Search

Objective: Sentinel node biopsy (SNB) is a surgical staging test in which sentinel nodes (SNs) undergo intensive histological analysis. SNB diagnoses early cancer spread, but can also reveal unexpected findings within the SNs. We review cases of incidental thyroid cells (TC) found in SNs from patients with oral squamous cell carcinoma (OSCC) to assess the prevalence of TC, and the clinical significance of these. Methods: Multicenter retrospective review of SNB performed for cT1‐T2N0 OSCC. Incidental TC were identified by TTF‐1 or thyroglobulin positivity. Anatomical location of nodes containing TC, TC morphology, and ongoing management/follow up of this incidental finding was recorded. Neck dissections performed during the same period were reviewed to establish the expected incidence of TC in neck nodes without serial sectioning analysis. Results: 278 SNB cases were reviewed. Ten procedures detected TC in nine patients (10/278, 3.6%). During the same time period 725 neck dissections were performed, six containing TCs (6/725, 0.8%). One patient underwent SNB twice with TC identified on both occasions. Three patients had both OSCC metastasis and thyroid cells. All SNB patients with TC identified underwent thyroid USS with no primary tumours identified. Three patients underwent thyroidectomy, in all cases no primary thyroid tumour was found. Conclusion: Prevalence of incidental TC in SNs appears to be higher than that reported in neck dissections, these are not likely to be clinically relevant and can be managed on a conservative basis in the absence of clear metastatic features. Level of Evidence: Multicentre retrospective cohort study, 3 Laryngoscope, 134:1278–1281, 2024 [ABSTRACT FROM AUTHOR]

Objectives: This review aims to analyse the recurrence rate in BRAFv600e+ and BRAFv600e− ameloblastomas and explore its association with clinicopathological variables. Methods: A comprehensive search was conducted using databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, Google Scholar and grey literature, without any limitation on start date or language up to 20 June 2023. A random effect meta‐analysis was conducted and Metaregression analyses were performed based on available clinicopathological factors. Results: Fifteen studies met the criteria for meta‐analysis of outcomes. There was no significant difference in overall recurrence rates between the two groups (risk difference = 0.001, p‐value = 0.987). Increasing male:female ratio in the BRAFv600e+ group was associated with a lower reported recurrence, suggesting a higher recurrence rate in females. The odds of having mandibular lesion were four times higher in BRAFv600e+ cases compared to BRAFv600e− cases (confidence interval: 2.121–7.870, p < 0.001, I2 = 28.37%). Conclusion: Within the BRAFv600e+ group, females showed a higher reported recurrence rate. This specific clinical group may benefit from BRAFv600e mutation investigation and potential upscaled surgical treatment and additional BRAF inhibitor therapy, which needs validation in future studies. [ABSTRACT FROM AUTHOR]

Computational pathology refers to applying deep learning techniques and algorithms to analyse and interpret histopathology images. Advances in artificial intelligence (AI) have led to an explosion in innovation in computational pathology, ranging from the prospect of automation of routine diagnostic tasks to the discovery of new prognostic and predictive biomarkers from tissue morphology. Despite the promising potential of computational pathology, its integration in clinical settings has been limited by a range of obstacles including operational, technical, regulatory, ethical, financial, and cultural challenges. Here, we focus on the pathologists' perspective of computational pathology: we map its current translational research landscape, evaluate its clinical utility, and address the more common challenges slowing clinical adoption and implementation. We conclude by describing contemporary approaches to drive forward these techniques. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

The suggestion that the systemic immune response in lymph nodes (LNs) conveys prognostic value for triple‐negative breast cancer (TNBC) patients has not previously been investigated in large cohorts. We used a deep learning (DL) framework to quantify morphological features in haematoxylin and eosin‐stained LNs on digitised whole slide images. From 345 breast cancer patients, 5,228 axillary LNs, cancer‐free and involved, were assessed. Generalisable multiscale DL frameworks were developed to capture and quantify germinal centres (GCs) and sinuses. Cox regression proportional hazard models tested the association between smuLymphNet‐captured GC and sinus quantifications and distant metastasis‐free survival (DMFS). smuLymphNet achieved a Dice coefficient of 0.86 and 0.74 for capturing GCs and sinuses, respectively, and was comparable to an interpathologist Dice coefficient of 0.66 (GC) and 0.60 (sinus). smuLymphNet‐captured sinuses were increased in LNs harbouring GCs (p < 0.001). smuLymphNet‐captured GCs retained clinical relevance in LN‐positive TNBC patients whose cancer‐free LNs had on average ≥2 GCs, had longer DMFS (hazard ratio [HR] = 0.28, p = 0.02) and extended GCs' prognostic value to LN‐negative TNBC patients (HR = 0.14, p = 0.002). Enlarged smuLymphNet‐captured sinuses in involved LNs were associated with superior DMFS in LN‐positive TNBC patients in a cohort from Guy's Hospital (multivariate HR = 0.39, p = 0.039) and with distant recurrence‐free survival in 95 LN‐positive TNBC patients of the Dutch‐N4plus trial (HR = 0.44, p = 0.024). Heuristic scoring of subcapsular sinuses in LNs of LN‐positive Tianjin TNBC patients (n = 85) cross‐validated the association of enlarged sinuses with shorter DMFS (involved LNs: HR = 0.33, p = 0.029 and cancer‐free LNs: HR = 0.21 p = 0.01). Morphological LN features reflective of cancer‐associated responses are robustly quantifiable by smuLymphNet. Our findings further strengthen the value of assessment of LN properties beyond the detection of metastatic deposits for prognostication of TNBC patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Cytolytic proteins and peptide toxins are classical virulence factors of several bacterial pathogens which disrupt epithelial barrier function, damage cells and activate or modulate host immune responses. Such toxins have not been identified previously in human pathogenic fungi. Here we identify the first, to our knowledge, fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity. Membrane permeabilization is enhanced by a positive charge at the carboxy terminus of the peptide, which triggers an inward current concomitant with calcium influx. C. albicans strains lacking this toxin do not activate or damage epithelial cells and are avirulent in animal models of mucosal infection. We propose the name 'Candidalysin' for this cytolytic peptide toxin; a newly identified, critical molecular determinant of epithelial damage and host recognition of the clinically important fungus, C. albicans., The ability of mucosal surfaces to discriminate between commensal and pathogenic microbes is essential to human health. The fungus Candida albicans is normally a benign member of the human microbiota, [...]

Objectives: To report clinical outcomes of relapsed oropharyngeal squamous cell carcinoma (OPSCC) after definitive intensity‐modulated (chemo)radiotherapy [(C)RT]. Materials and methods: Data for all relapsed patients treated for OPSCC with definitive (C)RT between 2010 and 2016 were collected. Primary end‐point was post‐failure survival (PFS). Results: Overall, 273 OPSCC patients completed definitive (C)RT. Of these, 42 cases (n = 26 human papilloma virus (HPV)‐negative; n = 16 HPV‐positive) had relapsed (n = 23 persistent disease; n = 19 recurrent disease) and were included in the final analysis. Two‐year PFS for the entire population was 30.6%; 20.5% for HPV‐negative and 43.8% for HPV‐positive patients. Salvage curative surgery was associated with a significantly higher 2 years PFS rate (56.2%) compared with palliative treatment (22.9%) and best supportive care (0%) (p < 0.001). A positive trend in 2 years PFS was recorded in the early complete response cases (49.5%) versus patients who did not achieve a complete response within 3 months of the end of (C)RT (23.0%) (p = 0.11). Conclusion: A higher PFS rate is achieved when relapsed OPSCC cases are treated with salvage curative intent. HPV‐positive disease and early complete response within 3 months from the end of (C)RT may be related to better PFS. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node biopsy is an increasingly recognised option for accurate staging and subsequent management of the clinically negative neck in early stage oral cavity squamous cell carcinoma. However, the technique is currently underused due to several logistic constraints including increased burden on pathology services. Here, we describe the feasibility of an outsourced centralised pathology processing and reporting service for sentinel lymph node biopsies in oral cavity squamous cell carcinoma. Patients and methods: The Southeast England Consortium comprises four surgical centres utilising a central pathology service. Consecutive cases between January 2016 and February 2020 were retrospectively evaluated for survival outcomes and laboratory turnaround times. Results: Twenty‐eight per cent from a cohort of 139 patients had positive sentinel nodes. There was a trend towards greater overall, disease‐free and disease‐specific survival (OS, DFS and DSS, respectively) in sentinel node negative compared to sentinel node positive patients, but these differences were not statistically significant. The sensitivity, negative predictive value and false negative rate were 92.8%, 97.0% and 6.8%, respectively. The mean and mode laboratory TAT were 5 and 4 working days, respectively. Conclusion: An outsourced centralised pathology service is a feasible option to widen the availability of sentinel node biopsy in oral cavity squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

The incidence of metastases following neck dissection in the apparent lymph node negative neck in oral cancer is between 7% and 33%; early resection of cervical metastases may well increase survival. Modern imaging techniques can reduce the yield of previously undiagnosed metastatic nodes in elective neck dissection (END). An audit of 112 consecutive cases was conducted to determine the proportion of undiagnosed nodal metastases, after END. There were neck metastases in 10 cases (9%), which were mainly (but not all) micrometastic. The 20% likelihood of nodal metastases was only apparent in primary tumours greater than 6 mm thick. The length of inpatient stay was increased from 3.7 to 16.5 days with free vascularised transfer. There were complications including cranial nerve damage. There were two peri-operative deaths. No ipsilateral neck failures occurred, median follow up was 937 days. To reduce unnecessary END, resection can be undertaken as a prior procedure, subsequently only carrying out END on tumours greater than 6 mm, or with unfavourable tumour characteristics. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node (SLN) biopsy is an accurate staging modality in early oral squamous cell carcinoma (OSCC), but its accuracy relies on labor‐intensive histopathology protocols. We sought to determine whether serial step sections with immunohistochemistry (SSSIHC) at narrow intervals of the entire SLN are required to accurately exclude metastasis. Methods: Consecutive SLN biopsies over a 13‐year period were retrospectively evaluated. If the index section was negative for carcinoma, the entire SLN was subjected to SSSIHC at 150 μm intervals. The first section level and total number of section levels to contain carcinoma were recorded. Results: One hundred and eighteen SLN+ from 90 patients were included. SSSIHC upstaged the nodal status in 19.5% of patients. Metastasis was identified in 16.7% and 10.2% beyond section levels 4 and 6, respectively. Among SLNs requiring SSSIHC, 47.5% contained carcinoma in a single section level. Conclusion: SSSIHC of the entire SLN at 150 μm intervals are required to identify occult metastasis in OSCC. [ABSTRACT FROM AUTHOR]

High-risk Human Papillomavirus (HPV) infections have recently emerged as an independent risk factor in head and neck squamous cell carcinoma (HNSCC). There has been a marked increase in the incidence of HPV-induced HNSCC subtype, which demonstrates different genetics with better treatment outcome. Despite the favourable prognosis of HPV-HNSCC, the treatment modality, consisting of high dose radiotherapy (RT) in combination with chemotherapy (CT), remains similar to HPV-negative tumours, associated with toxic side effects. Epidermal growth factor receptor (EGFR) is overexpressed in over 80% of HNSCC and correlates with RT resistance. EGFR inhibitor Cetuximab is the only FDA approved targeted therapy for both HNSCC subtypes, however the response varies between HNSCC subtypes. In HPV-negative HNSCC, Cetuximab sensitises HNSCC to RT improving survival rates. To reduce adverse cytotoxicity of CT, Cetuximab has been approved for treatment de-escalation of HPV-positive HNSCC. The results of several recent clinical trials have concluded differing outcome to HPV-negative HNSCC. Here we investigated the role of EGFR in HPV-positive HNSCC response to RT. Remarkably, in HPV-positive HNSCC cell lines and in vivo tumour models, EGFR activation was strongly indicative of increased RT response. In response to RT, EGFR activation induced impairment of DNA damage repair and increased RT response. Furthermore, EGFR was found to downregulate HPV oncoproteinE6 expression and induced p53 activity in response to RT. Collectively, our data uncovers a novel role for EGFR in virally induced HNSCC and highlights the importance of using EGFR-targeted therapies in the context of the genetic makeup of cancer. [ABSTRACT FROM AUTHOR]

Background: The current diagnostic standard for detection of high‐risk human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is via a two‐stage algorithm, namely p16 immunohistochemistry followed by HPV DNA in situ hybridization in p16 positive cases. This study evaluated the feasibility of automated RNA in situ hybridization on a clinical platform as a single‐step alternative to the two‐stage algorithm within a routine diagnostic histopathology setting. Methods: Thirty‐eight cases positive for both p16 and DNA in situ hybridization, 42 p16 negative cases and 20 cases positive for p16 but negative for DNA in situ hybridization were randomly selected. High‐risk HPV RNA in situ hybridization was undertaken on all cases on an automated clinical platform. Manufacturer‐recommended and on‐slide additional p16/HPV positive and negative controls were used. Test quality assurance and diagnostic RNA in situ hybridization were independently assessed by two observers. A consensus diagnosis was reached in the presence of a third observer on discordant cases. All RNA in situ hybridization results were then correlated against p16 and DNA ISH status. Results: Inter‐slide RNA in situ hybridization staining variation was observed in control sections. RNA in situ hybridization demonstrated a high inter‐observer agreement rate (κ =.897, P <.001). Following consensus review, there was full concordance between RNA in situ hybridization and the current standard. Conclusion: Human papillomavirus testing by standalone automated RNA in situ hybridization on a clinical diagnostic platform currently available in routine diagnostic histopathology laboratories is a feasible alternative to the two‐step algorithm of p16 and DNA in situ hybridization. Control tissue staining procedures need to be adapted to achieve the most accurate results. [ABSTRACT FROM AUTHOR]

Objectives: Dental rehabilitation post‐radiotherapy often requires the consideration of dental implants. However, these are tentatively prescribed due to the concern of hypovascularisation and possible osteoradionecrosis. Hence, the current study assessed the microvasculature of the dento‐alveolar bone at implant sites taking into consideration the exact radiotherapy dose received to the region. Materials and methods: Bone cores were taken from nine patients during implant treatment and compared to nine control patients. Specimens were stained using CD31 and digitalised using a high‐resolution scanner for qualitative and quantitative assessment of the microvasculature. Monaco® treatment planning system was used to volume the implant site providing mean dose (Dmean) and maximum dose (Dmax). Results: A total of 23 bone cores were retrieved for analysis. The cohort had a Dmean of 38.4 Gy (59.6‐24.3 Gy). Qualitative analysis identified a clear reduction in the miniscule terminal capillaries and high incidence of obliterated lumens with increasing radiotherapy. Microvasculature density of irradiated patients was markedly reduced (P =.0034) compared to the control group with an inverse correlation to RT doses (P <.0001). Specifically, doses up to 30 Gy appear to preserve sufficient vascularisation (~77% in comparison with control) and tissue architecture. By contrast, exposure to higher doses 40%‐61% of the micro‐vessels were lost. Conclusion: Intensity‐modulated radiotherapy doses above 30 Gy identified reduction in microvasculature which is a lower threshold than previously accepted. In pharyngeal cancer patients' doses to the jaw bones often exceed this threshold. Coupled with favourable survival in certain oropharyngeal and nasopharyngeal cancer, dental rehabilitation via implants provides a significant clinical challenge. [ABSTRACT FROM AUTHOR]

Adenoid ameloblastoma (AA) was recently recognised as a separate tumour type in the most recent World Health Organisation (WHO) classification of head and neck tumours. This decision has been considered controversial by several groups, who have described AA as a subtype of ameloblastoma, a hybrid odontogenic tumour or to fall within the spectrum of other recognised odontogenic tumours, including dentinogenic ghost cell tumour and adenomatoid odontogenic tumour. Here we review the reasons for the WHO decision to classify AA as a separate tumour type. We also critique molecular and histological findings from recent reports published since the WHO classification. While acknowledging that the classification of tumours is constantly evolving, the balance of current evidence suggests that AA should remain a distinct tumour type, and not a subtype of ameloblastoma, pending further molecular characterisation. [ABSTRACT FROM AUTHOR]