8/17- Lymphoproliferative Disorders II: DLBCL, T-cell Lymphomas, Hodgkin's

Question 1

What are indolent subtypes of T-cell lymphoma?

Answer 1

Cutaneous T- cell lymphoma (Mycosis Fungoides)

Question 2

Characteristics of Mycosis Fungoides

• Cells involved
• Organ/location
• Treatment
• Forms

Answer 2

• Malignancy of CD4+ T cells
• Affinity for skin (often diagnosed for years with cirriasis)

Can be treated with:

• XRT
• UV light
• Topical or systemic chemotherapy agents

Leukemic form is known as Sézary syndrome

• Convoluted (“cerebriform”) nuclei are characteristic

Question 3

What is this?

Answer 3

Mycosis Fungoides

Question 4

What is this?

Answer 4

Mycosis Fungoides

Question 5

What is this?

Answer 5

Mycosis Fungoides

Question 6

What are aggressive subtypes of T-cell lymphoma?

Answer 6

Anaplastic large cell lymphoma

Question 7

Characteristics of anaplastic Large Cell Lymphoma?

• Genetics
• Prognosis
• Cell markers
• Organs/cells involved

Answer 7

• 1/3 have t(2;5), which correlates with expression of ALK (anaplastic lymphoma kinase); excellent prognosis
• CD30 positive
• Skin often involved

Question 8

What are highly aggressive subtypes of T-cell lymphoma?

Answer 8

• Lymphoblastic Lymphoma/Leukemia
• Adult T cell Lymphoma/Leukemia

Question 9

Characteristics of Lymphoblastic Lymphoma?

• Cells involved
• Specific populations affected
• Variant of what
• Prognosis

Answer 9

• Usually a T cell malignancy
• Male adolescents
• Mediastinal mass
• Lymphoma variant of T cell acute lymphoblastic leukemia (ALL)
• Prognosis improving with intensive ALL regimens

Question 10

What is this?

Answer 10

Lymphoblastic Lymphoma?

Question 11

What is this?

Answer 11

Adult T-cell leukemia/lymphoma

• Characteristic flower cells (mature CD4+)

Question 12

Characteristics of Adult T-cell Leukemia/Lymphoma?

• Associations
• Epidemiology

Answer 12

• Associated with HTLV-I infection
• Japan, Caribbean
• Frequent hypercalcemia
• Cells (flower cells) are mature CD4+

Question 13

Characteristics of Hodgkin Lymphoma (HL)?

Answer 13

• Previously called Hodgkin’s disease
• 7x LESS common than non-Hodgkin lymphoma
• Highly treatable and curable, even when disseminated
• Presence of Reed-Sternberg cell is necessary to make diagnosis of classic HL

Question 14

Etiology of Hodgkin Lymphoma?

Answer 14

Reed-Sternberg cells are the malignant cells (LP cells in non-classic HL)

• Minor population in the malignant tissues (under 2%)
• Many normal lymphocytes, eosinophils, other cells Cell of origin is B cell

Some R-S cells contain EBV genomes (especially in mixed cellularity disease)

Majority of cases do not have clear etiology

Question 15

What is this? What cell markers are present?

Answer 15

Reed-Sternberg Cell

• CD15+
• CD30+
• CD20+ in up to 1/3, but negative for other B cell antigens

Question 16

What are these showing (left vs. right)

Answer 16

Left: R-S cell

Right: LP (L and H) cell

Question 17

Subtypes of Hodgkin Lymphoma?

Answer 17

Classic Hodgkin lymphoma (95% of cases):

• Nodular sclerosis
• Mixed cellularity
• Lymphocyte predominant
• Lymphocyte depleted

Non-classic Hodgkin lymphoma (5% of cases):

• Nodular lymphocyte-predominant Hodgkin lymphoma

Histologic subtype of classic HL does not determine how the disease is treated (stage is most important)

Question 18

What determines how HL is treated?

Answer 18

Stage, NOT histological subtype (classic vs. non-classic)

Question 19

Epideimology of Hodgkin Lymphoma?

Answer 19

• Bimodal distribution in developed countries (young adulthood and > 50 yo)
• More common in affluent families with few siblings
• In developing countries, more common in young children

Question 20

Signs and Symptoms of Hodgkin Lymphoma?

Answer 20

• Lymph node enlargement, usually cervical or mediastinal
• Systemic B symptoms common
• Pel-Ebstein fever (relapsing, high-grade fever that can reach 105-106°F, periodicity of 7-10 days, abrupt in onset and resolution)
• Pruritus
• Pain on drinking alcohol (where the disease is located, e.g. lymph node in neck)

Other Clinical Features:

• T cell mediated immune deficiency, even in early stage disease (and may persist even after lymphoma is cured), so prone to infections:

—-Herpes zoster (“shingles”) in 1/4

—-Fungal or mycobacterial infections

• Predictable contiguous spread of disease (though to be thru lymph system rather than hematogenous)

—-Cervical nodes -> mediastinum or axilla

—-Mediastinum to periaortic nodes or spleen, etc. (This is the basis for staging and treatment options)

Question 21

Diagnosis of Hodgkin Lymphoma

Answer 21

• Requires excisional biposy of LN (like all lymphomas)
• Fine needle aspirate is NOT sufficient to make the dx; architecture of node is important (and to see subtype/differentiate from others)

Question 22

Staging of Hodgkin Lymphoma

Answer 22

Basically the same as NHL:

• H+P, labs, CT scans, BM biopsy

PLUS:

• PET (or Gallium) scan
• Lymphangiogram or staging laparotomy ONLY if results would affect treatment decisions

Question 23

Treatment of Hodgkin Lymphoma

Answer 23

• Controversial, especially for early stages
• In general, XRT alone is reserved for very favorable early stage disease (IA, upper neck)

Otherwise, trend nowadays is:

- Early stage (I/II): Chemotherapy + XRT

- Advanced stage (III/IV): Chemotherapy ± XRT (bulky disease sites)

Number of cycles, type of chemotherapy and radiation dose depends on staging specifics

Question 24

Chemotherapy regimens for Hodgkin Lymphoma?

Answer 24

ABVD (current standard)

• Adriamycin
• Bleomycin
• Vinblastine
• Dacarbazine

BEACOPP (advanced stage w/ risk factors)

• Etoposide
• Cyclophosphamide

Brentuximab (for recurrent disease)

• Anti-CD30 monoclonal antibody

Question 25

What is the prognosis for Hodgkin Lymphoma?

Answer 25

- **One of the best survivals of lymphomas** - Often, pts who relapse after radiotherapy can be cured by salvage chemotherapy (Quoted cure rates by stage: - IA: 95% - IIA: 85% - IB/IIB: 70% - IIIA: 70% - IIB/IV: 50%)

Question 26

What is a late complication of Hodgkin Lymphoma?

Answer 26

**_High incidence of second malignancies_** **(leukemia first 10 yrs, solid tumors over time)** - **Leukemia** in pts receiving **alkylating** agents or **combined** chemo/XRT - **Lung** cancer and **breast cancer** in pts receiving **XRT** to chest (lung cancer especially high in smokers) - Hypothyroidism after irradiation of the neck - **Constrictive pericarditis** after **radiotherapy** to the mediastinum - **Infertility** after use of **alkylating** agents - **Heart failure** after **Adriamycin** treatment So focus is on minimizing amount of therapy without compromising immediate outcomes

Question 27

Which of the following findings is usually not associated with non-Hodgkin lymphomas at presentation? A. Anemia B. Fever C. Leukopenia D. Lymphadenopathy E. Weight loss

Answer 27

Which of the following findings is usually not associated with non-Hodgkin lymphomas at presentation? A. Anemia B. Fever **C. Leukopenia** D. Lymphadenopathy E. Weight loss Leukopenia is really not (neutropenia may occur with involvement in BM, but then you will see circulating lymphocytes and then lymphocytosis...)

Question 28

Which of the following stage III lymphomas is more likely to be curable with chemotherapy? A. Diffuse large B cell lymphoma B. Follicular lymphoma C. Marginal zone lymphoma D. Small lymphocytic lymphoma

Answer 28

Which of the following stage III lymphomas is more likely to be curable with chemotherapy? **A. Diffuse large B cell lymphoma** B. Follicular lymphoma C. Marginal zone lymphoma D. Small lymphocytic lymphoma Choices B-D are indolent lymphomas; the aggressive lymphomas are the ones we can typically cure just with chemotherapy?

Question 29

Which of the following lymphomas is expected to be CD4 positive? A. Burkitt lymphoma B. Diffuse large B-cell lymphoma C. Follicular lymphoma D. Hodgkin lymphoma E. Mycosis fungoides

Answer 29

Which of the following lymphomas is expected to be CD4 positive? A. Burkitt lymphoma B. Diffuse large B-cell lymphoma C. Follicular lymphoma D. Hodgkin lymphoma **E. Mycosis fungoides** Mycosis fungodes is a T cell lymphoma while the others are B cell lymphomas

Question 30

The following associations between a specific lymphoma type and microorganism are correct EXCEPT: A. Adult t-cell leukemia/lymphoma and human T lymphotropic virus type I (HTLV-1) B. Burkitt lymphomas and EBV C. Hodgkin lymphoma and Parvovirus B19 D. Marginal zone lymphoma and Helicobacter pylori

Answer 30

The following associations between a specific lymphoma type and microorganism are correct EXCEPT: A. Adult t-cell leukemia/lymphoma and human T lymphotropic virus type I (HTLV-1) B. Burkitt lymphomas and EBV **C. Hodgkin lymphoma and Parvovirus B19** D. Marginal zone lymphoma and Helicobacter pylori Parvovirus B19 is associated with aplastic crisis because it causes red blood cell aplasia

Question 31

A 70 yo male presents with generalized lymphadenopthy and leukocytosis. he is otherwise asymptomatic. His peripheral blood smear is shown (lymphocytes same size as RBC; can see smudge cell). **What is the most likely diagnosis?** A. ALL B. AML C. CLL D. CML **Does this pt need treatment?**

Answer 31

What is the most likely diagnosis? A. ALL B. AML **C. CLL** D. CML Does this pt need treatment? **No.** This pt does not need treatment (asymptomatic and elderly)

Question 32

A 65 yo male presents w/ fatigue, generalized lymphadenopathy and mild normocytic anemia. he is otherwise asymptomatic. An excisional biopsy of a cervical LN was done (can see germinal center-like structures). **What is the most likely diagnosis?** A. ALL B. CLL C. DLBCL- Diffuse large B cell lymphoma D. Follicular lymphoma **Does this pt need treatment?**

Answer 32

What is the most likely diagnosis? A. ALL B. CLL **C. DLBCL- Diffuse large B cell lymphoma** D. Follicular lymphoma Does this pt need treatment? **Maybe**. Treatment would depend on whether you can find a reason for him to be fatigued (shouldn't be caused by just mild anemia). No pressing reason to treat

Question 33

A 55 yo male presents w/ 2 mo Hx of progressively increasing L cervical LNs. He does not smoke. A fine needle aspirate of a cervical LN is reading as showing "malignant B lymphocytes consistent with NHL". What should be the next step in the mgmt of this pt? A. Do an emergent CT scan of the neck with contrast B. Do an emergent PET scan of the whole body C. Obtain and excisional biopsy of a L cervical node D. Start chemotherapy with R-CHOP E. Start chemotherapy with ABVD

Answer 33

What should be the next step in the mgmt of this pt? A. Do an emergent CT scan of the neck with contrast B. Do an emergent PET scan of the whole body **C. Obtain and excisional biopsy of a L cervical node** D. Start chemotherapy with R-CHOP E. Start chemotherapy with ABVD Adequate pathology is important; emergent scan not needed

Question 34

Which of the following therapeutic approaches is LESS likely to be useful in the treatment of a pt with biopsy-proven, symptomatic stage II anaplastic large cell lymphoma? A. multi-agent chemotherapy B. Radiation therapy C. Combined modality therapy (chemo + radiation) D. Surgical resection of affected LNs

Answer 34

Which of the following therapeutic approaches is LESS likely to be useful in the treatment of a pt with biopsy-proven, symptomatic stage II anaplastic large cell lymphoma? A. multi-agent chemotherapy B. Radiation therapy C. Combined modality therapy (chemo + radiation) **D. Surgical resection of affected LNs**

Question 35

A 30 yo female present with 40 lb weight loss and recurrent fever over the previous 6 mo. Bone marrow aspirate and biopsy are done as part of a workup for fever of unknown origin. The pathologist calls you saying that the pt has classic Hodgkin lymphomas. What large cells did she see under the microscope to make this diagnosis?

Answer 35

Reed-Sternberg cells (owl-eye cells) (pic D)

Question 36

A 22 yo male presents with a 2 mo Hx of fever, 15% weight loss and night sweats. Further evaluation reveals a large mediastinal mass. Biopsy demonstrates mixed cellularity Hodgkin Lymphoma. Which of the following factors is the LEAST important in planning the therapy for his dz? A. Evidence of BM involvement by lymphoma B. Hx of B Symptoms C. Mixed cellularity histology D. Presence of additional areas of lymphadenopathy E. Size of the mediastinal mass

Answer 36

Which of the following factors is the LEAST important in planning the therapy for his dz? A. Evidence of BM involvement by lymphoma B. Hx of B Symptoms **C. Mixed cellularity histology** D. Presence of additional areas of lymphadenopathy E. Size of the mediastinal mass Size corresponds to staging, which is what is used to determine treatment (rather than cellular histology)