WBC Disorders - Leukemia and Myeloproliferative Disorders

Question 1

Acute Leukemia

Answer 1

Neoplastic proliferation of blasts.
>20% blasts in bone marrow (normal 1-2%)
Crowds out normal hematopoiesis –> acute.
Anemia (fatigue), thrombocytopenia (bleeding), neutropenia (infection).
High WBC count.
Blasts = large, immature cells w punched-out nucleoli.
ALL and AML subtypes.

Question 2

Acute Lymphoblastic Leukemia (ALL)

Answer 2

Lymphoblasts.
TdT stain+ (DNA polymerase).
Kids, Down’s, >5 y/o.

B-ALL most common.
Expresses CD10, CD19, CD20 surface markers.
Excellent response to chemo (req’s prophylaxis to scrotum and CSF bc can’t cross those barriers).
t(12;21) - good prognosis - kids.
t(9;22) - poor prognosis - adults (Philadelphia+ALL).

T-ALL
CD2-CD8.
Do NOT express CD10.
Teens w Thymic (mediastinal) mass = acute lymphoblastic lymphoma).

Question 3

Acute Myeloid Leukemia (AML)

Answer 3

Immature myeloid cells.
MPO +stain –> crystal aggregates = Auer rods.
Older adults (50-60).
May arise from pre-existing dysplasia, esp w alkylating agents of radiotherapy.
Myelodysplastic syndromes w cytopenia, hyper cellular bone marrow, abnormal maturation of cells, ^blasts. Usu pts die, but some may progress to AML.

Acute promyelocytic leukemia (APL)
t(15;17) moves retinoid acid receptor (RAR) –> blocks maturation–> ^ promyelocytes (blasts).
Have numerous primary granules –> DIC.
Tx: all-trans-retinoic acid (ATRA, vit A deriv) that binds RAR and causes blasts to mature.

Acute monocytic leukemia
Proliferation of monoblasts.
Lack MPO.
Blasts infiltrate gums.

Acute megakaryoblastic leukemia
Proliferation of megakaryoblasts.
Lack MPO.
Down’s; <5 y/o.

Question 4

Chronic Leukemia

Answer 4

Neoplastic proliferation of mature circulating lymphocytes.
High WBC count.
Insidious onset; older adults.

Question 5

Chronic Lymphocytic Leukemia (CLL)

Answer 5

Naive B cells.
Co-express CD5 and CD20.
Most common leukemia overall.
^lymphocytes and smudge cells on smear.
Lymph node involvement –> generalized LAD (small lymphocytic lymphoma).
Complications:
-Hypogammaglobulinemia - Infection most common cause of death.
-Autoimmune hemolytic anemia
-Transformation to diffuse large B-cell lymphoma (Richter transformation) - enlargING lymph node or spleen.

Question 6

Hairy Cell Leukemia

Answer 6

Mature B cells.
Have hairy cytoplasmic processes.
TRAP+ (tartrate-resistant acid phosphatase).
Splenomegaly (hairy cells trapped in red pulp).
Dry tap on bone marrow aspiration (marrow fibrosis).
Usu NO LAD.
Responds well to 2-CDA (cladribine) - adenosine deaminase inhibitor (adenosine accumulates toxically).

Question 7

Adult T Cell Leukemia/Lymphoma (ATLL)

Answer 7

Mature CD4+ T cells.
HTLV-1.
Japan and Caribbean.
Rash, generalized LAD, hepatosplenomegaly, lytic (punched-out) bone lesions w hypercalcemia.

Question 8

Mycosis Fungoides

Answer 8

Mature CD4+ T cells.
Infiltrate skin –> localized skin rash, plaques, nodules.
Aggregates in epidermis = Pautrier micro abscesses.
Spread to blood –> Sezary syndrome w lymphocytes w cerebriform nuclei (Sezary cells) on smear.

Question 9

Myeloproliferative Disorders (MPD)

Answer 9

Neoplastic proliferation of mature cells of myeloid lineage.
Late adulthood (50-60).
High WBC count.
Hypercellular bone marrow.
Cells of all myeloid lineages are increased, but classified based on predominant one.
Complications:
-hyperuricemia and gout bc high cell turnover
-progression to marrow fibrosis
-transformation to acute leukemia

Question 10

Chronic Myeloid Leukemia (CML)

Answer 10

MPD - especially granulocytes and their precursors.
Basophils increased.
t(9;22) (Philadelphia) –> BCR-ABL fusion protein w ^tyrosin kinase activity –> overgrowth.
Tx: imatinib (blocks tyrosine kinase activity).
Splenomegaly - enlarging spleen suggests accelerated phase of disease w acute leukemia shortly.
–> AML (2/3)
–> ALL (1/3)
Mutation in pluripotent stem cell.

Distinguish from leukomoid rxn (reactive neutrophilic leukocytosis) aka infection…

• leukocyte alkaline phosphatase (LAP) -
• ^ basophils
• t(9;22)

Question 11

Polycythemia Vera (PV)

Answer 11

MPD - especially RBCs.
Granulocytes and platelets also ^
JAK2 kinase mutation.
Hyperviscocity of blood.
Blurry vision, headache, venous thrombosis (Budd-Chiari), flushed face (plethora), itching after bathing (histamine from ^mast cells).
Tx w phlebotomy or hydroxyurea or die w/in 1 yr.

Distinguish from reactive polycythemia…

• EPO v and Sao2 normal
• RP has Sao2 v and EPO ^ (high altitude or lung disease).
• RP hase Sao2 normal and EPO ^ (renal cell carcinoma).

Question 12

Essential Thrombocythemia (ET)

Answer 12

MPD - especially platelets.
RBCs and granulocytes also ^
JAK2 kinase mutation.
^ risk or bleeding, thrombosis.
Rarely progresses to marrow fibrosis or acute leukemia.
No risk of hyperuricemia or gout.

Question 13

Myelofibrosis

Answer 13

MPD - especially megakaryocytes.
JAK2 kinase mutation (50%).
Megakaryocytes produce excess platelet-derived growth factor (PDGF) –> marrow fibrosis.
Splenomegaly (bc extra medullary hematopoiesis).
Leukoerythroblastic smear - tear drop RBCs, nucleated RBCs, immature granulocytes.
^ infection, thrombosis, bleeding.