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PA19.4 | Spleen Disorders — Case Study
CLINICAL SCENARIO
A structured case-study assignment in which students work through a patient presenting with massive splenomegaly, build a mechanism-based differential diagnosis, systematically narrow the diagnosis using clinical and laboratory clues, arrive at a final diagnosis of Chronic Myeloid Leukaemia (CML), and discuss the pathophysiology of hypersplenism and the consequences of splenectomy.
Instructions
Read the clinical vignette carefully. Complete all five sections in order — each section builds on the previous. Use the guidance notes as scaffolding, not as a checklist to copy verbatim. Cite at least two pathology references (e.g. Robbins & Kumar, Harsh Mohan) to support your reasoning. Total recommended word count: 900–1,100 words. Submit as a single document. Your submission will be peer-reviewed by two classmates using the provided rubric before faculty grading.
Length: 900–1,100 words total across all five sections. Suggested distribution: Section 1 (150–180 words), Section 2 (180–220 words), Section 3 (180–220 words), Section 4 (180–200 words), Section 5 (200–250 words). Quality over quantity — precise, referenced answers are preferred to padding.
What to Submit
Section 1 — Clinical Vignette & Mechanism-Based Differential
Vignette: A 38-year-old male farmer from Odisha presents with a 6-month history of progressive left hypochondrial fullness and early satiety. He denies fever. Examination reveals a firm, non-tender spleen palpable 14 cm below the costal margin (estimated weight ~1.2 kg) with a splenic notch. The liver is enlarged 4 cm below the costal margin. There is no lymphadenopathy. He looks pale.
Task: List at least six causes of massive splenomegaly (spleen >1 kg), organised by pathophysiological mechanism (reticuloendothelial hyperplasia, haematopoietic infiltration, venous congestion, deposition, infection/parasitic). For each mechanism, name one or two representative disorders.
Guidance: Think in mechanisms, not lists. Massive splenomegaly has a narrower differential than moderate splenomegaly — anchor on the weight/size threshold. Include at least one tropical infection (malaria, kala-azar), one myeloproliferative neoplasm, one storage disorder, and one cause of portal hypertension.
Section 2 — Interpreting the Investigations
Laboratory results (provided):
| Investigation | Result | Reference range |
|---|---|---|
| Haemoglobin | 8.4 g/dL | 13.5–17.5 g/dL |
| Total WBC | 1,24,000/µL | 4,000–11,000/µL |
| Differential | Neutrophils 42%, Myelocytes 18%, Metamyelocytes 12%, Basophils 9%, Eosinophils 6%, Lymphocytes 13% | — |
| Platelets | 6,40,000/µL | 1,50,000–4,00,000/µL |
| Peripheral smear | Myeloid cells at all stages of maturation; no blast crisis; no dysmorphic red cells | — |
| Serum LDH | 980 IU/L (elevated) | <250 IU/L |
| Malarial antigen (RDT) | Negative | — |
| Leishmania rK39 Ab | Negative | — |
| Bone marrow aspirate | Hypercellular; granulocytic hyperplasia with full maturation; megakaryocytes normal to increased | — |
Task: Interpret these findings. Which features support or argue against each mechanism/disorder in your Section 1 differential? Explicitly address the basophilia, the negative serology results, and the bone marrow picture.
Guidance: Basophilia >2% in the context of a left-shift myeloid picture is a strong pointer — discuss why. Negative malarial antigen and negative rK39 antibody do not completely exclude tropical infections, but explain why the haematological picture makes them less likely here. The bone marrow finding of full maturation without excess blasts is a key distinguishing feature from acute leukaemia.
Section 3 — Reaching a Diagnosis
Confirmatory test result: BCR-ABL1 fusion transcript (p210) detected by RT-PCR; Philadelphia chromosome (t(9;22)(q34;q11)) confirmed by cytogenetics.
Task: State your final diagnosis with full justification. Explain the molecular pathogenesis of CML: what the BCR-ABL1 fusion gene produces, how its constitutive tyrosine kinase activity drives myeloproliferation, and why the spleen becomes the predominant site of extramedullary haematopoiesis leading to massive splenomegaly.
Guidance: Connect the molecular event (t(9;22) → p210 BCR-ABL1 → constitutive tyrosine kinase → block in apoptosis + unrestrained proliferation) directly to the clinical findings. Explain extramedullary haematopoiesis — why the spleen reverts to a haematopoietic role and what this does to splenic architecture. Keep molecular detail at Year-2 level: mechanism of action of imatinib can be mentioned briefly as context but is not the focus.
Section 4 — Hypersplenism and Its Consequences
Task: This patient develops worsening anaemia (Hb 6.1 g/dL) and thrombocytopenia (platelets 52,000/µL) after 4 months despite stable WBC. The treating haematologist attributes this to hypersplenism.
(a) Define hypersplenism. Describe the three mechanisms by which an enlarged spleen causes cytopenias.
(b) How does hypersplenism differ from a primary bone marrow failure in terms of peripheral blood and bone marrow findings?
(c) In CML specifically, what additional mechanism beyond sequestration may contribute to anaemia?
Guidance: Three mechanisms of hypersplenism: (i) increased sequestration/pooling of formed elements; (ii) dilutional effect from expanded splenic blood volume; (iii) possibly immune-mediated destruction. For part (b), the distinguishing feature is a hyperplastic (not hypoplastic) marrow in hypersplenism. For part (c), consider cytokine milieu, ineffective erythropoiesis, and treatment effects.
Section 5 — Splenectomy: Indications and Consequences
Task: The haematology team considers splenectomy for refractory hypersplenism. Discuss:
(a) What haematological changes appear in the peripheral blood immediately after splenectomy? Name at least four specific morphological findings and explain the physiological basis of each.
(b) What is Overwhelming Post-Splenectomy Infection (OPSI)? Which organisms are primarily responsible, and why are asplenic patients specifically vulnerable?
(c) What preventive measures should be taken before and after splenectomy? (Vaccinations, antibiotic prophylaxis schedule, patient education.)
(d) What is the significance of Howell-Jolly bodies as a marker of splenic hypofunction, and how might their presence be used clinically?
Guidance: Part (a): Howell-Jolly bodies (DNA remnants no longer pitted), target cells (loss of remodelling), thrombocytosis (loss of pooling), Pappenheimer bodies, acanthocytes. Part (b): OPSI — encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae type b, Neisseria meningitidis) because the spleen is the primary site for IgM production against T-independent polysaccharide antigens and for opsonisation of encapsulated bacteria. Part (c): Pneumococcal (PCV13 + PPSV23), Hib, meningococcal vaccines ideally 2 weeks pre-splenectomy; penicillin prophylaxis for at least 2 years (lifelong in children/immunocompromised); patient alert card.
Grading Rubric — Spleen Disorders Case-Study Rubric (30 points)
| Criterion | Points | Full-marks descriptor |
|---|---|---|
| Mechanism-based differential diagnosis (Section 1): completeness, correct mechanistic grouping, appropriate breadth including tropical infections and myeloproliferative neoplasms | 6 pts | Six or more causes listed; correctly grouped under ≥4 mechanisms; tropical infections and myeloproliferative neoplasms both included; concise and accurate descriptions |
| Laboratory interpretation and differential narrowing (Section 2): correct interpretation of basophilia, negative serology, bone marrow picture; logical exclusion of competing diagnoses | 7 pts | Basophilia correctly flagged as pointing to myeloproliferative neoplasm; negative serology interpreted with appropriate nuance (not absolute exclusion); bone marrow full maturation vs blast crisis vs hypoplasia clearly distinguished; all major competing diagnoses explicitly addressed |
| Molecular diagnosis and pathogenesis of CML (Section 3): accuracy of BCR-ABL1 mechanism, link to splenomegaly via extramedullary haematopoiesis | 7 pts | t(9;22) translocation correctly described; p210 BCR-ABL1 fusion and constitutive tyrosine kinase activity explained; mechanism linking apoptosis block + unrestrained proliferation to myeloid expansion; extramedullary haematopoiesis in spleen clearly connected to splenic architecture changes and massive splenomegaly |
| Hypersplenism (Section 4): definition, three mechanisms of cytopenia, distinction from marrow failure, additional CML-specific mechanism | 5 pts | Hypersplenism clearly defined; all three mechanisms (sequestration, dilutional, immune-mediated) explained; marrow hyperplasia vs hypoplasia distinction correctly used to differentiate from primary marrow failure; at least one CML-specific additional mechanism identified (cytokine milieu, ineffective erythropoiesis) |
| Splenectomy consequences and OPSI prophylaxis (Section 5): post-splenectomy blood changes with physiological basis, OPSI organisms and vulnerability mechanism, preventive protocol, Howell-Jolly bodies as clinical marker | 5 pts | Four or more post-splenectomy morphological changes named with correct physiological basis; OPSI defined; all three major encapsulated organisms listed; polysaccharide antigen / IgM opsonisation mechanism explained; complete vaccination + prophylaxis + education protocol; Howell-Jolly bodies discussed as a clinical marker of splenic hypofunction |
PEER REVIEW
You will review two classmates' submissions using the rubric above. For each criterion, select the rating that best matches the submission and write 2–3 sentences of specific, constructive feedback explaining your rating. Do not simply copy the rubric descriptor — reference the student's actual content. Tone must be professional and educational. Avoid personal comments. Your peer review will be evaluated for its quality, specificity, and fairness.