Extranodal extension in oral cancer : a role for the nodal microenvironment?

Oral squamous cell carcinoma (OSCC) is a significant cause of morbidity and mortality worldwide and accounts for the majority of head and neck cancers. Metastasis of primary tumours, primarily to cervical lymph nodes in the neck, is associated with worsening prognosis. Furthermore, the prognosis of patients with extranodal extension of metastatic tumour from the lymph nodes into the neck tissues is particularly poor. The factors affecting this process are poorly understood, and detection is difficult pre‐surgery. Mounting evidence shows that components of the tumour microenvironment including cancer‐associated fibroblasts, vascular and lymphatic endothelial cells, the extracellular matrix and inflammatory immune cells, are important modulators of tumour behaviour in primary OSCC and other cancers. However, little is known about the lymph node microenvironment, its response to tumour presence and role in extranodal extension. In addition, there are many lymph node‐specific cell types and structures, such as fibroblast reticular cells and high endothelial venules, making the lymph node microenvironment distinct from that found at primary tumour sites, and which contribute to the nodal response to tumour presence. This review details the current knowledge regarding the lymph node tumour microenvironment in OSCC and its role in lymph node metastasis and extranodal extension and relates this to features of the primary tumour. Understanding the role that the lymph node microenvironment plays in promoting tumour development and extranodal extension may aid the identification of novel biomarkers and alternative treatment strategies to improve the prognosis of patients with advanced OSCC

Beauty is only mucosa deep : a retrospective analysis of oral lumps and bumps caused by cosmetic fillers

Introduction: The injection of dermal fillers into orofacial tissues is becoming increasingly popular for cosmetic purposes, in particular for lip augmentation. Both natural and synthetic filler materials are available, producing a spectrum of clinical and histological appearances. Aims: The aim of this study was to review the clinicopathological characteristics of dermal filler cases from 2006 to 2016, reported at a specialist oral pathology unit. Methods: An archival search of the pathology database was performed to retrieve cases reported as being consistent with cosmetic fillers. Results: Ten cases of orofacial cosmetic fillers were retrieved. Of these cases, 100% were from female patients and the mean age of presentation was 47.6 years (range 24-68 years). The lips were the most frequently involved site (80%, n = 8). The majority of provisional diagnoses were related to salivary gland disease, including neoplasms (30%, n = 3), cysts (20%, n = 2) or inflammatory disease (10%, n = 1). Only two cases (20%) were clinically thought to be related to previous cosmetic injections. A variety of filler materials were seen, including collagen, hydroxyapatite and silicone. However, hyaluronic acid-based materials were the most common (50%, n = 5). Conclusions: Complications of cosmetic dermal fillers are becoming more common and should be considered within a differential diagnosis for unusual orofacial swellings

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

Cytogenetic and immunohistochemical characterization of Mammary Analogue Secretory Carcinoma of salivary glands

Objectives: Mammary analogue secretory carcinoma (MASC), initially considered a sub-set of acinic cell carcinoma (ACC) harbours an ETV6 translocation [t(12:15)(p13:25q)] and is now regarded as a distinct entity. Several putative markers to differentiate MASC from ACC have been reported however, the immunohistochemical profile is still being explored and updated. The purpose of this study was to further explore the cytogenetic and immunohistochemical profile of MASC. Study design: Cases were analysed for ETV6 translocation using fluorescent in situ hybridisation(FISH) and stained for CK8, amylase, mammaglobin, GCDFP 15, MUC1, MUC4, STAT5a, Ki 67 (n=37), CK7, Cam5.2, CK14, SMA, p63, S100, vimentin and DOG- 1 (n=42). Histochemical stains for mucins were also performed and data collected for age, gender and site. Results: FISH showed nine cases with ETV6 rearrangement and two with increased ETV6 copies. These eleven cases showed absence of PAS-D resistant granules with 10/11 showing strong S100, mammaglobin and Stat5a staining. All ACCs showed diffuse DOG-1 staining whereas 8/11 MASCs were negative and three showed only focal DOG1 staining. Conclusion: DOG-1 can be used in conjunction with PAS-D, S100 and mammaglobin to identify MASCs. Cases with increased ETV6 copies are a novel finding with a similar immunostaining profile and should be considered as MASCs

Self-Path: self-supervision for classification of pathology images with limited annotations

While high-resolution pathology images lend themselves well to ‘data hungry’ deep learning algorithms, obtaining exhaustive annotations on these images for learning is a major challenge. In this paper, we propose a self-supervised convolutional neural network (CNN) frame-work to leverage unlabeled data for learning generalizable and domain invariant representations in pathology images. Our proposed framework, termed as Self-Path, employs multi-task learning where the main task is tissue classification and pretext tasks are a variety of self-supervised tasks with labels inherent to the input images.We introduce novel pathology-specific self-supervision tasks that leverage contextual, multi-resolution and semantic features in pathology images for semi-supervised learning and domain adaptation. We investigate the effectiveness of Self-Path on 3 different pathology datasets. Our results show that Self-Path with the pathology-specific pretext tasks achieves state-of-the-art performance for semi-supervised learning when small amounts of labeled data are available. Further, we show that Self-Path improves domain adaptation for histopathology image classification when there is no labeled data available for the target domain. This approach can potentially be employed for other applications in computational pathology, where annotation budget is often limited or large amount of unlabeled image data is available

High-grade urothelial carcinoma with squamous differentiation metastasizing to the tongue.

Tumors metastasizing to the head and neck region are uncommon. Metastasis of urothelial carcinoma to the maxillofacial region is exceedingly rare and mostly involves the jaw. We present a case of urothelial carcinoma metastasizing to the tongue. Immunohistochemistry in conjunction with fluorescent in situ hybridization was used to confirm the relation between the primary and metastatic lesions, making it the first such reported case employing the UroVysion (Catalogue number 02 J27-025, Abbott Molecular Inc., Des Plaines, IL, USA) fluorescent in situ hybridization probe in a metastatic lesion in the head and neck region

Oral cancer stem cells drive tumourigenesis through activation of stromal fibroblasts

Background Cancer stem cells are responsible for tumour progression and chemoresistance. Fibroblasts surrounding a tumour also promote progression and fibroblast “activation” is an independent prognostic marker in oral cancer. Cancer stem cells may therefore promote tumourigenesis through communication with stromal fibroblasts. Methods Cancer stem cells were isolated from oral cancer cell lines by adherence to fibronectin or cisplatin resistance. Fibroblasts were exposed to conditioned medium from these cells, and the activation markers, alpha smooth muscle actin and interleukin‐6, were assessed using qPCR and immunofluorescence. Stem cell markers and smooth muscle actin were examined in oral cancer tissue using immunohistochemistry. Results Adherent and chemoresistant cells expressed increased levels of stem cell markers CD24, CD44 and CD29 compared with unsorted cells. Adherent cells exhibited lower growth rate, higher colony forming efficiency and increased cisplatin resistance than unsorted cells. Smooth muscle actin and Interleukin‐6 expression were increased in fibroblasts exposed to conditioned medium. In oral cancer tissue, there was a positive correlation between expression of αSMA and stem cell markers. Conclusions Adherence to fibronectin and chemoresistance isolates stem‐like cells that can activate fibroblasts, which together with a correlation between markers of both in vivo, provides a mechanism by which such cells drive tumourigenesis

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

The chemokine lymphotactin and its recombinant variants in oral cancer cell regulation

Background The expression of XCR1 receptor and its metamorphic ligand lymphotactin (hLtn) has been shown in cancers but their precise role in tumorigenesis is poorly understood including the significance of the physiologically existing hLtn monomeric (CC3) and dimeric (W55D) confirmations where the latter thought to function as the receptor antagonist. The aim of this study was to explore the functional role of bioengineered hLtn variants and the role of fibroblasts in XCR1/hLtn expression regulation in oral cancer cells (OCCL). Material and methods qRT‐PCR and flow cytometry were performed to evaluate mRNA and protein expression of XCR1 and hLtn. Recombinant hLtn variants (wild‐type, CC3 and W55D mutant) were designed, expressed, purified and evaluated using proliferation, adhesion and chemotaxis assays. XCR1 and hLtn expression regulation by fibroblasts was determined using indirect co‐culture. XCR1 and hLtn expression in primary and metastatic OSCC tissue was assessed using immunohistochemistry. Results hLtn caused a significant decrease in OCCL XCR1 surface protein expression. hLtn CC3 mutant was highly functional facilitating proliferation and migration. Conditioned media from primary cancer‐associated and senescent fibroblasts significantly upregulated XCR1 and hLtn mRNA expression in OCCL. Immunohistochemistry revealed higher XCR1 and hLtn expression in metastatic tumour deposits and surrounding stroma compared to primary OSCC tissue. Conclusions The development of hLtn biological mutants, regulation of XCR1 expression by its ligand hLtn and crosstalk with fibroblasts are novel findings suggesting an important role for the XCR1/hLtn axis within the OSCC tumour microenvironment. These discoveries build upon previous studies and suggest that the hLtn/XCR1 axis has a significant role in stromal crosstalk and OSCC progression

CEOT variants or entities: Time for a rethink? A case series with review of the literature

The first detailed description of calcifying epithelial odontogenic tumor (CEOT) are ascribed to Jens Pindborg, but this tumor was described some years previously. Subsequently, CEOT was included in the 1971 WHO classification of odontogenic tumors and a since then number of variants have been described, which have added confusion to the diagnostic criteria. We aimed to survey the literature on the variants of CEOT, in parallel with a review of our single institution experience of CEOTs. Cases identified were collated, including available clinical, radiological and histological information and then reviewed, taking into account changes in the understanding and classifications of odontogenic tumors since initial diagnosis. We identified 26 cases from 1975 to 2017 for which histological material was available. Of these, only 13 (50%) showed the “classic” histological appearance, whilst two cases were identified as recognized variants. In 11 cases, other diagnoses or a differential diagnosis were preferred, with no agreed diagnosis in four of these. The proliferation fraction (Ki67) in the 10 cases tested was 2.1% ± 0.18. These findings illustrate the diagnostic challenges in this group of tumors and highlight the gaps in knowledge. Techniques, such as EWSR1 gene cytogenetic analysis, may be helpful in cases with clear cells. However, in other areas of controversy, including the non-calcifying and Langerhans cell rich variants, further investigation, perhaps utilizing sequencing technologies may be needed to refine the classification. Owing to the relative rarity of these lesions it would be beneficial if future work could be pursued as an international collaboration