Practice Paradigms Before and After Introduction of the Diagnosis-Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): an Institutional Experience.

The recently adopted terminology of "Noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) reflects the indolent behavior of these tumors. In contrast to conventional papillary thyroid carcinomas, NIFTP can be managed conservatively. The purpose of this study was to investigate changes in surgical and pathologic practice patterns at our institution since the introduction of the NIFTP diagnosis in 2016. A retrospective analysis of all thyroid specimens received in our laboratory between January 2015 and April 2017 was performed. The final cohort consisted of 1508 thyroidectomy specimens from 1508 patients (1153 (76.5%) women and 355 (23.5%) men), of which 1011 (67%) were total thyroidectomies and 497 (33%) were partial thyroidectomies. There were 558 (69.2%) total thyroidectomies and 248 (30.8%) partial thyroidectomies performed prior to introduction of the NIFTP diagnosis and 453 (64.5%) and 249 (35.5%) total and partial thyroidectomies, respectively, after the change in nomenclature. Within a year following the initial use of this diagnosis, 67 NIFTP cases were identified (9.5% of all thyroidectomies), whereas compared with the year preceding it, malignant diagnoses decreased from 54.5 (439) to 44.6% (313), and the benign category remained unchanged from 44.5 (367) to 45.9% (322). For the entirely submitted 67 NIFTP cases, the mean number of blocks submitted was 14.7 (0.98 blocks/g); for malignant lesions 17.7 (0.92 blocks/g); and for benign lesions 16.6 (0.75 blocks/g). The results of our study suggest that NIFTP are encountered in almost 10% of thyroidectomies at our institution with expected shifts in cytology and surgical pathology diagnoses as a result of the change in nomenclature. During this time period, significant shifts towards less aggressive surgical management were not observed. All 67 NIFTP nodules were submitted entirely with no significant difference in the number of cassettes submitted for NIFTP nodules as compared with follicular variant papillary thyroid carcinoma (PTC), classic variant PTC, or follicular adenoma.

The coming 15 years in gynaecological pathology: digitisation, artificial intelligence, and new technologies.

Surgical pathology forms the cornerstone of modern oncological medicine, owing to the wealth of clinically relevant information that can be obtained from tissue morphology. Although several ancillary testing modalities have been added to surgical pathology, the way in which we view and interpret tissue morphology has remained largely unchanged since the inception of our profession. In this review, we discuss new technological advances that promise to transform the way in which we access tissue morphology and how we use it to guide patient care.

Ex Vivo Microscopy: A Promising Next-Generation Digital Microscopy Tool for Surgical Pathology Practice.

CONTEXT.­: The rapid evolution of optical imaging modalities in recent years has opened the opportunity for ex vivo tissue imaging, which has significant implications for surgical pathology practice. These modalities have promising potential to be used as next-generation digital microscopy tools for examination of fresh tissue, with or without labeling with contrast agents. OBJECTIVE.­: To review the literature regarding various types of ex vivo optical imaging platforms that can generate digital images for tissue recognition with potential for utilization in anatomic pathology clinical practices. DATA SOURCES.­: Literature relevant to ex vivo tissue imaging obtained from the PubMed database. CONCLUSIONS.­: Ex vivo imaging of tissues can be performed by using various types of optical imaging techniques. These next-generation digital microscopy tools have a promising potential for utilization in surgical pathology practice.

Identity determination in diagnostic surgical pathology.

From a technical perspective, specimen identity determination in surgical pathology over the last several decades has primarily focused on analysis of repetitive DNA sequences, specifically microsatellite repeats. However, a number of techniques have recently been developed that have similar, if not greater, utility in surgical pathology, most notably analysis of single nucleotide polymorphism (SNPs) and gene panels by next generation sequencing (NGS). For cases with an extremely limited sample or a degraded sample, sequence analysis of mitochondrial DNA continues to be the method of choice. From a diagnostic perspective, interest in identity determination in surgical pathology is usually centered on resolving issues of specimen provenance due to specimen labeling/accessioning deficiencies and possible contamination, but is also frequently performed in cases for which the patient's clinical course following definitive therapy is remarkably atypical, in cases of an unexpected diagnosis, and by patient request for "peace of mind". However, the methods used for identity determination have a much broader range of applications in surgical pathology beyond tissue provenance analysis. The methods can be used to provide ancillary information for cases in which the histomorphology is not definitively diagnostic, as for example for tumors that have a virtually identical microscopic appearance but for which the differential diagnosis includes synchronous/metachronous tumors versus a metastasis, and for the diagnosis of hydropic early gestations versus hydatidiform molar pregnancies. The methods also have utility in several other clinical settings, for example to rule out a donor-transmitted malignancy in a transplant recipient, to monitor bone marrow transplant engraftment, and to evaluate natural chimerism.

Disease activity and mucosal healing in inflammatory bowel disease: a new role for histopathology?

Histologic evaluation of disease activity in the setting of inflammatory bowel disease is gaining interest within the gastroenterology community. Recent data suggests that histologic measurements of inflammation in ulcerative colitis are more sensitive at detecting disease activity and perform better than endoscopic measurements in predicting clinical outcomes. Histologic measurements are also increasingly used in ulcerative colitis clinical trials to assess response to new therapies. Histologic measurements of disease activity are less well studied in Crohn's disease, but are gaining attention. Current published treatment algorithms in inflammatory bowel disease do not take into consideration histologic activity; however, this may change in the near future. In order for histologic measurements to be included in clinical decision-making, validated, reliable, and responsive histologic scoring systems are needed. In this review, the recent literature on the significance of histologic activity in both ulcerative colitis and Crohn's disease is summarized. Histologic scoring systems are also briefly discussed.

Recent Developments in Surgical Pathology of the Uterine Corpus.

There have been several updates recently on the classification of uterine tumors. Endometrial carcinomas have traditionally been divided into 2 types, but some are difficult to classify and do not fit readily into either of the currently recognized categories. The Cancer Genome Atlas Research Network has recently defined 4 new categories of endometrial cancer on the basis of mutational spectra, copy number alteration, and microsatellite instability, which might provide independent prognostic information beyond established risk factors. The Society of Gynecologic Oncology, moreover, now recommends systematic screening of every patient with endometrial cancer for Lynch syndrome. The new definition of high-grade endometrial stromal sarcoma disregards the number of mitotic figures as a primary diagnostic criterion and instead specifies moderate atypia still resembling stromal origin but lacking the pleomorphism of undifferentiated uterine sarcoma; these tumors also harbor a JAZF1-SUZ12 gene rearrangement. Mitotic count, atypia, and coagulative necrosis are the main histologic criteria that define leiomyosarcoma. Determining the type of necrosis can be very challenging in patients receiving various treatment modalities for symptomatic fibroids before myomectomy, since key histologic features of ischemic-type necrosis are often absent. Ancillary stains including p16, p53, MIB-1, trichrome, and reticulin may be helpful in tumors harboring necrosis that is difficult to classify. Minimally invasive gynecologic surgeries have introduced histologic artifacts that complicate the diagnosis. It is essential to recognize these as procedure-related artifacts to avoid upstaging tumors and triggering unnecessary adjuvant treatment.

Digital pathology in clinical use: where are we now and what is holding us back?

Whole slide imaging is being used increasingly in research applications and in frozen section, consultation and external quality assurance practice. Digital pathology, when integrated with other digital tools such as barcoding, specimen tracking and digital dictation, can be integrated into the histopathology workflow, from specimen accession to report sign-out. These elements can bring about improvements in the safety, quality and efficiency of a histopathology department. The present paper reviews the evidence for these benefits. We then discuss the challenges of implementing a fully digital pathology workflow, including the regulatory environment, validation of whole slide imaging and the evidence for the design of a digital pathology workstation.

The changing landscape of gynaecological cancer diagnosis: implications for histopathological practice in the 21st century.

The era of molecular medicine has led to dramatically improved understanding of the genetic events that give rise to different types of cancers. In the case of gynaecological malignancies, this has resulted in distinct shifts in how these tumours are diagnosed in routine surgical pathology practice, with an increased emphasis on accurate subtype diagnosis. This has happened across all sites in the gynaecological tract and for most cell types, but in ways that are site-specific and may appear to be subtle, as in most instances the diagnostic terminology has not changed. For example, the diagnosis of clear cell carcinoma of the ovary is still in use, but the diagnostic criteria and clinical implications are different in 2017 from what they were in 2000. As a result, there can be a failure to appreciate how important these changes are and the resulting necessity of incorporating them into our daily practice. In this review we will describe changes in diagnostic surgical pathology occasioned by improved understanding of molecular events during pathogenesis, for cancers of ovary/tube, endometrium, cervix and vulva, and highlight how current practice differs from that of only a few years ago.

Ex Vivo (Fluorescence) Confocal Microscopy in Surgical Pathology: State of the Art.

First developed in 1957, confocal microscopy is a powerful imaging tool that can be used to obtain near real-time reflected light images of untreated human tissue with nearly histologic resolution. Besides its research applications, in the last decades, confocal microscopy technology has been proposed as a useful device to improve clinical diagnosis, especially in ophthalmology, dermatology, and endomicroscopy settings, thanks to advances in instrument development. Compared with the wider use of the in vivo tissue assessment, ex vivo applications of confocal microscopy are not fully explored. A comprehensive review of the current literature was performed here, focusing on the reliable applications of ex vivo confocal microscopy in surgical pathology and on some potential evolutions of this new technique from pathologists' viewpoint.

The evolution of pre-analytic factors in Anatomic Pathology.

Anatomic Pathology has continuously evolved since launch by Virchow in Berlin. The era from 1990 to 2010 saw the rise of immunohistochemistry and its application for diagnosis, prognosis, and prediction of response to therapy. Currently the next wave of evolution is ongoing; molecular pathology, with emphasis on alterations to DNA, and expression of mRNA as biomarkers. The interrogation of biomolecules by specific probes is more demanding on specimens than the traditional application of histologic stains to tissue. This issue is juxtaposed to the fact that the majority of specimens are purely evaluated by histomorphology, for which current specimen practices are adequate. The capacity to identify a priori which cassette of tissue is appropriate for molecular analysis is difficult, if not impossible, the goal is to improve the quality of all pathology specimens in an economically viable model to enable advanced assay, when applicable.

Current projects in Pre-analytics: where to go?

The current clinical practice of tissue handling and sample preparation is multifaceted and lacks strict standardisation: this scenario leads to significant variability in the quality of clinical samples. Poor tissue preservation has a detrimental effect thus leading to morphological artefacts, hampering the reproducibility of immunocytochemical and molecular diagnostic results (protein expression, DNA gene mutations, RNA gene expression) and affecting the research outcomes with irreproducible gene expression and post-transcriptional data. Altogether, this limits the opportunity to share and pool national databases into European common databases. At the European level, standardization of pre-analytical steps is just at the beginning and issues regarding bio-specimen collection and management are still debated. A joint (public-private) project entitled on standardization of tissue handling in pre-analytical procedures has been recently funded in Italy with the aim of proposing novel approaches to the neglected issue of pre-analytical procedures. In this chapter, we will show how investing in pre-analytics may impact both public health problems and practical innovation in solid tumour processing.