The bigger picture: a gorlin-goltz case report

Investigations

The radiolucency on the intra-oral radiograph appeared to extend beyond the margins of the image. A DPT was taken (Figure 1) showing multiple large radiolucencies in the mandible and maxilla. In the anterior mandible there was a large well-defined uniformly radiolucent lesion, with scalloped margins, extending from the superior to the inferior border of the mandible and from the distal root of LL7 to the distal root of LL6, displacing the roots of LL12 and LL5. Similar radiolucencies were present in the left posterior mandible and the right and left posterior maxilla. These radiolucencies were suspected to be OKCs owing to their unilocular, well defined and corticated uniformly radiolucent appearance. Nevertheless, histopathological evaluation was required to confirm such a diagnosis.

Diagnosis

A discussion with the patient followed the extraordinary findings of the DPT. He denied any history or awareness of jaw cysts. When asked if he was familiar with the term ‘Gorlin-Goltz syndrome’, the patient showed immediate recognition: his son was being treated at Great Ormond Street Hospital for the same condition. Upon further questioning it was found that his father had suffered from oral cysts in the past.

The patient was subsequently sent for a CT head and neck scan (Figures 2 and 3) to ascertain the extent of the cysts and to detect other radiographic markers of Gorlin-Goltz. He was also listed for biopsy of the anterior cyst under local anaesthetic to verify OKC.

The CT scans clearly showed calcified falx cerebri and other meninges, other major criteria for the syndrome, as well as cervical vertebral ribs (a minor criterion). The biopsy result confirmed the cyst is an OKC.

Treatment

The patient was understandably overwhelmed by the diagnosis. He felt that he would like to concentrate on his son's treatment and postpone the removal of any cysts. He is therefore continuing to be reviewed at our clinic with a view to treatment in the future.

Gorlin-Goltz syndrome

Gorlin-Goltz is a multisystemic autosomal dominant inherited disorder characterized by multiple odontogenic keratocysts (OKCs), basal cell carcinomas (BCCs), palmar or plantar pits and other dental, skeletal, ophthalmic, neurological abnormalities and facial dysmorphia.¹ It was first reported in 1894, although Gorlin and Goltz did not formally document its clinical features until the 1960s.² It is caused by a mutation in the patched gene (a tumour suppressor gene) due to abnormalities on the long arm of chromosome 9, causing cell proliferation and producing multiple OKCs and BCCs.³ It is estimated that the prevalence of Gorlin-Goltz syndrome is 1 in 60,000 generally, and 1 in 57,000–164,000 in England.⁴ Males and females are affected equally, although simple keratocysts are found more commonly in males.⁵ Caucasians tend to be most affected by the syndrome, and it usually presents in patients aged 17–35.⁶

Its diagnosis is based on the presence of two major criteria and one minor clinical criterion, or one major and two minor criteria (Tables 1 and 2). Early diagnosis and treatment of Gorlin-Goltz syndrome are essential as 10% of patients are at risk of aggressive basal cell carcinoma and the development of other malignant neoplasia. Over 100 minor criteria have been described, hence patients with a myriad of clinical presentations may be seen.³

Our aforementioned patient fulfilled three major criteria for Gorlin-Goltz syndrome: OKC confirmed histologically, calcified falx cerebri and a first degree relative suffering the same condition. As with previously described cases, our patient's initial finding was the identification of multiple lesions in the mandible which were confirmed as OKCs. Less than 10% of patients with multiple OKCs have other manifestations of Gorlin-Goltz syndrome and previous reports have suggested multiple OKCs alone may be enough to establish this disorder.^7,8 In Gorlin-Goltz, OKCs tend to occur more commonly in the mandible with approximately a third affecting the maxilla.^9,10 Within the mandible the most common areas include:⁵

Patients should be informed that, although benign in nature, the OKC is locally destructive and has a recurrence rate of 3–60%.¹¹

Odontogenic keratocysts

The odontogenic keratocyst has a colourful history with regards to nomenclature and classification. It has experienced many name changes owing to its combined cystic nature and neoplastic potential. In 2005, the WHO changed the classification of OKC from a cyst to a tumour because of certain neoplastic features, including recurrence, potentially aggressive and destructive behaviour, and pathogenesis associated with mutation of the ‘patched’ tumour suppressor gene (PTCH).¹² It therefore received the name ‘keratocystic odontogenic tumour’. However, in 2017, the evidence to class it as a neoplasm was deemed insufficient and it was redesignated as a cyst and regained the name ‘odontogenic keratocyst’.¹³

Differential diagnosis of jaw radiolucencies

Cysts tend to have smooth, well-defined margins and be uniformly radiolucent. They are usually well corticated, although the level of cortication may be influenced by the presence of infection. They tend to be slow growing and cause displacement of adjacent structures and bony expansion in the later stages.¹⁴ Cysts may be differentiated from each other radiographically by their location and association with adjacent structures, eg impacted teeth or non-vital teeth.¹⁵ Some cysts may display calcification (eg calcifying epithelial odontogenic tumour), which helps to distinguish them from other cysts.¹⁶

Benign tumours are slow growing, well-defined lesions with smooth borders. Similarly to cysts they tend to cause displacement and expansion rather than resorption. However, these tumours have varying radiodensities, and may appear as radiolucent, mixed or radio-opaque, depending on the lesion.¹⁷

Malignant tumours can be distinguished from benign jaw radiolucencies by their poorly-defined radiographic appearance and irregular margins.¹⁴ Due to their fast and aggressive pattern of growth, they tend to resorb roots and erode adjacent structures rather than displace or expand.¹⁸ Some benign lesions, such as odontogenic keratocysts, may also exhibit aggressive growth and require prompt management. It is crucial to be able to distinguish these characteristics from those of benign lesions to ensure rapid referral.

Table 3 highlights distinguishing features of some jaw radiolucencies to aid differentiation. This is by no means an extensive list and further reading is encouraged.