| Written | 2012-04 | André Fehr, Göran Stenman |
| Sahlgrenska Cancer Center, Department of Pathology, University of Gothenburg, Box 425, SE-405 30 Gothenburg, Sweden |
| 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 |
| Location | 6q23 |
| 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 |
| Location | 9p23-p22 |
| 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 |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Jun 17 12:10:52 CEST 2017 |
For comments and suggestions or contributions, please contact us