Basal celi nevus syndrome 
Clinical study 
BASAL CELL NEVUS SYNDROME. 
TUMOR SITES AND THERAPY 
Analysis of 5 6 cases 
B. Haferkamp, K.-J. Ernst and M. Hundeiker 
ABSTRACT 
In 56 patients with basal celi nevus syndrome, clinical manifestations and therapy in various tumor sites 
were reviewed and contrasted with data from literature. For differential diagnosis, it is essential to ascertain 
a complete history and to search for further symptoms of the syndrome. The most important alternatives in 
therapy are surgery and cryosurgery. The latter is particularly suitable in cases with large numbers of 
superficial basal celi carcinomas located on the trunlc and extremities and for treatment during early growth 
stages. Cryosurgery sessions are short and the method can be employed in out-patient care, which is of 
special significance as basal cel\ nevus syndrome patients require life-long attention. 
KEY WORDS 
basal cell nevus syndrome, 56 patients, accompanying symptoms, tumor sites, therapy 
INTRODUCTION 
The basal celi nevus syndrome (BCNS, more 
accurate: nevoid basal celi carcinoma syndrome) is a 
genetically determined, polysymptomatic disease. By 
some authors it has therefore been labelled „fifth 
phacomatosis" (1). Musger (1964) (2) defined 
„phacomatosis" as heterogeneous alterations which 
are capable of progression and originate in dysplasias 
or early embryonic differentiation disorders. Apart 
from the skin, the basal celi nevus syndrome can 
involve to a various extent the skeleta! system, the 
central nervous system, the eyes, and the endocrine 
organs. The disease shows an autosomal dominant 
pattern of inheritance with high penetrance and 
varying expressivity. The defect has recently been 
acta dennatovenerologica A.P.A. Vol 6, 97, No 1 
located to chromosome 9q in section q22-23 (3,4). 
Since the close of the 19th century, cases of 
multiple basal celi carcinoma, osseous anomalies, 
mandibular cysts and retardation have been reported. 
Binkley and Johnson (5) described the cases of a 
mother and her daughter who both showed more 
than 1000 basal celi carcinomas and various growth 
defects. More publications, predominantly individual 
case reports, followed (6,7,8,9,10). Thies et al. (11), 
and a little later Gorlin and Goltz (12) identified 
the disease as a separate syndrome. 
Characteristically, the tumor growth is initially 
very slow (nevoid growth stage) and becomes inv'asive 
la ter ( oncotic growth stage) (13). It is not yet 
certain what causes this development. The multiple 
3 
Basal celi nevus syndrome 
Table l. Age Distribution (Age at Diagnosis) of the 56 
patients with basal cel! nevus syndrome 
Age Absolute Relative 
Group Frequency Frequency % 
15 - 20 Years 5 8,9 
21 - 40 Years 26 46,4 
41 - 60 Years 17 30,4 
61 - 80 Years 7 12,5 
> 81 Years 1 1,8 
and repetitious appearance of tumors causes difficulty 
in choosing an appropriate course of therapy. 
The leading diagnostic criterion is the presence of 
multiple basal cell carcinomas. However, the first 
symptoms noted are often maxillary, :;ometimes mandi-
bulary cysts. Additional findings in descending order 
of frequency are: calcification of the dura mater, 
dyskeratotic defects of the palms and soles, milia 
and epithelial cysts, malformation of the spine, and 
others. There is a higher-than-chance association 
between BCNS and other malignancies ( squamous 
cell carcinomas of the skin, larynx and anal region; 
ameloblastomas; brain tumors; ovarian carcinomas; 
carcinomas of the mamma; renal cell carcinomas; 
Bowen's disease ). 
MATERIALS AND METHODS 
In the Fachklinik Hornheide, 15,437 patients were 
treated for basal cell carcinoma between 1961 and 
1994. Of these, 63 had been diagnosed with BCNS. 
Diagnosis, tumor site and treatment procedures were 
analysed from these patients' records. The diagnosis 
was accepted if any of the following criteria were 
met: positive family history, typical symptoms or 
occurrence of tumors at a young age, whereas 
multiple epitheliomas in arsenic patients, striated 
and segmentary basal cell nevi, epidermal nevi, 
nevoid basal cell epitheliomas of the Jablonska type, 
multiple basal cell carcinomas after exposition to 
radiation and epithelioma adenoides cysticum Brooke 
were ruled out in differential diagnosis. Seven patients, 
in whom the diagnosis of BCNS was doubtful, were 
not included in the evaluation. 
RESULTS 
l. Family History. Family history was positive in 17 
4 
(30%) of the patients. In 14 (25 % ), no data could 
be obtained from the records. 
2. Distribution of Age and Sex. Among the 56 
patients who were evaluated in the study 21 were 
males and 35 females. The diagnosis of BCNS was 
established as being most frequent between 21 and 
40 years (Table 1), and in 30.4% of cases at an age 
between 41 and 60 years. 
3. Accompanying Findings. The most frequently 
observed accompaniments were osseous anomalies 
and defective dentition, especially maxillomandibular 
cysts (38 patients, 68%, Table 2). A radiography of 
the maxillary region was performed in all patients 
except one, the skull was examined radiographically 
in 38 (67%) and the spine in 12 (21 % ) patients. 
Spinal involvement in the form of fused vertebrae 
and scoliosis was found in 9 patients (16% ). Bifid, 
synostotic or missing ribs ( 4 patients, 7%) were 
rarely diagnosed. In 50% of the patients a calcified 
dura was found. Apart from basal cell carcinoma, 
the skin was affected mainly in the form of 
palmoplantar dyskeratotic defects (27%) and milia/ 
epithelial cysts (21 % ). Eye involvement [hypertelorism, 
dystopia canthorum ( 4%) and motility defects (9% )] 
were unusual. Endocrine organs were not affected 
in our patients. 
4. Occurrence of other Neoplasias. Of 56 patients, 
13 (23%) developed other malignant tumors apart 
from basal cell carcinomas. Squamous cell carcinomas 
of the skin were found in 5 patients under the age 
of 50 years. Squamous cell carcinomas also appeared 
in the larynx and anal region. Further neoplasias 
were ameloblastomas, brain tumors, ovarian carcinomas, 
carcinomas of the mamma, renal cell carcinomas 
and Bowen's disease. 
5. Histology of Nevoid Basal Cell Carcinomas. The 
histologic differentiation of basal cell carcinomas 
was possible in specimens of complete excisions, 
resections and biopsies. A large amount of superficial 
BCCs were treated with cryotherapy and were not 
evaluated. Regarding the large number of tumors 
treated during one session, their small size and the 
necessity to avoid unnecessary scarring, the requirement 
to verify each single tumor histologically is impossible 
to meet in these patients. Among the tumors that 
were histologically examined, solid-growing BCCs 
accounted for the majority (906, 52.5% ). Less 
frequently, tumors were superficial (293, 17%) or 
multicentric (193, 11.2%). Other types of basal cell 
carcinomas ( adenoid, cystic, sclerosing, keratotic, 
metatypical) were less common. 
acta dermatovenerologica A.P.A. Vol 6, 97, No 1 
Basal celi nevus syndrome 
6. Tumor Site and Treatment. In our patients, the 
preferred location of basal cell carcinomas was the 
trunk (2457 tumors, 53.8% ), followed by the face 
(1397 tumors, 30.6%; Table 3). In the latter area 
apart from other facial sites (877 tumors, 19.2%) 
the periorbital region and the nase were often 
affected. Surgical treatment was the method of 
choice for facial lesions, whereas basal cell carcinomas 
of the trunk were treated cryosurgically, especially if 
growing superficially. Less frequently, they were excised 
and very rarely irradiated. Irradiation in soft-X-ray 
technique was used until 1982 for the lips, ear and 
nase region and for the periorbital area. In other 
facial areas, cryotherapy has always been preferred 
to radiotherapy. For tumors situated on the capillitium 
(441, 9.7%), excisions and cryosurgery were employed 
in the first instance. Tumors of the extremities were 
rare. They were also treated cryosurgically or surgically. 
Radiotherapy was not used for these areas. In rare 
instances facial and trunk lesions were treated with 
5-fluorouracil, retinoic acid and laser therapy. 
DISCUSSION 
The basal cell nevus syndrome presents great 
difficulties to the responsible doctor, partially due 
to diagnostic problems in cases of incomplete pene-
trance, partially due to choosing a therapeutic strategy 
for numerous and successively emerging tumors. 
By no means do multiple BCCs alone give reason 
to suspect a basal cell nevus syndrome (14). Neverthe-
less, the syndrome has to be considered in cases 
where they appear at a young age (15). In our 
Table 2. Accompanying symptoms in the 56 patients with basal celi nevus syndrome in our database (compilation 
as proposed by Gorlin and Sedano 1971) 
Accompaniments of multiple nevoid basal cell carcinoma AlJ&otute 
Freqaency 
I. Skin 
l. Palmoplantar keratinisation defects (pits) 15 
2. Milia, epithelium cysts 12 
3. Fibromas or neurofibromas 2 
4. Lipomas 5 
II. Osseous and Dental Anomalies 
l. Multiple maxillomandibular cysts 38 
2. Ribs: bifid, synostotic, missing ribs 4 
3. Spine: scoliosis, fusions 9 
4. Frontal bossing 1 
5. Progenia o 
6. Anomaly of the sella turcica o 
III. Central Nervous System 
l. Dura calcification (falx, tentorium) 28 
2. Imbecility 1 
3. Medulloblastoma 1 
4. Alteration of the EEC 4 
IV. Eyes 
l. Hypertelorism, dystopia canthorum 2 
2. Motility disorder 5 
3. Cataract ( congenital or early onset) o 
4. Inhibition deformities o 
V. Endocrine Organs 
l. Ovarian fibroma o 
2. Male hypogonadism o 
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Reliltive 
Freljue:ney fq , 
ft ,, ml l:i 
27 
21 
4 
9 
68 
7 
16 
2 
o 
o 
50 
2 
2 
7 
4 
9 
o 
o 
o 
o 
5 
Basal celi nevus syndrome 
Table 3. Choice of treatment as related to tumor site in basal celi nevus syndrome patients 
Tumor Site Absolute Relative Total Total 
Frequency Frequency % Absolute Relative · % 
Capillitium 441 9.7 
l. Excision 288 6.3 
2. Cryotherapy 133 2.9 
3. Soft X-ray irradiation 20 0.4 
Lips 66 1.4 
l. Excision 49 1.1 
2. Cryotherapy 1 
3. Soft X-ray irradiation 16 0.3 
Eyes 255 5.6 
l. Excision 216 4.7 
2. Cryotherapy 3 0.1 
3. Soft X-ray irradiation 33 0.7 
4. Interferon-alpha 3 0.1 
Ears 64 1.4 
l. Excision 41 0.9 
2. Cryotherapy 9 0.2 
3. Soft X-ray irradiation 12 0.3 
4. Interferon-alpha 1 
5. 5-Fluorouracil ointment 1 
Nose 135 3.0 
l . Excision 104 2.3 
2. Cryotherapy 1 
3. Soft X-ray irradiation 30 0.7 
Other Sites (Facial) 877 19.2 
l. Excision 678 14.9 
2. Cryotherapy 118 2.6 
3. Soft X-ray irradiation 80 1.8 
4. Argon Laser 1 
Trunk 2457 53.8 
l. Excision 462 10.1 
2. Cryotherapy 1929 42.3 
3. Soft X-ray irradiation 54 1.2 
4. 5-Fluorouracil ointment 6 0.1 
5. Retinoic acid 1 
6. Argon Laser 5 0.1 
Upper Extremity 80 1.7 
l. Excision 29 0.6 
2. Cryotherapy 51 1.1 
Lower Extremitiy 190 4.2 
l. Excision 40 0.9 
2. Cryotherapy 150 3.3 
Total 4565 
6 acta dermatovenerologica A.P.A. Vol 6, 97, No 1 
Basal celi nevus syndrome 
experience, the age of the patients at the tirne of 
diagnosis was remarkably advanced compared to 
data in literature. A significant proportion of the 
patients was between 21 and 60 years old. This may 
be due to the retrospective nature of the study. 
Treatment received in other institutions was incon-
sistently documented. Another reason could be the 
fact that the basal cell nevus syndrome shows a 
widely varying phenotypic expressivity: we observed 
a patient who developed BCCs in childhood, while 
other patients showed signs of the disease at an age 
typical for sporadic BCCs. In 1960 Thies et al. (11) 
indicated that abortive forms without affection of 
the skin can occur. They also assumed a manifestation 
that is not restricted to juvenile age. However, the 
disease is often detected late because the BCCs 
mimic nevi in the beginning of their development. 
The frequency of maxillomandibular cysts ( 68%) 
in our patients is in accordance with data in literature. 
These cysts are considered to be the most important 
factor and can precede the skin affection by years. 
Histologically, the cysts are lined with one or more 
layers of squamous epithelium with a varying tendency 
of keratinisation. Proliferation from these cysts with 
the characteristics of an ameloblastoma has been 
reported (16) . In our series there was also a patient 
who developed an ameloblastoma. A further sign 
(50%) is early calcification of the dura mater. 
Defects of the palms and soles, histologically focal 
dyskeratosis with accumulation of multi-layered basal 
cells, were rare in comparison to literature reports 
(27% vs. 50%) (17). As the palmoplantar pits are 
normally asymptomatic and clinically indistinct, they 
can easily be overlooked unless these defects are 
directly searched for. 
In agreement with the literature in our study 
there is a strong association with further malignancies 
(23 %) (18) . This was similarly reported for other 
phacomatoses such as von Recklinghausen's or 
Boumeville-Pringle's disease. It can possibly be related 
to increased chromosomal instability (19). In one 
patient we observed a coincidence of basal cell 
nevus syndrome, neurofibromatosis and Tumer's 
syndrome (20). 
Histologically, BCCs of BCNS patients do not 
differ from those of the common form. The frequency 
distribution of the various BCC types in our excision 
specimens was similar to that of sporadic BCCs 
(21,22,23). 
The distribution of sites of BCCs in BCNS differs 
from that of the solar-induced type (Table 3). 
Typically, the BCCs of basal cell nevus syndrome 
are not only found in continuously light-exposed 
areas of the skin, but also on the trunk, the 
capillitium and the extremities. In the patients treated 
in our clinic, location on the trunk clearly predomi-
nated. Facial occurrences correspond to the behaviour 
of sporadic BCCs, which appear mainly in the 
centrofacial (periorbital and nose) region. Thus, 
exposure to ultraviolet radiation seems to be a 
tumor-stimulating factor in BCNS-patients, too. 
Immune deficiency possibly promotes growth like it 
does in other tumors. Beyond that, this condition 
might induce the development of squamous cell 
carcinoma from a basal cell carcinoma (24). 
The figures on tumor numbers are at the low end 
of the range: on the one hand, many patients are 
not exclusively treated in the Fachklinik Homheide. 
Because of the chronicity of the disease, cooperation 
.. \ . 
' 
- • 
.. " ·~ .. .. ... 
Figure 1 a. Patient with basal cell nevus syndrome before cryosurgery of numerous basal celi carcinomas 
Figure 1 b. Patient with basal cel! nevus syndrome after c,yosurgery of numerous basal cel! carcinomas 
acta dermatoveneroloRica A .P.A. Vol 6, 97, No 1 7 
Basal celi nevus syndrome 
with otber doctors is essential. On tbe otber band, 
due to tbeir nmltiplicity not all of tbe tumours 
could be numerically registered. Especially tbe number 
of tumors eligible for cryosurgery often exceeded 
tbe limit in number tbat can possibly be documented 
during daily routine: occasionally, bundreds of basal 
cell carcinomas were treated in a single series (Fig. 
la, lb). 
Regarding tbe multiplicity of tumors different 
traemtment regimens bave to be cbosen. Tbe most 
important treatment modalities ( standard tberapies) 
used in our clinic are surgery and cryosurgery (25). 
Tumor excision is indicated in cases of extended, 
especially facial, tbick tumors, in certain bistologic 
growtb patterns (sclerosing, ,,savage") and in relapsing 
tumors. Tbe advantage of surgical treatment is its 
security and tbe possibility of bistological verification. 
However, one must consider tbat BCCs often are 
multicentric and appear in close vicinity of eacb 
otber. In sucb cases tbey cannot be totally removed, 
Fig. 2. Basal cel! nevus syndrome. Lesions treated by 
c,yotherapy. 
8 
and otber metbods bave to be employed. Cryotberapy 
is best suited bere (26). It is appropriate for tbe 
numerous superficial tumors on tbe trunk and 
extremities wbicb can be detected in early stages at 
follow-up examinations (Fig. 2, 3). Tbe bandling is 
easy and treatment of multiple BCCs can be done 
in a sbort tirne. Tbe metbod implies little incon-
venience for tbe patient wbile cosmetic results are 
good. Tbe disadvantages are a bigber relapse-risk in 
cases of large deeply infiltrating tumors and prolonged 
wound bealing. Tbe combination of surgery and 
cryosurgery is possible and, in tbe cases listed, 
reasonable. 
Restricted application is reseved for soft X-ray-, 
laser- and pbotodynamic tberapies. Irradiation of 
basal cell nevus patients was employed in our clinic 
from 1954 to 1982. Due to tbe genetic patbogenesis 
of tbe disease and tbe risk of tumor induction, tbe 
metbod was abandoned. For example we observed a 
14-year-old female wbo received radiotberapy for 
Fig. 3. Basal cel! nevus syndrome. Treated lesions 
compared to untreated. 
acta dermatovenerologica A.P.A. Vol 6, 97, No 1 
Basal cel! nevus syndrome 
medulloblastoma. In consequence she developed a 
large number of BCCs in the exposed area (capillitium) 
and a few on the trunk, while the face remained 
unaffected. Relative indications for soft X-ray therapy 
are complicated tumor locations in the face and 
patients above the age of 60 years (27). Deeply 
infiltrating tumors should be treated with other 
methods. The skin of the trunk and extremities is 
more susceptible to radiogenic scarring than the 
face. Therefore, cryotherapy or surgery are preferable. 
Laser therapy is suitable only for small, demarcated 
tumors. For larger BCCs, the method is not safe 
enough. The situation is similar in regard to the 
recently propagated photodynamic therapy (28,29). 
Moreover, the method is inconvenient for the patient 
and cannot be recommended at this experimental 
stage. The same applies to interferon treatment. 
Infiltrations with interferon have to be continued 
for severa! weeks. They are not at all as sure to 
succeed as other methods. Adverse effects (fever, 
shivering fits, fatigue, cephalgia), though less intensive 
than in systemic administration, are difficult to handle 
(30). A good result in early superficial lesions can 
also be obtained with 5-fluorouracil ointment and 
local application of retinoids. But it bas to be 
considered that their use is very complicated and 
lengthy as opposed to cryotherapy. Miltefosin in 
topic application is currently being tested in a 
multi-center study. Prevention: the most important 
provoking factor in this genodermatosis is ultraviolet-
radiation. That, s why skin protection especially in 
childhood is necessary. Some authors have recommen-
ded retinoids as systemic chemopreventive agents 
reducing recurrences of basal-cell-carcinomas (31,32). 
Other authors, however, are not convinced of their 
efficiency. The numerous adverse effects of systemically 
administered retinoids, including increase in serum 
lipids, skin and mucosal damage and teratogenesis 
have to be considered (33). In summary different 
treatment modalities depending on localization, tumor 
size, side effects and patient compliance have to be 
considered in every case in order to achieve the 
best long-term result. 
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AUTHORS' ADDRESSES 
10 
Birgit Haferkamp MD, Department of Dermatology, University of Wurzburg 
J. Schneider-Strasse 2, 97080 Wurzburg, Germany 
Klaus-Jochen Ernst MD, Department of Dermatology, Fachklinik Hornheide, 
Westfalische Wilhelms Universitat, Munster, Dorbaumstrasse 300, 48157 Munster, Germany 
Max Hundeiker MD, professor of dermatology, same address 
acta dennatovenerologica A.P.A. Vol 6, 97, No 1