HAEM4:Cutaneous Mastocytosis
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
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
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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
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