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.

American Society of Cytopathology Telecytology validation recommendations for rapid on-site evaluation (ROSE).

Telecytology has multiple applications, including rapid onsite evaluation (ROSE) of fine-needle aspiration (FNA) specimens. It can enhance cytopathology practice by increasing productivity, reducing costs, and providing subspecialty expertise in areas with limited access to a cytopathologist. However, there are currently no specific validation guidelines to ensure safe practice and compliance with regulations. This initiative, promoted by the American Society of Cytopathology (ASC), intends to propose recommendations for telecytology implementation. These recommendations propose that the validation process should include testing of all hardware and software, both separately and as a whole; training of all individuals who will participate in telecytology with regular competency evaluations; a structured approach using retrospective slides with defined diagnoses for validation and prospective cases for verification and quality assurance. Telecytology processes must be integrated into the laboratory's quality management system and benchmarks for discrepancy rates between preliminary and final diagnoses should be established and monitored. Special attention should be paid to minimize discrepancies that downgrade malignant cases to benign (false positive on telecytology). Currently, billing and reimbursement codes for telecytology are not yet available. Once, they are, recommendation of the appropriate usage of these codes would be a part of the recommendations. These proposed guidelines are intended to be a resource for laboratories that are considering implementing telecytology. These recommendations can help to ensure the safe and effective use of telecytology and maximize its benefits for patients.

Role of flow cytometric immunophenotyping in the diagnosis of breast implant-associated anaplastic large cell lymphoma: A 6-year, single-institution experience.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon mature T-cell neoplasm occurring in patients with textured breast implants, typically after 7-10 years of exposure. Although cytopathologic or histopathologic assessment is considered the gold standard diagnostic method for BIA-ALCL, flow cytometry (FC)-based immunophenotyping is recommended as an adjunct test. However, the diagnostic efficacy of FC is not well reported. We reviewed 290 FC tests from breast implant pericapsular fluid and capsule tissue from 182 patients, including 16 patients with BIA-ALCL over a 6-year period, calculating diagnostic rates and test efficacy. FC showed an overall sensitivity of 75.9%, specificity of 100%, and negative and positive predictive values of 95.4% and 100%, respectively. Blinded expert review of false-negative cases identified diagnostic pitfalls, improving sensitivity to 96.6%. Fluid samples had better rates of adequate samples for FC testing compared with tissue samples. Paired with FC testing of operating room (OR)-acquired fluid samples, capsulectomy FC specimens added no diagnostic value in patients with concurrent fluid samples; no cases had positive capsule FC with negative fluid FC. Fluid samples are adequate for FC testing more often than tissue. Capsule tissue FC specimens do not improve FC efficacy when paired with OR-acquired fluid FC samples and are often inadequate samples. FC is 100% specific for BIA-ALCL and can serve as a confirmatory test but should not be the sole diagnostic method. Awareness of sample-specific diagnostic pitfalls greatly improves the sensitivity of BIA-ALCL testing by FC.

Sensitivity of urine cytology in detecting high-grade urothelial carcinoma in patients with neoplastic urinary bladder diverticula: A major cancer center experience.

BACKGROUND: Bladder diverticula are herniations of bladder urothelium and mucosa through the muscularis propria. The reported incidence of neoplasia arising in bladder diverticula is widely variable. The authors' objective was to study the characteristics and sensitivity of urine cytology in these patients with emphasis on primary intradiverticular bladder cancer (IDBC). METHODS: A 17-year, retrospective review of all resected bladder diverticula associated with bladder carcinoma was performed. Cases that had complete diverticular resections and preresection urine samples were included in this study. The cases were divided into either primary IDBC or primary extradiverticular bladder cancer (EDBC). Demographic data and urine cytology characteristics were recorded, and sensitivity was calculated. For IDBC, a comparison between voided and cystoscopic urines was done for cases that had both collection methods performed. RESULTS: Of 70 patients with IDBC, 47 patients had urine cytology results that were either positive for high grade-urothelial carcinoma (HG-UC) or suspicious for HG-UC. The sensitivity for HG-UC in IDBC samples was 80%, compared with 82% in EDBC samples (p > .05). Also, 28 patients in the IDBC group had both voided and cystoscopic urine samples for comparisons; in seven patients, the voided urine sample yielded a more definitive diagnosis; in 10 patients, the cystoscopic urine sample yielded a more definitive diagnosis; and, in 11 patients, both samples were equally diagnostic (p > .05). CONCLUSIONS: The characteristics and sensitivity of urine cytology in bladder diverticula were investigated in association with neoplasia, with an emphasis on primary intradiverticular bladder cancer. The results indicated that urine cytology remains a reliable screening and diagnostic test for detecting IDBC, with sensitivity similar to that for detecting EDBC, and no significant difference was noted between voided and cystoscopic samples.

Digital pathology operations at a tertiary cancer center: Infrastructure requirements and operational cost.

Whole slide imaging is revolutionizing the field of pathology and is currently being used for clinical, educational, and research initiatives by an increasing number of institutions. Pathology departments have distinct needs for digital pathology systems, yet the cost of digital workflows is cited as a major barrier for widespread adoption by many organizations. Memorial Sloan Kettering Cancer Center (MSK) is an early adopter of whole slide imaging with incremental investments in resources that started more than 15 years ago. This experience and the large-scale scan operations led to the identification of required framework components of digital pathology operations. The cost of these components for the 2021 digital pathology operations at MSK were studied and calculated to enable an understanding of the operation and benchmark the accompanying costs. This paper describes the unique infrastructure cost and the costs associated with the digital pathology clinical operation use cases in a large, tertiary cancer center. These calculations can serve as a blueprint for other institutions to provide the necessary concepts and offer insights towards the financial requirements for digital pathology adoption by other institutions.

Risk of Carcinoma in Pleomorphic Adenomas of the Parotid.

Importance: Surgery is the mainstay of treatment for pleomorphic adenomas (PAs) of the parotid to prevent further growth and potential future malignant transformation. While historical case series have reported transformation rates as high as 10%, there is a lack of contemporary methodologically sound data. Objective: To examine the rate of carcinoma ex pleomorphic adenoma (CXPA) detection in untreated PAs and investigate factors associated with malignant neoplasm. Design, Setting, and Participants: This cohort study reviewed all cases of primary PAs managed at a quaternary referral center between December 1990 and January 2015. Patients whose clinical presentation was compatible with a primary benign PA and whose history indicated tumor duration of over 1 year were included. Data were analyzed from January to April 2023. Exposure: Untreated PA. Main Outcomes and Measures: Rate of CXPA detection among untreated PAs and association of tumor duration with rates of CXPA detection. Pathology slides of patients who underwent surgery were reviewed by a single expert pathologist for the presence of CXPA. Univariable logistic regression was performed to evaluate possible factors associated with CXPA. Results: A total of 260 patients (median age, 47 years [IQR, 38-60 years]; 174 [66.9%] female) had a median tumor duration of 3.2 years (range, 1-30 years; mean [SD], 5.7 [5.5] years). Patients were divided into 4 groups by tumor duration: 1 to 4 years (158 [60.7%]), 5 to 9 years (47 [18.1%]), 10 to 14 years (27 [10.4%]), and 15 to 30 years (28 [10.8%]). In 156 of 170 patients who underwent preoperative fine-needle aspiration (91.8%), a benign tumor was diagnosed; 5 of these patients (3.2%; 95% CI, 1.4%-7.3%) were later diagnosed with CXPA on pathology after eventual excision, and the rate of high grade CXPA was 1.3%. None of the patients had permanent facial nerve paralysis. Tumor size at presentation (odds ratio [OR], 1.66; 95% CI, 1.22-2.24) and incremental (per year) increase in age (OR, 1.04; 95% CI, 1.01-1.08) were found to be associated with CXPA, whereas tumor duration was not (OR, 1.00; 95% CI, 1.00-1.01). Conclusions and Relevance: In this study, the rate of malignant neoplasm detection among initially untreated PA was 3.2%. The results suggest that tumor size and older age are associated with the development of CXPA, while tumor duration is not. Observation of PA for longer periods was not associated with serious permanent complications.

Feasibility and tissue concordance of genomic sequencing of urinary cytology in upper tract urothelial carcinoma.

BACKGROUND: There is limited ability to accurately diagnose and clinically stage patients with upper tract urothelial carcinoma (UTUC). The most easily available and widely used urinary biomarker is urine cytology, which evaluates cellular material yet lacks sensitivity. We sought to assess the feasibility of performing next-generation sequencing (NGS) on urine cytology specimens from patients with UTUC and evaluate the genomic concordance with tissue from primary tumor. METHODS: In this retrospective study, we identified 48 patients with a diagnosis of UTUC treated at Memorial Sloan Kettering Cancer Center (MSK) between 2019 and 2022 who had banked or fresh urine samples. A convenience cohort of matching, previously sequenced tumor tissue was used when available. Urine specimens were processed and the residual material, including precipitated cell-free DNA, was sequenced using our tumor-naïve, targeted exome sequencing platform that evaluates 505 cancer-related genes (MSK-IMPACT). The primary outcome was at least 1 detectable mutation in urinary cytology specimens. The secondary outcome was concordance to matched tissue (using ANOVA or Chi-Square, as indicated). RESULTS: Genomic sequencing was successful for 45 (94%) of the 48 urinary cytology patient samples. The most common mutations identified were TERT (62.2%), KMT2D (46.7%), and FGFR3 (35.6%). All patients with negative urine cytology and low-grade tissue had successful cytology sequencing. Thirty-six of the 45 patients had matching tumor tissue available; concordance to matched tissue was 55% overall (131 of the total 238 oncogenic or likely oncogenic somatic mutations identified). However, in 94.4% (n = 34/36) of patients, the cytology had at least 1 shared mutation with tissue. Eleven (30.6%) patients had 100% concordance between cytology and tissue. CONCLUSIONS: Sequencing urinary specimens from selective UTUC cytology is feasible in nearly all patients with UTUC. Prospective studies are underway to investigate a clinical role for this promising technology.

Digital Examination of LYmph node CYtopathology Using the Sydney system (DELYCYUS): An international, multi-institutional study.

BACKGROUND: After a series of standardized reporting systems in cytopathology, the Sydney system was recently introduced to address the need for reproducibility and standardization in lymph node cytopathology. Since then, the risk of malignancy for the categories of the Sydney system has been explored by several studies, but no studies have yet examined the interobserver reproducibility of the Sydney system. METHODS: The authors assessed interobserver reproducibility of the Sydney system on 85 lymph node fine-needle aspiration cytology cases reviewed by 15 cytopathologists from 12 institutions in eight different countries, resulting in 1275 diagnoses. In total, 186 slides stained with Diff-Quik, Papanicolaou, and immunocytochemistry were scanned. A subset of the cases included clinical data and results from ultrasound examinations, flow cytometry immunophenotyping, and fluorescence in situ hybridization analysis. The study participants assessed the cases digitally using whole-slide images. RESULTS: Overall, the authors observed an almost perfect agreement of cytopathologists with the ground truth (median weighted Cohen κ = 0.887; interquartile range, κ = 0.210) and moderate overall interobserver concordance (Fleiss κ = 0.476). There was substantial agreement for the inadequate and malignant categories (κ = 0.794 and κ = 0.729, respectively), moderate agreement for the benign category (κ = 0.490), and very slight agreement for the suspicious (κ = 0.104) and atypical (κ = 0.075) categories. CONCLUSIONS: The Sydney system for reporting lymph node cytopathology shows adequate interobserver concordance. Digital microscopy is an adequate means to assess lymph node cytopathology specimens.

Current status of machine learning in thyroid cytopathology.

The implementation of Digital Pathology has allowed the development of computational Pathology. Digital image-based applications that have received FDA Breakthrough Device Designation have been primarily focused on tissue specimens. The development of Artificial Intelligence-assisted algorithms using Cytology digital images has been much more limited due to technical challenges and a lack of optimized scanners for Cytology specimens. Despite the challenges in scanning whole slide images of cytology specimens, there have been many studies evaluating CP to create decision-support tools in Cytopathology. Among different Cytology specimens, thyroid fine needle aspiration biopsy (FNAB) specimens have one of the greatest potentials to benefit from machine learning algorithms (MLA) derived from digital images. Several authors have evaluated different machine learning algorithms focused on thyroid cytology in the past few years. The results are promising. The algorithms have mostly shown increased accuracy in the diagnosis and classification of thyroid cytology specimens. They have brought new insights and demonstrated the potential for improving future cytopathology workflow efficiency and accuracy. However, many issues still need to be addressed to further build on and improve current MLA models and their applications. To optimally train and validate MLA for thyroid cytology specimens, larger datasets obtained from multiple institutions are needed. MLAs hold great potential in improving thyroid cancer diagnostic speed and accuracy that will lead to improvements in patient management.

Salivary gland fine-needle aspiration biopsy: quality assurance results from a tertiary cancer center.

INTRODUCTION: Fine-needle aspiration biopsy (FNAB) plays a critical role in the management of patients with salivary gland lesions. A specific diagnosis can be difficult due to the wide range of lesions with overlapping morphologic features, potentially leading to interpretation errors. We analyzed the cytologic-histologic discrepancies identified in the quality assurance program of a major cancer center in cases of salivary gland FNAB and performed a root cause analysis. MATERIALS AND METHODS: Salivary gland FNAB specimens performed during a 12-year period at a major tertiary cancer center were reviewed. The inclusion criteria for this study included FNAB cases of salivary glands with subsequent histologic or flow cytometry follow up. The cytologic diagnoses for these cases were recategorized according to the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) based on the original reports. The risk of neoplasm and malignancy based on the cases with subsequent resection or flow cytometry and the most common causes of discrepancy were analyzed. RESULTS: The risk of neoplasm ranged from 41% to 99% and the risk of malignancy ranged from 22% to 99% among the different MSRSGC categories. Lymphoid and myoepithelial rich lesions were the most common miscategorized lesions using the MSRSGC. Reactive changes due to inflammation were associated with overcalls. The most common malignancy in the atypical category was mucoepidermoid carcinomas. CONCLUSIONS: Myoepithelial and lymphoid rich lesions arising in the salivary gland are associated with a higher risk of misclassification. The use of category IVB in the MSRSGC is appropriate for lesions with abundant myoepithelial cells. Reactive atypia seen in sialadenitis was the most common feature associated with overcall.

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

PURPOSE: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma. MATERIALS AND METHODS: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months. Patients who had residual or recurrent upper tract urothelial carcinoma (any grade/size) failing prior endoscopic treatment or unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200 mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days posttreatment. RESULTS: Fourteen (74%) patients received the maximally tolerated dose of 200 mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up. CONCLUSIONS: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for upper tract urothelial carcinoma. The recently initiated multicenter Phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.

Diagnostic Discrepancies in Small-volume Biopsy for the Initial Diagnosis, Recurrence, and Transformation of Follicular Lymphoma: A Multi-Institutional Collaborative Study.

Small-volume biopsies (SVBs) including fine-needle aspiration (FNA), cell block, and needle core biopsies (NCB) are increasingly utilized to diagnose and guide the clinical management of lymphoma. We established a multi-institutional interdisciplinary collaboration of cytopathologists, hematopathologists, and oncologists focused on the role of SVB in the management of patients with follicular lymphoma (FL). To assess the performance characteristics of SVB in this setting, we evaluated all consecutive SVBs performed for clinical indications of initial diagnosis, recurrence, or transformation of FL over a 5-year period and focused on the 182 that had at least one subsequent biopsy within 3 months as part of the same clinical work-up. The most common outcome of a subsequent biopsy as part of the same clinical work-up was a more specific diagnosis usually assigning the pathologic grade (111/182, 61%), followed by a complete agreement with the SVB (24/182, 13%), and change from nondiagnostic on initial biopsy to diagnostic on subsequent biopsy (21/182, 12%). A minority resulted in a diagnostic change from benign to lymphoma (17/182, 9%), a change in FL grade (5/182, 3%), or change in the lymphoma diagnostic category (4/182, 2%). There were no cases where an initial diagnosis of lymphoma was overturned. The distribution of discrepancies was similar across initial SVB types (FNA, FNA + cell block, NCB with or without FNA). Tissue limitations were noted in a minority of cases (53/182, 29%) and were enriched among initially nondiagnostic biopsies (16/21, 76%). Flow cytometry immunophenotyping was performed in the majority of cases both at the first and last biopsy (147/182, 81%). SVB can be a powerful method to detect FL in various clinical indications, with discrepant cases mostly resulting from a refinement in the initial diagnosis.

Small volume biopsy diagnostic yield at initial diagnosis versus recurrence/transformation of follicular lymphoma: A retrospective Cyto-Heme Interinstitutional Collaborative study.

BACKGROUND: Few studies have evaluated diagnostic yield of small volume biopsies (SVB) for the diagnosis and management of follicular lymphoma (FL). METHODS: The authors performed a multi-institutional retrospective analysis of SVBs including fine-needle aspiration (FNA) and needle core biopsy (NCB) for initial FL diagnosis and suspected recurrence or transformation of FL. A total of 676 workups beginning with SVB were assessed for the mean number of biopsies per workup, the proportion of workups requiring multiple biopsies, and the proportion with a complete diagnosis including grade, on initial biopsy. RESULTS: Compared to workups performed for question transformation/recurrence, those done for initial FL diagnosis were significantly more likely to require multiple biopsies (p < .01), had a higher mean number of biopsies per workup (1.7 vs. 1.1, absolute standardized difference = 1.1), and a lower complete diagnosis rate at initial biopsy (39% vs. 56%). At initial FL diagnosis, NCB +/- FNA was associated with fewer biopsies per workup compared to FNA +/- CB (1.2 vs. 1.9), fewer workups requiring multiple biopsies (23% vs. 83%), and a higher complete diagnosis rate (71% vs. 18%). In contrast, during assessment for transformation/recurrence, NCB and FNA showed a similar mean number of biopsies per workup (1.2 vs. 1.2) and few workups required multiple biopsies (6% vs. 19%). CONCLUSIONS: SVB at initial FL diagnosis often required additional biopsies to establish a complete diagnosis. In contrast, when assessing for transformed/recurrent FL, additional biopsies were generally not obtained regardless of SVB type, suggesting that in these clinical settings SVB may be sufficient for clinical decision-making.

Active Surveillance of Papillary Thyroid Cancer: Frequency and Time Course of the Six Most Common Tumor Volume Kinetic Patterns.

Background: The change in size of the papillary thyroid cancer (PTC) nodule during active surveillance has traditionally been characterized as either stable, increasing, or decreasing based on changes in maximal tumor diameter or tumor volume. More recently, it has been observed that the changes in tumor size observed during observation are more complex with tumor volume kinetic patterns that can be characterized either as stable (Pattern I), early increase in volume (Pattern II), later increase in volume (Pattern III), early increase in volume followed by stability (Pattern IV), stability followed by an increase in volume (Pattern V), or a decrease in tumor volume (Pattern VI). Methods: The frequency, time course, and clinical correlates of these six tumor volume kinetic patterns were analyzed in a cohort of 483 patients with low-risk PTC up to 1.5 cm in maximal diameter followed with active surveillance at our center for a median of 3.7 years. Results: The cumulative incidence of an increase in tumor volume for the entire cohort was 15.9% [confidence interval (CI) 11.8-20.0] at 5 years. At 5 years, most tumors demonstrated stability (78.8%, Pattern I) with 10.0% showing early growth (Pattern II), 4.1% late growth (Pattern III), 1.9% growth then stability (Pattern IV), 0.6% stability then growth (Pattern V), and 5.6% with a decrease in tumor volume (Pattern VI). Tumor volume doubling time during exponential growth significantly differed across the kinetic patterns, with median values of 2.4, 7.1, and 3.3 years for Patterns II, III, and IV, respectively (p < 0.01). Similarly, the time to a change in tumor volume was significantly different across the kinetic patterns, with median values of 1.5, 3, 1.6, 4.7, and 4.1 years for Patterns II, III, IV, V, and VI, respectively (analysis of variance, p < 0.01). Clinical correlates at baseline were not associated with tumor volume kinetic pattern. Conclusions: These six kinetic tumor volume patterns provide a comprehensive description of the changes in PTC tumor volume observed during the first 5 years of active surveillance.

Multi-institutional validation of a modified scheme for subcategorizing salivary gland neoplasm of uncertain malignant potential (SUMP).

BACKGROUND: The salivary gland neoplasm of uncertain malignant potential (SUMP) category in the Milan System is diagnostically challenging. This study aims to validate a modified scheme for subcategorizing SUMP in a large multi-institutional cohort. METHODS: Retrospective review of salivary gland fine-needle aspirations (FNAs) from 10 institutions were classified based on the Milan System. Cases diagnosed as SUMP with available cytology slides and surgical follow-up were retrieved for review and subcategorized based on a modified scheme as follows: basaloid SUMP (B1: absent/scant nonfibrillary matrix; B2: presence of nonfibrillary/mixed-type matrix), oncocytic/oncocytoid SUMP (O1: with mucinous background; O2: without mucinous background), and SUMP not otherwise specified (NOS). RESULTS: A total of 742 (7.5%) cases from 9938 consecutive salivary gland FNAs were classified as SUMP. Among them, 525 (70.8%) had surgical follow-up and 329 (62.7%) were available for review. The overall risk of malignancy (ROM) of SUMP was 40.4%. There were 156 cases (47.4%) subcategorized as basaloid SUMP with a ROM of 36.5%, 101 (30.7%) as oncocytic/oncocytoid SUMP with a ROM of 52.5%, and 72 (21.9%) as SUMP NOS with a ROM of 31.9%. The ROM of oncocytic/oncocytoid SUMP was significantly higher than basaloid SUMP (P = .0142) and SUMP NOS (P = .0084). No significant differences in ROM were noted between B1 and B2 (36.7% vs 36.4%, P = 1.0000) and O1 and O2 (65.2% vs 48.7%, P = .2349). CONCLUSIONS: The ROM of oncocytic/oncocytoid SUMP was 52.5% and significantly higher than that of basaloid SUMP (36.5%, P = .0142) and SUMP NOS (31.9%, P = .0084), whereas no significant differences in ROM were noted for cases with different types of extracellular matrix or background material.

Yield of flow cytometry in addition to cytology for lymph node sampling in patients with incidental axillary adenopathy without a concurrent diagnosis of primary breast malignancy.

PURPOSE: Non-specific lymphadenopathy is increasingly being reported especially given the COVID-19 vaccination campaign and is a diagnostic dilemma especially in oncology patients. The purpose of this study was to evaluate the diagnostic accuracy and discordance rate between fine-needle aspiration (FNA) cytology and flow cytometry (FC) immunophenotyping in axillary FNA in patients with morphologically abnormal axillary lymph nodes on imaging and no concurrent diagnosis of primary breast malignancy. METHODS: This retrospective study included 222 patients who underwent screening or diagnostic axillary ultrasound that yielded suspicious lymphadenopathy without concurrent or recent prior diagnosis of breast cancer and who had subsequent image-guided axillary FNA and FC. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive value (PPV and NPV) were reported for FNA with cytology alone, and FC alone, and in combination. Discordance rate between FNA cytology and FC was assessed. Discordant cases were evaluated with histology or clinical and imaging follow-up. RESULTS: Diagnostic sensitivity, specificity, PPV, NPV, and diagnostic accuracy were 88%, 92%, 77%, 96%, and 91%, for FNA alone, 98%, 98%, 92%, 99%, and 98% for FC alone, and 100%, 92%, 79%, 100%, and 94% when combined. The overall discordance rate between FNA and FC was 7% (16/222). 7/16 (44%) patients with discordant results were diagnosed with lymphoma, while 9/16 (56%) patients with discordant results had benign findings. CONCLUSION: With a diagnostic accuracy of 91%, FNA with cytology is sufficient to screen patients with indeterminate and incidental lymphadenopathy. Flow cytometry could be initially deferred in patients with low pretest probability of lymphoma.

Global Cytopathology-Hematopathology Practice Trends.

OBJECTIVES: Small-volume biopsy-fine-needle aspiration biopsy (FNAB) with or without core biopsy-is in increasing use in diagnosis and management of lymphoma patients. Our objective was to survey the current practice in small-volume biopsy diagnosis of lymphoma, focusing on the interaction among hematopathologists and cytopathologists and the integration of FNAB, core biopsy, and flow cytometry studies at sign-out. METHODS: This study used a cross-sectional survey design employing the RedCap database distributed via nine pathology professional society email listservs. The survey consisted of 25 multiple-choice questions and several free text fields. In total, 128 pathologists participated. RESULTS: Most respondents indicated that FNAB specimens in which lymphoma is a diagnostic consideration (FNAB-L) are seen daily or weekly (68/116; 58.6%). However, most institutions have separate hematopathology and cytopathology services (72/116; 62.1%) with inconsistent communication. When communication occurred, respondents were frequently inclined to reconsider their original diagnoses. Barriers identified included lack of communication, inadequate access to diagnostic studies, no formal subspecialty training, and various opinions regarding FNAB in diagnosing lymphoma. CONCLUSIONS: This survey showed that FNAB-L specimens are common, with a lack of uniformity in how complementary fine-needle aspiration and core biopsy specimens or flow immunophenotyping results are shared across hematopathology and cytopathology services.

Role of Flow Cytometric Immunophenotyping for Classic Hodgkin Lymphoma in Small Biopsy and Cytology Specimens.

CONTEXT.­: The diagnosis of classic Hodgkin lymphoma (CHL) traditionally requires surgical tissue biopsy because of the paucity of diagnostic Hodgkin and Reed-Sternberg cells. Diagnosis can be challenging in small core needle and cytologic biopsies, which are increasingly used because of reduced costs and minimal invasiveness. Flow cytometric (FC) identification of Hodgkin and Reed-Sternberg cells is possible, but FC test efficacy is not well studied outside of validation settings, especially in small specimens. OBJECTIVE.­: To assess the testing efficacy of FC performed on small biopsy and cytology specimens for the diagnosis of CHL. DESIGN.­: We reviewed 131 patients with CHL and 459 patients without CHL during a 3-year period who underwent a small biopsy procedure, including core biopsy and/or cytology evaluation, with concurrent routine clinical FC testing for CHL, assessing performance of FC in small specimens. RESULTS.­: Evaluating testing efficacy, sensitivity was 95.4% and specificity was 98.2%, whereas positive and negative predictive values were 92.2% and 99.0%, respectively. Although there were more false-positive results than compared with published validation studies, expert review identified distinct diagnostic pitfalls; awareness of these may improve testing efficacy. CONCLUSIONS.­: Although FC diagnosis of CHL was historically considered unfeasible, our findings in a real-world clinical setting suggest that FC adds diagnostic value to small biopsy evaluation, reducing time to treatment, costs, and invasive excisional procedures.

Digital validation of breast biomarkers (ER, PR, AR, and HER2) in cytology specimens using three different scanners.

Progression in digital pathology has yielded new opportunities for a remote work environment. We evaluated the utility of digital review of breast cancer immunohistochemical prognostic markers (IHC) using whole slide images (WSI) from formalin fixed paraffin embedded (FFPE) cytology cell block specimens (CB) using three different scanners.CB from 20 patients with breast cancer diagnosis and available IHC were included. Glass slides including 20 Hematoxylin and eosin (H&E), 20 Estrogen Receptor (ER), 20 Progesterone Receptor (PR), 16 Androgen Receptor (AR), and 20 Human Epidermal Growth Factor Receptor 2 (HER2) were scanned on 3 different scanners. Four breast pathologists reviewed the WSI and recorded their semi-quantitative scoring for each marker. Kappa concordance was defined as complete agreement between glass/digital pairs. Discordances between microscopic and digital reads were classified as a major when a clinically relevant change was seen. Minor discordances were defined as differences in scoring percentages/staining pattern that would not have resulted in a clinical implication. Scanner precision was tabulated according to the success rate of each scan on all three scanners.In total, we had 228 paired glass/digital IHC reads on all 3 scanners. There was strong concordance kappa ≥0.85 for all pathologists when comparing paired microscopic/digital reads. Strong concordance (kappa ≥0.86) was also seen when comparing reads between scanners.Twenty-three percent of the WSI required rescanning due to barcode detection failures, 14% due to tissue detection failures, and 2% due to focus issues. Scanner 1 had the best average precision of 92%. HER2 IHC had the lowest intra-scanner precision (64%) among all stains.This study is the first to address the utility of WSI in breast cancer IHC in CB and to validate its reporting using 3 different scanners. Digital images are reliable for breast IHC assessment in CB and offer similar reproducibility to microscope reads.

Impact of initial biopsy type on the time to final diagnostic biopsy in patients with follicular lymphoma and suspected histologic transformation.

Diagnosis of histologic transformation (HT) of follicular lymphoma (FL) requires tissue biopsy. While surgical biopsy represents the gold standard, less invasive procedures such as fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are frequently performed. In this retrospective multi-institutional study including 269 patients with FL and suspected HT, the median time from initial clinical suspicion to final diagnostic biopsy was similar whether the workup began with FNAB, CNB, or surgical biopsy (4, 9, and 6 days, respectively; p=.27), despite more subsequent biopsies performed following initial FNAB. Periprocedural complications were uniformly minimal. Biopsy-proven HT was more common in the initial surgery group and in workups including positron emission tomography/computed tomography (PET/CT). Our findings, derived from US academic centers with specialized procedural and pathology expertise, suggest that FNAB, CNB, and surgical biopsy are all viable initial diagnostic procedures that can inform clinical decision-making in select FL patients with suspected HT.