Presentation
Good morning, sir. I examined the abdomen of a chronically ill-looking man. He is pale, not jaundiced, and has no lymphadenopathy or signs of chronic liver disease. The abdomen is asymmetrically distended, fuller on the left, and is not tender. The liver is palpable 8 cm below the right costal margin, firm and smooth, with a span of 13 cm. The spleen is palpable 15 cm below the left costal margin towards the right iliac fossa; it is firm and smooth, I can feel a notch, I cannot get above it, and it is dull to percussion. The kidneys are not ballotable and there is no ascites. Bowel sounds are normal and there are no bruits.
Diagnosis
Hepatosplenomegaly with massive splenomegaly, most likely chronic myeloid leukaemia (CML).
Differential diagnoses
- Primary myelofibrosis — usually older; teardrop red cells, a leucoerythroblastic film, and a "dry tap" on marrow aspiration
- Hyperreactive malarial splenomegaly — a lifelong resident of a malarial area with very high IgM and malaria antibody levels, whose spleen shrinks on antimalarial prophylaxis
- Visceral leishmaniasis (kala-azar) — fever, weight loss, pancytopenia, darkening skin
- Lymphoma or chronic lymphocytic leukaemia — lymphadenopathy, night sweats
- Schistosomiasis with portal hypertension — history of fresh-water exposure, varices, preserved liver function
Investigations
| Test | What you expect or look for |
|---|---|
| Full blood count and film | CML: very high white count with every stage of myeloid maturation, basophilia and eosinophilia, normocytic anaemia, normal or high platelets. Myelofibrosis: teardrop cells and a leucoerythroblastic picture |
| BCR-ABL1 by quantitative PCR | The diagnostic test for CML, and the baseline for monitoring |
| Cytogenetics | The Philadelphia chromosome, t(9;22) |
| Bone marrow aspirate and trephine | Hypercellular marrow; the blast percentage defines chronic or blast phase; fibrosis in myelofibrosis |
| JAK2, CALR and MPL mutations | Myelofibrosis |
| Malaria films, serum IgM, malaria antibody titres | Hyperreactive malarial splenomegaly |
| rK39 rapid test; splenic or marrow aspirate for Leishman–Donovan bodies | Visceral leishmaniasis |
| LDH, uric acid, urea and creatinine, liver function | Raised LDH and urate; baseline organ function |
| Abdominal ultrasound | Size of liver and spleen, splenic infarcts, portal vein, nodes |
| HIV, hepatitis B and C | Baseline before treatment |
| ECG | QT interval before some tyrosine kinase inhibitors |
Management
Management is led by a haematologist. I would counsel the patient that CML is a leukaemia controlled — usually for many years — by a daily tablet that must not be stopped.
Non-pharmacological
- Referral to a haematology centre
- Adequate hydration and nutrition
- Avoiding contact sports while the spleen is large, because of the risk of rupture
- Contraception, because tyrosine kinase inhibitors harm the fetus
- Adherence counselling and access to patient assistance programmes, which provide imatinib at designated centres in Nigeria
Pharmacological
Chronic myeloid leukaemia
- Imatinib 400 mg once daily with food, continued long term
- Second-generation inhibitors — nilotinib, dasatinib or bosutinib — for intolerance or resistance
- Hydroxycarbamide to bring down a very high count while the diagnosis is confirmed
- Allopurinol and generous fluids to prevent urate nephropathy
- Monitor BCR-ABL1 by PCR every 3 months: aim for 10% or less at 3 months, 1% or less at 6 months, and 0.1% or less (major molecular response) at 12 months
Hyperreactive malarial splenomegaly
- Long-term antimalarial prophylaxis, such as proguanil 200 mg daily, while living in a malarial area; the spleen should shrink over months
Visceral leishmaniasis
- Specialist treatment by the regional WHO regimen — for example sodium stibogluconate 20 mg/kg daily with paromomycin, or liposomal amphotericin B
Myelofibrosis
- A JAK inhibitor such as ruxolitinib for symptomatic splenomegaly, with transfusion support
Surgical and interventional
- Allogeneic stem cell transplantation for blast phase or failure of several tyrosine kinase inhibitors
- Splenectomy only for selected complications
Complications and follow-up
- Splenic infarction, with sudden left upper quadrant pain
- Splenic rupture
- Hypersplenism with cytopenias
- Leucostasis from very high counts
- Gout and urate nephropathy
- Progression to blast crisis
- Drug effects: fluid retention, muscle cramps, low blood counts
Follow up in the haematology clinic with blood counts every few weeks at first, and BCR-ABL1 PCR every 3 months.
Examiner questions
References
- Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, et al., eds. Harrison's Principles of Internal Medicine. 22nd ed. New York: McGraw Hill; 2025.
- World Health Organization. WHO guidelines for malaria. Geneva: WHO (living guideline, updated periodically).