Academe Learn
CBME Curriculum Preview

Page 12 of 12

PA19.4 | Spleen Disorders — PBL Case

CLINICAL SETTING

Ramaiah, a 52-year-old rice farmer from a village in Mandya district, Karnataka, walks into the district hospital's general medicine OPD supported by his son. Over the past eight months he has noticed his abdomen growing larger, forcing him to loosen his dhoti and stop wearing his usual shirt because he cannot button it across his belly. He also reports dragging discomfort in the left flank, especially after a meal. He feels easily tired while irrigating his fields and has lost nearly 6 kg without changing his diet. He denies fever or night sweats. On examination: BMI 19.2 kg/m², mild pallor, no icterus, no peripheral lymphadenopathy. Abdomen is distended; the spleen is massively enlarged crossing the midline and reaching the right iliac fossa (estimated 22 cm below the left costal margin). The liver edge is just palpable 2 cm below the right costal margin. No ascites. Peripheral blood film: leukocytosis 78 × 10⁹/L with a 'full-spectrum' myeloid shift (myelocytes, metamyelocytes, bands), basophilia 4%, platelet count 620 × 10⁹/L, haemoglobin 8.8 g/dL.

Trigger 1: Initial Presentation

Ramaiah's son tells the medical officer that his father has been 'growing a second belly' on the left side. The medical officer notes the massive spleen — extending well into the right iliac fossa — which he estimates weighs several kilograms. Ramaiah recalls that a fellow villager with a similar swelling was treated for 'kala azar' in Bihar but responded slowly. Ramaiah himself has never left Karnataka and has no history of travel to Bihar or Assam. Vital signs: BP 118/76 mmHg, HR 92/min, afebrile. Hb 8.8 g/dL (normocytic), WBC 78 × 10⁹/L with a full left shift, basophilia 4%, platelets 620 × 10⁹/L.

DISCUSSION POINTS

  • What are the five mechanistic categories of splenomegaly, and which category does Ramaiah's massive splenomegaly most likely fall into, given the peripheral blood film findings?
  • Construct a ranked differential diagnosis for massive splenomegaly using the classic short-list. What clinical and laboratory features would help you prioritise each possibility in an Indian district hospital setting?
  • Why is malaria an unlikely cause here despite it being a common Indian cause of splenomegaly? What features would make you confidently include or exclude an infective cause?
  • The peripheral blood film shows a 'full-spectrum' myeloid shift with basophilia. What is the pathological significance of basophilia in the context of this clinical picture?
Click to reveal Trigger 2: Investigations (discuss previous trigger first!)

Trigger 2: Investigations

Investigations are sent to the district hospital laboratory. Results return: • Hb 8.8 g/dL; MCV 84 fL; reticulocytes 1.2% • WBC 78 × 10⁹/L: segmented neutrophils 42%, bands 8%, metamyelocytes 10%, myelocytes 9%, promyelocytes 1%, blasts 2%, eosinophils 3%, basophils 4%, lymphocytes 21% • Platelets 620 × 10⁹/L • Leukocyte alkaline phosphatase (LAP) score: 12 (reference 40–130) • Serum B12: markedly elevated (>2000 pg/mL) • Uric acid: 9.1 mg/dL • Peripheral film: no schistocytes; no teardrop poikilocytes noted • rK39 serology: negative • Bone marrow aspirate: hypercellular with marked myeloid hyperplasia and full maturation; megakaryocytes prominent; M:E ratio 12:1; no fibrosis on aspirate

DISCUSSION POINTS

  • Interpret the full blood count pattern: what does the combination of marked leukocytosis with a full myeloid spectrum, basophilia, thrombocytosis, low LAP score, and markedly elevated B12 tell you about the underlying pathology?
  • How does the low LAP score help you differentiate between a leukaemoid reaction and the most likely diagnosis? What is the cellular basis of this difference?
  • The bone marrow aspirate shows myeloid hyperplasia with full maturation and no fibrosis, yet the spleen is massively enlarged. Explain the mechanism by which the pathological clone produces splenic infiltration.
  • What single confirmatory molecular test would clinch the diagnosis, and what is its pathological basis? Why is this test superior to cytogenetics alone in the modern era?
Click to reveal Trigger 3: Diagnosis & Management (discuss previous trigger first!)

Trigger 3: Diagnosis & Management

The district physician refers Ramaiah to the tertiary referral centre in Bengaluru, where BCR-ABL1 RT-PCR returns positive (IS 68%). Cytogenetics confirms t(9;22)(q34;q11) in 94% metaphases — the Philadelphia chromosome. He is diagnosed with Chronic Myeloid Leukaemia (CML), chronic phase. Haematology discussion: Ramaiah is started on imatinib 400 mg/day. Three months later his spleen has reduced to 5 cm below the costal margin, WBC is 7 × 10⁹/L, and BCR-ABL1 is 8.5% (IS). At this visit, his haematology registrar notes that his platelet count has now fallen to 65 × 10⁹/L and haemoglobin to 7.2 g/dL despite clinical improvement — the registrar explains a secondary process.

DISCUSSION POINTS

  • Explain the concept of hypersplenism in the context of Ramaiah's presentation. Which four criteria must be fulfilled for a diagnosis of hypersplenism, and how does this differ from the cytopenia caused by the CML clone itself?
  • Now that Ramaiah is responding to imatinib and his spleen is shrinking, what is the expected effect on his cytopenias — and what does the initial fall in platelet count and haemoglobin during treatment tell us about the role of the spleen?
  • If Ramaiah's CML eventually progressed to blast crisis requiring splenectomy, what haematological changes would you expect on the post-splenectomy blood film, and what major infective risk would he face?
  • Compare the mechanism of massive splenomegaly in CML with two other diseases from the classic massive-splenomegaly list: myelofibrosis and visceral leishmaniasis. What distinguishes their splenic histopathology?

Group Task Assignments

Group 1: Mechanistic classification of splenomegaly

  • Map each cause of splenomegaly from the syllabus (cirrhosis, malaria, CML, myelofibrosis, Gaucher, leishmaniasis, thalassaemia, rheumatoid arthritis) to one of the five mechanistic categories using a table format.
  • Identify three diseases that can cause both congestive and haematological splenomegaly simultaneously, and explain the dual mechanism.

Competencies: PA19.4

Group 2: Massive splenomegaly short-list and differentiation

  • Construct a comparative table for the six causes of massive splenomegaly (CML, myelofibrosis, visceral leishmaniasis, β-thalassaemia major, malaria [hyperreactive malarial splenomegaly], Gaucher disease), listing: mechanism of splenomegaly, key peripheral blood finding, and one confirmatory investigation for each.
  • Explain how the LAP score and BCR-ABL1 distinguish CML from a leukaemoid reaction in a patient from a malaria-endemic area.

Competencies: PA19.4

Group 3: Hypersplenism — definition, mechanism, consequences

  • Define hypersplenism using all four diagnostic criteria and explain the mechanism of each cytopenia in the context of an enlarged spleen.
  • Distinguish hypersplenism from primary bone marrow failure using marrow biopsy findings and the peripheral blood film.

Competencies: PA19.4

Group 4: Post-splenectomy haematology and infective risk

  • List the blood film changes expected within 1 week of splenectomy and explain the pathological mechanism of each (Howell-Jolly bodies, target cells, acanthocytes, thrombocytosis).
  • Classify the organisms responsible for overwhelming post-splenectomy infection (OPSI) and explain why encapsulated bacteria are specifically dangerous in the asplenic patient.

Competencies: PA19.4

Group 5: Indian clinical context — infective vs haematological causes

  • Compare the epidemiology and presentation of two major infective causes of splenomegaly in India — visceral leishmaniasis (kala azar) and malaria — with emphasis on the geographic, seasonal, and morphological clues that distinguish them from haematological causes.
  • Describe the clinical approach to differentiating the cause of splenomegaly using the three axes: degree of enlargement, associated features (jaundice, lymphadenopathy, fever), and laboratory pattern.

Competencies: PA19.4

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [PA19.4] What are the five mechanistic categories of splenomegaly, and what are the key causes, pathological mechanisms, and clinical differentiators within each category, including the diseases that cause massive splenomegaly and the definition and criteria for hypersplenism?