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PA19.4 | Splenomegaly — Causes & Differentiation — SDL Guide (Part 3)

Category 4 — Infiltrative and Storage Splenomegaly

A five-panel pathology diagram compares infiltrative and storage causes of splenomegaly: Gaucher disease, Niemann-Pick disease, amyloidosis, and sarcoidosis. — **Panel A:** Enlarged spleen, red pulp, white pulp, splenic macrophages, abnormal material accumulation, expanded reticuloendothelial system, splenomegaly. **Panel B:** Gaucher cells, crumpled tissue paper cytoplasm, glucocerebrosidase deficiency, glucocerebroside accumulation, massive splenomegaly, Erlenmeyer flask deformity of femur. **Panel C:** Foam cells, lipid vacuoles, sphingomyelinase deficiency, sphingomyelin accumulation, moderate splenomegaly, neurological features. **Panel D:** Amyloid deposits, splenic sinusoids, splenic follicles, sago spleen, tapioca-like follicular nodules, lardaceous spleen, diffuse waxy pale red pulp. **Panel E:** Non-caseating granulomas, white pulp, epithelioid histiocytes, giant cells, moderate splenomegaly, hilar lymphadenopathy.

Abnormal material accumulates within splenic macrophages or the reticuloendothelial system, expanding the organ.

Gaucher disease — deficiency of glucocerebrosidase → glucocerebroside accumulates in macrophages (Gaucher cells: crumpled tissue paper cytoplasm). Massive splenomegaly; bone marrow replacement; Erlenmeyer flask deformity of femur on X-ray. Enzyme replacement therapy available.
Niemann-Pick disease — sphingomyelinase deficiency → sphingomyelin in macrophages (foam cells); moderate splenomegaly; neurological features.
Amyloidosis — AA or AL amyloid deposits in splenic sinusoids and follicles; sago spleen (follicular deposits, gross: tapioca-like nodules) or lardaceous spleen (diffuse red pulp deposits, gross: large, waxy, pale).
Sarcoidosis — non-caseating granulomas in white pulp; moderate splenomegaly; associated hilar lymphadenopathy.

Category 5 — Immune/Inflammatory Splenomegaly

Four-panel diagram showing immune and inflammatory causes of moderate splenomegaly, including Felty syndrome, SLE onion-skin lesions, and chronic immune stimulation. — **Panel A:** Moderate splenomegaly; enlarged spleen cutaway; white pulp follicular hyperplasia; red pulp macrophage expansion; chronic autoimmune activation.. **Panel B:** Felty syndrome triad; rheumatoid arthritis; splenomegaly; neutropenia; IgG-coated neutrophils; splenic macrophage sequestration; increased infection risk.. **Panel C:** SLE spleen; central arteriole; periarterial fibrosis; onion-skin lesion; anti-platelet antibodies; splenic platelet sequestration; thrombocytopenia.. **Panel D:** Chronic immune stimulation; chronic haemolytic state; secondary white pulp hyperplasia; red pulp work hypertrophy; clinical pearl: massive splenomegaly shortlist including CML and myelofibrosis..

Chronic autoimmune activation drives follicular hyperplasia and macrophage expansion.

Rheumatoid arthritis + splenomegaly + neutropenia = Felty syndrome — a triad to memorise. IgG-coated neutrophils are sequestered in spleen; the neutropenia increases infection risk. Splenomegaly here is moderate.
Systemic lupus erythematosus (SLE) — periarterial fibrosis ("onion-skin" lesion) of central arterioles is the pathognomonic splenic finding. Moderate splenomegaly; thrombocytopenia from anti-platelet antibodies + splenic sequestration.
Chronic immune stimulation — e.g., chronic haemolytic states produce secondary white pulp hyperplasia in addition to red pulp work hypertrophy.

CLINICAL PEARL

Massive splenomegaly — the high-yield short list (commit to memory):

Disease	Category	Key pointer
CML	Haematological (infiltration)	Leukocytosis, basophilia, BCR-ABL
Myelofibrosis	Haematological (EMH)	Leukoerythroblastic film, dry tap
Kala-azar (VL)	Infective	Bihar/Jharkhand, pancytopenia, rK39
Malaria (chronic/tropical)	Infective	Haemozoin, tropical splenomegaly syndrome
Gaucher disease	Infiltrative/storage	Gaucher cells, Erlenmeyer flask
Thalassaemia major	Haematological (EMH)	Childhood onset, target cells, HbF ↑

Mnemonic: "Come Meet Kala-azar — Gaucher Takes priority" (CML, Myelofibrosis, Kala-azar, Malaria, Gaucher, Thalassaemia).

Hypersplenism — Definition and Mechanism

Diagram showing hypersplenism as an enlarged spleen that traps and destroys blood cells despite compensatory hypercellular bone marrow, with diagnostic criteria and comparison to myelosuppression. — **Panel A:** Enlarged spleen, splenic sinusoids, trapped RBCs/WBCs/platelets, macrophage destruction, reduced peripheral blood cells, hypercellular bone marrow, compensatory haematopoiesis. **Panel B:** Splenomegaly, cytopenias, hypercellular bone marrow, correction by splenectomy, all four criteria required. **Panel C:** Hypersplenism with hypercellular marrow and peripheral destruction versus myelosuppression with hypocellular marrow and reduced production; common causes include portal hypertension, kala-azar, Gaucher disease, and myelofibrosis.

Hypersplenism is defined by four criteria (all four must be present):
1. Splenomegaly (of any cause)
2. Cytopenias — one or more cell lines reduced (anaemia, leucopenia, thrombocytopenia, or pancytopenia)
3. Hypercellular bone marrow — compensatory expansion (marrow is doing its job; the problem is peripheral destruction)
4. Correction by splenectomy

Mechanism: enlarged spleen traps and destroys blood cells at a rate exceeding marrow compensation. The specific cell line most affected depends on the underlying cause.

Distinguish from myelosuppression: in hypersplenism the marrow is hyperplastic (reactive); in myelosuppression (aplastic anaemia, chemotherapy) the marrow is hypocellular.

Common causes of hypersplenism: portal hypertension (cirrhosis, NCPF), kala-azar, Gaucher, myelofibrosis.

SELF-CHECK

Which one of the following is NOT a criterion for diagnosing hypersplenism?

A. Hypocellular bone marrow

B. Splenomegaly

C. Pancytopenia

D. Correction of cytopenias by splenectomy

Reveal Answer

Answer: A. Hypocellular bone marrow

Hypersplenism requires a HYPERCELLULAR marrow — the marrow is working harder to compensate for peripheral destruction. A hypocellular marrow points to aplastic anaemia or marrow infiltration, not hypersplenism. The other three (splenomegaly, cytopenias, correction by splenectomy) are all included in the classic four-criterion definition.