Primary Effusion Lymphoma in an HIV-Negative Patient with Chronic Myeloid Leukemia Treated with Dasatinib.

INTRODUCTION: Primary effusion lymphoma (PEL) is a malignant lymphomatous effusion, which by definition is Kaposi sarcoma herpesvirus/human herpesvirus 8-positive. PEL typically occurs in HIV-infected patients but can also occur in HIV-negative individuals, including in organ transplant recipients. Tyrosine kinase inhibitors (TKIs) are currently the standard of care for patients with chronic myeloid leukemia (CML), BCR::ABL1-positive. Although TKIs are extremely effective in treating CML, they alter T-cell function by inhibiting peripheral T-cell migration and altering T-cell trafficking and have been associated with the development of pleural effusions. CASE PRESENTATION: We report a case of PEL in a young, relatively immunocompetent patient with no history of organ transplant receiving dasatinib for CML, BCR::ABL1-positive. DISCUSSION: We hypothesize that the loss of T-cell function secondary to TKI therapy (dasatinib) may have resulted in the unchecked cellular proliferation of Kaposi sarcoma herpesvirus (KSHV)-infected cells, leading to the emergence of a PEL. We recommend cytologic investigation and KSHV testing in patients being treated with dasatinib for CML who present with persistent or recurrent effusions.

Cytopathology of rare gastric mesenchymal neoplasms: A series of 25 cases and review of literature.

BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm arising in the stomach. However, a number of other rare mesenchymal neoplasms do occur at this anatomic site, which often presents a diagnostic challenge for cytopathologists on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Our study aims to selectively present the clinico-radiological and cytopathological characteristics of these rare "non-GIST" neoplasms, as well as their differential diagnoses. MATERIAL AND METHODS: We performed a 20 year retrospective search in the cytopathology database of our two large medical institutions for non-GIST mesenchymal neoplasms arising in the stomach and diagnosed on EUS-FNA. Data regarding the patients' demographics and radiological findings were analysed. All available cytopathology specimens were reviewed. The cytomorphological characteristics and the accompanying immunohistochemical stains, when available, were subsequently analysed. RESULTS: Twenty-five cases of gastric mesenchymal tumours were selectively included in the study after excluding all cases of GIST (n = 113) diagnosed on FNA. These cases included 10 leiomyomas (40%), eight schwannomas (32%), five glomus tumours (20%), one perivascular epithelioid cell neoplasm, and one desmoid tumour. The specimen cellularity was variable and ranged from hypocellular to highly cellular. Most smears were composed of spindle cells with a few showing epithelioid morphology. Cell blocks were available in 20 cases and a range of immunohistochemical ancillary studies were performed. DOG-1, c-KIT, smooth muscle actin (SMA), and S100-protein were the most common immunomarkers done. CONCLUSION: Our study highlights important cytomorphological characteristics of rare mesenchymal neoplasms arising in the stomach. In the appropriate clinical setting and with the help of immunohistochemistry, an accurate diagnosis of these neoplasms can be achieved.

Arginase-1: a highly specific marker separating pancreatic adenocarcinoma from hepatocellular carcinoma.

BACKGROUND: Arginase-1 and HepPar-1 are effective immunohistochemical (IHC) markers for hepatocellular carcinoma (HCC). In this study, we explored the possible efficacy of these stains in diagnosing pancreatic adenocarcinoma (PAD). STUDY DESIGN: Arginase-1 and HepPar-1 IHC was performed on formalin-fixed, paraffin-embedded fine needle aspiration (FNA) cell blocks (CB) of PAD (n = 46), tissue microarray (TMA) of PAD (n = 33), FNA CB of HCC (n = 44) and TMA of HCC (n = 85). Negative controls without carcinoma were also applied (pancreas CB, n = 7; pancreas TMA, n = 3). RESULTS: PAD CB demonstrated arginase-1 positivity in 0 of 46 cases and HepPar-1 positivity in 7 of 46 cases (15%). PAD TMA demonstrated arginase-1 positivity in 0 of 33 cases and HepPar-1 positivity in 4 of 33 cases (12%). HCC CB demonstrated arginase-1 positivity in 37 of 44 cases (84%) and HepPar-1 positivity in 32 of 44 cases (72%). HCC TMA demonstrated arginase-1 positivity in 75 of 85 cases (88%) and HepPar-1 positivity in 80 of 85 cases (94%). CONCLUSION: Both arginase-1 and HepPar-1 are effective IHC markers of hepatocellular differentiation. Arginase-1 demonstrates superior sensitivity and specificity compared with HepPar-1 in the diagnosis of HCC. However, both arginase-1 and HepPar-1 have a low sensitivity and a very high specificity for PAD.

Galectin-3 and PTEN expression in pancreatic ductal adenocarcinoma, pancreatic neuroendocrine neoplasms and gastrointestinal tumors on fine-needle aspiration cytology.

OBJECTIVE: Galectin-3 has been implicated in the carcinogenesis of pancreatic ductal adenocarcinoma (PDAC). Its applicability in pancreatic fine-needle aspiration (FNA) in separating malignant from benign lesions has never been addressed. In addition, a correlation between Galectin-3 and tumor suppressor phosphatase and tensin homolog (PTEN) and their potential diagnostic value has never been tested. STUDY DESIGN: This study analyzed Galectin-3 immunohistochemical expression in FNA cell blocks of PDAC, pancreatic neuroendocrine neoplasms (PNEN), gastrointestinal stromal tumors (GIST) and non-tumor pancreatic tissue. In parallel, Galectin-3 and PTEN levels were evaluated in a tumor tissue microarray (TMA). RESULTS: Forty-four of 46 PDAC FNA and 32 of 33 PDAC TMA demonstrated tumor-specific Galectin-3 positivity. In contrast, Galectin-3 was not detected in PNEN and GIST. Total loss of PTEN was displayed by 26 of 33 PDAC, while non-neoplastic tissues all retained PTEN expression. CONCLUSION: Galectin-3 could be a valuable marker to help diagnose PDAC and rule out PNEN and GIST. In addition, PTEN positivity strongly argues against a diagnosis of PDAC. These data also advocate their potential diagnostic roles in the work up of challenging cytologic cases requiring ancillary test confirmation.

Challenges and Pitfalls in Pancreatobiliary Cytopathology.

INTRODUCTION: The advances of minimally invasive endoscopy-guided procedures that usually yield limited diagnostic material changed pancreaticobiliary cytopathology into one of the most challenging areas of cytopathology given the abundance of differential diagnoses to be considered when dealing with limited specimens. CASE PRESENTATION: We describe a few challenging examples of potential pitfalls in pancreatobiliary cytopathology evaluation collected from a busy academic hospital (tertiary) center. Case 1 illustrates the challenges in handling paucicellular specimens from pancreatic solid lesions in which differential diagnoses may include acinar cell carcinoma, neuroendocrine tumors, adenocarcinoma, or even benign pancreatic tissue, among others. Case 2 illustrates the pitfalls in evaluating limited specimens from patients with chronic pancreatitis, specially when distinguishing exuberant reactive atypia from dysplastic changes is mandatory. Case 3 illustrates pitfalls in distinguishing malignancy from reactive changes in biliary brushing specimens from patients with primary sclerosing cholangitis. Finally, cases 4 and 5 highlight the importance of including the possibility of pancreatic metastasis in the differential diagnoses of some pancreatic lesions. CONCLUSION: Over time, there has been an increasing demand for pathologists to render diagnoses on limited specimens obtained through minimally invasive procedures which can be frequently challenging even for the most experienced professionals. In many difficult cases, salvaging additional material for a cell block can turn out to be extremely helpful given the possibility of utilizing additional ancillary tests for diagnostic confirmation.

Impact of serous fluid volume on next-generation sequencing: a significant step forward for optimization of serous fluid sample collection.

Current literature lacks data regarding the influence of serous fluid volume (SFV) on next-generation sequencing (NGS) performed on malignant cases. In this study, we highlight the impact of SFV and other parameters influencing the outcome of NGS analysis. We evaluated 827 samples of serous fluids from 607 patients. Of these, 72 samples underwent NGS analysis. Effusion volume, tumor cellularity, DNA, and RNA quality metrics, as well as clinicopathologic and molecular data were evaluated. Pleural fluid accounted for 56.3% of the fluid samples collected. The most common primary tumor site was gastrointestinal/pancreatobiliary, adenocarcinoma was the most common histologic type. Overall mean volume was 293 mL. The mean Qubit DNA of the 72 effusion samples that underwent NGS analysis was 14.3 ng/µL and mean Qubit RNA was 28.2 ng/µL. The mean Qubit DNA concentration increases in SFV up to 100 mL only. No correlation exists between SFV and mean tumor cellularity. In addition, 74.6% (50 of 67) of sequenced samples showed oncogenic drivers; KRAS was the most common driver followed by EGFR. Three cases displayed ALK fusions, and 1 case displayed NTRK1 fusion. The DNA yield is higher in SFV of 100 mL as a cutoff. Beyond 100 mL, there is no impact of SFV on DNA yield. SFV does not impact RNA yield and mean tumor cellularity. Effusion samples should be submitted for molecular testing despite low tumor cellularity. Our results as a pilot study are important in optimization of SFV for both diagnosis as well as NGS analysis for improving management.

Interobserver agreement and risk of malignancy using the International Academy of Cytology Yokohama System for reporting breast FNA biopsy in a liquid-based exclusive cohort.

BACKGROUND: Per the College of American Pathologist's National Breast Fine Needle Aspiration Biopsy (FNAB) Practice Survey, ∼40% of laboratories use liquid-based cytology (LBC) for breast FNAB. The reproducibility of the International Academy of Cytology Yokohama System (YS) for reporting breast FNAB on LBC was explored. DESIGN: Breast FNAB specimens submitted as LBC only (all ThinPrep) between January 2017 and January 2021 were retrieved. Cases without histopathologic follow-up were excluded. Clinical and radiologic information was collected. One cytologist and six cytopathologists rendered diagnoses per YS. All reviewers were blinded to the original diagnosis and histopathologic follow-up. The risk of malignancy was calculated. Concordance rates were calculated by a weighted Cohen Kappa score (κ). RESULTS: Review of 110 cases demonstrated substantial to near-perfect agreement between each reviewer (κ = 0.73-0.91) and follow-up histopathology (κ = 0.66-0.85). The agreement was lowest in the inadequate (κ = 0.05) and atypical (κ = 0.04) categories. The lack of concordance in the atypical category was common in cases with low cellularity or incomplete structural features. The risk of malignancy for inadequate, benign, atypical, suspicious for malignancy, and malignant categories were 12.5% (2/16), 3% (2/65), 67%, (8/12) 100% (1/1), and 100% (16/16). CONCLUSION: Interobserver agreement is excellent using the five YS categories in LBC. Lack of cellularity and incomplete architectural features were barriers to perfect agreement. Established pitfalls in the interpretation of LBC were cause for atypical diagnoses. Continuous training and education are recommended to avoid misdiagnosis because of the nonconventional cytomorphologic features of LBC and to improve inadequate and atypical rates within YS.

Diagnostic interobserver agreement for thyroid fine-needle aspirates: Effects of reviewer experience and molecular diagnostics.

OBJECTIVES: Few cytologically indeterminate thyroid fine-needle aspirations (FNAs) harbor BRAF V600E. Here, we assess interobserver agreement for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III (atypia of undetermined significance [AUS]) FNAs harboring BRAF V600E and contrast their features with those harboring non-BRAF V600E alterations, with attention to cytopathology experience. METHODS: Seven reviewers evaluated 5 AUS thyroid FNAs harboring BRAF V600E. To blind reviewers, cases were intermixed with 19 FNAs falling within other TBSRTC categories and in which genetic alterations other than BRAF V600E had been identified (24 FNAs total). Interobserver agreement against both "index" and most popular ("mode") diagnoses was calculated. Four additional BRAF V600E cases were independently reviewed. RESULTS: Reviewers included 3 trainees and 3 American Board of Pathology (board)-certified cytopathologists. Board-certified cytopathologists, whose experience ranged from 2 to more than 15 subspecialty practice years, had known AUS rates. BRAF V600E was identified in 5 of 260 (2%) AUS FNAs. Interobserver agreement was higher among cytopathologists with more experience. Mode diagnosis differed from index diagnosis in 6 of 11 cases harboring RAS-like alterations; mode diagnosis was AUS in 4 of 5 BRAF V600E FNAs. CONCLUSIONS: Atypia of undetermined significance of thyroid FNAs harboring BRAF V600E is uncommon yet relatively reproducible, particularly among pathologists with experience. It is advisable to sequence BRAF across V600 in such cases.

Use of the Afirma Xpression Atlas for cytologically indeterminate, Afirma Genomic Sequencing Classifier suspicious thyroid nodules: Clinicopathologic analysis with postoperative molecular testing.

OBJECTIVES: Afirma has recently introduced its Xpression Atlas (XA) as an adjunct to its Genomic Sequencing Classifier (GSC) for risk stratification of cytologically indeterminate thyroid nodules. We evaluated the performance of Afirma XA and associated pathologic findings for Afirma GSC suspicious nodules. METHODS: Intradepartmental records of thyroid fine-needle aspirations (FNAs) from January 2021 to December 2022 were identified and reviewed for patient and nodule characteristics, FNA findings, molecular test results, and final surgical pathology, if available. RESULTS: Material for Afirma GSC testing was collected in 624 thyroid FNAs, and 148 (24%) were classified as cytologically indeterminate. Afirma GSC testing was successful in 132 (89%) of those cases, of which 35 (27%) were Afirma GSC suspicious. Afirma XA testing was positive in 11 cases (11/35 [31%]). Eight (73%) patients underwent surgery that revealed 7 patients with papillary thyroid carcinoma and 1 patient with noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (risk of malignancy: 100% [8/8]). Among the 24 patients with negative Afirma XA results, 19 (79%) underwent surgery, revealing 5 patients with malignancy and 3 patients with NIFTP (risk of malignancy: 42% [8/19]). Overall, the risk of malignancy for Afirma GSC suspicious nodules was 59% (16/27). CONCLUSIONS: Afirma XA improved risk stratification of thyroid disease with a high risk of malignancy in Afirma GSC suspicious nodules. A negative Afirma XA result, however, should not be used as a rule-out test.

Unsatisfactory Pap Test Results: A Critical Patient Management Problem Pre-Analytically Addressed by the Cytopathology Laboratory.

BACKGROUND: The unsatisfactory rate of Pap tests (PT) is an important quality assurance (QA) metric for a cytopathology laboratory. At our institution, an unsatisfactory PT slide is followed by a second ThinPrep (TP) slide. The aim of this study is to evaluate this QA practice. METHODS: Our laboratory processes an unsatisfactory TP PT with a follow-up second TP slide with or without glacial acetic acid. The correlation between the unsatisfactory rate and the second slide rate test was examined. RESULTS: A total of 2739 cases with a second TP slide were prepared for an unsatisfactory initial TP PT. After second slide preparation, 780 cases (28%) remained unsatisfactory. Using Spearman's rank correlation test, there was a notable negative correlation between the unsatisfactory rate and the second slide rate (rho = -0.42). Of those PTs recategorized as satisfactory TP, 1742 were negative for intraepithelial lesion or malignancy (NILM) (89%), 135 as atypical squamous cells of undetermined significance (ASC-US) (7%), 37 as low-grade squamous intraepithelial lesion (LSIL) (1.9%), 11 as atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) (0.6%), 8 as high-grade squamous intraepithelial lesion (HSIL) (0.4%), and 20 as atypical glandular cells (AGC) (1%). The final Bethesda categorization for all cases and the human papilloma virus (HPV) data was tabulated. CONCLUSIONS: A second slide preparation significantly reduced the unsatisfactory rate of the PT. This also had a significant impact by detecting clinically significant lesions. HPV testing can also be performed on slides reclassified from unsatisfactory to ASC-US or higher.

The World Health Organization Reporting System for Pancreaticobiliary Cytopathology: Overview and Summary.

The recently published WHO Reporting System for Pancreaticobiliary Cytopathology (World Health Organization [WHO] System) is an international approach to the standardized reporting of pancreaticobiliary cytopathology, updating the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSC System). Significant changes were made to the categorization of benign neoplasms, intraductal neoplasms, mucinous cystic neoplasms, and malignant neoplasms considered low grade. Benign neoplasms, such as serous cystadenoma, categorized as Neoplastic: benign in the PSC system, are categorized as Benign/negative for malignancy in the WHO system. Pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, and gastrointestinal stromal tumor, categorized as Neoplastic: other in the PSC system, are categorized as Malignant in the WHO System in accord with their classification in the 5th edition WHO Classification of Digestive System Tumours (2019). The two new categories of Pancreaticobiliary Neoplasm Low-risk/grade and Pancreaticobiliary Neoplasm High-risk/grade are mostly limited to intraductal neoplasms and mucinous cystic neoplasms. Low-risk/grade lesions are mucinous cysts, with or without low-grade epithelial atypia. High-risk/grade lesions contain neoplastic epithelium with high-grade epithelial atypia. Correlation with clinical, imaging, and ancillary studies remains a key tenet. The sections for each entity are written to highlight key cytopathological features and cytopathological differential diagnoses with the pathologist working in low resource setting in mind. Each section also includes the most pertinent ancillary studies useful for the differential diagnosis. Sample reports are provided for each category. Finally, the book provides a separate section with risk of malignancy and management recommendations for each category to facilitate decision-making for clinicians.

Digital cytology part 1: digital cytology implementation for practice: a concept paper with review and recommendations from the American Society of Cytopathology Digital Cytology Task Force.

Digital cytology and artificial intelligence (AI) are gaining greater adoption in the cytopathology laboratory. However, peer-reviewed real-world data and literature are lacking regarding the current clinical landscape. The American Society of Cytopathology in conjunction with the International Academy of Cytology and the Digital Pathology Association established a special task force comprising 20 members with expertise and/or interest in digital cytology. The aim of the group was to investigate the feasibility of incorporating digital cytology, specifically cytology whole slide scanning and AI applications, into the workflow of the laboratory. In turn, the impact on cytopathologists, cytologists (cytotechnologists), and cytology departments were also assessed. The task force reviewed existing literature on digital cytology, conducted a worldwide survey, and held a virtual roundtable discussion on digital cytology and AI with multiple industry corporate representatives. This white paper, presented in 2 parts, summarizes the current state of digital cytology and AI practice in global cytology practice. Part 1 of the white paper presented herein is a review and offers best practice recommendations for incorporating digital cytology into practice. Part 2 of the white paper provides a comprehensive review of AI in cytology practice along with best practice recommendations and legal considerations. Additionally, the results of a global survey regarding digital cytology are highlighted.

Digital cytology part 2: artificial intelligence in cytology: a concept paper with review and recommendations from the American Society of Cytopathology Digital Cytology Task Force.

Digital cytology and artificial intelligence (AI) are gaining greater adoption in the cytology laboratory. However, peer-reviewed real-world data and literature are lacking in regard to the current clinical landscape. The American Society of Cytopathology in conjunction with the International Academy of Cytology and the Digital Pathology Association established a special task force comprising 20 members with expertise and/or interest in digital cytology. The aim of the group was to investigate the feasibility of incorporating digital cytology, specifically cytology whole slide scanning and AI applications, into the workflow of the laboratory. In turn, the impact on cytopathologists, cytologists (cytotechnologists), and cytology departments were also assessed. The task force reviewed existing literature on digital cytology, conducted a worldwide survey, and held a virtual roundtable discussion on digital cytology and AI with multiple industry corporate representatives. This white paper, presented in 2 parts, summarizes the current state of digital cytology and AI practice in global cytology practice. Part 1 of the white paper is presented as a separate paper which details a review and best practice recommendations for incorporating digital cytology into practice. Part 2 of the white paper presented here provides a comprehensive review of AI in cytology practice along with best practice recommendations and legal considerations. Additionally, the cytology global survey results highlighting current AI practices by various laboratories, as well as current attitudes, are reported.

The current state of digital cytology and artificial intelligence (AI): global survey results from the American Society of Cytopathology Digital Cytology Task Force.

INTRODUCTION: The integration of whole slide imaging (WSI) and artificial intelligence (AI) with digital cytology has been growing gradually. Therefore, there is a need to evaluate the current state of digital cytology. This study aimed to determine the current landscape of digital cytology via a survey conducted as part of the American Society of Cytopathology (ASC) Digital Cytology White Paper Task Force. MATERIALS AND METHODS: A survey with 43 questions pertaining to the current practices and experiences of WSI and AI in both surgical pathology and cytology was created. The survey was sent to members of the ASC, the International Academy of Cytology (IAC), and the Papanicolaou Society of Cytopathology (PSC). Responses were recorded and analyzed. RESULTS: In total, 327 individuals participated in the survey, spanning a diverse array of practice settings, roles, and experiences around the globe. The majority of responses indicated there was routine scanning of surgical pathology slides (n = 134; 61%) with fewer respondents scanning cytology slides (n = 150; 46%). The primary challenge for surgical WSI is the need for faster scanning and cost minimization, whereas image quality is the top issue for cytology WSI. AI tools are not widely utilized, with only 16% of participants using AI for surgical pathology samples and 13% for cytology practice. CONCLUSIONS: Utilization of digital pathology is limited in cytology laboratories as compared to surgical pathology. However, as more laboratories are willing to implement digital cytology in the near future, the establishment of practical clinical guidelines is needed.

Automated and manual human papilloma virus in situ hybridization and p16 immunohistochemistry: comparison in metastatic oropharyngeal carcinoma.

OBJECTIVES: We compared the efficacy of automated and manual human papilloma virus (HPV) in situ hybridization (ISH) and p16 immunohistochemical staining (IHC) in fine needle aspiration (FNA) of metastatic oropharyngeal carcinoma. STUDY DESIGN: A total of 41 FNA cell blocks (CB) were evaluated. HPV ISH was interpreted as positive if a minimum of one tumor cell showed punctate dot-like nuclear positivity. p16 was interpreted as positive if ≥70% of tumor cells showed brown nuclear and cytoplasmic staining. RESULTS: Thirty of 41 CB (73%) were positive by automated HPV ISH, 25 of 41 CB (60%) with manual HPV ISH. Eighteen of 41 CB (43%) were positive for p16 IHC. Twelve of 41 CB (29%) with automated HPV ISH and 2 of 41 CB (4%) with the manual method were positive at 10× magnification. Three of 41 CB (7%) with automated HPV ISH and 14 of 41 CB (34%) with the manual method were positive at 20× magnification. Fifteen of 41 CB (36%) with automated HPV ISH and 9 of 41 CB (21%) with the manual method were positive at 40-60× magnification. CONCLUSION: Automated HPV ISH plays a more significant role in determining the HPV status in CB. However, the failure to use high magnification in the evaluation can give false-negative results.

The differential diagnosis of squamous cells in pancreatic aspirates: from contamination to adenosquamous carcinoma.

BACKGROUND: This study was conducted to describe the frequency and significance of squamous cells in fine needle aspiration (FNA) specimens of the pancreas in benign and malignant processes. METHODS: A retrospective review was performed of 102 patients with squamous cells in their pancreatic FNA specimens from 1986 to 2012. The malignant cases were classified as adenosquamous carcinoma (ASqC) or metastatic squamous cell carcinoma, and a double institutional review of the ASqC cases was undertaken to characterize the clinical and pathological features and survival statistics of patients who present with unresectable or metastatic ASqC and have no follow-up surgery. Survival analyses were performed. RESULTS: Of the 4,094 pancreas FNA procedures performed in the study, squamous features were found in 102 (2.5%) of all cases, and 48% of these cases represented ASqC. The other cases were contamination (52%) or atypical (<1%). ASqC constituted 4.5% (46/1,025) of all primary pancreatic exocrine malignancies. When compared with conventional adenocarcinoma, ASqC demonstrated a significantly poorer overall median survival (11.0 vs. 6.51 months; p = 0.023), and this difference was also seen in patients presenting with metastatic disease (median survival of 9.1 vs. 4.2 months; p = 0.025). CONCLUSIONS: Squamous cells in FNA specimens from the pancreas have a broad differential diagnosis that ranges from contamination to ASqC.

Lymphoproliferative disorders of the kidney on fine-needle aspiration: cytomorphology and radiographic correlates in 33 cases.

BACKGROUND: Unless renal lesions present in the setting of widespread lymphoma, biopsy can be indicated to differentiate from metastases, hypovascular renal cell carcinoma, urothelial carcinoma or infection. We review our experience with lymphoproliferative disorders in the kidney diagnosed by fine-needle aspiration (FNA), and focus on clinicopathologic and radiographic features. DESIGN: All cases of non-Hodgkin lymphoma diagnosed on renal FNA at 2 academic institutions between 1989 and 2011 were reviewed. Clinical history, radiographic and cytomorphologic features, and follow-up were assessed. RESULTS: 33 cases were identified, with 15 primary tumors and 18 recurrences/secondary tumors including 1 acute lymphoblastic lymphoma. The majority were aggressive/high-grade lesions (25/33). 25 cases were substantiated by positive flow cytometry results. Most were detected at follow-up/incidentally. 22 cases showed multiple renal and/or retroperitoneal masses or a significant component of adenopathy; others showed a solitary renal mass. Salient radiologic features included hypodense, infiltrative and ill-defined masses. Cytomorphology showed a monotonous population of large atypical lymphoid cells, often with lymphoglandular bodies. CONCLUSION: Cytologic diagnosis of renal lymphoma requires analysis of morphological, clinical and immunophenotypic information. Helpful features for diagnosis include: multiple masses on computed tomography, a monotonous population of abnormal cells in a background of lymphoglandular bodies and immunophenotyping demonstrating light chain restriction.

Are we on track for diagnosing high-grade urothelial carcinoma with a minimum quantity of five malignant cells in lower tract specimens? Critical analysis of The Paris System Quantitation Criteria.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) has gained universal acceptance as the standard for reporting urine cytology requiring at least 5-10 malignant cells to diagnose high-grade urothelial carcinoma (HGUC) in lower and upper urinary tract specimens, respectively. These quantitation criteria are still subject to discussion, and this study specifically aims to validate the quantitation criterion of HGUC in lower urinary tract. DESIGN: The authors reviewed two cohorts of lower urinary tract cases. The first cohort consisted of 100 liquid-based ThinPrep slides with the diagnosis of HGUC having positive histology on concurrent or follow-up biopsies within 3 months. The second cohort was 36 HGUC cases with negative histology on concurrent biopsies and within 3 months. The number of high-grade cells (HGCs) meeting the TPS qualitative criteria were counted under the light microscope driven in a grid-like manner. RESULTS: The first 100 urine samples showed five cases (5.0%) with three HGCs, three cases (3.0%) had four HGCs, five cases (5.0%) showed five HGCs, and 25 cases (25.0%) had between 6-10 HGCs. The risk of high-grade malignancy (ROHM) in cases with five or more HGCs was 100%, whereas those with three HGCs was 60.0%. The second cohort of HGUC was considered "positive" despite a negative histology. CONCLUSION: This study confirms that quantitation is an essential key to diagnose HGUC. The current TPS criterion of a minimum of five malignant cells in lower tract is robust with a ROHM of 100%. Diagnosing HGUC with less than five HGCs runs the risk of lowering the ROHM.

Optimal fluid volume for detecting malignancy in serous effusions: a single institution experience.

INTRODUCTION: Detection of malignant cells in serous fluids is an indicator of advanced stage of malignancy and is critical in clinical management decisions and prompt treatment initiation. The minimum volume which is ideal for detecting malignancy in serous fluid is not well established. In this study, we aim to identify optimal volume that will be ideal for adequate cytopathological diagnosis. MATERIALS AND METHODS: A total of 1597 samples of serous fluids from 1134 patients were included in the study. Samples were diagnosed based on International System for Reporting Serous Fluid Cytopathology (ISRSFC). Clinicopathologic results from different diagnostic groups were compared and statistically analyzed. RESULTS: Pleural fluids comprised 890 (55.7%) specimens, followed by 456 (28.6%) peritoneal, 128 (8%) ascites, and 123 (7.7%) pericardial fluid specimens. The majority were negative for malignancy (1138, 71.3%), followed by malignant (376, 23.5%), atypical (59, 3.7%), and suspicious for malignancy (24, 1.5%). Malignancy was identified in sample with volumes from 5 mL to 5000 mL. Rate of detection of malignant cells increased significantly with higher sample volumes. For malignancy detection the optimal volume for overall serous fluid is 70 mL. Pericardial fluid is an exception, with lower mean volume and significantly lower proportion of cases with malignant diagnosis. CONCLUSIONS: Our study indicates that higher fluid volumes have a higher rate of malignancy detection and a low false-negative rate. We recommend a minimum of 70 mL of serous fluid for optimal cytopathologic examination and malignancy detection. Pericardial fluid is an exception, with lower mean volume and thus lower requirement.

Optimal carcinoembryonic antigen (CEA) cutoff values in the diagnosis of neoplastic mucinous pancreatic cysts differ among assays.

AIM: Pancreatic cyst fluid carcinoembryonic antigen (CEA) is a pivotal test in the diagnosis and management of neoplastic mucinous cysts (NMC) of the pancreas. Cyst fluid CEA levels of 192 ng/mL have been widely used to identify NMC. However, CEA values are unique to and significantly differ between individual assays with various optimal cutoffs reported in the literature for NMC. Here, we investigate the optimal CEA cut-off value of pancreatic cysts from two different assays to identify differences in thresholds. METHODS: Pancreatic cyst fluid CEA levels, CEA assay platform (Beckman Dxl (BD) or Siemens Centaur XP (SC)), and clinical/pathological information were retrospectively collected. Cases were categorised into either NMC or non-NMC. Optimal CEA cut-off values were calculated via a receiver operator characteristic curve. Cut-off values were then identified separately by assay platform. RESULTS: In total, 149 pancreatic cystic lesions with concurrent CEA values (SC: n=47; BD: n=102) were included. Histological correlation was available for 26 (17%) samples. The optimal CEA cut-off value for all samples at the study institution was 45.9 ng/mL (area under the curve (AUC)=86, Sn=85.7%, Sp=73.8%). When analysed separately by CEA assay, the cut-off values were 45.9 ng/mL (AUC=84.27, Sn=89.7%, Sp=71.4%) for BD and 24.4 ng/mL (AUC=77, Sn=81.8%, Sp=75%) for SC (p=0.48). CONCLUSIONS: This study showed an optimal pancreas cyst CEA cut-off threshold of 45.9 ng/mL, which is lower than commonly cited literature with different cutoffs on the two separate platforms (BD: 45.9 ng/mL, SC: 24.4 ng/mL).