Mast cell leukemia overview: Difference between revisions
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{{CMG}}; {{AE}}{{NM}} | {{CMG}}; {{AE}}{{NM}} | ||
==Overview== | ==Overview== | ||
'''Mast cell leukemia''' was first described in 1906 by G. Joachim.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Mast cell leukemia may be classified into two categories based on [[prognosis]].<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Based on the duration of symptoms, mast cell leukemia may be classified into either acute or chronic.<ref name="SaviniRondoni2015">{{cite journal|last1=Savini|first1=P.|last2=Rondoni|first2=M.|last3=Poletti|first3=G.|last4=Lanzi|first4=A.|last5=Quercia|first5=O.|last6=Soverini|first6=S.|last7=De Benedittis|first7=C.|last8=Musardo|first8=G.|last9=Martinelli|first9=G.|last10=Stefanini|first10=G. F.|title=Serum Total Tryptase Level Confirms Itself as a More Reliable Marker of Mast Cells Burden in Mast Cell Leukaemia (Aleukaemic Variant)|journal=Case Reports in Hematology|volume=2015|year=2015|pages=1–4|issn=2090-6560|doi=10.1155/2015/737302}}</ref> Genes involved in the pathogenesis of mast cell leukemia include ''KIT'' D816V and non-''KIT'' D816V.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="KristensenVestergaard2011">{{cite journal|last1=Kristensen|first1=Thomas|last2=Vestergaard|first2=Hanne|last3=Møller|first3=Michael Boe|title=Improved Detection of the KIT D816V Mutation in Patients with Systemic Mastocytosis Using a Quantitative and Highly Sensitive Real-Time qPCR Assay|journal=The Journal of Molecular Diagnostics|volume=13|issue=2|year=2011|pages=180–188|issn=15251578|doi=10.1016/j.jmoldx.2010.10.004}}</ref> There are no characteristic findings of mast cell leukemia on gross pathology.<ref name=Grosspathology>Horvai AE, Link TM. Bone and Soft Tissue Pathology. Elsevier Health Sciences (2012). http://books.google.com?id=p2DV6VWdXx8C. Accessed on November 30, 2015.</ref> On microscopic histopathological analysis, multifocal sheets and clusters of mast cells in bone marrow sections are findings of mast cell leukemia.<ref name="ValentSotlar2014">{{cite journal|last1=Valent|first1=P.|last2=Sotlar|first2=K.|last3=Sperr|first3=W. R.|last4=Escribano|first4=L.|last5=Yavuz|first5=S.|last6=Reiter|first6=A.|last7=George|first7=T. I.|last8=Kluin-Nelemans|first8=H. C.|last9=Hermine|first9=O.|last10=Butterfield|first10=J. H.|last11=Hagglund|first11=H.|last12=Ustun|first12=C.|last13=Hornick|first13=J. L.|last14=Triggiani|first14=M.|last15=Radia|first15=D.|last16=Akin|first16=C.|last17=Hartmann|first17=K.|last18=Gotlib|first18=J.|last19=Schwartz|first19=L. B.|last20=Verstovsek|first20=S.|last21=Orfao|first21=A.|last22=Metcalfe|first22=D. D.|last23=Arock|first23=M.|last24=Horny|first24=H.- P.|title=Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal|journal=Annals of Oncology|volume=25|issue=9|year=2014|pages=1691–1700|issn=0923-7534|doi=10.1093/annonc/mdu047}}</ref> Common causes of mast cell leukemia include [[mutation|genetic mutations]]. Common genetic mutations involved in the development of mast cell leukemia can be found [[Mast cell leukemia pathophysiology|'''here''']].<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="KristensenVestergaard2011">{{cite journal|last1=Kristensen|first1=Thomas|last2=Vestergaard|first2=Hanne|last3=Møller|first3=Michael Boe|title=Improved Detection of the KIT D816V Mutation in Patients with Systemic Mastocytosis Using a Quantitative and Highly Sensitive Real-Time qPCR Assay|journal=The Journal of Molecular Diagnostics|volume=13|issue=2|year=2011|pages=180–188|issn=15251578|doi=10.1016/j.jmoldx.2010.10.004}}</ref> Mast cell leukemia must be differentiated from other diseases such as [[systemic mastocytosis]], myelomastocytic leukemia, [[hairy cell leukemia]], reactive mast cell hyperplasia, and peripheral T-cell leukemia.<ref name="ValentSotlar2014">{{cite journal|last1=Valent|first1=P.|last2=Sotlar|first2=K.|last3=Sperr|first3=W. R.|last4=Escribano|first4=L.|last5=Yavuz|first5=S.|last6=Reiter|first6=A.|last7=George|first7=T. I.|last8=Kluin-Nelemans|first8=H. C.|last9=Hermine|first9=O.|last10=Butterfield|first10=J. H.|last11=Hagglund|first11=H.|last12=Ustun|first12=C.|last13=Hornick|first13=J. L.|last14=Triggiani|first14=M.|last15=Radia|first15=D.|last16=Akin|first16=C.|last17=Hartmann|first17=K.|last18=Gotlib|first18=J.|last19=Schwartz|first19=L. B.|last20=Verstovsek|first20=S.|last21=Orfao|first21=A.|last22=Metcalfe|first22=D. D.|last23=Arock|first23=M.|last24=Horny|first24=H.- P.|title=Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal|journal=Annals of Oncology|volume=25|issue=9|year=2014|pages=1691–1700|issn=0923-7534|doi=10.1093/annonc/mdu047}}</ref><ref name=Grosspathology>Horvai AE, Link TM. Bone and Soft Tissue Pathology. Elsevier Health Sciences (2012). http://books.google.com?id=p2DV6VWdXx8C. Accessed on November 30, 2015.</ref> The [[incidence]] of mast cell leukemia increases with age; the median age at diagnosis is 52 years.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Mast cell leukemia commonly affects individuals between 5 to 76 years of age.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Females are more commonly affected with mast cell leukemia than males. The female to male ratio is 1.5 to 1.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Mast cell leukemia usually affects individuals of the Caucasian race.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref>Risk factor for mast cell leukemia is [[systemic mastocytosis]], a premalignant condition. Factors involved in malignant transformation of systemic mastocytosis into mast cell leukemia include [[Age|advanced age]], [[Weight loss|history of weight loss]], [[anemia]], [[thrombocytopenia]], [[hypoalbuminemia]], and an excess of bone marrow blasts.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> According to the United States Preventive Services Task Force, there is insufficient evidence to recommend routine screening for mast cell leukemia.<ref name=USPSTF>Mast cell leukemia. USPSTF. http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=mast+cell+leukemia</ref> If left untreated, patients with mast cell leukemia may progress to develop weight loss, ascites, and bone abnormalities.<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> Common complications of mast cell leukemia include [[hepatosplenomegaly]], [[lymphadenopathy]], and [[osteoporosis]].<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> Prognosis is generally poor, and the median survival time is less than six months.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Symptoms of mast cell leukemia include [[fever]], [[weight loss]], [[weakness]], [[flushes]], and [[pruritis]].<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> Common physical examination findings of mast cell leukemia include [[hepatosplenomegaly]], [[lymphadenopathy]], bone abnormalities, and [[ascites]].<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> Laboratory findings consistent with the diagnosis of mast cell leukemia include abnormal [[complete blood count]], [[biochemistry]], and [[immunohistochemistry]].<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name=wikipedia>Biochemistry of mast cell leukemia. Wikipedia (2015). https://en.wikipedia.org/wiki/Mast_cell_leukemia. Accessed on December 1, 2015</ref> The mainstay of therapy for symptomatic mast cell leukemia patients is immunochemotherapy.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> | '''Mast cell leukemia''' was first described in 1906 by G. Joachim.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Mast cell leukemia may be classified into two categories based on [[prognosis]].<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Based on the duration of symptoms, mast cell leukemia may be classified into either acute or chronic.<ref name="SaviniRondoni2015">{{cite journal|last1=Savini|first1=P.|last2=Rondoni|first2=M.|last3=Poletti|first3=G.|last4=Lanzi|first4=A.|last5=Quercia|first5=O.|last6=Soverini|first6=S.|last7=De Benedittis|first7=C.|last8=Musardo|first8=G.|last9=Martinelli|first9=G.|last10=Stefanini|first10=G. F.|title=Serum Total Tryptase Level Confirms Itself as a More Reliable Marker of Mast Cells Burden in Mast Cell Leukaemia (Aleukaemic Variant)|journal=Case Reports in Hematology|volume=2015|year=2015|pages=1–4|issn=2090-6560|doi=10.1155/2015/737302}}</ref> Genes involved in the pathogenesis of mast cell leukemia include ''KIT'' D816V and non-''KIT'' D816V.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="KristensenVestergaard2011">{{cite journal|last1=Kristensen|first1=Thomas|last2=Vestergaard|first2=Hanne|last3=Møller|first3=Michael Boe|title=Improved Detection of the KIT D816V Mutation in Patients with Systemic Mastocytosis Using a Quantitative and Highly Sensitive Real-Time qPCR Assay|journal=The Journal of Molecular Diagnostics|volume=13|issue=2|year=2011|pages=180–188|issn=15251578|doi=10.1016/j.jmoldx.2010.10.004}}</ref> There are no characteristic findings of mast cell leukemia on gross pathology.<ref name=Grosspathology>Horvai AE, Link TM. Bone and Soft Tissue Pathology. Elsevier Health Sciences (2012). http://books.google.com?id=p2DV6VWdXx8C. Accessed on November 30, 2015.</ref> On microscopic histopathological analysis, multifocal sheets and clusters of mast cells in bone marrow sections are findings of mast cell leukemia.<ref name="ValentSotlar2014">{{cite journal|last1=Valent|first1=P.|last2=Sotlar|first2=K.|last3=Sperr|first3=W. R.|last4=Escribano|first4=L.|last5=Yavuz|first5=S.|last6=Reiter|first6=A.|last7=George|first7=T. I.|last8=Kluin-Nelemans|first8=H. C.|last9=Hermine|first9=O.|last10=Butterfield|first10=J. H.|last11=Hagglund|first11=H.|last12=Ustun|first12=C.|last13=Hornick|first13=J. L.|last14=Triggiani|first14=M.|last15=Radia|first15=D.|last16=Akin|first16=C.|last17=Hartmann|first17=K.|last18=Gotlib|first18=J.|last19=Schwartz|first19=L. B.|last20=Verstovsek|first20=S.|last21=Orfao|first21=A.|last22=Metcalfe|first22=D. D.|last23=Arock|first23=M.|last24=Horny|first24=H.- P.|title=Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal|journal=Annals of Oncology|volume=25|issue=9|year=2014|pages=1691–1700|issn=0923-7534|doi=10.1093/annonc/mdu047}}</ref> Common causes of mast cell leukemia include [[mutation|genetic mutations]]. Common genetic mutations involved in the development of mast cell leukemia can be found [[Mast cell leukemia pathophysiology|'''here''']].<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="KristensenVestergaard2011">{{cite journal|last1=Kristensen|first1=Thomas|last2=Vestergaard|first2=Hanne|last3=Møller|first3=Michael Boe|title=Improved Detection of the KIT D816V Mutation in Patients with Systemic Mastocytosis Using a Quantitative and Highly Sensitive Real-Time qPCR Assay|journal=The Journal of Molecular Diagnostics|volume=13|issue=2|year=2011|pages=180–188|issn=15251578|doi=10.1016/j.jmoldx.2010.10.004}}</ref> Mast cell leukemia must be differentiated from other diseases such as [[systemic mastocytosis]], myelomastocytic leukemia, [[hairy cell leukemia]], reactive mast cell hyperplasia, and peripheral T-cell leukemia.<ref name="ValentSotlar2014">{{cite journal|last1=Valent|first1=P.|last2=Sotlar|first2=K.|last3=Sperr|first3=W. R.|last4=Escribano|first4=L.|last5=Yavuz|first5=S.|last6=Reiter|first6=A.|last7=George|first7=T. I.|last8=Kluin-Nelemans|first8=H. C.|last9=Hermine|first9=O.|last10=Butterfield|first10=J. H.|last11=Hagglund|first11=H.|last12=Ustun|first12=C.|last13=Hornick|first13=J. L.|last14=Triggiani|first14=M.|last15=Radia|first15=D.|last16=Akin|first16=C.|last17=Hartmann|first17=K.|last18=Gotlib|first18=J.|last19=Schwartz|first19=L. B.|last20=Verstovsek|first20=S.|last21=Orfao|first21=A.|last22=Metcalfe|first22=D. D.|last23=Arock|first23=M.|last24=Horny|first24=H.- P.|title=Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal|journal=Annals of Oncology|volume=25|issue=9|year=2014|pages=1691–1700|issn=0923-7534|doi=10.1093/annonc/mdu047}}</ref><ref name=Grosspathology>Horvai AE, Link TM. Bone and Soft Tissue Pathology. Elsevier Health Sciences (2012). http://books.google.com?id=p2DV6VWdXx8C. Accessed on November 30, 2015.</ref> The [[incidence]] of mast cell leukemia increases with age; the median age at diagnosis is 52 years.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Mast cell leukemia commonly affects individuals between 5 to 76 years of age.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Females are more commonly affected with mast cell leukemia than males. The female to male ratio is 1.5 to 1.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Mast cell leukemia usually affects individuals of the Caucasian race.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Risk factor for mast cell leukemia is [[systemic mastocytosis]], a premalignant condition. Factors involved in malignant transformation of systemic mastocytosis into mast cell leukemia include [[Age|advanced age]], [[Weight loss|history of weight loss]], [[anemia]], [[thrombocytopenia]], [[hypoalbuminemia]], and an excess of bone marrow blasts.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> According to the United States Preventive Services Task Force, there is insufficient evidence to recommend routine screening for mast cell leukemia.<ref name=USPSTF>Mast cell leukemia. USPSTF. http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=mast+cell+leukemia</ref> If left untreated, patients with mast cell leukemia may progress to develop weight loss, ascites, and bone abnormalities.<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> Common complications of mast cell leukemia include [[hepatosplenomegaly]], [[lymphadenopathy]], and [[osteoporosis]].<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> Prognosis is generally poor, and the median survival time is less than six months.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> Symptoms of mast cell leukemia include [[fever]], [[weight loss]], [[weakness]], [[flushes]], and [[pruritis]].<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> Common physical examination findings of mast cell leukemia include [[hepatosplenomegaly]], [[lymphadenopathy]], bone abnormalities, and [[ascites]].<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> Laboratory findings consistent with the diagnosis of mast cell leukemia include abnormal [[complete blood count]], [[biochemistry]], and [[immunohistochemistry]].<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name=wikipedia>Biochemistry of mast cell leukemia. Wikipedia (2015). https://en.wikipedia.org/wiki/Mast_cell_leukemia. Accessed on December 1, 2015</ref> The mainstay of therapy for symptomatic mast cell leukemia patients is immunochemotherapy.<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> | ||
==Historical Perspective== | ==Historical Perspective== | ||
Revision as of 15:48, 23 December 2015
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Mast cell leukemia Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Mast cell leukemia overview On the Web |
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Risk calculators and risk factors for Mast cell leukemia overview |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nawal Muazam M.D.[2]
Overview
Mast cell leukemia was first described in 1906 by G. Joachim.[1] Mast cell leukemia may be classified into two categories based on prognosis.[1] Based on the duration of symptoms, mast cell leukemia may be classified into either acute or chronic.[2] Genes involved in the pathogenesis of mast cell leukemia include KIT D816V and non-KIT D816V.[1][3][4] There are no characteristic findings of mast cell leukemia on gross pathology.[5] On microscopic histopathological analysis, multifocal sheets and clusters of mast cells in bone marrow sections are findings of mast cell leukemia.[6] Common causes of mast cell leukemia include genetic mutations. Common genetic mutations involved in the development of mast cell leukemia can be found here.[1][3][4] Mast cell leukemia must be differentiated from other diseases such as systemic mastocytosis, myelomastocytic leukemia, hairy cell leukemia, reactive mast cell hyperplasia, and peripheral T-cell leukemia.[6][5] The incidence of mast cell leukemia increases with age; the median age at diagnosis is 52 years.[1] Mast cell leukemia commonly affects individuals between 5 to 76 years of age.[1] Females are more commonly affected with mast cell leukemia than males. The female to male ratio is 1.5 to 1.[1] Mast cell leukemia usually affects individuals of the Caucasian race.[1] Risk factor for mast cell leukemia is systemic mastocytosis, a premalignant condition. Factors involved in malignant transformation of systemic mastocytosis into mast cell leukemia include advanced age, history of weight loss, anemia, thrombocytopenia, hypoalbuminemia, and an excess of bone marrow blasts.[1] According to the United States Preventive Services Task Force, there is insufficient evidence to recommend routine screening for mast cell leukemia.[7] If left untreated, patients with mast cell leukemia may progress to develop weight loss, ascites, and bone abnormalities.[3] Common complications of mast cell leukemia include hepatosplenomegaly, lymphadenopathy, and osteoporosis.[3] Prognosis is generally poor, and the median survival time is less than six months.[1] Symptoms of mast cell leukemia include fever, weight loss, weakness, flushes, and pruritis.[3] Common physical examination findings of mast cell leukemia include hepatosplenomegaly, lymphadenopathy, bone abnormalities, and ascites.[1][3] Laboratory findings consistent with the diagnosis of mast cell leukemia include abnormal complete blood count, biochemistry, and immunohistochemistry.[1][3][8] The mainstay of therapy for symptomatic mast cell leukemia patients is immunochemotherapy.[1][3]
Historical Perspective
Mast cell leukemia was first described in 1906 by G. Joachim.[1]
Classification
Mast cell leukemia may be classified into two categories based on prognosis.[1] Based on the duration of symptoms, mast cell leukemia may be classified into either acute or chronic.[2]
Pathophysiology
Genes involved in the pathogenesis of mast cell leukemia include KIT D816V and non-KIT D816V.[1][3][4] There are no characteristic findings of mast cell leukemia on gross pathology.[5] On microscopic histopathological analysis, multifocal sheets and clusters of mast cells in bone marrow sections are findings of mast cell leukemia.[6]
Causes
Common causes of mast cell leukemia include genetic mutations. Common genetic mutations involved in the development of mast cell leukemia can be found here.[1][3][4]
Differentiating Mast cell leukemia from other Diseases
Mast cell leukemia must be differentiated from other diseases such as systemic mastocytosis, myelomastocytic leukemia, hairy cell leukemia, reactive mast cell hyperplasia, and peripheral T-cell leukemia.[6][5]
Epidemiology and Demographics
The incidence of mast cell leukemia increases with age; the median age at diagnosis is 52 years.[1] Mast cell leukemia commonly affects individuals between 5 to 76 years of age.[1] Females are more commonly affected with mast cell leukemia than males. The female to male ratio is 1.50 to 1.[1] Mast cell leukemia usually affects individuals of the Caucasian race.[1]
Risk Factors
Risk factor for mast cell leukemia is systemic mastocytosis, a premalignant condition. Factors involved in malignant transformation of systemic mastocytosis into mast cell leukemia include advanced age, history of weight loss, anemia, thrombocytopenia, hypoalbuminemia, and an excess of bone marrow blasts.[1]
Screening
According to the United States Preventive Services Task Force, there is insufficient evidence to recommend routine screening for mast cell leukemia.[7]
Natural History, Complications and Prognosis
If left untreated, patients with mast cell leukemia may progress to develop weight loss, ascites, and bone abnormalities.[3] Common complications of mast cell leukemia include hepatosplenomegaly, lymphadenopathy, and osteoporosis.[3] Prognosis is generally poor, and the median survival time is less than six months.[1]
Diagnosis
History and symptoms
Symptoms of mast cell leukemia include fever, weight loss, weakness, flushes, and pruritis.[3]
Physical Examination
Common physical examination findings of mast cell leukemia include hepatosplenomegaly, lymphadenopathy, bone abnormalities, and ascites.[1][3]
Laboratory Findings
Laboratory findings consistent with the diagnosis of mast cell leukemia include abnormal complete blood count, biochemistry, and immunohistochemistry.[1][3][8]
CT
CT scan may be helpful in the diagnosis of mast cell leukemia. Findings on CT scan of the abdomen suggestive of mast cell leukemia include ascites, hepatosplenomegaly, and upper abdominal lymphadenopathy.[9]
MRI
There are no MRI findings associated with mast cell leukemia.
Other Imaging Findings
There are no other imaging findings associated with mast cell leukemia.
Other Diagnostic Studies
Other diagnostic studies for mast cell leukemia include flow cytometry.[8]
Treatment
Medical therapy
The mainstay of therapy for symptomatic mast cell leukemia patients is immunochemotherapy.[1][3]
Surgery
The predominant therapy for mast cell leukemia is immunochemotherapy. Surgical management, such as splenectomy, or bone marrow transplantation may be required in certain cases.[1]
Prevention
There are no primary or secondary preventive measures available for mast cell leukemia.
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 Georgin-Lavialle, S.; Lhermitte, L.; Dubreuil, P.; Chandesris, M.-O.; Hermine, O.; Damaj, G. (2012). "Mast cell leukemia". Blood. 121 (8): 1285–1295. doi:10.1182/blood-2012-07-442400. ISSN 0006-4971.
- ↑ 2.0 2.1 Savini, P.; Rondoni, M.; Poletti, G.; Lanzi, A.; Quercia, O.; Soverini, S.; De Benedittis, C.; Musardo, G.; Martinelli, G.; Stefanini, G. F. (2015). "Serum Total Tryptase Level Confirms Itself as a More Reliable Marker of Mast Cells Burden in Mast Cell Leukaemia (Aleukaemic Variant)". Case Reports in Hematology. 2015: 1–4. doi:10.1155/2015/737302. ISSN 2090-6560.
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 Joris, Magalie; Georgin-Lavialle, Sophie; Chandesris, Marie-Olivia; Lhermitte, Ludovic; Claisse, Jean-François; Canioni, Danielle; Hanssens, Katia; Damaj, Gandhi; Hermine, Olivier; Hamidou, Mohammed (2012). "Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive". Case Reports in Hematology. 2012: 1–6. doi:10.1155/2012/517546. ISSN 2090-6560.
- ↑ 4.0 4.1 4.2 4.3 Kristensen, Thomas; Vestergaard, Hanne; Møller, Michael Boe (2011). "Improved Detection of the KIT D816V Mutation in Patients with Systemic Mastocytosis Using a Quantitative and Highly Sensitive Real-Time qPCR Assay". The Journal of Molecular Diagnostics. 13 (2): 180–188. doi:10.1016/j.jmoldx.2010.10.004. ISSN 1525-1578.
- ↑ 5.0 5.1 5.2 5.3 Horvai AE, Link TM. Bone and Soft Tissue Pathology. Elsevier Health Sciences (2012). http://books.google.com?id=p2DV6VWdXx8C. Accessed on November 30, 2015.
- ↑ 6.0 6.1 6.2 6.3 Valent, P.; Sotlar, K.; Sperr, W. R.; Escribano, L.; Yavuz, S.; Reiter, A.; George, T. I.; Kluin-Nelemans, H. C.; Hermine, O.; Butterfield, J. H.; Hagglund, H.; Ustun, C.; Hornick, J. L.; Triggiani, M.; Radia, D.; Akin, C.; Hartmann, K.; Gotlib, J.; Schwartz, L. B.; Verstovsek, S.; Orfao, A.; Metcalfe, D. D.; Arock, M.; Horny, H.- P. (2014). "Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal". Annals of Oncology. 25 (9): 1691–1700. doi:10.1093/annonc/mdu047. ISSN 0923-7534.
- ↑ 7.0 7.1 Mast cell leukemia. USPSTF. http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=mast+cell+leukemia
- ↑ 8.0 8.1 8.2 Biochemistry of mast cell leukemia. Wikipedia (2015). https://en.wikipedia.org/wiki/Mast_cell_leukemia. Accessed on December 1, 2015
- ↑ Systemic mastocytosis. Dr Alexandra Stanislavsky. Radiopaedia (2015). http://radiopaedia.org/cases/systemic-mastocytosis. Accessed on December 1, 2015