Developing a standardized approach for assessing mast cells and eosinophils on tissue biopsies: A Work Group Report of the AAAAI Allergic Skin Diseases Committee - 05/10/21

Doi : 10.1016/j.jaci.2021.06.030

Nives Zimmermann, MD ^a,^b, J. Pablo Abonia, MD ^a,^c, Stephen C. Dreskin, MD, PhD ^d, Cem Akin, MD ^e, Scott Bolton, MD ^c,^f, Corinne S. Happel, MD ^g, Mario Geller, MD ^h, Désirée Larenas-Linnemann, MD ⁱ, Anil Nanda, MD ^j,^k,^l, Kathryn Peterson, MD ^m, Anita Wasan, MD ⁿ, Joshua Wechsler, MD ^o, Simin Zhang, MD ^p, Jonathan A. Bernstein, MD ^p,^⁎
^a Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio
^b Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
^c Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
^d Division of Allergy and Immunology, Department of Internal Medicine, University of Colorado, Aurora, Colo
^e Division of Allergy and Immunology, Department of Internal Medicine, University of Michigan, Ann Arbor, Mich
^f Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
^g Division of Allergy and Immunology, Department of Internal Medicine, John Hopkins School of Medicine, Baltimore, Md
^h Department of Medicine, the Academy of Medicine of Rio de Janeiro, Rio de Janeiro, Brazil
ⁱ Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, México
^j Asthma and Allergy Center, Lewisville, Tex
^k Asthma and Allergy Center, Flower Mound, Tex
^l Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas, Tex
^m Division of Gastroenterology, Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah
ⁿ Division of Gastroenterology, Hepatology, and Nutrition, Allergy and Asthma Center, McLean, Va
^o Division of Allergy and Immunology, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill
^p Allergy Section, Division of Immunology, Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, Ohio

^∗Corresponding author: Jonathan A. Bernstein, MD, University of Cincinnati College of Medicine, Division of Immunology, Allergy Section, 231 Albert Sabin Way, ML#563, Cincinnati, OH 45367-0563.University of Cincinnati College of MedicineDivision of ImmunologyAllergy Section231 Albert Sabin WayML#563CincinnatiOH45367-0563

Abstract

Mast cells and eosinophils are commonly found, expectedly or unexpectedly, in human tissue biopsies. Although the clinical significance of their presence, absence, quantity, and quality continues to be investigated in homeostasis and disease, there are currently gaps in knowledge related to what constitutes quantitatively relevant increases in mast cell and eosinophil number in tissue specimens for several clinical conditions. Diagnostically relevant thresholds of mast cell and eosinophil numbers have been proposed and generally accepted by the medical community for a few conditions, such as systemic mastocytosis and eosinophilic esophagitis. However, for other mast cell– and eosinophil-associated disorders, broad discrepancies remain regarding diagnostic thresholds and how samples are processed, routinely and/or specially stained, and interpreted and/or reported by pathologists. These discrepancies can obfuscate or delay a patient’s correct diagnosis. Therefore, a work group was assembled to review the literature and develop a standardized consensus for assessing the presence of mast cells and eosinophils for a spectrum of clinical conditions, including systemic mastocytosis and cutaneous mastocytosis, mast cell activation syndrome, eosinophilic esophagitis, eosinophilic gastritis/enteritis, and hypereosinophilia/hypereosinophilic syndrome. The intent of this work group is to build a consensus among pathology, allergy, dermatology, hematology/oncology, and gastroenterology stakeholders for qualitatively and quantitatively assessing mast cells and eosinophils in skin, gastrointestinal, and bone marrow pathologic specimens for the benefit of clinical practice and patients.

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Key words : Systemic mastocytosis, cutaneous mastocytosis, biopsy, mast cells, eosinophils, bone marrow, skin, gastrointestinal tract, work group, consensus, allergy, dermatology, pathology, gastroenterology

Abbreviations used : CEL, NOS, CM, CSU, CTCL, EoE, FISH, GI, HαT, H&E, HE, HES, IBS, IBS-D, IHC, IHES, IQR, MCAS, MLNeo, NGS, SM, SM-AHN, WDSM, WHO

Plan

General principles in evaluating human biopsies for mast cells and eosinophils for clinical purposes

Tissue-specific recommendations by the location of tissue sampling: Skin, GI tract, bone marrow

Skin

GI tract

Bone marrow

Bone marrow biopsy: Interpretation

Gaps in knowledge

Standardizing measurements and units for assessing cell density

Establishing norms for mast cell levels in the GI tract in homeostasis and disease

Testing for targeted therapies

Researching mastocytic enterocolitis

Disclosure of potential conflict of interest: PA has received grants from the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (U54 AI117804 and R01 AI124355-01), the Patient-Centered Outcomes Research Institute (SC14-1403-11593), and Shire/Takeda. SCD has received grant support from the NIH and Genentech, Inc; is a member of the Medical Expert Panel, Department of Health and Human Services, and Division of Vaccine Injury Compensation; and serves on an advisory board and/or is a consultant for Allakos, CSL Behring, BioCryst, Grifols, and Ukko. CA has received research grant support from Blueprint Medicines and is a consultant for Blueprint Medicine and Novartis. DL-L has received personal fees from Allakos, Amstrong, AstraZeneca, DBV Technologies, Grunenthal, GlaxoSmithKline, MEDA, Mylan, Menarini, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, Siegfried, UCB, and Gossamer; and grants from Sanofi, AstraZeneca, Novartis, UCB, GlaxoSmithKline, Teva, and the Purina Institute. KP has received equity in Nexeos; research support from AstraZeneca, Ellodi, Sanofi- Regeneron, and Adare; independent grants from the NIH, Chobani, and Allakos; and consulting/advisory board fees from Alladapt, Eli Lily, Medscape, Ellodi, and Takeda. JBW has received consulting fees for medical advisory boards for Allakos and Regeneron. JAB is a consultant principal investigator for Blueprint Medicine, Celldex, Allakos, AstraZeneca, Sanofi-Regeneron, Novartis, Genentech, Shire/Takeda, CSL Behring, Pharming, Biomarin, Kalvista, Ionis, and Merck; and speaker for GlaxoSmithKline, Sanofi-Regeneron, AstraZeneca, Novartis, Genentech, Pharming, Optinose, CSL Behring, and Shire/Takeda. The rest of the authors declare that they have no relevant conflicts of interest.