High Grade Non-Hodgkins Lymphoma

Question 1

what is the definition of High Grade NHL?

Answer 1

Fast growing lymphomas, aggressive but treatable, diffuse large B-cell lymphoma (DLBCL) is commonest. Burkitt lymphoma is an example of a very high grade tumour

Question 2

what is the epidemiology of High Grade NHL?

Answer 2

Non-hodgkin = 6th most common type of cancer in UK
More common over 65
More frequent in men
DLBCL = 35% of NHL, Burkitt = 1% of NHL

Question 3

what is the aetiology of High Grade NHL?

Answer 3

Having a weaker immune system can increase the risk of developing certain types of NHL

Question 4

what are the risk factors for High Grade NHL?

Answer 4

Age
Race 
Family history minorly linked 
Male
Exposure to chemical/ drugs
Radiation exposure 
Weakened immune system/autoimmune disease

Question 5

what is the pathophysiology of High Grade NHL?

Answer 5

Most (80 to 85%) non-Hodgkin lymphomas arise from B lymphocytes; the remainder arise from T lymphocytes or natural killer cells. Either precursor or mature cells may be involved.
Grading of NHL:
Low grade e.g. Follicular Lymphoma
High grade e.g. Diffuse Large B Cell Lymphoma
Very high grade e.g. Burkitt’s Lymphoma

Question 6

what are the key presentations of NHL?

Answer 6

Nodal (75%) - superficial lymphadenopathy

Extranodal (25%) - skin, oropharynx, gut, small bowel, bone, CNS, lung - ⅓ have this in high grade

Question 7

what are the signs of high grade NHL?

Answer 7

Enlarged liver and spleen

Question 8

what are the symptoms of high grade NHL?

Answer 8

Sweats, unexplained weight loss, fever - B symptoms (stage B if these are present)
Pancytopenia - anaemia, infection and bleeding (due to reduced platelets) due to marrow involvement

Question 9

what are the first line investigations for high grade NHL?

Answer 9

FBC - Raised lactate dehydrogenase reflects worse prognosis since its a sign of increased cell turnover and thus cell proliferation

Question 10

what are the gold standard investigations for high grade NHL?

Answer 10

• Lymph node excision or bone marrow biopsy - Will NOT see mirror-image nuclei REED-STERNBERG CELLS or Reed-Sternberg variant cells - POPCORN CELLS
• Marrow and node biopsy for classification
• CT/MRI of chest, abdomen and pelvis for staging (Ann Arbor)
• Immunophenotyping
• Cytogenetics
  Organ functions, viral screen, G6PD, uric acid, LDH, B2 Microglobulin, ESR

Question 11

what are the differential diagnoses for high grade NHL?

Answer 11

Other hematologic malignancies or lymphoproliferative disorders

Question 12

how is high grade NHL managed?

Answer 12

Immunochemotherapy, autograft, Radiotherapy, Allograft, CheckPoint Inhibitors, BITE, CAR-T/NK
Early:
- 3 months R-CHOP regimen with radiotherapy
Late:
- 6 months R-CHOP regimen with radiotherapy
R-CHOP regimen:
• R - RITUXIMAB (monoclonal antibody - minimal side effects)
• C - CYCLOPHOSPHAMIDE
• H - HYDROXY-DAUNORUBICIN
• O - VINCRISTINE (Oncovin brand name)
• P - PREDNISOLONE

Question 13

how is high grade NHL monitored?

Answer 13

Scan to check the success of treatment, usually CT or PET-CT

Once in remission regular check ups by a specialist

Question 14

what are the complications of high grade NHL?

Answer 14

Respiratory problems, superior vena cava syndrome, neurological problems

Question 15

what is the prognosis for high grade NHL?

Answer 15

Affected by age, performance status, comorbidities, disease characteristics (stage, LDH, extranodal involvement, response to treatment) ad genetics
Early deaths are more frequent than in low grade lymphomas
The majority of patients who achieve a complete remission are cured of their disease.
In the long term, therefore, the prognosis of high grade lymphoma is better than low grade lymphoma