Produção Nacional
Revisado por pares
Developing a standardized approach for assessing mast cells and eosinophils on tissue biopsies: A Work Group Report of the AAAAI Allergic Skin Diseases Committee
2021; Elsevier BV; Volume: 148; Issue: 4 Linguagem: Inglês
10.1016/j.jaci.2021.06.030
ISSN1097-6825
AutoresNives Zimmermann, J. Pablo Abonia, Stephen C. Dreskin, Cem Akin, Scott M. Bolton, Corinne Savides Happel, Mário Geller, Désirée Larenas‐Linnemann, Anil Nanda, Kathryn A. Peterson, Anita N. Wasan, Joshua B. Wechsler, Simin Zhang, Jonathan A. Bernstein,
Tópico(s)Food Allergy and Anaphylaxis Research
ResumoMast 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. 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. AAAAI Position Statements,Work Group Reports, and Systematic Reviews are not to be considered to reflect current AAAAI standards or policy after five years from the date of publication. The statement below is not to be construed as dictating an exclusive course of action nor is it intended to replace the medical judgment of healthcare professionals. The unique circumstances of individual patients and environments are to be taken into account in any diagnosis and treatment plan. The statement reflects clinical and scientific advances as of the date of publication and is subject to change.For reference only. AAAAI Position Statements,Work Group Reports, and Systematic Reviews are not to be considered to reflect current AAAAI standards or policy after five years from the date of publication. The statement below is not to be construed as dictating an exclusive course of action nor is it intended to replace the medical judgment of healthcare professionals. The unique circumstances of individual patients and environments are to be taken into account in any diagnosis and treatment plan. The statement reflects clinical and scientific advances as of the date of publication and is subject to change. For reference only. Mast cells and eosinophils are commonly present in human tissue biopsies, but the clinical meaning of their presence, absence, quantity, and quality continues to be researched in homeostasis and disease. Current gaps in knowledge include what constitutes quantitatively relevant increases in mast cell and eosinophil numbers 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 mast cells in systemic mastocytosis (SM) and eosinophils in eosinophilic esophagitis (EoE).1Collins M.H. Capocelli K. Yang G.Y. Eosinophilic gastrointestinal disorders pathology.Front Med (Lausanne). 2017; 4: 261Crossref PubMed Google Scholar, 2Collins M.H. Martin L.J. Alexander E.S. Boyd J.T. Sheridan R. He H. et al.Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring.Dis Esophagus. 2017; 30: 1-8PubMed Google Scholar, 3Doyle L.A. Hornick J.L. Pathology of extramedullary mastocytosis.Immunol Allergy Clin North Am. 2014; 34: 323-339Abstract Full Text Full Text PDF PubMed Google Scholar, 4Doyle L.A. Sepehr G.J. Hamilton M.J. Akin C. Castells M.C. Hornick J.L. 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: 832-843Crossref PubMed Scopus (65) Google Scholar, 5Reichard K.K. Chen D. Pardanani A. McClure R.F. Howard M.T. Kurtin P.J. et al.Morphologically occult systemic mastocytosis in bone marrow: clinicopathologic features and an algorithmic approach to diagnosis.Am J Clin Pathol. 2015; 144: 493-502Crossref PubMed Google Scholar However, for other mast cell– and eosinophil-associated disorders, broad discrepancies remain in 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. Moreover, the diagnostic relevance of mast cell and/or eosinophil numbers and features in human biopsy specimens of different sampling locations (skin, gastrointestinal [GI] tract, bone marrow) and disease conditions is often undefined. In addition to the density, the activation status and degranulation of these cells likely have diverse roles in pathophysiology, but how these features should be assessed and interpreted for diagnostic purposes is poorly understood. Although there is an expansive literature pertaining to mast cell and eosinophil involvement in a spectrum of pulmonary disorders and SM, the literature pertaining to mast cell activation syndrome (MCAS) and skin, GI, and respiratory symptoms is less robust. 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 SM and cutaneous mastocytosis (CM), MCAS, EoE, eosinophilic gastritis/enteritis, and hypereosinophilia (HE)/hypereosinophilic syndrome (HES). 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, GI, and bone marrow pathologic specimens for the benefit of clinical practice and patients. We first discuss general principles in evaluating human biopsies for mast cells and eosinophils for clinical purposes and then tissue-specific recommendations by the location of tissue sampling (skin, GI tract, bone marrow). Mast cells have differing morphology depending on whether they are nonneoplastic or neoplastic. Nonneoplastic mast cells are generally round cells with a central round nucleus and relatively abundant granular cytoplasm, but they may have somewhat different phenotypes in different tissues and different locations (eg, mucosa, submucosa). Mast cell granules are not very conspicuous on hematoxylin and eosin (H&E)–stained slides and thus can be missed if cells are individually dispersed; after they start forming aggregates, their recognition becomes easier. In contrast to nonneoplastic mast cells, which are usually individually scattered in tissues, neoplastic mast cells tend to form multifocal dense aggregates of >15 cells (see the World Health Organization [WHO] major criterion for SM in Table I), are more likely to be spindle-shaped, and may have decreased to absent granule content. Specific morphologic alterations of mast cells seen on bone marrow aspirate smears in mast cell disorders have been previously described.6Sperr W.R. Escribano L. Jordan J.H. Schernthaner G.H. Kundi M. Horny H.P. et al.Morphologic properties of neoplastic mast cells: delineation of stages of maturation and implication for cytological grading of mastocytosis.Leuk Res. 2001; 25: 529-536Crossref PubMed Scopus (169) Google Scholar For a detailed description of histologic features and criteria for neoplasms of mast cell lineage, see past and current WHO books and review articles.7Horny H.P. Sotlar K. Sperr W.R. Valent P. Systemic mastocytosis with associated clonal haematological non-mast cell lineage diseases: a histopathological challenge.J Clin Pathol. 2004; 57: 604-608Crossref PubMed Scopus (125) Google Scholar, 8Horny H.P. Sotlar K. Valent P. Differential diagnoses of systemic mastocytosis in routinely processed bone marrow biopsy specimens: a review.Pathobiology. 2010; 77: 169-180Crossref PubMed Scopus (0) Google Scholar, 9Jaffe ES, Harris NL, Stein H, Vardiman JW. Pathology and Genetics: Tumours of Haematopoietic and Lymphoid Tissues. 3rd ed. World Health Organization Classification of Tumours. Geneva (Switzerland): World Health Organization; 2001.Google Scholar, 10Swerdlow S.H. Campo E. Pileri S.A. Harris N.L. Stein H. Siebert R. et al.The 2016 revision of the World Health Organization classification of lymphoid neoplasms.Blood. 2016; 127: 2375-2390Crossref PubMed Scopus (3571) Google Scholar, 11Swerdlow S.H. Campo E. Harris N.L. Jaffe E.S. Pileri S.A. Stein H. et al.WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues.4th ed. World Health Organization, Geneva (Switzerland)2008Google Scholar, 12Valent P. Horny H.P. Escribano L. Longley B.J. Li C.Y. Schwartz L.B. et al.Diagnostic criteria and classification of mastocytosis: a consensus proposal.Leuk Res. 2001; 25: 603-625Crossref PubMed Scopus (898) Google ScholarTable I2016 WHO classification criteria for mastocytosis• Cutaneous mastocytosis• Systemic mastocytosis• Mast cell sarcoma (localized mast cell tumors)For SM, there are 2016 WHO criteria for diagnosis and subclassification.Diagnostic criteriaMajor: Multifocal dense infiltrates of mast cells in bone marrow biopsies and/or sections of other extracutaneous organsMinor:Twenty-five percent of all mast cells are atypical on bone marrow smears or are spindle-shaped in mast cell infiltrates detected on sectionsKIT point mutation at codon 816 in the bone marrow or another extracutaneous organMast cells in bone marrow or blood or another extracutaneous organ exhibit CD2 and/or CD25∗Of note, CD25+ mast cells can appear in JAK2 myelodysplastic syndrome or FIP1L1-PDGFRA hypereosinophilic syndrome (HES) mutations and serum baseline tryptase levels >20 ng/mL can be seen in hereditary alpha tryptasemia (HαT) or advanced renal failure.Baseline serum tryptase level ≥20 ng/mL (in case of an unrelated myeloid neoplasm, this is not valid as an SM criterion)To diagnose SM, 1 major and 1 minor or 3 minor criteria should be met.Subclassification of SMIndolent SM (low mast cell burden, no C findings; see below)Smoldering SM (high mast cell burden, ≥ 2 B findings; see below)SM-AHNAggressive SM (≥1 C finding; see below)Mast cell leukemia (diffuse infiltrate, >20% mast cell in bone marrow aspirate that are atypical and immature, ± circulating mast cells)B findings: Indicate a high burden of mast cells and expansion of the neoplastic process into multiple hematopoietic lineages, without visible impairment of organ functionMast cell infiltration grade in the bone marrow >30% by histology and the basal serum tryptase level is >200 ng/mLHypercellular bone marrow with loss of fat cells, discrete signs of dysmyelopoiesis without substantial cytopenias or WHO criteria for an MDS or MPNOrganomegaly: palpable hepatomegaly, palpable splenomegaly, or palpable lymphadenopathy (on CT or ultrasound: >2 cm) without impaired organ functionC findings: Are indicative of organ damage produced by mast cell infiltration (should be confirmed by biopsy if possible)Cytopenia(s): ANC <1,000/μL or hemoglobin <10 g/dL or platelet count 20 ng/mL can be seen in hereditary alpha tryptasemia (HαT) or advanced renal failure. Open table in a new tab Mast cells can be stained histochemically or immunohistochemically; however, using immunohistochemical stains is recommended. Regarding histochemical staining, mast cell granules stain metachromatically with toluidine blue and Giemsa, orange-red with chloroacetate esterase (also known as Leder stain), and intense purple with pinacyanol-erythrosinate.13Sundram U.N. Natkunam Y. Mast cell tryptase and microphthalmia transcription factor effectively discriminate cutaneous mast cell disease from myeloid leukemia cutis.J Cutan Pathol. 2007; 34: 289-295Crossref PubMed Scopus (10) Google Scholar, 14Kawabori S. Denburg J.A. Schwartz L.B. Irani A.A. Wong D. Jordana G. et al.Histochemical and immunohistochemical characteristics of mast cells in nasal polyps.Am J Respir Cell Mol Biol. 1992; 6: 37-43Crossref PubMed Google Scholar, 15Ribatti D. The staining of mast cells: a historical overview.Int Arch Allergy Immunol. 2018; 176: 55-60Crossref PubMed Scopus (28) Google Scholar However, histochemical stains suffer from low sensitivity (eg, mast cell subtypes have been reported to be chloroacetate esterase–negative) and specificity (chloroacetate esterase stains other granulocytes); thus in clinical practice, these histochemical stains have been largely replaced by immunohistochemical stains, namely CD117/KIT and mast cell tryptase.16Horny H.P. Sillaber C. Menke D. Kaiserling E. Wehrmann M. Stehberger B. et al.Diagnostic value of immunostaining for tryptase in patients with mastocytosis.Am J Surg Pathol. 1998; 22: 1132-1140Crossref PubMed Scopus (195) Google Scholar CD117/KIT, a surface receptor that is highly sensitive for detecting mast cells, is involved in mast cell development and survival. However, KIT is also involved in the development of germ cells, melanocytes, hematopoietic stem cells, and interstitial cells of Cajal in the GI tract; thus, KIT is not a specific marker for mast cells. Therefore, KIT expression needs to be interpreted in the appropriate clinical and histological context. In contrast, immunohistochemistry (IHC) for mast cell tryptase is a granular cytoplasmic stain that has great specificity for mast cells. However, its expression is more variable than that of CD117/KIT; for example, in SM, neoplastic mast cells have less cytoplasm and fewer granules and thus may completely lose expression of tryptase.3Doyle L.A. Hornick J.L. Pathology of extramedullary mastocytosis.Immunol Allergy Clin North Am. 2014; 34: 323-339Abstract Full Text Full Text PDF PubMed Google Scholar Thus, in many clinical contexts, it is recommended to use both immunohistochemical stains, CD117/KIT and mast cell tryptase, to obtain optimal sensitivity and specificity or, if cost limitations exist, first to screen with the more sensitive stain, CD117/KIT, and second to confirm with the more specific one, mast cell tryptase. Mast cell clonality is usually conferred by activating mutations in the KIT gene, which lead to enhanced downstream signaling, including the PI3K/AKT, JAK/STAT, and RAS/MEK/ERK pathways, and confer resistance to apoptosis and increased proliferation. However, KIT.D816V is a relatively “weak driver” mutation and is unable to transform a stem cell clone into a full-blown malignancy by itself. Clonality can be assessed using expression of CD25 and/or CD2 as surrogate markers, but CD25 is recommended. CD25 expression, assessed by IHC or flow cytometry (most commonly performed as part of bone marrow evaluation), is a relatively specific and sensitive marker of clonality.16Horny H.P. Sillaber C. Menke D. Kaiserling E. Wehrmann M. Stehberger B. et al.Diagnostic value of immunostaining for tryptase in patients with mastocytosis.Am J Surg Pathol. 1998; 22: 1132-1140Crossref PubMed Scopus (195) Google Scholar Conversely, aberrant CD2 expression on mast cells can be challenging to interpret by IHC, especially when these aberrant mast cells do not demonstrate atypical clustering; CD2 is normally expressed on both T-cell lymphocytes and natural killer cells, making it difficult to differentiate scattered mast cells with aberrant CD2 expression from these other cells normally expressing CD2. One approach, albeit more subjective, is to perform IHC staining with CD3 in parallel with CD2 and compare levels of CD2- and CD3-positive cells. However, because CD25 is positive in almost all instances5Reichard K.K. Chen D. Pardanani A. McClure R.F. Howard M.T. Kurtin P.J. et al.Morphologically occult systemic mastocytosis in bone marrow: clinicopathologic features and an algorithmic approach to diagnosis.Am J Clin Pathol. 2015; 144: 493-502Crossref PubMed Google Scholar and is easier to interpret, CD25 is the recommended marker to assess mast cell clonality by IHC. CD2 may be more relevant when using flow cytometry than when using IHC, as flow cytometry technology more accurately distinguishes the specific cell types being assessed. In addition, other markers may be useful for specific conditions; for instance, CD30 is aberrantly expressed on mast cells in subsets of SM importantly including well-differentiated SM (WDSM), a condition in which other minor criteria are often not met.17Alvarez-Twose I. Jara-Acevedo M. Morgado J.M. Garcia-Montero A. Sanchez-Munoz L. Teodosio C. et al.Clinical, immunophenotypic, and molecular characteristics of well-differentiated systemic mastocytosis.J Allergy Clin Immunol. 2016; 137: 168-178.e1Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 18Blatt K. Cerny-Reiterer S. Schwaab J. Sotlar K. Eisenwort G. Stefanzl G. et al.Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis.Blood. 2015; 126: 2832-2841Crossref PubMed Scopus (0) Google Scholar, 19Sotlar K. Cerny-Reiterer S. Petat-Dutter K. Hessel H. Berezowska S. Mullauer L. et al.Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis.Mod Pathol. 2011; 24: 585-595Crossref PubMed Scopus (101) Google Scholar While initial studies have suggested CD30 is preferentially expressed in cases of advanced SM, other studies have shown its expression on more indolent forms and thus it is not considered useful for grading disease severity. However, particularly due to its expression on WDSM where CD25 is often negative, using CD30 in combination with CD25 has been shown to increase the diagnostic accuracy of SM.20Morgado J.M. Perbellini O. Johnson R.C. Teodosio C. Matito A. Alvarez-Twose I. et al.CD30 expression by bone marrow mast cells from different diagnostic variants of systemic mastocytosis.Histopathology. 2013; 63: 780-787Crossref PubMed Scopus (55) Google Scholar Thus, CD30 has recently been proposed as an additional minor diagnostic criterion of SM.21Valent P. Akin C. Hartmann K. Nilsson G. Reiter A. Hermine O. et al.Advances in the classification and treatment of mastocytosis: current status and outlook toward the future.Cancer Res. 2017; 77: 1261-1270Crossref PubMed Scopus (138) Google Scholar The main immunohistochemical markers and their interpretation are summarized in Table II.Table IIImmunohistochemical markers used in evaluating mastocytosisMarkerInterpretation∗Given the high sensitivity and low specificity of CD117 IHC and the low sensitivity and high specificity of Tryptase IHC, it is recommended to perform both tryptase and CD117 IHC to detect all mast cells and distinguish them from other cell types.CD117/KITSensitive, but not specific, marker of mast cells with membranous staining pattern.∗Given the high sensitivity and low specificity of CD117 IHC and the low sensitivity and high specificity of Tryptase IHC, it is recommended to perform both tryptase and CD117 IHC to detect all mast cells and distinguish them from other cell types.TryptaseSpecific, but not sensitive, marker of mast cells with granular cytoplasmic pattern. Staining can be patchy or even negative in neoplastic mast cells. However, it is highly sensitive for identifying over 95% of nonneoplastic human body mast cells.CD25 IHC is recommended to identify clonal mast cells.CD25Aberrantly expressed in neoplastic mast cells and thus can be used as surrogate of clonality. Mast cell expression of CD25 fulfills a minor WHO criterion for SM. CD25 is normally expressed in a subset of T cells.CD2Aberrantly expressed in neoplastic mast cells (smaller subset than CD25) and thus can be used as surrogate of clonality. However, CD2 is expressed in all T cells, and thus interpretation (confirming that CD2 is expressed on mast cells) can be difficult by IHC. Mast cell expression of CD2 fulfills a minor WHO criterion for SM.∗ Given the high sensitivity and low specificity of CD117 IHC and the low sensitivity and high specificity of Tryptase IHC, it is recommended to perform both tryptase and CD117 IHC to detect all mast cells and distinguish them from other cell types.∗∗ CD25 IHC is recommended to identify clonal mast cells. Open table in a new tab Although immunohistochemical stains are widely used to confirm mast cell lineage and to assess their clonality, assessing cell density in tissue to help diagnose mast cell–related diseases has been beset with limitations, including variable use of histochemical versus immunohistochemical stains; format of reported microscopic data (per hpf vs per mm2), microscopic field size (lack of standardization among microscopes), and hpf magnifications (eg, 200×, 250×, 400×); and use of average versus peak mast cell density counts.22Strobel S. Miller H.R. Ferguson A. Human intestinal mucosal mast cells: evaluation of fixation and staining techniques.J Clin Pathol. 1981; 34: 851-858Crossref PubMed Google Scholar Generally in normal tissues, histochemical stains are less sensitive for mast cells and yield lower mast cell densities than do immunohistochemical stains (Table III, Table IV and IV).23O'Neill M. Thomas L.M. Boyd A.S. Cutaneous mast cell counts—what constitutes a “normal” number?.J Cutan Pathol. 2010; 37: 919-921Crossref PubMed Scopus (4) Google Scholar, 24Ribatti D. Nico B. Finato N. Crivellato E. Beltrami C.A. Co-localization of tryptase and cathepsin-G in mast cells in cutaneous mastocytosis.Cancer Lett. 2009; 279: 209-212Crossref PubMed Scopus (10) Google Scholar, 25Janssens A.S. Heide R. den Hollander J.C. Mulder P.G. Tank B. Oranje A.P. Mast cell distribution in normal adult skin.J Clin Pathol. 2005; 58: 285-289Crossref PubMed Scopus (74) Google Scholar, 26Hahn H.P. Hornick J.L. Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for systemic mastocytosis.Am J Surg Pathol. 2007; 31: 1669-1676Crossref PubMed Scopus (0) Google Scholar, 27Chernetsova E. Sullivan K. de Nanassy J. Barkey J. Mack D. Nasr A. et al.Histologic analysis of eosinophils and mast cells of the gastrointestinal tract in healthy Canadian children.Hum Pathol. 2016; 54: 55-63Crossref PubMed Google Scholar, 28Saad A.G. Normal quantity and distribution of mast cells and eosinophils in the pediatric colon.Pediatr Dev Pathol. 2011; 14: 294-300Crossref PubMed Scopus (38) Google Scholar, 29Tison B.E. Debrosse C.W. Rainey H.F. Collins M.H. Putnam P.E. Rothenberg M.E. et al.Number and distribution of mast cells in the pediatric gastrointestinal tract [abstr].J Allergy Clin Immunol. 2010; 125: AB182Google Scholar, 30Barbara G. Stanghellini V. De Giorgio R. Cremon C. Cottrell G.S. Santini D. et al.Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome.Gastroenterology. 2004; 126: 693-702Abstract Full Text Full Text PDF PubMed Scopus (1076) Google Scholar, 31Guilarte M. Santos J. de Torres I. Alonso C. Vicario M. Ramos L. et al.Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum.Gut. 2007; 56: 203-209Crossref PubMed Scopus (305) Google Scholar, 32O'Sullivan M. Clayton N. Breslin N.P. Harman I. Bountra C. McLaren A. et al.Increased mast cells in the irritable bowel syndrome.Neurogastroenterol Motil. 2000; 12: 449-457Crossref PubMed Scopus (413) Google Scholar, 33Lloyd G. Green F.H. Fox H. Mani V. Turnberg L.A. Mast cells and immunoglobulin E in inflammatory bowel disease.Gut. 1975; 16: 861-865Crossref PubMed Google Scholar, 34Sarin S.K. Malhotra V. Sen Gupta S. Karol A. Gaur S.K. Anand B.S. Significance of eosinophil and mast cell counts in rectal mucosa in ulcerative colitis: a prospective controlled study.Dig Dis Sci. 1987; 32: 363-367Crossref PubMed Scopus (0) Google Scholar, 35Zare-Mirzaie A. Lotfi M. Sadeghipour A. Haghi-Ashtiani M.T. Analysis of colonic mucosa mast cell count in patients with chronic diarrhea.Saudi J Gastroenterol. 2012; 18: 322-326Crossref PubMed Scopus (6) Google Scholar Thus, it is generally recommended that immunohistochemical stains (CD117/KIT, mast cell tryptase) should be used to assess mast cell density in tissue sections. Other considerations for assessing mast cell density include the variable section thickness and specific tissue areas examined (eg, deep vs superficial dermis, bowel epithelium vs lamina propria).Table IIIMast cell density by tryptase IHC in normal skinRegionnMast cells/mm2Mast cells/hpf∗Converted values from Janssens et al25 assuming an hpf area of 0.15 mm2.MeanSDMeanSDTrunk23O'Neill M. Thomas L.M. Boyd A.S. Cutaneous mast cell counts—what constitutes a “normal” number?.J Cutan Pathol. 2010; 37: 919-921Crossref PubMed Scopus (4) Google Scholar19NDND10.26†Toluidine blue.1.91.2†Toluidine blue.Trunk24Ribatti D. Nico B. Finato N. Crivellato E. Beltrami C.A. Co-localization of tryptase and cathepsin-G in mast cells in cutaneous mastocytosis.Cancer Lett. 2009; 279: 209-212Crossref PubMed Scopus (10) Google Scholar8NDND12.53Trunk25Janssens A.S. Heide R. den Hollander J.C. Mulder P.G. Tank B. Oranje A.P. Mast cell distribution in normal adult skin.J Clin Pathol. 2005; 58: 285-289Crossref PubMed Scopus (74) Google Scholar1778.631.511.84.7Upper arm25Janssens A.S. Heide R. den Hollander J.C. Mulder P.G. Tank B. Oranje A.P. Mast cell distribution in normal adult skin.J Clin Pathol. 2005; 58: 285-289Crossref PubMed Scopus (74) Google Scholar4476.532.711.54.9Forearm25Janssens A.S. Heide R. den Hollander J.C. Mulder P.G. Tank B. Oranje A.P. Mast cell distribution in normal adult skin.J Clin Pathol. 2005; 58: 285-289Crossref PubMed Scopus (74) Google Scholar27101.232.615.24.9Upper leg25Janssens A.S. Heide R. den Hollander J.C. Mulder P.G. Tank B. Oranje A.P. Mast cell distribution in normal adult skin.J Clin Pathol. 2005; 58: 285-289Crossref PubMed Scopus (74) Google Scholar2974.938.811.25.8Lower leg25Janssens A.S. Heide R. den Hollander J.C. Mulder P.G. Tank B. Oranje A.P. Mast cell distribution in normal adult skin.J Clin Pathol. 2005; 58: 285-289Crossref PubMed Scopus (74) Google Scholar24113.246.717.07.0Data were modified from published work as noted.ND, Not determined (the area of hpf was not reported in these studies; thus, density per mm2 cannot be accurately determined).∗ Converted values from Janssens et al25Janssens A.S. Heide R. den Hollander J.C. Mulder P.G. Tank B. Oranje A.P. Mast cell distribution in normal adult skin.J Clin Pathol. 2005; 58: 285-289Crossref PubMed Scopus (74) Google Scholar assuming an hpf area of 0.15 mm2.† Toluidine blue. Open table in a new tab Table IVNormal mast cell counts in GI tract from varied articles and abstractsStainCount methodData reported asLocation(s), countAdult vs pediatricCommentReferenceTryptaseCD117CD25CD30400× magnification hpf (field size, 0.25 mm2)Mean ± SD (range)Colon, 19 ± 6.1 (7-39)AdultIBS and MCAS vs controlsDoyle et al4Doyle L.A. Sepehr G.J. Hamilton M.J. Akin C. Castells M.C. Hornick J.L. A clinicopathologic study of 24 cases of systemic mastocytosis
Referência(s)