Hematology Week 3: Mature Lymphoid Neoplasms

Question 1

Patient Presentation

Question 2

Question 1

Answer 2

A Mature Lymphocytes

Question 3

Most common mature lymphoid leukemia

Answer 3

Chronic Lymphocytic Leukemia (CLL)

Question 4

CLL neoplasm of what kind of cells?

Answer 4

CLL is a neoplasm of mature monoclonal B-cells

Question 5

What kind of cells?

Answer 5

Normal polyclonal B cells

Question 6

What Kind of Cells?

Answer 6

Monoclonal B cells can choose only Kappa or Lambda, in this case this clonal expansion expressed only lambda

Question 7

Clonal vs non-clonal

Answer 7

clonicity is a valuable diagnostic tool

Question 8

Abnormal immunophenotype for CLL

Answer 8

CD5 and CD23 on B cells

Question 9

CD5 is usually found on?

Answer 9

T cells

if found on B cells is indicative of CLL

or

Question 10

CLL Peripheral blood smear characteristic features

5 listed

Answer 10

• scant cytoplasm
• dark nuclear chromatin
• small
• uniform size
• “Smudge cells”

Question 11

CLL in the lymph node

Answer 11

referred to as small lymphocytic lymphoma

Question 12

CLL and SLL

Answer 12

are the same entity

same genetics

same treatment

the difference is if they are found in the blood or tissue vs BM

Question 13

CLL vs SLL

Answer 13

Question 14

Epidemiology of CLL/SLL

Answer 14

• Most common leukemia of adults in the US
• Patients typically elderly
• often asymptomatic at diagnosis (incidental)

Question 15

Most common leukemia in adults

Answer 15

CLL/SLL

Question 16

CLL/SLL Characteristic Cell findings

Answer 16

monoclonal small B-cells with aberrant co-expression of CD5 and CD23

Question 17

CLL/SLL Cytopenias from?

Answer 17

BM is filled up by CLL cells and is replaced by neoplastic cells

Question 18

CLL/SLL immune disruption

2 listed

Answer 18

• Hypogammaglobulinemia -> infections
• Autoimmune phenomena -> anemia, thrombocytopenia

Question 19

CLL/SLL clinical course

Answer 19

Typically indolent but variable

CLL follows the rule of 3rds

Question 20

Staging in CLL

Answer 20

Rai System

&

Binet System

Question 21

Lab studies for CLL/SLL

Answer 21

• CBC+Diff
• FISH (lesion at 17p is worst)
• CD49d expression (when not expressed is better prognosis)
• immunoglobulin heavy chain variable region somatic mutation (mutation is a good thing because that is what it is supposed to do)

Question 22

When are CLL/SLL patients treated?

5 listed

Answer 22

• treat symptoms
• threatened end-organ function
• progressive bulky disease
• progressive anemia/thrombocytopenia
• not curable so treat for symptom relief if the benefit is worth the cost of toxic treatment

Question 23

Symptoms treated for in CLL/SLL

4 listed

Answer 23

• Fever without infection
• Weight loss
• Night Sweats
• Severe fatigue

Question 24

the most common reason for treating CLL/SLL

Answer 24

Progressive anemia/thrombocytopenia

Question 25

How to treat CLL/SLL drug classes 4 listed

Answer 25

* Monoclonal Antibody * Chemotherapy * Biologic agents * Combinations of them

Question 26

Rituximab

Answer 26

* The prototype monoclonal antibody * Anti-CD20 * Usually used in combo with chemo

Question 27

Fludarabine

Answer 27

* Purine analog * specific toxicities * severe marrow toxicity * autoimmune phenomena * autoimmune hemolytic anemia * ITP

Question 28

Bendamustine and Chlorambucil

Answer 28

* Nitrogen mustards/alkylating agents * Marrow suppressive

Question 29

Ibrutinib

Answer 29

* Bruton tyrosine kinase inhibitor * Oraol * Extremely variable toxicity * GI upset (diarrhea) * bleeding * a-fib * immunosuppression * joint pain * nothing

Question 30

Idelalisib

Answer 30

PI3 Kinase Inhibitor Significant toxicity - infections (PJP pneumonia, CMV infection), liver toxicity

Question 31

Hairy Cell Leukemia morphology

Answer 31

shaggy cytoplasm "hairy cells"

Question 32

Hairy Cell Leukemia Immunophenotype

Answer 32

* Positive for TRAP (Tartrate-resistant acid phosphatase) * Negative for CD5

Question 33

BM of Hairy Cell Leukemia

Answer 33

difficult to get BM aspirate because cells are so tightly packed but can get a core biopsy

Question 34

Treatment of Hairy Cell Leukemia 2 listed

Answer 34

Responds very well to purine analogs * Cladribine * Pentostatin

Question 35

M Protein AKA

Answer 35

monoclonal paraprotein

Question 36

M protein interpretation

Answer 36

aka m spike can be IgM, IgG, IgA or whichever

Question 37

Multiple Myeloma pathophysiology 4 listed

Answer 37

* neoplasm of clonal bone marrow plasma cells * typically IgG or IgA * Most cases have CRAB * Hypercalcemia, Renal insufficiency, Anemia, Bone lytic lesions * Produce large amounts of M-protein

Question 38

Multiple Myeloma histological features

Answer 38

* very eccentric nucleus * prominent "hof" perinuclear clearing (pale area by nucleus which is very prominent Golgi apparatus) * bone marrow taken over by plasma cells

Question 39

CRAB

Answer 39

* Hypercalcemia * Renal insufficiency * anemia * bone lytic lesions In Multpile Myeloma

Question 40

Clues to Myeloma 5 listed

Answer 40

* Hypercalcemia - from bone resorption * Renal Failure - Filtering light chains is toxic to the renal tubules * Anemia - normal marrow is replaced by the plasma cells * Pathologic bone fractures - bone remodeling leavs out bony lesions * Rouleaux formation -Stacks of RBCs die to increased immunoglobulin

Question 41

Monoclonal gammopathy of undetermined significance

Answer 41

clonal expansion of plasma cells but ... lower amount of M-protein only few clonal plasma cells in bone marrow NO CRAB

Question 42

MGUS AKA

Answer 42

Monoclonal gammopathy of undetermined significance

Question 43

MGUS Treatment

Answer 43

do not treat at this stage

Question 44

MGUS evolution

Answer 44

this condition progresses to overt myeloma at the rate of 1-2% per year

Question 45

Lymphoplasmacytic Lymphoma

Answer 45

Monoclonal plasma cells and monoclonal lymphocytes mixed together

Question 46

What type of immunoglobulin in lymphoplasmacytic lymphoma?

Answer 46

IgM

Question 47

Hyperviscosity of the blood along with IgM M protein

Answer 47

Waldenstrom Macroglobulinemia

Question 48

M protein think about these diagnoses 3 listed

Answer 48

* Multiple Myeloma * MGUS * Lymphoplasmacytic lymphoma

Question 49

LPL AKA

Answer 49

Lymphoplasmacytic lymphoma

Question 50

A characteristic expression of LPL

Answer 50

* Hyperviscosity of the blood along with IgM M-protein * Waldenstrom Macroglobulinemia

Question 51

Treatment of Multiple Myeloma

Answer 51

Question 52

Treatment of Multiple Myeloma is only indicated if?

Answer 52

* CRAB is present * don't need to have all of them but can have some of them * not curable so only treat if it can benefit the patient

Question 53

Treatment of Multiple Myeloma drug classes 4 listed

Answer 53

* Immunomodulators (i.e. Thalidomide) * Proteasome inhibitors (Bortezomib) * Corticosteroids * Chemotherapy

Question 54

Thalidomide Toxicities

Answer 54

Marrow suppression peripheral neuropathy highly regulated teratogen (highly regulated)

Question 55

Bortezomib Toxicities

Answer 55

Toxic Neuropathy

Question 56

Chemotherapic agents in Multiple Myeloma 3 listed

Answer 56

* Cyclophosphamide * Liposomal doxorubicin * Melphalan

Question 57

Autologous Stem Cell Transplant in Multiple Myeloma

Answer 57

can collect cells before over-exposure to marrow toxic drugs

Question 58

Bone lesions in multiple myeloma

Answer 58

* Bisphosphanate therapy - same drugs used to treat osteoporosis * bone lytic lesions can be on skull which is very dangerous

Question 59

Clinical Overview

Answer 59