**Question:** Splenic macrophages in Gaucher's disease differ from those in ceroid histiocytosis by staining positive for

A. acid phosphatase
B. alpha-mannosidase
C. beta-glucocerebrosidase
D. lysozyme

**Core Concept:** Gaucher's disease and ceroid histiocytosis are two conditions involving macrophages and lipid storage. Gaucher's disease is caused by mutations in the GBA gene, leading to a deficiency in beta-glucocerebrosidase enzyme, which results in the accumulation of glucosylceramide in macrophages. Ceroid histiocytosis is a term used for a group of disorders characterized by abnormal lipid accumulation in macrophages, but it is not a specific diagnosis. Splenic macrophages in both conditions exhibit lipid storage but differ in the enzyme activity.

**Why the Correct Answer is Right:** In Gaucher's disease, splenic macrophages stain positive for acid phosphatase due to the deficiency of beta-glucocerebrosidase enzyme. In contrast, ceroid histiocytosis macrophages stain positive for alpha-mannosidase, as they primarily accumulate alpha-mannosidase-deficient lipids.

**Why Each Wrong Option is Incorrect:**

A. acid phosphatase: This is not specific to Gaucher's disease and can be present in ceroid histiocytosis macrophages as well, making it an incorrect choice.
B. alpha-mannosidase: As mentioned earlier, alpha-mannosidase is deficient in ceroid histiocytosis, making it the incorrect choice.
C. beta-glucocerebrosidase (the correct answer): This enzyme is deficient in Gaucher's disease, allowing splenic macrophages to stain positive for acid phosphatase.
D. lysozyme: Lysozyme is an antimicrobial enzyme and not specific to either Gaucher's disease or ceroid histiocytosis, rendering it an incorrect choice.

**Clinical Pearl:** A positive acid phosphatase stain in macrophages should raise suspicion for Gaucher's disease and guide further diagnostic evaluation, including genetic testing.

In summary, splenic macrophages in Gaucher's disease differ from those in ceroid histiocytosis by staining positive for acid phosphatase due to the deficiency of beta-glucocerebrosidase enzyme in Gaucher's disease. This characteristic staining helps differentiate between these two entities and guides appropriate further diagnostic workup.