Malignancy in a child: Lymphoma

Question 1

Define lymphoma.

Answer 1

Lymphomas are neoplasms of lymphoid cells, originating in lymph nodes or other lymphoid tissues (spleen, MALT), sometimes “anywhere” (skin, often T cell, CNS, testes, breast).

Question 2

Define Hodgkin’s Lymphoma.

Answer 2

Hodgkin’s lymphoma is characterised histopathologically by the presence of the Reed– Sternberg cell, and T-cell dysfunction.

Question 3

Define Non-Hodgkin’s Lymphoma.

Answer 3

NHLs are a diverse group, 85% B cell, 15% T cell, and NK cell neoplasms, ranging from indolent to aggressive disease, which can be referred to as low-, intermediate- and high-grade NHL.

Question 4

How can Non-Hodgkin’s Lymphoma be classified?

Answer 4

Mature or immature

Histology:

• High Grade:
  
  • Very Aggressive – Burkitt’s
  • Aggressive – Diffuse Large B-Cell*, Mantle Cell
• Low Grade:
  
  • Indolent – Follicular, Marginal Zone, Small Lymphocytic
  • Lineage: B or T Cell

Question 5

Explain the aetiology/risk factors for Hodgkin’s Lymphoma.

Answer 5

Likely to be due to environmental triggers in a genetically susceptible individual (may be due to defect in cell-mediated immunity). EBV genome has been detected in 50% of Hodgkin lymphomas, but its role in its pathogenesis is unclear.

Histological subtypes:

• Nodular sclerosing (70%)
• Mixed cellularity (20%)
• Lymphocyte predominant (5%)
• Lymphocyte depleted (5%)

Reed–Sternberg cell: Large cell with abundant pale cytoplasm and two or more oval lobulated nuclei containing prominent ‘owl-eye’ eosinophilic nucleoli.

Question 6

Explain the aetiology/risk factors for Non-Hodgkin’s Lymphoma.

Answer 6

Inherited or acquired immunodeficiency syndromes:

• HIV and high-grade B-cell lymphomas
• EBV and post-transplant lymphoproliferative disease
• Prior treatment with chemo- or radiotherapy.

Infective causes:

• HTLV-1 -> adult T-cell leukaemia/lymphoma
• EBV ->Burkitt lymphoma
• Helicobacter pylori -> MALT lymphoma.

Question 7

Summarise the epidemiology of lymphoma.

Answer 7

Incidence: 1/100,000/year. Non-Hodgkin (85%)>Hodgkin (15%).

Age of presentation: Late childhood/adolescence. M: F 2:1.

Question 8

What are the presenting symptoms of Hodgkin’s Lymphoma?

Answer 8

Enlarged lymph nodes: Painless enlarging mass, often in neck, occasionally axilla or groin.

Constitutional B symptoms: Fevers >38 C, night sweats, weight loss >10% bodyweight in 6 months.

Others: Pruritus, cough or dyspnoea with intrathoracic disease, SVC obstruction (blackouts, dyspnoea, feeling of fullness in the head).

Question 9

What are the presenting symptoms of Non-Hodgkin’s Lymphoma?

Answer 9

Presentation varies significantly from subtype to subtype.

Similarities: Painless lymphadenopathy, often involving multiple sites, constitutional symptoms, no pain after alcohol.

Question 10

What are the signs of Hodgkin’s Lymphoma?

Answer 10

• Non-tender firm lymphadenopathy (cervical, axillary or inguinal).
• Splenomegaly, occasionally hepatomegaly.
• Skin excoriations.
• Signs of intrathoracic disease: SVC obstruction (facial oedema, raised JVP).

Question 11

What is the Ann Arbor staging for Hodgkin’s Lymphoma?

Answer 11

I: Single LN region
II: One side of diaphragm
III: Both sides of diaphragm
IV: Disseminated

A: No systemic symptoms
B: Fever, night sweats, weight loss
E: Extralymphatic site
S: Splenic disease

Question 12

What are appropriate investigations for lymphoma?

Answer 12

Bloods: Low Hb (normochromic, normocytic), leucocytosis, eosinophilia, lymphopenia (with advanced disease), high ESR, high CRP, high LDH, high AST/ALT (with liver involvement).

Lymph node biopsy: Immunophenotyping, cytogenetics.

Bone marrow aspirate and trephine biopsy: Involvement seen only in very advanced disease. Imaging: CXR, CT (thorax, abdomen, pelvis), gallium scan, PET scan.

REED STERNBERG CELL

Question 13

What is the management plan for Hodgkin’s Lymphoma?

Answer 13

Treatment - prognosis excellent, especially in the young

• Combination chemotherapy:
  
  • Used in most cases
  • ABVD: Adriamycin, bleomycin, vinblastine and dacarbazine
  • 2-4 cycles in stage 1/2, 6-8 cycles in stage 3/
• Radiotherapy
  
  • Often used alongside chemo in bulky areas
• Intensive chemo and autologous SCT
  
  • Relapsed patients

Question 14

How do stem cell transplants/bone marrow transplants work?

Answer 14

Stem cells are harvested from one of three sources: peripheral blood (following stimulation by G-CSF), BM or umbilical cord blood. Used in leukaemia, lymphoma, multiple myeloma, aplastic anaemia, MDS, sickle cell anaemia and thalassemia major.

• Patients own SCs are harvested and frozen
• Enables high dose chemo +/- radiotherapy to eradicate malignant cells at the cost of partial or even complete bone marrow ablation
• Frozen SCs then reintroduced into patient
• Used more in multiple myeloma and lymphoma, particularly with relapse, less used in leukaemia
• No graft vesus host disease (GVHD) risk and lower risk of infection

Question 15

What is the management plan for T-Cell NHL?

Answer 15

Chemotherapy and CNS prophylaxis as for ALL. There is improved prognosis in T-cell stage III with the UK ALL X protocol giving a 90% 4-year survival.

Question 16

What is the management plan for B-Cell NHL?

Answer 16

Aggressive pulsed chemotherapy regimen for stage IV disease using alkylating agents and methotrexate is improving survival. Surgery is only indicated for emergency tumour obstruction of airways, bowel or bladder.

Question 17

What are features and treatment for anaplastic large cell lymphoma?

Answer 17

Children and young adults
Aggressive
Large “epitheloid” lymphocytes
t(2;5)
Alk-1 protein expression

Question 18

What are features of peripheral T-Cell Lymphoma?

Answer 18

Middle-aged and elderly
Aggressive
Large T-Cells

Question 19

What are features of Adult T-cell leukaemia/lymphoma?

Answer 19

Caribbean and Japanese
HTLV-1 infection, aggressive

Question 20

What are features of Enteropathy-associated T-cell lymphoma (EATL)?

Answer 20

Associated with longstanding coeliac disease

Question 21

What are the features of Cutaneous T-cell lymphoma?

Answer 21

Associated with mycosis fungoides

Question 22

What are the features and treatment for Burkitt’s Lymphoma?

Answer 22

Three types:
All very aggressive, fast growing t(8;14) translocation c-myc oncogene overexpression. Rapidly responsive to treatment

• Endemic: Most commmon malignancy in equatorial Africa. EBV associated; characteristic jaw involvement and abdominal masses.
• Sporadic: Found outside Africa. EBV-associated; jaw less commonly involved.
• Immunodeficiency: Non-EBV associated. HIV/post-transplant patients.

Histology: Starry sky appearance

Treatment: Chemotherapy - Rituximab (anti-CD20 - found on B-cells) and leukaemia protocol or SCT

Question 23

What are the features and treatment for Diffuse large B-cell (DLBC)?

Answer 23

Middle aged and elderly, aggressive. Richter’s transformation. Other lymphomas occur secondary to DLBCL.

Histology: Sheets of large lymphoid cells

Treatment: Rituximab - CHOP. Auto-SCT for relapse.

Question 24

What are the features and treatment for mantle cell lymphoma?

Answer 24

Middle-aged, M>F, aggressive. Disseminated at presentation. Median survival 3-5 years t(11;14) translocation. Cyclin-D1 deregulation.

Histology: Angular nuclei

Treatment: Rituximab-CHOP. Auto-SCT for relapse.

Question 25

What are the features and treatment for follicular lymphoma?

Answer 25

Indolent, mostly incurable. Median survival 12-15 years. t(14;18) translocation.

Histology: Follicular pattern, nodular appearance

Treatment: Watch and wait. Rituximab CVP.

Question 26

What are the features and treatment for mucosal associated lymphoid tissue (MALT)?

Answer 26

Marginal zone NHL. Middle aged.
Chronic antigen stimulation:

• H. pylori > gastric MALT lymphoma
• Sjogren’s syndrome > parotid lymphoma

Treatment: Remove antigenic stimulus e.g. H.pylori triple therapy, chemotherapy