Seminars in Diagnostic Pathology
Volume 29, Issue 1 , Pages 19-30 , February 2012

Mastocytosis and related disorders

  • April Chiu, MD

      Affiliations

    • Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
    • Corresponding Author InformationAddress reprint requests and correspondence: April Chiu, MD, Department of Pathology, Brigham and Women's Hospital, Amory 3-201, 75 Francis Street, Boston, MA 02115
  • ,
  • Attilio Orazi, MD, FRCPath

      Affiliations

    • Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York

References 

  1. Horny HP , Metcalfe DD , Bennett JM . Mastocytosis . In:  Swerdlow SH ,  Campo E ,  Harris NL , et al. editor. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues . (ed 2). Lyon: IARC Press; 2008;p. 54–63
  2. Valent P , Horny HP , Escribano L , et al.  Diagnostic criteria and classification of mastocytosis: A consensus proposal . Leuk Res . 2001;25:603–625
  3. Lawrence JB , Friedman BS , Travis WD , et al.  Hematologic manifestations of systemic mast cell disease: A prospective study of laboratory and morphologic features and their relation to prognosis . Am J Med . 1991;91:612–624
  4. Travis WD , Li CY , Bergstralh EJ , et al.  Systemic mast cell disease (Analysis of 58 cases and literature review) . Medicine (Baltimore) . 1988;67:345–368
  5. Czarnetzki BM , Kolde G , Schoemann A , et al.  Bone marrow findings in adult patients with urticaria pigmentosa . J Am Acad Dermatol . 1988;18:45–51
  6. Wolff K , Komar M , Petzelbauer P . Clinical and histopathological aspects of cutaneous mastocytosis . Leuk Res . 2001;25:519–528
  7. Chiu A , Nanaji NM , Czader M , et al.  The stromal composition of mast cell aggregates in systemic mastocytosis . Mod Pathol . 2009;22:857–865
  8. Lim KH , Tefferi A , Lasho TL , et al.  Systemic mastocytosis in 342 consecutive adults: Survival studies and prognostic factors . Blood . 2009;113:5727–5736
  9. Pardanani A , Lim KH , Lasho TL , et al.  WHO subvariants of indolent mastocytosis: Clinical details and prognostic evaluation in 159 consecutive adults . Blood . 2010;115:150–151
  10. Ault P , Lynn A , Tam CS , et al.  Systemic mastocytosis in association with chronic lymphocytic leukemia: A rare diagnosis . Leuk Res . 2007;31:1755–1758
  11. Horny HP , Sotlar K , Sperr WR , et al.  Systemic mastocytosis with associated clonal haematological non-mast cell lineage diseases: A histopathological challenge . J Clin Pathol . 2004;57:604–608
  12. Stellmacher F , Sotlar K , Balleisen L , et al.  Bone marrow mastocytosis associated with IgM kappa plasma cell myeloma . Leuk Lymphoma . 2004;45:801–805
  13. Sotlar K , Colak S , Bache A , et al.  Variable presence of KITD816V in clonal haematological non-mast cell lineage diseases associated with systemic mastocytosis (SM-AHNMD) . J Pathol . 2010;220:586–595
  14. Pardanani A , Lim KH , Lasho TL , et al.  Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other myeloid malignancies . Blood . 2009;114:3769–3772
  15. Miranda RN , Esparza AR , Sambandam S , et al.  Systemic mast cell disease presenting with peripheral blood eosinophilia . Hum Pathol . 1994;25:727–730
  16. Travis WD , Li CY , Hoagland HC , et al.  Mast cell leukemia: Report of a case and review of the literature . Mayo Clin Proc . 1986;61:957–966
  17. Baghestanian M , Bankl H , Sillaber C , et al.  A case of malignant mastocytosis with circulating mast cell precursors: Biologic and phenotypic characterization of the malignant clone . Leukemia . 1996;10:159–166
  18. Torrey E , Simpson K , Wilbur S , et al.  Malignant mastocytosis with circulating mast cells . Am J Hematol . 1990;34:283–286
  19. Arredondo AR , Gotlib J , Shier L , et al.  Myelomastocytic leukemia versus mast cell leukemia versus systemic mastocytosis associated with acute myeloid leukemia: A diagnostic challenge . Am J Hematol . 2010;85:600–606
  20. Sotlar K , Cerny-Reiterer S , Petat-Dutter K , et al.  Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis . Mod Pathol . 2011;24:585–595
  21. Valent P , Sotlar K , Horny HP . Aberrant expression of CD30 in aggressive systemic mastocytosis and mast cell leukemia: A differential diagnosis to consider in aggressive hematopoietic CD30-positive neoplasms . Leuk Lymphoma . 2011;52:740–744
  22. Brcić L , Vuletić LB , Stepan J , et al.  Mast-cell sarcoma of the tibia . J Clin Pathol . 2007;60:424–425
  23. Chott A , Guenther P , Huebner A , et al.  Morphologic and immunophenotypic properties of neoplastic cells in a case of mast cell sarcoma . Am J Surg Pathol . 2003;27:1013–1019
  24. Horny HP , Parwaresch MR , Kaiserling E , et al.  Mast cell sarcoma of the larynx . J Clin Pathol . 1986;39:596–602
  25. Kojima M , Nakamura S , Itoh H , et al.  Mast cell sarcoma with tissue eosinophilia arising in the ascending colon . Mod Pathol . 1999;12:739–743
  26. Charrette EE , Mariano AV , Laforet EG . Solitary mast cell “tumor” of lung (Its place in the spectrum of mast cell disease) . Arch Intern Med . 1966;118:358–362
  27. Kudo H , Morinaga S , Shimosato Y , et al.  Solitary mast cell tumor of the lung . Cancer . 1988;61:2089–2094
  28. Mylanus EA , Wielinga EW , van de Nes JA . A solitary manifestation of mastocytosis in the head and neck . Eur Arch Otorhinolaryngol . 2000;257:270–272
  29. Sherwin RP , Kern WH , Jones JC . Solitary mast cell granuloma (histiocytoma) of the lung; a histopathologic, tissue culture and time-lapse cinematographic study . Cancer . 1965;18:634–641
  30. Li CY . Diagnosis of mastocytosis: Value of cytochemistry and immunohistochemistry . Leuk Res . 2001;25:537–541
  31. Escribano L , Orfao A , Díaz-Agustin B , et al.  Indolent systemic mast cell disease in adults: Immunophenotypic characterization of bone marrow mast cells and its diagnostic implications . Blood . 1998;91:2731–2736
  32. Horny HP , Sillaber C , Menke D , et al.  Diagnostic value of immunostaining for tryptase in patients with mastocytosis . Am J Surg Pathol . 1998;22:1132–1140
  33. Yang F , Tran TA , Carlson JA , et al.  Paraffin section immunophenotype of cutaneous and extracutaneous mast cell disease: Comparison to other hematopoietic neoplasms . Am J Surg Pathol . 2000;24:703–709
  34. Miettinen M , Lasota J . KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation . Appl Immunohistochem Mol Morphol . 2005;13:205–220
  35. Valent P , Spanblöchl E , Sperr WR , et al.  Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long-term culture . Blood . 1992;80:2237–2245
  36. Escribano L , Díaz-Agustín B , Núñez R , et al.  Abnormal expression of CD antigens in mastocytosis . Int Arch Allergy Immunol . 2002;127:127–132
  37. Jordan JH , Walchshofer S , Jurecka W , et al.  Immunohistochemical properties of bone marrow mast cells in systemic mastocytosis: Evidence for expression of CD2, CD117/Kit, and bcl-x(L) . Hum Pathol . 2001;32:545–552
  38. Krokowski M , Sotlar K , Krauth MT , et al.  Delineation of patterns of bone marrow mast cell infiltration in systemic mastocytosis: Value of CD25, correlation with subvariants of the disease, and separation from mast cell hyperplasia . Am J Clin Pathol . 2005;124:560–568
  39. Sotlar K , Horny HP , Simonitsch I , et al.  CD25 indicates the neoplastic phenotype of mast cells: A novel immunohistochemical marker for the diagnosis of systemic mastocytosis (SM) in routinely processed bone marrow biopsy specimens . Am J Surg Pathol . 2004;28:1319–1325
  40. Escribano L , Diaz-Agustin B , López A , et al.  Immunophenotypic analysis of mast cells in mastocytosis: When and how to do it (Proposals of the Spanish Network on Mastocytosis (REMA)) . Cytometry B Clin Cytom . 2004;58:1–8
  41. Valent P , Cerny-Reiterer S , Herrmann H , et al.  Phenotypic heterogeneity, novel diagnostic markers, and target expression profiles in normal and neoplastic human mast cells . Best Pract Res Clin Haematol . 2010;23:369–378
  42. Garcia-Montero AC , Jara-Acevedo M , Teodosio C , et al.  KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: A prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients . Blood . 2006;108:2366–2372
  43. Nagata H , Worobec AS , Oh CK , et al.  Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder . Proc Natl Acad Sci U S A . 1995;92:10560–10564
  44. Akin C , Kirshenbaum AS , Semere T , et al.  Analysis of the surface expression of c-kit and occurrence of the c-kit Asp816Val activating mutation in T cells, B cells, and myelomonocytic cells in patients with mastocytosis . Exp Hematol . 2000;28:140–147
  45. Sotlar K , Fridrich C , Mall A , et al.  Detection of c-kit point mutation Asp-816 → Val in microdissected pooled single mast cells and leukemic cells in a patient with systemic mastocytosis and concomitant chronic myelomonocytic leukemia . Leuk Res . 2002;26:979–984
  46. Sotlar K , Marafioti T , Griesser H , et al.  Detection of c-kit mutation Asp 816 to Val in microdissected bone marrow infiltrates in a case of systemic mastocytosis associated with chronic myelomonocytic leukaemia . Mol Pathol . 2000;53:188–193
  47. Bodemer C , Hermine O , Palmérini F , et al.  Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations . J Invest Dermatol . 2010;130:804–815
  48. Yanagihori H , Oyama N , Nakamura K , et al.   c-kit mutations in patients with childhood-onset mastocytosis and genotype–phenotype correlation . J Mol Diagn . 2005;7:252–257
  49. Longley BJ , Metcalfe DD , Tharp M , et al.  Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis . Proc Natl Acad Sci U S A . 1999;96:1609–1614
  50. Fletcher JA , Rubin BP . KIT mutations in GIST . Curr Opin Genet Dev . 2007;17:3–7
  51. Hodi FS , Friedlander P , Corless CL , et al.  Major response to imatinib mesylate in KIT-mutated melanoma . J Clin Oncol . 2008;26:2046–2051
  52. Kemmer K , Corless CL , Fletcher JA , et al.  KIT mutations are common in testicular seminomas . Am J Pathol . 2004;164:305–313
  53. Paschka P , Marcucci G , Ruppert AS , et al.  Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): A Cancer and Leukemia Group B Study . J Clin Oncol . 2006;24:3904–3911
  54. Escribano L , Akin C , Castells M , et al.  Mastocytosis: Current concepts in diagnosis and treatment . Ann Hematol . 2002;81:677–690
  55. Pardanani A , Akin C , Valent P . Pathogenesis, clinical features, and treatment advances in mastocytosis . Best Pract Res Clin Haematol . 2006;19:595–615
  56. Butterfield JH , Tefferi A , Kozuh GF . Successful treatment of systemic mastocytosis with high-dose interferon-alfa: Long-term follow-up of a case . Leuk Res . 2005;29:131–134
  57. Hauswirth AW , Simonitsch-Klupp I , Uffmann M , et al.  Response to therapy with interferon alpha-2b and prednisolone in aggressive systemic mastocytosis: Report of five cases and review of the literature . Leuk Res . 2004;28:249–257
  58. Kluin-Nelemans HC , Oldhoff JM , Van Doormaal JJ , et al.  Cladribine therapy for systemic mastocytosis . Blood . 2003;102:4270–4276
  59. Pardanani A , Hoffbrand AV , Butterfield JH , et al.   Treatment of systemic mast cell disease with 2-chlorodeoxyadenosine . Leuk Res . 2004;28:127–131
  60. Tefferi A , Li CY , Butterfield JH , et al.  Treatment of systemic mast-cell disease with cladribine . N Engl J Med . 2001;344:307–309
  61. Patnaik MM , Rindos M , Kouides PA , et al.  Systemic mastocytosis: A concise clinical and laboratory review . Arch Pathol Lab Med . 2007;131:784–791
  62. Valent P , Akin C , Sperr WR , et al.  Aggressive systemic mastocytosis and related mast cell disorders: Current treatment options and proposed response criteria . Leuk Res . 2003;27:635–641
  63. Akin C , Fumo G , Yavuz AS , et al.  A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib . Blood . 2004;103:3222–3225
  64. Zhang LY , Smith ML , Schultheis B , et al.  A novel K509I mutation of KIT identified in familial mastocytosis-in vitro and in vivo responsiveness to imatinib therapy . Leuk Res . 2006;30:373–378
  65. Purtill D , Cooney J , Sinniah R , et al.  Dasatinib therapy for systemic mastocytosis: Four cases . Eur J Haematol . 2008;80:456–458
  66. Verstovsek S , Tefferi A , Cortes J , et al.  Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis . Clin Cancer Res . 2008;14:3906–3915
  67. Gotlib J , DeAngelo DJ , George TI , et al.  KIT inhibitor midostaurin exhibits a high rate of clinically meaningful and durable responses in advanced systemic mastocytosis: Report of a fully accrued phase II trial . ASH Annu Meet Abstracts . 2010;116:316
  68. Sperr WR , Drach J , Hauswirth AW , et al.  Myelomastocytic leukemia: Evidence for the origin of mast cells from the leukemic clone and eradication by allogeneic stem cell transplantation . Clin Cancer Res . 2005;11:6787–6792
  69. Valent P , Samorapoompichit P , Sperr WR , et al.  Myelomastocytic leukemia: Myeloid neoplasm characterized by partial differentiation of mast cell-lineage cells . Hematol J . 2002;3:90–94
  70. Valent P , Sperr WR , Samorapoompichit P , et al.  Myelomastocytic overlap syndromes: Biology, criteria, and relationship to mastocytosis . Leuk Res . 2001;25:595–602
  71. Samorapoompichit P , Schernthaner GH , Worda C , et al.  Evaluation of neoplastic human mast cells by tryptase-immunoelectron microscopy . Histopathology . 2006;48:247–257
  72. Valent P , Spanblöchl E , Bankl HC , et al.  Kit ligand/mast cell growth factor-independent differentiation of mast cells in myelodysplasia and chronic myeloid leukemic blast crisis . Blood . 1994;84:4322–4332
  73. Wimazal F , Sperr WR , Horny HP , et al.  Hyperfibrinolysis in a case of myelodysplastic syndrome with leukemic spread of mast cells . Am J Hematol . 1999;61:66–77
  74. Care RS , Valk PJ , Goodeve AC , et al.  Incidence and prognosis of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias . Br J Haematol . 2003;121:775–777
  75. Goemans BF , Zwaan CM , Miller M , et al.  Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia . Leukemia . 2005;19:1536–1542
  76. Cairoli R , Beghini A , Morello E , et al.  Imatinib mesylate in the treatment of core binding factor leukemias with KIT mutations (A report of three cases) . Leuk Res . 2005;29:397–400
  77. Cammenga J , Horn S , Bergholz U , et al.  Extracellular KIT receptor mutants, commonly found in core binding factor AML, are constitutively active and respond to imatinib mesylate . Blood . 2005;106:3958–3961
  78. Schnittger S , Kohl TM , Haferlach T , et al.  KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival . Blood . 2006;107:1791–1799
  79. Fritsche-Polanz R , Fritz M , Huber A , et al.  High frequency of concomitant mastocytosis in patients with acute myeloid leukemia exhibiting the transforming KIT mutation D816V . Mol Oncol . 2010;4:335–346
  80. Kohl TM , Schnittger S , Ellwart JW , et al.  KIT exon 8 mutations associated with core-binding factor (CBF)-acute myeloid leukemia (AML) cause hyperactivation of the receptor in response to stem cell factor . Blood . 2005;105:3319–3321
  81. Beghini A , Peterlongo P , Ripamonti CB , et al.  C-kit mutations in core binding factor leukemias . Blood . 2000;95:726–727
  82. Sperr WR , Escribano L , Jordan JH , et al.  Morphologic properties of neoplastic mast cells: Delineation of stages of maturation and implication for cytological grading of mastocytosis . Leuk Res . 2001;25:529–536
  83. Horny HP , Sotlar K , Valent P . Differential diagnoses of systemic mastocytosis in routinely processed bone marrow biopsy specimens: A review . Pathobiology . 2010;77:169–180
  84. Sperr WR , Jordan JH , Baghestanian M , et al.  Expression of mast cell tryptase by myeloblasts in a group of patients with acute myeloid leukemia . Blood . 2001;98:2200–2209
  85. Maric I , Robyn J , Metcalfe DD , et al.  KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities . J Allergy Clin Immunol . 2007;120:680–687
  86. Pardanani A , Reeder T , Li CY , et al.   Eosinophils are derived from the neoplastic clone in patients with systemic mastocytosis and eosinophilia . Leuk Res . 2003;27:883–885
  87. Cools J , DeAngelo DJ , Gotlib J , et al.  A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome . N Engl J Med . 2003;348:1201–1214
  88. Florian S , Esterbauer H , Binder T , et al.  Systemic mastocytosis (SM) associated with chronic eosinophilic leukemia (SM-CEL): Detection of FIP1L1/PDGFRalpha, classification by WHO criteria, and response to therapy with imatinib . Leuk Res . 2006;30:1201–1205
  89. Böhm A , Födinger M , Wimazal F , et al.  Eosinophilia in systemic mastocytosis: Clinical and molecular correlates and prognostic significance . J Allergy Clin Immunol . 2007;120:192–199
  90. Pardanani A , Ketterling RP , Brockman SR , et al.  CHIC2 deletion, a surrogate for FIP1L1–PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy . Blood . 2003;102:3093–3096

 Competing interests: The authors declare no conflict of interest.

PII: S0740-2570(11)00087-6

doi: 10.1053/j.semdp.2011.06.002

Seminars in Diagnostic Pathology
Volume 29, Issue 1 , Pages 19-30 , February 2012