[New edition of the Paris classification 2022: What is new?] / Neue Auflage der Paris-Klassifikation 2022: Was ist neu?

As an internationally accepted diagnostic system, the Paris classification has achieved a global breakthrough in the standardization of diagnoses in urine cytology. Based on experience over the past few years since its first publication, the new edition of the Paris classification refines the diagnostic criteria and discusses diagnostic pitfalls. While the detection of high-grade urothelial carcinoma remains the main focus, other aspects of urine cytology, including cytology of the upper urinary tract and the associated challenges, have also been addressed. Low-grade urothelial neoplasia is no longer listed as a separate category but is now included in the category "negative for high-grade urothelial carcinoma" (NGHUC). Essentially, the Paris classification provides an important basis for estimating the risk of malignancy and further clinical management.

Role of Pap Smear Cervical Cytology in the Diagnosis of Extrauterine Malignancies: Largest Study of 104 Cases from Tertiary Care Cancer Centre in India.

INTRODUCTION: Extrauterine malignancies in cervical samples are rarely seen. It is important to differentiate these cells from those of primary uterine malignancies to determine appropriate line of further investigations and management. Literature on these lesions is limited largely restricted to case reports. The aim of the present study was to study the spectrum and cytomorphological features of extrauterine malignancies in cervical Pap smears. MATERIALS AND METHODS: It is a retrospective and descriptive study conducted in Department of Cytopathology from January 2019 to July 2023. All cases of extrauterine malignancies with available cytology material were included in this study. All cases of primary uterine malignancies, i.e., uterine corpus or cervix confirmed by clinical, radiological, and histopathological examination were excluded. RESULTS: 104 out of 11,674 cytology Pap smears were those of extrauterine malignancy. Diagnosis of extrauterine malignancy was given in 47.1% cases, 30.9% were reported as positive for malignancy without giving the possibility of an extrauterine origin, and 22.0% were reported as atypical glandular cells only. In 56 cases where Pap smear was the first investigation which led to the diagnosis. Most common extrauterine malignancy was adenocarcinoma principally from ovarian, colorectal, and vaginal origin. Other epithelial malignancies noted were urothelial carcinoma and invasive breast carcinoma. Among non-epithelial malignancies, we reported vaginal mucosal melanoma, cutaneous melanoma, acute leukaemia, and anaplastic large cell lymphoma. CONCLUSION: High index of suspicion, presence of squamous and glandular elements with no atypical features, and occasional clusters of cells with marked atypia and usually no necrosis in the background are helpful cytomorphological clues to raise suspicion for extrauterine malignancy. Correlation with serology, radiology, and immunocytochemistry can help in reaching final diagnosis.

Factors affecting the diagnostic value of liquid-based cytology by EUS-FNA in the diagnosis of pancreatic cystic neoplasms.

Background and Objectives: This study retrospectively evaluated the value of liquid-based cytology (LBC) alone for diagnosing pancreatic cystic neoplasms (PCNs) in a large sample and initially estimated factors that might affect LBC diagnostic ability. Methods: From April 2015 to October 2022, we prospectively enrolled 331 patients with suspected PCNs in our prospective database. Among them, 112 patients chosen to receive surgical resection were included. Only 96 patients who underwent EUS-guided cystic fluid LBC were finally studied. The diagnostic values of LBC for differentiating benign and malignant PCNs and subtypes of PCNs were evaluated. Results: There were 71 female and 25 male patients with a mean age of 47.6 ± 14.4 years. The median cyst size was 43.4 mm. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of LBC for the differentiation of benign and malignant PCNs were 96.9%, 57.1%, 100%, 100%, and 96.7%, respectively. The overall diagnostic accuracy of LBC for specific cyst types was 33.3% (32/96). Cysts located in the pancreatic body/tail or with irregular shapes were more likely to obtain a definite LBC diagnosis. At the same time, age, sex, tumor size, cystic fluid viscosity, operation time, needle type, and presence of septation were not significantly different. Conclusion: Liquid-based cytology alone is useful for differentiating benign PCNs from malignant PCNs and can successfully characterize the PCN subtypes in one-third of patients. Pancreatic cystic neoplasms located in the body/tail or exhibiting irregular shapes are more likely to obtain a definite LBC diagnosis.

Comparative evaluation of the diagnostic and prognostic performance of CNSide™ versus standard cytology for leptomeningeal disease.

Background: This retrospective study compares the real-world performance of cerebrospinal fluid (CSF) CNSide™ versus cytology in leptomeningeal disease (LMD). Methods: Consecutive patients with suspected LMD who underwent lumbar punctures for CSF cytology and CNSide™ from January 2020 to December 2022 were reviewed. LMD was classified by EANO criteria. Descriptive statistics, confusion matrix, Kaplan-Meier curves, and Cox proportional regression were used. Results: Median age for 87 evaluable patients was 63 years (range: 23-93); 82 (94%) met EANO criteria for possible/probable/confirmed LMD (EANO/LMD). The commonest primary cancers were breast (36,44.0%) and lung (34,41.5%). Primary lung harbored actionable mutations in 18 (53.0%); primary breast expressed hormone receptors in 27 (75%), and HER2 amplification in 8 (22%). Uncontrolled systemic disease was detected in 35 (40%), while 25 (46%) received systemic therapy with medium/high CNS penetrance at LMD diagnosis. The median time from initial cancer to LMD diagnosis was 31 months (range: 13-73). LMD was confirmed by CSF cytology in 23/82 (28%), all identified by CNSide™. CNSide™ identified 13 additional cases (36/82, 43.9%), increasing diagnostic yield by 56.5%. Median overall survival (mOS) was 31 weeks (95%CI: 21-43), significantly worse for CNSide™ positive versus negative: 4.0 versus 16.0 weeks, respectively (HR = 0.50, P = .010). While survival since LMD diagnosis did not differ by histology, time to LMD diagnosis from initial cancer diagnosis was longer for breast (48.5 months, IQR: 30.0-87.5) versus lung (8 months, IQR:0.5-16.0) cohorts. mOS was longer for patients eligible for intrathecal chemotherapy (HR: 0.189, 95%CI: 0.053-0.672, P = .010). Conclusions: This retrospective, real-world analysis of CNSide™ showed increased sensitivity versus cytology and provided clinically relevant molecular CSF analyses.

Invasive Breast Cancer of No Special Type With Osteoclast-Like Giant Cells: A Cytological Clue Providing the Final Diagnosis for Histology.

Breast cancer associated with osteoclast-like giant cells (OGCs) refers to a morphological pattern of invasive breast carcinoma of non-special type. Their presence is sometimes subtle, but OGCs can be appreciated both histologically and immunohistochemically. The origin of OGCs as well as their implication for prognosis remain debated. We describe the case of a 65-year-old woman, wherein the presence of OGCs in the fine-needle aspiration cytology of a metastatic axillary lymph node suggested the final diagnosis on histology. The differential diagnosis is broad, and here we provide evidence for strict cytological-histological correlation when dealing with unusual breast lesions.

Interobserver agreement and diagnostic challenges of Congo red staining for amyloid detection on fat pad aspiration biopsies.

INTRODUCTION: Congo red staining of fat pad fine needle aspiration specimens is a method utilized for evaluation of amyloid deposition. However, these specimens can pose diagnostic challenges for cytopathologists. As part of ongoing internal quality improvement measures, the objective of this study was to evaluate the intradepartmental interobserver agreement of these specimens and to identify factors that affect the variability of the interpretations. MATERIALS AND METHODS: There were 7 participants, which included 3 trainees, 3 cytopathologists, and 1 cytotechnologist. Each participant reviewed 50 Congo red stained fat pad fine needle aspiration slides. The interpretations were categorized into 3 groups: negative, indeterminate/suspicious, and positive. The participants also noted any interpretation challenges they encountered for each case. RESULTS: There was only slight interobserver agreement among all participants (κ = 0.133). Stratified by participant group, the interobserver agreement among the trainees was slight bordering on poor (κ = 0.028) and among cytopathologists was fair (κ = 0.249). The highest agreement between 2 observers was between 2 cytopathologists and the level of agreement was moderate bordering on fair (κ = 0.426). There were only 3 cases (6.0%) with full agreement among observers, while in 25 cases (50.0%), there were 2 category differences in interpretations. The primary diagnostic challenge reported by participants was when weak or focal birefringence was encountered as well as cases complicated by poor stain quality and overstaining. CONCLUSIONS: We found only slight interobserver agreement among all study participants. A major area of challenge was cases with weak birefringence resulting in high variance of interpretation among participants.

Clinical and cytological characteristics of serous effusions in 69 cases of lymphoma patients.

BACKGROUND: To explore the value of cell morphology, immunophenotype, and gene alterations of serosal effusion in the diagnosis of lymphoma. METHODS: Serosal effusion of 69 cases of lymphoma patients were collected, including 36 cases with malignant effusion and 33 cases with nonmalignant effusion. Ordinary cytology, liquid-based cytology, cellblock, and immunocytochemical staining were performed in each case, some cases were detected by fluorescence in situ hybridization for C-MYC, BCL2, and BCL6 gene translocations. T/B cell ratio in malignant and nonmalignant serosal effusions was analyzed and compared by flow cytometry (FCM) and immunohistochemical (IHC), respectively. The prognostic value of serous effusion in diffuse large B-cell lymphoma (DLBCL) was investigated and another 20 DLBCL cases without effusion were successively selected as control. RESULTS: The number of naive lymphocytes, apoptotic bodies, and mitotic figures were more common in malignant effusions compared with nonmalignant effusions (p < .01). The top three lymphomas in malignant effusion were DLBCL (19/36, 52.8%), mantle cell lymphoma (MCL) (4/36, 11.1%, 3 blastoid variant) and high-grade B-cell lymphoma (HGBL) (4/36, 11.1%). T/B cell ratio by FCM analysis ranged from 0.00 to 0.55 (mean 0.084) in malignant effusion, and 2.58 to 984.00 (mean 249.9) in nonmalignant effusion. The difference was significant (p = .017). The T/B cell ratio by IHC analysis ranged from 0.02 to 3.00 (mean 0.200) in malignant effusion, and 2.00-100.00 (mean 34.10) in nonmalignant effusion. The difference was significant (p = .017). In the effusions involving DLBCL, most effusions were present at the time of diagnosis (57.9%); single pleural effusions were more common (36.8%). The median overall survival times of patients with malignant effusion, nonmalignant effusion and DLBCL without serous effusion were 11, 17, and 23 months respectively (p = .04). Three patients of HGBL died, and the overall survival times were 5, 8, and 9 months, respectively. CONCLUSIONS: The cytomorphological characteristics combined with immunophenotype, FCM, gene rearrangement, and other tests can diagnose and classify patients with effusion as the first symptom. The T/B cell ratio is less than 1 by FCM or IHC suggesting a malignant serosal effusion. The presence of malignant effusion in DLBCL patients is an important clue for poor prognosis.

Management of intrahepatic and perihilar cholangiocarcinomas: Guidelines of the French Association for the Study of the Liver (AFEF).

Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant primary liver cancer. iCCA may develop on an underlying chronic liver disease and its incidence is growing in relation with the epidemics of obesity and metabolic diseases. In contrast, perihilar cholangiocarcinoma (pCCA) may follow a history of chronic inflammatory diseases of the biliary tract. The initial management of CCAs is often complex and requires multidisciplinary expertise. The French Association for the Study of the Liver wished to organize guidelines in order to summarize the best evidence available about several key points in iCCA and pCCA. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe the epidemiology of CCA as well as how patients with iCCA or pCCA should be managed from diagnosis to treatment. The most recent developments of personalized medicine and use of targeted therapies are also highlighted.

Cytology or Multiparameter Flow Cytometry Positivity in the Cerebrospinal Fluid Before Transplantation is Predictive of Poor Outcomes After Allotransplantation in Acute Myeloid Leukemia Patients.

INTRODUCTION: Central nervous system leukemia (CNSL) remains a serious complication in patients with acute myeloid leukemia (AML) and an ambiguous prognostic factor for those receiving allo-geneic hematopoiesis stem cell transplantation (allo-HSCT). It is unknown whether using more sensitive tools, such as multiparameter flow cytometry (MFC), to detect blasts in the cerebrospinal fluid (CSF) would have an impact on outcome. METHODS: We retrospectively analyzed the clinical outcomes of 1472 AML patients with or without cytology or MFC positivity in the CSF before transplantation. Abnormal CSF (CSF+) was detected via conventional cytology and MFC in 44 patients at any time after diagnosis. A control group of 175 CSF-normal (CSF-) patients was generated via propensity score matching (PSM) analyses according to sex, age at transplant, and white blood cell count at diagnosis. RESULTS: Compared to those in the CSF-negative group, the conventional cytology positive and MFC+ groups had comparable 8-year nonrelapse mortality (NRM) (4%, 4%, and 6%, p = 0.82), higher cumulative incidence of relapse (CIR) (14%, 31%, and 32%, p = 0.007), lower leukemia-free survival (LFS) (79%, 63%, and 64%, p = 0.024), and overall survival (OS) (83%, 63%, and 68%, p = 0.021), with no significant differences between the conventional cytology positive and MFC+ groups. Furthermore, multivariate analysis confirmed that CSF involvement was an independent factor affecting OS and LFS. CONCLUSION: Our results indicate that pretransplant CSF abnormalities are adverse factors independently affecting OS and LFS after allotransplantation in AML patients.

Cytological and metabolomic analysis of Citrus fruit to elucidate puffing disorder.

Puffiness, a physiological disorder commonly observed during the ripening and post-harvest processes of fruits in Citrus reticulata, significantly affects the quality and shelf-life of citrus fruits. The complex array of factors contributing to puffiness has obscured the current understanding of its mechanistic basis. This study examined the puffing index (PI) of 12 citrus varieties at full ripeness, focusing on the albedo layer as a crucial tissue, and investigated the correlation between cellular structural characteristics, key primary metabolites and PI. The findings revealed that the cell gap difference and the number of lipid droplets were closely linked to PI. Chlorogenic acid, Ferulic acid, D-Galacturonic acid, D-Glucuronic acid, (9Z,11E)-Octadecadienoic acid, and 9(10)-EpOME were identified as pivotal primary metabolites for rind puffing. Determination of lignin, protopectin, cellulose and lipoxygenase content further validated the relationship between cell wall, lipid metabolism and rind puffing. This study furnishes novel insights into the mechanisms underlying puffing disorder.

Cytopathology and clinicopathological correlation of renal neuroendocrine neoplasms.

INTRODUCTION: There is a lack of documentation regarding cytopathology of renal neuroendocrine neoplasms (NENs) due to their rarity. MATERIALS AND METHODS: Five cytology cases were gathered from 3 institutes. RESULTS: Cohort consisted of 4 females and 1 male. Fine needle aspiration biopsy and touch preparation slides of core needle biopsy revealed cellular samples, composed of round, plasmacytoid, or columnar cells. Tumor cells were present in nested, acinar, 3D cluster, and individual cell patterns. Tumor cells in 3 cases exhibited uniformly round to oval small nuclei with inconspicuous nucleoli, finely granular chromatin, and smooth nuclear membranes, whereas 2 other cases showed pleomorphic nuclei with conspicuous nucleoli, nuclear molding, and irregular nuclear membranes. Tumor cells displayed pale or granular cytoplasm, with 1 case showing small vacuoles. Examination of cores and cell blocks demonstrated tumor cells in sheets, nests, or acini. All tumor cells were positive for neuroendocrine immunomarkers. Based on mitotic count, Ki-67 index and morphology, 3 tumors were graded as well-differentiated neuroendocrine tumor (WDNET) (1 grade [G] 3, 1 G2, 1 G1) and 2 as large cell neuroendocrine carcinoma. Deletion of 7q, 10q, and 19q was detected in WDNETs. Two patients with large cell neuroendocrine carcinoma and 1 with WDNET G3 underwent chemotherapy due to aggressiveness, whereas nephrectomy was performed for patients with WDNET G1 and 2 without metastasis. CONCLUSIONS: Cytopathological characteristics of renal NENs closely resemble those affecting other organs. Despite its rarity, renal NENs should be kept in mind when confronted with morphological resemblances to NENs, to prevent misdiagnosis and inappropriate therapeutic interventions.

Exploring a Desirable Quadr-mRNAs Panel for Non-invasive and Ultrasensitive Bladder Cancer Diagnosis: In-silico and Clinical Studies.

BACKGROUND: Most patients with non-muscle invasive bladder cancer (NMIBC) have a high direction for recurrence and disease progression, which remains a significant unresolved challenge in bladder cancer patients. Therefore, a constant search is necessary for identifying appropriate and reliable biomarkers for early diagnosis of NMIBC. The current study has aimed to search for valuable diagnostic biomarkers in the tissue and urine specimens of NMIBC patients. METHODS: The changes of twelve candidate mRNAs in a screening phase (40 tissue samples of NMIBC patients and their corresponding 40 urine specimens) and a subsequent independent validation phase (40 urine specimens) were estimated using real-time polymerase chain reaction (RT-qPCR). The receiver operating characteristic (ROC) analysis was executed to determine the potential diagnostic values of mRNAs. RESULTS: The mRNA levels of seven candidate genes were markedly higher in tissue specimens relative to their neighboring tissues. Among them, four mRNAs, including ERBB2, CCND1, MKI67, and MAGEA6, were differentially expressed in urine samples of NMIBC patients relative to control subjects. Further, the expression of these four mRNAs was validated in the validation step. Combining these biomarkers showed better diagnostic performance than single biomarkers in the urine sample for non-invasive NMIBC detection. The combination of these mRNAs and cytology enhanced the sensitivity of cytology from 37% to 87%. CONCLUSION: Our findings suggested that a four-mRNA panel may be promising in the non-invasive diagnosis of NMIBC, which deserves further investigation.

Micropropagation of Dipcadi montanum (Dalz.) Baker (Asparagaceae): a rare scapigerous herb.

Dipcadi montanum (Dalz.) Baker (Asparagaceae) is a rare scapigerous herb endemic to the Western Ghats, a global biodiversity hotspot running parallel to the western coast of India. This study reports the development of a reproducible protocol for mass propagation of this underutilized geophyte using bulb scale and immature leaf base explants. Miniature bulblets were successfully induced from both types of explants after 4 and 8 weeks of culture on full-strength semisolid MS basal medium fortified with 3% sucrose and varying levels of BAP (4.4-17.7 µM) and TDZ (4.5-18.1 µM). The addition of 2.7 µM NAA further enhanced the rate of microbulb induction. Rooting of the 8-week-old bulblets, obtained from both explants, was achieved with more than 90% efficiency on liquid as well as agar-gelled half-strength MS basal medium fortified with varying levels of IBA (2.46-9.84 µM) and NAA (2.68-10.74 µM), with or without 2.32 µM Kinetin. More than 95% of the rooted plants survived the initial acclimatization process under controlled ex-vitro conditions, and a survival rate of over 80% was recorded after 4 weeks of transfer to greenhouse conditions. After a brief dormancy, the regenerants resumed growth in the postmonsoon season and exhibited morphological resemblance to the donor plant. Comparative cytological analysis between the donor and 15 randomly selected regenerants revealed a stable somatic count of 2n = 20.

Diagnostic value of ultrasound-guided fine-needle aspiration cytology in the pathological natures of thyroid nodules: A retrospective study.

Objective: Thyroid nodules, a clinical disease with high incidence, include benign and malignant types. This study aims to evaluate the diagnostic value of ultrasound-guided fine-needle aspiration cytology (US-FNAC) in determining the pathological nature of thyroid nodules and to conduct an in-depth analysis of its diagnostic efficacy across nodules of varying sizes. Material and Methods: This retrospective study identified 116 patients undergoing thyroidectomy in Zibo Central hospital from January 2022 to March 2023, with 98 meeting the study's inclusion criteria. All patients received ultrasound and US-FNAC examinations before surgery to analyze the ultrasonic features of thyroid nodules. The diagnosis results of pathological natures obtained by US-FNAC were analyzed with the result of post-operative pathological examination as the gold standard. The patients were divided into four groups according to the median and quartile of nodular diameters to explore the diagnostic efficacy of US-FNAC for the pathological natures of thyroid nodules with various diameters and comprehensively evaluate its application value. The evaluation tool of diagnostic efficacy was the receiver operator characteristic (ROC) curve. Results: A total of 98 puncture nodules were evaluated, with a diameter of 0.8-5.2 cm. Post-operative pathological examination showed 10 (10.20%) benign and 88 (89.80%) malignant lesions. The ultrasound examination showed 14 (14.29%) benign and 84 (85.71%) suspected malignant lesions. The US-FNAC results showed 2 cases (2.04%) of type I, 9 cases (9.18%) of type II, 3 cases (3.06%) of type III, 29 cases (29.59%) of type IV, 39 cases (39.80%) of type V, and 16 cases (16.33%) of type VI, including 9 (9.18%) benign and 84 (85.72%) malignant lesions and 5 (5.10%) uncertain pathological natures. According to the median and quartile of nodular diameters, specifically, 1.90 (1.60, 2.30) cm, 93 nodules with decided pathological natures were divided into groups Q1 (n = 24, ≤1.6 cm), Q2 (n = 26, 1.7-1.9 cm), Q3 (n = 24, 2.0-2.3 cm), and Q4 (n = 19, >2.3 cm). The results of ROC analysis showed that the area under the curve (AUC), sensitivity, and specificity of US-FNAC diagnosis were 0.894, 98.80%, and 80.00%, respectively. The AUCs of US-FNAC in groups Q1, Q2, Q3, and Q4 were 0.978, 1.000, 0.977, and 0.971. The AUCs of Q1 group, Q2 group, Q3 group and Q4 group were all > 0.9, and US-FNAC had high diagnostic efficiency for the pathological properties of thyroid nodules with different diameters. Conclusion: US-FNAC has a high diagnostic efficiency for the pathological properties of thyroid nodules. Whether the nodule diameter has an effect on the accuracy of this method requires more clinical evidence.

Utility of immunocytochemistry in diagnosing abdominopelvic washings from patients undergoing radical surgery for endometrial cancer.

Objective: This study aimed to explore the efficacy of immunocytochemistry in diagnosing abdominopelvic washings (APWs) and evaluate the superiority of cytology combined with immunocytochemistry over cytology alone. Material and Methods: Data on APW cytology and available cell blocks from patients who underwent radical surgery for endometrial cancer between January 2021 and December 2022 were reviewed. Cytology was re-evaluated according to a five-tier system. Immunocytochemistry analysis for targets such as Sry box transcription factor 1(SOX17), Paired box gene 2 (Pax-2) protein, Phosphatase and tensin (PTEN), and ß-catenin was performed on each case with non-negative cytology. Mismatch repair (MMR) protein and P53 immunocytochemistry analyses were performed using cell blocks from cases with abnormal MMR or P53 expression in their primary lesion. The accuracies of cytology combined with immunocytochemistry and cytology alone were calculated. Results: Overall, 126 patients were included in this study, 18 of whom demonstrated non-negative cytology of APW. Cell blocks were successfully prepared for 16 cases. SOX17 positivity was observed in 16 cases, including 1 of serous carcinoma, 1 of clear cell carcinoma, and 14 of endometrioid carcinoma (EC). Loss of Pax-2 and PTEN expression was observed in the APWs of the 14 patients with EC. MMR deficiency was noted in two patients with EC, and P53 mutation was noted in another two patients with EC. Compared with 10 metastatic carcinomas (10/18, 55.56%) diagnosed by cytology alone, 15 malignant APWs (15/18, 83.33%) were confirmed through combination cytology and immunocytochemistry. APWs were more likely to be observed in cases with more than half myometrial invasion than those with no or less than half myometrial invasion (P = 0.0067). The probability of malignant APW occurrence was slightly elevated in cases of EC exhibiting microcystic, elongated, and fragmented(MELF) infiltrative growth (P = 0.039). Conclusion: SOX17 is a useful Müllerian marker for distinguishing endometrial epithelium in APW. Loss of Pax-2 and PTEN expression offers evidence of metastatic endometrial carcinoma. Furthermore, positive APWs retained molecular features similar to primary lesions. The use of multiple immunocytochemical markers can effectively enhance the diagnostic efficiency of APWs.

Cytomorphological characteristics of low-grade papillary urothelial carcinoma in voided urine samples: Distinction from benign and high-grade papillary urothelial carcinoma.

OBJECTIVE: Given its frequent recurrence and the potential for high-grade transformation, accurate diagnosis of low-grade papillary urothelial carcinoma (LGPUC) in urine cytology is clinically important. We attempted to identify cytomorphologic features in urine samples, which could be helpful for the identification of LGPUC. METHODS: We conducted a retrospective review of voided urine specimens collected from patients with histopathologic diagnoses of LGPUC. Their cytomorphological features were compared with those from patients with benign conditions and high-grade papillary urothelial carcinoma (HGPUC). RESULTS: A total of 115 voided urine specimens were evaluated, including 30 benign, 41 LGPUC, and 44 HGPUC cases. In LGPUC, 18 cases (44%) were diagnosed as atypical, a proportion significantly higher than that observed in benign cases (4 cases, 13%), while the remaining 23 cases (56%) were diagnosed as negative. LGPUC urine samples tended to have higher cellularity than benign cases, but the difference was not statistically significant. Three cytological features, namely nuclear enlargement, higher nuclear-to-cytoplasmic (N/C) ratio, and presence of small cell clusters, were statistically more prevalent in LGPUC compared to benign cases, although the changes were relatively subtle. In contrast, cytomorphological distinction between LGPUC and HGPUC was evident, as high cellularity, nuclear enlargement, hyperchromasia, high N/C ratio, irregular nuclear membrane, and apoptosis were significantly more prevalent in HGPUC cases. CONCLUSIONS: Several cytomorphologic features in voided urine samples were more prevalent in cases with LGPUC, albeit not observed in all instances. Since these alterations were relatively subtle, meticulous attention to these cytomorphologic details is crucial to suggest the possibility of LGPUC.

Diagnostic Accuracy of Fine-Needle Aspiration Cytology in Cervical Lymphadenopathies at a Tertiary Care Center in the Kingdom of Bahrain.

Introduction  Fine-needle aspiration cytology (FNAC) has become widely used as a first-line diagnostic tool in the evaluation of cervical lymphadenopathies (LADs). However, there are conflicting reports regarding its accuracy in differentiating between malignant and benign pathologies. In this study, we aim to determine the reliability of FNAC in distinguishing between benign and malignant pathologies causing cervical LAD. Methods This is a cross-sectional study reviewing the electronic medical records of all patients who underwent both FNAC and excisional biopsy of cervical LADs between January 2016 and December 2023 at a tertiary care center in the Kingdom of Bahrain. A comparison was conducted between the cytopathological results obtained by FNAC and the histopathological results obtained by excisional biopsy to determine the diagnostic accuracy of FNAC. Results In the study period, 83 patient records were reviewed and included in the data analysis. Fine-needle aspiration cytology yielded a sensitivity of 89.3%, a specificity of 55.6%, a positive predictive value (PPV) of 72.4%, a negative predictive value (NPV) of 80.0%, and an overall accuracy of 74.7% in diagnosing cervical LADs. Conclusion Despite FNAC being accessible, convenient, and cost-effective, it has certain limitations that can restrict its accuracy in diagnosing lymphomas. We recommend further studies to research these limitations and the possible tools, such as ancillary testing, that may be useful in overcoming them.

Noninvasive Tests for Bladder Cancer Detection and Surveillance: A Systematic Review of Commercially Available Assays.

BACKGROUND: An important reason for the high health care costs associated with bladder cancer is the need for frequent cystoscopy for detection and surveillance of this disease. Cytologic analysis of voided urine specimens can assist, but is too inaccurate to replace cystoscopy. In an effort to create reliable, objective, noninvasive mechanisms for detecting bladder cancer, a number of urine-based molecular tests have been developed with the ultimate goal of reducing the frequency of cystoscopy. OBJECTIVE: To summarize the performance of urine-based biomarker tests, currently commercially available in the US, as part of the initial workup for hematuria and for bladder cancer surveillance. METHODS: In accordance with PRISMA guidelines we performed a systematic review of the literature on the performance of NMP22, BTA, UroVysion, ImmunoCyt/uCyt, CxBladder, and Bladder EpiCheck. Median sensitivity, specificity, negative (NPV) and positive predictive values (PPV) were calculated for each test based on the included studies. RESULTS: Twenty-eight studies met inclusion criteria for the performance of five urine-based biomarker tests in the setting hematuria workup. Median sensitivity ranged from 65.7% -100% and specificity ranged from 62.5% -93.8%. Median NPV ranged from 94.2% -98.3% and PPV ranged from 29% -58.7%. Fourteen studies met inclusion criteria for the performance of six tests in the setting of bladder cancer surveillance. Median sensitivity ranged from 22.6% -92.0% and specificity from 20.5% -97.9%. Median NPV ranged from 52.9% -96.5% and PPV ranged from 48.1% -75.7%. CONCLUSIONS: Our analysis finds that while these tests may provide some clinical utility, none of the assays have thus far demonstrated objective evidence to supplant the gold diagnostic standard.

Intraoperative diagnosis of breast cancer metastasis in axillary lymph nodes: Cytological Smear vs. Frozen Section.

BACKGROUND: Intraoperative evaluation of axillary lymph nodes is sometimes required to determine the extent of surgery. In this study, we wished to assess the reliability of cytologic smear (CS) in determining lymph node involvement with tumor. Theoretically, CS provides more substance for examination than touch-imprint cytology and is faster to perform than frozen section (FS). We hypothesized that CS sensitivity for tumor cell detection in the lymph nodes would be similar to FS, at least 0.90. METHODS: This was a retrospective observational study at the Rambam Health Care Campus (January, 2013-June, 2020). Lymph nodes underwent intraoperative evaluation using either CS or FS, based on the availability of a cytologist at the time of the examination. Both intraoperative evaluations were compared to the final pathology following fixation with formalin. RESULTS: Eighty-eight patients undergoing intraoperative analysis were analyzed (51 CS, 37 FS). False-negative tests were recorded in only 1 patient evaluated by each of the 2 methods. This resulted in sensitivity 0.91 (95%CI 0.59, 1.00) for CS and 0.88 (95%CI 0.47, 1.00) for FS, specificity 1.00 (95%CI 0.91, 1.00) for CS and 1.00 (95%CI 0.88, 1.00) for FS, positive predictive value 1.00 (95%CI 0.69, 1.00) for CS and 1.00 (95%CI 0.59, 1.00) for FS, and negative predictive value 0.98 (95%CI 0.87, 1.00) for CS and 0.97 (95%CI 0.83, 1.00) for FS. CONCLUSIONS: The sensitivity of the CS in this study is comparable to that of FS and due to shorter analysis time required is the preferred method at our institution.