Mastocytosis: Part I: Pathogenesis, Clinical Presentation and Classification

Mast cells are tissue-resident immune cells which secrete numerous and varied immune mediators in response to a myriad of activation pathways and play an important physiological function in immunity, homeostasis, tissue repair, and nervous system regulation. New understandings in activation and signaling have led to new drug targets. Mastocytosis is a hematologic clonal neoplasm resulting from aberrant proliferation, maturation, and infiltration of mast cells. Symptoms may arise by localized effects of mast cell aggregation and infiltration in organs and inappropriate immune mediator release. Cutaneous signs of mastocytosis may take multiple forms, including erythematous to violaceous macules and papules, diffusely thickened skin, brown-yellow nodules, and telangiectatic tan-brown erythematous macules. Cutaneous findings may be associated with pruritus and Darier sign, in which an urticarial wheal is elicited by mechanical irritation. Systemic signs of mastocytosis include flushing, pruritus, syncope, liver dysfunction, splenic enlargement, lymphadenopathy, osteolytic lesions, pathologic fractures, and pancytopenia. Systemic mastocytosis (SM) is classified into subtypes by the World Health Organization (WHO) based on degree of associated findings, and classifications include indolent SM, smoldering SM, aggressive SM, SM with associated hematologic neoplasm, mast cell leukemia, and bone marrow mastocytosis. Prognosis depends upon classification, and ranges from benign to rapidly fatal.