MULTIPLE MUSHROOM-LIKE GROWING CYLINDROMAS OF THE SCALP (TURBAN TUMOR) IN A PATIENT WITH BROOKE-SPIEGLER SYNDROME: UNIQUE MANIFESTATION IN A BULGARIAN PATIENT

Abstract

Cutaneous cylindromas are rare, slow-growing adnexal tumors
commonly found on the capillitium or face. When located on
the capillitium, they can cluster together, forming a headgearlike structure that gives the characteristic “turban” appearance.
Brooke-Spiegler syndrome, an autosomal dominant condition,
is typically benign, though malignant transformation can occur.
We present a 61-year-old male with a 30-year history of
mushroom-like formations, clinically and histologically
confirmed as cylindromas, affecting approximately half of the
hairy part of the capillitium.
In addition, an erythematous-livid plaque with ulceration and
crusting was observed on both left and right lower legs. The
patient was suspected of having a sporadic, non-inherited form
of Brooke-Spiegler syndrome.
Surgical excision of the mushroom-like lesions was
recommended. In cases of non-inherited forms of BrookeSpiegler syndrome, early detection and preventative measures
are critical. A brief discussion focusing on the management of
the condition is provided, emphasizing whether true sporadic
cases of Brooke-Spiegler syndrome exist or if they represent
another clinically “silent” form of the condition.

Full text

EORGIAN
EDICAL
EWS
ЕЖЕМЕСЯЧНЫЙ НАУЧНЫЙ ЖУРНАЛ
Медицинские новости Грузии
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No 1 (322) Январь 2022
ISSN 1512-0112
ТБИЛИСИ - NEW YORK
NO 10 (355) Октябрь 2024

GMN: Georgian Medical News is peer-reviewed, published monthly journal committed to promoting
the science and art of medicine and the betterment of public health, published by the GMN Editorial
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GMN: Georgian Medical News is peer-reviewed, published monthly journal committed to promoting
the science and art of medicine and the betterment of public health, published by the GMN Editorial
Board since 1994. GMN carries original scientic articles on medicine, biology and pharmacy, which
are of experimental, theoretical and practical character; publishes original research, reviews, commen-
taries, editorials, essays, medical news, and correspondence in English and Russian.
GMN is indexed in MEDLINE, SCOPUS, PubMed and VINITI Russian Academy of Sciences. The full
text content is available through EBSCO databases.
GEORGIAN MEDICAL NEWS
GMN: Медицинские новости Грузии - ежемесячный рецензируемый научный журнал, издаётся
Редакционной коллегией с 1994 года на русском и английском языках в целях поддержки
медицинской науки и улучшения здравоохранения. В журнале публикуются оригинальные
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через БД EBSCO.
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avtorTa sayuradRebod!
redaqciaSi statiis warmodgenisas saWiroa davicvaT Semdegi wesebi:
1. statia unda warmoadginoT 2 calad, rusul an inglisur enebze, dabeWdili
standartuli furclis 1 gverdze, 3 sm siganis marcxena velisa da striqonebs
Soris 1,5 intervalis dacviT. gamoyenebuli kompiuteruli Srifti rusul da ing-
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masala da gamoyenebuli meTodebi; miRebuli Sedegebi da maTi gansja. eqsperimen-
tuli xasiaTis statiebis warmodgenisas avtorebma unda miuTiTon saeqsperimento
cxovelebis saxeoba da raodenoba; gautkivarebisa da daZinebis meTodebi (mwvave
cdebis pirobebSi).
4. statias Tan unda axldes reziume inglisur, rusul da qarTul enebze
aranakleb naxevari gverdis moculobisa (saTauris, avtorebis, dawesebulebis
miTiTebiT da unda Seicavdes Semdeg ganyofilebebs: mizani, masala da meTodebi,
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da sakvanZo sityvebis CamonaTvali (key words).
5. cxrilebi saWiroa warmoadginoT nabeWdi saxiT. yvela cifruli, Sema-
jamebeli da procentuli monacemebi unda Seesabamebodes teqstSi moyvanils.
6. fotosuraTebi unda iyos kontrastuli; suraTebi, naxazebi, diagramebi
- dasaTaurebuli, danomrili da saTanado adgilas Casmuli. rentgenogramebis
fotoaslebi warmoadgineT pozitiuri gamosaxulebiT ti formatSi. mikrofoto-
suraTebis warwerebSi saWiroa miuTiToT okularis an obieqtivis saSualebiT
gadidebis xarisxi, anaTalebis SeRebvis an impregnaciis meTodi da aRniSnoT su-
raTis zeda da qveda nawilebi.
7. samamulo avtorebis gvarebi statiaSi aRiniSneba inicialebis TandarTviT,
ucxourisa – ucxouri transkripciiT.
8. statias Tan unda axldes avtoris mier gamoyenebuli samamulo da ucxo-
uri Sromebis bibliografiuli sia (bolo 5-8 wlis siRrmiT). anbanuri wyobiT
warmodgenil bibliografiul siaSi miuTiTeT jer samamulo, Semdeg ucxoeli
avtorebi (gvari, inicialebi, statiis saTauri, Jurnalis dasaxeleba, gamocemis
adgili, weli, Jurnalis #, pirveli da bolo gverdebi). monografiis SemTxvevaSi
miuTiTeT gamocemis weli, adgili da gverdebis saerTo raodenoba. teqstSi
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mixedviT. mizanSewonilia, rom citirebuli wyaroebis umetesi nawili iyos 5-6
wlis siRrmis.
9. statias Tan unda axldes: a) dawesebulebis an samecniero xelmZRvane-
lis wardgineba, damowmebuli xelmoweriTa da beWdiT; b) dargis specialistis
damowmebuli recenzia, romelSic miTiTebuli iqneba sakiTxis aqtualoba, masalis
sakmaoba, meTodis sandooba, Sedegebis samecniero-praqtikuli mniSvneloba.
10. statiis bolos saWiroa yvela avtoris xelmowera, romelTa raodenoba
ar unda aRematebodes 5-s.
11. redaqcia itovebs uflebas Seasworos statia. teqstze muSaoba da Se-
jereba xdeba saavtoro originalis mixedviT.
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wardgenili iyo sxva redaqciaSi an gamoqveynebuli iyo sxva gamocemebSi.
aRniSnuli wesebis darRvevis SemTxvevaSi statiebi ar ganixileba.

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GEORGIAN MEDICAL NEWS
No 10 (355) 2024
© GMN 167
MULTIPLE MUSHROOM-LIKE GROWING CYLINDROMAS OF THE SCALP
(TURBAN TUMOR) IN A PATIENT WITH BROOKE-SPIEGLER SYNDROME: UNIQUE
MANIFESTATION IN A BULGARIAN PATIENT
Tchernev G1,2, Broshtilova V3, Kordeva S1.
1Onkoderma- Clinic for Dermatology, Venereology and Dermatologic Surgery, General Skobelev 26, 1606 Sofia, Bulgaria.
2Department of Dermatology and Venereology, Medical Institute of Ministry of Interior, General Skobelev 79, 1606, Sofia, Bulgaria.
3Department of Dermatology and Venereology, Medical Military Academy, Sofia, Bulgaria.
Abstract.
Cutaneous cylindromas are rare, slow-growing adnexal tumors
commonly found on the capillitium or face. When located on
the capillitium, they can cluster together, forming a headgear-
like structure that gives the characteristic “turban” appearance.
Brooke-Spiegler syndrome, an autosomal dominant condition,
is typically benign, though malignant transformation can occur.
We present a 61-year-old male with a 30-year history of
mushroom-like formations, clinically and histologically
conrmed as cylindromas, aecting approximately half of the
hairy part of the capillitium.
In addition, an erythematous-livid plaque with ulceration and
crusting was observed on both left and right lower legs. The
patient was suspected of having a sporadic, non-inherited form
of Brooke-Spiegler syndrome.
Surgical excision of the mushroom-like lesions was
recommended. In cases of non-inherited forms of Brooke-
Spiegler syndrome, early detection and preventative measures
are critical. A brief discussion focusing on the management of
the condition is provided, emphasizing whether true sporadic
cases of Brooke-Spiegler syndrome exist or if they represent
another clinically “silent” form of the condition.
Key words. Mushroom-like lesions, turban tumor,
cylindromas, Brooke-Spiegler syndrome, surgery.
Introduction.
Cutaneous cylindromas are rare, slow-growing adnexal
neoplastic lesions, typically located on the capillitium or face
[1]. They are predominantly derived from apocrine cells in
the dermis, specically within the hair follicle bulge [1,2].
These tumor formations on the capillitium can cluster together,
forming a headgear-like structure that gives the characteristic
“turban” appearance [1,3]. Rarely, pulmonary cylindromas can
develop in the large airways, potentially impairing the patient’s
breathing [1,4]. Men are rarely aected, with women being
approximately nine times more likely to develop the condition
[1].
The condition can be inherited or occur sporadically, with
sporadic cases typically observed in older patients [1]. It may
also present early in life, typically in the 20s or 30s, with
multiple lesions, which are frequently linked with cutaneous
syndromes such as Brooke-Spiegler syndrome, an autosomal
dominant condition caused by mutations in the CYLD gene
[1,5]. Although usually benign, malignant transformation can
rarely occur with fewer than 50 cases reported in the literature
[6].
Case report.
A 61-year-old man presented to the dermatology department
with a primary complaint of nodules, swelling, and redness on
the anterior surfaces of his lower legs and feet, persisting for the
past three weeks (Figures 1a & 1b). He also complained of pain
and itching both at rest and during movement.
The patient’s medical history includes arterial hypertension,
non-insulin-dependent diabetes mellitus, diabetic
polyneuropathy, ischemic heart disease, atrial brillation and
utter, mixed dyslipidemia, hypertensive heart disease without
congestive heart failure, idiopathic gout, and arthropathic
psoriasis. The patient is currently taking the following
medications: glimepiride 6 mg, metformin hydrochloride
1000 mg, empagliozin/linagliptin 10 mg, bisoprolol fumarate
10 mg, ivabradine 7.5 mg, amlodipine 5 mg, allopurinol 100
mg, doxazosin 7.5 mg, and etoricoxib 90 mg. The patient also
reports an allergy to contrast material.
Dermatological examination revealed an erythematous-livid
plaque with ulceration and crusting located on the medial
surface of the left lower leg (Figure 1a) and the second toe
of the right foot (Figure 1b). In the scalp region, exophytic
tumor-like formations were observed, presenting as multiple
conuent, monomorphic growths with a gyri-sulci like pattern
(Figures 2a & 2b). These mushroom-like formations clinically
resembled cylindromas or spiradenocarcinomas, involving
approximately half of the hairy part of the capillitium (Figures
2a & 2b). The patient reported a 30-year history of these lesions
Figure 1a,b. An erythematous-livid plaque with ulceration and
crusting located on the medial surface of the left lower leg (a) and the
second toe of the right foot (b).

168
with no family history of similar occurrences (none in the mother,
father, grandmother, or grandfather), suggesting the possibility
of a sporadic, non-inherited form of Brooke-Spiegler syndrome.
Additionally, he has a son who is also unaected by the condition.
Regarding the lesions on the anterior surface of the right and
left lower legs, the dierential diagnosis included vasculitis,
microembolization, and lichen aureus. Two punch biopsies were
performed. The biopsy taken from the left lower leg showed
no evidence of vasculitis. Instead, it revealed reactive changes
consistent with congestive heart failure and microangiopathy.
The biopsy taken from the formation covering the capillitium
revealed marked ortho- and follicular hyperkeratosis, irregular
acanthosis with elongation and owl-like dilatation of the distal
parts of the epidermal ridges. The dermal compartment was
densely hyalinized, with an underlying proliferation of atypical
basaloid keratinocytes forming zig-zag-shaped, multi-caliber
nests, surrounded by an eosinophilic periphery and demarcated
by mucinous, well-vascularized stroma. The histological
ndings were consistent with cylindroma (Figure 3a-c). The
patient was suspected of having Brooke-Spiegler syndrome.
Surgical removal of the tumor formations on the capillitium was
recommended under general anesthesia. The patient declined
surgical interventions and genetic testing for a CYLD gene
mutation due to personal reasons.
Outpatient regimen with pentoxifylline 600 mg twice daily,
acetylsalicylic acid 100 mg once daily, and heparin sodium gel
1000 ml applied twice daily to the lower leg for 10 days was
prescribed. Additionally, potassium permanganate compresses
were applied twice daily to the same area until the resolution of
the crusts. After consultation with a cardiologist, trimetazidine
dihydrochloride 35 mg twice daily was added to his existing
therapy.
Discussion.
The familial etiology of the condition is signicant and has been
consistently emphasized in the scientic literature [7]. Patients
with Brooke-Spiegler syndrome exhibit various mutations in
the tumor suppressor gene CYLD, located on chromosome
16q [8]. More than 50 germline mutations in the CYLD gene
have been identied, whereas somatic CYLD mutations remain
largely understudied [8].
Individuals with Brooke-Spiegler syndrome inherit a mutation
in one of the two copies of the CYLD gene present in all their
cells [9]. As a result, the altered copy of the CYLD gene is
unable to produce a functional CYLD protein [9]. The normal
copy of the CYLD gene typically produces enough protein to
regulate the cell growth eectively [9]. For a tumor to develop,
a second mutation or a deletion aecting the remaining copy of
the CYLD gene must occur in certain cells throughout the course
of life [9]. When both copies of the CYLD gene are aected,
the production of functional CYLD protein is disrupted [9]. The
absence of this protein leads to the loss of its regulatory role in
cell growth, allowing the aected cells to proliferate without
control, resulting in a tumor formation [9]. The absence of
CYLD protein in various skin cells contributes to the formation
of dierent skin appendage tumors [9]. This raises an intriguing
question: Are cases labelled as “sporadic” Brooke-Spiegler
syndrome truly sporadic, or could they represent autosomal
dominant inheritance where the second mutation has not yet
been identied or activated? This possibility highlights the need
for further genetic research to gain a deeper understanding of
these underlying genetic mechanisms.
An article by Sima et al. [8] showed that somatic events,
sequence mutations, or loss of heterozygosity, may vary among
multiple tumors of the same histologic type within the same
patient.
Various somatic mutations, including loss of heterozygosity, a
recurrent nonsense mutation, and a sequence mutation causing
exon skipping, were observed in a case of Brooke-Spiegler
syndrome with germline mutation in the CYLD gene [10].
These somatic alterations were detected in 4 dierent
cylindromas that were removed from the patient [10].
The absence of denitive genotype-phenotype correlations and
the presence of patients without germline CYLD mutations have
been also established [11]. Grossmann et al. [11] conducted a
study examining germline and somatic mutations of the CYLD
gene in patients with Brooke-Spiegler syndrome (n=49) and
multiple familial trichoepitheliomas - a phenotypic variant of
Brooke-Spiegler syndrome (n=18) using peripheral blood and
90 selected out of 379 available histological samples. Among
76 tumors from 32 patients with germline mutations, 26 were
identied as cylindromas [11].
Figure 2a,b. Exophytic nodular formations, conuent into a dense
plaque observed enclosing the capillitium.
Figure 3a-c. Histology panel: Marked ortho- and follicular
hyperkeratosis, irregular acanthosis with elongation and owl-like
dilatation of the distal parts of the epidermal ridges. The dermal
compartment is densely hyalinized, with an underlying proliferation of
atypical basaloid keratinocytes forming zig-zag-shaped, multi-caliber
nests, surrounded by an eosinophilic periphery and demarcated by
mucinous, well-vascularized stroma.
3a: Hyalinized cylindroma x HE x 40.
3b: Cylindroma x HE x 40.
3c: Cylindroma x HE x 100.

169
Somatic mutations were observed in 67 specimens of the 76
tumors (88%) [11].
Among these somatic mutations, 21 (31%) were sequence
alterations, 46 (69%) exhibited loss of heterozygosity [11].
In the remaining 9 cases (12%), the nature of the somatic
changes could not be determined [11].
Additionally, in 14 tumor samples from 8 patients without
germline mutation, somatic mutations were identied in 6
samples (43%) all consisting of sequence alterations; one
sample even contained 2 distinct sequence alterations [11].
In the last 8 samples (53%) no germline or somatic mutations
were identied [11].
The genetic basis of multiple cylindromas is well-established
but remains incompletely understood.
Cases such as the one we present suggest that turban tumors,
within the context of multiple scalp cylindromas, may arise
independently of autosomal dominant inheritance [1]. Clinical
ndings, including the absence of phenotypic expression in the
patient’s children, parents, and grandparents, provide further
evidence supporting this possibility. However, the hypothesis
that there are no sporadic cases of Brooke-Spiegler syndrome,
but rather only inherited forms where the second “activating”
mutation is absent, remains a possible explanation. In either
case, further research is necessary to conrm one of the
aforementioned hypotheses.
Rare and problematic cases are signicant because even
benign tumors can cause serious challenges and potential
complications such as unilateral hearing loss [12]. At the
time of the consultation, no potential complications related to
the syndrome were identied in our patient. Discomfort was
experienced due to the clinical appearance of the tumors.
The treatment of Brooke-Spiegler syndrome remains complex
due to the rarity of the condition [13]. Dierent therapeutic
approaches have been employed, including surgical excision,
electrodesiccation, dermabrasion, cryotherapy, radiotherapy,
and laser treatments such as argon, CO2, and erbium: Yag
CO2 lasers [14,15]. Sodium salicylate and prostaglandin A1
are being explored for their potential to restore growth control
by inhibiting NF-B activity [14,16]. Additionally, therapies
such as a combination of aspirin and adalimumab, and topical
imiquimod, have shown potential [13]. Systemic chemotherapy
or targeted therapies, including sonic hedgehog inhibitors like
vismodegib, have demonstrated some ecacy [13].
“Scalp-sparring” approaches, such as early primary excision or
tumor enucleation with direct skin closure, as well as excision
followed by secondary wound healing, are among the techniques
employed in the treatment of cylindromas [5]. Inltration of the
deep compartment can sometimes pose a signicant challenge,
resulting in persistent and long-lasting consequences for the
patients [17]. For these patients, the surgical approach is the
most preferred and eective treatment; however, it can be
challenging to perform in areas such as the capillitium and
face [18]. In dicult cases involving the scalp and face, scalp
excision and combined reconstruction with articial dermis and
split skin graft can be an eective approach [18].
A case of sporadic cylindroma in the external auditory canal
required ve stages of surgical intervention to achieve complete
removal [19,20]. The estimated recurrence rate of these
lesions after surgical excision is reported to be approximately
42% [20,21]. For smaller tumor formations, techniques such
as hyfrecation or laser ablation may be used, whereas Mohs
micrographic surgery is an option for recurrent cases [5].
Conclusion.
The mutation pattern plays a crucial role in determining
whether phenotypic manifestation will occur. In the absence of
a triggering or terminating second mutation, this manifestation
may not appear until several generations later. This delay in
phenotypic presentation highlights the complexity of genetic
inheritance and the role of additional factors in genetics.
A thorough investigation into potential causes or external factors
contributing to the development of these tumors is crucial.
Understanding the role of non-inherited mutations in the
pathogenesis of this syndrome should be a priority.
It is still a mystery whether sporadic cases of Brooke-Spiegler
syndrome exist, as some of these cases may simply represent
inactive forms of the syndrome, where the second mutation
required for full phenotypic manifestation has not yet occurred.
In such cases, the disease may remain clinically “silent” until
the second mutation or trigger is present, leading to the classical
clinical presentation of the tumors. This suggests that what is
often considered a sporadic case might actually represent a
“silent” autosomal dominant form of the disease.
In either case, prevention plays a crucial role, with surgical
excision being one of the most studied and preferred options for
management, particularly in achieving disease-free rates.
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