Search

Telecytology offers a suitable solution to the cost and time efficiency questions on rapid onsite evaluation (ROSE). An increasing number of institutions are adopting new telecytology systems to meet the increasing ROSE requests, although there is no agreement on the details of how a telecytology validation study needs to be conducted. We propose a standardized approach for telecytology validation studies that could be done in a variety of practices. Consecutive cases from 6 months prior were chosen to reflect a case mix comparable to real life. A fellow assessed the slides at the ROSE site while 6 cytopathology faculty convened in a conference room with a television screen, and noted the adequacy, diagnostic category, and specific diagnoses. All participants were blinded to the original adequacy assessment and final diagnoses. For each case, evaluation time and the slides counts were noted. Fine-needle aspiration specimens from 52 patients were included in the study. Of these, 13 cases were used in the first "test" session. The adequacy concordance rates ranged between 92.3% and 100%, with an overall concordance rate of 94.8%. The diagnostic category concordance rates ranged between 90.3% and 95.5%, with an overall concordance rate of 91.9%. The specific diagnosis concordance rates ranged between 84.6% and 92.9%, with an overall concordance rate of 88.1%. Validation of telecytology requires a standardized approach just like any other new technology. In this study, we propose an efficient and accurate method for cytopathology departments of various case volumes to conduct telecytology validation studies. • A standardized approach to telecytology validation studies is presented. • A retrospective case mix comparable to real life was included after a 6-month wash-out period. • All cytopathologists were exposed to the same images at the same time, using a dynamic digital pathology tool. • The study was conducted in 2 steps where a small number of cases were used for the "training" phase, and a larger number of cases were used for "validation". • Overall concordance rate among 4 cytopathologists was 94.8% for adequacy, not crediting any discrepancies. • Overall concordance rate among 4 cytopathologists was 91.9% for diagnostic category, not crediting any discrepancies. [ABSTRACT FROM AUTHOR]

According to the Clinical Laboratory Improvement Amendments 1988 regulations, 5-year retrospective review (5YRR) of normal Papanicolaou tests in patients with a newly diagnosed high grade squamous intraepithelial lesion or above (HSIL+) is mandatory. Since this mandate has been in place, a multitude of changes have taken place in the screening and management guidelines of cervical cancer. The aim of this study is to assess the role of this mandate in our laboratory and to investigate the lessons learned. The cytopathology electronic database and institutional quality assurance records at Loyola University Medical Center were searched from January 2009 to December 2019 to identify all Papanicolaou tests diagnosed as new "HSIL and above" (HSIL+). Major discrepancy (2+) was defined as initial negative diagnosis changed to HSIL+. A total of 153,083 Papanicolaou tests were performed during this period; out of these, 1452 (0.94%) were diagnosed as HSIL+. A total of 695 HSIL+ Papanicolaou tests had a negative prior Papanicolaou and in 615 of 695 there was agreement with the initial negative diagnosis. In 61 Papanicolaou tests, the initial diagnosis was changed from negative and they were reclassified on review as 3 HSIL, 9 ASC-H, 7 AGC, and 42 ASCUS or LSIL. Major discrepancy rate was calculated as 3 of 695 (0.43%). None required an amended report. It is important to revisit the 5YRR as a method of implementing the quality indicators in gynecologic cytology so that the process retains its value without overburdening cytology laboratories and personnel. • Five year retrospective review (5YRR) is an integral part of gynecologic cytology quality assurance practices as mandated by CLIA and this requirement has remained largely unchanged for the last 3 decades. • Since this mandate has been in place, a multitude of changes have taken place in the screening and management guidelines of cervical cancer, including the latest 2019 ASCCP guidelines, availability of HPV vaccination, the utilization of HPV cotesting, and primary HPV testing. • The aim of this study is to assess the role of this mandate in our laboratory and to investigate the lessons learned. • We retrospectively searched for cases diagnosed as HSIL and above (HSIL+). The prior negative Papanicolaou tests within previous 5 years for the same patients were re-reviewed where available. • Major discrepancy was defined as a prior negative Papanicolaou test that was reclassified HSIL+ on review. • Out of 153,083 Papanicolaou tests 1452 were diagnosed as HSIL+. Out of these, 695 HSIL+ Papanicolaou tests had a negative prior Papanicolaou result. • On review, 61 Papanicolaou tests originally reported as negative were reclassified as follows: 3 HSIL, 9 ASC-H, 7 AGC, and 42 ASCUS or LSIL. Major discrepancy rate was calculated as 3 of 695 (0.43%). • None required an amended report. • The time, money, and the resources that are needed to perform these reviews could be significantly decreased without sacrificing the benefits of the quality assurance practices. • With the advent of newer testing modalities, clinical guidelines, and management strategies in cervical cancer screening, we believe it is time now to revisit the 5YRR rule. [ABSTRACT FROM AUTHOR]

The Paris System (TPS) for Reporting Urinary Cytology (UCyto) was published in 2016, but to date, no study addressing the unsatisfactory (UNSAT) category has been published. We aimed to identify the negative predictive value (NPV) for UNSAT UCyto after the implementation of TPS at our institution. For the period from January 1, 2017, to December 31, 2019, we identified all cases with UNSAT diagnosis on UCyto specimens and available cytologic and/or surgical pathology follow-up within 6 months from the UNSAT diagnosis. Cases were deemed true negative (TN) if the follow-up was "negative for high-grade urothelial carcinoma" (NHGUC). Information regarding previous medical history, clinical indications, and specimen type were tabulated and analyzed. From 6348 UCyto specimens, there were 230 (3.6%) UNSAT diagnoses made on 209 patients (112 [53.6%] men and 97 [46.4%] women) with a median age of 64 years. Of these, 116 UCyto specimens from 106 patients, which had cytologic and/or surgical pathology follow-up within 6 months, were further studied. Most UNSAT UCyto specimens were bladder washing/barbotage (BW/BB), and the most common indication for UCyto was cancer surveillance. The main cause of UNSAT UCyto was low cellularity. There were 5 false-negative (FN) results for high-grade urothelial carcinoma (HGUC), which corresponds to an overall NPV of 84.4%. NPV was highest for patients with UCyto for hematuria, and for patients with BW/BB as UCyto specimen type. Our results show that UNSAT diagnoses have a lower NPV than that typical of NHGUC diagnoses, and should be managed accordingly. • In 2016, The Paris System (TPS) for Reporting Urinary Cytology (UCyto) was published and still there have not been any publications focusing on the outcome, risk of malignancy, or negative predictive value (NPV) of the unsatisfactory (UNSAT) category. We aimed to identtify the outcome and the NPV for UNSAT after the implementation of TPS at our institution. • The cases were deemed true negative (TN) if the 6 month follow up was negative. The urine specimen was considered "UNSAT" when it did not meet the adequacy criteria per TPS. • There were 230 (3.6%) UNSAT specimens from a total of 6348 UCyto specimens. Of these, 116 UCyto specimens from 106 patients, which had cytologic and/or surgical pathology follow-up within 6-months, were further studied. Only 50.7 % (106 of 209) of the patients had a follow-up. • An overall NPV of 84.4% was calculated for UNSAT UCyto. When this was compared with previous published worked for "negative" UCyto, it showed that the UNSAT UCyto according to TPS were lower for all indications and specimen types. • UNSAT UCyto is not equivalent to other UCyto categories and does not represent a "true negative" result. All other parameters, like history, clinical presentation, cystoscopy findings, and any prior UCyto or biopsy result, should be considered and patients managed accordingly. [ABSTRACT FROM AUTHOR]

The Paris System for Reporting Urinary Cytology (TPS) was developed for standardization purposes and it placed an emphasis on screening for high-grade urothelial carcinoma (HGUC). Since then, it has shown to reduce atypia rates and better correlate with surgical specimens. The aim of this study was to calculate the negative predictive value (NPV) of urinary cytology for detecting HGUC using TPS and compare these data to our recently published pre-TPS cohort. As a screening test, it is imperative that TPS has a high NPV. A search of our institution's pathology database for the term "negative for HGUC" from January 1, 2016, to December 31, 2017, was conducted. A true negative was defined as a patient with at least 1 subsequent negative urine cytology/surgical biopsy specimen or the patient being clinically negative for 6 months. NPV rates were calculated based on the data obtained. The cohort consisted of 2960 urine cytology specimens from 1894 patients. A total of 99 false negatives were identified, generating a NPV of 96.7% (2861/2960). This NPV is identical to our previously published pre-TPS cohort (years 2012-2013; NPV: 96.7%). The clinical indication most effected NPV, with a history of urothelial carcinoma with a NPV of 93.9% followed by hematuria at 98.9%. The atypia rate in years 2012-2013 was 8.2% and in 2016-2017 it was 5.7% (P < 0.001). We demonstrate that TPS did not alter the NPV for detecting HGUC compared to our pre-TPS cohort. We believe that TPS is an effective reporting system for screening HGUC in urinary cytology. • The overall negative predictive value (NPV) was 96.7% (same as pre-TPS). • Patient with a history of urothelial carcin.oma had a NPV of 93.9% followed by hematuria at 98.9% • Voided urine had the highest NPV of 98.9%, followed by washing at 96.6% and brushing 81.3%. • The atypia rate in years 2012-2013 was 8.2% and in 2016-2017 it was 5.7% (P < 0.001). [ABSTRACT FROM AUTHOR]

The introduction of a new generation of core needle biopsies (CNBs) for endoscopic procedures has prompted reconsideration of the role of cytopathologists in the handling of small biopsies. The American Society of Cytopathology (ASC) has therefore conducted a survey with the intention of elucidating current practices regarding the handling of small CNBs. The membership of the ASC was invited by email to participate in an online survey over a 2-month period. The survey consisted of 20 multiple choice questions with 2-8 possible responses per question. Of 2651 members contacted by e-mail, 282 (10.6%) responded to the survey questions, including 196 pathologists (69.5%) and 86 cytotechnologists (30.5%). Of these, 265 respondents were from the US/Canada (94.0%), with 156 from academic institutions (58.9%) and 109 from non-academic practices (41.1%); 17 were from other countries (6.0%). In 18.8% of all practices, cytopathologists sign out >90% of small CNBs from endoscopic and radiologically guided procedures; in 36.5% of practices >90% are signed out by surgical pathologists; the remainder have such cases divided more evenly between cytopathologists and surgical pathologists. Responses show that 78.0% of all respondents are interested in signing out more small biopsies in the future, and 80.5% desire increased small biopsy-related resources from the ASC. The survey responses indicate that practices currently vary widely across institutions. Most indicated an interest in greater incorporation of small biopsies into the practice of cytopathology. • The introduction of a new generation of core needle biopsies for endoscopic procedures has prompted reconsideration of the role of cytopathologists in the handling of small biopsies. The ASC has therefore conducted a survey with the intention of elucidating current practices and opinions regarding the handling of small biopsies. • The survey found that small core needle biopsies from endoscopic and radiologically guided procedures are currently being distributed to cytopathologists and surgical pathologists in a wide variety of different combinations in the laboratories of the respondents. • There is an approximately even division among laboratories of the respondents regarding the practice of issuing separate or unified reports in instances where both small core needle biopsies and cytology specimens are generated from the same site and same procedure. • The great majority of respondents have an interest in signing out more small biopsies in the future and want the American Society of Cytopathology to provide more education and other support in this area. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) is a pandemic caused by the SARS-CoV-2 virus. The infection has predominantly respiratory transmission and is transmitted through large droplets or aerosols, and less commonly by contact with infected surfaces or fomites. The alarming spread of the infection and the severe clinical disease that it may cause have led to the widespread institution of social distancing measures. Because of repeated exposure to potentially infectious patients and specimens, health care and laboratory personnel are particularly susceptible to contract COVID-19. This review paper provides an assessment of the current state of knowledge about the disease and its pathology, and the potential presence of the virus in cytology specimens. It also discusses the measures that cytology laboratories can take to function during the pandemic, and minimize the risk to their personnel, trainees, and pathologists. In addition, it explores potential means to continue to educate trainees during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Vaping-associated pulmonary injury (VAPI) is a severe respiratory disorder associated with the inhalation of nicotine, tetrahydrocannabinol, cannabidiol, or other active substances through a personal vaporizer ("vaping"). Within 2 months after its description, the disease has reached epidemic proportion, affecting over 2000 people and resulting in a number of fatalities. The substance(s) responsible for the lung injury are still unknown, and the pathophysiology of the disease is still incompletely understood. The manifestations of the disease are protean, and the insidiously starting respiratory, gastrointestinal, and constitutional symptoms may initially resemble a viral flu-like illness. The disease may increase in severity, requiring hospitalization, and in more severe cases, mechanical ventilation. The diagnosis of VAPI currently relies on the identification of pulmonary infiltrates on imaging studies in patients who have used vaping products, after excluding infections and other plausible alternative diagnoses. Because VAPI is currently a diagnosis of exclusion, some authors have suggested the use of lipid-laden macrophages (LLM) as a diagnostic test to confirm the disease. We review the current state of the knowledge about the pathologic basis of VAPI, and the literature on the analytic performance of the LLM test to better understand the potential utility of this test in the diagnosis of VAPI. Our review finds little evidence to suggest the use of LLM in the diagnosis of VAPI, since its underlying pathology is acute lung injury, which is unrelated to LLM, and the frequency of their detection varies greatly in different reported series. [ABSTRACT FROM AUTHOR]

The color of urine, once considered by uroscopists to give the most important clues to the diagnosis, still can provide some diagnostic clues in modern medicine. Pigmented cells are an uncommon and surprising find in urine cytology and can at the same time provide important diagnostic clues or represent a dangerous pitfall. We present a review of the significance of pigmented cells in urine cytology. The presence of intracellular pigment granules; their color, size, shape, and variation in size and shape; as well as their staining reactions with special stains can provide useful diagnostic insight, especially when interpreted in the cytologic context (type of pigmented cell and its degree of atypicality) and patient's clinical context. The main differential diagnosis of cytoplasmic pigmented granules includes hemosiderin, lipofuscin, and melanin, each having a different pathogenesis and significance. The goal of this paper is to describe the morphological, histochemical, and ultrastructural characteristics of the pigments seen in urinary cytology, and to review the benign and malignant conditions associated with them. [ABSTRACT FROM AUTHOR]

Flat urothelial lesions fall into one of four diagnostic categories including urothelial carcinoma in-situ (CIS). There is morphologic overlap between the categories leading to immunohistochemistry (IHC) utilization in difficult cases. The purpose of this study was to examine the frequency, variation and utility of IHC use in bladder biopsy specimens over a 17 year period. A search of "CD44", "p53", and "CK20" keywords was conducted from the pathology files (1/1/2003 to 12/31/2017) on bladder biopsy specimens at our institution. Atypical (AUS), dysplastic (UD) and CIS rates were calculated. A total of 4597 cases were identified. IHC was performed on 345 specimens (7.5%, 345/4597). For cases without IHC (H&E only), the AUS rate was 4.8% (206/4252), UD rate was 9.4% (399/4252), and the CIS rate was 8.4% (359/4252). For IHC cases, the AUS rate was 5.2% (18/345), the UD rate was 8.1% (28/345), and the CIS rate was 11.3% (39/345). There was no statistical difference between the H&E only or IHC rates (p > 0.05). The absolute number IHC orders per year increased until 2011 (60 cases) but drastically declined over the last five years (5 total cases in 2017). The CIS rates have remained relatively constant. We found the AUS, UD and CIS rates were similar regardless of IHC use. Our institution was an early adopter of IHC and it quickly fell out of favor. We agree with the ISUP in that IHC has limited clinical utility for flat urothelial lesions and morphology remains the gold standard. • Examined the frequency and utility of IHC in bladder biopsies over 17 year period. • There were 345 specimens (7.5%, 399/4252) in which IHC was ordered. • Atypical, dysplastic and carcinoma in-situ rates were similar regardless of IHC use. • IHC orders have drastically fallen off in last 5 years (only 5 cases in 2017). [ABSTRACT FROM AUTHOR]

Leydig cell tumors are rare sex cord-stromal tumors that account for less than 1% of all testicular tumors. Less than 10% of these tumors show metastatic malignant behavior. Herein we present a case of metastatic malignant Leydig cell tumor in an iliac lymph node diagnosed on fine-needle aspiration (FNA) in a 70-year-old man. The patient was referred from an outside institution with lymphadenopathy and had a past medical history of lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia and past surgical history of orchiectomy. An iliac lymph node FNA was performed demonstrating large discohesive plasmacytoid cells with indistinct cell borders; abundant and finely granular cytoplasm; round, eccentric nuclei with evenly distributed chromatin; and prominent nucleoli. The tumor cells were positive for inhibin and negative for calretinin and keratin leading to the diagnosis of metastatic malignant Leydig cell tumor. Review of the patient's history and of previous pathologic material, careful evaluation of cytomorphologic features, and the judicious use of immunohistochemistry can allow an accurate diagnosis of metastatic Leydig cell tumor. [ABSTRACT FROM AUTHOR]

Rosai-Dorfman disease (RDD) is a rare usually self-limited non–Langerhans cell histiocytosis of unknown etiology. Nodal and extranodal RDD appear to represent distinct conditions with different molecular alterations and prognosis. They also pose different diagnostic challenges on biopsies and fine-needle aspiration (FNA) cytology. The aim of this study was to report on 3 cases of intra-abdominal RDD and perform an extensive review of the literature on FNA findings of RDD. We reviewed FNA specimens from cases diagnosed histologically or cytologically as RDD during the past 10 years. We searched the PubMed and Google Scholar databases for cases of RDD sampled by FNA. We identified 3 cases of intra-abdominal RDD, involving the kidney, periportal lymph node, and pancreas. FNA of the latter was hypocellular with fibrosis and was nondiagnostic. FNA of the first 2 yielded hypercellular smears that were diagnosed as RDD due to the identification of emperipolesis occurring in large uni- or binucleated histiocytes with large nuclei, fine chromatin, and prominent nucleoli in smears and cell-block sections. Immunohistochemistry showed positive staining for S100 and CD68 and negative staining for CD1a. The large histiocytes with emperipolesis were more difficult to identify histologically and their demonstration required immunohistochemical stains. Our experience and an extensive review of the literature suggest that extranodal RDD can be diagnosed on FNA, and that the recognition of histiocytes with emperipolesis may be less challenging cytologically than histologically. The fibrosis frequently seen in extranodal RDD may lead to nondiagnostic aspirates, however. [ABSTRACT FROM AUTHOR]

Objectives We studied the frequency, inter-pathologist variation, appropriateness and utility of immunohistochemistry (IHC) performed on prostate biopsies (PB) to determine the significance of foci of suspicious glands/atypical small acinar proliferations (ASAP). Methods We calculated the rate of IHC use and diagnostic rate of ASAP and adenocarcinoma in PB from 01/01/2008 to 06/30/2015 for individual pathologists working in a tertiary academic institution, and correlated them with the pathologists' experience, subspecialization and PB volume with the aim of determining the interpathologist variation and appropriateness of use of IHC according to recently published recommendations, and the usefulness of IHC to resolve foci of ASAP as either benign or adenocarcinoma. Results IHC was used in 966/2652 (36.4%, 95% CI 33.4–39.4%) PB cases and 1915 of 16,359 (11.7%, 95% CI 11.2%–12.2%) of PB blocks and allowed definitive diagnosis of either benign or malignant in 75.8% (95% CI 73.9–77.7%) of blocks. By pathologist, IHC use rates varied more than twofold (22.8–50.5%); higher use was found for pathologists with genitourinary pathology specialization, higher PB volume and more experience, and correlated with higher rates of both ASAP and adenocarcinoma diagnoses. The use of IHC stains was considered appropriate in 822/966 (85.1%, 95% CI 82.9–87.4%) cases. Conclusions Despite the fact that the use of IHC stains was considered useful and deemed appropriate in the majority of cases, it showed wide variation between pathologists, suggesting monitoring of IHC use rates may be useful to standardize its use. [ABSTRACT FROM AUTHOR]

Introduction Urinary tract cytology (UTCy) allows the accurate diagnosis of high grade urothelial carcinoma. Rare malignancies characterized by the presence of small cells may be more difficult to recognize, however. The aim of this study was to review our experience with liquid-based (ThinPrep) UTCy specimens showing small atypical cells and characterize their cytomorphology, potential differences from previously reported morphologic features, and discuss their differential diagnostic considerations. Materials and methods Among 18,859 UTCy specimens reviewed during a 13-year period (2001-2012), we identified 13 cases corresponding to surgical pathology specimens diagnosed as small cell carcinoma (6), melanoma (3), lymphoma (3), and leukemic involvement of the urinary tract (1). We recorded the original diagnoses made on these cases and 10 cytomorphologic features that could aid in their diagnosis. Results We identified 13 cases in UTCy of 7 men and 6 women; 11 of which were diagnosed as positive or suspicious for malignancy. In 8 out of 13 cases (62%) the type of malignancy was correctly reported. Of the 10 recorded features, cellular clustering and nuclear molding were seen only in small cell carcinoma, whereas prominent nucleoli and an inflammatory background or diathesis were noted in lymphoma and melanoma cases. Intracellular pigment and multinucleation were recorded in melanoma cases. Conclusion The presence of small atypical cells in liquid-based UTCy should raise the suspicion of underlying malignancy involving the urinary tract. Cell clustering, nuclear molding, and hyperchromasia are helpful hints for the diagnosis of small cell carcinoma and the presence of small atypical cells with prominent nucleoli raises the possibility of lymphoma or melanoma. [ABSTRACT FROM AUTHOR]

The utility of intraoperative frozen sections for determining ureteral and urethral margin status is controversial. In this study, we evaluated the sensitivity and specificity of frozen section diagnosis with the corresponding final tissue diagnosis in a series of 364 patients undergoing radical cystectomy for urothelial carcinoma of the urinary bladder. Multiple definitions of a positive diagnosis were analyzed. We then used clinical follow-up data to determine the effect of various frozen section diagnoses, frozen/permanent section discordance, and surgical margins on overall survival and disease-free survival. Increasing severity of dysplasia was associated with corresponding increases in positive likelihood ratio, with carcinoma displaying the highest positive likelihood ratio (211.43) for an accurate frozen section diagnosis. A diagnosis of carcinoma on frozen section did not affect overall or disease-free survival nor did a positive surgical margin. Frozen/permanent discordance did not show significant associations with overall survival or disease-free survival. The lone variable approaching statistical significance was an association between frozen/permanent discordance of ureteral samples and disease-free survival (hazard ratio, 3.23; P = .07; multivariate Cox proportional hazards model). The results of this study, the first to evaluate the use of different cutoffs for a positive diagnosis and the effects of frozen/permanent discordance, do not support the routine use of intraoperative frozen section during radical cystectomy for urothelial carcinoma. However, subgroups at high risk for positive ureteral margins may benefit from intraoperative frozen section evaluation. [ABSTRACT FROM AUTHOR]

Introduction Adequacy criteria are well established in some areas of cytopathology to prevent false negative diagnoses. To date, no such criteria have been proposed and validated for urinary tract specimens. Our aim was to determine a cellularity cutoff point that significantly affects the sensitivity of detecting high-grade or in situ urothelial carcinoma (HGUC or UCIS) in bladder barbotage/washing specimens. Materials and methods Bladder barbotage specimens collected in liquid-based media were selected. Specimens diagnosed as “positive for HGUC” (with histologic confirmation) composed the study group, with negative cases as control specimens. Samples were serially diluted and ThinPrep slides of decreasing cellularity were made and reviewed for diagnosis and cellularity. In a retrospective validation study, we identified cases with a “negative for malignancy” bladder barbotage/washing and a surgical pathology diagnosis of UCIS or HGUC (ie, false negative cytology). Cellularity was assessed. Results A distinct difference in sensitivity was noted at a cutoff point of 2644 (20 per 10 high-power fields) urothelial cells. Sensitivities increased for atypical or higher (68.3% versus 100%) and HGUC (43.3% versus 88.0%) after application of this cutoff point with high statistical significance ( P = 0.001 and 0.0001, respectively). For the retrospective review, cases below the cutoff point were reclassified as unsatisfactory, and sensitivity rose from 76.3% to 84.8% ( P = 0.0027). Conclusions Our results indicate that, in the absence of atypical or malignant cells, an adequate bladder barbotage specimen should have a minimum of 2644 (20 per 10 high-power fields) well-visualized, well-preserved urothelial cells to increase the positive predictive value of this test. [ABSTRACT FROM AUTHOR]

Introduction The ability to consistently diagnose low-grade urothelial carcinoma (LGUC) in urinary tract cytology (UTCy) specimens remains controversial, as the reported sensitivity of UTCy in the detection of LGUC is as low as 10%. To determine whether a consistent cytologic diagnosis of LGUC is possible, we assessed the presence and frequency of previously described cytomorphologic features of LGUC in UTCy from patients with LGUC and a negative control group. Materials and methods Biopsy-proven cases of LGUC from June 1, 2010 to January 31, 2014 were identified; UTCy obtained within 3 months prior to biopsy composed the study group (n = 98). The negative control group consisted of UTCy obtained from patients with negative cystoscopy and biopsy (n = 53). All specimens were masked and reviewed in random order to evaluate 17 cytomorphologic parameters. Results Univariate statistical analyses demonstrated that the prevalence of paired cells, clumpy chromatin, and cytoplasmic homogeneity was higher in the study group; however, multivariate analysis did not show these features as significant predictors of LGUC. Conclusions No cytomorphologic feature was statistically significant in the LGUC group versus the negative control group. The presence of 3-dimensional papillary structures with fibrovascular cores is diagnostic of LGUC, but it is only seen in a small minority (2 of 98) cases. Our results reemphasize the fact that urinary tract cytology has a low sensitivity for the diagnosis of LGUC and suggest that, instead of striving to detect LGUC in urine specimens, we should concentrate on the clinically relevant goal of urine cytology—the detection of high-grade lesions. [ABSTRACT FROM AUTHOR]

Introduction Upper tract urothelial carcinoma (UTUC) is defined as urothelial carcinoma (UC) arising in the renal pelvis and ureter. Upper tract (UT) cytology and biopsy evaluation can be technically challenging. The aim of the study is to evaluate the diagnostic modality and sensitivity of urine cytology and ureteroscopic biopsy for the diagnosis of UTUC. Material and methods All patients with UTUC who underwent radical nephroureterectomy or ureterectomy with preoperative cytology and/or biopsy from January 1, 2000 to September 30, 2011 at our institution were included in this study. The sensitivity of each diagnostic modality was calculated with respect to tumor grade, stage, and size. Results A total of 143 cytology specimens and 54 biopsies from 65 patients were evaluated. For low-grade UTUC, the sensitivities for biopsy, lower tract cytology, and UT cytology were 68.4%, 27.3%, and 37.5%, respectively. These numbers were 82.9%, 40.7%, and 80.6% for high-grade UTUC. By combining the UT cytology and biopsy, the diagnostic sensitivities were increased to 87.5% for low-grade UTUC and 100% for high-grade UTUC. The consistency of tumor grade between biopsy and surgical specimen were 63.2% for low-grade UTUC and 68.6% for high-grade UTUC. Conclusions Both UT cytology and biopsy showed higher sensitivity in detecting high-grade UTUC versus low-grade UTUC. The sensitivities of UT cytology and ureteroscopic biopsy in detecting high-grade UTUC were comparable. The sensitivity was greatly improved when these diagnostic modalities were combined. As expected, the selective UT cytology evaluation had superior sensitivity in detecting UTUC than did the lower tract cytology sampling. [ABSTRACT FROM AUTHOR]

The term “atypical” was introduced by the founder of modern cytodiagnosis, Dr. George N. Papanicolaou, to convey a very low suspicion of (pre)malignancy. Despite controversies concerning its ambiguous and imprecise definition and its uncertain optimal use, the term “atypia” has continued to be used in cytopathology, and has recently been increasingly used in standardized nongynecologic cytopathology diagnostic reporting terminologies. Its increasing use suggests that “atypia” continues to be a useful category to fill the gap between what we can recognize as entirely normal (including reactive changes) and what we can recognize as clearly abnormal (premalignant or malignant). However, this diagnosis should be used parsimoniously, since the potential overuse of “atypia” diagnoses can lead to the erosion of clinicians' confidence in cytopathology, their misunderstanding of the cytopathology report, and to an increase the clinicians' diagnostic uncertainty, with negative consequences on patients' satisfaction and wellbeing, and on health care costs. A clinically meaningful, standardized cytodiagnostic category of “atypia” requires a narrow definition, quantitative criteria, agreed-upon reference images, a clear clinical meaning (likelihood of underlying malignancy or premalignancy) and, ideally, well-defined management options. The successful implementation of such a standardized “atypia” diagnostic category requires continuous education of cytology professionals and quality assurance efforts to monitor its use. The interobserver variability and potential excessive use of the diagnosis of “atypia” may be reduced by considering and addressing the major factors involved in its variable use, namely the quality of the sample, the definition of “atypia”, the education/training of the cytologist/pathologist, and cytologist/pathologist-related “supracytologic” factors. [ABSTRACT FROM AUTHOR]

PURPOSE: Oral papillary squamous cell carcinoma (OPSCC) is a histologic variant of SCC with a growth pattern suggesting human papillomavirus (HPV) infection. The aim of this study was to investigate the presence of HPV genotypes in OPSCC. MATERIALS AND METHODS: All cases with a histologic diagnosis of OPSCC from 1993 through 2008 were retrieved and confirmed. Immunohistochemical evaluation for the surrogate marker p16(INK4A) and HPV polymerase chain reaction were performed in tissue and DNA derived from formalin-fixed paraffin-embedded tissue. RESULTS: Forty-four patients with confirmed OPSCC (mean age, 71.96 yr; female-to-male ratio, 1.75:1) comprised the study population. The most common site of involvement was the gingiva followed by the palate and buccal mucosa. Forty cases exhibited an invasive component, 1 was noninvasive, and in 3 cases invasion could not be confirmed owing to suboptimal thickness of the biopsy. Paraffin tissue blocks were available in 41 cases. Twenty-three cases (56.1%) exhibited positive p16(INK4A) staining, which was primarily weak to moderate with a generally focal pattern. Polymerase chain reaction assays were negative for HPV DNA in all cases. CONCLUSIONS: In this study, there was a clinical predilection of OPSCC in older women, with most cases occurring in the masticatory mucosa. Weak to moderate and focal p16(INK4A) staining was appreciated in contrast to reported staining properties in genital and oropharyngeal PSCC. Failure of the polymerase chain reaction assay to exhibit transcriptionally active HPV genotypes suggests that HPV is not associated with OPSCC tumorigenesis. [ABSTRACT FROM AUTHOR]

Purpose: Oral papillary squamous cell carcinoma (OPSCC) is a histologic variant of SCC with a growth pattern suggesting human papillomavirus (HPV) infection. The aim of this study was to investigate the presence of HPV genotypes in OPSCC. Materials and Methods: All cases with a histologic diagnosis of OPSCC from 1993 through 2008 were retrieved and confirmed. Immunohistochemical evaluation for the surrogate marker p16INK4A and HPV polymerase chain reaction were performed in tissue and DNA derived from formalin-fixed paraffin-embedded tissue. Results: Forty-four patients with confirmed OPSCC (mean age, 71.96 yr; female-to-male ratio, 1.75:1) comprised the study population. The most common site of involvement was the gingiva followed by the palate and buccal mucosa. Forty cases exhibited an invasive component, 1 was noninvasive, and in 3 cases invasion could not be confirmed owing to suboptimal thickness of the biopsy. Paraffin tissue blocks were available in 41 cases. Twenty-three cases (56.1%) exhibited positive p16INK4A staining, which was primarily weak to moderate with a generally focal pattern. Polymerase chain reaction assays were negative for HPV DNA in all cases. Conclusions: In this study, there was a clinical predilection of OPSCC in older women, with most cases occurring in the masticatory mucosa. Weak to moderate and focal p16INK4A staining was appreciated in contrast to reported staining properties in genital and oropharyngeal PSCC. Failure of the polymerase chain reaction assay to exhibit transcriptionally active HPV genotypes suggests that HPV is not associated with OPSCC tumorigenesis. [ABSTRACT FROM AUTHOR]

Objective: To present the clinicopathologic features and confirm the presence of the IGH/BCL2 gene fusion in an oral follicular lymphoma (OFL) series. Study design: Cases of OFLs were retrieved from a data base of non-Hodgkin lymphomas (NHL). Fluorescence in situ hybridization (FISH) was performed to confirm the IGH/BCL2 fusion. Results: Eight (8.7%) of 92 NHL were OFLs. Six (75%) patients were male and two female (mean age: 73.4 ± 14.8). The most frequent site was the palate. Five of the 8 patients are alive and without disease. Five (three grade 1 and two grade 2) of six successfully hybridized cases revealed the IGH/BCL2 gene fusion. The sixth case, a grade 3 follicular lymphoma (FL), demonstrated multiple BCL2 signals without IGH/BCL2 fusion. Conclusions: OFLs exhibit an indolent clinical behavior. In the present study, 5/6 cases in which FISH was successful had an IGH/BCL2 fusion as would result from the t(14; 18)(q32; q21) translocation commonly seen in FL of extraoral sites. [ABSTRACT FROM AUTHOR]

Abstract: We report a case of a 40-year-old woman with renal angiomyoadenomatous tumor, a rare neoplasm with only 6 previous cases reported in the literature. Unlike our case, most tumors have been identified in middle-aged males; they present as well-circumscribed, encapsulated tan-brown masses with variably prominent cystic areas. Microscopically, the tumors have a variably thick leiomyomatous capsule, which invaginates into the tumor and intermixes with tubules or solid nests of clear epithelial cells. The epithelial cells have low-grade basally oriented nuclei, and their basement membranes are intimately linked to a labyrinthine network of capillaries and pericytes. Microscopically, these tumors can be confused with clear cell carcinoma, papillary carcinoma, mixed epithelial and stromal tumors, and angiomyolipoma. This is also the first case report correlating the radiographic and morphological findings of this rare entity. The differentiating features of these neoplasms and a review of literature of are herein presented. [Copyright &y& Elsevier]

Recent literature suggests that giant cell angiofibroma (GCAF) is a variant of solitary fibrous tumor (SFT) and not just a related lesion. Herein we present a case of apparent SFT with giant cells, including floret cells and focal pseudovascular areas, which are defining features of GCAF. The tumor occurred in the tongue of an 84-year-old female and depicted an encapsulated, patternless spindle cell proliferation in a fibromyxoid stroma with focal dense collagenous areas and scattered floret-type multinucleated giant cells seen primarily in the periphery, as well as pseudovascular spaces, numerous capillaries, and hemangiopericytomalike areas. Immunohistochemical investigation revealed positive staining for CD34 and positive immunoreaction for estrogen and progesterone receptors. We support the present notion that GCAF is a histologic subtype of SFT. [Copyright &y& Elsevier]

• Impossible to diagnose LGUC on urine? • Enter "TPS" in 2016. • Special edition has papers addressing gaps found in TPS 1.0. • New modalities/techniques highlighted. • Looking forward to TPS 2.0. [ABSTRACT FROM AUTHOR]

Summary: Adenoid cystic carcinoma (ACC) is an uncommon salivary gland malignancy characterized by indolent yet relentless growth that exhibits inherent resistance to systemic chemotherapy, surgical salvage and conventional radiotherapy. We used microarray analysis to characterize gene expression changes associated with ACC. Eight ACC patient specimens were compared with normal parotid gland tissue and the ACC3 cell line. Differentially expressed genes were identified (512 total) using supervised analysis methods and functional categories assigned using OntoExpress. Genes associated with morphogenesis, neurogenesis, proliferation and apoptosis characterized ACC tumors. Genes associated with saliva production and immune response characterized normal parotid tissues while the ACC3 cell line expressed genes primarily associated with proliferation, chromosome maintenance and the cell cycle. These results demonstrate that ACC tumors express genes associated with early developmental processes including morphogenesis and neurogenesis implicating oncogenic events that result in dedifferentiation of normal salivary glands. [Copyright &y& Elsevier]

Papillary serous ovarian carcinoma, the most common type of ovarian cancer, displays different biological behavior in different patients. This heterogeneity cannot be recognized by light microscopy. In this study, gene expression in 29 papillary serous ovarian carcinoma samples (21 invasive tumors and 8 borderline tumors), and 17 nonmalignant tissue types comprising 512 samples, was determined using Affymetrix U_133 oligonucleotide microarrays (Affymetrix, Inc., Santa Clara, Calif) representing approximately 40,000 known genes and expression sequence tags (ESTs). Differences in gene expression were quantified as the fold change in gene expression between the various sets of samples. A set of genes was identified that was over-expressed in the invasive ovarian carcinoma samples compared with the normal ovary samples. Principle component analysis of the set of invasive ovarian carcinomas using this set of genes revealed the existence of 2 major subgroups among the invasive ovarian carcinomas. A series of principle component analyses of the ovarian carcinomas using different gene sets composed of genes involved in different metabolic pathways also revealed the same 2 major subgroups of the invasive ovarian carcinomas. Review of the pathology by a single pathologist in a blinded manner suggested that these 2 subgroups differed in pathologic grade. Genes differentially expressed between the 2 ovarian carcinoma subsets were identified. Examination of gene expression in each ovarian carcinoma subset compared with that in 17 different normal tissue types (512 samples) revealed genes specifically over-expressed in ovarian carcinoma compared with these normal tissues. It is concluded that gene expression patterns may be useful in helping to further classify subtypes of papillary serous ovarian carcinoma that may have clinical significance. In addition, the genes identified as over-expressed in each set of serous ovarian carcinoma compared with normal tissues may represent potential biomarkers and/or targets for therapy. [Copyright &y& Elsevier]

Clear cell carcinoma of the kidney, the most common subtype of renal cell cancer, displays different biological behavior in different patients. This heterogeneity cannot be recognized by light microscopy. In this study, gene expression in 16 clear cell renal cell carcinoma samples and 17 non-malignant tissue types comprising 539 samples was determined using oligonucleotide microarrays representing approximately 40,000 known genes and ESTs. Differences in gene expression were quantified as the fold change in gene expression between the various sets of samples. A set of genes was identified that was overexpressed in the renal cell carcinoma samples compared with the normal kidney samples. Principle component analysis of the set of renal cell carcinomas using this set of genes overexpressed in renal cell cancer revealed the existence of 2 major subgroups among the renal carcinomas. A series of principle component analyses of the set of renal cell carcinomas using different gene sets composed of genes involved in different metabolic pathways also revealed the same 2 major subgroups of the renal cell cancers. Eisen clustering using the same genes also revealed the same 2 major renal cell cancer subsets. Review of the pathology suggested that these 2 subgroups differed in pathologic grade. Genes differentially expressed between the 2 renal cell cancer subsets were identified. Examination of gene expression in each renal cell cancer subset and the pool of renal cell carcinoma samples compared with that in 17 different normal tissues revealed genes specifically overexpressed in renal cell cancer compared with these normal tissues. The authors conclude that gene expression patterns may be useful in helping to further classify subtypes of renal cell carcinoma that may have clinical significance. In addition, the genes identified as overexpressed in each set of clear cell renal cell carcinomas compared with normal tissues may represent useful targets for therapy. [Copyright &y& Elsevier]

Grand Rounds are held with variable frequency in many academic pathology departments, but their exact goal is uncertain, and the type of subjects covered, and presenters have not been studied. We aimed to gather information about the current state of pathology grand rounds (PGR). We identified all US pathology residency programs accredited by the Accreditation Council for Graduate Medical Education (ACGME) and searched their websites for information regarding PGR, extracting data on their existence, frequency and timing. For a representative subgroup of institutions from all US regions and program sizes, we tabulated the 2017–2018 PGR titles and presenters (gender, degree(s), resident/fellow, faculty academic rank). We found that 71 of 142 (50%) ACGME-accredited programs had PGR, more often in programs with >12 residents (53/88, 60%). PGR were scheduled most commonly weekly, on Thursdays, and at noon. We analyzed 1019 PGR presentations from 41 institutions located in 26 US states. Among the 1105 presenters, 183 (16.56%) were trainees, 74 (6.7%) were non-academic, and 848 (76.7%) were faculty, 559 male and 289 female (M/F = 1.93). M/F ratio increased with academic rank, from 1.0 (117/115) for assistant, to 2.0 (135/68) for associate, and 2.9 (307/106) for full professors. Topics covered by PGR belonged to anatomic pathology (357), clinical pathology (209), research (184) or other medical or surgical specialties (149). Our study suggests that trainees are a major intended audience of pathology grand round. Unfortunately, there is a gender gap among pathology grand round presenters that widens with increasing academic rank of presenters. • Pathology Grand Rounds have a wide variety, in terms of their frequency, timing, presenters, topics covered and them • Residents and fellows were the presenters of a significant minority of Pathology Grand Rounds • Compared to their proportion of pathology residents, women are underrepresented as Pathology Grand Rounds presenters [ABSTRACT FROM AUTHOR]