Hodgkin's lymphoma

Question 1

List some DDx for a presentation of:

• fever, night sweats (3/52)
• dry cough, nil pharyngitis
• R cervical lymphadenopathy, non-tender

Answer 1

PDx. Hodgkin's lymphoma
DDx.
Reactive lymphoma (prev URTI)
- viral: EBV, CMV, adenovirus
- bacterial: strep pneumoniae, staph aureus, TB
- AI: SLE, RA
Thyroid- Hashimoto's 
Neoplasm
- primary: lymphoma (HL 40% , NHL 60%), leukaemia (ALL, CLL) 
- secondary: head/neck primary mets
Drugs- pheyntoin

Question 2

What investigations would you order?

Answer 2

Diagnostic:
- excisional biopsy 
- flow cytometry 
Bedside
- nasopharyngeal swab MCS, EBV monospot
Lab:
- FBC (anaemia of chronic disease)
- blood smear (blasts)
- CRP/ESR
- EUC (hyperuricaemia in increased cell turnover)
- lactate dehydrogenase (LDH) (high cell turnover)
- LFT
- AI panel: ANA, anti-phospholipid Abs, anti-Sm (SLE), anti-CCP (RA)
Imaging:
- CXR: infection, mediastinal mass
- contrast CT abdo/neck/pelvis- staging
- PET- mets
- Echo- cardiotoxic chemo baseline

Question 3

Describe the microscopic features of HL?

Answer 3

• Reed-Sternberg cells (tumour giant cells of stunted group without hypermutation -> cannot express IgG): bilobed nuclei (owl eyed), prominent neuclosus
• RS variants: lacunar cells (nodular sclerosis) and popcorn cells (lymphohistiocytic variant)

Question 4

What are the different HL subtypes?

Answer 4

Classic HL (95%)
- Nodular sclerosis (70%)- LN divided fibrosis bands w Lacunar cells
- Mixed cellularity (25%)- eosinophil increased (IL5)
- Lymphocyte-rich (5%)- lots of lymphocytes, normal RS cells, best prognosis
- Lymphocyte-depleted (<1%)- less lymphocytes, normal RS cells, worst prognosis
Nodular lymphocyte-predominant HL (5%)
- popcorn cells (RS variant)

Question 5

Compare HL and NHL?

Answer 5

HL (40%):
Epi: young adults, >70yo
Histo: intermittent malignant cells (RS and variants)
Path: B-cell malignancy
Clinical: B symptoms (RS secrete cytokines)
LNs: cervical, supraclavicular, axilla
Spread: contiguous, mets/extranodal involvement less common
Risk: EBV, FMHx
Rx: Better Rx response. Stage 1-2 radiotherapy, stage 3-4 chemo

NHL (60%):
Epi: >50yo
Histo: big masses of malignant cells
Path: B, T or NK cell malignancy
Clinical: less type B symptoms
LN: many groups
Spread: haem, non-contiguous, mets/extranodal involvement common
Risk: eviro (UV, radiation, chemicals), infection (EBV), immunosuppression (malnutrition, HIV), AI (SLE, RA), male, elderly, FMHx 
Rx. Poorer response, chemo

Question 6

How is HL staged? What does stage IIA mean?

Answer 6

Ann-Arbor staging system:
I- single LN region or single extranodal site
II- 2 or more LN regions on same side of diaphragm
III- LN regions on both sides of diaphragm
IV- non-contigous involvement of one or more extralymphatic site

A- no B symptoms
B- B symptoms <6 months (weight loss >10%, recurrent/persistent fever), night sweats)
X- bulky disease (>6cm)
E- extension to single extralymphatic organ

Therefore: IIA means two or more affected LN groups on one side of diaphragm, with no B symptoms

Question 7

Why is it more important to stage Hodgkin’s compared to Non-Hodgkin’s?

Answer 7

HL has contiguous and a more predictable spread -> staging has more prognostic value, can guide treatment
NHL tends to present with disseminated disease
- prognostic: grade, bone marrow involvement, B symptoms and the international prognostic index

Question 8

Describe the histopathology of NHL?

Answer 8

E.g. Diffuse large B-cell lymphoma (most common NHL)

• poor differentiation, v aggressive
• neoplastic large B cells grow in sheets
• Heterogenous large cells w vesicular chromatic and prominent nuclei

Question 9

Compare the prognosis of HL and NHL?

Answer 9

HL: 5yr survival 87%
- best prognosis in lymphocyte-rich subtype as Rx targets lymphocytes, worse in lymphocyte-depleted subtype
NHL: diffuse large B-cell 5yr survival 47%

Question 10

Describe LN anatomy

Answer 10

Structure: small, bean-shaped masses of lymphoid tissue enclosed by a capsule of connective tissue that occur in association with the lymphatic vessels
- capsule: outer CT layer
- cortex (outer and inner): containing B cells (active in germinal centres of cortex, inactive in margin) and T cells (inner cortex)
- medulla: activated plasma cells
Function: filter for the blood, foreign antigens trapped and exposed to cells of the immune system for destruction