Abstracts S125
J ALLERGY CLIN IMMUNOL VOLUME 117, NUMBER 2
Longitudinal Disease Progression in Mastocytosis Syndromes: a Retrospective Chart Review N. M. Vogel1, A. E. Lichtin2, F. H. Hsieh1; 1Pulmonary, Allergy and Critical Care Medicine, Cleveland Clinic Foundation, Cleveland, OH, 2Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH. RATIONALE: Mastocytosis consists of a group of disorders characterized by the abnormal growth and accumulation of mast cells in various organs. The spectrum of mastocytosis syndromes includes cutaneous forms to systemic forms including indolent systemic mastocytosis (ISM) and more aggressive variants. The progression of either cutaneous or ISM to more advanced forms of mastocytosis has not commonly been reported. METHODS: Patient records from a tertiary care institution over a 5 year period from 2000-2005 were reviewed. Fifty-two adult patients and 74 pediatric patients with the diagnosis of mastocytosis were included in the study. Classification of mastocytosis was based on the 2001 World Health Organization criteria. Clinical symptoms, serum tryptase, c-kit mutational analysis, skin and bone marrow biopsies at the time of diagnosis and most recent evaluation were reviewed. RESULTS: None of the 74 pediatric patients had diagnostic findings of progression to more advanced forms of mastocytosis. Of the 52 adult patients, eleven patients (21%) were considered to have possible progression from either cutaneous mastocytosis or ISM to a more advanced form of systemic mastocytosis. Six of these 11 patients (11% of total) had definite clinical or histopathologic findings suggestive of progression from cutaneous mastocytosis to indolent or aggressive disease. Two of these 6 patients(4% of total) who initially presented with cutaneous mastocytosis died from complications directly related to aggressive systemic mastocytosis.
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CONCLUSIONS: Patients with mastocytosis may progress from cutaneous or indolent disease to more aggressive disease. Improved diagnostic techniques may allow clinicians to risk-stratify patients with mastocytosis and offer therapy to interrupt disease progression. Acquired Angioedema Type I (AAE-I) Associated to NonHodgkin Lymphoma P. Vasquez, M. A. Sgrazzutti, P. Domenichini, A. E. Romanelli, R. D. Rebagliati, G. D. Ramón, S. Garbiero; Allergy and Immunology, Hospital Italiano Regional del Sur, Bahía Blanca, ARGENTINA. RATIONALE: To report a 47 year old female patient with a history of several episodes of angioedema, including two acute edemas in the glottis. In these crises she showed no response to antihistamines, steroids or epinephrine, whether intravenous or intramuscular. The patient was diagnosed a low degree Non-Hodgkin lymphoma (follicular lymphoma) a year and a half ago. The patient referred angioedema and acute abdominal pain episodes 8 years before presenting the lymphoma. Specific analyses were performed, including sub-varieties of the complement. METHODS: Biological and hematological tests in peripheral blood and bone marrow were performed in order to determine the type of lymphoproliferative disease. In addition, immunological tests to confirm the acquired angioedema diagnosis were carried out. RESULTS: The patient has a follicular lymphoma with liver and spleen (hepatosplenomegaly) and bone marrow involvement, but without involvement of retroperitoneal adenopathies. An immunophenotypical study of peripheral blood cells showed a B strain clonal population with positive CD 20, CD 22, CD 79b, CD 19, CD 23 and FMC7 and negative CD 10 and CD 5 with lambda monoclonality in the cellular membrane. Near the last crisis of angioedema we found complement C4 Beta 1E <10 mg/dl, C1q inhibitor 70 mg/L and Complement C1q (11S protein) 95 mg/L. CONCLUSIONS: Faced with the current evidence, it is concluded that the patient has Acquired Angioedema Type I associated to Non-Hodgkin, follicular type or low degree lymphoma.
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Mastocytosis in the Child
A. C. Zenea-Capote1, J. Moneda2; 1Pediatric, Health Center Montesa, Madrid, SPAIN, 2Dermatology, “William Soler” Pediatric Hospital, La Habana, CUBA. RATIONALE: 340 patients affected with cutaneous mastocytosis, children aged to birth -14, from the Department of Allergy and Clinical Immunology of the “William Soler” Pediatric Hospital were studied, to contribute to the better knowledge of mastocytosis so as to facilitate its precise diagnosis. METHODS: All patients underwent a thorough physical examination, cutaneous biopsy and clinical survey. The lab tests included hemogram, erythrocyte sedimentation, stools, serology, eosinophils count, functional hepatic tests, glutamic-piruvic transaminase, alkaline fosfatase, glycaemia, blood coagulation tests, bone marrow examination, 5-hydroxy-indoleacetic (to those who suffered from flushing), protein electrophoresis, immunoelectrophoresis, cellular immunity, serum complement, phagocyte index. The following radiological examinations were made: bone survey, intestinal tract and visceral and bone scintigraphy with Tc 99. RESULTS: Of the 340 patients studied so far, all of them had positive Darier´s sign; 297, pruritus; 30, flushing; and, other manifestations (abdominal pain, diarrhea, etc). Systemic mastocytosis was no reported and examinations made are considered normal. It is observed and increased of cutaneous mastocytosis in Cuba. The disease begins when children are under 5. The maculopapular manifestations are the most common. CONCLUSIONS: Darier´s sign proved to be important for diagnosed the disease. The therapy to be applied varied according to the symptoms and consisted mainly in Cimetidine, Disodium Cromoglycate and Histamine H1 receptor blockades. Funding: “William Soler” Pediatric Hospital
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Indolent Systemic Mastocitosis with Germline D816V Somatic c-kit Mutation Evolving to an Acute Myeloid Leukemia L. Escribano1, R. Núñez-López1, M. Jara2, A. García-Montero2, A. Prados1, C. Teodosio2, A. Iglesias1, M. Sanchez2, A. Orfao2; 1Mast Cell Unit, Hospital Ramón y Cajal, Madrid, SPAIN, 2Servicio de Citometría, Centro de Investigación del Cáncer y Departamento de Medicina, Universidad de Salamanca, Salamanca, SPAIN. RATIONALE: We present a case of indolent systemic mastocitosis, carrying a germline D816V mutation, evolving to an acute myeloid leukemia 20 years after the onset. METHODS: A 37-years-old woman, diagnosed of indolent systemic mastocytosis (ISM) at the age of 17 years, was referred to Ramón y Cajal’s Mast Cell Unit in May 2004 for evaluation. She presented urticaria pigmentosa; but she did not show organomegalies or lymph node enlargement. Peripheral blood cell counts and routine biochemistry were within the normal range. Baseline tryptase was of 188g/L. The bone marrow (BM) study, including cytology, histology and immunophenotyping was consistent with ISM without other associated changes. The activating D816V c-kit mutation was detected in mast cells, CD34+ hematopoietic precursors, monocytes, eosinophils, and neutrophils. RESULTS: Since December 2004 the patient noted constitutional syndrome. She presented anemia, thrombocytopenia and leukocytosis with 20% of blasts. Serum tryptase was of 157g/L. A new BM study revealed, apart from mastocytosis, marked dysplasia and 22% blast cells. FISH analysis revealed trisomy 4 in 15% of the cells. Additionally, D816V c-kit mutation was also detected in blast cells, lymphocytes, erythroid precursors and cells from the oral mucosa. The patient was diagnosed as having an AML-M1 subtype of the FAB associated to a SM. Different chemotherapeutic regimens failed to induce a response and she died on June 2005. CONCLUSIONS: This is the first case described in which an AML appears in an ISM patient, carrying a germline D816V mutation, highlighting the interest of the study of c-kit mutations in mastocitosis in all hematopoietic lineages. Funding: Spanish Ministry of Health, ISCIII.G03/007. FIS 03/770
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