Cutaneous mastocytosis
Haematolymphoid Tumours (5th ed.)
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editHAEM5 Conversion NotesThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Cutaneous Mastocytosis.
(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)
Primary Author(s)*
S. Shawn Liu, MD, PhD and Thuy Phung, MD, PhD
Cancer Category / Type
Cancer Sub-Classification / Subtype
Cutaneous Mastocytosis
Definition / Description of Disease
Cutaneous mastocytosis is a mast cell disorder that primarily affects the skin.
Synonyms / Terminology
Urticaria pigmentosa
Epidemiology / Prevalence
Cutaneous mastocytosis (CM) most commonly affect children, which is usually diagnosed prior to 2 years old with slight male predominance [1][2]. Approximately 80% of patient of mastocytosis develop cutaneous lesion [3].
Clinical Features
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| Signs and Symptoms | EXAMPLE Asymptomatic (incidental finding on complete blood counts)
EXAMPLE B-symptoms (weight loss, fever, night sweats) EXAMPLE Fatigue EXAMPLE Lymphadenopathy (uncommon) |
| Laboratory Findings | EXAMPLE Cytopenias
EXAMPLE Lymphocytosis (low level) |
editv4:Clinical FeaturesThe content below was from the old template. Please incorporate above.There are three typical variants of cutaneous mastocytosis: 1) urticaria pigmentosa (UP)/maculopapular cutaneous mastocytosis (MPCM), 2) diffuse CM, and 3) mastocytoma of skin. UP/MPCM is the most common type and presents as brown or red macule or macule and papules with melanin pigmentation. Diffuse CM is almost exclusively in childhood and presents as diffusely thickened skin, pachydermia. Familial cases and germline mutations can be associated diffuse CM. Cutaneous mastocytoma is also known as solitary mastocytoma of skin, which is single or less than 3 lesions without predilection for presenting site. In addition, CM cannot be diagnosed if the features or criteria of systemic mastocytosis are met.
Sites of Involvement
Cutaneous mastocytosis can present in any location of the body with common involvement of extremities and trunk.
Morphologic Features
Histologically, CM demonstrates increased number of mast cells in skin lesion. UP/MPCM reveals spindle-shaped mast cells in papillary dermis with extension to reticular dermis. Diffuse CM demonstrate highest number of mast cells in sheets filling papillary and upper reticular dermis. Cutaneous mastocytoma usually involves subcutaneous tissue with abundant granular cytoplasm of mast cells.
Immunophenotype
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| Finding | Marker |
|---|---|
| Positive (universal) | CD117; Tryptase |
| Positive (subset) | Aberrant CD25 and CD2; CD30 in well-differentiated mastocytosis |
| Negative (universal) | B-cell antigens; CD3; CD5; CD7; MPO; CD15; CD21; CD34 |
Chromosomal Rearrangements (Gene Fusions)
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| Chromosomal Rearrangement | Genes in Fusion (5’ or 3’ Segments) | Pathogenic Derivative | Prevalence | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|
| EXAMPLE t(9;22)(q34;q11.2) | EXAMPLE 3'ABL1 / 5'BCR | EXAMPLE der(22) | EXAMPLE 20% (COSMIC)
EXAMPLE 30% (add reference) |
Yes | No | Yes | EXAMPLE
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). |
Individual Region Genomic Gain / Loss / LOH
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| Chr # | Gain / Loss / Amp / LOH | Minimal Region Genomic Coordinates [Genome Build] | Minimal Region Cytoband | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|
| EXAMPLE
7 |
EXAMPLE Loss | EXAMPLE
chr7:1- 159,335,973 [hg38] |
EXAMPLE
chr7 |
Yes | Yes | No | EXAMPLE
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). |
| EXAMPLE
8 |
EXAMPLE Gain | EXAMPLE
chr8:1-145,138,636 [hg38] |
EXAMPLE
chr8 |
No | No | No | EXAMPLE
Common recurrent secondary finding for t(8;21) (add reference). |
Characteristic Chromosomal Patterns
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| Chromosomal Pattern | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|
| EXAMPLE
Co-deletion of 1p and 18q |
Yes | No | No | EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). |
Gene Mutations (SNV / INDEL)
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| Gene; Genetic Alteration | Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) | Prevalence (COSMIC / TCGA / Other) | Concomitant Mutations | Mutually Exclusive Mutations | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|---|
| EXAMPLE: TP53; Variable LOF mutations
EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations |
EXAMPLE: TSG | EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference) |
EXAMPLE: IDH1 R123H | EXAMPLE: EGFR amplification | EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).
|
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
editv4:Gene Mutations (SNV/INDEL)The content below was from the old template. Please incorporate above.Put your text here and/or fill in the tables
Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other) c-KIT c.2447A>T; p.D816V (Chr 4: 54733154-54733155)
Oncogene GOF 40-80%[4][5] c-KIT[4][6] [7] c.2446G>T; p.D816Y (Chr 4: 54733153-54733154) Oncogene GOF c-KIT[4] c.2446_2447delinsAT; p.D816I (Chr 4: 54733153-54733155) Oncogene GOF c-KIT[4] c.1715A>C; p.D572A (Chr 4: 54727482-54727483) Oncogene GOF c-KIT[4] c.1526A>T; p.K509I (Chr 4: 54726035-54726036) Oncogene LOF c-KIT[4] c.1621A>C; p.M541L (Chr 4: 54727297-54727298) Oncogene LOF c-KIT[4] c.1328G>A; p.C443Y (Chr 4: 54723679-54723680) Oncogene LOF c-KIT[4] c.1427G>T; p.S476I (Chr 4: 54725936-54725937) Oncogene LOF c-KIT[4] c.1255_1257del; p.D419del (Chr 4: 54723606-54723609) Oncogene c-KIT[4] c.1249_1255delinsT; p.T417_D419delinsY (Chr 4: 54723601-54723607) Oncogene LOF c-KIT[4] c.1255insTTCTTC; p.D419insFF (Chr 4: 54723606-54723607) Oncogene c-KIT[4] c.1500_1505dup; p.S501‐A502dup (Chr 4: 54726014-54726016) Oncogene c-KIT[4] ITD AY502‐503 Oncogene LOF c-KIT[4] ITD NFAF505‐508 Oncogene c-KIT D815K Oncogene <5% [7] c-KIT[6] E839K Oncogene LOF c-KIT c.2446_2447delincTT; p.D816F (Chr 4: 54733153-54733155) Oncogene GOF <5%[6][7] c-KIT c.2446_2448delinsCAT; p.D816H (Chr 4: 54733153-54733156) Oncogene GOF <5% [8] c-KIT c.2459A>G; p.D820G (Chr 4: 54733166-54733167) Oncogene <5% [9] c-KIT c.2449A>G; p.I817V (Chr 4: 54733156-54733157) Oncogene <5% [10] c-KIT c.2446_2447insTCATAG; p.R815_D816insVI (Chr 4: 54733153-54733155) Oncogene <5% [10] c-KIT c.1598C>A; p.A533D (Chr 4: 54727274-54727275) Oncogene Germline <5% [11] c-KIT F522C Oncogene Germline <5% [12] c-KIT Y560G Oncogene <5%[13] TET2 [14] 1777_1778insG Suppressor TET2[14] 723_724delAG Suppressor TET2[14] 3248_delT Suppressor TET2[14] 278_279insA Suppressor TET2[14] 1554_delG Suppressor TET2[14] 1305A>G Suppressor TET2[14] 2628C>T Suppressor TET2[14] 231C>T Suppressor TET2[14] 695_696insT Suppressor TET2[14] 3070_3071insA Suppressor TET2[14] 955-956insT Suppressor TET2[14] 2812-2813insT Suppressor TET2[14] 252_262delCTCTACAGAAG Suppressor TET2[14] 236_delG Suppressor TET2[14] 2468_2469insA Suppressor TET2[14] 208C>T Suppressor NRAS[15] c.35G>A; p.G12D (Chr 1: 114716125-114716126) Oncogene NRAS[15] c.38G>A; p.G13D (Chr 1: 114716122-114716123) Oncogene Other Mutations
Type Gene/Region/Other Concomitant Mutations EXAMPLE IDH1 R123H Secondary Mutations EXAMPLE Trisomy 7 Mutually Exclusive EXAMPLE EGFR Amplification
Epigenomic Alterations
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Genes and Main Pathways Involved
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| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
| EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
Genetic Diagnostic Testing Methods
Put your text here
Familial Forms
c-KIT A533D [11]
c-KIT F522C [12]
Additional Information
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Links
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References
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- ↑ Castells, Mariana; et al. (2011-08-01). "Diagnosis and treatment of cutaneous mastocytosis in children: practical recommendations". American Journal of Clinical Dermatology. 12 (4): 259–270. doi:10.2165/11588890-000000000-00000. ISSN 1179-1888. PMC 4126834. PMID 21668033.
- ↑ Hartmann, Karin; et al. (2002-02). "Cutaneous mastocytosis -- clinical heterogeneity". International Archives of Allergy and Immunology. 127 (2): 143–146. doi:10.1159/000048187. ISSN 1018-2438. PMID 11919426. Check date values in:
|date=(help) - ↑ Pardanani, A.; et al. (2006). "Pathogenesis, clinical features, and treatment advances in mastocytosis". Best Practice & Research. Clinical Haematology. 19 (3): 595–615. doi:10.1016/j.beha.2005.07.010. ISSN 1521-6926. PMID 16781490.
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 Bodemer, Christine; et al. (2010-03). "Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations". The Journal of Investigative Dermatology. 130 (3): 804–815. doi:10.1038/jid.2009.281. ISSN 1523-1747. PMID 19865100. Check date values in:
|date=(help) - ↑ Longley, B. J.; et al. (2001-07). "Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy". Leukemia Research. 25 (7): 571–576. doi:10.1016/s0145-2126(01)00028-5. ISSN 0145-2126. PMID 11377682. Check date values in:
|date=(help) - ↑ 6.0 6.1 6.2 Longley, B. J.; et al. (1999-02-16). "Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis". Proceedings of the National Academy of Sciences of the United States of America. 96 (4): 1609–1614. doi:10.1073/pnas.96.4.1609. ISSN 0027-8424. PMC 15534. PMID 9990072.CS1 maint: PMC format (link)
- ↑ 7.0 7.1 7.2 Sotlar, Karl; et al. (2003-03). "One-step detection of c-kit point mutations using peptide nucleic acid-mediated polymerase chain reaction clamping and hybridization probes". The American Journal of Pathology. 162 (3): 737–746. doi:10.1016/S0002-9440(10)63870-9. ISSN 0002-9440. PMC 1868096. PMID 12598308. Check date values in:
|date=(help) - ↑ Pullarkat, V. A.; et al. (2000-12). "Mast cell disease associated with acute myeloid leukemia: detection of a new c-kit mutation Asp816His". American Journal of Hematology. 65 (4): 307–309. doi:10.1002/1096-8652(200012)65:43.0.co;2-f. ISSN 0361-8609. PMID 11074560. Check date values in:
|date=(help) - ↑ Pignon, J. M.; et al. (1997-02). "A new c-kit mutation in a case of aggressive mast cell disease". British Journal of Haematology. 96 (2): 374–376. doi:10.1046/j.1365-2141.1997.d01-2042.x. ISSN 0007-1048. PMID 9029028. Check date values in:
|date=(help) - ↑ 10.0 10.1 Garcia-Montero, Andres C.; et al. (2006-10-01). "KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients". Blood. 108 (7): 2366–2372. doi:10.1182/blood-2006-04-015545. ISSN 0006-4971. PMID 16741248.
- ↑ 11.0 11.1 Tang, X.; et al. (2004-06). "A germline mutation in KIT in familial diffuse cutaneous mastocytosis". Journal of Medical Genetics. 41 (6): e88. doi:10.1136/jmg.2003.015156. ISSN 1468-6244. PMC 1735799. PMID 15173254. Check date values in:
|date=(help) - ↑ 12.0 12.1 Akin, Cem; et al. (2004-04-15). "A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib". Blood. 103 (8): 3222–3225. doi:10.1182/blood-2003-11-3816. ISSN 0006-4971. PMID 15070706.
- ↑ Lim, Ken-Hong; et al. (2009-06-04). "Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors". Blood. 113 (23): 5727–5736. doi:10.1182/blood-2009-02-205237. ISSN 1528-0020. PMID 19363219.
- ↑ 14.00 14.01 14.02 14.03 14.04 14.05 14.06 14.07 14.08 14.09 14.10 14.11 14.12 14.13 14.14 14.15 Tefferi, A.; et al. (2009-05). "Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates". Leukemia. 23 (5): 900–904. doi:10.1038/leu.2009.37. ISSN 1476-5551. PMC 4654631. PMID 19262599. Check date values in:
|date=(help) - ↑ 15.0 15.1 Wilson, Todd M.; et al. (2011-03). "Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis". Haematologica. 96 (3): 459–463. doi:10.3324/haematol.2010.031690. ISSN 1592-8721. PMC 3046279. PMID 21134978. Check date values in:
|date=(help)
Notes
*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome. *Citation of this Page: “Cutaneous mastocytosis”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 02/27/2024, https://ccga.io/index.php/HAEM5:Cutaneous_mastocytosis.