Review: Lymphomas

Question 1

Lymphomas are divided into what categories

Answer 1

Hodgkin’s Lymphoma

NH Lymphoma

Question 2

What is germinal center

Answer 2

Where B-cells undergo somatic hypermutation (process B-cells undergo to produce selective Ab) and class-switching (IgM => other Ig Ab)

Question 3

Have HL B-cells already undergone somatic hypermutation?

Answer 3

Yes => thus all monoclonal

Question 4

What is HL?

Answer 4

Malignant proliferation of mutated B-cell in the germinal center of LN (MC cervical) due to EBV infection (most).

Question 5

Markers of HL

Answer 5

Not usual B-cell markers:

CD15/30+
PAX5+
Surface IgG

If nodular lymphocytic predominant: CD20+ and BCL6+

Question 6

HL is MC when?

Answer 6

Bimodal age distribution: 20 & 65. Average age = 32YO.

Question 7

How are lymphomas different from reactive lymphocytosis?

Answer 7

Cells are monoclonal

Question 8

How does HL spread?

Answer 8

Begins in a single, localized LN (MC = cervical = neck) and spreads in a predictable fashion.

Question 9

Presentation of HL

Answer 9

1. Painless mass in cervical LN (head/neck): spreads from node- node in predictable manner
2. Mediastinal mass (if nodular sclerotic type)
3. B-symptoms (d/t cytokines released from B- cells): fever, chills, night sweats, WL: Indicates WORSE prognosis
4. Extranodal involvement = rare
5. Hypercalcemia

Question 10

What types of HL are NOT associated with EBV?

Answer 10

1. Nodular sclerosis

2. Lymphocyte predominant

Question 11

Which type of HL is the worse prognosis?

Who/where is it MC in?

Answer 11

Lymphocyte depleted: MC in older males, HIV and developing countries

Question 12

RF of HL

Answer 12

1. Prior EBV
2. Immunosuppresion
3. AI diseases (RA, SLE)

Question 13

Prognosis of HL

Answer 13

Highly curable.

Question 14

What are NHL?

Answer 14

Proliferation of MATURE B-cells.

• Affects multiple LN and NON-contiguously
• Extranodal involvement common (spleen, GI tract, respiratory tract) and NON-lymphoid tissue (CNS)

Question 15

What NHL are B-cells MC in?

Answer 15

More aggressive types: Burkitt and DLBC

Question 16

DLBL markers, MC in, genetics

Answer 16

1. CD19+/20+
2. BCL6/2
3. Surface Ig

Older patients (>60)

1. Dysregulation of BCL6 (too much or too little), which is required for formation of NL germinal centers
2. Small % have t(14:18): translocation = BCL2-IgG fusion gene: if BCL2 rearrangements is present => usually NO BCL6 rearrangements (thus, BCL6 is NL). Thus, they could have previously been follicular lymphomas

Question 17

Follicular B-cell lymphoma markers, MC in, genetics

Answer 17

1. CD19/20+
2. CD10+
3. surface Ig,
4. BCL6 and BCL2 in 90% of cases.

Middle aged adults (M=F); rare in AZNs

1. (14:18) -translocation = BCL2-IgG fusion gene => overexpression of BCL2 => blocks apoptosis => uncontrolled growth of B-cells.

Germinal center B-cells usually lack Bcl2 because frequently under apoptosis, unless selected by somatic hypermutatioon.

Overexpression of Bcl2 prevents death of germinal center B cells => growth

Question 18

Burkitt Lymphoma markers, MC in, genetics

Answer 18

1. CD19+/20+
2. CD10+
3. IgM
4. BCL6
5. NO anti-apoptotic BCL2

Children or young adults

1. t(8:14) = ↑↑↑ c-MYC => increase transcription of genes needed for aerobic glycolysis (Warburg effect), allowing cells to make their own building blocks needed for cell growth and division.

Question 19

Mantle Cell Lymphoma markers, MC in, genetics

Answer 19

1. CD19/20
2. CD5*, usually a T-cell marker
3. Cyclin D1

Adult males (50- 60 YO)

1. t(11:14) => overexpression of cyclin D1: G1 => S phase

Question 20

Marginal Zone Lymphoma genetics

Answer 20

1. t(11:18) translocation*
2. t(14:18) translocation
3. t(1:14) translocation

All upregulate BCL10 or MALT1

Question 21

Small cell lymphocytic lymphoma/ Chronic lymphocytic leukemia markers, MC in, genetics

Answer 21

1. CD19/20+
2. CD5+***, just like Mantle Cells
3. CD23+
4. Surface IgM/IgD

Older adults (60Y M)

Unlike other lymphoid malignancies, translocations rare:

1. Trisomy 12: deletion of 11q, 13q and 17p.
2. GOF NOTCH1 mutation  worse prognosis

Question 22

Presentation of Burkitt Lymphoma

Answer 22

Rapidly growing tumor that arises in extranodal site:

B-cell sx

1. • Endemic = mass in the jaw/mandible in 4-7YO AF child
2. • Sporadic = abdominal mass (ileocecum or peritoneum, ovary adrenals) in children
3. • Immunodeficiency related BL = older adults with mass in LN (lymphadenopathy

Question 23

Prognosis of Burkitt cell

Answer 23

Very aggressive – rapid proliferation (fastest growing of all)

However, responds WELL to intensive chemotherapy.
Most children, young adults can be cured.

Question 24

Histology of Burkitt

Answer 24

Starry-sky morphology: sheets of highly mitotic lymphocytes with interspersed tingible body MO (have clear cytoplasms

Question 25

Presentation of Follicular Lymphoma

Answer 25

1. Painless, generalized waxing and waning LAD (extra nodal involvement is RARE) 2. By the time of dx, BM is almost always invaded! 3. Indolent and non-aggressive, but Incurable and can transform into DLBL or Burkitt lymphoma

Question 26

Histology of Follicular Lymphoma

Answer 26

1. Nodular pattern of growth: cell pattern looks similar to NL LN follicles 2. Follicular hyperplasia 3. If BM involved = paratrabecular LN aggregates

Question 27

treatment of follicular lymphoma

Answer 27

Treatment = palliative treatment with low dose chemo or anti-CD20 Ab when symptomatic.

Question 28

Diffuse Large B-cell Lymphhoma presentation

Answer 28

Appears as a rapidly growing mass at nodal site or extranodal site: 1. Walter ring, 1'/2' involvement of spleen or liver, GI tract, skin, bone and brain

Question 29

Prognosis of DLBCL

Answer 29

Aggressive, rapidly fatal without treatment.

Question 30

Histology of DLBCL

Answer 30

1. Diffuse, large B-cells | 2. Obliteration of LN architecture, especially follicles

Question 31

In BM involved in DLBCL?

Answer 31

Uncommon: pts still make an adequate amount of RBC, WBC, platelets

Question 32

Which lymphomas commonly undergo a leukemic phase (malignant cells in peripheral BS)?

Answer 32

1. Follicular B-cell (10% of cases have lymphocytosis) 2. Mantle cell 3. Small cell lymphocytic leukemic/ CLL

Question 33

Presentation of Mantle Cell Lymphoma

Answer 33

At time of dx: spread to bone, liver or GI tract disease (late-stage). Symptoms are due to extra nodal involvement 1. . Painless lymphadenopathy (LAD) 2. Extranodal involvement: gut, spleen, liver => hepatosplenomegaly 3. Polyp like lesions (lymphomatoid polyposis) in mucosa of SI/colon

Question 34

Histology of Mantle Zone lymphoma

Answer 34

1Homogenous expanding population of small lymphoid cells in mantle zone (surrounding a small, atrophic germinal center.

Question 35

Marginal Zone Lymphoma = what is it?

Answer 35

Neoplasm of mature memory B-cells at site of chronic inflammation, due to the formation of a marginal zone.

Question 36

What rule does Marginal Zone lymphoma NOT follow?

Answer 36

RMBR; true malignancies exhibit monoclonality. This is an exception Marginal zone lymphomas begin as reactive lymphoid neoplasia  [translocations] lymphoma. Thus, they begin as polyclonal  monoclonal transformation.

Question 37

Presentation of Marginal Zone lymphoma?

Answer 37

Presents as a mass in extranodal sites associated with chronic inflammation. 1. Sjrogens => salivary glands 2. Hashimoto => thyroid 3. H.Pylori => produces a MALToma in the stomach Remains localized for prolonged periods of time May regress if inciting agent goes away.

Question 38

What is Small cell lymphocytic lymphoma/ chronic lymhocytic leukemia?

Answer 38

Neoplasm of naïve lymphocytes (NOT lymphoblasts), called prolymphocytes.

Question 39

SLL = Lymphocyte count < _____ (leukopenia) CLL = Lymphocyte count >_____ (leukocytosis)

Answer 39

SLL = Lymphocyte count < 5000 (leukopenia) CLL = Lymphocyte count >5000 (leukocytosis)

Question 40

What are complications in Small cell lymphocytic lymphoma/ chronic lymphocytic leukemia?

Answer 40

1. *Hypogammaglobinemia (usually IgG/A/M) => ↑↑↑ susceptibility to bacterial infections because disrupts NL immune function 2 Autoimmune hemolytic anemia due to production of autoAB 3. Thrombocytopenia 4. Richter syndrome: prolymphocytes can transform into an aggressive DLBL (Diffuse Large B-cell Lymphoma) = survival of less than 1 year.

Question 41

Presentation of Small cell lymphocytic lymphoma/ chronic lymphocytic leukemia?

Answer 41

Older patient, often asymptomatic at diagnosis and progresses slowly. If symptomatic, non-specific with recurring infections. 1. *Non-specific symptoms = fatigue, WL, anorexia 2. *50-60% = Generalized LAD and hepatosplenomegaly* 3. *Small monoclonal Ig “spike” is present in blood of some low rade

Question 42

Histology findings for Small cell lymphocytic lymphoma/ chronic lymphocytic leukemia?

Answer 42

1. Prolymphocyte centers = loose aggregates of large lymphocytes with mitotically active cells 2. Smudge cell 3. Scattered spherocytes (round cells) 4. Prolymphcytes in LN