Brendan Conn

In vitro examination of suspicious oral lesions using optical coherence tomography

We compared findings of optical coherence tomography (OCT) with histopathological results of suspicious oral lesions to assess the feasibility of using OCT to identify malignant tissue. Thirty-four oral lesions from 27 patients had swept-source frequency-domain OCT. Four variables were assessed (changes in keratin, epithelial, and sub-epithelial layers, and identification of the basement membrane) and from this we calculated whether or not there were architectural changes. These data were then compared with histopathological results. Two clinicians, who were unaware of the clinical and histopathological diagnoses, decided whether biopsy was necessary. The basement membrane was recognised in only 15 oral lesions. OCT could identify diseased areas but could not provide a diagnosis or differentiate between lesions. The two clinicians, who recommended biopsy agreed in all cases. This pilot study confirms the feasibility of using OCT to identify architectural changes in malignant tissues.

Formalin fixed paraffin embedded (FFPE) material is amenable to HPV detection by the Xpert® HPV assay

BACKGROUND The Xpert(®) HPV Assay (Cepheid(®), Sunnyvale, USA) is a rapid, cartridge-based HPV test validated for use on cervical cytology samples. However, there is an increasing demand for HPV annotation of formalin fixed paraffin embedded (FFPE) material. OBJECTIVES The aim of this study was to determine the suitability of the Xpert HPV assay for the detection of nucleic acid (NA) derived from FFPE samples. STUDY DESIGN A total of 88, 10 μm sections derived from FFPE tissue blocks were assessed, 74 originated from oropharyngeal squamous cell carcinomas (OPSCC) and 14 from a range of other sites. All had previously been tested with a sensitive Luminex(®) based assay with a component also tested with p16 immunohistochemistry (IHC). NA was extracted from samples using the easyMag(®) platform and after dilution was added directly to the Xpert cartridge. Agreement between assays was assessed. RESULTS Overall agreement between the assays was 92%; with a Kappa for HR-HPV detection of 0.833 (95% CI 0.725-0.953). In the 50 samples that had been annotated for p16 status overall agreement between the Xpert assay and the p16 IHC was 90%. CONCLUSIONS These data indicate that FFPE material is amenable to HPV detection by the Xpert assay. To our knowledge, this is the first study to interrogate the use of the Xpert(®) HPV assay for this application.

Sclerosing microcystic adenocarcinoma of the tongue: a report of two further cases and review of the literature.

We present 2 further cases of sclerosing microcystic adenocarcinoma occurring in the tongue in 2 female patients, one age 68 years and the other 49 years. Histopathologically, both tumors were characterized by a diffusely infiltrative lesion consisting of small cuboidal cells arranged in discrete dispersed cords, isolated tubules, and bilayered strands with intervening microcystic lumina set in a sclerotic background. Both lesions showed striking neurotropism with perineural and intraneural infiltration. Extensive invasion of adjacent skeletal muscle was also observed. The tumor cells showed diffuse staining with antibodies to cytokeratin 7 (CK7). A dual population of ductal and myoepithelial cells was identified, with antibodies to CAM5.2 and CK5/6 decorating the inner epithelial layer and antibodies to p63, p40, and S100 staining the outer myoepithelial cell layer. The Ki-67 proliferation index in both cases was less than 5%. An initial diagnosis of adenocarcinoma NOS (not otherwise specified) of salivary gland origin was made on both incisional biopsies and a possible metastatic origin, particularly from the breast, also raised. A local minor salivary gland origin was confirmed after staging investigations and surgical resection. Both patients were t.

Population-based p16 and HPV positivity rates in oropharyngeal cancer in Southeast Scotland

We assessed a population-based cohort of patients diagnosed with oropharyngeal squamous cell carcinoma in Southeast Scotland over 13 months. p16 and human papilloma virus (HPV) expression were determined, and correlated with stage, treatment, smoking and alcohol history, and disease outcomes. Retrospective analysis was performed on 60 patients. p16 immunohistochemistry and HPV genotyping were performed on formalin-fixed paraffin-embedded tissues. HPV infection (as defined by p16 positivity and/or HPV PCR positivity) was identified in 57% of samples, while dual positives were detected in 45% of cases. HPV16 was most prevalent of the HPV types and was associated with 90% of positive samples. Cause-specific 1-year and 2-year survivals were 82.5% and 78.2%, respectively. The p16-positive and HPV-positive groups demonstrated significantly increased cause-specific survival in comparison with their negative counterparts.

Copy number gain of 11q13.3 genes associates with pathological stage in hypopharyngeal squamous cell carcinoma.

Squamous cell carcinomas of the hypopharynx (HPSCC) and oropharynx (OPSCC) have markedly different patient outcomes. Differences in HPV prevalence between these two patient groups may account for some of this difference, but other molecular markers of prognosis or pathological phenotype have not been established. Copy number gain of oncogenes is a well‐established molecular change contributing to HNSCC development. Quantitative PCR was used to explore copy number gains of specific genes (3q—PIK3CA, TP63; 11q13.3—CCND1, ANO1) in tumor DNA recovered from HPSCC (n = 48) and OPSCC (n = 52) patients. Associations between copy number gain, patient demographics, HPV/p16INK4a status and pathological stage were examined. HPV/p16 prevalence in HPSCC and OPSCC groups was 2.1% and 46.0%, respectively. HPSCCs had frequent gains of CCND1 (56.3%) and ANO1 (56.3%) but few gains of PIK3CA (6.3%). By contrast, OPSCCs had significantly fewer CCND1 (23.1%) and ANO1 (17.3%) gains, and significantly more PIK3CA (26.9%) gains. A mutually exclusive relationship between HPV/p16 and 11q13.3 gains was observed in OPSCCs, while PIK3CA and TP63 gains were similar across HPV‐associated and smoking/alcohol‐associated patients. ANO1 gain was significantly linked to tumor pathology in HPSCC, associating with nodal metastasis and smaller and less invasive tumors at presentation (P = 0.010). Our results provide a convincing link between a specific molecular change and disease phenotype that appears unique to our HPSCC population, supporting a model of 11q13.3 in promoting metastatic disease progression in HNSCC, and suggest a role for ANO1 as a molecular marker of metastatic disease.

Metastasising Pleomorphic Salivary Adenoma: A Rare Case Report of a Massive Untreated Minor Salivary Gland Pleomorphic Adenoma with Concurrent Ipsilateral Cervical Node Metastases

Salivary gland tumours constitute approximately 1–5% of all human neoplasms. Pleomorphic adenoma (PA) is the commonest benign neoplasm affecting the parotid gland most often (> 75%), followed by the submandibular gland (13%), then the palate (9%). Metastasising pleomorphic adenoma (MPA) is extremely rare. The effects can be severe and a reported 40% of MPA patients die with disease. This case represents the first known case in English literature of an untreated minor salivary gland PSA of the palate metastasising to an ipsilateral cervical node. We report a 61 year old female who presented with a large tumour occupying the palatal vault, and cervical neck mass. The oral tumour was believed to have been growing over four decades. The patient died eight months following surgical resection. Of known cases, male: female ratio is 35:51 and the mean age at diagnosis is 49.2. Most commonly, MPA is detected in bone 33.3% (n = 29), lung 31% (n = 27) and cervical lymph nodes 20.7% (n = 18). Thorough reporting is deemed essential to further understand the biological differences of non metastasising and metastasising PAs, treatment outcomes, prognosis and survival rates.

Bilateral submandibular gland nodular oncocytic hyperplasia with papillary cystadenoma-like areas

A 57-year-old man presented in 2016 with a 4-month history of a right submandibular mass, having undergone left submandibular gland (SMG) excision in 2003. Imaging suggested a benign tumour and subsequent core biopsy findings suggested a nodular oncocytic hyperplasia, similar to the tumour removed from the contralateral side. This was confirmed on histological analysis following right submandibular gland excision which showed characteristic features of nodular oncocytic hyperplasia along with an unusual diffuse papillary cystadenoma-like ductal proliferation, similar to that seen in the 2003 specimen. A diagnosis of multinodular adenomatous oncocytic hyperplasia (MAOH) was rendered in order to communicate the unique histological features that have otherwise not been described in the literature. We believe that this is the first reported case of non-synchronous multinodular oncocytic hyperplasia and the first case affecting the submandibular glands.

Necrotising sialometaplasia in the floor of mouth

IntroductionNecrotising sialometaplasia is a benign self-limiting inflammatory process which occurs in the salivary gland tissue. The condition is a diagnostic challenge mimicking malignancy both clinically and histopathologically. Commonly, it presents in the hard palate.Case reportHere, we report an unusual case in a 56-year-old man which presented in the floor of the mouth.