Skin: Cylindroma

2012-04-01   André Fehr , Goran Stenman 

Clinics and Pathology

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 description

RefSeq DNA sequence: NC_000006.11, NT_025741.15.

Protein description

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 description

RefSeq DNA sequence: NC_000009.11, NT_008413.18.

Result of the chromosomal anomaly

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 protocole

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

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

Note

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

Pubmed IDLast YearTitleAuthors
108356292000Identification of the familial cylindromatosis tumour-suppressor gene.Bignell GR et al
215724062011Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms.Brill LB 2nd et al
216185412011The MYB-NFIB gene fusion-a novel genetic link between adenoid cystic carcinoma and dermal cylindroma.Fehr A et al
180083752007Cylindromatosis and the CYLD gene: new lessons on the molecular principles of epithelial growth control.Massoumi R et al
198412622009Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck.Persson M et al
206477652010New tricks from an old oncogene: gene fusion and copy number alterations of MYB in human cancer.Stenman G et al

Citation

André Fehr ; Goran Stenman

Skin: Cylindroma

Atlas Genet Cytogenet Oncol Haematol. 2012-04-01

Online version: http://atlasgeneticsoncology.org/solid-tumor/6377/skin-cylindroma