immunology allergic disorders
Mastocytosis and Mast Cell Activation Syndrome
Diagnosis of Mastocytosis
Clinical evaluation Bone marrow biopsy Serum tryptase levels (baseline and during symptoms if possible) Diagnosis of mastocytosis is suggested by clinical presentation. However, similar symptoms can be caused by many other disorders such as Carcinoid Syndrome , Diagnosis requires bone marrow biopsy and tryptase levels (a marker of mast cell degranulation) in most patients. Skin biopsy can be done to check for mast cells, but this test does not replace the need for a bone marrow biopsy to classify the diagnosis and staging. Diagnosis of mastocytosis is confirmed when one major criterion and at least one minor criterion or ≥ 3 (of 4) minor criteria are met. Themajor criterion is The presence of multifocal, dense aggregates of > 15 mast cells in bone marrow (preferred) or other extracutaneous organs (except the GI tract, lymph nodes, liver, or spleen) The 4minor criteriaare Atypical morphology or spindle shapes in > 25% of the mast cells in bone marrow biopsy sections or aspirate Akitmutation at codon 816 (commonly Asp816Val) in bone marrow, peripheral blood, or other tissue Bone marrow or other extracutaneous mast cells expressing the surface markers CD2, CD25, or both Baseline serum tryptase levels > 20 ng/mL (> 20 mcg/L); values > 11.4 ng/mL (11.4 mcg/L) are considered elevated in most diagnostic laboratories) The baseline level of tryptase is elevated in systemic mastocytosis but is typically normal in cutaneous mastocytosis and mast cell activation syndrome. Diagnostic criteria for mast cell activation syndrome include all of the following: Typical clinical symptoms of mast cell mediator release During symptoms, a substantial transient increase in total serum tryptase level or an increase in other mast cell–derived mediators, such asN-methyl histamine or prostaglandin D2, leukotriene E4, or their urinary metabolites A clinical response to drugs that attenuate the production or activities of mast cell mediators Patients with mast cell activation typically have a normal bone marrow biopsy if it is done. If the diagnosis is uncertain, levels of mast cell mediators and their metabolites (eg, 24-hourN-methylhistamine, prostaglandin D2, leukotriene E4) may be measured in plasma and urine; elevated levels support the diagnosis of mast cell disease but not necessarily systemic mastocytosis. A bone scan and GI evaluation, can also be helpful in cases where the diagnosis requires confirmation. 1. Adapted from Horny HP, Akin C, Arber DA, et al: Mastocytosis. InWHO (World Health Organization) Classification of Tumors of Hematopoietic and Lymphoid Tissues, edited by SH Swerdlow, E Campo, and NL Harris, et al, Lyon, IARC (International Agency for Research on Cancer) Press, 2017, p. 62. 