1. Pointers to lymphoma and acute lymphoid leukaemia diagnosis
Prof Ivy A E Ekem
16th September 2016

2. Blood

4. en.wikipedia.org / M. Komorniczak . Accessed 08.09.16

5. Development of blood cells
en.wikipedia.org

6. Site of blood formation
Library

7. Peripheral blood and marrow

9. Outline What lymphoma and acute lymphoid leukaemia are Who they affect
How they present and why
How the diagnosis made
Cardinal points in making diagnosis ----history, examination, selected investigations and their proper interpretation

10. What is lymphoma? What is acute lymphoid leukaemia (ALL)?
Lymphoma – cancer of a white cell in the lymph nodes. Two broad groups:
Hodgkin lymphoma
Non-Hodgkin lymphoma e.g. DLBCL, Burkitt
Acute lymphoid / lymphoblastic leukaemia - cancer of a white cell in the marrow. Three subgroups: L1 L2
L3 (Burkitt type)

11. Lymphoma Affects lymph nodes; the spleen; thymus gland.
Lymph nodes: neck, armpits, groin, chest, abdomen and pelvis.
A lymphoma develops when an abnormal clone develops

12. Acute lymphoid leukaemia
Affects the bone marrow
Immature lymphoid cells called lymphoblasts appear
Proliferate rapidly to populate the bone marrow and blood
Depopulate the marrow of normal cells – red cells, normal white cells, platelets
‘Bone marrow failure’
Lymph nodes, spleen may also be affected

13. Same disease?
World Health Organization (WHO) classification of lymphoid tumours – listed together
Same cell, different stages of the cell at genetic change and type of change

14. Who they affect All ages and sexes, but in lymphoma, In leukaemia
Hodgkin lymphoma bimodal peak, third and eighth decades
NHL increases with age
In leukaemia
ALL is more common in childhood, especially between 2 and 5 years of age.
Risk increases again in people aged 45 and above.

15. How they present and why
ALL
Bone marrow failure
Fever, night sweats
Enlarged lymph nodes
Lymphoma
Unexplained weight loss

16. Why?
Lymphoma is the most common etiology of neoplastic fever of unknown origin.
The pathophysiology: tumour necrosis factor and interleukins 1, 2, 4
Night sweats: body temperature regulation and circadian rhythm. Periodic increases in interleukins (IL-1α, IL-2, IL-4, IL-6) and tumor necrosis factor. No research found to support this though.

17. How the diagnosis made History, physical examination for both
Blood film and marrow for ALL
Lymph node / tissue biopsy for lymphoma
Other tests for further classification and staging

18. History: Onset; suddenness in ALL. Swelling, systemic symptoms
Cardinal points in making diagnosis: history, examination, selected investigations and their proper interpretation
History: Onset; suddenness in ALL. Swelling, systemic symptoms
examination: lymph node areas

19. Lymph node areas

20. Case ‘stories’ Father insistence on marrow examination
Bone marrow trephine revealed diagnosis posthumous
Bone lesions in the young followed as for the elderly

21. Case 1: Father insists
A 14 year old previously well BECE candidate is admitted with unexplained fever and difficulty in walking of 2 weeks duration unto the medical ward.
Examination reveals a febrile young boy, well nourished and with paraparesis

22. Investigations among others reveal a normal blood count
Marrow is requested (by father), not obliged (re…route of request).
Father insists a friend’s son presented similarly and was found to have leukaemia
Patient seen though, but on account of normal counts……marrow not done

23. Case 1 continued…..
Investigations continue for TB, viral illnesses etc.
LDH done
Presented at clinical meeting for leads to diagnosis
Bone marrow suggested and done on account of same history and high LDH
Diagnosis – Acute lymphoid leukaemia. Father was right.

24. Case 2: Posthumous diagnosis
51 year old man
Splenectomized for pancytopaenia 4 years earlier
Presented with febrile illness and severe joint pain
Managed for sepsis and rheumatoid arthritis…….improved
Pancytopaenia recurred when steroids were tapered

25. Some FBC results
Hb – 8.1 g/dl; WBC x 109/l with 85%L; Platelets – 63 x 109/l
Hb g/dl; WBC x 109/l with 79.8L; Platelets – 111 x 109/l
Hb g/dl; WBC – x 109/l with 93.6%L; Platelets – 34 x 109/l

26. Case 2 ctd…. Hb dropping Trephine biopsy done
Read after patients demise
Diagnosis - ALL

27. Case 3: Bone lesions in the young
A young man, early 30s presented with features of a rapidly evolving debilitating illness
Amongst investigations, x-rays showed lytic lesions
Investigations continued as for myeloma….
More investigations revealed an LDH of over 2000U/L
?? Myeloma…. Patient demise
Post mortem: Lymphoma

28. A note on Lactate dehydrogenase (LDH)
An enzyme found in nearly all living cells (animals, plants, and prokaryotes).
Catalyzes the inter-conversion of lactate to pyruvic acid and so doing converts NAD+ to NADH and back.
Raised levels in numerous medical conditions from haemolysis, through heart failure to malignancies however……

29. LDH ctd… Involved in tumor initiation and metabolism.
Cancer cells rely on increased glycolysis rather than aerobic respiration, thus increased lactate production
This allows tumour cells to convert the majority of their glucose stores into lactate thus shifting use of glucose metabolites from simple energy production to the promotion of accelerated cell growth and replication.

30. The unusual presenter
Listen. Follow every lead in the history. Retake history as often as necessary
Chase every result requested for. It must have been needed for it to have been requested. Consult the laboratory physician
Interpret results with patient in mind. Remember that every patient is unique in their signs and symptoms.

31. Take home messages for all of us
Keep learning
Don’t take patient for granted
Lymphomas and acute lymphoid leukaemias can be difficult to diagnose but
good history taking,
efficient investigations and interpretation
Will give the diagnosis away in the great number of cases.