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Data on Afirma's genomic sequencing classifier (GSC) performance in atypia of undetermined significance (AUS) subcategories is limited. This study investigated GSC performance in AUS nodules with architectural atypia (AUS-A), cytological atypia (AUS-C), architectural and cytological atypia (AUS-AC), and predominantly Hürthle cells (AUS-HC).This study retrieved consecutive thyroid nodules having a recurrent cytologic diagnosis of AUS with qualifiers and a concurrent GSC diagnostic result. All nodules were followed by either surgical intervention or clinical and/or ultrasound monitoring (≥6 months). GSC benign call rate (BCR), rate of histology-proven malignancy, and diagnostic parameters of GSC were calculated for individual AUS subcategories. Statistical analysis was performed using the Fisher exact test.A total of 135 AUS nodules fulfilled inclusion criteria, including 79 AUS-A, 9 AUS-C, 29 AUS-AC, and 18 AUS-HC. BCR was 72.2%, 66.7%, 44.8%, and 77.8% in AUS-A, AUS-C, AUS-AC, and AUS-HC, respectively. AUS-A showed a greater BCR than AUS-AC (p lt; .05). All GSC-benign nodules were considered benign on clinical or surgical follow-up. Among GSC-suspicious nodules, histology-proven malignancies represented 4.5% of AUS-A, 0% of AUS-C, 56.3% of AUS-AC, and 25.0% of AUS-HC cases. AUS-AC demonstrated a higher malignant rate compared with AUS-A (p lt; .05). GSC offers 100% NPV and a wide range (5%-56%) of PPV across all AUS subcategories. AUS-AC demonstrated a greater PPV compared with AUS-A (p lt; .05).BCR of GSC and malignant rates associated with suspicious GSC may differ in various AUS subcategories. GSC-suspicious nodules with both architectural and cytologic atypia are more likely to be malignant. These findings may improve clinical triage and/or management of patients with AUS thyroid nodules.

Medical school curricula have focused more on early clinical exposure with compressed didactic curricula, raising questions on how pathology can be effectively integrated into clinically relevant medical education. This study highlights how a required 1-week pathology rotation embedded within a surgery clerkship can impact students' knowledge base and perspectives of pathology.One hundred ninety-two medical students rotated through a newly designed mandatory 1-week pathology rotation during surgery clerkship. Post-rotation feedback and survey data from students were collected to evaluate their perspectives of pathology. Pathology residents and faculty were surveyed about changes on workflow imposed by the new rotation.Eighty percent of student respondents agreed the rotation improved understanding of pathology workflow and its integration into the larger picture of healthcare delivery. 62% and 66% reported the rotation had a positive impact on their perspectives of pathology and pathologists, respectively. However, a significant number pathology resident respondents noted that integration of students into clinical activities either slightly (42%) or significantly (5%) decreased their own learning. Both pathology faculty and residents also noted medical student presence either slightly (19% and 37%, respectively) or significantly (63% and 58%, respectively) decreased workflow efficiency.Integration of pathology rotations into surgical clerkships is a viable strategy to remedy decreased pathology contact and education due to curricular restructuring that condenses preclinical time while offering medical students a more integrated and practical perspective of pathology as a field. It is essential for pathology departments to prioritize and actively participate in both preclinical and clinical curricular development.The online version contains supplementary material available at 10.1007/s40670-022-01569-y.

Urine cytology is an economical and convenient method of triaging patients who present with urinary symptoms as well as surveying those who have previously been diagnosed with urothelial carcinoma for recurrent or persistent disease. While the vast majority of malignancies diagnosed in urine cytology are urothelial carcinomas, it is important to recognize nonurothelial elements to inform patient prognosis and raise the possibility of involvement by a urothelial carcinoma variant, nonurothelial malignancy of the bladder, or a nonbladder primary, which may alter patient management pathways. As such, becoming familiar with morphologic features of nonurothelial malignancies in urine cytology as well as their related clinical risk factors, radiologic and cystoscopic features, differential diagnostic considerations, and the utility and pitfalls of ancillary tests can facilitate optimal patient care.

Background: Thyroid fine needle aspiration (T-FNA) is a mainstay in management of thyroid nodules. However, the preparation of T-FNA specimens varies across institutions. Prior studies have compared diagnostic rates between different specimen preparations of T-FNA specimens and their associated advantages and disadvantages. However, few have compared the rates of all diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) between liquid-based preparations (LBPs) and a combination of LBP and conventional smear (CS) preparations. Our study compares TBSRTC diagnostic rates between these 2 cohorts and correlates cytologic diagnoses with subsequent thyroid resections to evaluate rates of neoplasia (RON) and malignancy (ROM). Methods: 584 consecutive thyroid FNA specimens were collected and stratified by preparation type (ThinPrep [TP] vs. CS & TP). Diagnostic rates for each TBSRTC diagnostic category were calculated. The institution’s electronic medical records database was searched for histologic diagnoses of previously sampled thyroid nodules to evaluate the RON and ROM. Results: Of 584 thyroid FNA specimens, 73 (12.5%) and 511 (87.5%) were evaluated by TP only and CS & TP, respectively, reflecting the predominance of rapid on-site evaluation (ROSE) with CS for T-FNAs at our institution. Of the TP only and CS & TP cohorts, 29 (39.7%) and 98 (19.2%) had subsequent resections, respectively. The frequency of non-diagnostic cases was lower in the CS & TP cohort (12.7% vs. 26%). While the diagnostic rate of follicular lesion of undetermined significance was similar for both cohorts, SFN categorization was only utilized in the CS & TP cohort (1.5% vs. 0%). Although RON and ROM were similar between cohorts in many of the TBSRTC categories, there was a higher RON associated with non-diagnostic specimens in the TP only cohort when the denominator included all non-diagnostic cases. Conclusion: The combination of CS and LBP may potentially decrease the non-diagnostic rate of T-FNA specimens as well as the number of passes required for diagnosis, particularly with ROSE. Evaluation of morphologic features highlighted in conventional smears may facilitate diagnostic categorization in the “suspicious for follicular neoplasm” category.

Purpose To assess, from the student perspective, medical school training in genetics and genomics. Methods In 2019, the Undergraduate Training in Genomics (UTRIG) Working Group developed genetics-related survey and knowledge questions for the RISE-FIRST, an exam administered to postgraduate year 1 (PGY1) pathology residents in the United States during their first months of training. Survey questions focused on perceived knowledge in genetics and the structure and quality of training with responses compared with those in control areas. Results There were 401 PGY1 pathology residents who took the 2019 RISE-FIRST (65% of those in the United States). There was significantly lower perceived understanding of genetics compared with nongenetics topics. Respondents also reported less time spent learning genetics and lower quality training compared with control areas. Only 53% indicated an interaction during medical school with a medical geneticist. Residents also did not perform as well on the UTRIG-developed knowledge questions than those in other areas of pathology. Conclusion The RISE-FIRST is a useful tool in assessing the current state of medical school training in genetics. This needs assessment may serve as a call to action to improve medical school genetics education and promote greater understanding of the role of genetics professionals in patient care.

Fine needle aspiration (FNA) has become increasingly popular in the evaluation of lymph nodes for lymphoproliferative disorders, but there are limitations to accurate subclassification of lymphoma using morphology alone. This case aims to expand diagnostic considerations of large B-cell populations identified on FNA material. We also address the significance of Epstein-Barr virus (EBV) DNA in the workup of patients with suspected lymphoma by FNA.

Background: In the face of rapid technological advances in computational cytology including artificial intelligence (AI), optimization of its application to clinical practice would benefit from reflection on the lessons learned from the decades-long journey in the development of computer-assisted Pap test screening. Summary: The initial driving force for automated screening in cytology was the overwhelming number of Pap tests requiring manual screening, leading to workflow backlogs and incorrect diagnoses. Several companies invested resources to address these concerns utilizing different specimen processing techniques and imaging systems. However, not all companies were commercially prosperous. Successful implementation of this new technology required viable use cases, improved clinical outcomes, and an acceptable means of integration into the daily workflow of cytopathology laboratories. Several factors including supply and demand, Food and Drug Administration (FDA) oversight, reimbursement, overcoming learning curves and workflow changes associated with the adoption of new technology, and cytologist apprehension, played a significant role in either promoting or preventing the widespread adoption of automated screening technologies. Key Messages: Any change in health care, particularly those involving new technology that impacts clinical workflow, is bound to have its successes and failures. However, perseverance through learning curves, optimizing workflow processes, improvements in diagnostic accuracy, and regulatory and financial approval can facilitate widespread adoption of these technologies. Given their history with successfully implementing automated Pap test screening, cytologists are uniquely positioned to not only help with the development of AI technology for other areas of pathology, but also to guide how they are utilized, regulated, and managed.

BACKGROUND Cytologic detection of malignant cells in pleural, peritoneal, or pericardial effusion most likely indicates advanced stage of malignant disease. There are a few studies updating the categorization of malignant effusions. METHODS The electronic pathology database was searched to identify consecutive cases of malignant effusion during a 6-year period. Patient age and gender, origins of known malignancy, and cytologic diagnoses were recorded and summarized. RESULTS A total of 1059 specimens included 561 (53%) pleural, 441 (41.6%) peritoneal, and 57 (5.4%) pericardial fluids. Most of the pleural (516, 92.0%), peritoneal (418, 94.8%), and pericardial (53, 93.0%) specimens were derived from patients with a single known malignancy. More common origins involving pleural fluid were lung (152, 27.1%) followed by breast (103, 18.4%) and gastrointestinal tract (76, 13.5%). The most common etiology for women and men was breast (102, 30.8%) and lung (67, 36.2%), respectively. More common origins involving peritoneal fluid were gastrointestinal (158, 35.8%) and gynecologic (156, 35.4%) tracts, and breast (46, 10.4%). The most common etiology for women and men was Mullerian (156, 55.5%) and gastrointestinal tract (94, 68.6%), respectively. Most common origins involving the pericardial fluid were breast (20, 37.7%) and lung (17, 29.8%). Breast and lung were the most common etiology for women (20, 57.1%) and men (8, 44.4%), respectively. CONCLUSIONS Breast and lung remain to be the most common origin of both malignant pleural and pericardial effusion for women and men, respectively. The most common origin involving peritoneal effusion is Mullerian for women and gastrointestinal tract for men.

Background\ud The COVID-19 pandemic spurred an abrupt transition away from in-person educational activities. This systematic review investigated the pivot to online learning for nonclinical undergraduate medical education (UGME) activities and explored descriptions of educational offerings deployed, their impact, and lessons learned.\ud \ud Methods\ud The authors systematically searched four online databases and conducted a manual electronic search of MedEdPublish up to December 21, 2020. Two authors independently screened titles, abstracts and full texts, performed data extraction and assessed risk of bias. A third author resolved discrepancies. Findings were reported in accordance with the STORIES (STructured apprOach to the Reporting in healthcare education of Evidence Synthesis) statement and BEME guidance.\ud \ud Results\ud Fifty-six articles were included. The majority (n = 41) described the rapid transition of existing offerings to online formats, whereas fewer (n = 15) described novel activities. The majority (n = 27) included a combination of synchronous and asynchronous components. Didactics (n = 40) and small groups (n = 26) were the most common instructional methods. Teachers largely integrated technology to replace and amplify rather than transform learning, though learner engagement was often interactive. Thematic analysis revealed unique challenges of online learning, as well as exemplary practices. The quality of study designs and reporting was modest, with underpinning theory at highest risk of bias. Virtually all studies (n = 54) assessed reaction/satisfaction, fewer than half (n = 23) assessed changes in attitudes, knowledge or skills, and none assessed behavioral, organizational or patient outcomes.\ud \ud Conclusions\ud UGME educators successfully transitioned face-to-face instructional methods online and implemented novel solutions during the COVID-19 pandemic. Although technology’s potential to transform teaching is not yet fully realized, the use of synchronous and asynchronous formats encouraged virtual engagement, while offering flexible, self-directed learning. As we transition from emergency remote learning to a post-pandemic world, educators must underpin new developments with theory, report additional outcomes and provide details that support replication.

Adequate tumor yield in core-needle biopsy (CNB) specimens is essential in lung cancer for accurate histological diagnosis, molecular testing for therapeutic decision-making, and tumor biobanking for research. Insufficient tumor sampling in CNB is common, primarily due to inadvertent sampling of tumor-associated fibrosis or atelectatic lung, leading to repeat procedures and delayed diagnosis. Currently, there is no method for rapid, non-destructive intraprocedural assessment of CNBs. Polarization-sensitive optical coherence tomography (PS-OCT) is a high-resolution, volumetric imaging technique that has the potential to meet this clinical need. PS-OCT detects endogenous tissue properties, including birefringence from collagen, and degree of polarization uniformity (DOPU) indicative of tissue depolarization. Here, PS-OCT birefringence and DOPU measurements were used to quantify the amount of tumor, fibrosis, and normal lung parenchyma in 42 fresh, intact lung CNB specimens. PS-OCT results were compared to and validated against matched histology in a blinded assessment. Linear regression analysis showed strong correlations between PS-OCT and matched histology for quantification of tumors, fibrosis, and normal lung parenchyma in CNBs. PS-OCT distinguished CNBs with low tumor content from those with higher tumor content with high sensitivity and specificity. This study demonstrates the potential of PS-OCT as a method for rapid, non-destructive, label-free intra-procedural tumor yield assessment.

Background Afirma gene expression classifier (GEC) is an adjunct to thyroid fine needle aspiration shown to improve pre-operative risk assessment and reduce unnecessary surgery of indeterminate thyroid nodules. Genomic sequencing classifier (GSC) is a newer version aiming to improve specificity and positive predictive value (PPV) of Afirma testing. There are limited studies comparing GSC vs GEC. This study was undertaken to compare these classifiers in terms of diagnostic performance and effect on clinical management of indeterminate thyroid nodules. Methods The study cohort consisted of patients with thyroid nodules that had a recurrent cytologic diagnosis of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) and were tested by either GEC or GSC. Patient demographics, nodule size, and clinical follow-up were recorded. Benign call rate (BCR) of Afirma testing, rate of subsequent surgery (RSS), rate of histology-confirmed malignancy (RHM), as well as diagnostic sensitivity, specificity, PPV, negative predicative value (NPV), and accuracy were calculated and compared between GSC and GEC cohorts. Results Among 264 AUS/FLUS thyroid nodules, 127 and 137 were tested with GEC and GSC, respectively. Compared to GEC, GSC demonstrated increased BCR (77.3% vs 52%), decreased RSS (31.4% vs 51.2%), greater RHM (29% vs 9.8%) associated with a suspicious Afirma result, as well as improved specificity (82.8% vs 54.5%), PPV (29% vs 9.8%), and diagnostic accuracy (83.9% vs 56.7%), while maintaining high sensitivity and NPV. Conclusion Afirma GSC substantially improved BCR, RSS, RHM, and diagnostic performance, enhancing appropriate triage and thereby helped avoid unnecessary surgery in AUS/FLUS thyroid nodules.

BACKGROUND Few studies focus on pediatric thyroid nodules categorized under indeterminate diagnostic categories. The current study was conducted to assess the risk of malignancy of indeterminate pediatric thyroid nodules. METHODS A search of the institutional electronic pathology database from 01/2011 to 09/2018 was performed to identify pediatric (

Five percent of urothelial carcinoma occurs in the upper urinary tract (UUT), a challenging location to biopsy. We aim to evaluate concordance between biopsy, cytology, and resection specimens in a large upper tract urothelial carcinoma (UTUC) cohort. One hundred seventeen UTUC resections with UUT biopsy and/or cytology specimens from 2000 to 2016 were retrieved; pathologic material was re-reviewed, evaluated for concordance, and correlated with clinical information. Fourteen percent of preoperative biopsies, including 8 from the renal pelvis and 6 from the ureter, lacked neoplastic diagnoses. Seventy-seven percent of diagnostic biopsies included subepithelial tissue; 11% demonstrated reclassification of grade and 30% demonstrated reclassification of invasion status. Twenty-six percent of renal pelvis UTUC and 36% of ureter UTUC were invasive only on resection. Of 18 UTUCs reclassified from noninvasive high-grade papillary urothelial carcinoma to invasive high-grade papillary urothelial carcinoma, 39% had prior radical cystectomy (versus 8% invasive UTUC and 11% noninvasive UTUC with concordant biopsies). Most high-grade UTUC (88%) and some low-grade UTUC (58%) resections had abnormal cytology results. Biopsy-resection pairs with concordant invasion status and pairs with discordant invasion status showed similar rates of recurrence (38% versus 38%) and metastasis (25% versus 27%). Fourteen percent of UUT biopsies lacked diagnostic neoplastic material. Grade concordance between biopsy and resection was high (89%), but 30% of cases showed invasion only on resection. Subepithelial tissue was less commonly present in ureter biopsies, particularly from the midureter or proximal ureter. UTUC in patients with prior cystectomy were more likely to show invasion on resection but not biopsy.

Background The Paris System (TPS) introduced diagnostic criteria for urine cytology to improve reproducibility among pathologists. Thus far, most cytology studies have investigated application of TPS on lower urinary tract specimens. Also, it is unclear which cytologic features are most predictive of malignancy, particularly in the upper urinary tract. We evaluate concordance rates of preoperative upper urinary tract cytology specimens before and after application of TPS criteria with surgical resections and assess cytologic features associated with malignancy. Design 54 resections with high- and low-grade urothelial carcinoma (HGUC, LGUC) from 2000-2016 with available preoperative cytology (n = 61) were identified. Cytology was re-reviewed to evaluate cytologic features and provide diagnoses before and after TPS implementation. Results The most common cytologic features associated with HGUC were N:C ratios ≥0.7 (88%), hyperchromasia (83%), coarse chromatin distribution (67%), and nuclear pleomorphism in cell clusters (65%). Application of TPS criteria resulted in 10 diagnostic downgrades and 6 diagnostic upgrades. After TPS criteria were applied, the sensitivity of a positive diagnosis decreased from 29% to 19%. The morphologic feature most consistently associated with a downgrade from positive to suspicious was a lack of marked nuclear contour irregularities in atypical urothelial cells. Conclusion Using strict TPS criteria in upper urinary tract cytology specimens may decrease the frequency of positive diagnoses with a concurrent increase in suspicious diagnoses. These findings may indicate that different morphologic features, particularly markedly irregular nuclear contours, may have different predictive values for HGUC in upper urinary tract cytology specimens compared with those from the lower urinary tract.

Copyright © 2021 Informa UK Limited, trading as Taylor & Francis Group, Background: COVID-19 has fundamentally altered how education is delivered. Gordon et al. previously conducted a review of medical education developments in response to COVID-19; however, the field has rapidly evolved in the ensuing months. This scoping review aims to map the extent, range and nature of subsequent developments, summarizing the expanding evidence base and identifying areas for future research. Methods: The authors followed the five stages of a scoping review outlined by Arskey and O'Malley. Four online databases and MedEdPublish were searched. Two authors independently screened titles, abstracts and full texts. Included articles described developments in medical education deployed in response to COVID-19 and reported outcomes. Data extraction was completed by two authors and synthesized into a variety of maps and charts. Results: One hundred twenty-seven articles were included: 104 were from North America, Asia and Europe; 51 were undergraduate, 41 graduate, 22 continuing medical education, and 13 mixed; 35 were implemented by universities, 75 by academic hospitals, and 17 by organizations or collaborations. The focus of developments included pivoting to online learning (n = 58), simulation (n = 24), assessment (n = 11), well-being (n = 8), telehealth (n = 5), clinical service reconfigurations (n = 4), interviews (n = 4), service provision (n = 2), faculty development (n = 2) and other (n = 9). The most common Kirkpatrick outcome reported was Level 1, however, a number of studies reported 2a or 2b. A few described Levels 3, 4a, 4b or other outcomes (e.g. quality improvement). Conclusions: This scoping review mapped the available literature on developments in medical education in response to COVID-19, summarizing developments and outcomes to serve as a guide for future work. The review highlighted areas of relative strength, as well as several gaps. Numerous articles have been written about remote learning and simulation and these areas are ripe for full systematic reviews. Telehealth, interviews and faculty development were lacking and need urgent attention.

Strategies that interfere with the binding of the receptor programmed cell death protein-1 (PD-1) to programmed death ligand-1 (PD-L1) have shown marked efficacy against many advanced cancers, including those that are negative for PD-L1. Precisely why patients with PD-L1 negative tumors respond to PD-1/PD-L1 checkpoint inhibition remains unclear. Here, we show that platelet-derived PD-L1 regulates the growth of PD-L1 negative tumors and that interference with platelet binding to PD-L1 negative cancer cells promotes T cell-induced cancer cytotoxicity. These results suggest that the successful outcomes of PD-L1 based therapies in patients with PD-L1 negative tumors may be explained, in part, by the presence of intra-tumoral platelets. Altogether, our findings demonstrate the impact of non-cancer/non-immune cell sources of PD-L1 in the tumor microenvironment in the promotion of cancer cell immune evasion. Our study also provides a compelling rationale for future testing of PD-L1 checkpoint inhibitor therapies in combination with antiplatelet agents, in patients with PD-L1 negative tumors.

Introduction The rate of malignancy (ROM) in thyroid fine needle aspirations (FNA) classified under "atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), including Hurthle cell type (HLUS)" category of The Bethesda system for reporting thyroid cytopathology (TBSRTC) in literature is highly variable. The 2018 TBSRTC was updated to note a preferred categorization of AUS cases into subcategories. This study evaluates the impact of AUS subclassification on rates of neoplasia (RON), rates of malignancy (ROM), and cytopathologist (CP) concordance. Methods 93 thyroid FNAs previously diagnosed as FLUS or HLUS from January 1, 2013 to December 31, 2014 with subsequent surgical resection were identified. Four CPs reclassified these cases using TBSRTC AUS subcategories of follicular cells with architectural and/or cytologic atypia, predominantly Hurthle cells, and atypical lymphocytes. RON and ROM were calculated for each diagnostic subcategory for each CP. Results The original RON and ROM for FLUS cases were 31.4% and 15.1% and were 77.8% and 22.2% for HLUS cases. 10.8% of cases showed diagnostic concordance amongst the four CPs. The most frequently utilized subcategory was architectural atypia. RON ranges for architectural atypia, cytologic atypia, architectural and cytologic atypia, and predominantly Hurthle cells were 28.1% to 35.7%, 0% to 33.3%, 35.3% to 66.7%, and 57.1% to 87.5%. The range of ROM was 13.9% to 16.7%, 0% to 33%, 0% to 42.9%, and 0% to 25%, respectively. Conclusion RON for AUS predominantly Hurthle cells subcategory was higher than previously reported, which may indicate use for tailored patient management pathways. AUS subclassification can result in significant interobserver variability. Therefore, institutions may consider consensus/quality control sessions to optimize diagnostic concordance.

Both fine-needle aspiration (FNA) and core needle biopsy (CNB) are widely used to obtain liver biopsy specimens, particularly from mass lesions. However, the advantages and disadvantages of FNA versus CNB in terms of appropriate use, diagnostic yield, complications, and whether or not specimens should be handled by cytopathologists, surgical pathologists, or both remain subjects of controversy. This review addresses the issues of sample adequacy, appropriate use of each technique and complications, and challenges regarding the diagnosis of both hepatic tumors and non-neoplastic liver disease.

Introduction Low-grade squamous intraepithelial lesion (LSIL) Papanicolaou test is associated with moderate risk of high-grade squamous intraepithelial lesion (HSIL) at colposcopic biopsy. High-risk human papillomavirus (hrHPV) cotesting risk stratifies patients with LSIL Papanicolaou test, with higher rates of HSIL for those hrHPV+. hrHPV genotyping is not considered in current LSIL management algorithms. Materials and methods We performed a 2-year retrospective review of LSIL Papanicolaou tests in patients 25 to 65 years old to assess rates of follow-up and HSIL at biopsy. Patient age, hrHPV cotest and genotype results, prior screening results, and follow-up testing for 3 years were recorded. Results A total of 71.5% (376 of 526) of patients had at least 1 follow-up colposcopic biopsy; 18% had HSIL on follow-up, including 20% of hrHPV+ and 12% of hrHPV−. HSIL at biopsy was most common when HPV16/18 was present (32%) and when multiple subtypes were detected (46%) versus when non-16, non-18 hrHPV alone was present (16%) or hrHPV was negative (12%). Of those hrHPV−, 5 of 22 (23%) with a prior screening abnormality had HSIL versus 1 of 27 (4%) for those without prior abnormalities. Follow-up occurred more commonly for hrHPV+ cotests (82%) than hrHPV− cotests (54%). No differences in follow-up rate based on hrHPV genotyping was seen. Conclusions The highest HSIL rates were seen when HPV16/18 was present (32%). HSIL rates were similar for those hrHPV− (12%) and non-16, non-18 hrHPV+ (16%). Follow-up was more common for those hrHPV+, but genotype results did not impact follow-up rates. Past screening results may impact risk of HSIL for hrHPV− cases.

Ocular cytology specimens are relatively uncommon, adding to the difficulty of their evaluation by cytopathologists. While melanomas account for a majority of primary intraocular pigmented lesions, other diagnostic considerations must be included in the differential. This brief report highlights a case of a pigmented ocular lesion in a 24-year-old man and key morphologic, immunohistochemical, and clinical differences between melanoma, melanocytoma, choroidal nevus, and retinal pigment epithelium (RPE) adenoma.

Aims Renal cell carcinomas are relatively rare in children and young adults. While well characterised in adults, the morphological and molecular characterisation of these tumours in young patients is relatively lacking. The objective of this study was to explore the spectrum of renal cell carcinoma (RCC) subtypes in children and young adults and to determine their clinico-pathological, immunohistochemical and molecular characteristics by evaluating a large retrospective cohort of renal cell carcinoma patients age 30 years or younger. Methods and results Sixty-eight cases with confirmed diagnosis of renal cell carcinoma at age 30 years or younger were identified at our institution. Clear cell carcinoma accounted for the most common subtype seen in this age group. Translocation renal cell carcinoma and rare familial syndrome subtypes such as succinate dehydrogenase deficient renal cell carcinoma and tuberous sclerosis complex-associated renal cell carcinoma were found relatively more frequently in this cohort. Despite applying the 2016 WHO classification criteria, a high proportion of the tumours in our series remained unclassified. Conclusions Our results suggest that renal cell carcinoma in children and young adults is a relatively rare disease that shares many histological similarities to renal cell carcinoma occurring in adults and yet demonstrate some unique clinical-pathological differences. Microphthalmia-associated transcription (MiT) family translocation RCC and rare familial syndrome subtypes are relatively more frequent in the paediatric and adolescent age groups than in adults. Clear cell RCC still accounted for the most common subtype seen in this age group. MiT family translocation RCC patients presented with advanced stage disease and had poor clinical outcomes. The large and heterogeneous subgroup of unclassified renal cell carcinoma contains phenotypically distinct tumours with further potential for future subcategories in the renal cell carcinoma classification.

Metastases to the thyroid are uncommon [

Telomerase reverse transcriptase (TERT) is a ribonucleoprotein involved in maintaining the length of telomeres. In the absence of TERT expression, differentiated cells can only divide a finite number of times before undergoing cellular senescence – often referred to as the Hayflick limit. Mutations within the promoter region of TERT that create consensus binding sequences for ETS family transcription factors are a common mechanism by which neoplastic cells increase TERT expression and overcome this limit [1]. TERT promoter mutations are common in many cancer types including 60-80% of urothelial carcinomas (UC) [2,3]. Given the high frequency of these mutations in UC and absence of these mutations in non-neoplastic/benign mimics of UC [4], TERT promoter mutations may serve as potential biomarker for monitoring patients with a history of malignancy. This article is protected by copyright. All rights reserved.

The frequency of co-occurrence between germ cell tumor (GCT) components in non-seminomatous germ cell tumor (NSGCT) orchiectomy specimens and their correlation with histologic findings in subsequent retroperitoneal lymph node dissection (RPLND) specimens have not been well characterized. The objective of the study was to report the first detailed clinicopathologic analysis of NSGCT orchiectomy and RPLND samples to determine the likelihood and agreement of the co-occurrence of GCT components. A total of 118 consecutive patients with NSGCT treated between 1988 and 2012 who underwent both orchiectomy and RPLND at a single academic tertiary care center were analyzed. Statistical analysis of co-occurrence likelihood and agreement of GCT components was performed, both within and between orchiectomy and RPLND specimens. Embryonal carcinoma was the most frequent component present in orchiectomy specimens, and there were multiple significant associations between orchiectomy GCT components; seminoma occurred less frequently with embryonal carcinoma (OR 0.29 [95% confidence interval (CI) 0.11–0.75]; p

BACKGROUND It is not uncommon to encounter challenges in the immunohistochemical confirmation of metastatic breast cancer given the limited sensitivities of mammaglobin and gross cystic disease fluid protein 15 (GCDFP-15/BRST-2) and the significant proportion of triple-negative breast carcinomas (ie, tumors that are negative for estrogen receptor [ER], and progesterone receptor [PgR], and human epidermal growth factor 2 [HER2]). GATA binding protein 3 (GATA3) has emerged as a potentially useful immunohistochemical adjunct during the evaluation of metastatic breast carcinomas in cytology specimens. The objective of the current study was to examine GATA3 expression in the context of malignant effusions secondary to both mammary and extramammary malignancies. METHODS In total, 306 malignant effusions (from 62 metastatic breast carcinomas and 244 extramammary malignancies) were examined using GATA3 immunohistochemistry. Effusions with metastatic breast carcinoma were also examined using immunohistochemistry for additional breast markers (ER, PgR, HER2, mammaglobin, and GCDFP-15/BRST-2). RESULTS GATA3 immunohistochemistry highlighted the tumor cells in 58 of the 62 samples (93.5%) from patients with metastatic breast carcinoma, which was higher than the observed sensitivity of immunohistochemistry for ER (63.8%), PgR (41.4%), HER2 (15.5%), mammaglobin (22.4%), and GCDFP-15/BRST-2 (5.2%). GATA3 expression also was observed in a subset of malignant effusions secondary to extramammary primaries, specifically, in 28 of 244 specimens (11.5%). CONCLUSIONS GATA3 is a highly sensitive marker for the detection of metastatic breast carcinomas in effusion specimens. However, this marker is not entirely specific for malignancies of breast origin. Thus, GATA3 should be used in conjunction with additional immunohistochemical markers during the cytologic evaluation of malignant effusions. Cancer (Cancer Cytopathol) 2015;123:576-81. © 2015 American Cancer Society.

Introduction Fine-needle aspirations (FNAs) of palpable masses are often performed by cytopathologists without ultrasound (US) guidance. Nonetheless, variations in the actual depth of palpable masses lead to occasional challenges. US guidance allows cytopathologists to visualize the mass and guide needle placement. This study retrospectively addressed the utility of US by comparing FNAs performed by cytopathologists on palpable masses with and without US guidance. Materials and methods Cytopathologist-performed FNAs with and without US guidance from March 1, 2013 to July 1, 2014 were identified. The number of passes, location of lesions, and interpretations were recorded. Available slides were reviewed to determine the proportion of passes that contained diagnostic cellular material and cases in which diagnostic material was present on the first needle pass. Results In this study, 134 palpation-guided FNAs and 118 US-guided FNAs were analyzed. The percentage of nondiagnostic cases was significantly lower for US-guided FNAs (2.5%) than for palpation-guided FNAs (12.7%; P = 0.004). The average number of needle passes was significantly lower for US-guided FNAs (2.9) than for palpation-guided FNAs (3.6; P = 0.0002). Twenty-two of 118 of US-guided FNAs (18.6%) and 6 of 134 palpation-guided FNAs (4.5%) were completed after only a single pass ( P = 0.0008). The percentage of passes with diagnostic material was significantly higher for US-guided FNAs (73.6% versus 60%; P = 0.0002). Conclusions For palpable masses, US-guidance adds value to cytopathologists in obtaining diagnostic cellular material more often on the first pass and with fewer passes overall than by palpation alone. This has a potentially beneficial impact on patient care owing to the increased precision and accuracy of needle guidance with ultrasonography.

Objective: Malignant effusions due to papillary thyroid carcinoma (PTC) are rare, but portend a poor prognosis. PTC metastases, although rare, most frequently occur in the lungs and bone. Therefore, differentiating thyroid etiology of malignant effusions from other sites becomes clinically significant in patient management. This study examines morphologic and immunocytochemical findings in 5 cases of malignant effusions with PTC involvement. Study Design: The electronic database at the University of Michigan was searched from January 1, 1995 to December 31, 2014 for malignant pleural effusions with PTC involvement. Clinicopathologic data were obtained from electronic medical records. Cytologic slides were reviewed. Results: Five cases of malignant effusions due to PTC were identified. Characteristic cytologic features of PTC, including ovoid nuclei, irregular nuclear contours, and psammomatous calcifications, were seen. However, the predominant cytologic feature observed was moderate amounts of delicate to vacuolated cytoplasm within the tumor cells. A review of immunocytochemistry demonstrated that all 5 cases showed patchy to diffuse TTF-1 positivity and diffuse positivity for Pax-8. Thyroglobulin only showed focal to patchy positivity in 3 of 5 cases. Conclusion: Given the morphologic features found in our case series, an immunocytochemical workup for the evaluation of involvement of an effusion by a thyroid primary is crucial for accurate diagnosis and appropriate clinical treatment.

Background Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC) has recently been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Implementation of the new terminology may alter the implied risk of malignancy (ROM) across the six categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Methods The study cohort consisted of thyroid fine needle aspiration (FNA) cases which were assessed between January 2011 and June 2016 and led to surgical resections. For each case, patient demographics as well as cytologic and corresponding histologic diagnoses were recorded. The surgical specimens diagnosed as follicular variant of PTC (FVPTC) were re-reviewed to identify cases that met the diagnostic criteria for NIFTP. The ROM with and without exclusion of NIFTP from malignant categorization, as well as the relative change in ROM were calculated for individual categories of TBSRTC. Results A total of 908 FNA cases with surgical follow-up were retrieved and PTC was identified in 252 (27.8%) surgical specimens. Twenty-nine of 252 (11.5%) were initially classified as FVPTC, of which 17 (6.7%) were reclassified as NIFTP. The cytologic interpretations for the majority of NIFTP cases were atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS, n = 8) or follicular neoplasm/suspicious for neoplasm/(FN/SFN, n = 4). Excluding NIFTP from malignant categorization resulted in a relative decrease in ROM in AUS/FLUS (25.8%) and FN/SFN (22.3%) categories. Conclusion Our institutional data demonstrates that eliminating NIFTP from malignant categorization may result in a reduction of the implied ROM for AUS/FLUS and FN/SFN categories.

Spindle cell lesions of the gastrointestinal tract are relatively uncommon compared with the frequency of their epithelial counterparts. Although gastrointestinal stromal tumors and leiomyomas are the most commonly encountered spindle cell lesions in the stomach and esophagus, respectively, there are other less common diagnostic entities that should be considered for accurate diagnoses as well as appropriate patient treatment and clinical follow-up. Given the morphologic overlap of low-grade spindle cell lesions on cytologic preparations, ancillary studies play a key role in differentiating these lesions from one another.

IgG4-related disease, a newly established multisystemic disease can affect virtually every organ. Histologically, it is characterized by the presence of a dense lymphoplasmacytic infiltrate, storiform-type fibrosis, and obliterative phlebitis. The disease shows elevated serum and tissue IgG4. The pancreas and hepatobiliary tract are involved far more commonly than the tubular gut. This review summarizes the clinical and pathologic features of the gastrointestinal manifestations of IgG4-related disease and discusses the wide spectrum of diseases that this entity may mimic.

A premature newborn boy was admitted to the hospital because of respiratory distress. On his sixth day of life, sudden clinical deterioration and multiorgan system failure developed, and he died on his seventh day. An autopsy was performed.

Metastases to the thyroid are uncommon [0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37-year-old female with a history of metastatic ductal carcinoma of the breast (modified Bloom-Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly-shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA-3 (+), ER (+), PAX-8 (-), and TTF-1 (-) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA-3, hormonal marker(s), PAX-8, and TTF-1, may be useful in some cases. GATA-3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530-534. © 2016 Wiley Periodicals, Inc.

Anterior-predominant prostate cancer (APC) is an incompletely understood entity which can be difficult to sample via transrectal biopsy. Seemingly favorable biopsy results may belie the potential aggressiveness of these tumors. Here, we attempt to characterize APC by retrospectively examining the clinicopathologic features of APC at radical prostatectomy and comparing our findings with prior biopsy information. We found that 17.4 % of patients in our study had APC. APC demonstrated a significantly lower (P value < 0.05) Gleason score (GS) and pathologic stage than non-APC tumors, including the absence of seminal vesicle invasion by APC. A subset (5.6 %) of APC consisted of high-grade tumors (GS ≥ 8), and these tumors were more often detected on transperineal saturation biopsy than non-transperineal saturation (i.e., transrectal ultrasound guided) biopsy strategies. Four patients (7 %) without transperineal saturation biopsy exhibited a significantly worse GS at RP than biopsy, compared to five patients (36 %) with transperineal saturation biopsy. Our findings corroborate the difficulty in detecting APC and suggest that APC is not a uniform disease with a wholly indolent phenotype. Dedicated long-term outcome data are needed in these patients. Additionally, alternative pathologic staging parameters may be necessary.