Background. The diagnosis of mastocytosis in absence of the typical skin lesions is often difficult. It should be considered in the differential diagnosis of a number of unexplained clinical conditions, such as severe anaphylaxis, osteoporosis, neurological or constitutional symptoms, and chronic diarrhoea. Isolated bone marrow mastocytosis (BMM) is considered a rare subcategory of indolent systemic mastocytosis (ISM), characterized by low burden of mast cells (MC), absence of skin, lymph node or multiorgan involvement, slightly elevated serum tryptase (sT) levels, and a good prognosis. The term Monoclonal Mast cell Activation Syndrome (MMAS) is used to define those patients with mediator-related symptoms and absence of skin lesions in which bone marrow (BM) biopsy fails to demonstrate multifocal MC aggregates (i.e. the major criterion for diagnosing mastocytosis), but there is a proof of MC clonality (abnormal MC immunophenotype or detection of a KIT mutation). Data about these conditions are scanty. Aims. To define the frequency and characteristics of clonal MC disorders limited to BM in a cooperative multidisciplinary setting. Methods. From January 2006 to December 2009 144 adult patients with a clinical suspect of mastocytosis were referred to our multidisciplinary ambulatory for Mastocytosis, based on close collaboration between Hematologists, Allergists, Dermatologists and Rheumatologists. All patients underwent BM evaluation that included histology/citology, flow cytometry, and detection of KIT mutations, performed as described (Bonadonna et al., JACI 2009).Results. According to the current WHO guidelines, we made 111 diagnoses of clonal MC disorders: ISM with skin involvement were 48 (43.2%), BMM 40 (36%), MMAS 13 (11.7%). The remaining patients had Cutaneous Mastocytosis (9) and Mast Cell Leukemia (1). Among the 53 patients with clonal MC disorders limited to BM, the large majority of them (96%) had experienced one or more episodes of severe ana- phylaxis after hymenoptera sting, drug or food or showed unexplained anaphylaxis. Two patients were referred to our Ambulatory because of unexplained osteoporosis. Compared to cases of ISM with skin involvement, patients with BMM or MMAS were predominantly males and, as expected, they had an inferior burden of MC, as suggested by the lower sT levels and the inferior percentage of BM abnormal MC at flow cytometry. Moreover, mediator-related symptoms other than anaphylaxis, such as pruritus, flushing, diarrhoea, hypotension,were less frequent in patients with MC disease limited to BM. Densitometric examination revealed 22/76 cases (29%) of osteoporosis or osteopenia, according to WHO definitions, without differences between subgroups. After a median follow-up of 22 months (range 1-48) all patients are alive and have stable disease. Conclusions. Clonal MC disorders limited to BM are a challenge for the physician. A close collaboration between different specialists may allow that more patients with clinical suspicion of mastocytosis could be referred to the opportune diagnostic procedures. In our experience this led to individuate 53 cases of isolated BMM or MMAS, the largest series reported to date. Besides making a correct diagnosis, this approach revealed a significant proportion of patients with loss of bone mineral density, so improving the management of this disease.

Clonal mast cell disorders limited to bone marrow: not a negligible disease.

BONIFACIO, Massimiliano;ARTUSO, ANNA;BONADONNA, PATRIZIA;PERBELLINI, Omar;CARUSO, BEATRICE;ZAMO', Alberto;SCHENA, DONATELLA;ROSSINI, Maurizio;ZANOTTI, ROBERTA
2010

Abstract

Background. The diagnosis of mastocytosis in absence of the typical skin lesions is often difficult. It should be considered in the differential diagnosis of a number of unexplained clinical conditions, such as severe anaphylaxis, osteoporosis, neurological or constitutional symptoms, and chronic diarrhoea. Isolated bone marrow mastocytosis (BMM) is considered a rare subcategory of indolent systemic mastocytosis (ISM), characterized by low burden of mast cells (MC), absence of skin, lymph node or multiorgan involvement, slightly elevated serum tryptase (sT) levels, and a good prognosis. The term Monoclonal Mast cell Activation Syndrome (MMAS) is used to define those patients with mediator-related symptoms and absence of skin lesions in which bone marrow (BM) biopsy fails to demonstrate multifocal MC aggregates (i.e. the major criterion for diagnosing mastocytosis), but there is a proof of MC clonality (abnormal MC immunophenotype or detection of a KIT mutation). Data about these conditions are scanty. Aims. To define the frequency and characteristics of clonal MC disorders limited to BM in a cooperative multidisciplinary setting. Methods. From January 2006 to December 2009 144 adult patients with a clinical suspect of mastocytosis were referred to our multidisciplinary ambulatory for Mastocytosis, based on close collaboration between Hematologists, Allergists, Dermatologists and Rheumatologists. All patients underwent BM evaluation that included histology/citology, flow cytometry, and detection of KIT mutations, performed as described (Bonadonna et al., JACI 2009).Results. According to the current WHO guidelines, we made 111 diagnoses of clonal MC disorders: ISM with skin involvement were 48 (43.2%), BMM 40 (36%), MMAS 13 (11.7%). The remaining patients had Cutaneous Mastocytosis (9) and Mast Cell Leukemia (1). Among the 53 patients with clonal MC disorders limited to BM, the large majority of them (96%) had experienced one or more episodes of severe ana- phylaxis after hymenoptera sting, drug or food or showed unexplained anaphylaxis. Two patients were referred to our Ambulatory because of unexplained osteoporosis. Compared to cases of ISM with skin involvement, patients with BMM or MMAS were predominantly males and, as expected, they had an inferior burden of MC, as suggested by the lower sT levels and the inferior percentage of BM abnormal MC at flow cytometry. Moreover, mediator-related symptoms other than anaphylaxis, such as pruritus, flushing, diarrhoea, hypotension,were less frequent in patients with MC disease limited to BM. Densitometric examination revealed 22/76 cases (29%) of osteoporosis or osteopenia, according to WHO definitions, without differences between subgroups. After a median follow-up of 22 months (range 1-48) all patients are alive and have stable disease. Conclusions. Clonal MC disorders limited to BM are a challenge for the physician. A close collaboration between different specialists may allow that more patients with clinical suspicion of mastocytosis could be referred to the opportune diagnostic procedures. In our experience this led to individuate 53 cases of isolated BMM or MMAS, the largest series reported to date. Besides making a correct diagnosis, this approach revealed a significant proportion of patients with loss of bone mineral density, so improving the management of this disease.
Indolent Systemic Mastocytosis; bone marrow mastocytosis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/893595
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