Question

A 45-year-old male presents with recurrent episodes of flushing, abdominal discomfort, and splenomegaly. Laboratory studies show elevated serum tryptase levels. Bone marrow biopsy reveals mast cells positive for CD117 and CD25. According to the WHO criteria, which of the following findings fulfills the major diagnostic criterion for systemic mastocytosis?

• A. Multifocal dense infiltrates of abnormal mast cells in bone marrow or other extracutaneous organs
• B. Elevated baseline serum tryptase $>$ 20 ng/mL
• C. Mast cells expressing CD25 and/or CD2
• D. Presence of KIT D816V mutation

Hint:

Remember the WHO criteria for Systemic Mastocytosis using the distinction between anatomical/structural (Major) and molecular/biochemical (Minor).
The major criterion is purely morphological/histological (dense clusters of $\geq$ 15 mast cells). All flow cytometry, genetic (KIT), and serum (tryptase) markers are classified as minor criteria.

Answer 1

The Correct Option is A

Concept:
Systemic Mastocytosis (SM) is a clonal disorder characterized by the abnormal proliferation and accumulation of mast cells in various organs, most commonly the bone marrow, skin, liver, spleen, and lymph nodes.
The World Health Organization (WHO) has established specific major and minor criteria for the definitive diagnosis of systemic mastocytosis.
Explanation:
• To diagnose systemic mastocytosis, a patient must meet either one major criterion plus one minor criterion, or three minor criteria.

• The single major criterion for systemic mastocytosis is the presence of multifocal dense infiltrates of mast cells ($\geq$ 15 mast cells in aggregates) detected in sections of bone marrow or other extracutaneous organs.

• The minor criteria include four specific findings.

• First minor criterion: $>$ 25% of mast cells in the bone marrow or other extracutaneous organs have an atypical or spindle-shaped morphology.

• Second minor criterion: Detection of a KIT point mutation at codon 816 (most commonly KIT D816V) in the bone marrow, blood, or another extracutaneous organ.

• Third minor criterion: Mast cells in bone marrow, blood, or other extracutaneous organs aberrantly express CD2 and/or CD25 (in addition to normal mast cell markers like CD117).

• Fourth minor criterion: A persistently elevated baseline serum total tryptase level strictly $>$ 20 ng/mL (this criterion is not valid if an associated clonal myeloid disorder is present).

• Based on the options provided, options (B), (C), and (D) represent the minor criteria.

• Only option (A) correctly identifies the major criterion required by the WHO guidelines.
Final answer:
The major diagnostic criterion is the presence of multifocal dense infiltrates of abnormal mast cells in the bone marrow or other extracutaneous organs.