Practical considerations for optimising homologous recombination repair mutation testing in patients with metastatic prostate cancer.

Analysis of the genomic landscape of prostate cancer has identified different molecular subgroups with relevance for novel or existing targeted therapies. The recent approvals of the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and rucaparib in the metastatic castration-resistant prostate cancer (mCRPC) setting signal the need to embed molecular diagnostics in the clinical pathway of patients with mCRPC to identify those who can benefit from targeted therapies. Best practice guidelines in overall biospecimen collection and processing for molecular analysis are widely available for several tumour types. However, there is no standard protocol for molecular diagnostic testing in prostate cancer. Here, we provide a series of recommendations on specimen handling, sample pre-analytics, laboratory workflow, and testing pathways to maximise the success rates for clinical genomic analysis in prostate cancer. Early involvement of a multidisciplinary team of pathologists, urologists, oncologists, radiologists, nurses, molecular scientists, and laboratory staff is key to enable optimal workflow for specimen selection and preservation at the time of diagnosis so that samples are available for molecular analysis when required. Given the improved outcome of patients with mCRPC and homologous recombination repair gene alterations who have been treated with PARP inhibitors, there is an urgent need to incorporate high-quality genomic testing in the routine clinical pathway of these patients.

[Resolution of the All-Russian Scientific and Practical Internet Conference with International Participation «Molecular Diagnostics and Biosafety-2020¼ (Moscow, October 6-8, 2020)].

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Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.

What is New in Neuro-oncology?

Neuro-oncology is a rapidly developing field. A continuous evolution in the understanding of the molecular underpinnings of central nervous system tumors has helped reconfigure the classification of brain tumors. More importantly, it has laid the path forward for the development and investigation of new therapeutics. The authors discuss the classification of brain tumors and novel therapies in brain tumors as well as promising treatments underway.

Molecular Diagnostics of Vascular Tumors of the Skin.

In this article, the authors have reviewed all the recent news regarding how the discovery of some novel and recurrent molecular and genetic changes has modified the classification of some entities and have addressed to the description of new variants of vascular tumors. And even more important, the authors also reviewed on how these findings, in addition to gain insight into the tumoral biology, portend significant clinical consequences not only regarding to their diagnosis but also to their management and prognosis because some of these mutations are potential targets for treatment. The authors have also highlighted immunohistochemical markers can help us as a surrogate marker of those molecular alterations.

Advances and Challenges in Pediatric and Childhood Cancers.

As we continue to learn about the unique biology of pediatric and childhood cancers and as new therapies are being developed, we asked some experts to highlight the most notable advances in our understanding of these diseases and in the development of treatments in the past decade, and to point out current challenges that still need to be addressed.

A semicentennial of pancreatic pathology: the genetic revolution is here, but don't throw the baby out with the bath water!

The last 50 years have witnessed an explosion in our understanding of the pathology of pancreatic diseases. Entities known to exist 50 years ago have been defined more precisely and are now better classified. New entities, previously not recognized, have been discovered and can now be treated. Importantly, new tools have been developed that have unraveled the fundamental biological drivers of a number of pancreatic diseases. Many of these same tools have also been applied clinically, supplementing the tried and true hematoxylin and eosin stained slide with a plethora of new, highly sensitive and specific tests that improve diagnostic accuracy and delineate best treatments. As exciting as these many advances are, our knowledge of pancreatic pathology remains incomplete, and there is much to be learned.

Fifty years of thyroid pathology: concepts and developments.

The past half century has seen a number of advances in pathology of thyroid diseases, especially neoplastic lesions. These include the description of new entities, the definition of prognostically important lesions, the incorporation of fine needle aspiration biopsy and its functional risk stratification of diagnoses into the clinical evaluation and therapeutic recommendations of the patient with thyroid nodules and the understanding of thyroid neoplastic development, diagnostic and prognostic parameters by use of molecular analysis so that such techniques are becoming standard of care for patients with thyroid tumors. The histopathologist and cytopathologist have been and continue to be at the forefront in the definition and understanding of these areas of thyroid disease. This review describes many of the most important advances in this area in an attempt bring the practicing pathologist up to date in these developments.

"Hey! Whatever happened to hemangiopericytoma and fibrosarcoma?" An update on selected conceptual advances in soft tissue pathology which have occurred over the past 50 years.

Hemangiopericytoma and fibrosarcoma represented at one time two of the most common diagnoses in soft tissue pathology. Both terms are now largely extinct. This article will review the clinicopathologic, immunohistochemical and molecular genetic advances that have led to these changes, and review the pathologic features of a select group of soft tissue tumors previously classified as hemangiopericytoma or fibrosarcoma.

From Breslow to BRAF and immunotherapy: evolving concepts in melanoma pathogenesis and disease progression and their implications for changing management over the last 50 years.

Since it was first recognized as a disease entity more than two centuries ago, advanced melanoma has, until recently, followed a very aggressive and almost universally fatal clinical course. However, over the past 50 years crucial ground breaking research has greatly enhanced our understanding of the etiology, risk factors, genomic pathogenesis, immunological interactions, prognostic features and management of melanoma. It is this combined body of work which has culminated in the exciting improvements in patient outcomes for those with advanced melanoma over the last ten years. In this the 50th anniversary of Human Pathology, we highlight the key developments in melanoma over this period.

Pathology of breast cancer in the last half century.

The past 50 years has been an era of technological innovation converging with the now dominant culture of testing hypotheses using clinical trials and case cohort methodology with rigorous statistical analysis. Great advances have been made in early diagnosis and, especially, less toxic and disfiguring primary therapy. Many of the advances in pathology have been in conjunction with efforts to support clinical initiatives, improve diagnostic reliability and translate basic science discoveries into tests that stratify patient management. Pathologists, with the support of epidemiologists, have lead significant advancements in the description and clinical significance of benign breast disease. Despite considerable efforts, the cure for breast cancer awaits better understanding of the pathophysiology of metastasis. We stand now at the brink a new era of technology, in which powerful genomic assays may be put to use in uncovering targets of therapy and defining mechanisms of disease progression. Pathologists must be active in ensuring that discoveries in this realm are optimized by assuring association with appropriate histological correlation and valid clinical endpoints.

A half century of change in diagnostic neuropathology: from the giants of yore to current brain tumor classification.

The first issue of Human Pathology contains a laudatory review of one of the most treasured books in the history of neuropathology: Neurological Clinicopathological Conferences of the Massachusetts General Hospital, a collection of neurological cases that appeared first in the New England Journal of Medicine in the 1940s, 1950s, and 1960s. Each patient history is discussed by well-known neurologists, neurosurgeons, and neuropathologists. Review of these cases provides a framework to explore diagnostic shifts that have occurred over the past half century. Importantly, while the discussants of these cases were great diagnosticians, they were somewhat limited by the methods available to them at the time; subsequent novel technologies provided opportunities for new insights that were made by the next generation of experts. Today's pathologists (whether neuropathologists or any other pathology subspecialists) are similarly skilled at diagnosis, although their diagnoses are now more often made on biopsies (rather than autopsies) and informed by pre-operative imaging studies as well as post-operative molecular analyses. In turn, one would conclude that, even in the face of future technological changes brought about by disruptive innovations like artificial intelligence and deep molecular analyses, a need will continue for the expertise of pathologists and other clinical diagnosticians.

Five decades of urologic pathology: the accelerating expansion of knowledge in renal cell neoplasia.

Those who are knowledgeable in cosmology inform us that the expansion of the universe is such that the velocity at which a distant galaxy is receding from the observer is continually increasing with time. We humbly paraphrase that as "The bigger the universe gets, the faster it gets bigger." This is an interesting analogy for the expansion of knowledge in the field of renal tumor pathology over the past 30 to 50 years. It is clear that a multitude of dedicated investigators have devoted incalculable amounts of time and effort to the pursuit of knowledge about renal epithelial neoplasms. As a consequence of the contributions of numerous investigators over many decades, the most recent World Health Organization classification of renal neoplasms includes about 50 well defined and distinctive renal tumors, as well as various miscellaneous and metastatic tumors. In addition, a number of emerging or provisional new entities are under active investigation and may be included in future classifications. In this review, we will focus on a number of these tumors, tracing as accurately as we can the origins of their discovery, relating relevant additions to the overall knowledge base surrounding them, and in some instances addressing changes in nomenclature.

The Journal of Molecular Diagnostics: 20 Years of Clinical Innovation.

This guest editorial highlights 20 years of clinical innovation in JMD.

Optical biosensors based on refractometric sensing schemes: A review.

Biosensor technology is an active field of research and development presenting rapid progress in recent decades, and the subfield of optical biosensors based on refractometric sensing schemes has developed dramatically during this time. This review focuses on advances in the refractometric sensing-based guided-wave optical biosensors particularly in the last two decades. It starts with a concise discussion on the underlying principles of label-free refractometric biosensor. Subsequently, advances in biosensor design, especially the transducer configuration and the integration of the sensing device are reviewed, highlighting the challenges and efforts dedicated to improving this technology. Various surface functionalization strategies designed to produce well-defined and reproducible surface properties are introduced for evaluation. Refractometric sensing scheme-based optical biosensors have found versatile applications varying from environmental monitoring and food safety to clinical diagnostics, together with advances in these applications and others are described. This paper concludes with a brief discussion on the outlook for integrating biosensors with emerging technologies.

Biochemical diagnostics of pancreatic cancer - Present and future.

Pancreatic cancer is one of the deadliest cancers having an exceptionally high mortality rate. Despite a relatively low incidence (10th among cancers), it is the fourth leading cause of cancer-related deaths in most developed countries. Improving early diagnosis of pancreatic cancer and strengthening the standardised comprehensive treatment remain the main focus of pancreatic cancer research. Tumor markers are usually tumor-associated proteins of clinical relevance in these patients. Although tumor markers carbohydrate antigen (CA 19-9) and carcino-embryonic antigen (CEA) are commonly used, neither demonstrate high diagnostic accuracy. Recently, hematopoietic growth factors (HGFs) and various enzymes have been reported as potential biomarkers for pancreatic cancer. These include macrophage-colony stimulating factor (M-CSF) and granulocyte-colony stimulating factor (G-CSF), interleukin-3 (IL-3), macrophage inhibitory cytokine (MIC-1) and various enzymes (alcohol dehydrogenase, aldehyde dehydrogenase, lysosomal exoglycosidases). With the development of molecular technology, detecting K-ras mutation in serum via polymerase chain reaction (PCR) is becoming more common and efficient. Because K-ras mutation rates are high in many cancers, some regard it as a potential tumor marker. Others have shown the value of serum miRNAs in detection of pancreatic cancer. Unfortunately, there are currently no effective methods of sufficient diagnostic accuracy to detect early-stage surgically resectable pancreatic cancer. In this article we highlight these biomarkers and summarise recent developments in the diagnosis and treatment of pancreatic cancer.