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978            Part VII:  Neutrophils, Eosinophils, Basophils, and Mast Cells                                                                                   Chapter 63:  Basophils, Mast Cells, and Related Disorders          979




               recommended to determine if there is evidence of an expanding mast   Mast Cell Sarcoma
               cell compartment.                                      This is an exceedingly rare tumor, characterized by nodules at various
                                                                      cutaneous and mucosal sites. 164,176
               Mast Cell Activation Syndrome
               The term mast cell activation syndrome (MCAS) is sometimes applied
               as a diagnosis for patients with episodic allergic-like signs and symp-  REFERENCES
               toms, including flushing, urticaria, diarrhea, and wheezing, involving
               two or more organ systems; and where an extensive medical evaluation     1.  Galli SJ, Dvorak AM, Dvorak HF: Basophils and mast cells: Morphologic insights into
                                                                         their biology, secretory patterns, and function. Prog Allergy 34:1–141, 1984.
               has failed to identify an etiology. 227,228  The assumption is that individuals     2.  Dvorak AM. Basophil and Mast Cell Degranulation and Recovery, vol. 4. Springer, New
               to whom this diagnosis is applied are having episodes caused by release   York, 1991.
               of mediators associated with hyperreactivity of mast cells that then acti-    3.  Valent P: Immunophenotypic characterization of human basophils and mast cells.
                                                                         Chem Immunol 61:34–48, 1995.
               vate spontaneously.                                      4.  Metz M, Brockow K, Metcalfe D, et al: Mast cells, basophils and mastocytosis, in Clin-
                   Diagnostic criteria have been proposed to separate this proposed   ical Immunology: Principles and Practice edited by Rich RR, Fleisher TA, Shearer WT,
               entity from other causes of such clinical findings. These criteria include   Schroeder HW Jr, Frew AJ, Weyand CM, p 285. Elsevier Saunders, Philadelphia, 2013.
               response to antimediator therapy and an elevation in a marker of mast     5.  Voehringer D: Protective and pathological roles of mast cells and basophils. Nat Rev
                                                                         Immunol 13:362–375, 2013.
                                                          227
               cell activation, such as serum tryptase, with an episode.  Primary     6.  Murakami M, Izumi H, Morimoto S, et al: Thalassemia intermedia complicated by
               (clonal) and other clinical disorders associated with mast cell activation,   hemochromatosis: Clinical and autopsy report of a case. Nihon Ketsueki Gakkai Zasshi
                                                                         32:336–352, 1969.
               as well as other conditions associated with vasoactive mediator release,     7.  Dvorak AM, Monahan RA, Osage JE, et al: Crohn’s disease: Transmission electron
               must be eliminated as possible causes of the clinical findings, including   microscopic studies. II. Immunologic inflammatory response. Alterations of mast cells,
               allergic diseases, mast cell activation associated with chronic inflamma-  basophils, eosinophils, and the microvasculature. Hum Pathol 11:606–619, 1980.
               tory or neoplastic disorders and chronic autoimmune urticaria. Once     8.  Juhlin L: Basophil leukocyte differential in blood and bone marrow. Acta Haematol
                                                                         29:89–95, 1963.
               the diagnostic criteria are met, therapy is symptomatic. Patients must     9.  Ducrest S, Meier F, Tschopp C, et al: Flow cytometric analysis of basophil counts in
               be followed regularly in the event that one of the diagnoses eliminated   human blood and inaccuracy of hematology analyzers. Allergy 60:1446–1450, 2005.
               during the initial evaluation reaches the level of diagnosis.    10.  Gilbert HS, Ornstein L: Basophil counting with a new staining method using Alcian
                                                                         blue. Blood 46:279–286, 1975.
                                                                        11.  Ishizaka T, Iwata M, Ishizaka K: Release of histamine and arachidonate from mouse
               Splenectomy                                               mast cells induced by glycosylation-enhancing factor and bradykinin.  J Immunol
               Splenectomy has been performed on patients with severe aggressive   134:1880–1887, 1985.
               mastocytosis in an attempt to improve their limiting cytopenias.      12.  Ganser A, Lindemann A, Seipelt G, et al: Effects of recombinant human interleukin-3
                                                                 229
                                                                         in aplastic anemia. Blood 76:1287–1292, 1990.
               Based on comparisons to historical controls, splenectomy increased     13.  Lantz CS, Boesiger J, Song CH, et al: Role for interleukin-3 in mast-cell and basophil
               survival by an average of 12 months. Patients who had undergone sple-  development and in immunity to parasites. Nature 392:90–93, 1998.
               nectomy appeared to be better able to tolerate chemotherapy. Splenec-    14.  Lantz CS, Min B, Tsai M, et al: IL-3 is required for increases in blood basophils in nem-
               tomy is of no value in the management of indolent mast cell disease.  atode infection in mice and can enhance IgE-dependent IL-4 production by basophils
                                                                         in vitro. Lab Invest 88:1134–1142, 2008.
                                                                        15.  Li L, Li Y, Reddel SW, et al: Identification of basophilic cells that express mast cell gran-
               COURSE AND PROGNOSIS                                      ule proteases in the peripheral blood of asthma, allergy, and drug-reactive patients. J
                                                                         Immunol 161:5079–5086, 1998.
               The prognosis of adult patients with mast cell disorders is related to the     16.  Kitamura Y: Heterogeneity of mast cells and phenotypic change between subpopula-
               disease category. The vast majority of patients who present with UP and   tions. Annu Rev Immunol 7:59–76, 1989.
               indolent systemic mastocytosis (ISM) have a chronic protracted course     17.  Galli SJ, Zsebo KM, Geissler EN: The kit ligand, stem cell factor. Adv Immunol 55:1–96,
                                                                         1994.
               that responds to symptomatic medical management. A normal life span     18.  Rodewald HR, Dessing M, Dvorak AM, et al: Identification of a committed precursor
               is expected. Few of these patients progress to more severe forms of the   for the mast cell lineage. Science 271:818–822, 1996.
               disease; some patients may even experience a diminution in the sever-    19.  Chen CC, Grimbaldeston MA, Tsai M, et al: Identification of mast cell progenitors in
                                                                         adult mice. Proc Natl Acad Sci U S A 102:11408–11413, 2005.
               ity of skin lesions in later years, while their marrow findings remain     20.  Franco CB, Chen CC, Drukker M, et al: Distinguishing mast cell and granulocyte dif-
               unchanged.  However, elevated serum lactate dehydrogenase levels, a   ferentiation at the single-cell level. Cell Stem Cell 6:361–368, 2010.
                        230
               late age of onset, and, in patients with SM-AHNMD, presence of a sig-    21.  Galli SJ, Borregaard N, Wynn TA: Phenotypic and functional plasticity of cells of innate
                                                                         immunity: Macrophages, mast cells and neutrophils. Nat Immunol 12:1035–1044, 2011.
               nificant hematologic abnormality (such as a myeloproliferative or mye-    22.  Galli SJ, Iemura A, Garlick DS, et al: Reversible expansion of primate mast cell popula-
               lodysplastic disorder or, more rarely, overt leukemia) are indicators of   tions in vivo by stem cell factor. J Clin Invest 91:148–152, 1993.
               a poor prognosis and shortened survival.  The prognosis for patients     23.  Costa JJ, Demetri GD, Harrist TJ, et al: Recombinant human stem cell factor (kit ligand)
                                             189
               with SM-AHNMD depends on the course of the associated hematologic   promotes human mast cell and melanocyte hyperplasia and functional activation in
                                                                         vivo. J Exp Med 183:2681–2686, 1996.
               disorder.                                                24.  Smith MA, Court EL, Smith JG: Stem cell factor: Laboratory and clinical aspects. Blood
                                                                         Rev 15:191–197, 2001.
               Mast Cell Leukemia                                       25.  Bischoff SC, Dahinden CA: C-kit ligand: A unique potentiator of mediator release by
                                                                         human lung mast cells. J Exp Med 175:237–244, 1992.
               MCL is relatively rare and prognosis is poor. 195,222  A major differential     26.  Columbo M, Horowitz EM, Botana LM, et al: The human recombinant c-kit recep-
               diagnosis to MCL is myelomastocytic leukemia (MML).  Patients with   tor ligand, rhSCF, induces mediator release from human cutaneous mast cells and
                                                       231
               MCL may have fever, anorexia, weight loss, fatigue, severe abdominal   enhances IgE-dependent mediator release from both skin mast cells and peripheral
                                                                         blood basophils. J Immunol 149:599–608, 1992.
               cramping, nausea, vomiting, diarrhea, flushing, hypotension, pruritus,     27.  Wershil BK, Tsai M, Geissler EN, et al: The rat c-kit ligand, stem cell factor, induces c-kit
               or bone pain. Peptic ulcer and gastrointestinal bleeding, hepatomeg-  receptor-dependent mouse mast cell activation in vivo. Evidence that signaling through
               aly, splenomegaly, and lymph node enlargement are frequent findings.   the c-kit receptor can induce expression of cellular function. J Exp Med 175:245–255,
                                                                         1992.
               Anemia is a constant feature, and thrombocytopenia is nearly always     28.  Finotto S, Mekori YA, Metcalfe DD: Glucocorticoids decrease tissue mast cell number
               present. The total leukocyte count varies from 10,000 to 150,000/μL (10   by reducing the production of the c-kit ligand, stem cell factor, by resident cells: In vitro
               to 150 × 10 /L), and mast cells compose 10 to 90 percent of leukocytes.   and in vivo evidence in murine systems. J Clin Invest 99:1721–1728, 1997.
                        9
               Marrow biopsy shows a striking increase in mast cells, sometimes up to     29.  Irani AA, Schechter NM, Craig SS, et al: Two types of human mast cells that have dis-
                                                                         tinct neutral protease compositions. Proc Natl Acad Sci U S A 83:4464–4468, 1986.
               90 percent of marrow cells, although the leukemic mast cells often are     30.  Galli SJ: New insights into “the riddle of the mast cells”: Microenvironmental regulation
               hypogranular or agranular. 195,231                        of mast cell development and phenotypic heterogeneity. Lab Invest 62:5–33, 1990.



          Kaushansky_chapter 63_p0965-0982.indd   978                                                                   9/18/15   11:01 PM
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