UPDATES ON SINONASAL PATHOLOGY: NOTHING TO SNEEZE AT!
The sinonasal tract is home to some of the most diverse pathology in the entire body. Neoplasms are myriad and biologic behaviour ranges from essentially harmless to highly lethal. There are many uncommon tumors and diagnostic pitfalls. Indeed, in head and neck services where there is mandatory second review of outside pathology specimens, the sinonasal tract was higher than average for discrepancies, ranging from 11 to 25%, with many of those being major discrepancies. Making things more challenging, there are a number of newly described tumors that pathologists may be unfamiliar with. This talk will detail some of the newly described neoplasms of this anatomic area, with an emphasis on differential diagnosis, utilizing an algorithmic approach and judicious use of ancillary studies.
NEWLY DEFINED (AND RECENTLY REFINED) SALIVARY GLAND TUMOURS
The surgical pathology of major and minor salivary glands is acknowledged as one of the most challenging aspects in all of head and neck pathology. Salivary gland tumors are rare, so extensive experience and comfort with them is difficult to obtain. There are dozens of well-recognized tumors, and each one of is incredibly diverse with numerous variant morphologies. On top of that, the classification of salivary gland tumors is still being revolutionized by the discovery of several tumor-defining chromosomal rearrangements. In this talk, we will review a number of examples demonstrating how molecular findings have altered salivary gland tumor classification. These cases will illustrate how these genetic discoveries have informed and refined our histologic examinations, and how selective utilization of molecular assays can prevent misdiagnoses and their disastrous consequences.
Keynote Lecture I
Chair: Sonja Boy
Keynote Lecture II
Chair: Willie van Heerden
Symposium I: Cancer Immunology and Immunotherapy
Chairs: Gareth Thomas & Tuula Salo
IMMUNOTHERAPY FOR SQUAMOUS CELL CANCER OF THE HEAD AND NECK
In recent years, immune-oncology (IO) therapies have revolutionized the clinical management of many different types of solid cancers, including squamous cell cancers of the head and neck (SCCHN). In this lecture, I will trace preclinical and clinical data underpinning the development of IO agents in patients with SCCHN. In particular, the initial developments in the context of post-platin, second-line therapy will be discussed and their transition to first-line approaches will be described. Subsequent strategies in which IO agents are combined with radiotherapy will be outlined. The final part of the talk will discuss the problem of primary and acquired resistance to IO agents and how these issues might be addressed with novel drugs.
PHASE I EVALUATION OF PAN-ErbB TARGETED CAR T-CELL IMMUNOTHERAPY OF LOCALLY ADVANCED/RECURRENT HEAD AND NECK CANCER
T4 immunotherapy consists of autologous T-cells that have been engineered to express a Pan-ErbB targeted CAR (T1E28z) and an IL-4 responsive chimeric cytokine receptor, 4ab. Cell products are manufactured from a blood draw in a 2 week closed GMP process. Fifteen patients have received intra-tumoural T4 CAR T-cells at doses of up to 1 billion cells. To date, no dose-limiting toxicities have been encountered. None patients have achieved stable disease and a lymphodepletion cohort is now planned.
IMPROVING IMMUNOTHERAPY: TARGETING THE TUMOUR MICROENVIRONMENT
Immunotherapy, treatments that harness and enhance the intrinsic powers of the immune system, is the most promising new cancer therapy for several decades. Immune checkpoint inhibitors against CTLA4 and PD1/PDL1 have shown efficacy across cancer types, and the recent trials treating HNSCC patients with a-PD1 have produced response rates of around 15%. Use of checkpoint inhibitors is predicated upon boosting a pre-existing anti-tumour immune response, and the morphological correlate of this in cancer tissues is the presence of tumour-infiltrating lymphocytes (TIL); it is likely that most patients who respond to checkpoint inhibitors have this tumour feature. In most patients however, TIL are either absent or excluded from the tumour, and for these tumours, alternative strategies to promote tumour immune recognition and/or TIL tumour infiltration are required. This presentation considers our current understanding of mechanisms regulating response/non-response to immunotherapy and ideas for developing combination immunotherapy to overcome resistance mechanisms.
USING 'OMICS DATA TO STUDY THE HNSCC IMMUNE MICROENVIRONMENT
Recent large-scale cancer ‘omics projects, such as The Cancer Genome Atlas (TCGA) have provided rich molecular datasets, affording new insight into tumour biology. I will discuss some of the questions we’ve addressed by applying novel bioinformatics approaches to HNSCC datasets, including our use of DNA methylation data to estimate the cellular composition of solid tumours. I will explain how integrating genomic and gene expression data with tumour deconvolution enabled us to identify genomic correlates of cytotoxic T-lymphocyte infiltration with implications for potentiation of immunotherapy. I will also present insights from our recent multi-region host and viral sequencing studies in HPV+ OPSCC.
Symposium II: Precursor Lesions of the Head and Neck
Chairs- Wanninayake Tilakaratne & Grace Bradley
PREMALIGNANCY OF THE ORAL CAVITY: FROM MOLECULAR PROLFILING TO PERSONALIZED PREVENTION STRATEGIES
Head and neck squamous cell carcinomas (HNSCC) remain frequent and the oral cavity the most frequent subsite. In western countries, risk factors associated with oral cavity SCC (OSCC) include tobacco and alcohol. Non-smoker non-drinker (NSND) patients represent 15% of all OSCC with no involvement of HPV. OSCC may be preceded by premalignant lesions (PMLs) and patients undergoing surgical resection for OSCC are at high risk of second primary tumors (SPTs). Loss of heterozygosity (LOH) is the most validated biomarker of risk or oral transformation or SPTs, based on the analysis of PMLs or adjacent mucosa on the resected tumor. But the natural history of OSCC remains poorly understood and no standard pharmacological intervention i.e. chemoprevention, has been set so far. We will summarize our recent work to identify new biomarkers of risk of oral cancer and to build a framework for the development of personalized interception strategies.
INFLAMING PROGRESSION: UNDERSTANDING THE ROLE OF INFLAMMATION IN ORAL MALIGNANT TRANSFORMATION
Oral squamous cell carcinoma (OSCC) is a devastating disease and its poor prognosis has changed minimally in the past several decades. As in many other malignancies, invasion and metastasis are hallmarks of malignant transformation and underlie most of the morbidity and mortality of the disease. The presence of inflammatory cells may modify the tumour microenvironment to increase invasion and decrease response to treatment. This is particularly important in the context of OSCC because the oral cavity is a unique environment combining well developed innate and adaptive immune responses. OSCC is commonly preceded by a range of potentially malignant disorders (OPMD) and we have evaluated how inflammatory responses in the microenvironment of OPMD and OSCC can influence diseases progression. Our results show a specific pattern of OSCC and OPMD-associated inflammation that can promote cellular invasion and disease progression and potentially be explored as new opportunities for treatment.
THE USE OF NON-INVASIVE OPTICAL AND MOLECULAR TESTS IN MANAGEMENT OF AN ORAL LESION
Despite advances in treatment modalities, 5-year survival rate for oral cancer (OC) remains at 30-60% with minimal progress over the past 5 decades. The key to improving survival rates is the early identification of high-risk oral potentially malignant lesions (OPMLs) and followed with effective management strategies. However, the uncertainty of OC risk for these lesions has created a significant management dilemma – watchful waiting with increased patient psychological and economic burdens vs. unnecessary aggressive surgery with reduced quality of life and compromised daily functions.
Our group have spearheaded the use of a set of biomarkers using loss of heterozygosity (LOH). Recently we have transformed it to an actionable test, which has shown a high specificity in identifying OPMLs progressed within 3 years. In this talk, we will discuss the role of such molecular tests in triaging ways (surgery, cryotherapy and topical photodynamic therapy) of OPMLs’ management.
HUMAN PAPILLOMAVIRUS ASSOCIATED ORAL EPITHELIAL DYSPLASIA
Within the context of recent international recognition that high-risk types of human papillomavirus (HPV) are associated with a clinically distinct variant of head and neck cancer, there is growing awareness that this virus is also associated with a subgroup of histologically dysplastic mucosal lesions of the oral cavity. However, HPV-associated oral epithelial dysplasia (OED) is still poorly understood since there are no agreed diagnostic criteria and the overall prevalence of this disease as well as its clinical significance are largely unknown. This presentation will briefly outline the historical background of this disease and its evolving terminology. Distinct histological features of HPV-associated OED and issues around diagnostic testing methods will also be presented. Finally, this talk will touch on challenges surrounding unresolved clinico-pathological issues requiring urgent research.
PROLIFERATIVE VERRUCOUS LEUKOPLAKIA AND ANEUPOLIDY
Proliferative verrucous leukoplakia (PVL) is a clinical term for a treatment resistant wide spread oral mucosal disease with high risk of malignancy. PVL is clinically challenging to distinguish from conventional leukoplakia and it may also exhibit lichenoid features. Furthermore, there is a lack of histopathological diagnostic criteria. For differential clinical and histopathological diagnostics as well as for patient follow-up and treatment, it would be important to discover a biomarker which could serve to identify patients who have PVL and who are more prone to develop carcinoma. Twenty-two different biomarkers have been evaluated in predicting PVL behavior. According to our meta-analysis, aneuploidy seems to be the most promising biomarker for PVL. In this presentation, data regarding the use of aneuploidy as a prognostic marker in a group of Finnish PVL patients will be presented with special reference to their histopathological presentation.
GRADING LARYNGEAL DYSPLASIA: ORDER FROM CHAOS?
A review of the current WHO grading system for laryngeal dysplasia will be presented, with a historical perspective on its development and a comparison with grading systems used in oral dysplasia. The advantages and deficiencies will be illustrated with practical tips on grading.
Digital Pathology & Artificial Intelligence: Friends or Foes
Chairs- Ali Khurram & Pablo Vargas
AI-BASED CANCER HISTOLOGY IMAGE ANALYTICS
The visual cortex is extremely efficient at recognising people and objects and building an understanding of the natural world around us. However, it is not ideal at objectively measuring what we see and complex spatial patterns hidden in plain sight cannot sometimes be deciphered by the naked eye. Computational Pathology is an emerging discipline concerned with the study of computer algorithms for understanding disease from the analysis of digitised histology images. I will show some snippets of computational pathology research in my group to demonstrate the value of Artificial Intelligence (AI) based analytics of information-rich, high-resolution whole-slide images (WSIs, the so-called Big Cancer Image Data) for cancer diagnosis and prognosis. I will show examples of how histological motifs extracted from digital pathology image data are likely to lead to patient stratification for precision medicine. I will then discuss some of the main challenges in digital pathology and open challenges.
DIGITAL PATHOLOGY FOR ROUTINE CLINICAL PRACTICE- THE LEEDS EXPERIENCE
Leeds Teaching Hospitals NHS Trust has been scanning all surgical pathology specimens including all maxillofacial and oral pathology biopsies, resections, and immunohistochemistry slides since September 2018. We are now in the process of transitioning to using a digital reporting platform exclusively for diagnostic practice. This transitional process potentially will deliver huge benefits and open up the possibility of implementing exciting opportunities such as automated report generation and artificial intelligence tools, though this process is not significant challenges. The process of departmental / regional digitalisation, the diagnostic validation process and the practicalities of day-to-day utilisation of digital reporting will be discussed. Challenges such as the adoption of a digital workflow process, practical lessons learnt and future directions and opportunities will also be considered.
ALAN ROGER DOS SANTOS-SILVA
DIGITAL MICROSCOPY IN THE DIAGNOSES OF ORAL DISEASES
The first digital pathology platform receiving FDA approval is leading the development of whole slide imaging systems (WSI) for diagnoses across a variety of diseases. However, concerns about how the introduction of these computational tools will impact the pathologists were raised. Given the highly specialized nature of Oral Pathology, additional training on WSI may be necessary to overcome limitations in methods of preparation and cases interpretations. Therefore, the goal of this talk is to address current challenges in the validation of digital microscopy for histopathological diagnosis in oral diseases and review the main reasons for the occurrence of diagnostic discordances, limitations and pitfalls for WSI primary diagnoses.
ARTIFICIAL INTELLIGENCE IN ORAL & MAXILLOFACIAL PATHOLOGY: MAN Vs MACHINE or MAN + MACHINE?
Machine learning, a branch of Artificial Intelligence (AI), has been shown to aid pathology diagnosis and predict disease behaviour. Use of machine learning can remove subjectivity and variability by standardisation providing a quantitative output to inform treatment decisions whereas AI can leverage ‘big data’ from information-rich multi-gigapixel whole slide images (WSIs). Despite accurate and consistent performance of AI-related tools in a range of pathologies and cancers, significant cynicism and a degree of threat remains within the pathology community about its adoption. Furthermore, there has been limited exploration of application and use of AI in Oral and Maxillofacial Pathology.
This talk will provide a background of Artificial Intelligence in Pathology and share findings from some collaborative studies specific to Oral and Maxillofacial Pathology.
Symposium IV: Clinical Trials
Chairs- Esther O'Regan & Raghu Radhakrishnan
CANCER CLINICAL TRIALS - WHAT IS THE ROLE OF PATHOLOGY AND THE PATHOLOGIST?
The treatment of cancers has improved with the introduction of new oncologic therapies such as immunotherapy (checkpoint inhibitors) and targeted therapies that capitalize on tumor specific genetic mutations. These new methodologies have been introduced to augment traditional oncologic modalities of surgery, radiation and chemotherapies. In order to know if new cancer therapies work, they must be tested and validated in large scale, multi-institutional trials. In North America much of this testing is conducted by 5 NCI-funded National Clinical Trial Network (NCTN) groups that design and execute phase II and III trials with employment of biomarker- and biologic pathway-defined approaches to risk stratification, investigational therapy assignment, and clinical trial decision-making. A key component is the assessment of biomarkers using patient derived fluid and tissue based biospecimens. Thus, pathology and pathologists play an increasingly important role in this process as the number of biomarkers and pathologic variables expands. This lecture will cover NCTN cancer trials, the role of the pathologist and biomarker testing in the context of advances in head and neck cancer management.
TRAINING AND ACCREDITATION FOR PATHOLOGISTS UNDERTAKING CLINICAL TRIALS RESEARCH
Clinical trials rely on multidisciplinary teams, but specific training and accreditation for pathologists is limited. This has led to a reduced level of engagement in clinical trials research over recent years. Pathologists should be involved in trial design from the outset to deliver maximum data collection and translational research opportunities. Clinical trials must be performed according to the principles of Good Clinical Practice (GCP) and pathologists involved in the delivery of clinical trials are required to undergo formal GCP training. Further training should be provided through trial-specific investigator meetings and pathologists should undertake External Quality Assurance schemes relevant to the trial. General clinical trials training should ideally be provided to all pathologists, including those in training, through national and local educational events. It is hoped such training will increase the interest in clinical trials research to ensure a high standard of data collection and to maximise translational research opportunities.
INTEGRATED PATHOLOGY PRACTICE IN AN ERA OF PRECISION MEDICINE
This talk will describe the newly formed Precision Medicine Centre of Excellence (PMC) at Queen’s University Belfast. This is a new clinical laboratory bringing together high-throughput genomics, digital pathology and big data analytics in a fully integrated fashion to deliver a regional clinical diagnostic service and support academic and commercial research.
The PMC aims to accelerate the translation of potentially relevant diagnostic, prognostic and therapeutic findings into clinically actionable information by applying state-of-the-art technology in an accredited laboratory environment.
The lecture will describe how the laboratory has formed partnerships and collaborations with industry, academia and healthcare organisations to potentially capitalise on integrated clinical and biomarker information in order to improve patient’s outcomes. A number of exemplars will be presented to outline the integrated activity of the Centre.
Clinical Trials Showcase
SEND FROM GLASGOW TO NICE: THE SENTINEL NODE BIOPSY TRIALS
This overview will cover the history of the Sentinel Lymph Node clinical trials in head and neck cancer, from inception in Glasgow to NICE approval. This is an exemplar of the role that effective clinical trial design, with pathology input as a central component, can lead to changes in clinical practice.
Pathologists have a pivotal role in clinical trials ensuring accurate diagnosis and staging. More recently, pathology data around prognostic and predictive tests are being used to enroll, stratify and randomize patients to experimental treatments. In addition, pathological parameters are employed as primary and secondary outcome measures either as standalone classifiers or in combination with clinical data. This presentation will highlight the opportunities and challenges of getting involved in clinical trials as a pathologist. I will describe my experiences of developing and delivering PATHOS in the UK and scaling up to a worldwide phase III trial.(Owadally W, Hurt C, Timmins H, Parsons E, Townsend S, Patterson J, Hutcheson K, Powell N, Beasley M, Palaniappan N, Robinson M, Jones TM, Evans M. PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for Human papillomavirus (HPV) positive oropharyngeal cancer. BMC Cancer 2015; 15:602).
WHO says 'developing odontoma': Who says 'neoplasia'?
Chairs- Takashi Takata & John Wright
The ameloblastic fibro-odontoma (AFO) is a well-recognized mixed odontogenic “tumour.” In 2017, the WHO eliminated AFO as a standalone entity in its classification of odontogenic tumours and argued that most AFOs are developing odontomas. Odontomas are generally considered to be hamartomas. Four IAOP members will debate the merits of AFO as a hamartoma vs a neoplasm. Professors John Wright (USA) and Tie-Jun Li (China) will argue for hamartoma while Professors Marilena Vered (Israel) and Merva Soluk Tekkesin (Turkey) will offer counter arguments for neoplasm. In addition to debating the merits of the biologic behaviour of AFO, an additional goal is to outperform the OKC/KCOT IAOP debate in Brisbane (2006). The ultimate decision is yours.
Slide Seminar I : Sinonasal Pathology
Chair- Bill Barrett
Panel- Justin Bishop & Ketan Shah
The histopathology of the sinonasal tract encompasses a range of uncommon inflammatory and neoplastic entities encountered with varying frequency by oral and maxillofacial pathologists. Recent developments in molecular genetics have identified several new sinonasal tumours, some of which have morphological features similar to those with which oral and maxillofacial pathologists are familiar in other contexts. The content of this seminar will reflect the material submitted by members of the IAOP, but as we are fortunate to have the benefit of two experts, Justin Bishop and Ketan Shah, we will also see examples of novel neoplasms few delegates will have seen before.
Slide Seminar II :
Diagnostic Pitfall in Oral & Maxillofacial Pathology
Chairs- Brendan Conn & Mary Toner
This slide seminar will focus on commonly encountered traps which may mislead pathologists when reporting seemingly routine oral pathology cases. Cases will be presented by a multinational panel of respected diagnostic pathologists with many years of experience in the field.