OBJECTIVE: Dysregulation of the Hedgehog (Hh) pathway has been described in a variety of cancers, including cervical cancer, a disease which shares a common aetiology with vulval squamous cell carcinoma (VSCC). Here, we investigate a large number of primary VSCC cases for evidence of Hedgehog pathway activation and examine the implications of pathway activity on clinical outcomes in a cohort of patients with primary VSCC. METHODS: Archival histology blocks containing VSCC and histologically normal adjacent epithelium were retrieved from a cohort of 91 patients who underwent treatment for primary VSCC. Immunohistochemistry staining was undertaken to assess for the expression of key Hh pathway components (SHH, PTCH1, GLI1). A competing risks statistical model was used to evaluate the implications of the levels of key Hh pathway components on clinical outcomes. RESULTS: We show that 92% of primary VSCC cases over-expressed one or more components of the Hh signalling pathway when compared to the adjacent normal epithelium. While expression of SHH and GLI1 did not correlate with any clinicopathological criteria, over- or under-expression of PTCH1 was associated with a reduced or increased risk of developing a local disease recurrence, respectively. In VSCC arising on a background of Lichen Sclerosus, the risk of local recurrence was potentiated in cases where PTCH1 was under-expressed. CONCLUSIONS: Our findings reveal, for the first time, that the Hh pathway is activated in VSCC and that PTCH1 expression can be used as a biomarker to stratify patients and inform clinicians of the risk of their local recurrence, particularly in cases of VSCC associated with LS.

• MeSH
• Vulvar Lichen Sclerosus complications   genetics   metabolism   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local genetics   metabolism   pathology   MeSH
• Vulvar Neoplasms complications   genetics   metabolism   pathology   MeSH
• Patched-1 Receptor genetics   metabolism   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Carcinoma, Squamous Cell complications   genetics   metabolism   pathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVES: Identification of early presenting signs of the Basal Cell Nevus (BCNS; synonyme Gorlin-Goltz) syndrome, which is associated with a principal triad of multiple basal cell nevi, jaw odontogenic keratocysts, and skeletal anomalies, in stomatological and neurological practices. Proposal of multidisciplinary diagnostic algorithm comprising other medical specialists, including pathology, imaging, laboratory and molecular analyses based on the study outcomes. DESIGN: Case report of a male patient reporting paresthesia of their lower jaw, with right facial asymmetry (maxilla and mandible) and radiological detection of large osteolytic lesions in both jaws, including a retrospective analysis of a representative Czech cohort with BCNS from within the last decade. SETTING: Clinical, imaging and laboratory analyses were carried out at a national tertiary centre. RESULTS: A multidisciplinary clinical approach followed by surgical management lead to the identification of odontogenic cysts, which were substantiated by histological examination. DNA sequencing of the PTCH1 gene detected a c.2929dupT resulting in p. Tyr977Leufs*16 pathogenic variant. This finding confirmed the clinical and laboraoty diagnosis of BCNS. Parental DNA analysis showed that this causal genetic defect arose de novo. Surgical management and orthodontic therapy were successful. CONCLUSIONS: Analysis of the reported case and retrospective data analysis provided evidence that paresthesia of the lower jaw should be considered as one of the early presenting signs of this rare disorder in stomatological and neurological practice. Obtained results allowed us to formulate recommendations for diagnostic practice in stomatology and neurology.

• MeSH
• Anodontia diagnostic imaging   etiology   MeSH
• Early Diagnosis MeSH
• Jaw diagnostic imaging   MeSH
• Child MeSH
• Gene Duplication MeSH
• Cohort Studies MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Odontogenic Cysts diagnostic imaging   etiology   MeSH
• Paresthesia etiology   MeSH
• Tomography, X-Ray Computed MeSH
• Child, Preschool MeSH
• Patched-1 Receptor genetics   MeSH
• Radiography, Panoramic MeSH
• Retrospective Studies MeSH
• Sequence Analysis, DNA MeSH
• Practice Guidelines as Topic MeSH
• Basal Cell Nevus Syndrome complications   diagnosis   genetics   MeSH
• Imaging, Three-Dimensional MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Geographicals
• Czech Republic MeSH