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in Oncology and Haematology
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Cancer Prone Disease Section
Short Communication
Brooke-Spiegler syndrome
Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
(JLH)
Published in Atlas Database: November 2011
Online updated version : http://AtlasGeneticsOncology.org/Kprones/BrookeSpieglerID10097.html
DOI: 10.4267/2042/47310
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Spiradenomas are usually located on the face, the trunk
and extremities. A frequent symptom is pain. They
present as bluish nodules of basaloid cells in the
dermis, with presence of numerous lymphocytes, in
contrast to what is found in cylindromas. There are
hybrid forms between cylindromas and spiradenomas.
Trichoepitheliomas typically occur on the face,
predominantly on the nose, the nasolabial folds, and the
lips. Trichoepitheliomas derive from the trichoblast
(i.e. the folliculo-sebaceous-apocrine germ). They are
small skin-colored papules or nodules, with nests of
basaloid cells forming cysts containing horn cells (with
keratin) (Lee et al., 2005; Kim et al., 2007; Blake and
Toro, 2009).
Identity
Other names
Ancell-Spiegler cylindromas, Familial cylindromatosis,
Turban
tumor
syndrome,
Brooke-Fordyce
trichoepitheliomas,
Multiple
familial
trichoepitheliomas
Note
Familial cylindromatosis/Turban tumor syndrome and
multiple familial trichoepitheliomas were considered as
separate diseases; it is now known that they are allelic
diseases and represent two ends of the Brooke-Spiegler
syndrome spectrum (Welch et al., 1968; Young et al.,
2006).
Familial
cylindromatosis/Turban
tumor
syndrome is characterized by cylindromas and multiple
familial trichoepitheliomas by trichoepitheliomas as the
only tumor type.
Inheritance
Autosomal dominant disease, with high penetrance, and
penetrance increasing with age, and variable
expressivity. Female predominance (8M/13F).
Neoplastic risk
Apart from cylindromas, spiradenomas, and
trichoepitheliomas, patients with Brooke-Spiegler
syndrome are also at risk of basal cell carcinomas and
syringomas. Cylindromas may transform into
cylindrocarcinomas, which are locally aggressive and
metastasize. Spiradenomas may transform into
spiradenocarcinomas
or
show
sarcomatous
differentiation. An increased risk of developing tumors
of the salivary glands has also been described (basalcell adenomas and adenocarcinomas of the parotid
glands and minor salivary glands) (Lee et al., 2005;
Kim et al., 2007; Blake and Toro, 2009).
Clinics
Phenotype and clinics
Brooke-Spiegler syndrome is a skin appendage tumors
syndrome, with development of cylindromas,
spiradenomas, and/or trichoepitheliomas, from late
childhood, and gradually increase in size and numbers.
Cylindromas are dermal papules and nodules. They
grow slowly. They classically occur on the scalp and
occasionally on the face, trunk or extremities. Scalp
cylindromas can become numerous and may eventually
cover the entire scalp ("turban tumors").
They present as multinodular, well circumscribed nest
of undifferentiated basaloid cells in a charateristic
"jigsaw puzzle" pattern.
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4)
Treatment
Removal by surgery. Salicylic acid is efficient in only a
small proportion of tumours.
Genes involved and proteins
Note
Although most cases of Brooke-Spiegler syndrome
have been described with a mutation in CYLD (Bignell
et al., 2000; 68 unique CYLD mutations have been
304
Brooke-Spiegler syndrome
Huret JL
Schrander-Stumpel C, Beemer FA, van Den Ouweland A,
Halley D, Delpech B, Cleveland MG, Leigh I, Leisti J,
Rasmussen S. Identification of the familial cylindromatosis
tumour-suppressor gene. Nat Genet. 2000 Jun;25(2):160-5
identified so far), some cases do not have mutations or
loss of heterozygosity in CYLD gene (Ponti et al.,
2011).
Transcriptome of the tumors: cylindroma and
spiradenoma tumours showed similar profile, with
LOH at 16q found in the majority of the tumours, and
upregulation of TRKB, TRKC, NT3/NT4, and BDNF,
and ERK and BCL2 as well, while the transcriptome of
trichoepitheliomas was different (Rajan et al., 2011).
Lee DA, Grossman ME, Schneiderman P, Celebi JT. Genetics
of skin appendage neoplasms and related syndromes. J Med
Genet. 2005 Nov;42(11):811-9
Young AL, Kellermayer R, Szigeti R, Tészás A, Azmi S, Celebi
JT. CYLD mutations underlie Brooke-Spiegler, familial
cylindromatosis, and multiple familial trichoepithelioma
syndromes. Clin Genet. 2006 Sep;70(3):246-9
CYLD
Kim C, Kovich OI, Dosik J. Brooke-Spiegler syndrome.
Dermatol Online J. 2007 Jan 27;13(1):10
Location
16q12.1
Protein
Description
Member of the deubiquitinase family. Cleaves Lys-63linked polyubiquitin chains. Negative regulator of NFkappaB and JNK signalings. Binds NEMO, TRAF2
and TRAF6 and deubiquitinates them. Participates in
antimicrobial defense and inflammation (Review in
Courtois, 2010).
Mutations
Germinal
Most of the mutations produce large deletions of the
protein.
Somatic
Different types of somatic mutations in benign and
malignant tumors (Kazakov et al., 2010).
Blake PW, Toro JR. Update of cylindromatosis gene (CYLD)
mutations in Brooke-Spiegler syndrome: novel insights into the
role of deubiquitination in cell signaling. Hum Mutat. 2009
Jul;30(7):1025-36
Courtois G.. CYLD (cylindromatosis (turban tumor syndrome)).
Atlas Genet Cytogenet Oncol Haematol. May 2010. URL:
http://AtlasGeneticsOncology.org/Genes/CYLDID40232ch16q1
2.html
Kazakov DV, Schaller J, Vanecek T, Kacerovska D, Michal M..
Brooke-Spiegler syndrome: report of a case with a novel
mutation in the CYLD gene and different types of somatic
mutations in benign and malignant tumors. J Cutan Pathol.
2010 Aug;37(8):886-90. Epub 2010 Feb 4.
Ponti G, Nasti S, Losi L, Pastorino L, Pollio A, Benassi L,
Giudice S, Bertazzoni G, Veratti E, Azzoni P, Scarra GB,
Seidenari S.. Brooke-Spiegler syndrome: report of two cases
not associated with a mutation in the CYLD and PTCH tumorsuppressor genes. J Cutan Pathol. 2011 Nov 12. doi:
10.1111/j.1600-0560.2011.01813.x. [Epub ahead of print]
Rajan N, Elliott R, Clewes O, Mackay A, Reis-Filho JS, Burn J,
Langtry J, Sieber-Blum M, Lord CJ, Ashworth A.. Dysregulated
TRK signalling is a therapeutic target in CYLD defective
tumours. Oncogene. 2011 Oct 13;30(41):4243-60. doi:
10.1038/onc.2011.133. Epub 2011 May 9.
References
Welch JP, Wells RS, Kerr CB. Ancell-Spiegler cylindromas
(turban tumours) and Brooke-Fordyce Trichoepitheliomas:
evidence for a single genetic entity. J Med Genet. 1968
Mar;5(1):29-35
This article should be referenced as such:
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,
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4)
Huret JL. Brooke-Spiegler syndrome. Atlas Genet Cytogenet
Oncol Haematol. 2012; 16(4):304-305.
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