Blood Dyscrasia

Question 1

Acute Lymphocytic Leukemia (ALL)

Answer 1

MC malignancy in children under <15 years

Most responsive to therapy

Question 2

ALL Clinical Features

Answer 2

CNS Involvement

Abnormal mucosal or cutaneous bleeding (due to thrombocytopenia)

Splenomegaly, hepatomegaly, lymphadenopathy

Bone and joint pain (invasion of the periosteum)

Anterior mediastinal mass (T-cell ALL)

Question 3

ALL Diagnostics/Labs

Answer 3

WBC count is variable (from 1,000/mm3 to 100,000/mm3); significant numbers of blast cells (immature cells) in peripheral blood

Thrombocytopenia

Granulocytopenia

Electrolyte disturbances: hyperuricemia, hyperkalemia, hyperphosphatemia

Bone marrow biopsy:
Required for diagnosis

Question 4

ALL Treatment

Answer 4

Tumor lysis syndrome:

Potential complication of chemotherapy seen in acute leukemias and high-grade Non-Hodgkin Lymphoma

Rapid cell death with release of intracellular contents

Causes hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia with resultant sequelae related to each imbalance

Treat as a medical emergency

More than 75% of all children with ALL achieve complete remission

Question 5

Acute myelogenous leukemia (AML)

Answer 5

Neoplasm of myelogenous progenitor cells

Occurs mostly in adults (accounts for 80% of adult acute leukemias)

Question 6

AML Risk Factors

Answer 6

Radiation exposure

Myeloproliferative syndromes

Down syndrome

Chemotherapy (particularly alkylating agents: cyclophosphamide, cisplatin)

Question 7

AML Clinical Features

Answer 7

Increased risk of bacterial infections (due to neutropenia)

Pneumonia, UTIs, cellulitis, pharyngitis, esophagitis

Associated with high morbidity and mortality; potentially life-threatening

Abnormal mucosal or cutaneous bleeding (due to thrombocytopenia)

CNS involvement: diffuse or local neurologic dysfunction (e.g., meningitis, seizures)

Skin nodules

Question 8

AML Diagnostics

Answer 8

WBC count is variable (from 1,000/mm3 to 100,000/mm3); significant numbers of blast cells (immature cells) in peripheral blood

Bone marrow biopsy (required for diagnosis): Auer Rods

Question 9

AML Auer Rods

Answer 9

Granules and eosinophilic rods inside malignant cells

Present in AML, but not in ALL

Particularly noted if it is the APL phenotype

Question 10

AML Treatment

Answer 10

Tumor Lysis syndrome (like in ALL)

Aggressive, combo chemotherapy for several weeks at high doses until remission

More difficult to treat than ALL

Does not respond as well to chemotherapy

Bone marrow transplantation gives the best chance of remission or cure

Question 11

Chronic Lymphocytic Leukemia (CLL)

Answer 11

Most common: most people with CLL are greater than 60 years of age

Leukemia occurring after age 50

Most common leukemia in the Western world

Monoclonal proliferation of B-type lymphocytes that are morphologically mature, but functionally defective

Generally regarded as the least aggressive type of leukemia

Question 12

CLL Clinical Features

Answer 12

Usually asymptomatic at time of diagnosis; CLL may be discovered on a routine CBC (lymphocytosis)

Generalized painless LAD (nontender lymph nodes), splenomegaly

Question 13

CLL Diagnostics

Answer 13

CBC – WBC of 50,000 to 200,000

Pancytopenia is common (anemia, thrombocytopenia, neutropenia)

Peripheral blood smear often diagnostic

Absolute lymphocytosis – almost all WBCs are mature, small lymphocytes

Presence of smudge cells – “fragile” leukemic cells that are broken when placed on glass slide

Question 14

CLL Treatment

Answer 14

Chemotherapy:
Little effect on overall survival

Given for symptomatic relief and reduction of infection
Patients are often observed until symptoms develop

Question 15

Chronic Myelogenous Leukemia (CML)

Answer 15

Associated with translocation t(9,22)

The fusion of the BCR gene on chromosome 22 with the ABL1 gene on chromosome results in the Philadelphia chromosome (present in > 90% of patients with CML)

Results in a constitutively active tyrosine kinase protein (targeted by imatinib (Gleevec))

Question 16

CML Treatment

Answer 16

Treatment of CML = one of the great stories of modern medicine

After mechanism was identified, the oral TK inhibitor imatinib (Gleevec) was developed (one of the first targeted chemotherapies)

Drug targets the dysfunctional chimeric protein bcr-abl formed by the t(9,2) Philadelphia chromosome

Question 17

Hodgkin Lymphoma (HL) General

Answer 17

Bimodal age distribution:
X1: 15 to 30 years of age
X2: > 50 years of age

Reed-Sternberg Cells

Question 18

HL Clinical Features

Answer 18

Most common symptom is a painless lymphadenopathy

Constitutional (B) symptoms: weight loss, fever, night sweats, anorexia

Pruritus

Cough: secondary to mediastinal lymph node involvement

Question 19

HL Diagnosis

Answer 19

Lymph node biopsy:
The presence of Reed-Sternberg cells is required to make the diagnosis

Neoplastic, large cell with two or more nuclei; looks like owl’s eyes

Usually B-cell phenotype

Presence of inflammatory cell infiltrates

Differentiates Hodgkin from non-Hodgkin lymphoma

Question 20

Non-Hodgkin Lymphoma (NHL)

Answer 20

Twice as common as Hodgkin disease

NHL tends to present with more advanced disease than those with HL

Etiology: unknown

Question 21

NHL Risk Factors

Answer 21

HIV/AIDS

Immunosuppression (e.g., organ-transplant recipient)

History of certain viral illnesses (e.g., EBV, HTLV-1)

History of Helicobacter pylori (risk of primary associated gastric lymphoma)

Autoimmune disease (e.g., Hashimoto’s thyroiditis or Sjögren syndrome (risk of mucosa-associated lymphoid tissue [MALT])

Question 22

NHL General

Answer 22

Classification:

More than 20 different subtypes of NHL

Question 23

NHL Indolent/Low Grade Subtype

Small lymphocytic lymphoma

Answer 23

Closely related CLL, more common in elderly patients

Indolent course

Question 24

NHL Indolent/Low Grade Subtype

Follicular, primarily small, cleaved-cell lymphoma

Answer 24

Most common form of NHL

Presents with painless, peripheral lymphadenopathy

Mean age of onset: 55 years of age

Question 25

NHL Intermediate Grade Subtype Diffuse, large-cell lymphoma

Answer 25

Predominantly B-cell origin Middle-aged and elderly patients Locally invasive; presents as large extranodal mass

Question 26

NHL High Grade Subtype Lymphoblastic lymphoma

Answer 26

T-cell lymphoma; more common in children May progress to T-ALL Aggressive with rapid dissemination, but may respond to combination chemotherapy

Question 27

NHL High Grade Subtype Burkitt (small, non-cleaved cell) lymphoma

Answer 27

B-cell lymphoma; more common in children African variety linked with EBV infection Associated w/ specific translocation: t(8;14)

Question 28

NHL Miscellaneous Lymphomas Mycosis fungoides

Answer 28

Presents with eczamatoid skin lesions that progress to generalized erythroderma Cribiform shape of lymphocytes

Question 29

NHL Clinical Features

Answer 29

Lymphadenopathy: Sometimes the only manifestation of the disease Lymph nodes are usually painless, firm, and mobile

Question 30

NHL Diagnosis

Answer 30

Lymph node biopsy: Definitive diagnosis Any lymph node > 1 cm present for more than 4 weeks that cannot be attributed to infection should be biopsied

Question 31

Multiple Myeloma (MM)

Answer 31

Neoplastic proliferation of a single plasma cell line that produces monoclonal immunoglobulin Incidence increases after age 50 years; twice as common in African-American patients than Caucasian patients As the disease progresses, bone marrow elements are replaced by malignant plasma cells

Question 32

MM Clinical Features

Answer 32

Bone pain due to osteolytic lesions, fractures, and vertebral collapse Anemia: Normocytic normochromic Myeloma nephrosis: Immunoglobulin precipitation in renal tubules leads to tubular casts of Bence Jones protein Up to 70% of patients die from infection: pulmonary or urinary tract are most common Cord compression: Secondary to a plasmacytoma or fractured bone fragment

Question 33

MM Diagnostics - Labs

Answer 33

Hypercalcemia: due to bone destruction Peripheral smear: RBCs seen in rouleaux formation Urine: large amounts of free light chains called Bence Jones proteins Leukopenia, thrombocytopenia, and anemia Elevated creatinine = renal insufficiency

Question 34

MM Clinical Manifestations Pneumonic: CRAB

Answer 34

``` C = Calcium issues) hypercalcemia) R = Renal insufficiency A = Anemia B = Bone lesions and pain ```

Question 35

MM Treatment

Answer 35

Preferred treatment is autologous hematopoietic cell transplantation (HCT)

Question 36

Monoclonal gammaopathy of undetermined significance (MGUS)

Answer 36

Asymptomatic premalignant clonal plasma cell proliferation Less than 10% plasma cells in bone marrow Bence-Jones proteinuria < 1 gram/24 hours Should also be NO end-organ damage (e.g., lytic bone lesions, anemia, hypercalcemia, etc.) Almost like a minor form of MM

Question 37

Polycythemia vera (PV)

Answer 37

Malignant clonal proliferation of hematopoietic stem cells leading to excessive erythrocyte production Mutations of the JAK2 tyrosine kinase are found in >90% of polycythemia vera cases

Question 38

PV Clinical features

Answer 38

Symptoms due to hyperviscosity: HA, dizziness, weakness, pruritus, visual impairment, dyspnea Thrombotic phenomena Bleeding Splenomegaly, hepatomegaly HTN

Question 39

PV Diagnostics

Answer 39

Rule out causes of secondary polycythemia (e.g., hypoxia, CO exposure) CBC: Elevated RBC count, H/H (usually >50%) Thrombocytosis, leukocytosis may be present Serum erythropoietin levels are reduced Elevated vitamin B12 level Hyperuricemia is common Bone marrow biopsy confirms

Question 40

PV Differential Diagnosis

Answer 40

1. Smoking: Lab evaluation shows increased Hct, RBC mass, EPO level, and carboxyhemoglobin No splenomegaly on PE 2. Hypoxemia (secondary polycythemia): Living for prolonged periods at high altitudes Pulmonary fibrosis Congenital cardiac lesions Laboratory evaluation shows decreased arterial oxygen saturation No splenomegaly on PE

Question 41

PV Treatment

Answer 41

Repeated phlebotomy to lower the hematocrit

Question 42

Myelodysplatstic Syndrome

Answer 42

Class of acquired clonal blood disorders Characterized by ineffective hematopoiesis, with apoptosis of myeloid precursors Result is pancytopenia, despite normal or hypercellular bone marrow

Question 43

Myelodysplastic Syndrome Etiologies

Answer 43

Usually idiopathic Exposure to radiation Immunosuppressive agents Certain toxins

Question 44

Myelodysplastic Syndrome Diagnosis

Answer 44

Bone marrow biopsy typically shows dysplastic marrow cells with blasts or ringed sideroblasts

Question 45

Myelodysplastic Syndrome Treatment

Answer 45

Pharmacologic therapies Bone marrow transplantation is the only potential cure