Bone marrow nonneoplastic
Normal
Mast cells
Authors: Ramya Gadde, M.D., Rose Beck, M.D., Ph.D.
Editorial Board Members: Anamarija M. Perry, M.D., Alexa J. Siddon, M.D.
Last author update: 3 May 2023
Last staff update: 18 September 2024
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: Bone marrow mast cells
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Gadde R, Beck R. Mast cells. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrowmastcells.html. Accessed December 22nd, 2024.
Definition / general
- Mast cells are important cells of the hematopoietic lineage and play a crucial role in regulating the immune system, causing allergy and autoimmunity
Essential features
- Mast cells are oval, irregular and sometimes show elongated shapes with cytoplasmic extensions
- Dense, granular cytoplasm packed with basophilic granules is seen
- Neoplastic mast cells may have an atypical spindled shape or decreased granulation
- Mast cell granules show metachromatic staining with Wright, Giemsa and Leishman stains
- Wright stain of bone marrow shows deep pink to dark purple chunky granules that obscure the nucleus
- On H&E they exhibit bland nuclei and pale pink, granular cytoplasm; single cells are often difficult to visualize on H&E
- Also positive for toluidine blue and positive for immunostains tryptase and CD117 (bright expression)
- Reference: Immunol Allergy Clin North Am 2014;34:315, Leuk Res 2001;25:537, Int Arch Allergy Immunol 2018;176:55
Terminology
- Mastocyte; labrocyte
Pathophysiology
- Mast cells originate from the same multipotent hematopoietic progenitor cells of the bone marrow as neutrophils, eosinophils, basophils and monocytes (CD34+, KIT+, CD13+) and mature under the influence of the c-kit ligand, thrombopoietin, FLT3 ligand and IL6
- Under normal conditions, mature mast cells do not circulate in the bloodstream
- Mast cells are usually found in mucosal and epithelial tissues, all vascularized tissues except for the central nervous system and retina as well as in normal bone marrow (Blood 2008;112:946, J Histochem Cytochem 2014;62:698)
- Cytoplasm of the mast cell contains numerous large granules that store predominantly histamine, heparin, eicosanoids, cytokines, chondroitin sulfate and neutral proteases (J Histochem Cytochem 2014;62:698)
- Mast cells are known to participate in IgE mediated allergic reactions through FcεRI receptors and activation takes place via cross linking of antigen / IgE / FcεRI (Eur J Immunol 2014;44:2558)
- Mast cells play a key role in the regulation of physiological processes (e.g., vasodilation), enhancement of angiogenesis and elimination of bacteria and parasites (Front Immunol 2016;6:620)
Clinical features
- Reactive mast cell hyperplasia is often associated with chronic inflammatory, fibrogenic conditions and solid tumors (Am J Gastroenterol 2020;115:224)
- Mast cell hyperplasia in bone marrow may be seen in cases of hematologic malignancies such as lymphoplasmacytic lymphoma, chronic lymphocytic leukemia (CLL), myelodysplasia and acute myeloid leukemia (Cytometry B Clin Cytom 2021;100:331)
- Mastocytosis is a hematologic neoplasm defined by expansion and accumulation of neoplastic mast cells (MC) in the skin or in internal organs, such as the bone marrow (BM), spleen, lymph nodes, liver and gastrointestinal tract
- World Health Organization, 5th edition (WHO) and International Consensus classification (ICC) of myeloid neoplasms delineates mastocytosis into cutaneous mastocytosis (CM), systemic mastocytosis (SM) and mast cell sarcoma (MCS) (Leukemia 2022;36:1703, Blood 2022;140:1200)
- Based on disease specific features, systemic mastocytosis is further divided into indolent (ISM), smoldering (SSM), aggressive (ASM), systemic mastocytosis with an associated hematopoietic neoplasm (SM AHN) and mast cell leukemia (MCL) (Hemasphere 2021;5:e646)
Microscopic (histologic) description
- Rare in normal marrow, usually concentrated within particles on aspirate smears and perivascular on biopsy sections
- Mast cells are oval or irregularly shaped cells
- Up to 100% larger than basophils with irregular, elongated shapes and cytoplasmic extensions
- Dense, granular cytoplasm packed with basophilic granules is seen, often obscuring the nucleus and other organelles
- When it can be visualized, the nucleus is round and central (StatPearls: Histology, Mast Cells [Accessed 2 March 2023])
Microscopic (histologic) images
Contributed by Ramya Gadde, M.D. and AFIP
Scattered mast cells
Spindle shaped mast cells
Tryptase
Scattered mast cells with basophilic granules
Positive stains
- Mast cell granules can show metachromatic staining with the Romanowsky combinations (Wright, Giemsa, May-Grünwald Giemsa and Leishman), toluidine blue
- Tryptase, CD117 (Int Arch Allergy Immunol 2018;176:55)
- Aberrant expression of various other hematopoietic antigens by neoplastic mast cells in systemic mastocytosis has been documented; the following antigens may be abnormally expressed, in varying frequency and intensity (Immunol Allergy Clin North Am 2014;34:315):
- Myelomonocytic antigens: CD14, CD33, CD61, CD63, CD68, CD203c, 2D7, myeloperoxidase, naphthol AS-D chloroacetate esterase
- Lymphoid antigens: CD2, CD9, CD25, CD26, CD30, CD52, CD79a
- Stem cell associated antigens: CD44
- Natural killer cell associated antigen: CD57
- Dendritic cell associated antigens: CD35, CD123
- Other antigens: CD99, SDF1 (Immunol Allergy Clin North Am 2014;34:315)
Electron microscopy description
- Electron microscopy demonstrates mast cells, highly granulated cells of the immune system
- Mast cells can be identified by their central nucleus and numerous granules containing histamine and enzymes
- Upon stimulation by an antigen, the cell degranulates
- Reference: Ribatti: Milestones in Immunology - Based on Collected Papers, 1st Edition, 2017
Electron microscopy images
Images hosted on other servers:
Degranulating mast cell
Mast cells with abundant granules
Differential diagnosis
- Systemic mastocytosis:
- Major criteria:
- Multifocal dense infiltrates of mast cells (≥ 15 mast cells in aggregates) in bone marrow biopsies or in sections of other extracutaneous organ(s)
- Minor criteria:
- ≥ 25% of all mast cells are atypical cells or spindle shaped mast cell infiltrates detected in sections of bone marrow or other extracutaneous organs
- KIT activating KIT point mutation(s) at codon 816 or in other critical regions of KIT in bone marrow or another extracutaneous organ
- Mast cells in bone marrow, blood or another extracutaneous organ express 1 or more of CD2, CD30 or CD25
- Baseline serum tryptase concentration > 20 ng/mL (in cases of SM AHN, an elevated tryptase does not count as an SM criterion; in the case of a known hereditary alpha-tryptasaemia, the tryptase level should be adjusted)
- If at least 1 major and 1 minor or 3 minor criteria are fulfilled → the diagnosis is SM can be made (Leukemia 2022;36:1703, Blood 2022;140:1200)
- Major criteria:
Board review style question #1
What are the common immunostains used to differentiate reactive and neoplastic mast cells?
- CD2, CD25 and CD30
- CD13 and CD33
- CD34 and CD117
- CD117 and tryptase
Board review style answer #1
A. CD2, CD25 and CD30 show aberrant expression in neoplastic mast cells and are useful to differentiate reactive mast cells from neoplastic mast cells. CD13, CD33 and CD34 are negative in mast cells; CD117 and tryptase are positive in both reactive and neoplastic mast cells.
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Board review style question #2
Detection of which of the following activating mutations is used as one of the minor criteria for diagnosis of systemic mastocytosis?
- JAK2
- KIT
- NPM1
- RUNX1
Board review style answer #2
B. KIT. Presence of KIT mutation is one of the minor criteria for diagnosis of systemic mastocytosis. JAK2, NPM1 and RUNX1 are associated with myeloid neoplasms and not with mastocytosis.
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