Macroscopy of specimens from the head and neck.

Macroscopic examination of surgical resections from the head and neck may be difficult due to the complex anatomy of this area. Recognition of normal anatomical structures is essential for accurate assessment of the extent of a disease process. Communication with the surgical team, correct specimen orientation and sampling are critical for assessment and the importance of radiological and clinical correlation is emphasised. Tumour involvement at each subsite is highlighted with reference to where there are implications on pathological staging and the potential need for adjuvant therapy.

Macroscopic examination of pathology specimens: a critical reappraisal.

Meticulous macroscopic examination of specimens and tissue sampling are crucial for accurate histopathology reporting. However, macroscopy has generally received less attention than microscopy and may be delegated to relatively inexperienced practitioners with limited guidance and supervision. This introductory paper in the minisymposium, Macroscopy Under the Microscope, focuses on issues regarding macroscopic examination and tissue sampling that have been insufficiently addressed in the published literature. It highlights the importance of specimen examination and sampling, discusses some general principles, outlines challenges and suggests potential solutions. It is critical to get macroscopy right the first time as it may not be possible to rectify errors even with expert histological assessment or to retrospectively collect missing data after the specimen retention period. Dissectors must, therefore, receive adequate guidance and supervision until they are proficient in macroscopic specimen examination. We emphasise the importance of the clinical context, optimal specimen fixation, succinct and clinically relevant macroscopic descriptions, macrophotography and judicious tissue sampling. We note that current recommendations based on the number of blocks to be submitted per maximum tumour dimension are ambiguous as the amount of tissue submitted in a cassette is not standardised and it is unclear whether 'block' refers to a tissue block or a paraffin block. Concerns around potential oversampling of 'therapeutic' specimens that could result in overdiagnosis due to detection of incidentalomas are also discussed. We hope that the issues discussed in this paper will engender debate on this clinically critical aspect of pathology practice.

Head and neck cancer explained: an overview of management pathways.

Head and neck cancer is a rare disease and general dental practitioners (GDPs) are at the forefront of head and neck assessment for malignancy in the community. Having an awareness of the signs and symptoms with which head and neck cancers can present promotes earlier diagnosis and increases the potential for better prognosis and quality of life. This article will outline the head and neck cancer pathway from presentation, diagnosis and management planning, to treatment and beyond. This should help to give GDPs insight into the process their patients will experience while under the care of the multidisciplinary team and enable them to give patients returning to primary care the best support. This article is part of a larger series that will explore each facet of care in greater detail to give a significantly greater understanding of the pathway.

IL-34 Suppresses Candida albicans Induced TNFα Production in M1 Macrophages by Downregulating Expression of Dectin-1 and TLR2.

Candida albicans is a fungus that is an opportunistic pathogen of humans. Normally, C. albicans exists as a harmless commensal and does not trigger inflammatory responses by resident macrophages in skin mucosa, which may be caused by a tolerance of skin macrophage to C. albicans. IL-34 is a recently discovered cytokine, constitutively expressed by keratinocytes in the skin. IL-34 binds to the receptor of M-CSF, thereby stimulating tissue macrophage maturation and differentiation. Resident macrophages exhibit phenotypic plasticity and may transform into inflammatory M1 macrophages for immunity or anti-inflammatory M2 macrophages for tissue repair. M1 macrophages produce higher levels of inflammatory cytokines such as TNFα in response to C. albicans stimulation. In this study, it was demonstrated that IL-34 attenuated TNFα production by M1 macrophages challenged with heat killed Candida (HKC). The molecular mechanism of IL-34 mediated suppression of HKC induced TNFα production by M1 macrophages was by the inhibition of M1 macrophage expression of key C. albicans pattern recognition receptors (PPRs), namely, Toll-like receptor (TLR) 2 and Dectin-1. The results of this study indicated that constitutive IL-34 expressed by skin keratinocytes might suppress resident macrophage responses to C. albicans colonisation by maintaining low levels TLR2 and Dectin-1 expression by macrophages.

ADAM 10 is over expressed in oral squamous cell carcinoma and contributes to invasive behaviour through a functional association with αvß6 integrin.

A disintegrin and metalloprotease (ADAM) proteins are upregulated in cancer and can interact with integrin receptors. We investigated whether such interactions may have functional significance in oral squamous cell carcinoma (OSCC). ADAM 10 expression was increased in OSCC tissue and cell lines compared to normal oral mucosa. Silencing of ADAM 10 reduced migration and invasion specifically in OSCC cells over-expressing αvß6 integrin. This may result from ADAM 10-induced up-regulation of MMPs. We conclude ADAM 10 may influence OSCC invasion by functionally interacting with αvß6 integrin which we have previously shown is over expressed in OSCC.

Histopathological features that predict the recurrence of odontogenic keratocysts.

BACKGROUND: Odontogenic keratocysts (OKCs) constitute between 1.8% and 21.5% of odontogenic cysts and are associated with higher propensity to recur than other odontogenic cysts following surgical removal. Previous studies have been performed to identify clinico-pathological predictive factors in relation to such behaviour. The relationship between the presence of hyalinisation and recurrence of the OKC has not been explored. METHODS: A total of 110 OKCs were selected, comprising 53 non-recurrent cases, 50 cases known to subsequently recur and seven syndromic cases. Cases were examined blind, and histological assessment of the epithelial lining, connective tissue capsule and cyst lumen was made. Statistical analysis was completed using Pearson Chi-square, Fisher's exact test and logistic regression analysis. RESULTS: Subepithelial hyalinisation of the underlying connective tissue capsule (P = 0.006) was significantly more common in OKC that recurred. Recurring cysts demonstrating hyalinisation were seen in a younger age group (mean = 40.8 years) than the non-recurrent cysts (mean = 56.4 years). In addition, subepithelial splitting (P = 0.015) and the position of mitotic figures (P = 0.033) were more common in recurring cysts. CONCLUSION: In this case series, several differences were found in relation to histological features of recurring and non-recurring OKCs. There are many factors responsible for the high recurrence rate of OKCs, and the presence of subepithelial hyalinisation may be used as an additional histopathological feature to predict a greater tendency for recurrence.

MicroRNA-124 suppresses oral squamous cell carcinoma motility by targeting ITGB1.

Alterations in the levels of molecules which interact with the extracellular matrix, such as integrins, are associated with invasion of oral squamous cell carcinomas (OSCC). The molecular mechanisms underlying dysregulation of integrin expression in OSCC, however, remain unclear. Here, we show that microRNA-124, a small non-coding RNA down-regulated in OSCC, is able to downregulate expression of integrin beta-1 (ITGB1) by interacting with its 3' untranslated region. Over-expression of miR-124 attenuates endogenous ITGB1 expression and reduces the adherence and motility of OSCC cells, suggesting disruption of miR-124-mediated repression of ITGB1 may be a key factor in OSCC progression.