W4- L5-Hodkins lymphoma

Question 1

Affect young adults (15-40 years). Some areas see second
late age peak (6/7th decade) – has bimodal distribution

Answer 1

Hodkin’s lymphoma

Question 2

Why is there high prevalence of Hodkin’s lymphoma in South Africa?

Answer 2

Coz of high HIV incidence in the country;
Increasing association with HIV

Question 2

How can one cure Hodkin’s Lymphoma?

Answer 2

• Chemotherapy and
  -Radiotherapy in the majority of
  patients.

*Response less favourable
with associated HIV

Question 2

What is the characteristic malignant cell of Hodkin’s lymphoma?

Answer 2

Reed-Sternberg cell

*Abnormal, large, multinucleated cells typically derived from B lymphocytes

Question 3

Which cell line gives rise to Hodkin’s lymphoma?

Answer 3

B- lymphoid lineage.

Specifically caused by a B-cell with a ‘crippled’ immunoglobulin gene, caused by the acquisition of mutations that prevent synthesis of full
length immunoglobulin

*This “crippling” of the immunoglobulin genes means that the affected B-cells cannot produce functional antibodies.

Question 4

What other factors seem to associate with, and might be causing Hodkin’s lymphoma?

Answer 4

• Association with EBV. EBV genome detected in >50%. ?
  role in pathogenesis (direct/indirect)

-There is increased prevalence with HIV;
-Higher prevalence with prior infectious mononucleosis
infection

Question 5

Where to establish or confirm diagnoses diagnoses with Hodkin’s lymphoma?

Answer 5

• Lymph node biopsy
• Infrequently, the diagnosis is made from extranodal
  tissue such as a bone marrow or liver biopsy

Question 6

What are the 2 broad categories of Hodkin’s lymphoma?

Answer 6

1. Nodular lymphocyte predominant HL - 5%
2. Classical HL - 95%
   -Nodular sclerosis classical HL (commonest subtype in
   developed countries, children and young adults. More
   common in young females, frequent mediastinal
   involvement)
   -Mixed cellularity classical HL (common in developing
   countries, commonest subtype in HIV, SA public sector
   in adults)
   -Lymphocyte depleted classical HL (rare, increasing
   with HIV pandemic, advanced stage disease)
   -Lymphocyte rich classical HL (nodular and diffuse
   types)

Question 7

What is required when investigating for a presence of Hodkins lymphoma (HL)?

Answer 7

After diagnosis with HL; define extent of disease (spread) = staging. You define the extent in addition to clinical features. Defining the extent of the HL is based on the following investigations:

1. Blood
   FBC with diff; U&E; LFT&LDH; Uric acid; Beta-2
   microglobulin; CMP; HIV; ±B12; folate; iron studies
2. Bone marrow aspirate and trephine
3. Radiological
   CXR; CT scan or PET/CT scan ideally – whole body or
   head, neck, chest, abdomen and pelvis. Other: MRI,
   Gallium scan etc.

Question 7

What are the clinical features of Hodkin’s lymphoma?

Answer 7

Nodal, extranodal, paraneoplastic

1. Lymphadenopathy
   (Classic sites. Characteristics)
2. Constitutional symptoms/`B symptoms’
   Fever; night sweats; weight loss
3. Hepatomegaly, splenomegaly, bone marrow infiltration
4. Extranodal disease (lung, CNS, skin etc.) -(contiguous;distant)
5. Paraneoplastic manifestations
6. Other – pruritis (significance)

Question 7

What are the HL complications?

Answer 7

Complications are related to the disease or secondary to therapy

1. Early:
   - Complications of the disease: e.g. SVC syndrome, SCC
   (spinal cord compression), liver dysfunction with
   hepatic involvement etc.

• Complications related to chemotherapy e.g. alopecia,
  nausea and vomiting, myelosuppression etc.

2. Late complications (usually therapy related)

a. Second malignancy (AML; NHL; solid tumour) -chemo/radiotherapy > if both used
b. Infertility – chemotherapy; inverted ‘y’ radiotherapy
c. Adverse effects on thyroid, CVS and lungs (mantle
radiotherapy and chemotherapy)
d. Psychosocial
e. Other

Question 8

Describe the prognosis of HL

Answer 8

Prognosis Traditionally related to
i) host (patient i.e. age and
performance status),
ii) tumour (e.g. stage, ‘B’
symptoms) and
iii) comorbidities (e.g. HIV)

PROGNOSIS:
1. Stage of disease
2. ‘B’ symptoms
3. Bulk disease
4. Extranodal disease
5. Age > 40 years
6. ±Histological subtype
(e.g. lymphocyte depleted –adverse)
7. Other – HIV seropositive, EORTC classification for early
stage disease; Hasenclever index (age, gender, alb
level, Hb, stage, wcc, lymphocyte count) for advanced
stage disease etc.

Question 8

How to manage Hodkin’s lymphoma?

Answer 8

Principles of treatment

1. Supportive care
2. Specific modalities
   a. Chemotherapy – modality of choice.
   -Early stage (stage I and II – favourable and unfavourable with “B” symptoms and bulk disease) and late/advanced stage (stage III & IV) disease
   (ABVD – adriamycin, bleomycin, vinblastine and DTIC is
   the standard of care in most patients; other regimes
   include BEACOPP; BCVPP etc.)

b. Radiotherapy – indications
Adjuvant radiotherapy e.g. bulk disease, spinal cord
compression

c. Stem cell transplantation (usually autologous SCT)
Other/newer therapies – Brentuximab vedotin, PD-1
inhibitors etc. either alone or in combination with
other agents

Question 8

Used for HL staging

Answer 8

ANN-ARBOR STAGING CLASSIFICATION (AND
COTSWOLD MODIFICATION

Question 9

Comment on the disease prognosis of those with both HL and HIV?

Answer 9

• Presentation is more aggressive
• and atypical Management usually includes a combination of chemotherapy and cART
• Overall poorer prognosis than HIV negative HL