Special Edition 2011-2012 The Mastocytosis Chronicles TABLE OF CONTENTS T ABLE OF CONTENTS TMS Board of Directors.................02 By The Mastocytosis Society, Inc. TMS Board of Directors...............02 Mastocytosis Explained.............01-03 Minor criteria 1. In biopsy of bone marrow or other extracutaneous organ(s), more than 25% of the mast cells show abnormal morphology (that is, are atypical mast cell type I or are spindle-shaped) in multifocal lesions in histological examination. 2. Detection of a point mutation at codon 17th Annual Conference..............04 Medical Advisory Board.................04 Conference DVD Order Form ........05 AAAAI Task Force.........................05 Medical Advisory Board...............06 Pediatric Mastocytosis...............06-08 AAAAI Task Force Report.............07 Medical and Research Centers............................................09 TMS Research Committee News..07 Area Support Groups......................10 Pediatric Mastocytosis..................08 Printed Material..............................12 Area Support Groups....................10 Membership Renewal.....................13 Medical Centers............................12 2011 Conference Speakers..............14 European Centers.........................13 TMS Conference Order Form.........15 TMS Printed Material.....................14 mast cell photo provided by Dr. Mariana Castells ture as an abnormal accumulation of tissue mast cells in one or more organ systems. Broadly separated into two categories – cutaneous mastocytosis (CM) and systemic mastocytosis (SM), the disease occurs in both children and adults. CM is a benign skin disease representing the ing puberty and is not associated with systemic involvement, but because only a small subgroup of people with CM display a KIT mutation, not much is known about the factors that contribute to the accumulation of mast cells in the skin. Alternatively, most adult patients are diagnosed with SM. Skin involvement, typically urticaria pigmentosa, is common in adult patients and can provide an important clue to accurate diagnosis. In all SM categories, the common histological marker is the clustering of mast cells in visceral organs. CM is diagnosed by the presence of typical skin lesions and a positive skin biopsy demon- 1 ©2012 The Masocytosis Society All rights reserved All rights reserved preferred method of diagnosing SM is via bone tion (WHO) has established criteria for diagnosing SM, restated below: Major criterion (>15 in aggregate) in tryptase-stained biopsy sections of the bone marrow or of another extracutaneous organ. be found in bone marrow, blood or other internal organ. 3. KIT-positive Mast cells in bone marrow, blood, or other internal organs are found to express CD2 and/or CD25. 4. Serum total tryptase level persistently not be used if the patient has a clonal nonmast cell associated hematologic disorder. teria or three minor criteria constitute the diagnosis of systemic mastocytosis. Diagnostic following categories: Cutaneous mastocytosis Urticaria pigmentosa (UP) — also known as maculopapular cutaneous mastocytosis (DCM), and solitary mastocytoma. Indolent systemic mastocytosis temic mastocytosis and may have an enlarged - category. Mediator-related symptoms are comis low, usually less than 5 percent. Mast cells usually co-express CD2 and CD25 with KIT and contain the KIT mutation D816V. In most patients the serum tryptase concentration exceeds 20 ng/mL, but a normal level of tryptase does not rule out either mastocytosis or another mast cell activation disorder. Treatment usually includes mediator-targeting drugs, including antihistamines, but does not usually require cytoreductive agents, except for considering IFNIsolated Bone Marrow Mastocytosis (BMM) and Smouldering Systemic Mastocytosis (SSM) are subvariants of indolent SM. continued on page SE 3 BMM is characterized by absence of skin lesions, lack of multiorgan involvement, and low or normal serum tryptase level. BMM patients may or may not require treatment for mediator-related symptoms. In SSM two or three of the following, which indicate high burden of mast cells may be observed: 1. total tryptase levels greater than 200 ng/mL. 2. Hypercellular marrow with loss of fat cells, discrete signs of dysmyelopoiesis without substantial cytopenias or WHO criteria for an MDS or MPD. 3. Organomegaly: Palpable hepatomegaly, splenomegaly, or lymphadenopathy (on CT or ultrasound) greater than 2 cm without impaired organ function. Systemic mastocytosis with Associated clonal hematologic non-mast cell lineage disease (AHNMD ) liferative syndrome, acute myeloid leukemia, or non-Hodgkin’s lymskin lesions. Successful treatment of the hematologic disorder has not been shown to change or improve their systemic mastocytosis. Aggressive systemic mastocytosis systemic mastocytosis; and their bone marrow biopsy reveals abnormarrow aspirate smears showing less than 20% of the cells to be mast 1. 2. 3. 4. 5. 6. An abnormal blood count; An enlarged liver, and liver function is impaired; An enlarged spleen, and its function is abnormal; Malabsorption with weight loss is present and is due to mast cell tion; Bone involvement is seen with large areas of calcium loss and/or pathologic fractures; or impairment of organ function. Mast cell leukemia temic mastocytosis, and a bone marrow aspirate smear shows that 20% or more of the cells are mast cells or 10% or more mast cells are malignant features. Mast cell sarcoma Mast cell sarcoma is an extremely rare tumor. In three cases reported so far, the tumor has been located in the larynx, in the colon, and inside the skull. Prognosis is very poor. People with a mast cell lesions, and pathological examination of the tumor shows it to be highly malignant with an aggressive growth pattern. Extracutaneous mastocytoma have no skin lesions, and pathological examination of the lesion shows it to be made up of normal or nearly normal-appearing mast cells with a non-aggressive growth pattern. When aggressive disease or an associated hematological disorder is suspected, further evaluation of the patient may include: 1. cantly enlarged lymph nodes (greater than 2 cm in diameter); 2. 3. X-ray of the skeletal system, looking for osteoporosis, osteosclerosis, or areas where calcium has been completely lost from bone; CT scan or ultrasound of the abdomen, looking for enlarged 4. and Endoscopy and biopsy of the GI tract, looking for evidence of Other tests may be done, as indicated, if there is a suspected hematologic disorder or to evaluate the individual patient’s symptoms. By contrast, further testing should be kept to a minimum when the disSymptoms Patients with mastocytosis may or may not have constitutional symptoms, which include weight loss, pain, nausea, headache, proliferation of mast cells or involvement of distinct organs, such as the stomach and intestines, or bone or bone marrow. Constitutional symptoms also can result from high systemic levels of mast cell meing, and recurrent presence of the following symptoms, singly or in combination, may be recorded as part of the diagnosis of mastocytosis: syncope, hypotensive shock, nausea, vomiting, diarrhea with abdominal pain, uterine cramps or bleeding, shortness of breath, dysphonia, ECG alterations that can include ischemic ST-waves, arpain, urticaria, angioedema, severe headache, impaired level of consymptoms may appear in a compressed time frame (as in anaphylaxis) or as chronic conditions. It should be noted that the manifestation of anaphylaxis or similar symptoms among infants and preschoolers may be more difSM presented with recurring spells of apnea. Treatment Treatment of mastocytosis depends on the symptoms and Indolent mastocytosis may require no treatment, though most patients experience symptoms that require regular doses of H1 and H2 antihistamines. If symptoms are not adequately relieved, additional medications, including mast cell stabilizing drugs such as cromolyn sodium and/or ketotifen fumarate, a leukotriene inhibitor inhibitor (if needed to treat stomach hyperacidity) and where tolercialists agree that symptomatic treatment by blocking the formation or action of mast cell mediators is appropriate when the disease is indolent, and that cytoreductive treatment should be reserved for other categories of disease. Mastocytosis with an associated clonal, non-mast cell hematologic disorder should be treated as two separate disease entities: the mastocytosis should be treated appropriately for the disease, and the non-mast cell hematologic disorder should be treated appropriately for the type of disorder. Aggressive mastocytosis, mast cell sarcoma, and mast cell as well as with cytoreductive therapies. Several targeted therapeutic and progression of the mastocytosis may occur. continued on page SE 8 Special Edition 3 Research Committee Activities continued from page SE 5 survey results are also intended to be made freely available online, the articles must first be published before they can be posted on the TMS website. A research database for collecting and organizing scientific articles is also being developed for Research Committee use. This database was helpful when the Research Committee created a Needs Assessment document for use in the TMS applications for mast cell disorder courses for physician and nurse medical certification. These courses comprise the Physician and Allied Health Professional Continuing Medical Education Day to be held on October 27, 2011 in association with the TMS Conference in Boston. The research article database will also serve as a resource for the Research Committee in many other activities, including in their role as research advisors to the TMS Executive Board and in their review of research proposals for TMS fuding. The Research Committee welcomes the help of those with an interest in our activities. A background in medicine, public health or scientific research is particularly useful. If you are interested in becoming part of the TMS Research Committee, please send your resume or C.V. to [email protected]. Reference: Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal. In Press. 2011. SE 3 The Mastocytosis Chronicles 8