Surprising genetic and pathological findings in a patient with giant bilateral periadrenal tumours: PEComas and mutations of PTCH1 in Gorlin-Goltz syndrome

Gorlin-Goltz syndrome (GGS) or nevoid basal cell carcinoma syndrome is a rare tumour-overgrowth syndrome associated with multiple developmental anomalies and a wide variety of tumours. Here, we describe a case of a man aged 23 years with GGS with bilateral giant tumours adjacent to both adrenals that raised the suspicion of malignancy on imaging. Histological analysis of both surgically resected tumours revealed perivascular epitheloid cell tumours (PEComas) that were independent of the adrenals. Exome sequencing of the patient’s blood sample revealed a novel germline heterozygous frameshift mutation in the PTCH1 gene. As a second hit, a somatic five nucleotide long deletion in the PTCH1 gene was demonstrated in the tumour DNA of both PEComas. To the best of our knowledge, this is the first report on PEComa in GGS, and this finding also raises the potential relevance of PTCH1 mutations and altered sonic hedgehog signalling in PEComa pathogenesis. The presence of the same somatic mutation in the bilateral tumours might indicate the possibility of a postzygotic somatic mutation that along with the germline mutation of the same gene could represent an intriguing genetic phenomenon (type 2 segmental mosaicism).

1537 Squamous Cell Carcinoma Arising in A Maxillary Odontogenic Keratocyst in Gorlin Goltz Syndrome - A Rare Case Report

Introduction Gorlin Goltz syndrome (GGS) is a rare, hereditary, AD condition with multiple BCCs, odontogenic keratocysts (Jaw cysts), calcification of falx cerebri, skeletal anomalies & a predisposition to neoplasms like medulloblastomas, fibromas and rhabdomyosarcomas. Aim We present a rare case of a Squamous cell carcinoma (SCC) developing in a Maxillary odontogenic keratocyst in a 32-year male with GGS. Discussion This patient was referred to the OMFS unit with a non-healing UL3 extraction socket and exophytic growth. Initial biopsies suggested an atypical squamo-proliferative lesion, however a repeat biopsy demonstrated an invasive SCC arising from a background odontogenic keratocyst of the maxilla. He was initially reluctant to undergo a staging CT scan to avoid risks of developing further BCCs due to IR exposure. This was eventually performed as per H&N MDT recommendation & showed a T4aN0M0 SCC of the left maxilla and bilateral multiple mandibular odontogenic keratocysts. He underwent a left maxillectomy, left neck dissection & reconstruction with a DCIA free flap, but did not want his mandibular keratocysts treated at the same time. Complete tumour clearance was achieved with no involved neck nodes & he remains disease-free at 4 months postoperatively. Although for a T4 tumour he would have needed postoperative radiotherapy, in view of the GGS, no adjuvant treatment was indicated. Conclusions SCC developing in a maxillary OKC is exceedingly rare with only two previous cases reported in GG syndrome. This is the first reported case of a GGS patient with oral SCC undergoing a complex free flap reconstruction.

Multiple Odontogenic Keratocysts in a Non-syndromic Young Patient: An Unusual Case Report

Odontogenic keratocyst (OKC) is a benign intraosseous lesion with invasive and aggressive behavior. It comprises approximately 2-21.8% of all jaw cysts. Odontogenic keratocysts (OKCs) are believed to arise from remnants of the dental lamina most common site in the molar ramus area. OKCs have a specific histopathologic appearance and are found to be locally aggressive and have a high recurrence rate, thus requires close long-term follow-up. OKCs are one component of the Gorlin-Goltz syndrome and all patients with multiple OKCs should be evaluated for this syndrome. In this paper, we present a case of a 13-year old non-syndromic female patient with multiple OKCs located at symphysis and bilateral mandibular angle region who was treated surgically with no obvious post-operative complications during follow-up period.