Adult mastocytosis: a review of the Santo António Hospital 's experience and an evaluation of World Health Organization criteria for the diagnosis of systemic disease

Abstract

BACKGROUNDMastocytosis is a clonal disorder characterized by the accumulation of abnormal mast cells in the skin and/or in extracutaneous organs. OBJECTIVESTo present all cases of mastocytosis seen in the Porto Hospital Center and evaluate the performance of World Health Organization diagnostic criteria for systemic disease. METHODSThe cases of twenty-four adult patients with mastocytosis were reviewed. Their clinical and laboratorial characteristics were assessed, and the properties of the criteria used to diagnose systemic mastocytosis were evaluated. RESULTSThe age of disease onset ranged from 2 to 75 years. Twenty-three patients had cutaneous involvement and 75% were referred by dermatologists. Urticaria pigmentosa was the most common manifestation of the disease. One patient with severe systemic mast cell mediator-related symptoms showed the activating V560G KIT mutation. The bone marrow was examined in 79% of patients, and mast cell immunophenotyping was performed in 67% of the participants. Systemic disease was detected in 84% of cases, and 81% of the sample had elevated serum tryptase levels. All the diagnostic criteria for systemic mastocytosis had high specificity and positive predictive value. Bone marrow biopsy had the lowest sensitivity, negative predictive value and efficiency, while the highest such values were observed for mast cell immunophenotyping. Patients were treated with regimens including antihistamines, sodium cromoglycate, alpha-interferon, hydroxyurea and phototherapy. CONCLUSIONSCutaneous involvement is often seen in adult mastocytosis patients, with most individuals presenting with indolent systemic disease. Although serum tryptase levels are a good indicator of mast cell burden, bone marrow biopsy should also be performed in patients with normal serum tryptase, with flow cytometry being the most adequate method to diagnose systemic disease.

A 26-year-old Woman With Bilateral Leg Pain and Pruritus

“…3 A whole-body bone scan shows homogeneous symmetric diffuse increased radiotracer uptake along the bilateral proximal and distal femurs, proximal tibias, and calcanei. nonspecific nature of the symptoms, as was the case for our patient [4,14,17]. Systemic mastocytosis is characterized by a monoclonal proliferation of atypical mast cells resulting from activating somatic point mutations of the c-kit proto-oncogene.…”

“…Thus, therapeutic goals are symptom reduction and quality of life improvement rather than cure. For aggressive systemic mastocytosis, as in our patient, cytoreductive therapies including cladribine, interferonapha 2b, glucocorticoids, hydroxyurea, and tyrosine kinase inhibitors have been suggested [4,9].…”

“…The patient's long history of pruritus initially was presumed to be the result of her hepatobiliary disease, but in retrospect it most likely was caused by her systemic mastocytosis for which pruritus is a very common symptom [9,13,14]. The dermatologic findings at presentation were consistent with excoriations owing to diffuse pruritus [4,13,14]. The patient's chronic gastrointestinal symptoms with elevated liver enzymes also are consistent with systemic mastocytosis [14].…”

“…According to the WHO, systemic mastocytosis can be divided into several subtypes including, (1) indolent systemic mastocytosis; (2) systemic mastocytosis with associated clonal hematologic nonmast cell lineage disease; (3) mast cell leukemia; (4) mast cell sarcoma; and (5) aggressive systemic mastocytosis [4]. The major criterion for systemic mastocytosis is the presence of multifocal dense infiltrates of mast cells in the bone marrow; this finding has a 100% specificity, 100% positive predictive value, and 69% sensitivity for the presence of systemic mastocytosis [4]. Tryptase immunohistochemical staining is a highly sensitive marker for mast cells and can be used to help highlight mast cell infiltrates on biopsy [6,12].…”

“…Additional minor criteria for the diagnosis of systemic mastocytosis include detection of the c-kit mutation, organ system involvement other than skin, serum tryptase levels greater than 20 lg/L, and extracutaneous mast cells with CD2+ and/or CD25+ expression. The WHO criteria for the diagnosis of systemic mastocytosis states one must have one major criteria finding and one minor finding or three minor findings to have the diagnosis of systemic mastocytosis [4,9,12].…”