Frozen Sections Research Articles

Accuracy of prior cytology versus intraoperative consultation in predicting the final diagnosis of thyroid specimens

Abstract Introduction/Objective The aim of this study was to assess the accuracy of preoperative cytology and the additional contribution of intraoperative frozen section in predicting the final diagnosis of thyroid surgical specimens. Methods/Case Report A retrospective search was conducted for cases that underwent pre-surgical cytology of thyroid surgical specimens received from January 2017 to June 2022. A total of 99 cases were evaluated which were grouped into six categories according to the Bethesda system. The cytology results were compared with the corresponding frozen section and permanent section diagnoses. Indeterminate and discordant cases were further evaluated with molecular tests. Results (if a Case Study enter NA) Among the 99 cases, preoperative cytologic diagnoses were as follows: 1 was nondiagnostic, 9 were benign, 7 were AUS/FLUS, 3 were FN/SFN, 7 were suspicious for malignancy, and 72 were malignant. Using Bethesda categories V and VI as cytology “positive” cases and Bethesda category II as cytology “negative” cases, the sensitivity and specificity of cytology were 99% and 100%, respectively. The positive predictive value was 100%. The negative predictive value was 89%, which was affected by sampling error. Intraoperative frozen section was performed on 31 cases. In 4 indeterminate cytology cases (Bethesda III, IV), frozen section diagnosis was benign in 1 (confirmed on final) and remained indeterminate in 3 cases (3 benign on final). All 3 dual indeterminate cases showed a follicular pattern; molecular tests were predictive of the final diagnosis in these cases. All 21 malignant frozen section diagnoses had positive cytology. Conclusion Cytology has high sensitivity and specificity, making it a valuable preoperative tool in thyroid surgery. Practically, intraoperative frozen section has limited value in thyroid nodules classified as Bethesda categories V and VI. Additional evaluation may be helpful for cases classified as uncertain Bethesda categories. For follicular patterned lesions, frozen section may have less value.

Rapid On-Site AI-Assisted Grading for Lung Surgery Based on Optical Coherence Tomography.

The determination of resection extent traditionally relies on the microscopic invasiveness of frozen sections (FSs) and is crucial for surgery of early lung cancer with preoperatively unknown histology. While previous research has shown the value of optical coherence tomography (OCT) for instant lung cancer diagnosis, tumor grading through OCT remains challenging. Therefore, this study proposes an interactive human-machine interface (HMI) that integrates a mobile OCT system, deep learning algorithms, and attention mechanisms. The system is designed to mark the lesion's location on the image smartly and perform tumor grading in real time, potentially facilitating clinical decision making. Twelve patients with a preoperatively unknown tumor but a final diagnosis of adenocarcinoma underwent thoracoscopic resection, and the artificial intelligence (AI)-designed system mentioned above was used to measure fresh specimens. Results were compared to FSs benchmarked on permanent pathologic reports. Current results show better differentiating power among minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IA), and normal tissue, with an overall accuracy of 84.9%, compared to 20% for FSs. Additionally, the sensitivity and specificity, the sensitivity and specificity were 89% and 82.7% for MIA and 94% and 80.6% for IA, respectively. The results suggest that this AI system can potentially produce rapid and efficient diagnoses and ultimately improve patient outcomes.

Telepathology in intraoperative frozen section consultation of breast cancer sentinel node biopsy in Fukushima, Japan following the 2011 triple disaster: diagnostic accuracy and required time during the early implementation phase.

In breast cancer surgery, some medical facilities lack the necessary resources to conduct sentinel lymph node biopsy and its intraoperative frozen section consultation. In the coastal rural area of Fukushima, Japan, which has suffered from physician undersupply following the 2011 triple disaster of earthquake, tsunami and nuclear disaster, we explored the feasibility of telepathology by evaluating the diagnostic accuracy in remote intraoperative frozen section consultation of sentinel lymph node biopsy and its required time. Although examination time has room for improvement, telepathology can be one possible solution in resource-limited areas.

Paradigm Change for Intraoperative Surgical Margin Assessment for Oral Squamous Cell Carcinoma.

Achieving clear surgical margins is one of the primary surgical goals in treating oral squamous cell carcinoma (OSCC) and thus aiming to improve overall and disease-specific survival. Therefore, we developed the Goal-Oriented Assessment for Intraoperative Margin ('GAIM') protocol, a novel intraoperative approach for margin assessment, and present here our 5-year experience and outcomes. 'GAIM' is a 7-step procedure comprising systematic ruler-aided resection of labeled tumor-bed margins, frozen section (FS) co-produced by both pathologists and operating surgeons, and immediate extension of resection according to FS findings. Data from all patients operated using the 'GAIM' protocol at a single tertiary center between 2018 to 2022 were analyzed, including margin status on FS and final pathology (FP) records, recurrence, and mortality. A total of 196 patients were included, 56.6% (n = 111) stages I-II, and 43.4% (n = 85) stages III-IV. Using the 'GAIM' protocol, we achieved an overall 94.4% of clean and revised clean surgical margins. Patients with a 2-year and longer follow-up (n = 141) had local recurrence in 3.5% when both FS and final margins were clean, 8.1% when FP margins were clean, and 16.7% with close/positive final margins. The proposed 'GAIM' protocol is a novel, effective, reproducible, and safe approach for margin evaluation that can be systematically applied. It can increase the rate of final clean surgical margins and potentially improve patients' outcomes. 3 Laryngoscope, 134:1725-1732, 2024.

Characteristics of multilineage-differentiating stress-enduring cell clusters in different culture conditions.

To observe the morphological characteristics of clusters of Muse cells from normal human dermal fibroblasts (NHDFs) under different culture conditions. Muse cells were sorted by magnetic activated cell sorting (MACS) from NHDFs, and were evaluated by flow cytometry. Muse cells were cultured in suspension and in adherent conditions to obtain Muse cell clusters (M-clusters), which were further characterized by alkaline phosphatase (AP) staining, immunofluorescence (IF) staining and transmission electron microscopy (TEM). The M-clusters were further cultured on Lando artificial dermal regeneration matrix (LADRM) for analysis by scanning electron microscopy (SEM) and IF staining of frozen sections. The proportion of SSEA3 and CD105 double-positive cells obtained by MACS was 87.4%. The sorted cells rapidly formed M-clusters after suspension culture, and showed internal characteristics of stem cells under TEM. After adherent culture, M-clusters stained positively for AP, SSEA-3 and OCT-4. Each M-cluster on the surface of the LADRM displayed an outer membrane of amorphous materials under SEM. Frozen sections and fluorescence staining of LADRM loaded with M-clusters showed an uneven fluorescence intensity of SSEA-3 within the clusters. Muse cells sorted by MACS from NHDFs could generate M-clusters, which included cells of different stemness and are wrapped in membrane-like structures.

Cytologic features of mesenchymal, melanocytic and haematolymphoid tumours of the central nervous system and metastases.

The current World Health Organization (WHO) classification of central nervous system (CNS) tumours includes several neoplasms that, while occurring in this location, are more frequently seen extracranially. These include mesenchymal, melanocytic and haematolymphoid neoplasms, as well as metastases. A few of these entities are exclusive of the CNS and have no extracranial counterpart. Despite their diverse histogenesis, these neoplasms share a peculiar predilection for involving meningeal structures. In fact, in the context of an intraoperative pathologic consultation of a meningeal tumour, virtually all these entities should be considered as potential diagnoses. Metastases in the CNS are very common. Most are carcinomas that cytologically resemble their site of origin. Loss of differentiation with cell dissociation and anaplasia and presence of accompanying fibrillary brain parenchyma can be a source of diagnostic problems. In this review, we intend to show the most relevant cytologic features of these tumours, and it is especially aimed at their analysis during intraoperative studies.

Diagnostic Value of Smears and Frozen Sections in Neuropathology Practice: Institutional Experience

Diagnostic Value of Smears and Frozen Sections in Neuropathology Practice: Institutional Experience

Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors.

The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay. FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL. The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

Touch imprint cytology is useful for the intraoperative pathological diagnosis of PitNETs’ surgical margins

Touch imprint cytology (TIC) and frozen section (FS) procedures are essential for intraoperative pathological diagnosis (IPD). They are invaluable tools for therapeutic decision-making, helping surgeons avoid under or overtreatment of patients. Pituitary neuroendocrine tumors (PitNETs) are generally small, slow-growing tumors with low-grade malignancy located at the base of the skull where it is impossible to maintain a wide tumor margin. Therefore, transsphenoidal surgery (TSS) should be performed with necessary caution, and with sufficient and minimal resection. Thus, this study aimed to evaluate the diagnostic accuracy of TIC for the diagnosis of PitNET and determine its ability to accurately evaluate the surgical margin compared to the FS procedure. A total of 104 fresh specimens from 28 patients who underwent TSS for PitNETs were examined using TIC and FS. TIC specimens were categorized according to the cell imprinting pattern. All specimens with a large number of neuroendocrine cells diffusely attached to the glass surfaces had PitNET components. Contrarily, no rich or diffuse cell attachments were observed in any non-tumoral endocrine cells. In conclusion, recognizing a pattern of endocrine cell adherence to glass is highly effective in IPD to certify the existence of a PitNET component.

Three-Dimensional Customized Imaging Reconstruction for Urological Surgery: Diffusion and Role in Real-Life Practice from an International Survey.

Despite the arising interest in three-dimensional (3D) reconstruction models from 2D imaging, their diffusion and perception among urologists have been scarcely explored. The aim of the study is to report the results of an international survey investigating the use of such tools among urologists of different backgrounds and origins. Beyond demographics, the survey explored the degree to which 3D models are perceived to improve surgical outcomes, the procedures mostly making use of them, the settings in which those tools are mostly applied, the surgical steps benefiting from 3D reconstructions and future perspectives of improvement. One hundred responders fully completed the survey. All levels of expertise were allowed; more than half (53%) were first surgeons, and 59% had already completed their training. Their main application was partial nephrectomy (85%), followed by radical nephrectomy and radical prostatectomy. Three-dimensional models are mostly used for preoperative planning (75%), intraoperative consultation and tailoring. More than half recognized that 3D models may highly improve surgical outcomes. Despite their recognized usefulness, 77% of responders use 3D models in less than 25% of their major operations due to costs or the extra time taken to perform the reconstruction. Technical improvements and a higher availability of the 3D models will further increase their role in surgical and clinical daily practice.

Ability for fine needle aspiration and frozen section to predict extent of parotidectomy.

Several diagnostic modalities with various sensitivity and specificities can be used to evaluate a parotid mass. The aims of this project were to compare the diagnostic actionability, accuracy, and ability to accurately predict extent of surgery for FNA and frozen section during the evaluation of a parotid mass. A retrospective chart review of patients who underwent parotidectomy for a parotid mass from January 1, 2015 to January 30, 2022 was conducted. Actionability was defined as a pathology diagnosis or the histologic grade of a lesion, as this provided clear and useful information for the surgeon to act upon. Diagnostic accuracy was determined by comparing FNA and frozen section results to final pathology. Accuracy of extent of surgery was determined by comparing predicted extent of surgery from the FNA or frozen section result to the extent of surgery predicted by the final pathology. A total of 626 patients were included in this study. FNA was obtained in 396 (63%) patients, while all neoplasms were evaluated by frozen section analysis. FNA diagnosis was actionable in 318 (80%), while frozen section diagnosis was actionable in 616 (98%) patients. Exactly 294 (92.5%) FNA diagnoses were accurate compared with 600 (98%) frozen section diagnoses. The FNA diagnosis predicted appropriate extent of surgery in 294 (74%) while the frozen section diagnosis predicted appropriate extent of surgery in 600 (96%). Among the 396 patients with FNA, frozen section was significantly more likely to accurately predict appropriate extent of surgery compared with FNA (p < 0.001). Frozen section is more likely to yield actionable and accurate results compared with FNA. Additionally, frozen section is better than FNA in predicting the appropriate extent of surgery.

Utility of Whole Slide Imaging for Intraoperative Consultation: Experience of a Large Academic Center.

In the United States, review of digital whole slide images (WSIs) using specific systems is approved for primary diagnosis but has not been implemented for intraoperative consultation. To evaluate the safety of review of WSIs and compare the efficiency of review of WSIs and glass slides (GSs) for intraoperative consultation. Ninety-one cases previously submitted for frozen section evaluation were randomly selected from 8 different anatomic pathology subspecialties. GSs from these cases were scanned on a Leica Aperio AT2 scanner at ×20 magnification (0.25 μm/pixel). The slides were deidentified, and a short relevant clinical history was provided for each slide. Nine board-certified general pathologists who do not routinely establish primary diagnoses using WSIs reviewed the WSIs using Leica Aperio ImageScope viewing software. After a washout period of 2-3 weeks, the pathologists reviewed the corresponding GSs using a light microscope (Olympus BX43). The pathologists recorded the diagnosis and time to reach the diagnosis. Intraobserver concordance, time to diagnosis, and specificity and sensitivity compared to the original diagnosis were evaluated. The rate of intraobserver concordance between GS results and WSI results was 93.7%. Mean time to diagnosis was 1.25 minutes for GSs and 1.76 minutes for WSIs (P < .001). Specificity was 91% for GSs and 90% for WSIs; sensitivity was 92% for GSs and 92% for WSIs. Time to diagnosis was longer with WSIs than with GSs, and scanning GSs and uploading the data to whole slide imaging systems takes time. However, review of WSIs appears to be a safe alternative to review of GSs. Use of WSIs allows reporting from a remote site during a public health emergency such as the COVID-19 pandemic and facilitates subspecialty histopathology services.

DIAGNOSTIC ACCURACY AND PROCESS EVALUATION WITH HEALTH ECONOMICS ANALYSIS OF AN ULTRA-FAST DIGITAL CONFOCAL MICROSCOPY SCANNER FOR REAL-TIME INTRA-OPERATIVE BRAIN TUMOUR DIAGNOSIS

Abstract AIMS Real-time intra-operative brain tumour tissue analysis in theatre can shorten turnaround times and facilitate repeated sampling; the latter can improve diagnostic accuracy and guide resection to maximise extent. We were the first team in the world to demonstrate the feasibility of an ultra-fast confocal microscopy scanner (Histolog®, SamanTree Medical SA) for real-time intra-operative brain tumour tissue diagnosis. The aim of this study is to demonstrate the diagnostic accuracy of Histolog® within a larger cohort of patients with brain tumours. METHOD An observational study with varying brain tumour types was conducted in a Tessa Jowell Brain Tumour Centre of Excellence. Adult patients undergoing brain biopsies or tumour debulking surgery were included. Multiple, freshly excised tissue samples were stained, and images captured within 60 seconds on Histolog® in the OR in parallel to current diagnostic pathways which included frozen section and smear cytology. Quantitative blinded concordance analysis between Histolog® images and gold standard histopathology was performed by a Consultant Neuropathologist. RESULTS A total of 50 cases are included in this analysis. This will include the quantitative analysis of n=50 cases and the concordance rating between Histolog® and gold standard traditional (frozen section and smear cytology) intra- operative histopathological diagnosis. The pilot data (n=12) that led to this larger study indicated a concordance rate of 83%. CONCLUSIONS Histolog® demonstrates non-inferior diagnostic accuracy when compared to current gold standard but significantly reduces the intra-operative time to achieve diagnosis. Future studies will investigate the effect of real- time margin zone analysis and explore machine learning for automatic computer aided diagnosis.

Cytological features of central nervous system germ cell tumours and tumours of the sellar region.

Germ cell tumours of the central nervous system and tumours of the sellar region represent a diverse group of neoplasms. These tumours affect both paediatric and adult patients and represent some of the most common central nervous system tumours as well as rare entities. Diagnosis frequently relies on tissue sampling, and intraoperative consultation is often needed to guide surgical management. The focus of this article is to provide a reference for the intraoperative cytology of these entities. The cytological features of these tumours as well as their differential diagnoses are described.

Utility of intraoperative pathology consultations of whipple resection specimens and their impact on final margin status

The resection margin status is a significant surgical prognostic factor for the long-term outcomes of patients undergoing pancreaticoduodenectomy (Whipple procedure). As a result, surgeons frequently rely on intraoperative consults (IOCs) involving frozen sections to evaluate margin clearance during these resections. Nevertheless, the impact of this practice on final margin status and long-term outcomes remains a topic of debate. This study aimed to assess the impact of IOCs on the clearance rate of resection margins following Whipple procedure and distal pancreatectomy. A retrospective database review of all patients who underwent Whipple procedure or distal pancreatectomy at our institution between 2018 and 2020 was performed to evaluate the utility of IOCs by gastrointestinal surgeons and its correlation with final postoperative surgical margin status. A significant variation in the frequency of IOC requests for margins among surgeons was noted. However, the use of frozen section analysis for intraoperative margin assessment was not significantly associated with the clearance rate of final post-operative margins. More frequent use of IOC did not result in higher final margin clearance rate, an important prognostic factor following Whipple procedure.

Comparative Study between Intraoperative Ultrasound and Frozen Section in the Assessment of Margins in Conservative Breast Surgery

Comparative Study between Intraoperative Ultrasound and Frozen Section in the Assessment of Margins in Conservative Breast Surgery

Accuracy of frozen section remote subspecialty consultation using real-time telepathology and whole-slide imaging in gynecologic cases.

Intrapathology consultation is recommended for complex cases during frozen section (FS) as routine practice. In our institution, solicited second opinions were traditionally provided by in-person consultation (IPC). Whole-slide imaging (WSI) was implemented in 2018 as an alternative but replaced by videoconferencing in 2020. Here, we assess the accuracy of remote FS consultation using these digital modalities vs IPC. Gynecologic FS cases over a 4-year period overseen by 2 intraoperative consultants were grouped by consultation method: (1) IPC, (2) WSI, and (3) videoconferencing. Accuracy was determined by concordance between the FS and final report diagnoses. Turnaround time between the 3 groups was analyzed using SPSS statistical software (IBM). Using WSI and videoconferencing, 100% concordance was observed, while the IPC group had a 98.5% concordance rate. Videoconferencing, however, showed longer turnaround times (mean, 45.59 minutes) than IPC (mean, 33.36 minutes). Although turnaround time positively correlated with the number of FS specimens, blocks, and H&E slides per case, no statistically significant differences in the number of specimens, blocks, and H&E slides generated were found among the consultation methods. Even though turnaround time using videoconferencing is longer, the accuracy of WSI and videoconferencing for remote FS consultation is equivalent to IPC. It is therefore a safe method for conducting intrapathology FS consultation in challenging surgical cases.

Development of LOX-1 Antibody Modified Immuno-liposomes as Drug Carriers to Macrophages in Atherosclerotic Lesions.

We developed a drug delivery system for atherosclerotic lesions using immuno-liposomes. We focused on enhancing the delivery efficiency of the liposomes to macrophages in atherosclerotic lesions by antibody modification of lectinlike oxidized low-density lipoproteins (LDL) receptor 1 (LOX-1). The cellular accumulation of the liposomes in foam cells induced by oxidized LDL (oxLDL) in Raw264 mouse macrophages was evaluated. The cellular accumulation of LOX-1 antibody modified liposomes in oxLDL-induced foam cells and untreated Raw264 cells was significantly higher compared with that of unmodified liposomes. The liposomes were also administered intravenously to Apoeshl mice as an atherosclerosis model. Frozen sections were prepared from the mouse aortas and observed by confocal laser microscopy. The distribution of LOX-1 antibody modified liposomes in the atherosclerotic regions of Apoeshl mice was significantly greater compared with that of unmodified liposomes. The results suggest that LOX-1 antibody modified liposomes can target foam cells in atherosclerotic lesions, providing a potential route for delivering various drugs with pharmacological effects or detecting atherosclerotic foci for the diagnosis of atherosclerosis.

When hypercriminalization falls afoul of the constitution: the need to rethink the Trafficking in Persons (Prevention, Care and Rehabilitation) Bill 2021

ABSTRACT Trafficking is a transnational legal problem that has attracted considerable attention since the adoption of the UN Convention against Transnational Organized Crime. In derogation of a robust indigenous jurisprudence on forced labour, the Indian state has, since 2000, imported the criminal law model of the Convention culminating in the Trafficking in Persons (Prevention, Care and Rehabilitation) Bill 2021. This Bill is a hypercarceral law, the relationship of which with pre-existing labour laws is unclear even as it seeks to abolish sex work. In its zeal to crack down on criminals, its provisions violate fundamental principles of criminal liability and Articles 14, 19, and 21 of the Constitution even while it casts the net of the criminal law wide, threatening to freeze sections of the economy and render the Indian worker a victim who is confined to rehabilitation homes. The article argues for a fundamental rethink of the Bill.

Role of intraoperative touch imprint cytology and immunohistochemistry in the diagnosis of metastatic malignancies in the central nervous system: Cyto-histomorphological findings and differential diagnosis.

Brain metastases (BMs) are intracranial neoplasms that are more common in adults than primary brain tumors, causing significant mortality and morbidity in cancer patients. This study aimed to evaluate the definitive histopathological diagnosis using touch imprint cytology and the importance and use of immunohistochemistry in the diagnosis of primary origin. Cytological, paraffin section, and immunohistochemical study slides of all metastatic brain tumors consecutively consulted at the pathology department between 2018 and 2023 were evaluated. The sensitivity, specificity, and accuracy of patients' diagnostic results who underwent imprint cytology were compared based on the final diagnosis histopathological report. A total of 45 patients with and without intraoperative consultation were included in the study. The definitive histopathologic diagnosis and the diagnostic accuracy rate of imprint cytology for distinguishing glial and metastatic tumors on paraffin sections was 100%. Immunohistochemistry was performed in all patients (except one patient; immediate exitus) and histological classification of the primary tumor was performed by analysis of clinical findings and biomarkers. The primary origins of metastatic tumors were often lung and breast, with adenocarcinoma subtype histomorphology, cerebral hemispheres, and discrete foci of metastasis. TPs is a simple and rapid technique that supports diagnosis in intraoperative neuropathology and is a very cost-effective procedure. The pathologist's experience is the key factor in the diagnosis and reduces the need for a frozen section. In our series, the final histopathologic correlation of imprint cytology in the diagnosis of primary and metastatic tumors is 100%.