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CASE REPORT
Basal cell nevus syndrome in a 56-year old Filipino
female: a case report
Kathleen May V. Eusebio-Alpapara, MD, DPDS1, Cindy Pearl Sotalbo, MD, FPCR2, Cynthia Ciriaco-Tan,
MD, FPDS1
Introduction: Basal cell nevus syndrome (BCNS) (Gorlin-Goltz syndrome or Nevoid basal cell carcinoma syndrome) is a rare
inherited multisystem and tumor-predisposing disorder caused by the patched tumor suppressor gene mutations and
suppressor of fused gene. Its diagnosis follows a set of criteria based on specific cutaneous features and radiologic findings.
Although an autosomal dominant disorder with a high degree of penetrance, BCNS has variable expression making its
diagnosis difficult. The limited epidemiologic data among Asians especially in the Philippines hamper early detection or
cause frequent misdiagnosis of the condition.
Case report: A 56-year-old Filipino female with Fitzpatrick skin type V presented with early onset multiple basal cell
carcinomas and bilateral palmoplantar pits. Radiologic investigation reveals odontogenic keratocyst, calcification of the
falx cerebri, bridging of the sella turcica, bifid/splayed ribs and vertebral anomalies. The patient exhibits coarse facial
features and bilateral cataracts. Cranial computed tomography scan shows cerebrocerebellar atrophy with ventricular
dilatation. Management included wide excision of the nodular basal cell carcinomas (BCC), application of 5-flourouracil
cream on the superficial BCC and electrodessication and curettage of the smaller lesions. Oral acitretin was also prescribed.
Conclusion: This is a case that highlights the approach to diagnosis, clinical features and management of BCNS in a Filipino
patient. Since various phenotypic presentations may exist among dark-skinned individuals, early diagnosis poses a challenge
among physicians. Epidemiologic and prevalence studies among Filipinos may be done to aid in the diagnosis and early
management of this rare genodermatosis.
Keywords: Basal cell nevus syndrome, Gorlin-Goltz syndrome, Nevoid basal cell carcinoma syndrome, Basal Cell Carcinoma
INTRODUCTION
Basal cell nevus syndrome (BCNS) (Gorlin-Goltz syndrome
or Nevoid basal cell carcinoma syndrome) is a rare
inherited multisystem and tumor-predisposing disorder
caused by the patched
__________________________________________
1Section of Dermatology, Department of internal medicine, University
of the Philippines-Philippine General Hospital
2Department of Radiology, University of the Philippines-Philippine
General Hospital
Source of funding: none
Conflict of interest: none
Corresponding author:
Kathleen May V. Eusebio-Alpapara, MD, DPDS
tumor suppressor gene (PTCH1) mutations, in most cases,
and suppressor of fused (SUFU) gene. Diagnosis follows a
set of criteria based on specific cutaneous features and
radiologic findings. (Table 1) A patient must fulfill either
two major criteria or 1 major and 1 minor criterion to
make the diagnosis of BCNS.2, 3,4
42 J Phil Dermatol Soc · May 2019 · ISSN 2094-201X
Table 1. Criteria for the diagnosis of Basal Cell Nevus Syndrome 2,3,5
Major:
•Calcification of the falx cerebri
•Odontogenic keratocyst
•2 or more palmoplantar pits
•Multiple basal cell carcinomas, BCCs (>5) or appearance before the age of 30
•First degree relatives (Autosomal Dominant)
•PTCH gene mutation
Minor:
•Macrocephaly
•Childhood medulloblastoma
•Lymphomesenteric pleural cyst
•Congenital malformations: “Coarse face”, Cleft lip/ Palate, moderate or severe hypertelorism
•Skeletal abnormalities: Sprengel deformity, marked pectus deformity, marked syndactyly of
digits.
•Radiologic abnormalities: Bridging of the sella turcica, Rib anomalies (Bifid/splayed), Vertebral
anomalies, Flame-shaped lucencies of the hands and feet)
•Ovarian fibromas
•Ocular abnormalities (cataracts, developmental defects, pigmentary changes of retinal
epithelium)
Although an autosomal dominant disorder with a
high degree of penetrance is the usual mode of
inheritance, BCNS has variable expression making its
diagnosis difficult.2,6 Disease onset and clinical
presentation may vary among patients with different
races.3,4Majority of reported cases involve Caucasians. Its
limited epidemiologic data among Asians especially in the
Philippines hamper early detection or cause frequent
misdiagnosis of the condition.
We present a case of basal cell nevus syndrome
in a 56-year old Filipino female with Fitzpatrick skin type
V, the approach to diagnosis, its clinical features and
management.
CASE REPORT
A 56-year old female sought consult due to a 26-
year history of gradually enlarging multiple
hyperpigmented, non-pruritic, non-tender and non-
friable papules initially on the left cheek and the left ear,
patches on the forehead and pedunculated, slightly
pruritic papules on the neck and trunk with gradual
increased in size and number. The patient manifested a
hyperpigmented ulcerated and friable nodule on the left
forearm, excised by private physician without a follow up
histopathologic exam. The excised nodule recurred two
years prior to this consult. She had not undergone
immunosuppression, photosensitivity, radiation therapy
and persistent ultraviolet light exposure.
The patient had a solitary well defined
hyperpigmented ulcerated friable nodule on the left
cheek with rolled border and multiple hyperpigmented
non-friable, plaques and patches on the forehead and left
ear (Fig 1) and multiple hyperpigmented, some
pedunculated non-friable papules on the neck and trunk.
Palmar pits were also seen (Figure 2). She had coarse
facies, mandibular prognathis, broad nasal bridge and
ptosis. (Figure 1)
Histopathologic examination of the nodules on
the left forearm and left cheek showed nodular and
micronodular basal cell carcinoma (BCC) and the
hyperpigmented patch from the left lateral forehead
showed superficial BCC (Figure 3).
Panoramic radiograph revealed two cystic
structures in the mandible (Figure 4). Chest radiograph
showed osteosclerosis of the ribs and clavicles with
unremarkable cardiopulmonary findings. Plain skull
radiography indicated macrocephaly with intracranial
calcifications and calcification on the flax cerebri.
Craniofacial non-enhanced computed tomography (NECT)
scan revealed dense intracranial calcifications along the
falx cerebri and tentorium cerebelli, hyperostosis of the
J Phil Dermatol Soc · May 2019 · ISSN 2094-201X 43
skull and thickened cranium (Figure 5). The sella turcica
was deep with sellar bridging (Figure 6). Cerebrocerebellar
atrophy with ventricular dilatation was also noted. Chest
NECT scan showed bifid first set of ribs (Figure 10). The
first set of ribs and the scapulae were at the same level.
Wide excision of all nodular basal cell carcinomas
on the left cheek and left forearm was performed.
Electrodessication and curettage were done to remove
the multiple papules smaller than 1 cm on the neck and
trunk. Superficial basal cell carcinomas were treated with
4% 5-flourouracil cream twice daily. The patient was
further advised to take oral acitretin 20mg/day for six
months. Lipid profile and liver enzyme levels were
monitored for the first 2 months and every 2 to 3 months
thereafter.
Figure 1. Solitary well
defined
hyperpigmented
ulcerated friable
nodule on the left
cheek with rolled
border and multiple
hyperpigmented well-
defined and ill-
defined non-friable,
plaques and patches
on the forehead and
on the left ear
44 J Phil Dermatol Soc · May 2019 · ISSN 2094-201X
Figure 2. Palmar pits
Figure 3. Histopathology of the nodular basal cell carcinoma on the left forearm (a), nodular and micronodular basal
cell carcinoma on the left cheek (b)showing large and small aggregates of atypical basaloid cells with peripheral
palisading occupying the dermis with mucinous stroma and focal areas of retraction artifact. Histopathology of the
3a
3b
3a
3b
3c
J Phil Dermatol Soc · May 2019 · ISSN 2094-201X 45
superficial basal cell carcinoma on the forehead (c) showing
Figure 4. Panoramic radiograph (a) and NECT scan (b) showing two cystic structures in the mandible.
Figure 5. Sagittal and axial views of the bone window of Cranial CT showing dense intracranial calcifications along the
falx cerebri and tentorium cerebelli hyperostosis of the skull and thickened cranium.
Figure 6. Sella turcica Bridging
4a
4b
46 J Phil Dermatol Soc · May 2019 · ISSN 2094-201X
Figure 7. Chest NECT scan with reconstruction showing the bifid first set of ribs and the first set of ribs and the scapulae
that are at the same level.
DISCUSSION
It has an estimated prevalence of 1 in 31,000 to
1 in 164,000 without gender predilection. 2, 3 The
prevalence of basal cell nevus syndrome in the Philippines
is currently unknown. Table 2 shows the reported cases of
basal cell nevus syndrome in the country.
The pathogenesis of BCNS involves loss of
function mutations of a tumor suppressor gene, PTCH1,
located on chromosome 9q22.3. 2,3The PTCH protein is a
part of a complex along a transmembrane protein,
Smoothened (SMO). The Hedgehog (HH) protein binds to
the PTCH-SMO receptor complex regulating the sonic
hedgehog (SHH) signaling pathway. The SHH signaling
pathway is a major signal transduction pathway during
embryonic development which usually shuts down after
birth.Unregulated activity of SHH signaling pathway may
lead to tissue overgrowth and tumor induction. Activated
HH signaling caused by mutations in the tumor suppressor
gene, PTCH, and/or the G-protein coupled receptor SMO
promote oncogenic signaling and drives the growth of
multiple basal cell carcinomas. 10
The SUFU gene also encodes a path in the SHH
signaling pathway and is found among BCNS patients
without PTCH1 gene mutation. SUFU mutations were
reported to be associated with milder clinical feature such
as lesser BCC lesions and lack of odontogenic keratocysts
but an increased risk of developing childhood
medulloblastoma. 11
Although no similar cutaneous lesions were
found among the patient’s first-degree relatives, she was
observed to exhibit the same genetic phenotype as her
father presenting with course facial features with
hypertelorism. Her father died of lung carcinoma.
Disease manifestations among patients with
lighter skin types may differ from the those with darker
skin types. Around 70-80% of Caucasians with BCNS
manifest multiple BCCs in their early twenties. A 2012
survey conducted among 157 patients with BCNS in Japan
revealed a mean age of 37.4 years old.12The patient in this
case report started to develop multiple BCCs as early as 30
years old.
Approximately 65 percent of affected persons
have calcification of the falx cerebri.3,4 Other areas of
ectopic calcification include the diaphragma sellae and
tentorium cerebelli which is seen in 60 to 80% and 40% of
the cases, respectively.3, 4 Palmoplantar pits are highly
characteristic of BCNS, occurring in 80 percent of
diagnosed cases, specifically older individuals. They are
asymptomatic nonpalpable shallow depressions, which
results from partial or complete absence of stratum
corneum.3 All of these major features manifested in our
patient.
J Phil Dermatol Soc · May 2019 · ISSN 2094-201X 47
Other features present were macrocephaly,
which is seen in 27-80% of the cases, ophthalmologic
abnormalities (4.5-42%) and bifid ribs (16-26%). A study
on the radiological features of 82 BCNS patients in
Maryland, USA showed that 24% had dilated ventricles
and 10% with cerebral atrophy.4,5 Both findings were
found in the patient.
Surveillance among affected patients includes
baseline brain magnetic resonance imaging, dermatologic
examination every four months or more frequently if new
lesions continue to multiply and biannual panorex until
cyst free for two years. A major concern for patients with
BCNS is the development of multiple BCCs, which may
become invasive, penetrating underlying structures,
especially if located on the face. For non-morpheaform
BCCs that are not located on the canthus, nasolabial fold,
perioral and post auricular areas, excision or
electrodessication with curettage can be done. There is a
95% cure rate if a lesion greater than 2 cm in diameter is
excised with 1.2 cm margin and a recurrence rate of
17.6%.4With curettage and desiccation (C&D), the highest
cure rate (98%) is achieved for lesions less than 1 cm and
84% for lesions greater than 2 cm and is not
recommended for large BCCs. Recurrence rate is
approximately 40%. 4,5
Superficial BCCs can be treated with topical
medications. Imiquimod 5% cream can cause histologic
and clinical clearance rates of 73 to 75% if applied five to
seven times a week. 5-fluorouracil 4% cream treatment
exhibits a 90% histologic clearance rate after 3 weeks and
a 5-year recurrence rate of 21%, whichcan be reduced to
6% if curettage is performed initially. 4,5 Hence, 5-FU was
the treatment option for the patient’s superficial BCCs.
Other treatment options include cryosurgery,
photodynamic therapy and Mohs micrographic surgery,
which is superior among all the other treatment
modalities with a cure rate of as high as 99% and
recurrence rate of 1-5.6%. Radiation therapy can be used
as an adjunct when margins are positive after excision or
for extensive perineural involvement. 4
Second generation retinoids like acitretin were
found to dramatically reduce the development of
premalignant and malignant degeneration of cutaneous
lesion. Hence, the patient was advised to take acitretin at
a dose of 20mg/day for 6 months.13
In general, the prognosis of basal cell nevus
syndrome is excellent. Even recurrent BCCs have
favorable prognosis. Periodic full body examination
should be done to check for new lesions. The patient must
be advised that approximately 40-50% of patients with
primary carcinoma will develop one or more lesions within
5 years. 4,5
CONCLUSION
Basal cell nevus syndrome exists among Filipinos.
Because of a highly variable penetrance, various
phenotypic presentations exist. Since the disease presents
differently among dark-skinned individuals, early
diagnosis poses a challenge among physicians.
Epidemiologic and prevalence studies among Filipinos
may be done to aid in the diagnosis and early
management of this rare genodermatosis.
48 J Phil Dermatol Soc · May 2019 · ISSN 2094-201X
Table 2. Reported cases of Basal cell nevus syndrome 7,8,9
Author/ year
Journal
Gender /age of
diagnosis
Fitzpatrick
skin type
Major criteria
Minor criteria
Chief complaint
History
Management
Magbuhat
et.al. (2017)
Philippine
Journal Of
Otolaryngology-
Head And Neck
Surgery
Female/ 46 yo
V
Multiple BCCs
Calcification of
the falx cerebri
Odontogenic
keratocyst
Multiple
palmar pits
Vertebral
anomalies
(straightened
cervical vertebra
with spurs and
sclerosis on
endplates ,
decreased
intervertebral
space between
C4 and C5)
Necrotic ulcer over
the left orbital
region
10 years prior a
skin-colored, non-
pruritic, non-painful
papilla-like lesion
appeared on her
left upper eyelid
that eventually
became a
hyperpigmented
plaque and
developed non
healing ulcer with
occasional bleeding
and pustular
discharge.
Wide excision of the left
orbital mass with
exenteration,
excision of both paranasal
masses and the alar mass,
left total parotidectomy
with facial nerve
preservation, enucleation
of mandibular cyst, and
cervicofacial
reconstruction with left
orbital split thickness skin
graft and left ala full
thickness skin graft.
Sabido, et.al.
(2013)
Journal of
Philippine
Dermatological
society
Female/11 yo
III
Multiple BCCs
before 30 yo
Multiple
palmar pits
Bilateral ovarian
calcification
multiple discrete,
skin-colored to
speckled brown,
pearly papules on
the face,
clavicular area, and
upper back.
The lesions were
not present at birth,
and appeared a few
years prior to
consult with out
associated
pruritus, bleeding
and pain
Removal of the lesions
using ablative
erbium:YAG laser,
Imiquimod cream
application every other
night
Photoprotection
Ledesma-
Parcia et.al
(2009)
Journal of
Philippine
Dermatological
society
Female/67
V
Multiple BCCs
Odontogenic
keratocyst
Multiple
palmar pits
*
Multiple bluish
black papules,
plaques and tumors
on the face, trunk
and extremities
7 years prior to
consult, the lesions
started to appear
on the face , trunk
and anterior thighs
which gradually
increased in size
and bled with
trauma.
Excision of the large lesions
Electrocautery and
imiquimod cream
application thrice per week
on the smaller lesions
Photoprotection
Regular follow-up every 3
months
J Phil Dermatol Soc · May 2019 · ISSN 2094-201X 49
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