Teaching Case

A 21-year-old male presented to the dental department with a history of swelling in the left lower jaw of four-month duration, associated with exfoliation of two teeth from the 3^rd quadrant three months back. On oral examination, a hard-to-firm cystic swelling was seen arising from the 3^rd quadrant of the jaw.

Orthopantomogram revealed absent teeth 35 and 36 with two radiolucent, expansile lesions in the mandible, a larger one involving the 3^rd quadrant adjacent to the roots of teeth 32 to 37 and another one in the 4^th quadrant related to the root of teeth 47 (Figure 1).

A non-contrast CT scan revealed a cystic lesion with anteroposterior expansion seen in the 3^rd quadrant with multiple breaches in the anterior cortex and a soft tissue component extending outside the bone (Figures 2a, 2b and 2c). A smaller unilocular lesion is seen on the right side (Figure 3). These were seen to displace adjacent teeth. These were diagnosed as odontogenic keratocysts (OKC) confirmed by histopathological examination.

CT scan also revealed lamellar calcification of falx cerebri and calcifications in the tentorium (Figure 4) and large Wormian bones in the sagittal suture (Figure 5) and fusion of bilateral anterior and posterior clinoid processes.

The chest radiograph revealed bifid third, fourth, and sixth ribs on the right and hypoplastic third rib on the left (Figure 6). Spina bifida is seen at the C7 and T1 levels (Figure 7).

Multiple palmar pits were seen in the hands (Figure 8).

Background

Naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant hereditary condition first described in 1894 [1] and described in detail by Gorlin and Goltz in 1960 [2]. It is a rare disorder with incidence varying in different studies from 1/57,000 to 1/264,000 [3–5]. It is associated with developmental disorders and predisposition to benign and malignant tumours, including cutaneous basal cell carcinomas, odontogenic keratocysts, palmar/plantar dyskeratotic pits, intratarsal keratinous eyelid cysts, intracranial calcifications, macrocephaly, and medulloblastomas (desmoplastic/nodular subtypes). NBCCS is caused by germline pathogenic variants of genes encoding members of the hedgehog signalling pathway, including PTCH1, SUFU, and, exceptionally, GPR161 [6].

Signs and symptoms: Clinical manifestations vary widely with the involvement of multiple organ systems, criteria for diagnosis were described by Kimonis et al. in 1997 [7], which include:

Major Criteria:

• Multiple (>2) BCCs or one under 20 years.
• Odontogenic keratocyst of the jaws proven by histopathology. The overall prevalence of OKC in NBCCS is reported to be between 66% to 80%. However, the prevalence of OKC is age-dependent, reaching up to 90% at the age of 40 years [8].
• Palmar or plantar pits (3 or more).
• Bilamellar calcification of the falx cerebri.
• Bifid, fused, or markedly splayed ribs.
• First-degree relatives with NBCCS.

Minor Criteria:

• Macrocephaly.
• Congenital malformation: cleft lip or palate, frontal bossing, “coarse face”, moderate or severe hypertelorism.
• Other skeletal abnormalities: Sprengel deformity, marked pectus deformity, marked syndactyly of the digits.
• Radiological abnormalities: bridging of the sella turcica, vertebral anomalies such as hemivertebrae, fusion or elongation of the vertebral bodies, modelling defects of the hands and feet, or flame-shaped lucencies of the hands or feet.
• Ovarian fibroma.
• Medulloblastoma: About 1–2% of patients with NBCCS with germline PTCH1 pathogenic sequence variants develop medulloblastoma [9].

Diagnosis is made with the presence of two major criteria or 1 major and two minor criteria.

Imaging perspective

Imaging plays a very important role in the diagnosis of OKC and other manifestations like dural calcifications, bifid ribs, and skeletal abnormalities. MRI helps in more accurate and non-invasive diagnosis of OKC on the basis of morphology and signal characteristics. OKC are generally multiloculated cystic lesions of the jaw, which are hypointense on T1WI and mixed intensity on T2WI. The content of OKC do not enhance on gadolinium contrast administration [10].

Outcome

This case emphasises the role of radiological investigations especially CT scans in the early diagnosis of the syndrome, which is important in the prevention of basal cell carcinoma by protection from UV rays.

Take home message / Teaching points

1. Patients in whom NBCCS is suspected, should be evaluated by relevant specialists to confirm the diagnosis.
2. Role of MRI in more accurate and non-invasive diagnosis of OKC.
3. To summarise new classification and genetics of NBCCS.

Written informed consent from the patient was obtained for publication.