Validation of a digital pathology system including remote review during the COVID-19 pandemic.

Remote digital pathology allows healthcare systems to maintain pathology operations during public health emergencies. Existing Clinical Laboratory Improvement Amendments regulations require pathologists to electronically verify patient reports from a certified facility. During the 2019 pandemic of COVID-19 disease, caused by the SAR-CoV-2 virus, this requirement potentially exposes pathologists, their colleagues, and household members to the risk of becoming infected. Relaxation of government enforcement of this regulation allows pathologists to review and report pathology specimens from a remote, non-CLIA certified facility. The availability of digital pathology systems can facilitate remote microscopic diagnosis, although formal comprehensive (case-based) validation of remote digital diagnosis has not been reported. All glass slides representing routine clinical signout workload in surgical pathology subspecialties at Memorial Sloan Kettering Cancer Center were scanned on an Aperio GT450 at ×40 equivalent resolution (0.26 µm/pixel). Twelve pathologists from nine surgical pathology subspecialties remotely reviewed and reported complete pathology cases using a digital pathology system from a non-CLIA certified facility through a secure connection. Whole slide images were integrated to and launched within the laboratory information system to a custom vendor-agnostic, whole slide image viewer. Remote signouts utilized consumer-grade computers and monitors (monitor size, 13.3-42 in.; resolution, 1280 × 800-3840 × 2160 pixels) connecting to an institution clinical workstation via secure virtual private network. Pathologists subsequently reviewed all corresponding glass slides using a light microscope within the CLIA-certified department. Intraobserver concordance metrics included reporting elements of top-line diagnosis, margin status, lymphovascular and/or perineural invasion, pathology stage, and ancillary testing. The median whole slide image file size was 1.3 GB; scan time/slide averaged 90 s; and scanned tissue area averaged 612 mm2. Signout sessions included a total of 108 cases, comprised of 254 individual parts and 1196 slides. Major diagnostic equivalency was 100% between digital and glass slide diagnoses; and overall concordance was 98.8% (251/254). This study reports validation of primary diagnostic review and reporting of complete pathology cases from a remote site during a public health emergency. Our experience shows high (100%) intraobserver digital to glass slide major diagnostic concordance when reporting from a remote site. This randomized, prospective study successfully validated remote use of a digital pathology system including operational feasibility supporting remote review and reporting of pathology specimens, and evaluation of remote access performance and usability for remote signout.

Changes in the Diagnoses of Breast Core Needle Biopsies on Second Review at a Tertiary Care Center: Implications for Surgical Management.

Core needle biopsy (CNB) of breast lesions is routine for diagnosis and treatment planning. Despite refinement of diagnostic criteria, the diagnosis of breast lesions on CNB can be challenging. At many centers, including ours, confirmation of diagnoses rendered in other laboratories is required before treatment planning. We identified CNBs first diagnosed elsewhere that were reviewed in our department over the course of 1 year because the patients sought care at our center and in which a change in diagnosis had been recorded. The outside and in-house CNB diagnoses were then classified based on Breast WHO Fifth Edition diagnostic categories. The impact of the change in diagnosis was estimated based on the subsequent surgical management. Findings in follow-up surgical excisions (EXCs) were used for validation. In 2018, 4950 outside cases with CNB were reviewed at our center. A total of 403 CNBs diagnoses were discrepant. Of these, 147 had a change in the WHO diagnostic category: 80 (54%) CNBs had a more severe diagnosis and 44 (30%) a less severe diagnosis. In 23 (16%) CNBs, the change of diagnostic category had no impact on management. Intraductal proliferations (n=54), microinvasive carcinoma (n=18), and papillary lesions (n=35) were the most disputed diagnoses. The in-house CNB diagnosis was confirmed in most cases with available excisions. Following CNB reclassification, 22/147 (15%) lesions were not excised. A change affecting the surgical management at our center occurred in 2.5% of all CNBs. Our results support routine review of outside breast CNB as a clinically significant practice before definitive treatment.

Hormone receptor and HER2 assessment in breast carcinoma metastatic to bone: A comparison between FNA cell blocks and decalcified core needle biopsies.

BACKGROUND: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) guide the clinical management of breast cancer metastases. Decalcification of bone core needle biopsies (CNBs) can affect IHC. In the current study, the authors sought to define whether fine-needle aspiration (FNA) would be a better alternative to CNB for reliable IHC. METHODS: Patients with breast cancer metastases to bone that were sampled by both CNB and FNA were selected. ER, PR, and HER2 were performed in FNA cell blocks (FNA-CBs) and concurrent decalcified CNBs. Discrepancies were classified as minor when there was a difference of up to 30% nuclear staining in IHC for ER and PR between paired samples and as major when a clinically relevant change was observed (ie, positive vs negative). Quantitative reverse transcriptase-polymerase chain reaction of ESR1 messenger RNA levels was performed on FNA/CNB pairs with discrepancies for ER IHC. IHC status of the primary breast carcinoma was recorded. RESULTS: Concordance rates for ER, PR, and HER2 were 89%, 67%, and 93%, respectively, between FNA-CB and CNB pairs from 27 patients. Major discrepancies were noted in approximately 11% of FNA/CNB pairs for ER IHC and in 33% of FNA/CNB pairs for PR. ESR1 messenger RNA levels of FNA/CNB matched samples were similar and did not explain the differences in ER IHC expression in the majority of cases. Two of 27 FNA/CNB pairs had different results for HER2 IHC that changed from negative on CNB to equivocal (2+) on FNA-CB. Both cases had prior HER2 amplification by fluorescence in situ hybridization. CONCLUSIONS: FNA-CB and CNB appear to constitute acceptable methods for the assessment of ER, PR, and HER2 for clinical decision making.

Accuracy of Intraoperative Frozen Section of Sentinel Lymph Nodes After Neoadjuvant Chemotherapy for Breast Carcinoma.

False-negative (FN) intraoperative frozen section (FS) results of sentinel lymph nodes (SLN) have been reported to be more common after neoadjuvant chemotherapy (NAC) in the primary surgical setting. We evaluated SLN FS assessment in breast cancer patients treated with NAC to determine the FN rate and the histomorphologic factors associated with FN results. Patients who had FS SLN assessment following NAC from July 2008 to July 2017 were identified. Of the 711 SLN FS cases, 522 were negative, 181 positive, and 8 deferred. The FN rate was 5.4% (28/522). There were no false-positive results. Of the 8 deferred cases, 5 were positive on permanent section and 3 were negative. There was a higher frequency of micrometastasis and isolated tumor cells in FN cases (P<0.001). There was a significant increase in tissue surface area present on permanent section slides compared with FS slides (P<0.001), highlighting the inherent technical limitations of FS and histologic under-sampling of tissue which leads to most FN results. The majority (25/28, 89%) of FN cases had metastatic foci identified exclusively on permanent sections and were not due to a true diagnostic interpretation error. FN cases were more frequently estrogen receptor positive (P<0.001), progesterone receptor positive (P=0.001), human epidermal growth factor receptor-2 negative (P=0.009) and histologic grade 1 (P=0.015), which most likely reflects the lower rates of pathologic complete response in these tumors. Despite its limitations, FS is a reliable modality to assess the presence of SLN metastases in NAC treated patients.

Diagnostic pitfalls in fine needle aspiration biopsy of the spleen.

Fine needle aspiration (FNA) of the spleen is rarely performed, due to fear of procedure complications. The objective of this study is to review the cytologic diagnoses of aspiration biopsy of the spleen performed in a cancer center. Archival material (9-year period) was reviewed and correlated with histologic and ancillary test results, when available.Forty-one splenic FNA specimens were identified. There were no reported procedure complications. Nineteen cases were diagnosed as malignant. Of these, 11 were lymphomas. Nineteen cases were diagnosed as benign. There was one false-negative case and four false-positive cases. Primary splenic neoplasms were rare and misinterpreted as malignant. It is important to be familiar with the normal cytology of this uncommonly aspirated organ in order to successfully identify neoplastic and malignant processes. The use of ancillary studies is important in the definitive classification of benign and malignant splenic lesions.

Perspectives on Expanded Scope of Practice in Cytotechnology.

INTRODUCTION: In an effort to identify professional trends while offering meaningful resources to support decision making in the cytopathology community, the ASC/ASCP Workgroup: Focusing on Emerging Roles in Cytopathology conducted several data collection activities to assess the current state and professional trends of cytotechnologist (CT) practice. This information is intended to inform evidence- based development of education and workforce model(s). MATERIALS AND METHODS: Research was conducted through mixed-method data collection processes. These included the ASCP Board of Certification (BOC) Practice Analysis, focus groups used to gather qualitative data regarding the perceptions and experiences of current stakeholders in cytopathology through face-to-face discussion, and a RAND Delphi study conducted to gather qualitative data regarding the perspectives and "pulse" of decision makers influencing cytopathology practice. RESULTS: Research findings reveal that practice patterns with new and emerging technologies are changing the workplace for many cytotechnologists. Cytotechnologists are increasingly performing tasks within the laboratory that extend beyond their formal training and are looking to professional societies to bridge the gap. Although many laboratory leaders embrace the use of cytotechnologists in expanded roles, regulatory restrictions and reimbursement rules are among acknowledged barriers to change. CONCLUSIONS: This study examines current marketplace needs and cytotechnologists' perceptions of their evolving workplace demands through qualitative data collection. This study provides a snapshot of the cur- rent climate of cytopathology and data that will help direct future education, personnel training needs, and staffing decisions.

Voices from the Field: Supporting the Educational Needs of Cytotechnologists.

INTRODUCTION: Sustaining a well-trained, competitive, and marketable cytotechnology workforce is a major goal of the American Society of Cytopathology/American Society for Clinical Pathology Workgroup Focusing on Emerging Roles in Cytopathology (ASC/ASCP Workgroup). This article describes the data collection initiatives performed by the Workgroup to confirm cytotechnologist (CT) perceived educational needs to keep pace with emerging practice changes in the workplace. In response to data collected, the Workgroup created Advanced Cytopathology Education (ACE)da unique, innovative educational resource designed to fulfill this need. MATERIALS AND METHODS: Data collection efforts included annual needs assessment surveys to gauge CT participants' preferred topics and learning modalities. These data were used to design and prioritize ACE topics. Program evaluations were also administered to evaluate participants' perceptions of program quality and effectiveness at meeting their educational needs. RESULTS: Research findings reveal CT education needs to align with emerging practice areas as reported in other Workgroup data collection efforts. The incorporation of new entry-level competencies in cytotechnology training programs prepares new CT graduates, but there is no standardized mechanism for formal, robust, and recognized ongoing education for other practicing CTs. CONCLUSIONS: This article highlights the educational endeavors carried out by the Workgroup in fulfilling the educational needs of practicing CTs as communicated through various data collection efforts. As CT responsibilities evolve, ASC and Workgroup efforts will continue to focus on providing educational support for current practicing CTs who need training in emerging practice areas.

Voices from the field: supporting the educational needs of cytotechnologists.

INTRODUCTION: Sustaining a well-trained, competitive, and marketable cytotechnology workforce is a major goal of the American Society of Cytopathology/American Society for Clinical Pathology Workgroup Focusing on Emerging Roles in Cytopathology (ASC/ASCP Workgroup). This article describes the data collection initiatives performed by the Workgroup to confirm cytotechnologist (CT) perceived educational needs to keep pace with emerging practice changes in the workplace. In response to data collected, the Workgroup created Advanced Cytopathology Education (ACE)-a unique, innovative educational resource designed to fulfill this need. MATERIALS AND METHODS: Data collection efforts included annual needs assessment surveys to gauge CT participants' preferred topics and learning modalities. These data were used to design and prioritize ACE topics. Program evaluations were also administered to evaluate participants' perceptions of program quality and effectiveness at meeting their educational needs. RESULTS: Research findings reveal CT education needs to align with emerging practice areas as reported in other Workgroup data collection efforts. The incorporation of new entry-level competencies in cytotechnology training programs prepares new CT graduates, but there is no standardized mechanism for formal, robust, and recognized ongoing education for other practicing CTs. CONCLUSIONS: This article highlights the educational endeavors carried out by the Workgroup in fulfilling the educational needs of practicing CTs as communicated through various data collection efforts. As CT responsibilities evolve, ASC and Workgroup efforts will continue to focus on providing educational support for current practicing CTs who need training in emerging practice areas.

Perspectives on expanded scope of practice in cytotechnology.

INTRODUCTION: In an effort to identify professional trends while offering meaningful resources to support decision making in the cytopathology community, the ASC/ASCP Workgroup: Focusing on Emerging Roles in Cytopathology conducted several data collection activities to assess the current state and professional trends of cytotechnologist (CT) practice. This information is intended to inform evidence-based development of education and workforce model(s). MATERIALS AND METHODS: Research was conducted through mixed-method data collection processes. These included the ASCP Board of Certification (BOC) Practice Analysis, focus groups used to gather qualitative data regarding the perceptions and experiences of current stakeholders in cytopathology through face-to-face discussion, and a RAND Delphi study conducted to gather qualitative data regarding the perspectives and "pulse" of decision makers influencing cytopathology practice. RESULTS: Research findings reveal that practice patterns with new and emerging technologies are changing the workplace for many cytotechnologists. Cytotechnologists are increasingly performing tasks within the laboratory that extend beyond their formal training and are looking to professional societies to bridge the gap. Although many laboratory leaders embrace the use of cytotechnologists in expanded roles, regulatory restrictions and reimbursement rules are among acknowledged barriers to change. CONCLUSIONS: This study examines current marketplace needs and cytotechnologists' perceptions of their evolving workplace demands through qualitative data collection. This study provides a snapshot of the current climate of cytopathology and data that will help direct future education, personnel training needs, and staffing decisions.

Bethesda Interobserver Reproducibility Study-2 (BIRST-2): Bethesda System 2014.

INTRODUCTION: In concert with the 2014 update to the Bethesda System for Reporting Cervical Cytology, a Web-based image interobserver study was performed to evaluate concordance with the "expert panel" interpretation, as was done during the Bethesda 2001 update. The aim was to identify cytomorphologic features and Bethesda reporting categories that represent sources of poor interobserver agreement and see how the trends compared to the first Bethesda Interobserver Reproducibility Study (BIRST). MATERIALS AND METHODS: Participants were recruited online through national and international cytopathology professional societies. Study participants evaluated 84 previously unpublished web images chosen from the third Bethesda Atlas image set, prior to the release of the atlas. These images spanned all reporting categories and included typical and borderline cytomorphology. Demographic information was collected on level of training, practice patterns, and experience of the participants. Participation was restricted to those correctly answering 2 basic cytopathology questions, ensuring minimal knowledge of gynecologic cytopathology. RESULTS: A total of 1290 unique individuals attempted access to this Web-based study and 833 correctly answered the two qualifying questions. Of these, 518 respondents completed the survey. Participant origin included: 59% United States, 41% international; 48% cytotechnologists, 41% pathologists, 5% fellows, and 6% other. Practice types were: 39% academic institutions, 29% private hospitals, and 16% commercial laboratories. Overall, the mean participant agreement with the exact Bethesda panel interpretation was 62.8%. The best agreement was found for negative for intraepithelial lesion or malignancy (NILM; 74%) and low-grade squamous intraepithelial lesion (LSIL; 86%) categories. Squamous cell carcinoma (SCC) (63%), high-grade squamous intraepithelial lesion (HSIL; 60%), atypical squamous cells of undetermined significance (ASC-US; 62%) and atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H; 60%) showed slightly lower concordance with the panel interpretations. Cervical glandular lesions were more problematic (33%). Anal samples performed similarly to their gynecologic counterparts. There was similar diagnostic agreement across participant certifications and practice type (academic versus non-academic). Performance was higher for United States and other North America-based participants (P = 0.0104). This significance may be attributed to a language bias, as the survey was only offered in English. CONCLUSIONS: Similar to the BIRST-1 study conducted in 2001, the most important factor for diagnostic agreement by cytotechnologists, pathologists, and trainees was the a priori difficulty of an image rather than participant training, certification, or experience. Participants showed better general diagnostic agreement with the expert panel interpretations of the material in BIRST-2 than in BIRST-1. Agreement was highest for Bethesda categories of NILM, LSIL, HSIL, and SCC. Concordance for even the borderline ASC-US and ASC-H categories exhibited remarkable improvement in the BIRST-2.

Fine needle aspiration biopsy of primary mucinous carcinoma of the skin: a case report.

BACKGROUND: Primary mucinous carcinoma of the skin is a rare neoplasm of sweat gland origin. To date there are only 2 case reports in English describing its features on fine needle aspiration biopsy (FNAB). We describe an additional case and review the literature regarding this entity. To the best of our knowledge, this is the first reported case with a sentinel lymph node biopsy. CASE: A 78-year-old woman presented with a 3-cm left scalp mass at an outside institution. Following incomplete excision, multiple subcentimeter nodules developed in the skin adjacent to the biopsy site. FNAB of the nodules confirmed a recurrence of mucinous carcinoma. Clinical examination and extensive radiographic studies did not reveal primary disease elsewhere, thus supporting a diagnosis of primary mucinous carcinoma of the skin. At the time of wide excision of the residual tumor, sentinel lymph node biopsy revealed a single focus of micrometastasis. The patient declined adjuvant therapy and was disease free 6 months after the initial diagnosis. CONCLUSION: Cutaneous mucinous carcinoma is a tumor characterized by bland histocytologic features and abundant extracellular pools of mucin. Without a high index of suspicion, this rare entity may be overlooked or misdiagnosed. Numerous benign and malignant mucin-producing primary and secondary mimics exist, and immunohistochemistry offers limited benefits in differentiating them. Cytologic diagnosis of primary mucinous carcinoma of the skin is possible; however, correlation of clinical, radiologic and pathologic features is necessary to arrive at an accurate diagnosis.

Suitability of thoracic cytology for new therapeutic paradigms in non-small cell lung carcinoma: high accuracy of tumor subtyping and feasibility of EGFR and KRAS molecular testing.

INTRODUCTION: The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR and KRAS molecular testing. The aim of this study was to comprehensively review the performance of cytologic specimens for the above two goals in a high-volume clinical practice. METHODS: Subtyping of primary lung carcinomas by preoperative cytology was correlated with subsequent resection diagnoses during a 1-year period (n = 192). The contribution of various clinicopathologic parameters to subtyping accuracy and utilization of immunohistochemistry (IHC) for NSCLC subtyping were analyzed. In addition, the performance of cytologic specimens submitted for EGFR/KRAS molecular testing during a 1-year period (n = 128) was reviewed. RESULTS: Of the 192 preoperative cytology diagnoses, tumor subtype was definitive versus favored versus unclassified in 169 (88%) versus 15 (8%) versus 8 (4%) cases, respectively. Overall accuracy of cytologic tumor subtyping (concordance with histology) was 93% and accuracy of definitive diagnoses 96%. For a group of patients with ADC and SqCC (n = 165), the rate of unclassified cytologic diagnoses was 3% and overall accuracy 96%. IHC was used for subtyping of 9% of those cases, yielding 100% accuracy. The strongest predictors of difficulty in subtyping of ADC and SqCC were poor differentiation (p = 0.0004), low specimen cellularity (p = 0.019), and squamous histology (p = 0.003). Of 128 cytologic specimens submitted for molecular testing, 126 (98%) were suitable for analysis, revealing EGFR and KRAS mutations in 31 (25%) and 25 (20%) cases, respectively. CONCLUSIONS: Cytologic subtyping of NSCLC is feasible and accurate, particularly when morphologic assessment is combined with IHC. Furthermore, routine cytologic specimens can be successfully used for EGFR/KRAS mutation analysis. Our data strongly support the suitability of cytologic specimens for the new therapeutic paradigms in NSCLC.

Effectiveness of the Thin Prep Imaging System in the detection of adenocarcinoma of the gynecologic system.

BACKGROUND: The ThinPrep Imaging System (TIS) has been approved by the U.S. Food and Drug Administration for use to decrease the number of false-negative results in ThinPrep (TP) gynecologic specimens and increase cytotechnology productivity. Although the increased detection of squamous abnormalities using the TIS has been well documented, to the authors' knowledge, data regarding the impact of the TIS in the detection of glandular abnormalities is limited. The goal of the current study was to evaluate the effectiveness of the TIS in detecting glandular abnormalities in cervicovaginal specimens. METHODS: TIS evaluated TP tests with histologic confirmation of adenocarcinoma involving the gynecologic system were included in the current study. Two cytotechnologists independently reviewed the cases for the presence or absence of atypical glandular cells. Review results were correlated with initial cytologic and histologic diagnoses. RESULTS: A total of 124 cases met the criteria for inclusion in the current study. Seventy of these cases (56%) were found to contain atypical glandular cells on the TP slide. TIS was able to identify atypical cells in 97% of these cases (68 of 70 cases). Nine cases initially reported as benign were found to contain atypical glandular cells on secondary review. All but 1 of these cases contained atypical glandular cells detected by the TIS. The majority of these false-negative cases (6 of 9 cases) derived from endometrial adenocarcinoma. No cytologic evidence of a glandular abnormality was found in the 54 remaining cases. CONCLUSIONS: The TIS was found to be effective in identifying atypical glandular cells in specimens containing malignant glandular cells, leading to a full review of the slide.

Anorectal cytology as a screening tool for anal squamous lesions: cytologic, anoscopic, and histologic correlation.

BACKGROUND: Anorectal cytology has been increasingly used as a screening method for anal squamous lesions, particularly in high-risk, homosexual, patients with human immunodeficiency virus infection. The diagnostic cytologic, anoscopic, and histologic criteria bear some resemblance to the criteria used in cervicovaginal samples with few differences. It is important to recognize these differences because they can lead to an erroneous diagnosis of dysplasia and unnecessary procedures. METHODS: Seventy-eight anorectal cytology specimens from 51 patients were reviewed blindly. Of the 51 patients, 33 were HIV positive. The cytology specimens consisted of 75 ThinPrep (Cytyc, Boxborough, MA) and 3 conventional Papanicolaou-stained smear specimens. The revised diagnosis was compared with the original diagnosis, corresponding histology specimens, and anoscopic results, when available. RESULTS: Six specimens were unsatisfactory for review. The revised diagnosis was negative in 15 patients, atypical squamous cells of undetermined significance in 3 patients, low-grade squamous intraepithelial lesions in 24 patients, high-grade squamous intraepithelial lesions in 28 patients, and squamous cell carcinoma (SQC) in 2 patients. Five patients with an original diagnosis of SQC had the diagnosis revised upon review of their specimens. It is noteworthy that these five specimens showed the presence of atypical parakeratotic cells. Thirty-two patients had anoscopic evaluation and 30 patients had histologic correlation. Twenty-seven patients with abnormal anoscopic findings had confirmed abnormal histologic findings. Twenty- five of the 32 (78%) patients had abnormal cytology that correlated with abnormal anoscopic findings. CONCLUSIONS: Anorectal cytology is an accurate method for screening patients for anal squamous lesions. Atypical parakeratotic cells represent a potential pitfall. Anoscopy is important in confirming the presence of a lesion, but only a biopsy can accurately determine the grade of a lesion.