Hematologic Malignancies

Question 1

Normally, what percentage of the bone marrow is made up of blasts? In an acute leukemia, what percentage of the marrow will be made up of blasts?

Answer 1

Normal: 1-2% of marrow are blasts

Acute lukemia: 20% or greater

Question 2

Your patient has a super high WBC count and on peripheral smear you see blasts. Name two ways to figure out if these blasts are lymphoblasts vs. myeloblasts.

Answer 2

Lymphoblasts will have positive immunostaining for TdT

Presence of Auer rods = myeloblasts (Auer rods are precipitated MPO, which neutrophils use)

Question 3

Your 15 yo patient presents with recurrent infection and a CXR reveals a mediastinal mass. Blasts are seen on peripheral smear and immunostaining reveals positivity for CD10, CD19, and CD20. What is your Dx and what cytogenetic abnormalities (which translocations) are associated with a good prognosis and a poor prognosis, respectively?

Answer 3

This is a B cell acute lymphoblastic leukemia (B-ALL)

B-ALL w/ good prognosis: t(12;21)

B-ALL w/ bad prognosis: t(9;22) aka Philadelphia chromosome (seen in adults usually)

Question 4

What type of hematologic malignancy is known to arise from myelodysplastic syndrome secondary to prior chemotherapy with alkylating agents?

Answer 4

Acute myelogenous leukemia

Question 5

What is myelodysplastic syndrome?

Answer 5

When there is ineffective hematopoiesis despite having hypercellular bone marrow (but cellularity is <20%, or else that would be acute leukemia); it may progress to acute leukemia

Question 6

Acute promyelocytic leukemia is a subcategory of _______. Those with a 15;17 translocation are treated with _______ and prognosis for these patients is good.

Answer 6

subcategory of AML; all-trans retinoic acid is effective for treating t(15;17) acute promyelocytic leukemia

Question 7

Which type of leukemia is associated with increased risk of DIC?

Answer 7

AML

Question 8

Which type of leukemia is likely to infiltrate the gums?

Answer 8

Acute monocytic leukemia (subtype of acute myelocytic leukemia)

Question 9

Your 64 yo patients presents for routine check-up and CBC shows a highly elevated WBC count. You perform a blood smear, which is shown. Immunostaining reveals co-expression of CD5 and CD23. What is your Dx?

Answer 9

Chronic lymphocytic leukemia (CLL). Note the smudge cell (top left).

Question 10

Which hematologic malignancy is tartrate resistant acid phosphatase (TRAP) positive? What type of cells have proliferated in this disease?

Answer 10

Hairy cell leukemia - neoplastic proliferation of mature B cells

Question 11

What is most often the only abnormal physical exam finding in a patient with hairy cell leukemia? What typically happens when you try to get a marrow aspirate in these patients?

Answer 11

Splenomegaly is often the only abnormal finding. Myelophthisic process –> dry tap on marrow aspirate.

Question 12

Japanese patient presents with rash and lytic bone lesions on XR. What is your Dx and what virus is this associated with?

Answer 12

Adult T cell leukemia-lymphoma (ATLL). Associated with human T cell leukemia retrovirus-1

Question 13

Mycosis fungoides is characterized by a neoplastic proliferation of _____ cells that infiltrate the _____. If these cells infiltrate the blood, it is called _______ Syndrome, and a blood smear will show cells with _______ nuclei.

Answer 13

Proliferation of CD4 T cells that infiltrate the skin. If cells infiltrate the blood, it is called Sezary syndrome; blood smear shows lymphocytes with cerebriform nuclei.

Question 14

Define lymphoma.

Answer 14

A neoplastic proliferation of lymphoid cells that form a mass.

Question 15

How are lymphomas classified?

Answer 15

Hodgkin and non-Hodgkin

Question 16

Your 58 yo patient presents with a painless axillary mass. You do an excisional biopsy and the histological section is shown. What is your Dx and what CD marker would you expect the neoplastic cells to express? Also, what cytogenetic abnormality is often associated with these cancers and what is the corresponding gene product?

Answer 16

Follicular lymphoma.

B cells in these express CD20.

t(14;18) –> overexpression of Bcl2, an anti-apoptotic protein.

Question 17

Patients with follicular lymphoma who are symptomatic may be treated with _________.

Answer 17

Rituximab

Question 18

Which neoplasm is associated with a translocation between chromosomes 11 and 14 (cyclin D –> Ig heavy chain locus), is seen in older people, and is also associated with chronic inflammatory states as seen in Hashimoto’s thyroiditis, Sjogren syndrome, and H. pylori gastritis?

Answer 18

Mantle cell lymphoma

Question 19

What translocation is seen in Burkitt lymphoma? What are the two types and the typical presentation of each?

Answer 19

t(14;18)

c-myc –> Ig heavy chain

African/endemic form: presents as a jaw mass in a young child

Sporadic/American form: presents in the pelvis or GI tract

Question 20

Buzz word: starry-sky appearance

Answer 20

Burkitt lymphoma

Question 21

What is the most common type of non-Hodgkin lymphoma?

Answer 21

Diffuse large B cell lymphoma

Question 22

True or false: the mass of a Hodgkin lymphoma is comprised mostly of neoplastic cells.

Answer 22

False, the Reed-Sternberg cells release cytokines that recruit non-neoplastic cells and may also lead to fibrosis

Question 23

What are the classic symptoms seen in a patient with Hodgkin lymphoma?

Answer 23

B symptoms: fever, night sweats, chills from cytokines made by the RS cells

Question 24

Name the subtypes of Hodgkin lymphoma.

Answer 24

1. Nodular sclerosis
2. Lymphocyte-rich
3. Lymphocyte-depleted
4. Mixed cellularity
5. Nodular lymphocyte predominant

Question 25

Describe what a myeloproliferative disorder is.

Answer 25

Accumulation of mature cells of the myeloid lineage (granulocytes, monocytes, megakaryocytes, RBCs)

Question 26

What chromosomal translocation and protein product are associated with CML?

Answer 26

t(9;22) BCR-ABL, a tyrosine kinase

Question 27

Describe the clinical findings seen in the accelerated phase of CML.

Answer 27

Increasingly worsening splenomegaly 10-19% blasts Basophilia in peripheral blood (\>20%) Thrombocytopenia or thrombocytosis

Question 28

Which acute leukemia(s) can CML transform into?

Answer 28

Either AML (2/3) or ALL (1/3)

Question 29

Name a targeted therapy for CML.

Answer 29

Imatinib

Question 30

Polycythemia vera is associated with a ________ mutation, which causes proliferation of...?

Answer 30

Jak2 mutation --\> proliferation of mature RBCs

Question 31

Name five symptoms seen in polycythemia vera.

Answer 31

1. Headache 2. Pruritis, especially after hot showers (due to mast cell release of histamine - there are increased levels of mast cells) 3. Erythromelalgia - transient blockage of arterial flow to extremities followed by inflammation and hyperemia 4. Facial flushing 5. Claudication/angina

Question 32

What is the treatment for polycythemia vera?

Answer 32

Phlebotomy and aspirin to prevent thrombosis

Question 33

What disease is consistent with the following lab findings: - Hyperuricemia - Elevated Hct - Elevated Hb

Answer 33

Polycythemia vera

Question 34

What is reactive polycythemia and what can cause it?

Answer 34

When a primary disease process stimulates EPO production and an increase in Hb/Hct. Lung disease and kidney disease can cause it. It is important to investigate these possibilities when polycythemia vera is considered in the differential.

Question 35

Your patient presents with anemia and recurrent infection. Blood smear shows few RBCs that are in rouleaux formation. SPEP shows a M spike in the gamma globulin region. Why is there rouleaux formation on the blood smear?

Answer 35

Multiple myeloma - lots of Igs in the blood neutralize negative charges on RBCs so they no longer repel each other.

Question 36

Describe the pathophysiology behind this.

Answer 36

Neoplastic plasma cells can produce osteoclast activating factor aka RANKL —\> activation of RANK receptor on osteoclasts --\> osteoclasts resorb bone

Question 37

What is the most common primary malignancy of bone?

Answer 37

Multiple myeloma

Question 38

Is a M spike in the gamma globulin region on SPEP diagnostic for multiple myeloma?

Answer 38

No, it could also be MGUS (monoclonal gammopathy of undetermined significance) or Waldenstrom Macroglobulinemia. To make the Dx of multiple myeloma, there must also be other symptoms: AL amyloidosis, lytic bone lesions, Bence Jones protein in urine, CRAB: C = hyperCalcemia R = Renal insufficiency A = Anemia B = Bone lesions