Lymphomas

Question 1

What is a lymphoma?

Answer 1

A malignancy of lymphoid cells based in lymphoid tissues such as the lymph nodes, spleen, thymus, or MALT. It may involve the marrow and blood secondarily.

Question 2

B-ALL clinical presentation

Answer 2

Acute Several weeks of fatigue due to anemia Easy bruising due to thrombocytopenia Fever, signs of infection due to neutropenia May have pain in a single long bone, skin involvement

Question 3

B-ALL workup

Answer 3

Peripheral blood smear: lymphoblasts CBC: anemia, thrombocytopenia, granulocytopenia Bone marrow: lymphoblasts are >20% of marrow cellularity

Question 4

B-ALL flow cytometry

Answer 4

TdT+ CD19+ CD34+

Question 5

B-ALL age of peak incidence

Answer 5

3 (FYI this is the time of peak B cell production in the bone marrow)

Question 6

Does the presence of t(9;22) produce a good or bad prognosis?

Answer 6

Bad

Question 7

T-ALL peak incidence

Answer 7

15

Question 8

T-ALL clinical presentation

Answer 8

cough, shortness of breath, superior vena cava

Question 9

T-ALL clinical presentation

Answer 9

usually presents as a large thymus mass with cough, shortness of breath, superior vena cava syndrome (swelling and redness of face and upper extremities)

Question 10

T-ALL flow cytometry markers

Answer 10

TdT+ CD 2-8

Question 11

Are ALLs agressive tumors?

Answer 11

Yup! Treat early, treat fast!

Question 12

What are B symptoms?

Answer 12

fever night sweats weight loss

Question 13

Relative to T or NK cells, why are germinal center B cells most likely to give rise to neoplasms?

Answer 13

B cells rely on somatic hypermutation and class switching to function properly. Since their genomes are designed to be able to change, they are also most likely to mutate in a malignant way.

Question 14

What infections are associated with lymphoid neoplasms?

Answer 14

EBV HHV8 (kaposi sarcoma herpesvirus) HTLV-1 HIV H. pylori

Question 15

CLL/SLL pathogenesis

Answer 15

Not entirely understood but thought to involve deletions

Question 16

CLL workup (blood smear, bone marrow, etc)

Answer 16

Blood smear: increased numbers of small round lymphocytes, smudge cells

Bone marrow: aggregates of similar appearing tumor cells

Lymph nodes: diffusely infiltrated by small lymphocytes and patchy collections of larger, mitotically active cells known as proliferation centers.

CBC: lymphocytosis (lymphs > 5000)

Question 17

CLL clinical presentation

Answer 17

Often asymptomatic

May present with weight loss, fatigue, anorexia, diffuse LAD, or hepatosplenomegaly

Question 18

CLL flow cytometry

Answer 18

CD 5+

CD 10-

CD 20 +, CD 19+, CD23+

Question 19

What does this CBC suggest?

Answer 19

CLL

lymphocytosis with everything else fairly normal

Question 20

Answer 20

CLL

smudge cells

Question 21

Does CLL always require treatment?

Answer 21

No, approx. 60% of patients with CLL never require treatment.

High lymphocyte count alone is not an indication to start treatment

Question 22

What’s the significance of chromosome 17 in CLL?

Answer 22

Chromosome 17 is home to the p53 tumor suppressor gene. This is a common target for chemotherapy so CLL with deletions of this gene cannot be treated effectively with conventional chemo. They have a very poor prognosis.

Question 23

Answer 23

Hairy cell

Question 24

Hairy cell leukemia

Answer 24

• A tumor of mature B cells expressing CD20 but not CD5 of CD10
• Associated with BRAF mutations
• Often presents with splenomegaly and cytopenia, especially monocytopenia, and infections (especially with mycoplasma)
• Peripheral blood shows “hairy cells”

Question 25

What's this?

Answer 25

A healthy lymph node germinal center

Question 26

What's this? (Note: this is a low power view)

Answer 26

Lymph node germinal center in diffuse large B cell lymphoma

Question 27

What's this? (Note: this is high power)

Answer 27

Lymph node germinal center in diffuse large B cell lymphoma * large cells with prominent nucleoli

Question 28

DLBCL pathogenesis

Answer 28

Mutations involving BCL6 which codes for a transcription factor required for the maturation of germinal center B cells. * lead to survival and continued proliferation of B cells. * thought to be due to errors in class switching or somatic hypermutation

Question 29

DLBCL presentation

Answer 29

Can present with B symptoms and LAD or a rapidly enlarging mass

Question 30

Does DLBCL have an elevated LDH?

Answer 30

Yup.

Question 31

DLBCL flow cytometry

Answer 31

CD20+ may also express CD10 and surface Ig

Question 32

Burkitt Lymphoma

Answer 32

* Endemic (Africa): EBV+, jaw mass * Sporadic (US): may be EBV+, abdominal mass, spreads to the CNS * Associated with HIV * Associated with **c- MYC** gene mutations - **t(8;14)** * Express CD20, CD10, BCL6, but not usually BCL2 (distinguishes from DLBCL) * tissue histology shows "starry sky"

Question 33

Answer 33

Starry sky * Pale macrophages in the Burkitt's lymphoma

Question 34

Follicular lymphoma pathogenesis

Answer 34

* t(14;18) (plus other mutations) * causes overexpression of BCL2 which inhibits apoptosis. * FYI: Normal B cells downregulate BCL2, resulting in the death of cells that don't produce high affinity Abs. With the overexpression of BCL2, these cells do not die.

Question 35

Answer 35

Follicular lymphoma lymph node Nodular growth pattern

Question 36

Answer 36

Follicular lymphoma peripheral blood small to intermediate sized cells with cleaved nuclear contours and clumped chromatin

Question 37

What is a Non-Hodgkin's Lymphoma anyway?

Answer 37

Any lymphoma that isn't a Hodgkin's lymphoma.

Question 38

What's going on in Hodgkin's lymphoma?

Answer 38

Neoplastic cells are in the minority. They secrete cytokines and chemokines that attract inflammatory cells, which make up most of the tumor mass.

Question 39

Hodgkin Lymphoma subtypes

Answer 39

Classical vs nodular lymphocyte predominant Classical subtypes: * Nodular sclerosis * Mixed cellularity * Lymphocyte rich * Lymphocyte depleted

Question 40

Reed-Sternberg cells

Answer 40

The neoplastic cells of Hodgkin's lymphoma. They are derived from germinal center B cells and have clonal rearranged immunoglobulin heavy chains that have undergone somatic hypermutation. They express PDL-1 (programmed death ligand 1), inhibiting immune response. * express CD 15 and CD 30 * Do not express CD20 * "owl eyes"

Question 41

Answer 41

Nodular sclerosis HL

Question 42

Answer 42

Reed-Sternberg cell Characteristic of Hodgkin's lymphoma Large highly atypical cells with abundant cytoplasm, one or 2 nuclear lobes, vesicular chromatin, prominent eosinophilic nucleoli

Question 43

HL clinical presentation

Answer 43

Painless LAD * In nodular sclerosis subtype, may be in the mediastinum resulting in chest discomfort, cough, dypsnea, and/or SVC syndrome May have B symptoms May have itching

Question 44

HL workup

Answer 44

CBC: leukocytosis, eosinophilia * may show anemia in chronic state Lymph node biopsy: Reed Sternberg cell (owl eyes)

Question 45

Classical HL flow cytometry

Answer 45

CD 20- CD 15+ CD 30+