The antigen recognition site of IgG attaches to the bacteria, and the Fc portion of the immunoglobulin attaches to receptors in the plasma membrane of phagocytic leukocytes (neutrophils, monocytes, macrophages). This facilitates the phagocytosis of bacteria by triggering engulfment of bacteria by pseudopods and eventual formation of a phagocytic vacuole.

Question 18

Basophillic stipeling in a RBC in a kid who wone quit walking around the house eating things. Microcytic anemia and growth retardation with metallic densities in the abdomen. What is the problem ?

Answer 18

The peripheral smear shows hypochromic RBCs (increased central areas of pallor) and coarse basophilic stippling are present in one RBC, indicating the persistence of ribosomes. Lead, a heavy metal, denatures enzymes, deposits in the epiphyses of bone, and causes encephalopathy and peripheral neuropathy. The microcytic anemia is due to denaturation of ferrochelatase, which normally combines iron with protoporphyrin to form heme in the mitochondria. A decrease in heme causes a decrease in hemoglobin synthesis resulting in a microcytic hypochromic anemia. Lead also denatures ribonuclease, which normally degrades ribosomes. This explains the presence of coarse basophilic stippling. Lead deposits in the epiphyses of bone explain the patient’s growth retardation. Lead is also easily identified in an abdominal radiograph as metallic densities, which is evident in this patient. Since δ-aminolevulinic acid is proximal to the enzyme block in heme synthesis, it is increased and is responsible for the encephalopathy (demyelination and cerebral edema) and neuropathy in lead poisoning (abdominal colic, peripheral neuropathies). An increase in serum lead level confirms the diagnosis

Question 19

What is the most common cause of folate defficency in the US ?

Answer 19

Alcoholism. This will present as megaloblastic anemia without neurologic dysfunction.

Question 20

What are the symptoms of osteopyelitis ?

Answer 20

The patient has Salmonella osteomyelitis. The peripheral blood smear shows sickle cells (dense, boat-shaped RBCs) and numerous target cells (RBCs with a bull’s-eye appearance), the latter a common sign of a hemoglobinopathy. Sickle cell disease is the most common hemolytic disease in blacks and is due to a missense mutation resulting in replacement of glutamic acid by valine in the 6th position of the β-globin chain. The radiographic findings in the lower right femur (a periosteal reaction and lytic lesion in the metaphysis) are indicative of osteomyelitis, which in sickle cell disease is most often caused by S. paratyphi. This indicates that the patient most likely has autosplenectomy due to multiple infarctions of the spleen. A functioning spleen is required to remove Salmonella, Streptococcus pneumoniae, and Hemophilus influenzae from the blood. The spleen is a major site for synthesis of IgM; therefore, a decrease in IgM leads to decreased activation of the complement system and production of C3b, which is an opsonin that assists splenic macrophages remove these pathogens from the blood. Staphylococcus aureus is the usual pathogen causing osteomyelitis in patients without sickle cell disease.

Question 21

What will patients present with in Pyruvate Kinase Defficency ?

Answer 21

PK deficiency is an autosomal recessive hemolytic disease with extravascular hemolysis. PK normally converts phosphoenolpyruvate to pyruvate leading to a net gain of 2 adenosine triphosphate (ATP). In PK deficiency, lack of ATP damages the membrane causing a loss of K+ and dehydration of the RBC (echinocytes with thorny projections, arrow in the photograph). In homozygous variants, hemolytic anemia with jaundice begins at birth. There is an increase in 2,3 bisphosphoglycerate (BPG) proximal to the enzyme block, which right-shifts the O2-binding curve causing increased release of O2 to tissue.

Question 22

What will renal cell carcinoma do to your patients lab values ?

Answer 22

RCC will cause the eptopic production of Erythropoietin which will greatly increase the RBC production and mass.

Question 23

What will the lab findings in a Leukmoid reaction be ?

Answer 23

With a leukemoid reaction there is a marked increase in the WBC count with many neutrophils and metamyelocytes and myelocytes, but blasts are absent or rare. An infectious disease usually underlies a leukemoid reaction. Unlike CML, the leukocyte alkaline phosphatase is high with a leukemoid reaction.