The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localized and systemic disease is key to understanding breast cancer progression; however, our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data are derived from primary tumors. In 11 patients with treatment-naïve node-positive early breast cancer without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multiregion sequencing ( = 78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumor DNA (ctDNA). Linear evolution from primary to lymph node was rare (1/11), whereas the majority of cases displayed either early divergence between primary and nodes (4/11) or no detectable divergence (6/11), where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 of 7 subjects with evaluable plasma taken perioperatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA. This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients. .

Background Salivary gland tumours (SGT) are a relatively rare group of neoplasms with a wide range of histopathological appearance and clinical features. To date, most of the epidemiological studies on salivary gland tumours are limited for a variety of reason including being out of date, extrapolated from either a single centre or country studies, or investigating either major or minor glands only. Methods This study aimed to mitigate these shortcomings by analysing epidemiological data including demographic, anatomical location and histological diagnoses of SGT from multiple centres across the world. The analysed data included age, gender, location and histological diagnosis from fifteen centres covering the majority of the world health organisation (WHO) geographical regions between 2006 and 2019. Results A total of 5739 cases were analysed including 65% benign and 35% malignant tumours. A slight female predilection (54%) and peak incidence between the fourth and seventh decade for both benign and malignant tumours was observed. The majority (68%) of the SGT presented in major and 32% in the minor glands. The parotid gland was the most common location (70%) for benign and minor glands (47%) for malignant tumours. Pleomorphic adenoma (70%), and Warthin’s tumour (17%), were the most common benign tumours whereas mucoepidermoid carcinoma (26%) and adenoid cystic carcinoma (17%) were the most frequent malignant tumours. Conclusions This multicentre investigation presents the largest cohort study to date analysing salivary gland tumour data from tertiary centres scattered across the globe. These findings should serve as a baseline for future studies evaluating the epidemiological landscape of these tumours.

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.

Our study suggests that plasma cell mucositis does not meet microscopic criteria for IgG4-RD. It importantly reinforces the opinion that IgG4+ plasma cells are major components of chronic inflammation in the oral cavity and the pertinence of correct contextual interpretation of histopathological features with clinical findings.

Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer characterised by a high frequency of loss-of-function ARID1A mutations and a poor response to chemotherapy. Despite their generally low mutational burden, an intratumoural T cell response has been reported in a subset of OCCC, with ARID1A purported to be a biomarker for the response to the immune checkpoint blockade independent of micro-satellite instability (MSI). However, assessment of the different immune cell types and spatial distribution specifically within OCCC patients has not been described to date. Here, we characterised the immune landscape of OCCC by profiling a cohort of 33 microsatellite stable OCCCs at the genomic, gene expression and histological level using targeted sequencing, gene expression profiling using the NanoString targeted immune panel, and multiplex immunofluorescence to assess the spatial distribution and abundance of immune cell populations at the protein level. Analysis of these tumours and subsequent independent validation identified an immune-related gene expression signature associated with risk of recurrence of OCCC. Whilst histological quantification of tumour-infiltrating lymphocytes (TIL, Salgado scoring) showed no association with the risk of recurrence or ARID1A mutational status, the characterisation of TILs via multiplexed immunofluorescence identified spatial differences in immunosuppressive cell populations in OCCC. Tumour-associated macrophages (TAM) and regulatory T cells were excluded from the vicinity of tumour cells in low-risk patients, suggesting that high-risk patients have a more immunosuppressive microenvironment. We also found that TAMs and cytotoxic T cells were also excluded from the vicinity of tumour cells in ARID1A-mutated OCCCs compared to ARID1A wild-type tumours, suggesting that the exclusion of these immune effectors could determine the host response of ARID1A-mutant OCCCs to therapy. Overall, our study has provided new insights into the immune landscape and prognostic associations in OCCC and suggest that tailored immunotherapeutic approaches may be warranted for different subgroups of OCCC patients.

Dog attacks are extremely frequent and are thought to be responsible for an average of 250,000 minor injuries and emergency unit attendances each year. Children in particular are more likely to experience dog-bite injuries with 5–9-year olds most susceptible. The majority of injuries are to the head region, with the lips, cheeks, and nose often affected. Most injuries experienced are confined to the soft tissues; nevertheless, maxillofacial fracture is a potential albeit rare complication. The incidence of facial fractures in relation to dog bites is unknown; however, some have estimated that facial fractures could occur in 5% of dog attacks. However mandibular fracture following a dog bite is extremely rare, with review of the literature only identifying three cases. We present a further case in which a five-year-old sustained numerous soft-tissue lacerations to the face and hand, together with fracture of the mandibular symphysis following a dog attack. The fracture was successfully repaired using open reduction and internal fixation with titanium plates and screws. The case emphasises that although maxillofacial fracture is rare, it may occur following a dog bite and that thorough and systematic examination of the facial skeleton is crucial to exclude the presence of such injuries.

This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cancer stem cells undergo epithelial-mesenchymal transition (EMT) to drive metastatic dissemination in experimental cancer models. However, tumour cells undergoing EMT have not been observed disseminating into the tissue surrounding human tumour specimens, leaving the relevance to human cancer uncertain. Here, we identify an EMT stem cell state that retains EpCAM and CD24 after undergoing EMT and exhibits enhanced plasticity. This afforded the opportunity to investigate whether retention of EpCAM and CD24 alongside upregulation of the EMT marker Vimentin can identify disseminating EMT stem cells in human oral cancer specimens. Examining disseminating tumour cells in the stromal region of 3500 imaging fields from 24 human oral cancer specimens, evenly 2 divided into metastatic and non-metastatic specimens, we see a significant enrichment of EpCAM, CD24 and Vimentin co-stained cells in metastatic specimens. Through training an artificial neural network on the EpCAM, CD24 and Vimentin co-staining, we predict metastasis with high accuracy (F1 0.91; AUC 0.87). We have observed, for the first time, disseminating EMT stem cells in patient histological specimens and demonstrated their utility for predicting metastatic disease.