Negative Cytology Results Research Articles

Intraoperative ultrasound guided wire (IOUS-wire) localization biopsy with frozen section versus preoperative fine needle aspiration cytology (FNAC) for the evaluation of clinically positive nodes in patients with early breast cancer in China real-world clinical practice.

e12600 Background: Appropriate biopsy procedure for clinically positive (suspicious) lymph nodes (LN) plays a key role in accurate axillary staging of early breast cancer. Fine needle aspiration (FNA) is a recommended method for clinically suspicious nodes in the National Comprehensive Cancer Network (NCCN) guidelines. However, the false negative rate (FNR) of FNA remains too high. Therefore, it is valuable to explore an alternative and appropriate procedure in clinical practice. We conducted a retrospective review to compare the feasibility and diagnostic efficiency of using a novel procedure, the intraoperative ultrasound guided wire (IOUS-wire) localization biopsy with frozen section, to FNA for assessment of clinically positive nodes in patients with early breast cancer. Methods: Data on consecutive primary breast cancer patients with documented axillary ultrasound results who had clinically positive lymph nodes (cN1) between January 2015 and September 2023 either utilization of IOUS-wire localization or ultrasonography-guided fine-needle aspiration cytology (US-FNAC) for clinically positive lymph nodes were retrospectively analyzed. Sentinel lymph node biopsy (SLNB) was performed in patients with negative histopathological or cytological results. The false negative rate (FNR) of histopathology between two groups was calculated. Results: Eligible patients (n=198) referred to axillary biopsy by IOUS-wire localization biopsy(n=100) and US-FNAC(n=98) in this study. The FNR of clinically positive lymph nodes biopsy was 12.8 percent in the IOUS-wire localization group and 87.5 percent in the US-FNAC group.IOUS-wire failed in 5 patients. Among the remaining 32 successful identifications, 26 were IOUS-wire-node positive by intraoperative frozen section. 42 patients with additional lymph node metastases were found in FNAC-LN-negative patients by SLNB. The accuracy rate was respectively 95% and 57.1%. No significant difference was observed in complications and median number of SLNs harvested (5.3 versus 5.5; P=0.631) between the groups. Sufficient tissue samples can be obtained for intraoperative frozen pathology so the FNR is potentially reduced. In addition, the interval of waiting time for pathological results is reduced. Conclusions: Intraoperative US-guided wire localization biopsy is a feasible and alternative procedure compared to preoperative FNA for clinically node-positive patients with early breast cancer. This novel method is suitable for China's national conditions and should be further pursued as a potential biopsy method for evaluation of axillary node status in clinical practice.

Real-world use of a CSF circulating tumor cell assay in the diagnosis and management of leptomeningeal metastasis.

2029 Background: The diagnosis of leptomeningeal metastasis (LM) can be challenging due to variability in clinical symptoms, radiographic, and cerebrospinal fluid (CSF) findings. The National Comprehensive Cancer Network (NCCN) guidelines recommend assessment of circulating tumor DNA (ctDNA) to increase sensitivity of tumor cell detection and assess the response to treatment. We hypothesize that the real-world use of an assay for the direct detection and enumeration of circulating tumor cells (CTCs) in the CSF is clinically useful for accurate diagnosis of LM, particularly in an early stage of disease. Methods: We report a series of 55 patients treated at our institution with a cancer diagnosis and either neurological symptoms or radiographic findings that suggested LM. All patients underwent a lumbar puncture, assessment for CSF CTCs, and conventional hospital-based cytology testing between 6/1/2020 and 8/1/2023. Survival data cutoff was 12/31/2023. Patient outcomes are reported. Results: 55 patients were tested, and 30 patients were found to be positive for CTCs and diagnosed with LM. Only 10 patients were concurrently positive for CTCs and cytology at our institution, whereas 20 patients with positive CTCs had a negative or ambiguous cytology. No patients with a negative CTC result (25 patients) were subsequently diagnosed with LM, whereas 4 patients with a positive CTC result remained without progressive neurological symptoms. 5 patients diagnosed with LM were alive at the time of data cutoff. The histologic breakdown for LM was: breast (11), non-small cell lung cancer (NSCLC) (16), gastrointestinal (GI) (3). Median overall survival (OS) was longer in patients with a positive CTC and negative cytology result compared to patients with concurrent positive CTC and cytology (172 vs. 63 days, p = 0.06). Median OS was also longer in breast cancer LM compared to NSCLC LM (235 vs. 63 days, p = 0.008). Most patients diagnosed with LM received therapies including Ommaya reservoir placement, intrathecal chemotherapy, and/or radiation. Conclusions: The use of a CSF circulating tumor cell assay aided the diagnosis of LM and led to timely initiation of treatment. A negative result of the CTC assay was associated with ruling out LM. Diagnosis of LM with the CTC assay and negative cytology was associated with longer survival, possibly due to earlier treatment initiation, and not solely a lead time bias. Breast cancer LM patients had improved survival compared to NSCLC and GI cancer patients, possibly due to more effective treatment options.

Peritoneal lavage cytology in patients with curative resection for stage II and III colorectal cancer: A multi-institutional prospective study.

To clarify the usefulness of intraoperative lavage cytology in patients undergoing curative resection for pStage II-III colorectal cancer in a prospective multicenter study. Patients preoperatively diagnosed with stage II-III colorectal cancer between 2013 and 2017 from 20 hospitals were enrolled. Lavage cytology was performed twice during the surgery. The primary endpoint was the effect of lavage cytology on the 5-year relapse-free survival (RFS) in patients with pStage II-III colorectal cancer. The secondary endpoint was the effect of lavage cytology on the 5-year overall survival (OS) and peritoneal recurrence. A total of 1378 patients were eligible for analysis. The number of patients with pStage II-III colorectal cancer was 670 and 708, respectively. Fifty-four patients (3.9%) had positive cytological results. In pStage II patients, the 5-year RFS rates with positive and negative cytology were 61.1% and 81.6%, respectively (p = 0.023). The 5-year OS rates were 67.1% and 91.7%, respectively (p = 0.0083). However, there was no difference in RFS or OS between pStage III patients with positive and negative cytology results. The peritoneal recurrence rates were 11.8% and 1.5% in pStage II patients with positive and negative cytology results, respectively (p = 0.032). These rates were 10.5% and 2.5% in patients with stage III disease, respectively (p = 0.022). Stage II colorectal cancer patients with negative cytology had better outcomes than those with positive cytology. Peritoneal lavage cytology is useful for predicting peritoneal recurrence after curative resection of stage II-III colorectal cancer.

When cervical microglandular hyperplasia coincides with high-risk human papillomavirus infection: Diagnostic challenges and evidence

ABSTRACT Cervical microglandular hyperplasia (MGH) is a benign cervical lesion mimicking cervical malignancy, thereby making its pathogenesis diagnostically challenging for gynecologists and pathologists. While MGH is often associated with physiological or external hormonal factors, several cases remain unexplained. In this report, we present a case of a young primiparous woman without evident hormonal risk factors seeking gynecologic evaluation owing to abnormal vaginal discharge. During her clinical examination, we observed an irregular cervical lesion raising malignancy-related concerns and consequently planned a colposcopy. The human papillomavirus (HPV) polymerase chain reaction tested positive for two high-risk HPV genotypes (16 and 52), denoting that the patient did not have an HPV infection history. During colposcopy, we identified a friable papillary cervical mass at the transformation zone, bleeding significantly with minimal handling, from which we obtained multiple biopsies. Our subsequent histopathological examinations eventually confirmed the MGH diagnosis, ruling out malignancy. Intriguingly, a follow-up colposcopy 7 months later revealed the resolution of the initial cervical lesion, coinciding with negative HPV test and Pap smear cytology results. This case highlights the rare encounter of MGH concurrent with an initial high-risk HPV infection. Beyond a comprehensive review of related literature and clinical guidelines, we discuss the clinical and histopathological results in such a case.

Preoperative predictive factors for positive peritoneal cytology results in patients with pancreatic ductal adenocarcinomas: a retrospective study.

The clinical importance of positive peritoneal cytology results in patients with pancreatic ductal adenocarcinomas remains controversial. We evaluated the prognosis of these patients and the predictive preoperative risk factors for positive peritoneal cytology results. We retrospectively reviewed patients who underwent curative-intent surgery at our institution between May 2010 and June 2020. Preoperative risk factors for positive peritoneal cytology results were identified using logistic regression analysis. A scoring model was constructed using the total number of significant independent predictors for positive peritoneal cytology results. Of 233 patients, 18 (7.7%) had positive peritoneal cytology results. The recurrence-free survival and cancer-specific survival were markedly worse in patients with positive peritoneal cytology results than in those with negative peritoneal cytology results (recurrence-free survival: 6.0months vs. 16.6months, p = 0.050; cancer-specific survival: 19.4months vs. 47.5months, p = 0.034). Tumor location (odds ratio: 3.760, 95% confidence interval: 1.099-11.818, p = 0.023), tumor size > 25mm (odds ratio: 3.410, 95% confidence interval: 1.031-11.277, p = 0.046), preoperative serosal invasion (odds ratio: 5.193, 95% confidence interval: 1.099-24.531, p = 0.038), and preoperative carcinoembryonic antigen level > 5.6ng/mL (odds ratio: 3.816, 95% confidence interval: 1.248-10.667, p = 0.019) were identified as significant independent predictive factors. Our predictive model's optimal cutoff and positive predictive values for positive peritoneal cytology results were 3 and 27.9%, respectively. The indications for curative-intent surgery should be considered carefully in patients with high-risk factors for positive peritoneal cytology results.

Clinical impact of pleural fluid carcinoembryonic antigen on therapeutic strategy and efficacy in lung adenocarcinoma patients with malignant pleural effusion.

Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10-100 ng/mL, 100-500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.

Discussion on cervical cytology in postmenopausal women.

Considering the cervix at the climacteric period, important changes take place in the morphology of the epithelium and stroma due to hypoestrogenism. Therefore, the aim of the present study was to compare the presence of transformation zone cells in the cervix of premenopausal and postmenopausal women. In a private laboratory in São Paulo (Brazil) a retrospective analysis of cervical cytology results was performed. A total of 1,026,671 satisfactory cytology tests were evaluated between January 2010 and December 2015. A marked decline in transformation zone cells with age was evident, with a greater decrease in the ≥50 years age groups. Only 35% of women ≥50 years of age had transformation zone cells in cytology, while in those <50 years, the figure was 67.5% (P<0.001). The prevalence of negative cytological results in these two age groups was respectively 89.9% and 95.3%; however, it was observed that the most serious cytological results occurred in the group after menopause. Although cytology is the recommended screening method for cervical cancer in Brazil, the low number of transformation zone cells in cytology in menopausal patients could be less sensitive for screening of dysplasia and cancer. So, we suggest routine high-risk HPV DNA testing, when possible, given that this test is considered more sensitive for detecting cervical lesions in this group of patients. When HPV DNA testing is not possible, cytology should be collected, and for cytology sampling we suggest regular topical estrogenization and use of appropriate technique.

Feasibility and acceptability of telehealth and contactless delivery of human papillomavirus (HPV) self-testing for cervical screening with Māori and Pacific women in a COVID-19 outbreak in Aotearoa New Zealand.

To determine the feasibility and acceptability of a telehealth offer and contactless delivery of human papillomavirus (HPV) cervical screening self-test during the 2021 COVID-19 Level 4 lockdown in Auckland, New Zealand. A small proof-of-concept study was undertaken to test telehealth approaches in never-screened, due or overdue Māori and Pacific women enrolled in a local Primary Health Organisation (PHO). Study invitation, active follow-up, nurse-led discussions, result notification and a post-test questionnaire were all delivered through telehealth. A sample of 197 eligible Māori and Pacific women were invited to take part, of which 86 women were successfully contacted. Sixty-six agreed to take part. Overall uptake was 61 samples returned (31.8%) and uptake of all contactable women was 70.9%. Six of the 61 HPV self-tests (9.8%) were positive, all for non 16/18 types, and were referred for cytology. Three had negative cytology results, and three with positive cytology results were referred for colposcopy. The offer of HPV self-testing during COVID-19 lockdown was both feasible and highly acceptable for Māori and Pacific women. Importantly, HPV self-testing via telehealth and mail-out, alongside other options, offers a potential pro-equity approach for addressing the impact of deferred screens due to COVID-19 and other longstanding coverage issues.

Effectiveness of Different Testing Strategies Applied for Cervical Cancer Screening in Shuangliu District, Chengdu City

To evaluate the clinical value of different combination strategies of high-risk HPV (hr-HPV) testing and Thinprep cytology test (TCT), a cervical cytology test, for cervical cancer screening, especially for high or higher-grade squamous intraepithelial lesion (HSIL+) in Shuangliu District, Chengdu City. The study is a population-based randomized clinical trial. Women aged 35 to 65 years meeting the inclusion criteria were enrolled for the study. At the baseline screening conducted in the first year, the participants were randomly assigned to either cytology test or hr-HPV testing at a ratio of 1∶2. If the paticipants had positive results for the baseline hr-HPV test, they would then undergo either cytology test or colposcopy by random assignment. After 24 months, all participants were called back, and combined screening of cytology test and hr-HPV test were performed. Women who had negative results at baseline screening and who entered and completed the third-year follow-up were selected as the subjects of the study. Based on the aforementioned testing findings, the related data were extracted and four different screening protocols were simulated: 1) combined TCT and hr-HPV screening, with referral for colposcopy when there was positive results for either one of the two; 2) combined TCT and hr-HPV screening, with referral for colposcopy when both tests had positive results at the same time; 3) TCT was done for preliminary screening and those who were found to be positive would then undergo hr-HPV test for triage purpose, with subsequent referral made for colposcopy if the hr-HPV results were positive; 4) hr-HPV was done for preliminary screening and those who were found to be positive would then undergo TCT, with subsequent referral made for colposcopy if TCT results were positive. With the detection of HSIL+ on histological examination as the endpoint event, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve ( AUC) of different combination screening models were calculated. A total of 3102 women were screened, and 2967 women were included in the statistical analysis in this study. Among the 2967 women, 979 were randomized to cytology and 1988 to hr-HPV genotyping. For prescreening, the positive rate of the cytology group was 5.6% (55/979), with of HSIL+ positive rate being 0.2% (2/979), while the positive rate of the hr-HPV group was 7.5% (149/1988), with HSIL+ positive rate being 0.9% (18/1988). After 24 months, 2456 women were called back and were given cervical cytology test and hr-HPV test at the same time. Among them, the positive rate of the cytology group was 3.2% (78/2456), while the positive rate of hr-HPV group was 8.7% (215/2456). The overall positive rate of HSIL+ was 0.69%(17/2456). Women with a negative baseline hr-HPV had a lower incidence of HSIL+ lesions in the long term. The strategy of cervical cytology screening combined with hr-HPV test for triage purpose is the best method, with a sensitivity of 88.9%, a specificity of 58.3%, a PPV of 44.4%, a NPV of 93.3%, and an AUC of 0.736, P=0.039 (95% CI: 0.555-0.917). This randomized clinical trial from Shuangliu District, Chengdu City shows that the sensitivity of hr-HPV testing is better than that of cytology test, and the prevalence of HSIL+ in women with negative baseline hr-HPV results is lower than that of women with negative baseline cytology results. The screening program of TCT for prescreening plus subsequent hr-HPV test for triage purpose shows better value for the detection of HSIL+.

Superficial spreading cervical squamous cell carcinoma in situ involving the endometrium: a case report and review of the literature

BackgroundThe spread of cervical squamous cell carcinoma to the inner surface of the uterus with replacement of the endometrium is rare. Continuity of the lesion must be demonstrated to confirm superficial spread and rule out concomitant endometrial cancer.Case presentationWe present the case of a 66-year-old white woman with superficial spreading squamous cell carcinoma of the cervix that involved the endometrium. Her relevant past history included conization of the cervix to treat cervical intraepithelial neoplasia III with positive margins. She subsequently had three negative cervical vaginal cytology results, each with a positive high-risk human papillomavirus test. Transvaginal ultrasound showed occupation of the entire uterine cavity by dense material consistent with pyometra in addition to myometrial thinning due to tension and cervical dilation. The patient presented with greenish vaginal discharge of 3 months’ duration. The cervix was not visible during speculum examination. Access for endometrial sampling was not possible, raising suspicion of post-conization cervical stenosis. The patient was treated with laparoscopic hysterectomy with double adnexectomy. Histologic examination showed superficial squamous cell carcinoma invading the cervix to a depth of 2.8 mm; superficial spreading squamous cell carcinoma in situ was also observed in the lower uterine segment and endometrium. The patient was free of symptoms 12 months after surgery.ConclusionsSquamous cell carcinoma of the cervix with superficial spread to the endometrium is not included in the 2020 (fifth edition) World Health Organization Classification of Female Genital Tract Tumors or the 2018 International Federation of Gynecology and Obstetrics cervical cancer staging system. More clinical cases are needed to identify other prognostic factors and inform clinical practice guidelines on the management of this disease.

High Diagnostic Yield of Endoscopic Retrograde Cholangiopancreatography Brush Cytology for Indeterminate Strictures.

BackgroundEndoscopic retrograde cholangiopancreatography (ERCP) brush cytology is used frequently for sampling indeterminate biliary strictures. Studies have demonstrated that the diagnostic yield of brush cytology for malignant strictures is estimated to be 6%–70%. With improved diagnostic tools, sampling techniques and specimen processing, the yield of ERCP brush cytology may be higher. This study aimed to assess the yield of brush cytology and determine factors associated with a positive diagnosis.MethodsThis was a cohort study of patients who underwent ERCP brush cytology from October 2017 to May 2020. Patient demographics, clinical, procedural and pathological data were collected using chart review. Sampling data were captured up to 3 months post-index ERCP to capture repeat brushings, biopsies or surgical resections. Outcomes included the diagnostic yield, true/false positive values and true/false negative values of malignancy detection using ERCP brush cytology.ResultsA total of 126 patients underwent a brush cytology, 58% were male and 79% had a stricture in the extrahepatic region. Ninety-three patients were diagnosed with a malignancy, of which 78 had positive brush cytology results and 15 had a negative brush cytology result. The diagnostic yield, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 84%, 83%, 97%, 99%, 68% and 87% respectively.ConclusionERCP brush cytology performed using updated sampling technique is associated with high diagnostic yield. This allows for earlier malignancy diagnosis, timely treatment and decreased need for further investigation.

Prevalence and frequencies of human papilloma virus types in adenocarcinoma in situ of the uterine cervix

Objective: To examine the prevalence and frequencies of human papillomavirus (HPV) genotypes in cervical adenocarcinoma in situ (AIS). Methods: The cases of cervical AIS with concurrent tests of cytology and HPV typing from January 2007 to February 2020 in the Obstetrics and Gynecology Hospital of Fudan University were collected and analyzed. Results: A total of 478 cases of cervical AIS were obtained. The average age of the patients was 39.4 years (range, 19-81 years). The largest age group was 30-39 years (44.8%), followed by 40-49 years (34.7%). Among the 478 patients, 355 underwent high-risk HPV (hrHPV) testing and had a hrHPV-positive rate of 93.8%. Of the 355 patients, 277 also underwent HPV typing and were mostly positive for either or both HPV16 and HPV18 (93.1%), with 55.6% positive for HPV18 and 48.7% positive for HPV16. Among the 478 cases, 266 cases (55.6%) were diagnosed with both AIS and squamous intraepithelial lesion (SIL), while 212 cases (44.4%) were diagnosed with only AIS. Patients infected with HPV16 in the AIS and SIL group significantly outnumbered those in the AIS alone group (P<0.05). Moreover, the rate of positive cytology was 55.9% (167/299 cases), while that of negative cytology was 44.1% (132/299). Among the 109 patients with negative cytology results and co-tested hrHPV, there were 101 HPV-positive cases (92.7%), of which 88 cases were subject to HPV typing and showed an HPV16/18 positive rate of 94.3% (83/88 cases). Conclusions: The combination of HPV typing and cytological screening can maximize the detection rate of cervical AIS, and should continue to be utilized, ideally on a larger scale, in the future.

National experience in the first two years of primary human papillomavirus (HPV) cervical screening in an HPV vaccinated population in Australia: observational study.

ObjectiveTo review the first two years of the primary human papillomavirus (HPV) cervical screening programme in an HPV vaccinated population.DesignObservational study.SettingAustralia.Participants3 745 318 women with a primary HPV test between 1 December 2017 and 31 December 2019; most women aged <40 years had previously been offered vaccination against HPV16 and HPV18.InterventionsPrimary HPV screening with referral if HPV16 or HPV18 (HPV16/18) positive and triage with liquid based cytology testing (threshold atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion) for women who were positive for high risk HPV types other than 16/18. A 12 month follow-up HPV test was recommended in triaged women with a negative or low grade cytology result, with referral if they tested positive for any high risk HPV type at follow-up.Main outcome measuresProportion of women who had attended for their first HPV screening test, tested positive, and were referred for colposcopy; and short term risk of detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse, CIN grade 3 or worse, or cancer.Results54.6% (n=3 507 281) of an estimated 6 428 677 eligible women aged 25-69 had undergone their first HPV test by the end of 2019. Among those attending for routine screening, positivity for HPV16/18 and for HPV types not 16/18 was, respectively, 2.0% and 6.6% in women aged 25-69 (n=3 045 844) and 2.2% and 13.3% in highly vaccinated cohorts of women aged 25-34 (n=768 362). Colposcopy referral (ages 25-69 years) was 3.5%, increasing to an estimated 6.2% after accounting for women who had not yet had a 12 month repeat test. Cervical cancer was detected in 0.98% (456/46 330) of women positive for HPV16/18 at baseline, including 0.32% (89/28 003) of women with HPV16/18 and negative cytology. Women with HPV types not 16/18 and negative or low grade cytology at both baseline and 12 months were at low risk of serious disease (3.4% CIN grade 3 or worse; 0.02% cancer; n=20 019) but estimated to account for 62.0% of referrals for this screening algorithm.ConclusionsColposcopy referral thresholds need to consider underlying cancer risk; on this basis, women with HPV16/18 in the first round of HPV screening were found to be at higher risk regardless of cytology result, even in a previously well screened population. Women with HPV types not 16/18 and negative or low grade cytology showed a low risk of serious abnormalities but constitute most referrals and could be managed safely with two rounds of repeat HPV testing rather than one. HPV16/18 driven referrals were low in HPV vaccinated cohorts.

Characterization of women diagnosed with cervical cancer at age 65 or older

The objective of the study is to characterize the population of women diagnosed with cervical cancer after age 65. Current guidelines allow for discontinuation of cervical cancer screening at age 65 if women have met criteria for adequate screening, which is defined as three consecutive negative cytology results or two consecutive negative co-testing results within ten years before stopping screening, with the most recent test occurring within five years. However, 20% of incident cervical cancers occur in women over the age of 65.

Papilloplex HR-HPV test has non-inferior clinical performance for detection of human papillomavirus infection: assessment using the VALGENT framework

AimThe Papilloplex high-risk human papillomavirus (hrHPV) test (Genefirst, Oxford, UK) is a single tube real-time HPV test which provides multiplex detection and separate identification of 14 hrHPV types. Here, we...

Clinical suspicion of pancreatic cancer despite negative endoscopic ultrasound-guided fine-needle aspiration biopsy.

The early and accurate diagnosis of pancreatic ductal adenocarcinoma is vital for improving the efficacy of therapeutic interventions and to provide patients with the best chance of survival. While endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been demonstrated to be a reliable and accurate diagnostic tool for solid pancreatic neoplasms, the ongoing management of patients with a high clinical suspicion for malignancy but with a negative EUS-FNA biopsy result can prove a challenge. We describe five patients from a single centre who presented for further work-up of a pancreatic mass and/or imaging features concerning for a periampullary malignancy. All patients had at least one EUS-FNA biopsy performed which returned no malignant cells on cytology. Despite these negative cytology results, all patients underwent further invasive investigation through upfront resection (pancreaticoduodenectomy) or extra-pancreatic biopsy (laparoscopic biopsy of peritoneal nodule) due to worrisome features on imaging, biochemical factors and clinical presentation culminating in a high degree of suspicion for malignancy. The final tissue histopathological diagnosis in all patients was pancreatic ductal adenocarcinoma. This case series highlights the important clinical findings, imaging and biochemical features which need to be considered in patients who have high suspicion for malignancy despite having a negative EUS-FNA cytology result. In these patients with a high index of suspicion, surgical intervention through an upfront resection or further invasive investigation should not be delayed.

Clinical performance of methylation as a biomarker for cervical carcinoma in situ and cancer diagnosis: A worldwide study.

The shift towards primary human papillomavirus (HPV)-based screening has necessitated the search for a secondary triage test that provides sufficient sensitivity to detect high-grade cervical intraepithelial neoplasia (CIN) and cancer, but also brings an improved specificity to avoid unnecessary clinical work and colposcopy referrals. We evaluated the performance of the previously described DNA-methylation test (S5) in detecting CIN3 and cancers from diverse geographic settings in high-, medium- and low-income countries, using the cut-off of 0.80 and exploratory cut-offs of 2.62 and 3.70. Assays were performed using exfoliated cervical specimens (n=808) and formalin-fixed biopsies (n=166) from women diagnosed with cytology-negative results (n=220), CIN3 (n=204) and cancer stages I (n=245), II (n=249), III (n=28) and IV (n=22). Methylation increased proportionally with disease severity (Cuzick test for trend, P < .0001). S5 accurately separated women with negative-histology from CIN3 or cancer (P < .0001). At the 0.80 cut-off, 543/544 cancers were correctly identified as S5 positive (99.81%). At cut-off 3.70, S5 showed a sensitivity of 95.77% with improved specificity. The S5 odds ratios of women negative for cervical disease vs CIN3+ were significantly higher than for HPV16/18 genotyping at all cut-offs (all P < .0001). At S5 cut-off 0.80, 96.15% of consistently high-risk human papillomavirus (hrHPV)-negative cancers (tested with multiple hrHPV-genotyping assay) were positive by S5. These cancers may have been missed in current primary hrHPV-screening programmes. The S5 test can accurately detect CIN3 and malignancy irrespective of geographic context and setting. The test can be used as a screening and triage tool. Adjustment of the S5 cut-off can be performed considering the relative importance given to sensitivity vs specificity.

Characterization of women diagnosed with cervical cancer at age 65 or older

<h3>Objectives:</h3> The objective of this study is to characterize the population of women who are diagnosed with cervical cancer after age 65. Current guidelines allow for discontinuation of cervical cancer screening at age 65 if women have met criteria for adequate screening, which is defined as three consecutive negative cytology results or two consecutive negative co-testing results within ten years before stopping screening, with the most recent test occurring within five years. However, twenty percent of incident cervical cancers occur in women over the age of 65. <h3>Methods:</h3> A retrospective analysis of patients diagnosed with cervical cancer at age 65 or older from 2000-2020 at our institutions. Study subjects were identified by ICD-9 and ICD-10 codes. Demographic information, pathologic data, treatment history, and screening history were abstracted from the electronic medical record. <h3>Results:</h3> There were 53 patients diagnosed with cervical cancer at age 65 or older from 2000-2020 with sufficient records for review. The median age at diagnosis was 73.8 years, 59% were smokers, and 94% were White. The most common method of detection was the presence of symptoms (81%), and the most common presenting symptom was vaginal bleeding (70%), followed by vaginal discharge (23%), pelvic pain (17%), and bowel or urinary symptoms (13%). At diagnosis, 40% of patients had localized disease, 57% had regional disease, and 4% had distant disease at diagnosis. The histology distribution was 70% squamous cell carcinoma, 19% adenocarcinoma, 6% clear cell carcinoma, 4% small cell carcinoma, and 2% poorly differentiated carcinoma, unspecified. Only 19% of patients had a known history of prior abnormal screening, but prior screening history was not available for 32% of patients. A total of twelve patients (23%) had not met criteria for adequate cervical cancer screening; 3 patients (6%) had met criteria for adequate screening, and 4 patients (8%) were still undergoing screening due to abnormal results. For 34 patients (64%), however, there were insufficient screening records to determine whether they met criteria for adequate screening. <h3>Conclusions:</h3> Twenty percent of patients with complete records had met criteria to stop cervical cancer screening prior and went on to develop cervical cancer after age 65. This calls into question the current guidelines defining adequate screening prior to discontinuation. The remaining 80% of patients did not meet criteria for adequate screening and, thus, their cancers may have been detected and treated while still at a pre-invasive stage. Notably, there was not sufficient documented history of cervical cancer screening in 64% of these patients who were diagnosed with cervical cancer after age 65.

Risk factors of cervical cancer after a negative cytological diagnosis in Polish cervical cancer screening programme.

Risk factors of cervical cancer (CC) development are well investigated, however, those influencing the risk of a potential false negative cytology preceding diagnosis of an invasive CC are not. We have aimed to explore these factors according to the data from Organised Cervical Cancer Screening Programme (OCCSP) in Poland. A total of 2.36 million of Pap tests sampled in 2010–2012 within OCCSP were merged with the Polish National Cancer Registry to identify CC cases after abnormal cytology and after normal cytology within 3 years of screening. Of 1460 invasive CCs, 1025 were preceded by abnormal and 399 by normal cytology result. Multivariate logistic analysis indicated that the presence of microorganisms in the Pap (OR = 2.18, 95% CI 1.65–2.87), evaluation by smaller (below 9000 slides processed per year) laboratories (OR = 1.60, 95% CI 1.22–2.09) and non‐squamous histology of cancer increased the odds for a potential false negative result (OR = 3.39, 95% CI 2.37–4.85 for adenocarcinoma, OR = 1.99, 95% CI 1.11–3.55 for other types of carcinoma), whereas cervical ectropion, other macroscopic changes on the cervix and smoking decrease the odds for a potential false negative Pap test result preceding CC (OR = 0.61, 95% CI 0.45–0.82, OR = 0.41, 95% CI 0.25–0.67, OR = 0.60, 95% CI 0.46–0.78, respectively). Proper triage of women with microscopic signs of microorganisms in the Pap smear should be reconsidered and cytology should be assessed in laboratories processing over 9000 slides annually to decrease the odds for negative Pap test result in 2 years before CC diagnosis. Information on macroscopic changes on the cervix provided to cytomorphologist may reduce the risk of a potential false negative cytology result.

Artificial intelligence to improve cytology performances in bladder carcinoma detection: results of the VisioCyt test.

To explore the utility of artificial intelligence (AI) using the VisioCyt® test (VitaDX International, Rennes, France) to improve diagnosis of bladder carcinoma using voided urine cytology. A national prospective multicentre trial (14 centres) was conducted on 1360 patients, divided in two groups. The first group included bladder carcinoma diagnosis with different histological grades and stages, and the second group included control patients based on negative cystoscopy and cytology results. The first step of this VISIOCYT1 trial focussed on algorithm development and the second step on validating this algorithm. A total of 598 patients were included in this first step, 449 patients with bladder tumours (219 high-grade and 230 low-grade) and 149 as negative controls. The VisioCyt test was compared to voided urine cytology performed by experienced uro-pathologists from each centre. Overall sensitivity was highly improved by the VisioCyt test compared to cytology (84.9% vs 43%). For high-grade tumours the VisioCyt test sensitivity was 92.6% vs 61.1% for the uro-pathologists. Regarding low-grade tumours, VisioCyt test sensitivity was 77% vs 26.3% for the uro-pathologists. In comparison to routine cytology, the results of the first phase of the VISIOCYT1 trial show very clear progress in terms of sensitivity, which is particularly visible and interesting for low-grade tumours. If the validation cohort confirms these results, it could lead to the VisioCyt test being considered as a very useful aid for pathologists. Moreover, as this test is in fact software based on AI, it should become more and more efficient as more data are collected.