Systemic mastocytosis

Mastocytosis is a disease characterized by an abnormal increase in mast cells. Rare in occurrence, protean in its manifestations, it is a disease which is very seldom thought of and hence, possibly even overlooked. The last few decades have witnessed an upsurge in the understanding of the physiology and pathobiology of mast cells. Better means for diagnosis and follow-up have become available. Once a diagnosis is established histamine antagonists remain the mainstay of treatment. Most patients live and die with the disease rather than of it. The objective of this review is to discuss this entity with a special focus on diagnosis and treatment.     

Systemic mastocytosis

Systemic mastocytosis (SM) is a clonal disorder of hematopoietic system characterized by abnormal growth and accumulation of mast cells in various tissues. Its clinical spectrum ranges from mild disease to an aggressive course with life-threatening conditions. Some of the clinical signs or symptoms of SM (hyperhidrosis, syncope and hypotensive/tachycardiac attacks) require consideration of pheochromocytoma and carcinoid syndrome in the differential diagnosis. The diagnosis relies on the demonstration of mast cell aggregates in bone marrow or extracutaneous tissues. The World Health Organization categorizes SM into 6 variants: indolent SM, SM with associated clonal hematological nonmast cell lineage disease, aggressive SM, mast cell leukemia, mast cell sarcoma and extracutaneous mastocytosis. Patients with indolent SM have a favorable prognosis with a life expectancy comparable with the healthy population, and symptomatic treatment is usually sufficient. However, more aggressive forms may be life threatening, and cytoreductive treatment is indicated in most cases.     

Systemic mastocytosis in the elderly

“Later onset” of systemic mastocytosis (SM) has been associated with a poorer prognosis. We examined clinical and laboratory findings, associated disorders, and survival in an older mastocytosis population. After receiving Mayo Clinic Institutional Review Board approval, we identified 42 patients aged 70 years and older at the time of diagnosis of SM. Associated disorders, cytogenetic abnormalities, laboratory findings, and survival were recorded. Only 10 patients had no associated hematologic disorder. Single or multiple chromosomal abnormalities, exclusive of the KIT Asp816Val mutation, were detected in eight patients (19%). KIT Asp816Val mutation was present in 14 patients, negative in three, and not tested in 25. Slight to marked bone marrow hypercellularity was observed in 33 patients (79%). Concurrent hematologic abnormalities included chronic myelomonocytic leukemia (n = 7), acute myelocytic leukemia (n = 1), myelodysplastic syndrome (MDS; n = 7), eosinophilia (n = 7), myelofibrosis (n = 1), myeloproliferative disorder (n = 1), multiple myeloma (n = 1), B‐cell lymphoma (n = 1), and thrombocytopenia (n = 4). Eight patients had a hematologic disorder that preceded the diagnosis of SM. Tryptase levels were elevated in 38 of 39 patients tested. Survival from the diagnosis of SM was poor for patients with associated thrombocytopenia, leukemias, and MDS. In conclusion, patients with SM diagnosed at age 70 or older have an increased risk of secondary hematologic disorders and abnormal laboratory findings. Cytogenetic abnormalities are common, and survival is short in many SM patients with associated leukemias, MDS, or eosinophilia. Am. J. Hematol. 88:406–408, 2013. © 2013 Wiley Periodicals, Inc.     

Systemic mastocytosis and secondary acute myeloid leukemia

Systemic mast cell disease (SMCD) is an idiopathic disorder in which mast cells proliferate and accumulate in various organs including the skin, bone marrow, liver, spleen and lymph nodes. SMCD is regarded as a myeloproliferative disorder for any authors. Associated hematologic disorders can be found in up to one third of patients with SMCD. It may be due to the apparent close relationship between the mast cell and the myeloid cell.     

Systemic mastocytosis disclosed by rupture of esophageal varices

A 77-year-old woman had variceal bleeding related to systemic mastocytosis. Physical examination revealed minimal ascites and mild hepatomegaly noted 11 years before. Liver function tests were nearly normal. Because of early recurrent bleeding, a mesocaval shunt was performed. Wedged liver biopsy showed a moderate fibrosis of portal tracts and massive mast cell infiltration within portal tracts and sinusoids. Perisinusoidal collagen deposition was demonstrated ultrastructurally. We suggest that systemic mastocytosis be added to the list of diseases related portal hypertension with perisinusoidal fibrosis. As there is currently no specific treatment, a portocaval shunt should be discussed.     

Systemic mastocytosis: current concepts and treatment advances

Systemic mastocytosis (SM), as opposed to cutaneous-only mastocytosis, implies the presence of neoplastic mast cell infiltration in extracutaneous tissue. Mast cell disease in adults is often systemic and often involves the bone marrow. Typical clinical and laboratory features of SM include urticaria pigmentosa, mast cell mediator symptoms (eg, headache, flushing, lightheadedness, urticaria and pruritus, nausea, diarrhea, abdominal pain, and vasodilatory shock), bone pain (eg, osteoporosis, lytic bone lesions, and fractures), hepatosplenomegaly, cytopenia, eosinophilia, elevated serum tryptase and histamine, and bone marrow fibrosis and angiogenesis. SM may be indolent (no evidence of organ dysfunction), aggressive (presence of organ dysfunction), associated with another often chronic myeloid hematologic disease (SM-AHD), or present as mast cell leukemia or sarcoma. Mast cell-mediator symptoms are treated with histamine antagonists and cromolyn sodium. Indolent SM does not require cytoreductive therapy. Aggressive SM and SM-AHD are managed based on their molecular profile. Recent information suggests that FIP1-like-1-platelet-derived growth factor receptor-alpha(+) SM responds well to imatinib mesylate, whereas interferon-alpha should be considered as a first-line treatment in all of the other cases, including patients with Asp816Val(+) SM. Cladribine has been shown to be effective in patients who develop resistance to interferon treatment.