Cutaneous mastocytosis

From Compendium of Cancer Genome Aberrations
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Haematolymphoid Tumours (5th ed.)

editHAEM5 Conversion Notes
This 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

HAEM4:Mastocytosis

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 Features
The 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

Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis)

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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  1. ↑ 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.
  2. ↑ 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)
  3. ↑ 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. ↑ 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)
  5. ↑ 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. ↑ 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. ↑ 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)
  8. ↑ 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)
  9. ↑ 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. ↑ 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. ↑ 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. ↑ 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.
  13. ↑ 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. ↑ 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. ↑ 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.

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