Metastatic Breast Carcinoma in Cerebrospinal Fluid: A Cytopathological Review of 15 Cases.

The incidence of metastatic carcinoma to the meninges ("meningeal carcinomatosis" [MC]) is increasing due to longer survival of patients and improved imaging techniques. Currently, MC is best diagnosed by cytopathological evaluation of cerebrospinal fluid (CSF). Breast primaries are the commonest cause of MC; although cytopathological features thereof have not been, as yet, fully characterized. In this study of meningeal mammary carcinomatosis, relevant clinicopathological data and archived cytopathological preparations of all "suspicious" and "positive" CSF specimens (1992-2015), from patients with a history of breast carcinoma, were retrieved and reviewed. Twenty-three "positive" CSF specimens, derived from 15 patients formed the basis of this study. All specimens were processed as Cytospin preparations, and stained by Papanicolaou and Diff-Quik techniques. All patients were female, with a mean age of 57 (range: 32-85) years. Mean interval between initial diagnosis of breast carcinoma and "positive" CSF was 32 (range 6-84) months. All 23 specimens (100%) were "cellular" (>10 carcinoma cells). Eighteen (78%) specimens showed only isolated nonclustered cells, and 5 (22%) specimens showed both cell clusters and isolated cells. In most "positive" cases, metastatic breast carcinoma cells showed variation in cell size, with hyperchromatic nuclei, irregular nuclear membranes, prominent nucleoli and cytoplasmic vacuolization. The background in some CSF samples showed red blood cells and fibrin admixed with rare lymphocytes and histiocytes. One specimen showed necrotic debris. Papanicolaou and Diff-Quik-stained Cytospin preparations were equally diagnostic, as the aforementioned findings were present in both types of preparation.

High-risk human papillomavirus testing in cytology aspiration samples from the head and neck part 1: a review of the literature on available testing options.

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma is increasing in incidence and is often first diagnosed on a cytology fine needle aspiration (FNA) specimen of metastatic nodal disease of the neck. In the setting of oropharyngeal squamous cell carcinoma, HPV status defines the disease with HPV-associated tumors having better overall prognosis than those that are HPV negative. Furthermore, metastatic squamous cell carcinoma of the neck of unknown origin requires testing for HPV as a positive result suggests an oropharyngeal primary. As a result, HPV testing in aspirate samples is increasingly important for the proper diagnosis and treatment of patients with head and neck squamous cell carcinoma. Although HPV testing in cervicovaginal cytology specimens is common and well-established, testing in head and neck FNA samples remains challenging. p16 immunohistochemistry is an excellent surrogate marker for HPV in tumors of known or suspected oropharyngeal origin, but the criteria used in histologic specimens may not be appropriate in cytology samples. FNA samples are more frequently hypocellular, and cytology cell blocks have variable fixation and processing steps, limiting the utility of p16 immunohistochemistry. Other potential testing options have been reported in the literature including staining of aspirate smears and molecular testing of liquid-based samples. The American Society of Cytopathology Clinical Practice Committee recently surveyed the American Society of Cytopathology membership to determine the current state of HPV testing in aspirate samples, and this review article is designed to provide a summary of the current literature on various testing options in FNA samples.

Management of the low grade squamous intraepithelial lesion Pap smear in a cross-sectional, observational cohort.

OBJECTIVE: To evaluate the practice of delaying colposcopy until repeat cytology demonstrates persistent low grade squamous intraepithelial lesion (LSIL). STUDY DESIGN: A retrospective cross-sectional analysis was performed on patients diagnosed with LSIL in a high-risk urban population. Primary outcomes were defined as regression, persistence, progression and lost to follow-up. RESULTS: A total of 624 patients received an initial cytologic diagnosis of LSIL. Of these, 260 (42%) were lost to follow-up despite multiple contact attempts. Of the 364 patients available for full analysis, 168 (26%) regressed to negative cytology, 93 (15%) had persistent LSIL/cervical intraepithelial neoplasia (CIN) 1, and 103 (17%) progressed to high grade cervical intraepithelial neoplasia (HSIL)/CIN 2/3. Higher rates of LSIL regression were observed in teenagers (< or = 20) compared to women aged 21-30 or > 30 (51% vs. 43% vs. 45%), although this was not statistically significant (p = 0.29). CONCLUSION: Delaying colposcopy to repeat cytology resulted in a significant loss to follow-up in a population at high risk for poor compliance. In women with LSIL over 20 years of age, immediate colposcopy is recommended when optimal patient compliance cannot be ensured. Only 25% of patients avoided eventual colposcopy by regression to normal cytology.

Cytological diagnosis of papillary thyroid carcinoma with tall cells on ThinPrep liquid-based cytology.

BACKGROUND: The tall cell variant of papillary thyroid carcinoma (PTC-TC) has been associated with aggressive features including extrathyroidal extension, higher rate of lymph node and distant metastases, and higher recurrence rate. We aimed to evaluate the cytomorphologic features of PTC-TC on ThinPrep (TP) along with its diagnostic efficacy to detect PTC-TC. METHODS: Preoperative cytology samples from 30 cases of histologically-proven PTC-TC and 30 classical PTC controls were selected for this study. TP preparations were evaluated for varying architectural and cytomorphologic features. RESULTS: Tall cells were present in the majority of PTC-TC cases and were located at the periphery of cell clusters and as single cells. Cytoplasmic cuff along the periphery of cell clusters and soap-bubble pseudoinclusions were very specific features of PTC-TC, when present. PTC-TC cases were more likely to show abundant oncocytic cytoplasm and distinct cell borders. Cytoplasmic tails were more likely to be present and more numerous in PTC-TC. The presence of nuclear grooves, papillary architecture, and giant cells were not reliable distinguishing features of PTC-TC vs controls. CONCLUSION: Our results indicate that tall cell cytomorphologic and architectural features in PTC are identifiable on TP.

Results from the 2019 American Society of Cytopathology survey on rapid on-site evaluation-Part 1: objective practice patterns.

INTRODUCTION: Rapid on-site evaluation (ROSE) is a service provided by cytologists that helps ensure specimen adequacy and appropriate triage for ancillary testing. However, data on the current usage patterns across different practice settings have been lacking. MATERIALS AND METHODS: To obtain an accurate and timely assessment of the current state of practice of ROSE, a 14-question online survey was constructed by the Clinical Practice Committee of the American Society for Cytopathology. The survey was available to the membership of the American Society for Cytopathology for a 3-week period in early 2019. RESULTS: A total of 541 responses were received, including from 255 cytopathologists/pathologists, 261 cytotechnologists, 19 cytology resident/fellow trainees, and 6 others. ROSE was offered as a clinical service by 95.4% of the respondents, with telecytology for ROSE used in 21.9% of the practices. Endobronchial ultrasound-guided transbronchial needle aspiration was the procedure most frequently reported to use ROSE (mean, 59.1%; median, 70%). Cytotechnologists were involved in ROSE in most practices. The number of daily ROSE procedures correlated with the annual nongynecologic cytology volumes. Approximately 70% of ROSE procedures were reported to require >30 minutes, on average, for the cytologist. CONCLUSIONS: The results from our survey of cytologists have shown that the reported practice patterns for the usage of ROSE vary considerably. The presented data can help inform future guideline recommendations and the implementation of ROSE in different clinical settings.

Cyr61/CCN1 and CTGF/CCN2 mediate the proangiogenic activity of VHL-mutant renal carcinoma cells.

The von Hippel-Lindau (VHL) protein serves as a negative regulator of hypoxia-inducible factor (HIF)-alpha subunits. Since HIF regulates critical angiogenic factors such as vascular endothelial growth factor (VEGF) and lesions in VHL gene are present in a majority of the highly vascularized renal cell carcinoma (RCC), it is believed that deregulation of the VHL-HIF pathway is crucial for the proangiogenic activity of RCC. Although VEGF has been confirmed as a critical angiogenic factor upregulated in VHL-mutant cells, the efficacy of antiangiogenic therapy specifically targeting VEGF signaling remains modest. In this study, we developed a three-dimensional in vitro assay to evaluate the ability of RCC cells to promote cord formation by the primary human dermal microvascular endothelial cells (HDMECs). Compared with VHL wild-type cells, VHL-mutant RCC cells demonstrated a significantly increased proangiogenic activity, which correlated with increased secretion of cysteine-rich 61 (Cyr61)/cysteine-rich 61-connective tissue growth factor-nephroblastoma overexpressed (CCN) 1, connective tissue growth factor (CTGF)/CCN2 and VEGF in conditioned culture medium. Both CCN proteins are required for HDMEC cord formation as shown by RNA interference knockdown experiments. Importantly, the proangiogenic activities conferred by the CCN proteins and VEGF are additive, suggesting non-overlapping functions. Expression of the CCN proteins is at least partly dependent on the HIF-2alpha function, the dominant HIF-alpha isoform expressed in RCC. Finally, immunohistochemical staining of Cyr61/CCN1 and CTGF/CCN2 in RCC tissue samples showed that increased expression of these proteins correlates with the loss of VHL protein expression. These findings strengthened the notion that the hypervascularized phenotype of RCC is afforded by multiple proangiogenic factors that function in parallel pathways.

The expression ratio of Map7/B2M is prognostic for survival in patients with stage II colon cancer.

Colorectal cancer (CRC) is the second most frequent cause of cancer-related death in the United States. To determine whether certain molecular markers might be prognostic for survival, we measured by quantitative real-time RT-PCR the expression levels of 15 previously studied genes that are known to be up-regulated or down-regulated in the progression of epithelial cancers. The tumor samples were extracted from formalin-fixed paraffin-embedded primary tissues derived from patients with Stage II CRC who developed disease recurrence within two years (n=10), or were disease-free for at least 4 years (n=12). We were able to determine, by AUC curve analysis, that the ratio of microtubule associated protein 7 (Map7)/B2M was predictive of outcome in our sample set. Further, using Kaplan-Meier survival analysis, we observed significantly different curves as a function of marker positivity for the Map7/B2M (p=0.0001; HR=11) expression ratio. This suggests that the expression ratio of Map7/B2M may serve as a valuable prognostic marker in patients with Stage II colon cancer, and potentially guide therapeutic decision making.

Detection of mammaglobin mRNA in peripheral blood is associated with high grade breast cancer: interim results of a prospective cohort study.

BACKGROUND: We sought to examine the detection rate of cancer cells in peripheral blood (PBL) and in bone marrow (BM) using an established 7-gene marker panel and evaluated whether there were any definable associations of any individual gene with traditional predictors of prognosis. METHODS: Patients with T1-T3 primary breast cancer were enrolled into a prospective, multi-institutional cohort study. In this interim analysis 215 PBL and 177 BM samples were analyzed by multimarker, real-time RT-PCR analysis designed to detect circulating and disseminated breast cancer cells. RESULTS: At a threshold of three standard deviations from the mean expression level of normal controls, 63% (136/215) of PBL and 11% (19/177) of BM samples were positive for at least one cancer-associated marker. Marker positivity in PBL demonstrated a statistically significant association with grade II-III (vs. grade I; p = 0.0083). Overexpression of the mammaglobin (mam) gene alone had a statistically significant association with high tumor grade (p = 0.0315), and showed a trend towards ER-negative tumors and a high risk category. There was no association between marker positivity in PBL and the pathologic (H&E) and/or molecular (RT-PCR) status of the axillary lymph nodes (ALN). CONCLUSION: This study suggests that molecular detection of circulating cancer cells in PBL detected by RT-PCR is associated with high tumor grade and specifically that overexpression of the mam gene in PBL may be a poor prognostic indicator. There was no statistically significant association between overexpression of cancer-associated genes in PBL and ALN status, supporting the concept of two potentially separate metastatic pathways.

Use of the ThinPrep Imaging System does not alter the frequency of interpreting Papanicolaou tests as atypical squamous cells of undetermined significance.

BACKGROUND: Automated screening of Papanicolaou tests (Pap tests) improves the productivity of cytopathology laboratories. The ThinPrep Imaging System (TIS) has been widely adopted primarily for this reason for use on ThinPrep Pap tests (TPPT). However, TIS may also influence the interpretation of Pap tests, leading to changes in the frequency of various interpretive categories. The effect of the TIS on rates of TPPT interpretation as atypical squamous cells of undetermined significance (ASC-US) is of concern because any shift in the frequency of ASC-US will alter the sensitivity and specificity of the Pap test. We have sought to determine whether automated screening of TPPT has altered ASC-US rates in our institution when compared with manual screening (MS) of TPPT. METHODS: A computerized search for all ASC-US with reflex Human Papillomavirus (HPV) testing over a one-year-period (7/1/06 to 6/30/07) was conducted. Cases included both TPPT screened utilizing TIS and screened manually. HPV test results for both groups were recorded. Pertinent follow-up cervical cytology and histology results were retrieved for the period extending to 11/30/07. Automated screening was in clinical use for 10 months prior to the start of the study. RESULTS: Automated screening was performed on 23,103 TPPT, of which 977 (4.23%) were interpreted as ASC-US. Over the same period, MS was performed on 45,789 TPPT, of which 1924 (4.20%) were interpreted as ASC-US. Reflex HPV testing was positive for high risk (HR) types in 47.4% of the TIS cases and 50.2% of MS cases. Follow-up cervical dysplasia found by colposcopy was also distributed proportionally between the two groups. Cervical intraepithelial neoplasia (CIN) was found on follow-up biopsy of 20.1% of the TIS cases (5.2% CIN 2/3) and 21.2% of MS cases (5.1% CIN 2/3). None of these differences were statistically significant. CONCLUSION: Use of the ThinPrep Imaging System did not appreciably change ASC-US rates or follow-up reflex HPV test results in our laboratory. This demonstrates that the benefits of automated screening may be obtained without increasing the rate of referral to colposcopy for ASC-US follow-up.

Decreased UCHL1 expression as a cytologic biomarker for aggressive behavior in pancreatic neuroendocrine tumors.

BACKGROUND: There are currently no reliable markers associated with aggressive behavior in well-differentiated and moderately differentiated pancreatic neuroendocrine tumors. We aimed to determine whether expression of ubiquitin carboxyl-terminal hydrolase L1 in conjunction with Ki67 can identify metastatic potential of well-differentiated and moderately differentiated pancreatic neuroendocrine tumors from fine-needle aspiration samples obtained by endoscopic ultrasound. METHODS: Retrospective review of 48 patients with well-differentiated and moderately differentiated pancreatic neuroendocrine tumors diagnosed by endoscopic ultrasound fine-needle aspiration at a single center identified 35 biopsy samples with adequate material for analysis. Ubiquitin carboxyl-terminal esterase L1 immunocytochemistry of primary pancreatic neuroendocrine tumors was performed along with Ki67 staining and scored semiquantitatively. The combination of ubiquitin carboxyl-terminal esterase L1 score ≤4 (weak) and Ki67 ≥3% (high) was considered a positive test for predicting tumors associated with metastases. RESULTS: Weak ubiquitin carboxyl-terminal hydrolase L1 staining had 80% sensitivity, 65% specificity, 63% positive predictive value, and 81% negative predictive value to identify primary tumors associated with metastatic disease. The combination of weak ubiquitin carboxyl-terminal hydrolase L1 staining and high Ki67 staining increased the test specificity to 95%. On multivariable analysis, combined positive test of weak ubiquitin carboxyl-terminal esterase L1 staining and high Ki67 staining was an independent predictor of metastatic disease (P = .047). CONCLUSION: Ubiquitin carboxyl-terminal hydrolase L1 is a novel biomarker for identifying malignant potential of primary well-differentiated and moderately differentiated pancreatic neuroendocrine tumors and in combination with Ki67 is an independent predictor of development of metastatic disease.

Endobronchial ultrasound for the diagnosis of pulmonary sarcoidosis.

BACKGROUND: The diagnosis of pulmonary sarcoidosis can be established by a variety of techniques. Transbronchial lung biopsy is often the preferred approach, but it is frequently nondiagnostic and carries a risk of pneumothorax and bleeding. Mediastinoscopy is often suggested as the next diagnostic step but entails significant cost and associated morbidity. Endobronchial ultrasound (EBUS) with transbronchial needle aspiration (TBNA) is emerging as a safe, minimally invasive tool for the primary diagnosis of mediastinal and hilar lymphadenopathy. The purpose of this study was to assess the utility of EBUS-TBNA for pulmonary sarcoidosis. METHODS: Fifty consecutive patients who had been referred for EBUS-TBNA for suspected pulmonary sarcoidosis were included in the study. On-site cytology was used to assess the adequacy of the samples. The presence of noncaseating granulomas without necrosis in the appropriate clinical setting was deemed to be adequate for the diagnosis of pulmonary sarcoidosis. Patients with a negative EBUS-TBNA underwent further histologic biopsy or clinical follow-up to determine the final diagnosis. RESULTS: Eighty-two lymph nodes with a median size of 16 mm (range, 4 to 40 mm) were punctured. EBUS-TBNA demonstrated noncaseating granulomas without necrosis in 41 of 48 patients (85%) with a final diagnosis of sarcoidosis. EBUS-TBNA, therefore, has a sensitivity of 85% for the primary diagnosis of pulmonary sarcoidosis. CONCLUSIONS: EBUS-TBNA is a safe, minimally invasive tool for the primary diagnosis of pulmonary sarcoidosis that has a high diagnostic yield. EBUS-TBNA should be considered an appropriate alternative diagnostic technique for patients with suspected pulmonary sarcoidosis.

Desmoplastic melanoma morphology on Thinprep: a report of two cases.

BACKGROUND: Desmoplastic melanoma is a variant of malignant melanoma that can range in appearance from sarcomatoid to scar-like. Cytomorphology of desmoplastic melanoma has been previously described on conventional smears; however, to our knowledge, detailed cytomorphology on ThinPrep has so far not been described. Herein, we describe the cytomorphology of two cases of desmoplastic melanoma on fine needle aspiration processed as ThinPrep slides and compare it to that seen on conventional smears. Pertinent immunocytochemical stains, performed on ThinPrep slides are also discussed. CASE PRESENTATION: The first case is a woman with a history of desmoplastic melanoma of the scalp with previous local recurrences and lymph node metastasis with a new submandibular mass. The second case is a man with a previously resected desmoplastic melanoma with his first local recurrence. Conventional smears, including air-dried Diff-Quik-stained and alcohol-fixed Papanicolaou-stained smears, demonstrated aggregates of pleomorphic spindle cells admixed with fibrous stroma and single spindle cells. In both cases, nuclei were elongated and plump with irregular nuclear contours, deep grooves, and folds. Chromatin was dark and coarse with either inconspicuous or multiple prominent nucleoli. Cytoplasm was located at the nuclear poles and was fine, wispy, and delicate. The background was clean with no evidence of necrosis or melanin pigment. Papanicolaou-stained ThinPrep slides were prepared from needle rinses and demonstrated excellent correlation of nuclear and cytoplasmic detail of single spindle cells to that seen on conventional smears with the exception of only slight decrease in nuclear size; however, nuclear and cytoplasmic detail of spindle cells embedded in stroma was markedly attenuated. Confirmatory immunostain for S-100 protein in both cases was performed on ThinPrep slides demonstrating crisp cytoplasmic staining in the spindle cells. CONCLUSION: The cytomorphology of desmoplastic melanoma shows excellent correlation between cytomorphology of single spindle cells on conventional smears and on ThinPrep slides. The major difference noted on ThinPrep slides was attenuated nuclear and cytoplasmic detail of spindle cells embedded in fibrous stoma.

Non-gynecologic cytology on liquid-based preparations: A morphologic review of facts and artifacts.

Liquid-based preparations (LBP) are increasingly being used both for gynecologic (gyn) and non-gynecologic (non-gyn) cytology including fine needle aspirations (FNA). The two FDA-approved LBP currently in use include ThinPrep (TP), (Cytyc Corp, Marlborough, MA) and SurePath (SP), (TriPath Imaging Inc., Burlington, NC). TP was approved for cervico-vaginal (Pap test) cytology in 1996 and SP in 1999 and both have since also been used for non-gyn cytology. In the LBP, instead of being smeared, cells are rinsed into a liquid preservative collection medium and processed on automated devices. Even after a decade of use, the morphological interpretation of LBP remains a diagnostic challenge because of somewhat altered morphology and artifacts or facts resulting from the fixation and processing techniques. These changes include cleaner background with altered or reduced background and extracellular elements; architectural changes such as smaller cell clusters and sheets, breakage of papillae; altered cell distribution with more dyscohesion and changes in cellular morphology with enhanced nuclear features, smaller cell size and slightly more three-dimensional (3-D) clusters. Herein, we review the published literature on morphological aspects of LBP for non-gyn cytology.

Accuracy of next-generation sequencing for the identification of clinically relevant variants in cytology smears in lung adenocarcinoma.

BACKGROUND: Minimally invasive diagnostic procedures such as needle-core biopsy and fine-needle aspiration provide adequate material for molecular analyses. Advances in precision oncology are trending toward the interrogation of limited amounts of genomic material to guide clinical and therapeutic decisions. The aim of this study was to investigate the minimum cellularity needed on cytologic smears for the identification of clinically relevant variants with next-generation sequencing (NGS). METHODS: Thirty cases of cytologically diagnosed, resection-proven primary lung adenocarcinoma were identified. Nineteen of the 30 cases were known to harbor actionable variants. One Diff-Quik (DQ)-stained slide and 1 Papanicolaou (Pap)-stained slide were selected from each case. Cases were categorized as containing fewer than 100 tumor cells, 100 to 500 tumor cells, or more than 500 tumor cells. NGS was performed on the Ion Torrent platform. RESULTS: NGS was successfully performed on all cell blocks and on 90% of the smears. Paired DQ and Pap smears showed similar cellularity, and cases that differed in cellularity were within 1 category of each other. The cases with more than 100 tumor cells had a 93% success rate; this was significantly different from the situation for cases with fewer than 100 tumor cells, which were successfully sequenced only 67% of the time. Overall, NGS was able to provide clinically relevant information for 83% of DQ smears and for 90% of Pap smears tested. CONCLUSIONS: The data show a significantly higher likelihood of successful NGS with cytologic smears with more than 100 tumor cells. There was a trend for a higher NGS success rate with Pap smears versus DQ smears. Cancer Cytopathol 2017;125:398-406. © 2017 American Cancer Society.

Cytology Preparations of Formalin Fixative Aid Detection of Giardia in Duodenal Biopsy Samples.

Giardiasis is the most common intestinal parasitic infection in the United States. The organism elicits no, or minimal, inflammatory changes in duodenal biopsy samples, so it can be easily overlooked. We performed this study to determine whether Giardia could be isolated from the formalin fixative of biopsy samples, and to evaluate the value of fluid analysis in the assessment for potential infection. We prospectively evaluated duodenal biopsy samples from 92 patients with a clinical suspicion of giardiasis or symptoms compatible with that diagnosis (ie, diarrhea, bloating, or abdominal pain) Biopsy samples were routinely processed and stained with hematoxylin and eosin. Histologic diagnoses included giardiasis (5 cases, 4%), normal findings (64 cases, 70%), peptic injury/active duodenitis (12 cases, 13%), and intraepithelial lymphocytosis with villous blunting (10 cases, 12%). Fifteen cases (13%) showed detached degenerated epithelial cells or mucus droplets in the intervillous space that resembled Giardia. Cytology slides were prepared from formalin in the biopsy container using the standard Cytospin protocol and reviewed by a cytopathologist blinded to the biopsy findings. Cytologic evaluation revealed Giardia spp. in all 5 biopsy-proven cases, and identified an additional case that was not detected by biopsy analysis. Organisms were significantly more numerous (mean: 400 trophozoites; range, 120 to 810) and showed better morphologic features in cytology preparations compared with tissue sections (mean: 129 trophozoites; range, 37 to 253 organisms; P=0.05). Our findings suggest that cytology preparations from formalin fixative can resolve diagnostically challenging cases and even enhance Giardia detection in some cases.

Diagnostic yield of cytopathology in evaluating pericardial effusions: Clinicopathologic analysis of 419 specimens.

BACKGROUND: Pericardial effusions can cause considerable morbidity and potentially may lead to mortality. Malignant pericardial effusions are uncommon, and data on malignancies encountered in pericardial effusion cytology specimens are limited. METHODS: Relevant records of all pericardial effusions from January 2008 to September 2014 were examined and compared with pericardial biopsy results when performed. Discrepant cases were reviewed to determine the cause of the disagreement. RESULTS: In total, 419 pericardial effusion specimens obtained from 364 patients were examined. Cytologic diagnostic categories included: negative for malignancy (332 specimens; 79%), equivocal (25 specimens; 6%), and positive (62 specimens from 51 patients; 15%). Forty-seven patients who had positive effusions were known to have malignancy. The most common primary malignancies were breast (39.3%) and lung (39.3%) cancers in women and lung cancer (47.4%) in men. A concurrent pericardial biopsy was performed in 46% of patients. Excluding equivocal cytologic diagnoses, cytology and biopsy were concordant in 153 of 173 paired samples (88.4%). The sensitivity of cytology in diagnosing malignancy was 92.1% compared with 55.3% for pericardial biopsy. CONCLUSIONS: Cytologic examination has significant diagnostic utility in the evaluation of pericardial effusions and exhibits a lower false-negative rate compared with pericardial biopsy. Submission of pericardial biopsy alongside effusion cytology is associated with increased sensitivity for detecting malignancy and may be especially useful in the setting of low-volume pericardial effusion. Cancer Cytopathol 2017;125:128-137. © 2016 American Cancer Society.

Routine vaginal Pap test is not useful in women status-post hysterectomy for benign disease.

The US Preventive Services Task Force (USPTF) has recommended that routine vaginal Pap (V-Pap) screening is unnecessary for women status-post (S/P) total hysterectomy (T-Hyst) for benign disease (Guide to Clinical Preventive Services. 2nd ed. Baltimore, MD: Williams & Wilkins; 1996. p 105-118). However, many US women continue to have V-Pap despite no risk for cervical cancer and minimal risk for primary vaginal cancer (JAMA 2004;291:2990). Herein, we report our experience with such patients. Computerized data of patients S/P T-Hyst for benign conditions over a 6-yr-period were retrospectively evaluated. Pap diagnoses of epithelial abnormalities (Ep Abnl), negative for intraepithelial lesion or malignancy with/without nonneoplastic findings (NILM-NN and NILM), were reviewed based on three age groups: group A, 18-44 yr; group B, 45-64 yr; and group C, > or =65 yr (JAMA 2004;291:2990). A control group was used.Of 1,860 T-Hyst 1,303 (70%) were for benign disease. Of these 581/1303 (44.5%) patients had 819 current V-Paps (range, 1-5; mean, 1.4). The 581 patients were group A, 288 (49.5%); group B, 272 (46.8%); and group C, 21 (3.6%). Overall, the 819 V-Paps showed Ep Abnl, 28 (3.4%); NILM-NN, 252 (30.7%); and NILM, 539 (65.8%). Of the 28 Ep Abnl, 19 (67.8%) were atypical squamous cells of undetermined significance (ASCUS), and 9 (32%) were low-grade vaginal intraepithelial lesions (LG-VAIN). The NILM-NN findings included organisms, atrophy, and endometriosis. On the basis of individual age groups, Ep Abnl were only seen in V-Paps of 7/288 (2%) of group A and 21/272 (8%) of group B patients. In 23 control patients, 7/71 (9.8%) current V-Paps showed Ep Abnl (ASCUS, 4 (57%); LG-VAIN, 3 (43%)). Continued V-Pap in women S/P T-Hyst for benign disease does not appear to be useful, particularly in those aged > or =65 yr.

"Intercellular bridges" in a case of well differentiated squamous carcinoma.

Intercellular bridges may aide in definitive identification of malignant cell origin, especially in squamous cell carcinoma. They are difficult to identify in routine cytologic specimens and are especially rare in smear preparations. Herein, we present images of intercellular bridges from a case of well differentiated squamous cell carcinoma of the esophagus in a cytologic specimen obtained from FNA of a paraesophageal lymph node.

Diagnostic value of positive urinary cytology in the detection of recurrent urothelial carcinoma: 10-Year Experience at the Papanicolaou Cytology Laboratory.

INTRODUCTION: Urothelial carcinoma (UCC) of the bladder is the most common malignancy of the urinary tract. The performance of urine cytology (UCy) after radical cystectomy (RC) and urinary diversion is quite variable and there is no consensus regarding its role in post-treatment surveillance. The goal of this study is to retrospectively review the diagnostic value of positive (suspicious or positive for malignancy) diverted urine cytology (DUCy) in the detection of urinary tract recurrence of UCC. MATERIALS AND METHODS: A retrospective 10-year (January 2005 to January 2015) computerized search for all DUCy specimens was conducted. All suspicious (Susp) or positive for malignant cells (PMC) ThinPrep cases were identified and retrospectively reviewed. Clinical, surgical, and pathological follow-up for patients with Susp or PMC UCy were tabulated and analyzed. RESULTS: During the 10-year-period, 1,525 DUCy cases from 408 patients were identified. Of these, 25 cases (1.64%) from 10 patients were called either Susp (13; 0.85%) or PMC (12; 0.79%). The 25 DUCy cases occurred within a mean of 20 months post-RC. Out of 10 patients, 9 had a concurrent biopsy or a subsequent resection of the recurrent site. Of these 9 patients, 8 (89%) had subsequent biopsy or resection, which showed recurrent UCC. In 5/8 patients, positive DUCy was the very first manifestation of recurrence, which was subsequently confirmed by imaging or histology. CONCLUSION: It is our experience that patients with positive UCy after RC have a high likelihood of recurrent UCC and should be counseled and managed accordingly. Diagn. Cytopathol. 2016;44:975-979. © 2016 Wiley Periodicals, Inc.

Detection of in situ and invasive endocervical adenocarcinoma on ThinPrep Pap Test: Morphologic analysis of false negative cases.

BACKGROUND: The goal of this study was to calculate the sensitivity and false negative (FN) rate of ThinPrep Pap Test (TPPT) and carefully analyze missed cases for educational purposes. MATERIALS AND METHODS: Patients with histologically proven adenocarcinoma in-situ (AIS) or invasive endocervical adenocarcinoma (EAC) over a 17-year-period (1998-2015) were identified. The TPPT immediately preceding the histological diagnosis of AIS/ECA was designated as index Pap (IP). Paps up to 122 months before histologic diagnosis of AIS/ECA were considered for this study. All available negative and unsatisfactory TPPT were re-reviewed. RESULTS: There were 78 patients with histologically-proven AIS (56) or ECA (22) with 184 TPPTs, and 95 of these TPPTs were abnormal. Of the abnormal cases, 55.7% TPPTs were diagnosed as endocervical cell abnormality (atypical endocervical cells/AIS/ECA). Notably, 44.2% of abnormal TPPTs were diagnosed as squamous cell abnormality (atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion/high grade squamous intraepithelial lesion). Including the diagnoses of squamous cell abnormality, the sensitivity of index TPPT for histologically-confirmed AIS/ECA was 88%. Eighty-eight of 184 TPPT, including 10 IP, were negative = 87, or unsatisfactory = 1. Forty-two of these slides were available for re-review. Upon review, 21 TPPT (50%) were confirmed negative and 21 TPPT (50%) were reclassified as abnormal = 20, or unsatisfactory = 1. Of the FN cases, the main difficulty in correct diagnosis was the presence of few diagnostic cell clusters which had less feathering, and consisted of smaller, rounder cells in small and tighter clusters, with nuclear overlap. In particular, nuclear overlap in three-dimensional groups precluded the accurate diagnosis. Rare FN cases showed squamous cell abnormality on re-review, and rare cases showed obscuring blood or inflammation. CONCLUSION: A significant proportion of AIS/EAC is discovered after Pap showing squamous cell abnormality. FN cases were most commonly related to nuclear overlap in tight three-dimensional clusters.