Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-848d4c4894-sjtt6 Total loading time: 0 Render date: 2024-06-17T11:39:08.412Z Has data issue: false hasContentIssue false

Chapter 12 - Systemic Mastocytosis

Published online by Cambridge University Press:  12 November 2020

Jon van der Walt ,
Attilio Orazi  and
Daniel A. Arber
By
Tracy George  and
Amy Jencks
Jon van der Walt
Affiliation:
St Thomas’ Hospital, London
Attilio Orazi
Affiliation:
Texas Tech University
Daniel A. Arber
Affiliation:
University of Chicago
Get access

Summary

Mastocytosis is a diverse group of rare diseases due to a clonal proliferation of neoplastic mast cells that can involve a wide variety of organ systems. The two main categories of mastocytosis are cutaneous mastocytosis (CM) showing only skin involvement, and systemic mastocytosis (SM) with at least one extracutaneous organ involved. In many cases of SM, the bone marrow (BM) shows varying degrees of infiltration. Most cases of CM develop during childhood, while adult patients in their fifth and sixth decades tend to present with SM [1]. The clinical course can vary from spontaneous regression in young children with CM to a highly aggressive course primarily seen in adult patients. Even within the category of SM, the presentation can range from indolent to aggressive, and it is thus divided into five subcategories as outlined in the most recent edition of the 2016 World Health Organization (WHO) classification of mastocytosis (Table 12.1) [2]. Of note, mastocytosis is now considered a distinct clinicopathologic entity that is separate from other myeloproliferative neoplasms.

Keywords

Mastocytosismast cellsindolentisolatedsmolderingsystemicaggressiveleukemiasarcoma
Type
Chapter
Information
Diagnostic Bone Marrow Haematopathology , pp. 181 - 199
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

George, TI, Sotlar, K, Valent, P, Horny, HP. Mastocytosis. In Jaffe, ES, Arber, DA, Campo, E, Harris, NL, Quintanilla-Martinez, L. (eds) Hematopathology. 2nd edn. Philadelphia: Elsevier; 2017, 911–30.Google Scholar
Horny, HP, Akin, C, Arber, D, Peterson, LC. Mastocytosis. In Swerdlow, SH, Campo, E, Harris, NL, et al. (eds) World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2017, 62–9.Google Scholar
Beaven, MA. Our perception of the mast cell from Paul Ehrlich to now. Eur J Immunol. 2009;39:11–25.CrossRefGoogle Scholar
Metcalfe, DD. Mast cells and mastocytosis. Blood. 2008;112:946–56.Google Scholar
Valent, P, Akin, C, Sperr, WR, et al. Mastocytosis: pathology, genetics, and current options for therapy. Leuk Lymphoma. 2005;46:35–48.Google Scholar
Yong, LC. The mast cell: origin, morphology, distribution, and function. Exp Toxicol Pathol. 1997;49:409–24.Google Scholar
Galli, SJ, Gribaldeston, M, Tsai, M. Immunomodulatory mast cells: negative, as well as positive, regulators of innate and acquired immunity. Nat Rev Immunol. 2008;8:478–86.Google Scholar
Rivera, J, Gilfillan, AM. Molecular regulation of mast cell activation. J Allergy Clin Immunol. 2006;117:1214–25.Google Scholar
Valent, P, Horny, HP, Escribano, L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001;25:603–25.Google Scholar
Lim, KH, Tefferi, A, Lasho, TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113:5727–36.Google Scholar
Valent, P, Sperr, WR, Akin, C. How I treat patients with advanced systemic mastocytosis. Blood. 2010;116:5812–17.Google Scholar
Horny, HP, Valent, P. Diagnosis of mastocytosis: general histopathological aspects, morphological criteria, and immunohistochemical findings. Leuk Res. 2001;25:543–51.Google Scholar
Valent, P, Akin, C, Metcalfe, DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017;129:1420–7.Google Scholar
Johnson, RC, Savage, NM, Chiang, T, et al. Hidden mastocytosis in acute myeloid leukemia with t(8;21)(q22;q22). Am J Clin Pathol. 2013;140:525–35.Google Scholar
Wang, SA, Hutchinson, L, Tang, G, et al. Systemic mastocytosis with associated clonal hematological non-mast cell lineage disease (SM-AHNMD): clinical significance and comparison of chromosomal abnormalities in SM and AHNMD components. Am J Hematol. 2013;88:219–24.Google Scholar
Jawhar, M, Schwaab, J, Schnittger, S, et al. Molecular profiling of myeloid progenitor cells in multi-mutated advanced systemic mastocytosis identifies KIT D618V as a distinct and late event. Leukemia. 2015;29:1115–22.Google Scholar
Ustun, C, Gotlib, J, Popat, U, et al. Consensus opinion on allogeneic hematopoietic cell transplantation in advanced systemic mastocytosis. Biol Blood Marrow Transplant. 2016;22:1348–56.Google Scholar
Georgin-Lavialle, S, Lhermitte, L, Dubreuil, P, et al. Mast cell leukemia. Blood. 2013;121:1285–95.CrossRefGoogle ScholarPubMed
Sperr, WR, Escribano, L, Jordan, J-H, et al. Morphologic properties of neoplastic mast cells: delineation of stages of maturation and implication for cytological grading of mastocytosis. Leuk Res. 2001;25:529–36.CrossRefGoogle ScholarPubMed
Jawhar, M, Schwaab, J, Meggendorfer, M, et al. The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm. Haematologica. 2017;102:1035–43.CrossRefGoogle ScholarPubMed
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;85:600–6.Google Scholar
Valent, P, Soltar, K, Sperr, WR, et al. Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal. Ann Oncol. 2014;25:1691–700.Google Scholar
Ryan, RJ, Akin, C, Castells, M, et al. Mast cell sarcoma: a rare and potentially under-recognized diagnostic entity with specific therapeutic implications. Mod Pathol. 2013;26:533–43.CrossRefGoogle ScholarPubMed
Monnier, J, Georgin-Lavialle, S, Canioni, D, et al. Mast cell sarcoma: new cases and literature review. Oncotarget. 2016;7:66,299–309.Google Scholar
Horny, HP, Parwaresch, MR, Kaiserling, E, et al. Mast cell sarcoma of the larynx. J Clin Pathol. 1986;39:596–602.Google Scholar
Kojima, M, Nakamura, S, Itoh, H, et al. Mast cell sarcoma with tissue eosinophilia arising in the ascending colon. Mod Pathol. 1999;12:739–43.Google ScholarPubMed
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;27:1013–19.Google Scholar
Brcic, L, Vuletic, LB, Stepan, J, et al. Mast-cell sarcoma of the tibia. J Clin Pathol. 2007;60:424–5.Google Scholar
Bugalia, A, Abraham, A, Balasubramanian, P, Srivastava, A, Nair, S. Mast cell sarcoma of the small intestine: a case report. J Clin Pathol. 2011;64:1035–7.Google Scholar
Ma, HB, Xu, X, Liu, WP, et al. Successful treatment of mast cell sarcoma of the uterus with imatinib. Int J Hematol. 2011;94:491–4.CrossRefGoogle ScholarPubMed
Auquit-Auckbur, I, Lazar, C, Deneuve, S, et al. Malignant transformation of mastocytoma developed on skin mastocytosis into cutaneous mast cell sarcoma. Am J Surg Pathol. 2012;36:779–82.Google Scholar
Akin, C, Metcalfe, DD. The biology of KIT in disease and the application of pharmacogenetics. J Allergy Clin Immunol. 2004;114:13–19.Google Scholar
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. Cytometry B: Clin Cytom. 2004;48:1–8.Google Scholar
Chisholm, KM, Merker, JD, Gotlib, JR, et al. Mast cells in systemic mastocytosis have distinctly brighter CD45 expression by flow cytometry. Am J Clin Pathol. 2015;143: 527–34.Google Scholar
Escribano, L, Orfao, A, Villarrubia, J, et al. Immunophenotypic characterization of human bone marrow mast cells. A flow cytometric study of normal and pathological bone marrow samples. Anal Cell Pathol.1998;16:151–9.Google Scholar
Escribano, L, Díaz-Agustín, B, Bellas, C, et al. Utility of flow cytometric analysis of mast cells in the diagnosis and classification of adult mastocytosis. Leuk Res. 2001;25:563–70.Google Scholar
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;52:740–4.CrossRefGoogle ScholarPubMed
Morgado, JM, Perbellini, O, Johnson, RC, et al. CD30 expression by bone marrow mast cells from different diagnostic variants of systemic mastocytosis. Histopathol. 2013;63:780–7.CrossRefGoogle ScholarPubMed
Horny, HP, Sotlar, K, Valent, P. Differential diagnoses of systemic mastocytosis in routinely processed bone marrow biopsy specimens: a review. Pathobiology. 2010;77:169–80.Google Scholar
Han, X, Jorgensen, JL, Brahmandam, A, et al. Immunophenotypic study of basophils by multiparameter flow cytometry. Arch Pathol Lab Med. 2008;132:813–19.Google Scholar
Agis, H, Krauth, MT, Mosberger, I, Mullauer, L, et al. Enumeration and immunohistochemical characterization of bone marrow basophils in myeloproliferative disorders using the basophil specific monoclonal antibody 2D7. J Clin Pathol. 2006;59:396–402.CrossRefGoogle ScholarPubMed
Agis, H, Krauth, MT, Bohm, A, et al. Identification of basogranulin (BB1) as a novel immunohistochemical marker of basophils in normal bone marrow and patients with myeloproliferative disorders. Am J Clin Pathol. 2006;125:273–81.Google Scholar
Idoate, MA, Echeveste, J, Gil, P, Sanz, ML, Ferrer, M. Expression of the basophil-specific antibodies 2D7 and BB1 in patients with cutaneous mastocytosis. J Investig Allergol Clin Immunol. 2013;23:392–7.Google Scholar
Samorapoompichit, P, Kiener, HP, Schernthaner, G-H, et al. Detection of tryptase in cytoplasmic granules of basophils in patients with chronic myeloid leukemia and other myeloid neoplasms. Blood. 2001;98:2580–3.Google Scholar
Doyle, LA, Sepehr, GJ, Hamilton, MJ, et al. A clinicopathologic study of 24 cases of systemic mastocytosis involving the gastrointestinal tract and assessment of mucosal mast cell density in irritable bowel syndrome and asymptomatic patients. Am J Surg Pathol. 2014;38:832–43.Google Scholar
Horny, HP, Sotlar, K, Stellmacher, F, et al. The tryptase positive compact round cell infiltrate of the bone marrow (TROCI-BM): a novel histopathological finding requiring the application of lineage specific markers. J Clin Pathol. 2006;59:298–302.Google Scholar
Akin, C, Escribano, L, Nuñez, R, et al. Well-differentiated systemic mastocytosis: a new disease variant with mature mast cell phenotype and lack of codon 816 c-Kit mutations. J Allergy Clin Immunol. 2004;113:S327.Google Scholar
Álvarez-Twose, I, Jara-Acevedo, M, Mário Morgado, J, et al. Clinical, immunophenotypic, and molecular characteristics of well-differentiated systemic mastocytosis. J Allergy Clin Immunol. 2015;137:168–78.Google Scholar
Prokocimer, M, Polliack, A. Increased bone marrow mast cells in preleukemic syndromes, acute leukemia, and lymphoproliferative disorders. Am J Clin Pathol. 1981;75:34–8.Google Scholar
Care, RS, Valk, PJM, Goodeve, AC, et al. Incidence and prognosis of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukemias. Br J Haematol. 2003;121:775–7.Google Scholar
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;24:3904–11.Google Scholar
Schnittger, S, Kohl, T, Haderlach, T, et al. KIT-D618V mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood. 2006;107:1791–9.Google Scholar
Lyons, JJ. Hereditary alpha tryptasemia: Genotyping and associated clinical features. Immunol Allergy Clin North Am. 2018;38:483–95.Google Scholar
Carter, MC, Bai, Y, Ruiz-Esteves, KN, et al. Detection of KIT D816V in peripheral blood of children with manifestations of cutaneous mastocytosis suggests systemic disease. Br J Haematol. 2018;183:775–82.CrossRefGoogle ScholarPubMed
Nagata, H, Worobec, AS, Oh, CK, et al. Identification of a point mutation in the catalytic domain of the proto-oncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci USA. 1995;92:10,560–4.Google Scholar
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;108:2366–72.Google Scholar
Kristensen, T, Vestergaard, H, Bindslev-Jensen, C, et al. Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis. Am J Hematol. 2014;89:493–8.Google Scholar
Greiner, G, Gurbisz, M, Ratzinger, F, et al. Digital PCR: a sensitive and precise method for KIT D816V quantification in mastocytosis. Clin Chem. 2018;64:547–55.Google Scholar
Gotlib, J, Gerds, AT, Bose, P, et al. Systemic mastocytosis, version 2.2019, NCCN Clinical Practice Guidelines in oncology. J Natl Compr Canc Netw. 2018;16:1500–37.Google Scholar
Reiter, A, George, TI, Gotlib, J. New developments in diagnosis, prognostication, and treatment of advanced systemic mastocytosis. Blood. 2020;135:1365–76.Google Scholar
Jawhar, M, Schwaab, J, Schnittger, S, et al. Additional mutations in SRSF2, ASXL1, and/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis. Leukemia. 2016;30:136–43.Google Scholar
Jawhar, M, Schwaab, J, Alvarez-Twose, I, et al. MARS: mutation-adjusted risk score for advanced systemic mastocytosis. J Clin Oncol. 2019;37:2846–56.Google Scholar
Pardanani, A, Shah, S, Mannelli, F, et al. Mayo alliance prognostic system for mastocytosis: clinical and hybrid clinical-molecular models. Blood Adv. 2018;2:2964–72.Google Scholar
Sperr, WR, Kundi, M, Alvarez-Twose, I, et al. International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study. Lancet Haematol. 2019;6:e638–49.Google Scholar
Gotlib, J, Kluin-Nelemans, HC, George, TI, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis. New Engl J Med. 2016;374:2530–41.Google Scholar
Radia, D, Deininger, M, Gotlib, J, et al. Avapritinib, a potent and selective inhibitor of KIT D816V, induces complete and durable responses in patients (pts) with advanced systemic mastocytosis (AdvSM). Presented at the 24th European Hematology Association Congress. 15 June 2019. Amsterdam, the Netherlands.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×