Table 2.

Proposed Refined Major and Minor SM Criteria.

Major criterion:	Multifocal dense infiltrates of mast cells (≥15 mast cells in aggregates) in bone marrow biopsies and/or in sections of other extracutaneous organ(s)
Minor criteria:	a. ≥25% of all mast cells are atypical cells (type I or type II) on bone marrow smears or are spindle-shaped in mast cell infiltrates detected in sections of bone marrow or other extracutanous organsa
	b. KIT-activating KIT point mutation(s) at codon 816 or in other critical regions of KITb in bone marrow or another extracutaneous organ
	c. Mast cells in bone marrow, blood, or another extracutaneous organ express one or more of: CD2 and/or CD25 and/or CD30c
	d. Baseline serum tryptase concentration >20 ng/mL (in the case of an unrelated myeloid neoplasm, an elevated tryptase does not count as an SM criterion. In the case of a known HαT, the tryptase level should be adjustedd
	If at least 1 major and 1 minor or 3 minor criteria are fulfilled → the diagnosis is SM

^aIn tissue sections, an abnormal mast cell morphology counts in both a compact infiltrate and a diffuse (or mixed diffuse + compact) mast cell infiltrate. However, the spindle-shaped form does not count as an SM criterion when mast cells are lining vascular cells, fat cells, nerve cells, or the endosteal-lining cell layer. In the bone marrow smear, an atypical morphology of mast cells does not count as SM criterion when mast cells are located in or adjacent to bone marrow particles. Morphologic criteria of atypical mast cells have been described previously.⁶

^bAny type of KIT mutation counts as minor SM criterion when published solid evidence for its transforming behavior is available. A list of such KIT mutations (including variants in KIT codons 417, 501–509, 522, 557–560, 642, 654, 799, 816, 820, 822) is provided in Supplemental Digital Content, Table S6, http://links.lww.com/HS/A201 (KIT-activating mutations are labeled in bold).

^cAll 3 markers fulfill this minor SM criterion when expression in mast cells can be confirmed by either flow cytometry or by immunohistochemistry or by both techniques.

^dAlthough the optimal way of adjustment may still need to be defined, one way is to divide the basal tryptase level by 1 plus the extra copy numbers of the alpha tryptase gene. Example, when the tryptase level is 30 and 2 extra copies of the alpha tryptase gene are found in a patient with HαT, the HαT-corrected tryptase level is 10 (30/3 = 10) and thus is not a minor SM criterion.

HαT = hereditary alpha-tryptasemia; SM = systemic mastocytosis.