Article By

Edlyn Rodrigues

Vikas Dhupar

Francis Akarra

 

Abstract

Keratocystic odontogenic tumour (KCOT) can appear as solitary lesion or in association with Gorlin- Goltz syndrome (GGS). GGS affects the skin, jaw and brain. It has an autosomal dominant inheritance pattern. Therefore, a careful screening of first degree relatives is imperative to rule out nevoid basal cell carcinoma syndrome (NBCCS) once KCOT is suspected. Early diagnosis and long term surveillance is essential to intercept and manage this syndrome.

Introduction:

Gorlin or Gorlin-Goltz syndrome is a rare autosomal dominant inherited condition and an ectodermal polydysplasia. First described by Jarisch and White in 1894, its incidence varies from 1/57,000 to 1/256,000.[1] The principal genetic defect is mutation in the PTCH gene, which has been mapped to chromosome 9q22.3- q31.

Keratocystic odontogenic tumour (KCOT) can appear as solitary lesion. However, in 5-10% cases it occurs in association with nevoid basal cell carcinoma syndrome (NBCCS).[2-4] This predisposes the individual to recurrent destructive pathology involving the skin, jaw and brain. Therefore, a careful evaluation is mandatory to rule out NBCCS once KCOT is suspected.

Case Reports:

The case series represents three first-degree relatives (two siblings and their maternal aunt) presenting to the department of Oral and Maxillofacial Surgery, Goa Dental College and Hospital (OMFS-GDCH) at different times with a common clinical and histopathological manifestation of KCOT.

Case 1:

A 35-year-old lady reported to OMFS-GDCH in the year 2005 and was diagnosed with KCOT. The treatment carried out was enucleation, chemical cauterization and extraction of the mobile lower (left) first, second, and third molars. She was followed up for a span of three years and was disease free during the period. She then reported in the year 2013 with complaints of intra-oral pus discharge and pain in the left posterior mandibular region. She had no obvious facial asymmetry. However, she was elicited for paresthesia in relation to her left lower lip. Intraoral pus discharge was present. No tooth involvement in that region. Orthopantomogram (OPG) (Figure 1) revealed a multilocular radiolucency of left angle and ramus around the coronoid and condylar processes.

TC-Apr2017-021 - Orthopantomogram showing the KCOT in anterior mandible and an inferiorly displaced canine

Figure 1: Orthopantomogram showing the KCOT in anterior mandible and an inferiorly displaced canine, another cystic lesion involving impacted maxillary third molar on left side.

An aspiration biopsy was done and the protein estimate was 0.8g/100ml. Histopathological findings confirmed the parakeratinized variant of odontogenic keratocyst. Computed tomography (CT) brain showed calcification of falx cerebri (Figure 2) and dermatologic examination revealed palmar pits (Figure 3) and plantar pits (Figure 4). Chest screening was done and no abnormalities were detected. The patient underwent enucleation and peripheral ostectomy and is under a regular follow-up.

TC-Apr2017-022 - Sagittal section of CT scan showing calcification of falx cerebri

Figure 2: Sagittal section of CT scan showing calcification of falx cerebri

TC-Apr2017-023 - Palmar pits

Figure 3: Palmar pits

TC-Apr2017-024 - Plantar pits

Figure 4: Plantar pits

Case 2:

A 13-year-old female reported to OMFS-GDCH in the early part of 2014 with a chief complaint of a mobile upper right canine. On examination, a grade III mobile right canine with eggshell crackling effect and tenderness, was present on palpation. Orthopantomogram revealed a periapical lesion in relation to the affected tooth. She underwent enucleation and extraction of the mobile tooth in the right maxillary canine region. She then reported again later that year with a swelling and intra-oral discharge present on the left side of the mandible. Intra-oral examination revealed a mild swelling in left posterior mandibular region with no tenderness or nerve deficit. OPG showed a solitary welldefined unilocular radiolucency with well defined sclerotic margins. An aspiration biopsy suggested a protein estimate of 1.2g/100ml. Histopathological findings confirmed parakeratinised variant of KCOT. Chest screening was done and no skeletal abnormalities were detected. CT brain revealed calcification of falx cerebri and dermatologic examination revealed palmar and plantar pits. Patient underwent enucleation and chemical cauterization and was kept under regular followup. In the year 2016, the patient reported with pain and swelling in the left maxillary tuberosity region associated with an impacted upper (left) third molar. An aspiration biopsy was positive for KCOT. The patient underwent enucleation, curettage, chemical cauterization and is under regular follow-up.

Case 3:

A 19-year-old boy reported to OMFS-GDCH in the year 2015 with chief complaint of intra-oral swelling in anterior mandibular region. The patient also gave history of untreated congenital heart disease. The patient had facial asymmetry, bony hard swelling in the anterior mandible region, grade II mobility and teeth displacement in relation to the lower anterior teeth. Bifid uvula was present. No nerve deficits were noted. OPG revealed a solitary well defined radiolucent lesion in the anterior mandible, crossing the midline, with sclerotic borders, associated with an impacted left mandibular canine and almost involving the lower border of the mandible. Teeth within the lesion appeared displaced. Incidentally, two other solitary unilocular radiolucent lesion with well-defined sclerotic border were seen, one in relation with an impacted third molar tooth in the left maxillary region and other at the apices involving the right maxillary premolar and molar. An aspiration biopsy revealed thick cheesy aspirate with protein content of 0.6g/100ml. CT Brain showed calcification of falx cerebri. Dermatologic examination confirmed palmar and plantar pits. Histopathological findings confirmed parakeratinised variant of KCOT. Patient underwent enucleation, with chemical cauterization, peripheral ostectomy and extraction of mandibular anterior teeth. Enucleation of cystic lining followed by extraction of left maxillary third molar and enucleation of cyst in relation to right maxillary first molar was done.Patient is kept under observation and regular follow-up.

The mother of the two children (cases 2 and 3) was also screened, calcification of falx cerebri and palmar plantar pits were present; however, she did not show any evidence of KCOT. However, her sister (Case 1) had findings consistent with the other two.

It was also observed that the patients in the case series reported with new lesions in the jaw.

Discussion:

Gorlin-Goltz syndrome affects the skin, jaw and brain. To confirm the presence of this syndrome any of the following diagnostic criteria must be fulfilled:
a) two major criteria
b) major criteria and molecular confirmation
c) one major and two minor criteria.

These criteria were originally given by Evans 1993[5] and then modified by Kimonis in 1997[6] and Bree in 2007[7].

DIAGNOSTIC CRITERIA OF NBCCS[7]

MAJOR CRITERIA

  • Excessive number of basal cell carcinoma out of proportion with sun exposure and skin type or one under the age of 20 years
  • KCOT of the jaw prior to 20 years of age
  • Palmar or plantar pits
  • Lamellar calcification of falx cerebri
  • Medulloblastoma typically desmoplastic
  • First degree relative with NBCCS

MINOR CRITERIA

  • Rib anomalies – bifid, fused or splayed ribs
  • Macrocephaly
  • Congenital anomalies – cleft lip or palate, frontal bossing, hypertelorism
  • Skeletal malformations and radiological changes – vertebral anomalies, kyphoscoliosis, short 4th metacarpal, postaxial polydactyly
  • Fibromas – ovarian or cardiac
  • Lymphomesenteric cysts
  • Ocular abnormalities – strabismus, hypertelorism, congenital cataracts, glaucoma, coloboma

 

DIAGNOSTIC PROTOCOL FOR GGS:
Management of GGS requires a multidisciplinary approach. Regular follow up must be carried out by a team of specialists including dermatologist, neurologist, and maxillofacial surgeon[8,9].

Dental professionals may be the first to come across and identify this syndrome when cystic radiolucency is present on radiographs of the jaws. Therefore, the patient must be counselled for the same. The family members of patients with NBCCS may be screened.

Keratocysts are treated by surgical removal, yet tend to recur after surgical treatment. However, enucleation, chemical cauterization and peripheral ostectomy markedly decrease the rate of recurrence. Patients reporting with recurrent KCOT’s should be screened for NBCCS.

GUIDELINES FOR THE FOLLOW UP PERIOD:

  • Neurological examination at least twice a year; brain magnetic resonance imaging (MRI) once a year for 1-7 years of age.
  • Dermatological examinations annually
  • Cardiology examination based on signs and symptoms.
  • Dental screening with an orthopantomogram annually starting at the age of 8 years.
  • A regular follow up for the first three years following treatment biannually followed by annual check-up thereafter.

 

Conclusion:

The case series highlights the need of screening the first degree relatives of patients with known mutations and intervening at an early stage to reduce the destruction and deformities of skin, bones, and brain due to GGS. In view of the above, a multidisciplinary approach is strongly recommended. Frequent follow ups are mandatory to intercept the disease at an early stage and prevent its recurrence.

 

Edlyn Rodrigues, BDS, MDS Senior Resident

Vikas Dhupar, BDS, MDS Professor and Head of Department

Francis Akarra, BDS, MDS Professor Department of Oral & Maxillofacial Surgery Goa Dental College and Hospital Bambolim, Goa Email: edlynr@gmail.com

References:

1. Lo Muzio L. Nevoid basal cell carcinoma syndrome (Gorlin Syndrome). Orphanet J Rare Dis. 2008; 3:32.

2. Payne TF. An analysis of the clinical and histopathologic parameters of the odontogenic keratocyst. Oral Surg Oral Med Oral Pathol. 1972; 33:538-546.

3. Gustafson G, Lindahl RA, Dahl E, Srensson A. The nevoid basal cell carcinoma syndrome – Gorlin’s Syndrome. Swed Dent J. 1989; 13: 131-139.

4. Gorlin RJ, Vickers RA, Kellen E, Williamson JJ. Multiple basal cell nevi syndrome. An analysis of a syndrome consisting of multiple nevoid basal cell carcinoma, jaw cysts, skeletal anomalies, medullobastoma, and hyporesponsiveness to parathormone. 1965; 89-104

5. Evans DG, Ladusans EJ, Rimmer S, et al. Complication of nevoid basal cell carcinoma syndrome: results of a population based study. J Med Genet 1993; 30: 460-4.

6. 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(3):299-308.

7. Bree AF, Shah MR, BCNS Colloquium group. Consensus statement from the first colloquium on basal cell nevus syndrome (BCNS). Am J Med Genet A 2011; 155A: 2091-7.

8. Wang XX, Zhang J, Wei FC. Familial multiple odontogenic keratocysts. J Dent Child (Chic). 2007; 74:140-2

9. Raj A, Bahadur R, Bansal S, Kumar P. Intricate correlation and biological behavior of keratocyst in nevoid basal cell carcinoma syndrome: A comprehensive review of literature. Clin Cancer Investig J 2013; 2:185-8.