Chapter 6

Question 1

B-ALL surface markers

Answer 1

Usually characterized by lymphoblasts (TdT+) that express CD10, CD19, and CD20.

Question 2

T-ALL surface markers

Answer 2

T-ALL is characterized by lymphoblasts (TdT+) that express markers ranging from
CD2 to CD8 (e.g., CD3, CD4, CD7). The blasts do not express CD10.

Question 3

B-ALL’s prognosis is based off what cytogenetics?

Answer 3

Prognosis is based on cytogenetic abnormalities.
t(l2;2l) has a good prognosis; more commonly seen in children
t(9;22) has a poor prognosis; more commonly seen in adults (Philadelphia+ALL)

Question 4

how does T-ALL present?

Answer 4

Usually presents in teenagers as a mediastinal (thymic) mass (called acute lymphoblastic lymphoma because the malignant cells form a mass)

Question 5

how is AML characterized?

Answer 5

Myeloblasts are usually characterized by positive cytoplasmic staining for myeloperoxidase (MPO).

Crystal aggregates of MPO may be seen as Auer rods

Most commonly arises in older adults (average age is 50-60 years)

Question 6

AML can be subclassified based on cytogenetic abnormalities. What is the most important one?

Answer 6

Acute promyelocytic leukemia (APL)

i. Characterized by t(15;17), which involves translocation of the retinoic acid receptor (RAR) on chromosome 17 to chromosome 15; RAR disruption blocks maturation and promyelocytes (blasts) accumulate.
ii. Abnormal promyelocytes contain numerous primary granules that increase the risk for DIC.
iii. Treatment is with all-trans-retinoic acid (ATRA, a vitamin A derivative), which binds the altered receptor and causes the blasts to mature (and eventually die).

Question 7

AML can also be subclassified based on the lineage of myeloblasts. which are the two most important?

Answer 7

Acute monocytic leukemia

i. Proliferation of monoblasts; usually lack MPO
ii. Blasts characteristically infiltrate gums (Fig. 6.7).

3. Acute megakaryoblastic leukemia
   i. Proliferation of megakaryoblasts; lack MPO
   ii. Associated with Down syndrome (usually arises before the age of 5)

Question 8

what is a myelodysplastic syndrome?

Answer 8

AML may also arise from pre-existing dysplasia (myelodysplastic syndromes), especially with prior exposure to alkylating agents or radiotherapy.

l. Myelodysplastic syndromes usually present with
hypercellular bone marrow (however because the cells aren’t formed right, they don’t get out to the blood) –> therefore, they have cytopenias, abnormal maturation of cells, and increased blasts (< 20%).

2. Most patients die from infection or bleeding, though some progress to acute leukemia.

Question 9

what is CML? what is it driven by?

what is seen on the blood smear?

Answer 9

Neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors; basophils are characteristically increased

Driven by t(9;22) (Philadelphia chromosome) which generates a BCR-ABL fusion
protein with increased tyrosine kinase activity.

Question 10

what is found on physical exam with CML?

Answer 10

Splenomegaly is common. Enlarging spleen suggests accelerated phase of disease; transformation to acute leukemia usually follows shortly thereafter.

Question 11

what is the very feared complication of CML?

Answer 11

Can transform to AML (2/3 of cases) or ALL (l/3 of cases) since mutation is in a pluripotent stem cell.

Question 12

how is CML is distinguished from a leukemoid reaction

Answer 12

CML is distinguished from a leukemoid reaction (reactive neutrophilic leukocytosis) by

l. Negative leukocyte alkaline phosphatase (LAP) stain (granulocytes in a leukemoid reaction are LAP positive)
2. Increased basophils (absent with leukemoid reaction)
3. t(9;22) (absent in leukemoid reaction)

Question 13

what are the clinical features of myelofibrosis?

Answer 13

Megakaryocytes produce excess platelet-derived growth factor (PDGF) causing
marrow fibrosis (Fig. 6.13).
C. Clinical features include
l. Splenomegaly due to extramedullary hematopoiesis
2. Leukoerythroblastic smear (tear-drop RBCs, nucleated RBCs, and immature
granulocytes, Fig. 6.14)
3. Increased risk of infection, thrombosis, and bleeding

Question 14

what is CLL? what are the markers?

WHAT IS THE HALLMARK ON THE SMEAR

Answer 14

Neoplastic proliferation of naive B cells that co-express CD5 and CD20; most common leukemia overall

Increased lymphocytes and smudge cells are seen on blood smear

Question 15

What are the complications of CLL?

Answer 15

Complications include

1. Hypogammaglobulinemia: Infection is the most common cause of death in CLL.
2. Autoimmune hemolytic anemia

I mean these B cells just really don’t give a fuck

3. Transformation to diffuse large B-celllymphoma (Richter transformation)- marked clinically by an enlarging lymph node or spleen

Question 16

what is hairy cell?

Answer 16

Neoplastic proliferation of mature B cells characterized by hairy cytoplasmic
processes
Cells are positive for tartrate-resistant acid phosphatase (TRAP).

Get trapped in the spleen (splenomegaly), in the BM (get fribrosis). and can’t move to LN (adenopathy is absent)

Question 17

what is ATLL?

Answer 17

Neoplastic proliferation of mature CD4+ T cells

Associated with HTLV-1; most commonly seen in Japan and the Caribbean

Clinical features include rash (skin infiltration), generalized lymphadenopathy with hepatosplenomegaly, and lytic (punched-out) bone lesions with hypercalcemia.

Question 18

What is mycosis fungoides?

Answer 18

Neoplastic proliferation of mature CD4+ T cells that infiltrate the skin, producing
localized skin rash, plaques, and nodules. Aggregates of neoplastic cells in the
epidermis are called Pautrier microabscesses.
B. Cells can spread to involve the blood, producing Sezary syndrome.
l. Characteristic lymphocytes with cerebriform nuclei (Sezary cells) are seen on blood smear (Fig. 6.10).

Question 19

so how many chronic leukemias do i need to know involving b cells? what about t cells?

Answer 19

b cells = 2 –> CLL and hairy cell

t cells = also 2 –> ATLL and MF

Question 20

what precisely are RS cells? what are the cell markers?

Answer 20

Neoplastic proliferation of Reed-Sternberg (RS) cells, which are large B cells with multilobed nuclei and prominent nucleoli (‘owl-eyed nuclei’, Fig. 6.18); classically positive for CD15 and CD30

Question 21

what are the translocations for follicular, mantle cell, and burkitts lymphoma??

Answer 21

follicular t(l4;18)
mantle  t(ll;l4}
burritos t(8;14)

Question 22

what is the is the most common subtype of HL (70% of all cases)? what are the RS cells doing?

Answer 22

Nodular sclerosis is the most common subtype of HL (70% of all cases).
1. Classic presentation is an enlarging cervical or mediastinal lymph node in a
young adult, usually female.
2. Lymph node is divided by bands of sclerosis (Fig. 6.19A); RS cells are present in
lake-like spaces (lacunar cells, Fig. 6.19B).

Question 23

what are the characteristics of waldenstrom hyperglobulinemia?

Answer 23

1. Generalized lymphadenopathy; lytic bone lesions are absent.
2. Increased serum protein with M spike (comprised of lgM)
3. Visual and neurologic deficits (e.g., retinal hemorrhage or stroke) DUE TO lgM (large pentamer) causing serum hyperviscosity.
4. Bleeding-Viscous serum results in defective platelet aggregation.

Question 24

where are birbeck granules found?

Answer 24

LANGERHANS CELL HISTIOCYTOSIS

Langerhans cells are specialized dendritic cells found predominantly in the skin.

Derived from bone marrow monocytes
Present antigen to naive T cells

Langerhans cell histiocytosis is a neoplastic proliferation of Langerhans cells.

Characteristic Birbeck (tennis racket) granules are seen on electron microscopy

Cells are CDla+ and SlOO+ by immunohistochemistry.