Hematologic Malignancies Flashcards
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?
Normal: 1-2% of marrow are blasts
Acute lukemia: 20% or greater
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.
Lymphoblasts will have positive immunostaining for TdT
Presence of Auer rods = myeloblasts (Auer rods are precipitated MPO, which neutrophils use)
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?
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)
What type of hematologic malignancy is known to arise from myelodysplastic syndrome secondary to prior chemotherapy with alkylating agents?
Acute myelogenous leukemia
What is myelodysplastic syndrome?
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
Acute promyelocytic leukemia is a subcategory of _______. Those with a 15;17 translocation are treated with _______ and prognosis for these patients is good.
subcategory of AML; all-trans retinoic acid is effective for treating t(15;17) acute promyelocytic leukemia
Which type of leukemia is associated with increased risk of DIC?
AML
Which type of leukemia is likely to infiltrate the gums?
Acute monocytic leukemia (subtype of acute myelocytic leukemia)
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?
Chronic lymphocytic leukemia (CLL). Note the smudge cell (top left).
Which hematologic malignancy is tartrate resistant acid phosphatase (TRAP) positive? What type of cells have proliferated in this disease?
Hairy cell leukemia - neoplastic proliferation of mature B cells
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?
Splenomegaly is often the only abnormal finding. Myelophthisic process –> dry tap on marrow aspirate.
Japanese patient presents with rash and lytic bone lesions on XR. What is your Dx and what virus is this associated with?
Adult T cell leukemia-lymphoma (ATLL). Associated with human T cell leukemia retrovirus-1
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.
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.
Define lymphoma.
A neoplastic proliferation of lymphoid cells that form a mass.
How are lymphomas classified?
Hodgkin and non-Hodgkin
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?
Follicular lymphoma.
B cells in these express CD20.
t(14;18) –> overexpression of Bcl2, an anti-apoptotic protein.
Patients with follicular lymphoma who are symptomatic may be treated with _________.
Rituximab
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?
Mantle cell lymphoma
What translocation is seen in Burkitt lymphoma? What are the two types and the typical presentation of each?
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
Buzz word: starry-sky appearance
Burkitt lymphoma
What is the most common type of non-Hodgkin lymphoma?
Diffuse large B cell lymphoma
True or false: the mass of a Hodgkin lymphoma is comprised mostly of neoplastic cells.
False, the Reed-Sternberg cells release cytokines that recruit non-neoplastic cells and may also lead to fibrosis
What are the classic symptoms seen in a patient with Hodgkin lymphoma?
B symptoms: fever, night sweats, chills from cytokines made by the RS cells
Name the subtypes of Hodgkin lymphoma.
- Nodular sclerosis
- Lymphocyte-rich
- Lymphocyte-depleted
- Mixed cellularity
- Nodular lymphocyte predominant
Describe what a myeloproliferative disorder is.
Accumulation of mature cells of the myeloid lineage (granulocytes, monocytes, megakaryocytes, RBCs)
What chromosomal translocation and protein product are associated with CML?
t(9;22)
BCR-ABL, a tyrosine kinase
Describe the clinical findings seen in the accelerated phase of CML.
Increasingly worsening splenomegaly
10-19% blasts
Basophilia in peripheral blood (>20%)
Thrombocytopenia or thrombocytosis
Which acute leukemia(s) can CML transform into?
Either AML (2/3) or ALL (1/3)
Name a targeted therapy for CML.
Imatinib
Polycythemia vera is associated with a ________ mutation, which causes proliferation of…?
Jak2 mutation –> proliferation of mature RBCs
Name five symptoms seen in polycythemia vera.
- Headache
- Pruritis, especially after hot showers (due to mast cell release of histamine - there are increased levels of mast cells)
- Erythromelalgia - transient blockage of arterial flow to extremities followed by inflammation and hyperemia
- Facial flushing
- Claudication/angina
What is the treatment for polycythemia vera?
Phlebotomy and aspirin to prevent thrombosis
What disease is consistent with the following lab findings:
- Hyperuricemia
- Elevated Hct
- Elevated Hb
Polycythemia vera
What is reactive polycythemia and what can cause it?
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.
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?
Multiple myeloma - lots of Igs in the blood neutralize negative charges on RBCs so they no longer repel each other.
Describe the pathophysiology behind this.
Neoplastic plasma cells can produce osteoclast activating factor aka RANKL —> activation of RANK receptor on osteoclasts –> osteoclasts resorb bone
What is the most common primary malignancy of bone?
Multiple myeloma
Is a M spike in the gamma globulin region on SPEP diagnostic for multiple myeloma?
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
