Year : 2006 | Volume
: 17 | Issue : 1 | Page : 50--53
Nevoid basal cell carcinoma syndrome
Karthiga S Kannan1, Sivapatha B Sundharam2, R Manikandan3,
1 Department of Oral Medicine & Radiology, Sree Mookambika Institute of Dental Sciences, V.P.M. Hospital Complex, Padanilam, Kulasekharam-629 161, India
2 Department of Oral and Maxillofacial Pathology, Meenakshi Ammal Dental College and Hospial, Madhuravoyal, Chennai-602 102, India
3 Department of Oral and Maxillofacial Surgery, Meenakshi Ammal Dental College and Hospial, Madhuravoyal, Chennai-602 102, India
Karthiga S Kannan
Department of Oral Medicine & Radiology, Sree Mookambika Institute of Dental Sciences, Padanilam, Kulasekharam-629 161
Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS). NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.
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Kannan KS, Sundharam SB, Manikandan R. Nevoid basal cell carcinoma syndrome.Indian J Dent Res 2006;17:50-53
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Kannan KS, Sundharam SB, Manikandan R. Nevoid basal cell carcinoma syndrome. Indian J Dent Res [serial online] 2006 [cited 2022 Sep 25 ];17:50-53
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Nevoid basal cell carcinoma syndrome (NBCCS) is a hereditary disorder, inherited as autosomal dominant trait. The prevalence of this condition is about 1 per 60,000 . Cutaneous malformations include multiple basal cell carcinoma (BCC) from childhood involving skin over the nose, upper eyelid, cheeks, trunk, arms and neck, which appear as flesh coloured to ulcerated brown papules . Apart from this milia, epitheliomas, comedones, palmar plantar dyskeratosis, palmar pitting, dermal calcinosis were also reported ,,. Dental malformations include multiple odontogenic keratocysts (OKC) and dilaceration of the roots of the teeth adjacent to the cyst . Skeletal malformations present are frontal, temporo-parietal bossing giving a pagetoid appearance, prominent supra orbital ridge giving the eyes a sunken appearance, broad nasal root, hypertelorism, dystopia canthoram, mild mandibular prognathism , cleft lip and cleft palate . Other skeletal anomalies include bifid ribs, involving more than one rib unilaterally or bilaterally Synostosis of ribs, kyphoscoliosis, fusion of vertebrae, cervical rudimentary rib, spina bifida, shortened fourth metacarpals (Albright's sign) , enlarged hands and extra metatarsals and polydactyly  have also been reported . Ophthalmic malformations include congenital blindness, internal strabismus, congenital cataract, glaucoma and coloboma ,,. Neurologic malformations include mental retardation, calcification of dura, falx cerebri, agenesis of corpus callosum, congenital hydrocephalus, medulloblastoma, schizophrenic behaviour ,,. Sexual abnormalities include hypogonadism in males and ovarain tumours in females .
A seventeen-year-old female patient reported with the complaint of swelling and mild pain in the right side of the upper jaw. Swelling was noticed two months back and pain present for the past ten days. She gave history of a cystic swelling in the left side of maxillafor whch she underwent surgery in March 1996 and in August 1997 she underwent second surgery for the recurrence of the lesion in the same site. hn July 1999, she again underwent a surgery in the right side of maxilla for a similar cystic lesion, which has been histopathologically diagnosed as odontogenic keratocyst.
History revealed other family members were apparently healthy and they refused to undergo radiological screening. On general examination the patient was well built, face showed frontal bossing, depressed nasal bridge, hypertelorism, prominent supra-orbital ridges and mandibular prognathism [Figure 1,2]. There was mild diffuse swelling in the right side of the face. The skin, palm and soles were normal. Opthalmologic examination was non contributory.
Intra - oral examination revealed missing 18, 13, 24, 25, 28, 38, 48 grossly decayed 26 and gemination of 44. A single swelling obliterating the buccal sulcus extending from 13 region to 16 region was present. On palpation the lesion was fl uctuant, cystic and slightly tender [Figure 3,4].
Occlusal radiograph taken in 1996 showed retained 65 and impacted 25 with well-circumscribed unilocular radiolucency expanding both buccal and palatal cortex with sclerotic border and was surgically removed [Figure 5].
Occlusal radiograph taken in 1997 showed recurrence of the cystic lesion in the left side of maxilla which was enucleated while another small developing cystic lesion in the right side of maxilla with retained 53 and impacted 13, was leftuntreated [Figure 5].
Occlusal radiograph taken in 1999 showed enlarged, multilocular, well circumscribed radiolucency with bucally displaced 13 and retained 53 in the same site [Figure 5].
Present orthopantamogram revealed an irregular homogenous radiolucency present in the right maxilla approximately of 3 cm in diameter, extending from 12 to 15 region displacing the roots of 14 and 15 distally, associated with missing 13. Another well defined cystic radiolucency of 2 cm diameter in the mandible in relation to the horizontally impacted 48 is also seen. The previous surgical site on the left side of maxilla showed normal bone pattern [Figure 6].
PAview of chest revealed [Figure 7],[Figure 8].
Forked fourth rib on the right side, Synostosis of cervical rib with the first rib on the left side, Wide second rib on the left side, Widening of second intercostals space on the right side,.Spinabifida of C7,T1,T3,T4 vertebrae,Fusion and segmentation anomaly of upper dorsal vertebrae and lumber scoliosis with convexity to left side.
Lateral spine radiograph showed obvious kyphosis.
Incisional biopsy from cystic lesion in right maxilla showed the cystic lining, made up of parakeratinised stratified squamous epithelium which is more or less uniform in thickness with corrugated luminal surface. In one region there is presence of orthokeratin with prominent granular cell layer. Basal cells are palisaded. The stromal connective tissue is free from inflammation and there is no evidence of any satellite cysts.
Under general anaesthesia a crevicular incision was placed from the permanent left maxillary central incisor to the permanent right maxillary first molar. Mucoperiosteal flap was reflected. The cystic lining was dissected away from the mucosa and enucleation was done. Permanent right maxillary lateral incisor and first premolar were also extracted. Bone removal of 2mm was done all around to eliminate all the lining. Wound debridement was done and closed primarily with 3-0 vicryl sutures. An `L' flap was raised in the region of the right mandibular third molar. Bone fenestration was done with bur to expose the cystic lining. The lining was enucleated, the walls were trimmed, debridement was done with the removal of right lower third molar. The wound was closed primarily with 3-0 vicryl suture. Post operative phase was uneventful.
NBCCS is rare inherited disorder with multisystem manifestations, an autosomal dominant gene transmits it and whose mutation underlies NBCCS has been mapped to the long arm of chromosome 9 g22.3-g31. Data suggest that a product of this gene acts as tumor suppressor and NBCCS typical malforrnative pattern suggest that the main function is to control the growth and development of normal tissues . Similar to the present case those people who do not have any known family members affected with NBCCS may compose 60% of total NBCCS and 35 to 50% of these cases represent new mutations. NBCCS have equal sexpredilection  and it is associated with multiple OKCs in patients in the second decade of life mostly below sixteen years . In the present case the first sign that made us to suspect NBCCS is multiple cystic lesions involving the maxilla and mandible, which was histopathologically diagnosed as OKC. When the patient reported to us she was 17 years old, but history revealed that she underwent first surgery four years back, radiograph taken at that time revealed a cystic lesion in left maxila, so apparently at the age of 13 years. The occlusal radiograph taken at that time revealed cyst, with impacted 25 with a size of 3x4cm', this much of size indicates that the pathology would have started at a much earlier age. Generally OKC not associated with NBCCS occurs in adulthood, the peak incidence being third decade of life , but in NBCCS, OKC occurs in a much younger age group, the study done by Lorenzo Lo Muzio, Pierfranceso Nocini et al indicates OKC are often the first sign of NBCC (78%) and can be detected in patients younger than 10 years of age .
Regarding the male to female ratio, it was 1:0.62 for OKC not associated with NBCCS and 1:1.22 for OKC in NBCCS. This shows simple keratocyst are more common in males but more females seems to have NBCCS . The present case had a total of three cystic lesions in thej aw, two in the maxilla and one in mandible.
Cases were reported where six OKC occurred in NBCCS . Contrary to the present case the OKCs associated with NBCCS have more predilection for mandible than maxilla with 69% occuring in mandible and 31% in maxilla ,.
Regarding the site predilection, in mandible 43% occurs in molar ramus region followed by 18% in incisorcanine area. In maxilla 14% occurred in incisorcanine area followed by molar tuberosity with 12%, mandibular premolar region 7% and maxillary premolar region 3% . In the present case one of the cyst in maxilla occurred in left maxillary promolar region and the other occured in right canine region. The term multiple when applied to the cyst in NBCCS refers to the life time history of the patient and does not necessarily that more than one cyst is present at any given time .
Evans and colleagues proposed a diagnostic criteria for NBCCS, which is as follows
Diagnostic criteria for nevoid basal cell carcinoma syndrome 
More than two basal cell carcinomas (BCC) or one BCC at younger than thirty years of age; or more than ten basal cell nevi.Any odontogenic keratocyst (proven on histology) or polyostotieborie cystThree or more palmarorplantar pitsEctopic calcification: lamellar or early - at yotmger than twenty years of age-falx calcificationPositive family history of NBCCS
Congenital skeletal anomalies: bifid, fused, splayed or missing rib or bifid, wedged or fused verebraOccipital - frontal circuraferance more than 97 percentage, with frontal bossingCardiac or ovarian fibromaMedulloblastomaLymphomesentriccystsCongenital malformation such as cleft lip or palate, polydactylism or eye anomaly (cataract, coloboma, micropthalmos)
There should be atleast two major criteria or one major and two minor criteria for the diagnosis of NBCCS.
Despite the name of the syndrome multiple basal cell carcinomas occur only in 50% of cases . BCC most often proliferate between puberty and 35 years of age, although cases in patient as young as 3 or 4 have also been reported. BCC may vary in number from a few to 1000 and range in size from 1 to 1 Omm in diameter. BCC most often involve face and non-exposed areas such as the back and chest. Rarely it involves waist or extremities. They can vary from flesh colored papules to ulcerating plaques and may be mistaken for nevi, skin tags or hemangiomas. For BCC radiation therapy should be avoided because it causes invasion of BCCs years later. Management of superficial basal cell carinoma without hair follicle involvement can be accomplished by topical application of 0.1 % retinoin cream and 5% 5-Flourouracil to the entire body twice daily. Sanchez Conejo - Mir and Camacho reported that etretinate doses of 0.5 to 1 mg/kg/day can cause lesions that are less than 1 cm in diameter to regress and prevent new lesions . The incidence of BCC increases between puberty to 35 years . As the present case is only 17 years periodic visits to dermatologist is must.
The present case also exhibited the typical feature of temporo - parietal bossing with skull having pagetoid appearance, prominent supra-orbital ridge giving the eye a sunken appearance, broad nasal root, hypertelorism, posteriorly angulated ears and other skeletal abnormalities like bifid rib and spina bifida occulta. Study by Muzio LL et al revealed 28% abnormal skull configuration, 25% bifid ribs, 7% thoracic and cervical vertebral anomalies, 28% had posteriorly angulated ears .
In conclusion the occurrence of either multiple cyst in jaws or OKCs detected in much younger age group is an early clue to the dentist to detect presence of NBCCS.
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