Systemic Mastocytosis (SM) is characterized by infiltration of neoplastic MC in extracutaneous tissues, usually in bone marrow (BM). According to World Health Organization (WHO), SM diagnosis is defined by the presence of one major and one minor criterion or three minor criteria. However, the MC burden may be very low. Besides, in indolent disease, the presenting symptoms are frequently anaphylactic reactions or unexplained osteoporosis without typical skin lesions. Hence, the real incidence of SM may have been significantly underestimated so far. The study aimed to investigate the value of flow-cytometry analysis to identify neoplastic MC, mainly in patients with indolent disease. From May 2007 to March 2013 we studied 227 patients (102 Females, 125 Males; median age of 53 years, ranging from 14 to 83 years) suspected for SM. They were referred at our Multidisciplinary Mastocytosis Outpatient Clinic, because of mediator-related symptoms or anaphylaxis (68.2%), Urticaria Pigmentosa (21.8%), unexplained osteoporosis (7%), hematological abnormalities (3%). Patients underwent complete BM examination. Moreover, highly sensitive immunophenotype and molecular assays were performed to identify the clonal CD25+ MC and the presence of D816V KIT mutation respectively. One hundred fifty-nine of 227 patients were diagnosed with clonal MC disorders (146 SM, 7 monoclonal MC activation syndrome and 6 SM with an associated hematologic non–mast-cell lineage disorder). The most sensitive diagnostic tools were molecular biology and flow cytometry that were positive in 158/159 and in 155/159 cases respectively. The abnormal MC infiltration was documented by cytology and histology only in 123 and 73 cases respectively. Serum tryptase level was greater than 20 ng/ml in 93/159 patients. According to WHO criteria, in our experience, the minor criteria allowed us to establish the diagnosis of SM in all but one patient, without need of histological demonstration of multifocal MC clustering (major WHO criterion). Our experience reveals that the real incidence of clonal MC disorders is probably greater than the estimated one. This result relies certainly on the multidisciplinary approach to MC disorders, but also on the use of highly sensitive tools to identify neoplastic MC. In this context flow cytometry seems to be more suitable than molecular biology as regards the operating speed and the lower cost of technology.
Value of flow cytometry in the diagnosis of indolent systemic mastocytosis.
ARTUSO, ANNA;PERBELLINI, Omar;ZAMO', Alberto;BONADONNA, PATRIZIA;SCHENA, DONATELLA;ROSSINI, Maurizio;BONIFACIO, Massimiliano;ZANOTTI, ROBERTA
2013-01-01
Abstract
Systemic Mastocytosis (SM) is characterized by infiltration of neoplastic MC in extracutaneous tissues, usually in bone marrow (BM). According to World Health Organization (WHO), SM diagnosis is defined by the presence of one major and one minor criterion or three minor criteria. However, the MC burden may be very low. Besides, in indolent disease, the presenting symptoms are frequently anaphylactic reactions or unexplained osteoporosis without typical skin lesions. Hence, the real incidence of SM may have been significantly underestimated so far. The study aimed to investigate the value of flow-cytometry analysis to identify neoplastic MC, mainly in patients with indolent disease. From May 2007 to March 2013 we studied 227 patients (102 Females, 125 Males; median age of 53 years, ranging from 14 to 83 years) suspected for SM. They were referred at our Multidisciplinary Mastocytosis Outpatient Clinic, because of mediator-related symptoms or anaphylaxis (68.2%), Urticaria Pigmentosa (21.8%), unexplained osteoporosis (7%), hematological abnormalities (3%). Patients underwent complete BM examination. Moreover, highly sensitive immunophenotype and molecular assays were performed to identify the clonal CD25+ MC and the presence of D816V KIT mutation respectively. One hundred fifty-nine of 227 patients were diagnosed with clonal MC disorders (146 SM, 7 monoclonal MC activation syndrome and 6 SM with an associated hematologic non–mast-cell lineage disorder). The most sensitive diagnostic tools were molecular biology and flow cytometry that were positive in 158/159 and in 155/159 cases respectively. The abnormal MC infiltration was documented by cytology and histology only in 123 and 73 cases respectively. Serum tryptase level was greater than 20 ng/ml in 93/159 patients. According to WHO criteria, in our experience, the minor criteria allowed us to establish the diagnosis of SM in all but one patient, without need of histological demonstration of multifocal MC clustering (major WHO criterion). Our experience reveals that the real incidence of clonal MC disorders is probably greater than the estimated one. This result relies certainly on the multidisciplinary approach to MC disorders, but also on the use of highly sensitive tools to identify neoplastic MC. In this context flow cytometry seems to be more suitable than molecular biology as regards the operating speed and the lower cost of technology.
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