HAEM4Backup:Cutaneous Mastocytosis

Revision as of 12:28, 3 November 2023 by Bailey.Glen (talk | contribs) (Created page with " ==Primary Author(s)*== S. Shawn Liu, MD, PhD and Thuy Phung, MD, PhD __TOC__ ==Cancer Category/Type== Mastocytosis ==Cancer Sub-Classification / Subtype== Cutaneous...")
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)

Primary Author(s)*

S. Shawn Liu, MD, PhD and Thuy Phung, MD, PhD

Cancer Category/Type

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

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

Put your text here and/or fill in the table

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

Genomic Gain/Loss/LOH

Put your text here and/or fill in the table

Chromosome Number Gain/Loss/Amp/LOH Region
EXAMPLE 8 EXAMPLE Gain EXAMPLE chr8:0-1000000
EXAMPLE 7 EXAMPLE Loss EXAMPLE chr7:0-1000000

Gene Mutations (SNV/INDEL)

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

Familial Forms

c-KIT A533D [11]

c-KIT F522C [12]

References

(use "Cite" icon at top of page)

  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.