Standards of Pathology in the Diagnosis of Systemic Mastocytosis: Recommendations of the EU-US Cooperative Group

Karl Sotlar; Tracy I. George; Philip Kluin; Andreas Reiter; Juliana Schwaab; Jens Panse; Knut Brockow; Karin Hartmann; Wolfgang R. Sperr; Thomas Kristensen; Boguslaw Nedoszytko; Melody Carter; Patrizia Bonadonna; Jonathan J. Lyons; Hanneke C. Kluin-Nelemans; Olivier Hermine; Cem Akin; Sigurd Broesby-Olsen; Gregor Hoermann; Massimo Triggiani; Joseph H. Butterfield; Mohamad Jawhar; Jason Gotlib; Dean D. Metcalfe; Alberto Orfao; Michel Arock; Peter Valent; Hans Peter Horny

doi:10.1016/j.jaip.2022.05.036

Standards of Pathology in the Diagnosis of Systemic Mastocytosis: Recommendations of the EU-US Cooperative Group

Karl Sotlar^*, Tracy I. George, Philip Kluin, Andreas Reiter, Juliana Schwaab, Jens Panse, Knut Brockow, Karin Hartmann, Wolfgang R. Sperr, Thomas Kristensen, Boguslaw Nedoszytko, Melody Carter, Patrizia Bonadonna, Jonathan J. Lyons, Hanneke C. Kluin-Nelemans, Olivier Hermine, Cem Akin, Sigurd Broesby-Olsen, Gregor Hoermann, Massimo TriggianiJoseph H. Butterfield, Mohamad Jawhar, Jason Gotlib, Dean D. Metcalfe, Alberto Orfao, Michel Arock, Peter Valent, Hans Peter Horny

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Pathology plays a central role in the diagnosis of systemic mastocytosis (SM), its delineation from other neoplasms and reactive conditions, and in monitoring of SM under therapy. The morphologic hallmark of SM is the accumulation of spindle-shaped, hypogranulated mast cells (MCs) in bone marrow (BM) and other extracutaneous tissues. Four of the 5 World Health Organization–defined diagnostic criteria (ie, compact MC aggregates [=major criterion]; atypical MC morphology; activating KIT point mutations; aberrant expression of CD25 and/or CD2 and/or CD30 in MCs [=minor criteria]) can be addressed by the pathologist. The final classification of SM variants as either BM mastocytosis, indolent SM, smoldering SM, aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN), or MC leukemia (MCL) has important prognostic significance and requires the integration of certain morphological, clinical, radiological, and biochemical data, referred to as B- and C-findings. Substantial diagnostic challenges may be posed to the pathologist and clinician especially in the so-called advanced SM variants, that is, ASM, MCL, and SM-AHN. In this article, updated recommendations of the EU-US Cooperative Group regarding standards of pathology in the diagnosis of SM, presented during the year 2020 Working Conference held in September in Vienna, are reported.

Original language	English
Pages (from-to)	1986-1998.e2
Number of pages	15
Journal	The Journal of Allergy and Clinical Immunology: In Practice
Volume	10
Issue number	8
DOIs	https://doi.org/10.1016/j.jaip.2022.05.036
Publication status	Published - Aug-2022

Keywords

Associated hematologic neoplasm
CD117
CD25
Diagnosis
Diagnostic criteria
Immunohistochemistry
KIT p.D816V
Mast cell
Mastocytosis
Pathology
Tryptase

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Sotlar, K., George, T. I., Kluin, P., Reiter, A., Schwaab, J., Panse, J., Brockow, K., Hartmann, K., Sperr, W. R., Kristensen, T., Nedoszytko, B., Carter, M., Bonadonna, P., Lyons, J. J., Kluin-Nelemans, H. C., Hermine, O., Akin, C., Broesby-Olsen, S., Hoermann, G., ... Horny, H. P. (2022). Standards of Pathology in the Diagnosis of Systemic Mastocytosis: Recommendations of the EU-US Cooperative Group. The Journal of Allergy and Clinical Immunology: In Practice, 10(8), 1986-1998.e2. https://doi.org/10.1016/j.jaip.2022.05.036

@article{8e59fee44b034ec280077ffb14c87c46,

title = "Standards of Pathology in the Diagnosis of Systemic Mastocytosis: Recommendations of the EU-US Cooperative Group",

abstract = "Pathology plays a central role in the diagnosis of systemic mastocytosis (SM), its delineation from other neoplasms and reactive conditions, and in monitoring of SM under therapy. The morphologic hallmark of SM is the accumulation of spindle-shaped, hypogranulated mast cells (MCs) in bone marrow (BM) and other extracutaneous tissues. Four of the 5 World Health Organization–defined diagnostic criteria (ie, compact MC aggregates [=major criterion]; atypical MC morphology; activating KIT point mutations; aberrant expression of CD25 and/or CD2 and/or CD30 in MCs [=minor criteria]) can be addressed by the pathologist. The final classification of SM variants as either BM mastocytosis, indolent SM, smoldering SM, aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN), or MC leukemia (MCL) has important prognostic significance and requires the integration of certain morphological, clinical, radiological, and biochemical data, referred to as B- and C-findings. Substantial diagnostic challenges may be posed to the pathologist and clinician especially in the so-called advanced SM variants, that is, ASM, MCL, and SM-AHN. In this article, updated recommendations of the EU-US Cooperative Group regarding standards of pathology in the diagnosis of SM, presented during the year 2020 Working Conference held in September in Vienna, are reported.",

keywords = "Associated hematologic neoplasm, CD117, CD25, Diagnosis, Diagnostic criteria, Immunohistochemistry, KIT p.D816V, Mast cell, Mastocytosis, Pathology, Tryptase",

author = "Karl Sotlar and George, {Tracy I.} and Philip Kluin and Andreas Reiter and Juliana Schwaab and Jens Panse and Knut Brockow and Karin Hartmann and Sperr, {Wolfgang R.} and Thomas Kristensen and Boguslaw Nedoszytko and Melody Carter and Patrizia Bonadonna and Lyons, {Jonathan J.} and Kluin-Nelemans, {Hanneke C.} and Olivier Hermine and Cem Akin and Sigurd Broesby-Olsen and Gregor Hoermann and Massimo Triggiani and Butterfield, {Joseph H.} and Mohamad Jawhar and Jason Gotlib and Metcalfe, {Dean D.} and Alberto Orfao and Michel Arock and Peter Valent and Horny, {Hans Peter}",

note = "Funding Information: Conflicts of interest: K. Sotlar has served as a consultant for and has received honoraria from Novartis and Blueprint. T. I. George has served as a consultant for and is on the study steering committees for Blueprint, Celgene, and Incyte. A. Reiter has received honoraria for consultancy from Novartis, Blueprint, and Deciphera; and research support from Novartis . J. Schwaab is on the advisory board of and has received honoraria from Novartis and Blueprint Medicines. J. Panse has received honoraria from Alexion, Apellis, BMS, Boehringer Ingelheim, Gilead, MSD, Neopharm Israel, Novartis, Pfizer, Roche, Sobi, and SwixxBiopharma; and has served as consultant for Alexion, Amgen, Apellis, AstraZeneca, Blueprint Medicines, BMS, Boehringer Ingelheim, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, and Sobi. K. Brockow is on the advisory board (honoraria) of Blueprint. K. Hartmann has received research funding from Thermo Fisher ; and has served as a consultant for and has received honoraria from Allergopharma, ALK-Abello, Blueprint, Deciphera, Leo Pharma, Menarini, Novartis, Pfizer, Takeda, and Thermo Fisher. W. R. Sperr has received honoraria for consultancy from Thermo Fisher, AbbVie, Novartis, Pfizer, Incyte, Deciphera, Jazz, Teva, and Celgene. T. Kristensen received honoraria from Novartis and Blueprint Medicine and TKK, Odense University Hospital and the Region of Southern Denmark receive royalty from PentaBase ApS from the sale of PentaBase KIT D816Vassay pursuant to the Act on Inventions at Public Research Institutions (LBK210—paragraph 12, section 1 & 2). P. Bonadonna has received honoraria from Novartis and Blueprint. O. Hermine is a co-founder and stockholder of AB Science; and has received research grant from AB Science, Novartis, Celgene, and Lipomed. C. Akin has received honoraria for consultancy from Blueprint and Novartis, and research grant from Blueprint ; and is an investigator in a clinical trial for Blueprint. S. Broesby-Olsen is a study steering committee member for Blueprint Medicines; and has received speaker honoraria from Novartis and Thermo Fisher. G. Hoermann has received honoraria from Novartis and Incyte. M. Triggiani has received honoraria for consultancy from Novartis, Deciphera, and Blueprint; and is an investigator in a clinical trial for Blueprint. J. Gotlib has received research grant (funds for administration of clinical trials) from Novartis, Blueprint Medicines, Deciphera, and Cogent Biosciences; is on the advisory board of and has received honoraria from Blueprint Medicines, Novartis, Deciphera, and Cogent Biosciences; and has received reimbursement of travel expenses from Novartis and Blueprint. D. D. Metcalfe is an investigator in a clinical trial for Sanofi US Services. A. Orfao has received honoraria for consultancy from Novartis and Blueprint. M. Arock has received research grants from Blueprint and honoraria from AB Science, Blueprint, and Novartis. P. Valent is on the advisory board of and has received honoraria from Novartis, Blueprint, Deciphera, Celgene/BMS, Incyte, and Novartis. H.-P. Horny is on the advisory board of and has received honoraria from Novartis, Deciphera, and Blueprint Medicines. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: T. I. George was supported by the ARUP Institute for Clinical and Experimental Pathology . K. Hartmann was supported by the Swiss National Science Foundation , grant number 310030_207705 . D. D. Metcalfe, J. J. Lyons, and M. Carter were supported by the Division of Intramural Research , National Institutes of Allergic and Infectious Diseases , National Institutes of Health ( NIH ). The content is solely the responsibility of the authors and does not represent the official views of the NIH. P. Valent was supported by the Austrian Science Funds ( FWF ), projects F4701-B20 and F4704-B20. Funding Information: T. I. George was supported by the ARUP Institute for Clinical and Experimental Pathology. K. Hartmann was supported by the Swiss National Science Foundation, grant number 310030_207705. D. D. Metcalfe, J. J. Lyons, and M. Carter were supported by the Division of Intramural Research, National Institutes of Allergic and Infectious Diseases, National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not represent the official views of the NIH. P. Valent was supported by the Austrian Science Funds (FWF), projects F4701-B20 and F4704-B20.Conflicts of interest: K. Sotlar has served as a consultant for and has received honoraria from Novartis and Blueprint. T. I. George has served as a consultant for and is on the study steering committees for Blueprint, Celgene, and Incyte. A. Reiter has received honoraria for consultancy from Novartis, Blueprint, and Deciphera; and research support from Novartis. J. Schwaab is on the advisory board of and has received honoraria from Novartis and Blueprint Medicines. J. Panse has received honoraria from Alexion, Apellis, BMS, Boehringer Ingelheim, Gilead, MSD, Neopharm Israel, Novartis, Pfizer, Roche, Sobi, and SwixxBiopharma; and has served as consultant for Alexion, Amgen, Apellis, AstraZeneca, Blueprint Medicines, BMS, Boehringer Ingelheim, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, and Sobi. K. Brockow is on the advisory board (honoraria) of Blueprint. K. Hartmann has received research funding from Thermo Fisher; and has served as a consultant for and has received honoraria from Allergopharma, ALK-Abello, Blueprint, Deciphera, Leo Pharma, Menarini, Novartis, Pfizer, Takeda, and Thermo Fisher. W. R. Sperr has received honoraria for consultancy from Thermo Fisher, AbbVie, Novartis, Pfizer, Incyte, Deciphera, Jazz, Teva, and Celgene. T. Kristensen received honoraria from Novartis and Blueprint Medicine and TKK, Odense University Hospital and the Region of Southern Denmark receive royalty from PentaBase ApS from the sale of PentaBase KIT D816Vassay pursuant to the Act on Inventions at Public Research Institutions (LBK210—paragraph 12, section 1 & 2). P. Bonadonna has received honoraria from Novartis and Blueprint. O. Hermine is a co-founder and stockholder of AB Science; and has received research grant from AB Science, Novartis, Celgene, and Lipomed. C. Akin has received honoraria for consultancy from Blueprint and Novartis, and research grant from Blueprint; and is an investigator in a clinical trial for Blueprint. S. Broesby-Olsen is a study steering committee member for Blueprint Medicines; and has received speaker honoraria from Novartis and Thermo Fisher. G. Hoermann has received honoraria from Novartis and Incyte. M. Triggiani has received honoraria for consultancy from Novartis, Deciphera, and Blueprint; and is an investigator in a clinical trial for Blueprint. J. Gotlib has received research grant (funds for administration of clinical trials) from Novartis, Blueprint Medicines, Deciphera, and Cogent Biosciences; is on the advisory board of and has received honoraria from Blueprint Medicines, Novartis, Deciphera, and Cogent Biosciences; and has received reimbursement of travel expenses from Novartis and Blueprint. D. D. Metcalfe is an investigator in a clinical trial for Sanofi US Services. A. Orfao has received honoraria for consultancy from Novartis and Blueprint. M. Arock has received research grants from Blueprint and honoraria from AB Science, Blueprint, and Novartis. P. Valent is on the advisory board of and has received honoraria from Novartis, Blueprint, Deciphera, Celgene/BMS, Incyte, and Novartis. H.-P. Horny is on the advisory board of and has received honoraria from Novartis, Deciphera, and Blueprint Medicines. The rest of the authors declare that they have no relevant conflicts of interest. Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = aug,

doi = "10.1016/j.jaip.2022.05.036",

language = "English",

volume = "10",

pages = "1986--1998.e2",

journal = "The Journal of Allergy and Clinical Immunology: In Practice",

issn = "2213-2198",

publisher = "American Academy of Allergy, Asthma and Immunology",

number = "8",

}

Sotlar, K, George, TI, Kluin, P, Reiter, A, Schwaab, J, Panse, J, Brockow, K, Hartmann, K, Sperr, WR, Kristensen, T, Nedoszytko, B, Carter, M, Bonadonna, P, Lyons, JJ, Kluin-Nelemans, HC, Hermine, O, Akin, C, Broesby-Olsen, S, Hoermann, G, Triggiani, M, Butterfield, JH, Jawhar, M, Gotlib, J, Metcalfe, DD, Orfao, A, Arock, M, Valent, P & Horny, HP 2022, 'Standards of Pathology in the Diagnosis of Systemic Mastocytosis: Recommendations of the EU-US Cooperative Group', The Journal of Allergy and Clinical Immunology: In Practice, vol. 10, no. 8, pp. 1986-1998.e2. https://doi.org/10.1016/j.jaip.2022.05.036

TY - JOUR

T1 - Standards of Pathology in the Diagnosis of Systemic Mastocytosis

T2 - Recommendations of the EU-US Cooperative Group

AU - Sotlar, Karl

AU - George, Tracy I.

AU - Kluin, Philip

AU - Reiter, Andreas

AU - Schwaab, Juliana

AU - Panse, Jens

AU - Brockow, Knut

AU - Hartmann, Karin

AU - Sperr, Wolfgang R.

AU - Kristensen, Thomas

AU - Nedoszytko, Boguslaw

AU - Carter, Melody

AU - Bonadonna, Patrizia

AU - Lyons, Jonathan J.

AU - Kluin-Nelemans, Hanneke C.

AU - Hermine, Olivier

AU - Akin, Cem

AU - Broesby-Olsen, Sigurd

AU - Hoermann, Gregor

AU - Triggiani, Massimo

AU - Butterfield, Joseph H.

AU - Jawhar, Mohamad

AU - Gotlib, Jason

AU - Metcalfe, Dean D.

AU - Orfao, Alberto

AU - Arock, Michel

AU - Valent, Peter

AU - Horny, Hans Peter

N1 - Funding Information: Conflicts of interest: K. Sotlar has served as a consultant for and has received honoraria from Novartis and Blueprint. T. I. George has served as a consultant for and is on the study steering committees for Blueprint, Celgene, and Incyte. A. Reiter has received honoraria for consultancy from Novartis, Blueprint, and Deciphera; and research support from Novartis . J. Schwaab is on the advisory board of and has received honoraria from Novartis and Blueprint Medicines. J. Panse has received honoraria from Alexion, Apellis, BMS, Boehringer Ingelheim, Gilead, MSD, Neopharm Israel, Novartis, Pfizer, Roche, Sobi, and SwixxBiopharma; and has served as consultant for Alexion, Amgen, Apellis, AstraZeneca, Blueprint Medicines, BMS, Boehringer Ingelheim, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, and Sobi. K. Brockow is on the advisory board (honoraria) of Blueprint. K. Hartmann has received research funding from Thermo Fisher ; and has served as a consultant for and has received honoraria from Allergopharma, ALK-Abello, Blueprint, Deciphera, Leo Pharma, Menarini, Novartis, Pfizer, Takeda, and Thermo Fisher. W. R. Sperr has received honoraria for consultancy from Thermo Fisher, AbbVie, Novartis, Pfizer, Incyte, Deciphera, Jazz, Teva, and Celgene. T. Kristensen received honoraria from Novartis and Blueprint Medicine and TKK, Odense University Hospital and the Region of Southern Denmark receive royalty from PentaBase ApS from the sale of PentaBase KIT D816Vassay pursuant to the Act on Inventions at Public Research Institutions (LBK210—paragraph 12, section 1 & 2). P. Bonadonna has received honoraria from Novartis and Blueprint. O. Hermine is a co-founder and stockholder of AB Science; and has received research grant from AB Science, Novartis, Celgene, and Lipomed. C. Akin has received honoraria for consultancy from Blueprint and Novartis, and research grant from Blueprint ; and is an investigator in a clinical trial for Blueprint. S. Broesby-Olsen is a study steering committee member for Blueprint Medicines; and has received speaker honoraria from Novartis and Thermo Fisher. G. Hoermann has received honoraria from Novartis and Incyte. M. Triggiani has received honoraria for consultancy from Novartis, Deciphera, and Blueprint; and is an investigator in a clinical trial for Blueprint. J. Gotlib has received research grant (funds for administration of clinical trials) from Novartis, Blueprint Medicines, Deciphera, and Cogent Biosciences; is on the advisory board of and has received honoraria from Blueprint Medicines, Novartis, Deciphera, and Cogent Biosciences; and has received reimbursement of travel expenses from Novartis and Blueprint. D. D. Metcalfe is an investigator in a clinical trial for Sanofi US Services. A. Orfao has received honoraria for consultancy from Novartis and Blueprint. M. Arock has received research grants from Blueprint and honoraria from AB Science, Blueprint, and Novartis. P. Valent is on the advisory board of and has received honoraria from Novartis, Blueprint, Deciphera, Celgene/BMS, Incyte, and Novartis. H.-P. Horny is on the advisory board of and has received honoraria from Novartis, Deciphera, and Blueprint Medicines. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: T. I. George was supported by the ARUP Institute for Clinical and Experimental Pathology . K. Hartmann was supported by the Swiss National Science Foundation , grant number 310030_207705 . D. D. Metcalfe, J. J. Lyons, and M. Carter were supported by the Division of Intramural Research , National Institutes of Allergic and Infectious Diseases , National Institutes of Health ( NIH ). The content is solely the responsibility of the authors and does not represent the official views of the NIH. P. Valent was supported by the Austrian Science Funds ( FWF ), projects F4701-B20 and F4704-B20. Funding Information: T. I. George was supported by the ARUP Institute for Clinical and Experimental Pathology. K. Hartmann was supported by the Swiss National Science Foundation, grant number 310030_207705. D. D. Metcalfe, J. J. Lyons, and M. Carter were supported by the Division of Intramural Research, National Institutes of Allergic and Infectious Diseases, National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not represent the official views of the NIH. P. Valent was supported by the Austrian Science Funds (FWF), projects F4701-B20 and F4704-B20.Conflicts of interest: K. Sotlar has served as a consultant for and has received honoraria from Novartis and Blueprint. T. I. George has served as a consultant for and is on the study steering committees for Blueprint, Celgene, and Incyte. A. Reiter has received honoraria for consultancy from Novartis, Blueprint, and Deciphera; and research support from Novartis. J. Schwaab is on the advisory board of and has received honoraria from Novartis and Blueprint Medicines. J. Panse has received honoraria from Alexion, Apellis, BMS, Boehringer Ingelheim, Gilead, MSD, Neopharm Israel, Novartis, Pfizer, Roche, Sobi, and SwixxBiopharma; and has served as consultant for Alexion, Amgen, Apellis, AstraZeneca, Blueprint Medicines, BMS, Boehringer Ingelheim, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, and Sobi. K. Brockow is on the advisory board (honoraria) of Blueprint. K. Hartmann has received research funding from Thermo Fisher; and has served as a consultant for and has received honoraria from Allergopharma, ALK-Abello, Blueprint, Deciphera, Leo Pharma, Menarini, Novartis, Pfizer, Takeda, and Thermo Fisher. W. R. Sperr has received honoraria for consultancy from Thermo Fisher, AbbVie, Novartis, Pfizer, Incyte, Deciphera, Jazz, Teva, and Celgene. T. Kristensen received honoraria from Novartis and Blueprint Medicine and TKK, Odense University Hospital and the Region of Southern Denmark receive royalty from PentaBase ApS from the sale of PentaBase KIT D816Vassay pursuant to the Act on Inventions at Public Research Institutions (LBK210—paragraph 12, section 1 & 2). P. Bonadonna has received honoraria from Novartis and Blueprint. O. Hermine is a co-founder and stockholder of AB Science; and has received research grant from AB Science, Novartis, Celgene, and Lipomed. C. Akin has received honoraria for consultancy from Blueprint and Novartis, and research grant from Blueprint; and is an investigator in a clinical trial for Blueprint. S. Broesby-Olsen is a study steering committee member for Blueprint Medicines; and has received speaker honoraria from Novartis and Thermo Fisher. G. Hoermann has received honoraria from Novartis and Incyte. M. Triggiani has received honoraria for consultancy from Novartis, Deciphera, and Blueprint; and is an investigator in a clinical trial for Blueprint. J. Gotlib has received research grant (funds for administration of clinical trials) from Novartis, Blueprint Medicines, Deciphera, and Cogent Biosciences; is on the advisory board of and has received honoraria from Blueprint Medicines, Novartis, Deciphera, and Cogent Biosciences; and has received reimbursement of travel expenses from Novartis and Blueprint. D. D. Metcalfe is an investigator in a clinical trial for Sanofi US Services. A. Orfao has received honoraria for consultancy from Novartis and Blueprint. M. Arock has received research grants from Blueprint and honoraria from AB Science, Blueprint, and Novartis. P. Valent is on the advisory board of and has received honoraria from Novartis, Blueprint, Deciphera, Celgene/BMS, Incyte, and Novartis. H.-P. Horny is on the advisory board of and has received honoraria from Novartis, Deciphera, and Blueprint Medicines. The rest of the authors declare that they have no relevant conflicts of interest. Publisher Copyright: © 2022

PY - 2022/8

Y1 - 2022/8

N2 - Pathology plays a central role in the diagnosis of systemic mastocytosis (SM), its delineation from other neoplasms and reactive conditions, and in monitoring of SM under therapy. The morphologic hallmark of SM is the accumulation of spindle-shaped, hypogranulated mast cells (MCs) in bone marrow (BM) and other extracutaneous tissues. Four of the 5 World Health Organization–defined diagnostic criteria (ie, compact MC aggregates [=major criterion]; atypical MC morphology; activating KIT point mutations; aberrant expression of CD25 and/or CD2 and/or CD30 in MCs [=minor criteria]) can be addressed by the pathologist. The final classification of SM variants as either BM mastocytosis, indolent SM, smoldering SM, aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN), or MC leukemia (MCL) has important prognostic significance and requires the integration of certain morphological, clinical, radiological, and biochemical data, referred to as B- and C-findings. Substantial diagnostic challenges may be posed to the pathologist and clinician especially in the so-called advanced SM variants, that is, ASM, MCL, and SM-AHN. In this article, updated recommendations of the EU-US Cooperative Group regarding standards of pathology in the diagnosis of SM, presented during the year 2020 Working Conference held in September in Vienna, are reported.

AB - Pathology plays a central role in the diagnosis of systemic mastocytosis (SM), its delineation from other neoplasms and reactive conditions, and in monitoring of SM under therapy. The morphologic hallmark of SM is the accumulation of spindle-shaped, hypogranulated mast cells (MCs) in bone marrow (BM) and other extracutaneous tissues. Four of the 5 World Health Organization–defined diagnostic criteria (ie, compact MC aggregates [=major criterion]; atypical MC morphology; activating KIT point mutations; aberrant expression of CD25 and/or CD2 and/or CD30 in MCs [=minor criteria]) can be addressed by the pathologist. The final classification of SM variants as either BM mastocytosis, indolent SM, smoldering SM, aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN), or MC leukemia (MCL) has important prognostic significance and requires the integration of certain morphological, clinical, radiological, and biochemical data, referred to as B- and C-findings. Substantial diagnostic challenges may be posed to the pathologist and clinician especially in the so-called advanced SM variants, that is, ASM, MCL, and SM-AHN. In this article, updated recommendations of the EU-US Cooperative Group regarding standards of pathology in the diagnosis of SM, presented during the year 2020 Working Conference held in September in Vienna, are reported.

KW - Associated hematologic neoplasm

KW - CD117

KW - CD25

KW - Diagnosis

KW - Diagnostic criteria

KW - Immunohistochemistry

KW - KIT p.D816V

KW - Mast cell

KW - Mastocytosis

KW - Pathology

KW - Tryptase

U2 - 10.1016/j.jaip.2022.05.036

DO - 10.1016/j.jaip.2022.05.036

M3 - Article

C2 - 35724949

AN - SCOPUS:85135722907

SN - 2213-2198

VL - 10

SP - 1986-1998.e2

JO - The Journal of Allergy and Clinical Immunology: In Practice

JF - The Journal of Allergy and Clinical Immunology: In Practice

IS - 8

ER -

Standards of Pathology in the Diagnosis of Systemic Mastocytosis: Recommendations of the EU-US Cooperative Group

Abstract

Keywords

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