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CASE REPORT
Year : 2012  |  Volume : 3  |  Issue : 4  |  Page : 514-518  

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome)


Department of Pedodontics and Preventive Dentistry, Sri Siddhartha Dental College and Hospital, Agalakote, Tumkur, Karnataka, India

Date of Web Publication20-Feb-2013

Correspondence Address:
N K Kiran
Department of Pedodontics and Preventive Dentistry, Sri Siddhartha Dental College and Hospital, Agalakote, Tumkur 502 107, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-237X.107459

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   Abstract 

The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

Keywords: Bifid ribs, calcification of falx cerebri, nevoid basal cell carcinoma syndrome, odontogenic keratocysts, palmer and planter pits


How to cite this article:
Kiran N K, Tilak Raj T N, Mukunda K S, Reddy V R. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome) . Contemp Clin Dent 2012;3:514-8

How to cite this URL:
Kiran N K, Tilak Raj T N, Mukunda K S, Reddy V R. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome) . Contemp Clin Dent [serial online] 2012 [cited 2019 Jun 26];3:514-8. Available from: http://www.contempclindent.org/text.asp?2012/3/4/514/107459


   Introduction Top


Nevoid basal cell carcinoma syndrome (NBCCS) also known as Gorlin-Goltz syndrome is an infrequent multisystemic disease that is inherited in a autosomal dominant way, which shows the high level of penetrance and variable expressiveness. [1],[2],[3] NBCCS characterized mainly by the presence of multiple odontogenic keratocysts (75%), basal cell carcinoma (50-97%), bifid ribs (40%), palmar and planter pits (60-90%) and ectopic calcification of the falx cerebri (37-79%). [4] This syndrome has received several names throughout the times such as, basal cell nevus syndrome, multiple NBCCS, multiple basal-cell carcinoma syndrome, multiple basalioma syndrome, jaw cysts-basal cell tumor-skeletal anomalies syndrome, odontogenic keratocysts-skeletal anomalies syndrome and fifth phacomatosis. [5] Currently, this disorder is called as NBCCS, which was suggested by Professor Gorlin as this syndrome results from mutations in the PTCH1 gene. [6] The estimated prevalence varies from 1/57,000 to 1/256,000, with a male to female ratio of 1:1. [7]

Jarisch and White in 1894 made a first descriptions by highlighting the presence of multiple basocellular carcinomas in patients with this syndrome. [8],[9] Later in 1939 a familiar case was described by Straith in which multiple basocellular carcinomas and cysts appeared. [10] Gross in 1953 presented a case suggesting additional signs such as synostosis of the first left rib and bilateral bifurcation of the 6th ribs. [11] Palmar and planter pits which is associated with the syndrome was first described by Bettley and Ward. [12],[13] In 1960 Gorlin-Goltz established a classical triad of basal cell carcinoma, odontogenic keratocyst and bifid ribs, that characterizes the diagnosis of this syndrome. Later this triad was modified by Rayner et al., who established that for giving the diagnosis, at least cysts had to appear in combination with calcification of the falx cerebri or palmar and planter pits. [14],[15]


   Case Report Top


A 13-year-old-boy reported to the Department of Pedodontics and Preventive Dentistry with the chief complaint of swelling and pain in the lower left back teeth region. On clinical examination, extra oral swelling which was tender and hard in consistency extending from the anterior border of the left ramus to the left parasymphysis region measuring approximately 4×3 cm [Figure 1]a was observed. On physical examination, presence of dysmorphic facial features like relative macrocephaly and ocular hypertolorism were observed. Sprangal scapular deformity [Figure 1]b and palmar and planter pits [Figure 1]c were also observed. On intraoral examination, grossly decayed mandibular left second primary molar and swelling in the vestibule region was observed.

Intraoral periapical radiograph revealed the presence of large radiolucent area with sclerotic border, suggestive of a cyst. Orthopantomograph revealed the presence of multiple cysts both in maxilla and mandible [Figure 2]a. Considering the possibility of the NBCCS with the above features, further investigations were carried out. Computed tomography showed ectopic calcification of the falx cerebrai [Figure 2]b and presence of multiple cysts in the maxilla [Figure 2]c and mandible [Figure 2]d. Antero-posterior view of the chest showed the presence of bifid rib in the posterior aspect of the right 3 rd rib and rib expansion was noted in the anterior end of the left 3 rd and 4 th rib [Figure 2]e. Lateral cephalograph showed bridging of the sella turcica [Figure 2]f.
Figure 1

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Figure 2

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   Histopathological Findings Top


Histopathological findings of the incisional biopsy showed cystic lining overlying the connective tissue capsule. The lining epithelium was of 6-10 layers thick. The basal layer showed hyperchromatism and pallisading appearance [Figure 3]a. The surface was corrugated and showed pyknotic nuclei, the epithelium was folded and showed separation from the capsule in many areas. With all these histological findings the biopsy was confirmed as parakeratinized odontogenic keratocyst.
Figure 3: Photomicrograph of odontogenic keratocystcyst showing hyperchromatism and pallisading appearance (H and E, original magnification 40)

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With the above clinical, radiographic and histopathological findings the present case was diagnosed as the NBCCS.


   Discussion Top


NBCCS was first described by Jarisch and White in 1894 [9] and later established as a unique syndrome by Gorlin and Goltz in 1960. [14] The pathogenesis of NBCCS is attributed to abnormalities linked to the long arm of chromosome 9 (q22.3-q31) PTCH1 gene with no apparent heterogeneity. The malformative pattern of NBCCS suggests that the gene has a fundamental function in controlling growth and development of normal tissue and data suggests that the product of this gene acts as a tumor suppressor. This gene was first isolated in 1996 as the human homolog of the Drosophila PTCH1 gene, simultaneously in Australia and in the USA. NBCCS includes abnormalities in the skin, stomatologic system, ectopic calcification of the CNS and other brain signs, skeletal system, ocular system, genitor-urinary system, mesenteric cysts and cardiovascular system. The syndrome initially consisted of the triad of basal cell carcinoma, jaw cysts and skeletal anomalies. Basal cell carcinoma usually appears between puberty and 35 years of age, but cases have been reported in 3-4-year-old patients also. [5] The incidence varies widely among ethnic groups, studies have shown that only about 40% of black patients affected by NBCCS manifest basal cell carcinoma, while in whites they are reported in up to 90% of cases. Odontogenic keratocysts develop in more than 50% of NBCCS patients, often in the first decade of life. NBCCS is essentially a clinical and radiological diagnosis, and diagnosis of NBCCS can be made when two of the five major manifestations or one major and two minor manifestations are present. [15] The diagnostic criteria based on the most frequent and/or specific features of the syndrome are given by Evans et al. Later these criteria were modified by Kimonis et al. in 1997 [16] The major criteria and minor criteria for the diagnostic purpose are listed in [Table 1] [16] and the clinical examination protocol for patients with NBCCS as suggested by Lo Muzio are listed in [Table 2]. [5]

In our case four major manifestations such as odontogenic keratocysts, bifid rib, ectopic calcifications of the falx cerebri, palmar and planter pits were identified. Basal cell carcinoma was not found in our case as the patient was only 13-years-old, but cases have been reported in 3-4-year-old patients also. [5] And four minor manifestations such as ocular hypertolorism, macrocephaly, frontal bossing, bridging of sella tursica were identified and diagnosed as NBCCS.
Table 1: Diagnostic criteria for Gorlin syndrome

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Table 2: Diagnostic protocols in NBCCS

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Early diagnosis of NBCCS is crucial to the affected children and their families, considering the risk of developing malignancies such as medulloblastoma and aggressive skin cancers, [17] it is very important to screen for medulloblastoma in the early years of life in patients with NBCCS as it may be a potential cause of early death and early diagnosis is important to give adequate genetic advice. [4],[5] A negative family history could hamper the early clinical recognition of patients with NBCCS:Nonetheless, patient can be diagnosed during early childhood if the clinician is also aware of the minor clinical signs of the disease. [18]

The treatment of NBCCS is the specific therapeutics of its clinical manifestations. There are two methods for the treatment of odontogenic keratocysts, a conservative and an aggressive. In the conservative method, simple enucleation with or without curettage and marsupialization are suggested. Aggressive methods include peripheral ostectomy, chemical curettage with Carnoy's solution and resection. [19] Radicular interventions such as enucleation with shaving of surrounding bone or sometimes resection, might contribute to prevention of recurrences and improve the prognosis. [19],[20] However, serious consideration should be given to en bloc resection in the following cases (1) When odontogenic keratocysts recur despite previous enucleation with an adjunctive procedure. (2) When odontogenic keratocysts recur despite previous marsupialization followed by enucleation with an adjunctive procedure. (3) In cases of multilocular (multilobular) aggressive intraosseous odontogenic keratocysts. (4) In cases of multiple nonsyndromic and syndromic odontogenic keratocysts of NBCCS. (5) In a diagnosed odontogenic keratocysts exhibiting particularly aggressive clinical behavior that should require resection as the initial surgical treatment. [21]

If the patient is in the first decade and has still unerupted permanent teeth involving odontogenic keratocysts, it would be difficult to make a decision of aggressive surgery over conservative management. In children with unerupted teeth, conservative management should be considered first because an aggressive operation can have an adverse effect on the eruption process and the development of the involved jaw. [22] Thus, younger patients should usually receive conservative rather than aggressive treatment.


   Conclusions Top


The present case highlights the importance of awareness of this rare syndrome especially in young patients without skin lesions and its importance to make early diagnosis and its proper management, which has cancer predisposition. In order to arrive at an early diagnosis of the syndrome, specialists should carry out a clinical, radiographic testing in early ages of life. In this way, different health specialists like pediatricians, specialists in genetics, dentists, maxillofacial surgeons, dermatologists, etc., must have good basic knowledge of the main features of the syndrome to work accordingly in their different health specialities. [4] Guidelines for follow-up have been established and include the following: Neurological examination twice yearly, cerebral MRI once in a year for 1-7 years of age, orthopantomogram every 12-18 months starting at the age of eight years, yearly skin examination and cardiologic examination according to the signs and symptoms. [17] The families of the patients with NBCCS should be examined and genetic counseling should be offered, as it is inherited as an autosomal dominant disorder.

 
   References Top

1.Gu XM, Zhao HS, Sun LS, Li TJ. PTCH mutations in sporadic and Gorlin-syndrome-related odontogenic keratocysts. J Dent Res 2006;85:859-63.  Back to cited text no. 1
[PUBMED]    
2.R Yang X, Pfeiffer RM, Goldstein AM. Influence of glutathione-S-transferase (GSTM1, GSTP1, GSTT1) and cytochrome p450 (CYP1A1, CYP2D6) polymorphisms on numbers of basal cell carcinomas (BCCs) in families with the naevoid basal cell carcinoma syndrome. J Med Genet 2006;43:e16.  Back to cited text no. 2
[PUBMED]    
3.Veenstra-Knol HE, Scheewe JH, van der Vlist GJ, van Doorn ME, Ausems MG. Early recognition of basal cell naevus syndrome. Eur J Pediatr 2005;164:126-30.  Back to cited text no. 3
    
4.Ortega García de Amezaga A, García Arregui O, Zepeda Nuño S, Acha Sagredo A, Aguirre Urizar JM. Gorlin-Goltz syndrome: Clinicopathologic aspects. Med Oral Patol Oral Cir Bucal 2008;13:E338-43.  Back to cited text no. 4
    
5.Lo Muzio L. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis 2008;3:32.  Back to cited text no. 5
    
6.Gorlin RJ. Nevoid basal cell carcinoma (Gorlin) syndrome. Genet Med 2004;6:530-9.  Back to cited text no. 6
    
7.Evans DG, Ladusans EJ, Rimmer S, Burnell LD, Thakker N, Farndon PA. Complications of the naevoid basal cell carcinoma syndrome: Results of a population based study. J Med Genet 1993;30:460-4.  Back to cited text no. 7
    
8.Jarisch W. Zur lehre von den hautgeschwulsten. Archiv für Dermatologie und Syphilis. 1894;28:163-5.  Back to cited text no. 8
    
9.White JC. Multiple benign cystic ephiteliomata. J Cutan Dis 1894;12:477-81.  Back to cited text no. 9
    
10.Straith FE. Hereditary epidermoid cyst of the jaws. Am J Orthod Oral Surg 1939;25:673-7.  Back to cited text no. 10
    
11.Gross PP. Epithelioma adenoides cysticum with follicular cysts of maxilla and mandible. J Oral Surg (Chic) 1953;11:160-5.  Back to cited text no. 11
    
12.Bettley FR. Two cases of multiple naevoid basal cell epitheliomata? porokeratosis of Mantoux. Br J Dermatol 1953;65:219-21.  Back to cited text no. 12
    
13.Ward WH. Naevoid basal celled carcinoma associated with a dyskeratosis of the palms and soles. A new entity. Aust J Dermatol 1960;5:204-8.  Back to cited text no. 13
    
14.Gorlin RJ, Goltz RW. Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib. A syndrome. N Engl J Med 1960;262:908-12.  Back to cited text no. 14
    
15.Rayner CR, Towers JF, Wilson JS. What is Gorlin's syndrome? The diagnosis and management of the basal cell naevus syndrome, based on a study of thirty-seven patients. Br J Plast Surg 1977;30:62-7.  Back to cited text no. 15
    
16.Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997;69:299-308.  Back to cited text no. 16
    
17.Kim HM, Lee CH, Kim SK, Sung TJ. Basal cell nevus syndrome (Gorlin Syndrome) confirmed by PTCH mutations and deletions. Korean J Pediatr 2007;50:8.  Back to cited text no. 17
    
18.Veenstra-Knol HE, Scheewe JH, van der Vlist GJ, van Doorn ME, Ausems MG. Early recognition of basal cell naevus syndrome. Eur J Pediatr 2005;164:126-30.  Back to cited text no. 18
    
19.Kolokythas A, Fernandes RP, Pazoki A, Ord RA. Odontogenic keratocyst: To decompress or not to decompress? A comparative study of decompression and enucleation versus resection/ peripheral ostectomy. J Oral Maxillofac Surg 2007;65:640-4.  Back to cited text no. 19
    
20.Kuroyanagi N, Sakuma H, Miyabe S, Machida J, Kaetsu A, Yokoi M, et al. Prognostic factors for keratocystic odontogenic tumor (odontogenic keratocyst): Analysis of clinico-pathologic and immunohistochemical findings in cysts treated by enucleation. J Oral Pathol Med 2009;38:386-92.  Back to cited text no. 20
    
21.Tolstunov L, Treasure T. Surgical treatment algorithm for odontogenic keratocyst: Combined treatment of odontogenic keratocyst and mandibular defect with marsupialization, enucleation, iliac crest bone graft, and dental implants. J Oral Maxillofac Surg 2008;66:1025-36.  Back to cited text no. 21
    
22.Hyun HK, Hong SD, Kim JW. Recurrent keratocystic odontogenic tumor in the mandible: A case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:e7-10.  Back to cited text no. 22
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]


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