Skin: Cylindroma

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Skin: Cylindroma

Written	2012-04	André Fehr, Göran Stenman
		Sahlgrenska Cancer Center, Department of Pathology, University of Gothenburg, Box 425, SE-405 30 Gothenburg, Sweden

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C440-C449 SKIN

ICD-Morpho 8200/0 Cylindroma

Atlas_Id 6377

Phylum Lung, Heart, Skin, Other::Cylindroma

Other names Dermal cylindroma
Dermal eccrine cylindroma and (less specific) cylindroma

Clinics and Pathology

Disease Dermal cylindroma

Note Dermal cylindroma is a common benign adnexal tumor which occurs mainly in the head and neck region, especially on the scalp and face (Weedon, 2002; McNiff et al., 2006).

Clinics There is a strong predilection for middle-aged and elderly females. Dermal cylindromas may be found as solitary or multiple lesions, the latter being associated with the autosomal dominant Brooke-Spiegler syndrome (familial cylindromatosis; OMIM 605041) which is caused by mutations in the tumor suppressor gene CYLD (Bignell et al., 2000).

Pathology Microscopically, dermal cylindromas are composed of multiple tumor lobules arranged in a jigsaw pattern. The lobules are typically surrounded by a rim of PAS-positive basement membrane material and are composed of undifferentiated basaloid tumor cells. The histogenesis of dermal cylindroma is controversial. It is still uncertain whether they originate from apocrine or eccrine sweat glands or if they as recently suggested may be derived from hair follicle epithelium (reviewed in Weedon, 2002; Klein et al., 2005; Massoumi et al., 2006; Massoumi and Paus, 2007).

Cytogenetics

Cytogenetics
Morphological t(6;9)(q22-23;p23-24) translocation.

Genes involved and Proteins

Gene Name MYB (v-myb myeloblastosis viral oncogene homolog (avian))

Location 6q23.3

Note Leucine zipper transcription factor. MYB in solid tumors was recently reviewed by Stenman et al., 2010.

Dna / Rna RefSeq DNA sequence: NC_000006.11, NT_025741.15.

Protein The MYB protein plays an essential role in the regulation of hematopoiesis and may play a role in tumorigenesis. Alternative splicing results in multiple transcript variants.

Gene Name NFIB (nuclear factor I B)

Location 9p23

Note CCAAT-box-binding transcription factor.

Dna / Rna RefSeq DNA sequence: NC_000009.11, NT_008413.18.

Result of the chromosomal anomaly

Hybrid Gene
Note MYB-NFIB.

Description RT-PCR analysis revealed that 6 of 11 dermal cylindromas were positive for the MYB-NFIB fusion; one case had a fusion of MYB exon 12 to NFIB exon 9 and 5 cases had a fusion of MYB exon 14 to NFIB exon 8c. The composition of the chimeric transcript variants identified was identical to that previously reported in adenoid cystic carcinoma, suggesting a similar molecular mechanism of activation of MYB in both tumor types (Persson et al., 2009; Brill et al., 2011; Fehr et al., 2011).

Detection Described by Persson et al., 2009 and Fehr et al., 2011.

Fusion Protein
Description Analysis of MYB expression by immunohistochemistry using a monoclonal anti-MYB antibody recognizing an N-terminal peptide of the protein revealed overexpression of MYB in 6 of 10 cylindromas. Fusion-negative tumors lacked MYB expression, indicating that a subgroup of cylindromas in fact are MYB-negative (Fehr et al., 2011).

To be noted

The results from Fehr et al., 2011 indicate that MYB oncogene activation through gene fusion is an important pathogenetic mechanism that may contribute to cylindroma tumorigenesis. In this context it will be of interest to test also familial cases of cylindroma (Brooke Spiegler syndrome) for the MYB-NFIB fusion to determine whether MYB activation along with loss of CYLD1 simultaneously occur in these cases.

Bibliography

Identification of the familial cylindromatosis tumour-suppressor gene.

Bignell GR, Warren W, Seal S, Takahashi M, Rapley E, Barfoot R, Green H, Brown C, Biggs PJ, Lakhani SR, Jones C, Hansen J, Blair E, Hofmann B, Siebert R, Turner G, Evans DG, Schrander-Stumpel C, Beemer FA, van Den Ouweland A, Halley D, Delpech B, Cleveland MG, Leigh I, Leisti J, Rasmussen S.

Nat Genet. 2000 Jun;25(2):160-5.

PMID 10835629

Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms.

Brill LB 2nd, Kanner WA, Fehr A, Andren Y, Moskaluk CA, Loning T, Stenman G, Frierson HF Jr.

Mod Pathol. 2011 Sep;24(9):1169-76. doi: 10.1038/modpathol.2011.86. Epub 2011 May 13.

PMID 21572406

The MYB-NFIB gene fusion-a novel genetic link between adenoid cystic carcinoma and dermal cylindroma.

Fehr A, Kovacs A, Loning T, Frierson H Jr, van den Oord J, Stenman G.

J Pathol. 2011 Jul;224(3):322-7. doi: 10.1002/path.2909. Epub 2011 May 27.

PMID 21618541

Tumors of the epidermal appendages.

Klein W, Chan E, Seykora JT.

9th ed, Lippincott Williams & Wilkins: Philadelphia, 2005; 897-898.

Cylindromatosis and the CYLD gene: new lessons on the molecular principles of epithelial growth control.

Massoumi R, Paus R.

Bioessays. 2007 Dec;29(12):1203-14. (REVIEW)

PMID 18008375

Benign tumours with apocrine and eccrine differentiation.

McNiff JTHM, Requena L, Sangueza OP, Vassallo C, Rosso R, Borroni G, Glusac EJ, Pichardo RO.

World Health Organization Classification of Tumors Pathology and Genetics of Skin Tumours. Press: Lyon, France, 2006; 139-148.

Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck.

Persson M, Andren Y, Mark J, Horlings HM, Persson F, Stenman G.

Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18740-4. Epub 2009 Oct 19.

PMID 19841262

New tricks from an old oncogene: gene fusion and copy number alterations of MYB in human cancer.

Stenman G, Andersson MK, Andren Y.

Cell Cycle. 2010 Aug 1;9(15):2986-95. Epub 2010 Aug 28. (REVIEW)

PMID 20647765

Skin Pathology.

Weedon D.

2nd ed, Churchill-Livingstone: London, 2002; 890-891.

Citation

This paper should be referenced as such :

Fehr, A ; Stenman, G

Skin: Cylindroma

Atlas Genet Cytogenet Oncol Haematol. 2012;16(9):683-684.

Free journal version : [ pdf ] [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Tumors/SkinCylindromaID6377.html

Translocations implicated (Data extracted from papers in the Atlas)

t(6;9)(q23;p23) MYB/NFIB

External links

Mitelman database t(6;9)(q23;p23) [CaseList]     t(6;9)(q23;p23) [Transloc - MCList]   MYB/NFIB Fusion - MCList]
COSMIC [ MYB ]   [ NFIB ]

arrayMap Topo ( C44) arrayMap ((UZH-SIB Zurich) [auto + random 100 samples .. if exist ] [tabulated segments]

Mitelman database MYB/NFIB[MCList]    MYB (6q23.3) NFIB (9p23)   t(6;9)(q23;p22)

TCGA_Fusion MYB/NFIB    MYB (6q23.3) NFIB (9p23)

TICdb MYB/NFIB    MYB (6q23.3) NFIB (9p23)

Disease database Skin: Cylindroma

REVIEW articles automatic search in PubMed

Last year articles automatic search in PubMed

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For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.

ICD-Topo	C440-C449 SKIN
ICD-Morpho	8200/0 Cylindroma
Atlas_Id	6377
Phylum	Lung, Heart, Skin, Other::Cylindroma

Other names	Dermal cylindroma
	Dermal eccrine cylindroma and (less specific) cylindroma

Disease	Dermal cylindroma
Note	Dermal cylindroma is a common benign adnexal tumor which occurs mainly in the head and neck region, especially on the scalp and face (Weedon, 2002; McNiff et al., 2006).
Clinics	There is a strong predilection for middle-aged and elderly females. Dermal cylindromas may be found as solitary or multiple lesions, the latter being associated with the autosomal dominant Brooke-Spiegler syndrome (familial cylindromatosis; OMIM 605041) which is caused by mutations in the tumor suppressor gene CYLD (Bignell et al., 2000).
Pathology	Microscopically, dermal cylindromas are composed of multiple tumor lobules arranged in a jigsaw pattern. The lobules are typically surrounded by a rim of PAS-positive basement membrane material and are composed of undifferentiated basaloid tumor cells. The histogenesis of dermal cylindroma is controversial. It is still uncertain whether they originate from apocrine or eccrine sweat glands or if they as recently suggested may be derived from hair follicle epithelium (reviewed in Weedon, 2002; Klein et al., 2005; Massoumi et al., 2006; Massoumi and Paus, 2007).

Gene Name	MYB (v-myb myeloblastosis viral oncogene homolog (avian))
Location	6q23.3
Note	Leucine zipper transcription factor. MYB in solid tumors was recently reviewed by Stenman et al., 2010.
Dna / Rna	RefSeq DNA sequence: NC_000006.11, NT_025741.15.
Protein	The MYB protein plays an essential role in the regulation of hematopoiesis and may play a role in tumorigenesis. Alternative splicing results in multiple transcript variants.

Gene Name	NFIB (nuclear factor I B)
Location	9p23
Note	CCAAT-box-binding transcription factor.
Dna / Rna	RefSeq DNA sequence: NC_000009.11, NT_008413.18.

Hybrid Gene
Note	MYB-NFIB.
Description	RT-PCR analysis revealed that 6 of 11 dermal cylindromas were positive for the MYB-NFIB fusion; one case had a fusion of MYB exon 12 to NFIB exon 9 and 5 cases had a fusion of MYB exon 14 to NFIB exon 8c. The composition of the chimeric transcript variants identified was identical to that previously reported in adenoid cystic carcinoma, suggesting a similar molecular mechanism of activation of MYB in both tumor types (Persson et al., 2009; Brill et al., 2011; Fehr et al., 2011).
Detection	Described by Persson et al., 2009 and Fehr et al., 2011.
Fusion Protein
Description	Analysis of MYB expression by immunohistochemistry using a monoclonal anti-MYB antibody recognizing an N-terminal peptide of the protein revealed overexpression of MYB in 6 of 10 cylindromas. Fusion-negative tumors lacked MYB expression, indicating that a subgroup of cylindromas in fact are MYB-negative (Fehr et al., 2011).

Mitelman database	t(6;9)(q23;p23) [CaseList] t(6;9)(q23;p23) [Transloc - MCList] MYB/NFIB Fusion - MCList]
COSMIC	[ MYB ] [ NFIB ]
arrayMap	Topo ( C44) arrayMap ((UZH-SIB Zurich) [auto + random 100 samples .. if exist ] [tabulated segments]

Mitelman database	MYB/NFIB[MCList] MYB (6q23.3) NFIB (9p23) t(6;9)(q23;p22)
TCGA_Fusion	MYB/NFIB MYB (6q23.3) NFIB (9p23)
TICdb	MYB/NFIB MYB (6q23.3) NFIB (9p23)

Disease database	Skin: Cylindroma

REVIEW articles	automatic search in PubMed
Last year articles	automatic search in PubMed