Hedley Coleman

A novel approach to the management of a central giant cell granuloma with denosumab: A case report and review of current treatments

PURPOSE To describe the efficacy of denosumab in the treatment of an aggressive giant cell granuloma of the mandible. METHODS Denosumab was administered to a patient with a large aggressive giant cell granuloma of the mandible resistant to standard medical therapy. The effectiveness and response was measured on the basis of patient symptoms and radiological parameters. RESULTS A significant reduction in patient symptoms was reported in association with tumour regression on follow up radiographs. CONCLUSION This report demonstrates potential use of denosumab in aggressive giant cell granulomas of the jaws that have been resistant to medical therapy.

Membrane and cytoplasmic marker exchange between malignant neoplastic cells and fibroblasts via intermittent contact: increased tumour cell diversity independent of genetic change

We previously demonstrated that human osteosarcoma cells (SAOS‐2) induce contact‐dependent apoptosis in endothelium, and expected similar apoptosis in human gingival fibroblasts (h‐GF) using SAOS‐2 alkaline phosphatase (AP) to identify cells. However, h‐GF apoptosis did not occur, despite reduction in AP‐negative h‐GF number (p < 0.01) and enhancement of this by h‐GF TNFα pretreatment (p < 0.01). We suggest that TNFα‐enhanced transfer of membrane AP from SAOS‐2 to h‐GF would explain these data. This idea was investigated using fluorescence prelabelled cells and confocal laser scanning microscopy. Co‐cultures of membrane‐labelled h‐GF (marker‐DiO) and SAOS‐2 (marker‐DiD) generated dual‐labelled cells, primarily at the expense of single labelled h‐GF (p < 0.001), suggesting predominant membrane transfer from SAOS‐2 to h‐GF. However, opposite directional transfer predominated when membrane labels were reversed; SAOS‐2 further expressed green fluorescent protein (GFP) in cytoplasm and nuclei, and h‐GF additionally bore nuclear label (Syto59) (p < 0.001). Cytoplasmic exchange was investigated using h‐GF prelabelled with cytoplasmic DDAO‐SE and nuclear Syto59, co‐cultured with SAOS‐2 expressing GFP in cytoplasm and nuclei, and predominant cytoplasmic marker transferred from h‐GF to SAOS‐2 (p < 0.05). Pretreating h‐GF with TNFα increased exchange of membrane markers (p < 0.04) but did not affect either cell surface area profile or circularity. Dual‐labelled cells had a morphological phenotype differing from SAOS‐2 and h‐GF (p < 0.001). Time‐lapse microscopy revealed extensive migration of SAOS‐2 and cell process contact with h‐GF, with the appearance of SAOS‐2 indulging in ‘cellular sipping’ from h‐GF. Similar exchange of membrane was seen between h‐GF and with other cell lines (melanoma MeIRMu, NM39, WMM175, MM200‐B12; osteosarcoma U20S; ovarian carcinoma cells PE01, PE04 and COLO316), while cytoplasmic sharing was also seen in all cell lines other than U20S. We suggest that in some neoplasms, cellular sipping may contribute to phenotypic change and the generation of diverse tumour cell populations independent of genetic change, raising the possibility of a role in tumour progression. Copyright

Sentinel lymph node biopsy for early oral cancers: Westmead Hospital experience: SLNB for OCSCC: the Westmead experience

Sentinel lymph node biopsy (SLNB) has become an alternative option to elective neck dissection (END) for early oral cavity squamous cell carcinoma (OCSCC) outside of Australia. We sought to assess the technical feasibility of SLNB and validate its accuracy against that of END in an Australian setting.

Relationship between CO2 laser–induced artifact and glottic cancer surgical margins at variable power doses

The carbon dioxide laser can induce thermal cytologic artifacts at the margin of early glottic squamous cell carcinoma histologic specimens, which makes assessment of the margin difficult. This study assesses and correlates the depth of laser‐induced thermal artifact with laser power rating.

Bone tumours and tumour-like conditions of the head and neck and jaws

Almost all variants of malignant primary and secondary tumours of bone have been described as occurring within the head and neck and jaws. The most commonly occurring primary bone tumours affecting the jaws include osteosarcoma, Burkitt’s lymphoma and multiple myeloma, while secondary or metastatic tumours to the jaws are rare in contrast to the remainder of the skeleton. Management of patients with bone tumours and tumour-like lesions requires a team approach. Good communication between radiologist, attending head and neck surgeon and pathologist is imperative for accurate interpretation and diagnosis of these neoplasms. Pathologists who attempt to make a diagnosis of bony neoplasms without the clinical and radiographic information are at a distinct disadvantage and this is strongly discouraged. The objective of the slide seminar is to address some of the common as well as the less common bone tumours and tumour-like conditions of the head and neck and jaws.

Carcinomas of the jaws: report of a clear cell odontogenic carcinoma

Odontogenic neoplasms composed entirely or predominantly of clear cells are exceptionally rare. They include the clear cell variant of calcifying epithelial odontogenic tumour (CEOT), ameloblastoma and clear cell odontogenic carcinoma. Case report A 71-year-old female presented with a well-defined, expansile lesion of the left posterior mandible. There was altered sensation of the lower lip. Radiographs demonstrated an ill-defined radiolucent lesion. Microscopic examination revealed an infiltrative tumour composed of follicles and trabeculae of large round cells with clear cytoplasm. The nuclei were small and ovoid with little pleomorphism and very occasional mitoses. The tumour cells were surrounded by reactive bony trabeculae. Immunohistochem-istry was equivocal. A provisional diagnosis of clear cell odontogenic carcinoma was made with a recommendation that metastatic tumours be excluded clinically. Chest, abdominal and pelvic CT scans and a full clinical, head and neck and dermatological examination failed to reveal any primary tumour. The patient underwent a hemi-mandibulectomy with subsequent reconstruction. Discussion Specific histological and immunohistochemical features to identify clear cell odontogenic carcinomas are still lacking and the diagnosis is made only after exclusion of other clear cell tumour entities. The aggressive potential of these neoplasms is well documented with almost 30% of patients dying of disease.

An unusual cause of a ‘floating tooth’

Background Teeth that have lost their supporting alveolar bone may be described radiographically as ‘floating’. Common causes of this phenomenon include advanced periodontitis, Langerhans cell histiocytosis, Burkitt’s lymphoma and metastatic malignancy involving the jawbones. We report an unusual case of a ‘floating tooth’. Case report A 68-year-old male presented with an exophytic, multi-lobulated, red-blue swelling involving anterior maxillary gingiva with associated mobility of upper anterior teeth. His medical history included hypertension, chronic renal failure and hepatocellular carcinoma (HCC) with known lung metastases. An OPG radiograph demonstrated an ill-defined radiolucency associated with the maxillary anterior teeth, which appeared to be a ‘floating tooth’. Histopathological examination of the biopsy showed an ulcerated, infiltrating tumour with polygonal cells arranged in trabeculae and occasional gland-like structures. Individual tumour cells showed finely granular cytoplasm with central, hyperchromatic nuclei and prominent nucleoli. Immuno-peroxidase stains demonstrated positive staining with cytokeratin 20, 5D3 and alpha feto-protein. Staining with hepatocyte specific antigen demonstrated a granular cytoplasmic staining in almost all tumour cells. Conclusion HCC is the most common primary malignant neoplasm of the liver and is a common cause of cancer-related death worldwide. Metastasis of HCC to the jawbones is extremely uncommon and is an unusual cause of ‘floating teeth’.

Pathology reporting in oral cancer: a proposed structured reporting system for Australasia

Whilst schemes exist in the UK and North America, there is at present no internationally standardised instrument for reporting head and neck pathology. It can be difficult to assess and code information in reports across jurisdictions if there is lack of uniformity in content and presentation. Purpose The aim of this protocol is to ensure that oral cancer pathology reports are uniform in their content, contain relevant information and can be easily interpreted to direct further treatment and provide a guide for discussing prognosis. Methodology A multidisciplinary committee (comprising four pathologists, a head and neck surgeon and a radiation oncologist) was formed as part of the Cancer Services Advisory Committee of the Royal College of Pathologists of Australasia (RCPA) in 2010. Relevant stakeholders including the Australian and New Zealand Head and Neck Cancer Society will be invited to nominate a representative to review the protocol before endorsement by the RCPA. Results The group has developed the standards and guidelines to be used. The protocol is in its final draft format and is ready for review by stakeholders. Discussion It is envisaged that all oral cancer cases throughout Australasia will be reported according to this protocol, thus ensuring that all current histopathological prognosticators will be identified and included in a clinically and pathologically complete and standardised pathology report.

Bisphosphonate-related osteonecrosis of jaws and the relationship with actinomyces organisms

Background Actinomyces species are part of the normal oral flora. They may also be found in association with non-vital bony sequestra in suppurative osteomyelitis, osteoradionecrosis and bisphosphonate-related osteonecrosis of jaws (BRONJ). Methods Sixty-two cases of histologically diagnosed chronic suppurative osteomyelitis affecting the jawbones were retrieved from the archives at the ICPMR, Westmead Hospital. The haematoxylin and eosin-stained slides and the available clinical notes were reviewed. Results In 23 cases, a history of bisphosphonate use was established. Most cases presented in elderly females and the mandible was the most commonly affected site. Bacterial colonies with the morphological appearance of Actinomyces species were identified in 12 cases diagnosed as BRONJ (12 of 23 cases) while only four cases of non-specific suppurative osteomyelitis demonstrated these organisms (4 of 34 cases). The remaining five cases were diagnosed as osteoradionecrosis. Discussion Cervico-facial actinomycosis is a chronic bacterial infection of the soft tissue and jaws caused by the saprophytic Gram-positive, anaerobic bacteria Actinomyces species. In this study, Actinomyces species were frequently associated with BRONJ. As in cervico-facial actinomycosis, long-term use of an appropriate antibiotic, such as penicillin, may play a role in improving the outcome for these patients.

Salivary duct carcinom - report of two cases

Background Salivary duct carcinoma (SDC) is a distinctive salivary gland neoplasm which bears a histological similarity to ductal breast carcinoma including intraductal and invasive components. It was first described by Kleinsasser et al . in 1968 and has recently been included in the WHO Classification of Head and Neck Tumours (2005). Method Two cases of SDC are reported with their clinical and immunohistochemical findings. Results The tumour cells showed a characteristic immunophenotype with positivity for Androgen receptors (AR). There was no reaction with oestrogen or progesterone receptors. HER-2/neu 3+ staining was identified by immunohistochemistry together with gene amplification (SISH). Conclusion The strong and diffuse expression of AR and HER-2/neu overexpression lends further support to the role that anti-androgen and Herceptin therapy may have in patients with disseminated SDC.