Cancer-associated fibroblasts promote bone invasion in oral squamous cell carcinoma.

BACKGROUND: The molecular mechanisms involved in the invasion of bone by oral squamous cell carcinomas (OSCC) are poorly understood, and little is known about the role of cancer-associated fibroblasts (CAF), the presence of which confers a poor prognosis. METHODS: Clinicopathological data from 277 OSCC cases involving bone resections were reviewed, and 32 cases thoroughly analysed histologically. Immunohistochemistry was used to examine αSMA, RANKL and OPG. Western blotting and qPCR were used to assess myofibroblast (CAF-like) differentiation, RANKL and OPG expression in vitro, and RANKL secretion was analysed by ELISA. Osteoclastogenesis was examined using TRAP staining, multinucleation and pit forming assays. RESULTS: Fibrous stroma intervened between tumour and bone in the majority of cases, with no direct contact between cancer cells and bone. RANKL and OPG, two proteins key to regulating bone resorption, were expressed in tumour cells as well as fibrous stroma adjacent to bone and αSMA-positive myofibroblastic CAF were consistently seen infiltrating into bone ahead of tumour cells. Human primary osteoblasts cultured with conditioned media from human OSCC-derived cells and human primary CAF showed a significant increase in RANKL and a decline in OPG mRNA expression. RANKL secretion was significantly increased in primary oral fibroblasts induced to differentiate into a CAF-like phenotype by transforming growth factor-ß1 (TGF-ß1) treatment and in primary CAF. Indirect co-culture of murine macrophages with conditioned media from CAF (experimentally derived and isolated from OSCCs) resulted in a marked increase in osteoclastogenesis (in excess of that provoked by cancer cells) determined by tartrate-resistant acid phosphatase activity, multinucleation and resorption pit formation. CONCLUSIONS: This study is the first to describe a functional role for CAFs in bone invasion and turnover, identifying a novel potential therapeutic target and diagnostic indicator in this difficult to treat bone invasive malignancy.

Malignant transformation in a cohort of patients with oral epithelial dysplasia.

Oral epithelial dysplasia (OED) is often diagnosed in oral potentially malignant disorders (OPMD) and carries an increased risk of malignant transformation. Currently, the reported risk of malignant transformation for OED varies. Here we present the risk in a cohort of 150 patients with OED at a specialist centre. In this cohort 2.6%, 4.1%, and 29.2% cases of mild, moderate, and severe OED, respectively, progressed to oral squamous cell carcinoma at the dysplastic site, while a small number developed a malignant lesion elsewhere. Moreover, 17 patients experienced an increase in grade of dysplasia and two showed histological resolution of their lesions.

An unusual cause of a common presentation: a case of metastatic basal cell carcinoma.

Metastasis of basal cell carcinoma is exceedingly rare and usually not considered in the differential diagnosis of neck lumps. We present a case highlighting the importance of a thorough history and consideration of metastatic basal cell carcinoma in patients with a basaloid metastasis and an unknown primary.

Use of artificial intelligence in diagnosis of head and neck precancerous and cancerous lesions: A systematic review.

This systematic review analyses and describes the application and diagnostic accuracy of Artificial Intelligence (AI) methods used for detection and grading of potentially malignant (pre-cancerous) and cancerous head and neck lesions using whole slide images (WSI) of human tissue slides. Electronic databases MEDLINE via OVID, Scopus and Web of Science were searched between October 2009 - April 2020. Tailored search-strings were developed using database-specific terms. Studies were selected using a strict inclusion criterion following PRISMA Guidelines. Risk of bias assessment was conducted using a tailored QUADAS-2 tool. Out of 315 records, 11 fulfilled the inclusion criteria. AI-based methods were employed for analysis of specific histological features for oral epithelial dysplasia (n = 1), oral submucous fibrosis (n = 5), oral squamous cell carcinoma (n = 4) and oropharyngeal squamous cell carcinoma (n = 1). A combination of heuristics, supervised and unsupervised learning methods were employed, including more than 10 different classification and segmentation techniques. Most studies used uni-centric datasets (range 40-270 images) comprising small sub-images within WSI with accuracy between 79 and 100%. This review provides early evidence to support the potential application of supervised machine learning methods as a diagnostic aid for some oral potentially malignant and malignant lesions; however, there is a paucity of evidence using AI for diagnosis of other head and neck pathologies. Overall, the quality of evidence is low, with most studies showing a high risk of bias which is likely to have overestimated accuracy rates. This review highlights the need for development of state-of-the-art deep learning techniques in future head and neck research.

Chondroid tenosynovial giant cell tumour: a rarity in the temporomandibular joint.

Tenosynovial giant cell tumours of the temporomandibular joint (TMJ) are extremely rare, particularly the subset of chondroid tumours. They can be broadly divided into localised and diffuse types, of which we know of only 116 reported cases in the TMJ. Rarer still are the subset of chondroid tenosynovial giant cell tumours, of which we know of only 30 cases that have affected the TMJ. We present a case that involved the TMJ, and include a discussion of its management.

A Parapharyngeal Soft Tissue Chordoma Presenting with Synchronous Cervical Lymph Node Metastasis: An Unusual Presentation.

A 63 year old male presented with a three month history of dysphagia, neck swelling and an oropharyngeal swelling on examination. Initial fine needle aspiration cytology and magnetic resonance imaging (done at a peripheral hospital) suggested a salivary gland neoplasm with lymph node metastasis. An infra-temporal approach was employed to excise the tumour mass and a modified radical neck dissection undertaken to remove the cervical metastasis. Histopathological examination with immunohistochemistry confirmed this to be a soft tissue chordoma. To the best of our knowledge, this is the first documented report of an extra-axial soft tissue chordoma presenting with synchronous metastatic disease. Though rare, this adds to the list of differential diagnoses for complex parapharyngeal lesions. A multidisciplinary approach between head and neck surgery, histopathology, radiology and sarcoma teams is paramount for arriving at the correct diagnosis and to deliver optimal treatment.

Accuracy of clinical coding for procedures in oral and maxillofacial surgery.

Clinical coding has important financial implications, and discrepancies in the assigned codes can directly affect the funding of a department and hospital. Over the last few years, numerous oversights have been noticed in the coding of oral and maxillofacial (OMF) procedures. To establish the accuracy and completeness of coding, we retrospectively analysed the records of patients during two time periods: March to May 2009 (324 patients), and January to March 2014 (200 patients). Two investigators independently collected and analysed the data to ensure accuracy and remove bias. A large proportion of operations were not assigned all the relevant codes, and only 32% - 33% were correct in both cycles. To our knowledge, this is the first reported audit of clinical coding in OMFS, and it highlights serious shortcomings that have substantial financial implications. Better input by the surgical team and improved communication between the surgical and coding departments will improve accuracy.

Solitary myofibroma of the adult mandible: a case report.

A 43-year-old woman presented with a swelling in the anterior mandible appearing radiographically as a well-defined radiolucency causing mobility of the anterior teeth. A clinical diagnosis of a radicular cyst led to removal of the lesion and the associated mobile teeth. Postoperative histopathology led to a diagnosis of intraosseous solitary myofibroma of the mandible. Solitary lesions of myofibroma are exceedingly rare in adult jaws, with only 3 previously documented cases.