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

Blood

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

Development of blood cells en.wikipedia.org

Site of blood formation www.healthline.com>Ref Library

Peripheral blood and marrow

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

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)

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

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

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

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.

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

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.

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

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

Lymph node areas www.healthresource4u.com

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

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

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

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.

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

Some FBC results Hb – 8.1 g/dl; WBC - 3.66 x 109/l with 85%L; Platelets – 63 x 109/l Hb - 7.9 g/dl; WBC - 5.96 x 109/l with 79.8L; Platelets – 111 x 109/l Hb - 8.0 g/dl; WBC – 0. 88 x 109/l with 93.6%L; Platelets – 34 x 109/l

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

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

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……

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.

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.

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.