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Background: During sentinel node navigation surgery in patients with gastric cancer, intraoperative pathologic examination of sentinel nodes is crucial in determining the extent of surgery. In this study, we evaluated the feasibility and accuracy of intraoperative pathologic protocols using data from a prospective, multicenter, randomized trial., Methods: A retrospective analysis was conducted using data from the SEntinel Node ORIented Tailored Approach trials from 2013 to 2016. All sentinel lymph nodes were evaluated during surgery with hematoxylin-eosin (HE) staining using a representative section at the largest plane for lymph nodes. For permanent histologic evaluation, sentinel basin nodes were stained with HE and cytokeratin immunohistochemistry in formalin-fixed, paraffin-embedded (FFPE) sections and examined with HE for three deeper-step sections at 200-μm intervals. The failure rate of identification by frozen section and the metastasis rate in non-sentinel basins were investigated., Results: Of the 237 patients who underwent sentinel node basin dissection, 30 had lymph node metastases on permanent pathology. Thirteen patients had macrometastasis confirmed in frozen sections as well as FFPE sections (failure rate: 0%). Patients with negative sentinel nodes in frozen sections but micrometastasis in FFPE sections had no lymph node recurrence during the follow-up period (0%, 0/6). However, in cases with tumor-positive nodes in frozen sections, metastases in non-sentinel basins were detected in the paraffin blocks (8.3%, 2/24)., Conclusions: The single-section HE staining method is sufficient for detecting macrometastasis via intraoperative pathological examination. If a negative frozen-section result is confirmed, sentinel basin dissection can be performed safely. Otherwise, standard surgery is required., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Context.—: 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., Objective.—: To evaluate the safety of review of WSIs and compare the efficiency of review of WSIs and glass slides (GSs) for intraoperative consultation., Design.—: 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., Results.—: 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., Conclusions.—: 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., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Objective: To compare the staining quality between rapid hematoxylin and eosin (H&E) staining and routine H&E staining of frozen breast tissue sections., Methods: In this cross-sectional observational study, 120 frozen breast tissue sections were randomly assigned to rapid or routine H&E staining ( n =  60 per group). Rapid H&E staining used a 7:1 mixture of modified Gill's hematoxylin and alcohol-soluble 1% eosin Y. The staining quality of each section was evaluated and scored. A score of >7 was considered excellent, a score of 6 to 7 good, and a score of ≤5 poor., Results: The staining time for rapid staining was approximately 3 minutes, whereas that of routine staining was approximately 12 minutes. There were no significant differences in the staining quality scores or proportions of sections in each grade between the two staining methods. The proportions of sections that were classified as excellent or good were 96.7% and 98.3% for rapid and routine staining, respectively., Conclusions: In frozen breast tissue sections, rapid H&E staining may provide staining quality that is comparable to that of routine staining, while markedly reducing the staining time., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Background: Sentinel lymph node (SLN) is the first lymph node to drain the lymph from a particular region involved by cancer. The commonly performed intraoperative methods for SLN evaluation are touch imprint cytology (TIC) and frozen section (FS). The present study aimed to determine the sensitivity, specificity and accuracy of TIC and FS with histopathological diagnosis as gold standard., Materials and Methods: The nodes were bissected along their long axis and wet surface was imprinted on to clean glass slides followed by toluidine blue and rapid Papanicolaou staining. Subsequently the lymph node slices were cut at three levels using the cryostat machine and stained with Hematoxylin and eosin stain. The cytological and FS findings were compared and the specificity, sensitivity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of TIC and FS was evaluated taking histopathological diagnosis as gold standard. In addition, pooled sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for touch imprint cytology and frozen section were assessed for the studies included in the meta-analysis., Results: The specificity, sensitivity, diagnostic accuracy, positive predictive value and negative predictive value of touch imprint cytology were 100%, 88.2%, 90%, 100% and 60% respectively. The specificity, sensitivity, diagnostic accuracy, PPV and NPV of frozen section were 100%, 94.1%, 95%, 100% and 75% respectively. The sensitivity of TIC and FS for detection of micrometastasis was 60% and 80% respectively. The pooled sensitivity and specificity for touch imprint cytology were 85.24% (95% CI, 83.46%-86.90%), and 98.99% (95% CI, 98.69%-99.23%) respectively. The pooled sensitivity and specificity for frozen section examination were 90.45% (95% CI, 85.15%-94.34%), and 100% (95% CI, 99.24%-100%) respectively., Conclusion: Even though the sensitivity of FS was better than imprint cytology in detection of micrometastasis, TIC is a rapid inexpensive technique which can be utilized in remote areas in absence of cryostat machine. The sensitivity of the two techniques with respect to detection of macrometastasis was comparable. This meta-analysis highlights the accuracy of the touch imprint cytology and frozen section examination in the intra-operative detection of malignancy in breast cancer.

Aim and Objectives: To estimate and evaluate the optimal thickness of tissue section for skin and dermal appendages intra-operatively and to compare the morphology and architecture of the epidermis and its appendages at 7 and 10 microns., Methodology: After obtaining clearance from the institutional human ethical committee, 101 skin margins were prospectively analyzed using a two-step embedding technique. After multiple trials and errors, 7- and 10-micron thicknesses were selected for the present study. Artefacts, staining characteristics, cellular morphology, cellular outline, and nuclear outline were assessed and scored as unacceptable or acceptable. The data were entered in a Microsoft Excel spreadsheet and analyzed using SPSS software., Results: There was a statistically significant difference between the sections obtained at 7 microns and 10 microns (p-value: <0.001), the latter were better in all the parameters analyzed. However, no difference was noted in the characteristics of the dermal appendages (p-value: >0.05)., Conclusion: While mucosal margins can be obtained at the usual 5-7 microns, the same thickness is not optimal for skin margins intra-operatively. Frozen sections for the skin margins may be set at 10 microns, to save time, minimize artefacts, and for better readability.

Objectives: Intraoperative frozen-section evaluation is a valuable technique for detecting positive margins intraoperatively for oral squamous cell carcinoma. We conducted this study to determine the diagnostic accuracy of frozen section in detecting margin status and the effect of tumor grade and stage on diagnostic accuracy., Results: A total of 251 biopsy-proven cases of oral squamous cell carcinoma were included in this study. The tissue specimen resected during surgery was sent to the laboratory for frozen section evaluation. The frozen section results were then compared with the permanent section results to determine the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. The mean age of the patients included in the study was 51.65 ± 10.03 years, with male predominance (55.4%). The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of frozen section were 88.81%, 94.84%, 95.20%, 88.10%, and 91.63%, respectively. We conclude that frozen section is a useful technique in determining the margin status intraoperatively in oral cancers, with high diagnostic accuracy. Moreover, certain clinical parameters such as age, gender, disease duration, and tumor stage and grade appear to affect the diagnostic accuracy of frozen section., (© 2024. The Author(s).)

Context.—: Intraoperative diagnosis by frozen section is a mainstay of surgical pathology practice, providing immediate feedback to the surgical team. Despite good accuracy with modern methods, access to intraoperative surgical pathology with an appropriate turnaround time (TAT) has been a limiting factor for small or remote surgical centers, with negative impacts on cost and patient care. Telepathology offers immediate expert anatomic pathology consultation to sites without an in-house or subspecialized pathologist., Objective.—: To assess the utility of live telepathology in frozen section practice., Design.—: Frozen section diagnoses by telemicroscopy from 2 tertiary care centers with a combined 3 satellite hospitals were queried for anatomic site, TAT per block, pathologist, and concordance with paraffin diagnosis. TAT and concordance were compared to glass diagnoses in the same period., Results.—: For 748 intraoperative diagnoses by telemicroscopy, 694 had TATs with a mean of 18 minutes 56 seconds ± 8 minutes 45 seconds, which was slower than on glass (14 minutes 25 seconds ± 7 minutes 8 seconds, P < .001). Twenty-two (2.89% of available) were discordant, which was not significantly different from the on-glass rate (P = .44) or categorical distribution (P = .31). Two cases (0.27%) had technical failures., Conclusions.—: Although in-person diagnoses were statistically faster, the great majority of telemicroscopic diagnoses were returned in less than 20 minutes. This remained true through numerous pathologists, pathology assistants and/or technicians, different hospitals, and during a combined 6 years. The concentration of discordant diagnoses among relatively few pathologists suggests individual comfort with telepathology and/or frozen section diagnosis. In rare cases, technical issues prevented telemicroscopic diagnosis. Overall, this justifies continued use and expansion of telemicroscopic services in primary intraoperative diagnoses., (© 2024 College of American Pathologists.)

Stimulated Raman histology (SRH) is an ex vivo optical imaging method that enables microscopic examination of fresh tissue intraoperatively. The conventional intraoperative method uses frozen section analysis, which is labor and time intensive, introduces artifacts that limit diagnostic accuracy, and consumes tissue. SRH imaging allows rapid microscopic imaging of fresh tissue, avoids tissue loss, and enables remote telepathology review. This improves access to expert neuropathology consultation in both low- and high-resource practices. We clinically validated SRH by performing a blinded, retrospective two-arm telepathology study to clinically validate SRH for telepathology at our institution. Using surgical specimens from 47 subjects, we generated a data set composed of 47 SRH images and 47 matched whole slide images (WSIs) of formalin-fixed, paraffin-embedded tissue stained with hematoxylin and eosin, with associated intraoperative clinicoradiologic information and structured diagnostic questions. We compared diagnostic concordance between WSI and SRH-rendered diagnoses. Also, we compared the 1-year median turnaround time (TAT) of intraoperative conventional neuropathology frozen sections with prospectively rendered SRH-telepathology TAT. All SRH images were of sufficient quality for diagnostic review. A review of SRH images showed high accuracy in distinguishing glial from nonglial tumors (96.5% SRH vs 98% WSIs) and predicting final diagnosis (85.9% SRH vs 93.1% WSIs). SRH-based diagnosis and WSI-permanent section diagnosis had high concordance (κ = 0.76). The median TAT for prospectively SRH-rendered diagnosis was 3.7 minutes, approximately 10-fold shorter than the median frozen section TAT (31 minutes). The SRH-imaging procedure did not affect ancillary studies. SRH generates diagnostic virtual histologic images with accuracy comparable to conventional hematoxylin and eosin-based methods in a rapid manner. Our study represents the largest and most rigorous clinical validation of SRH to date. It supports the feasibility of implementing SRH as a rapid method for intraoperative diagnosis complementary to conventional pathology laboratory methods., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Despite the rapid developments in diagnostic techniques and medical sciences, pathologic diagnosis is still recognized as the gold standard for disease diagnose. Pathologic diagnosis is a time-consuming task performed for pathologists, needing profound professional knowledge and long-term accumulated diagnostic experience. Therefore, the development of automatic and precise histopathological image classification is essential for medical diagnosis. In this study, an improved VGG network was used to classify the breast cancer histopathological image from intraoperative rapid frozen sections. We adopt a transformed loss function by adding a penalty to cross-entropy in our training stage, which improved the accuracy on test data by 4.39%. Laplacian-4 was used for the enhancement of images, which contributes to the improvement of the accuracy. The accuracy of the proposed model on training data and test data reached 88.70% and 82.27%, respectively, which outperforms the original model by 9.39% of accuracy in test data. The process time was less than 0.25 s per image on average. Meanwhile, the heat maps of predictions were given to show the evidential regions in histopathological images, which could drive improvements in the accuracy, speed, and clinical value of pathological diagnoses. In addition to helping with the actual diagnosis, this technology may be a benefit to pathologists, surgeons, and patients. It might prove to be a helpful tool for pathologists in the future., (© 2023. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Context.—: With the adoption of Epic/Beaker at our institution, surgical pathology specimens are assigned a Current Procedural Terminology (CPT) charge code at the time of accessioning, and pathologists have been made responsible for verifying the accuracy of the code before signing out the case., Objective.—: To determine with what frequency attending pathologists reassigned the correct charge code to a specimen when the code assigned at accessioning was incorrect, as well as to estimate the potential financial impact of missed changes., Design.—: We reviewed all specimens received for frozen section during a 7-month period, identified specimens where the default charge code that our departmental protocol assigns at frozen section (88305) was incorrect, and assessed the rate of successful code change by pathologists and the potential financial cost of each missed change., Results.—: Three hundred fifty-two of 2191 frozen section specimens (16%) required a change in the 88305 charge code. The codes for 195 specimens (55%) were correctly changed by the attending pathologist, while 157 (45%) were not changed (149) or were changed to an incorrect charge code (8). Individual pathologist change rates ranged from 0% to 100%, with a mean and median change rate of 43% and 24%, respectively. Using average code reimbursements at our institution, the loss in revenue from the 157 missed and incorrect frozen section changes was estimated at $13 788 ($1970 per month)., Conclusions.—: Pathologists showed highly variable rates of correcting CPT charge codes when the incorrect code had been previously assigned to a case, with associated loss of revenue from missed and incorrect code changes., (© 2023 College of American Pathologists.)

Background: Preoperative fine-needle aspiration (FNA) is widely used to differentiate malignant from benign thyroid nodules, while intraoperative frozen sections (FS) are suggested as a systematic supplement for intraoperative decision-making, but limitations still remain for both procedures., Methods: Medical records of 3807 patients with thyroid nodules who underwent both pathological diagnoses (FS and FNA) at our hospital were reviewed. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA and FS were also evaluated. We further designed an optimal integration scheme (FNA+selective FS) to predict thyroid nodule malignancy. Finally, the efficiency of the proposed integrated diagnostic model was validated using an independent external cohort., Results: For distinguishing malignant nodules, FNA had an accuracy of 90.3%, sensitivity of 90.7%, specificity of 85.2%, PPV of 98.8% and NPV of 40.4%. In contrast, the FS represented higher discriminative power (Accuracy, 94.5%; Sensitivity, 94.1%; Specificity, 100%; PPV, 100%; and NPV, 55.6%). we proposed the selective usage of FS (removed nodules with Bethesda category VI from routine FS, ~1/3 of total). The integrated new diagnostic model of FNA plus selective FS (FNA+sFS) achieved accuracy of 96.9%, sensitivity of 97.3%, specificity of 92%, PPV of 99.4%, and NPV of 71.6% (NRI=0.135, 95% CI 0.103-0.167, P <0.001) and was successfully applied to an external cohort (N=554)., Conclusion: Compared with the FNA diagnostic system, FS has an increased ability to distinguish benign and malignant thyroid nodules. The newly proposed integrated diagnostic model of FNA + selective FS can optimize the accuracy of diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mao, Ding, Wen, Zhang, Wu, You, Wu, Luo, Teng and Wang.)

Purpose: This study aimed to compare the intraoperative frozen section with the surgical margin in the postoperative surgical margins of the postoperative pathology of oral squamous cell carcinomas in order to examine the reliability of the frozen section., Methods: A retrospective analysis was conducted for patients who underwent surgery for oral squamous cell carcinoma in a tertiary hospital between January 2018 and 2019. The intraoperative frozen section examinations, grade of the tumor, number of lymph nodes, number of affected lymph nodes, depth of invasion, perineural invasion, lymphovascular invasion, and extranodal extension were recorded from the pathological records. The concordance between the frozen section examination and postoperative pathology 2 methods was examined using the Cronbach α coefficient. Sensitivity, specificity, positive predictive value, negative predictive value regarding surgical margins, and accuracy were calculated and reported., Results: Overall, 181patients who underwent surgery for oral cavity cancers were included; 118 (65.2%) were males. The mean (± standard deviation) age of the included participants was 57.4 ± 16.1 years. The most common tumour subsite was the tongue (n = 71, 39.2%). There was concordancy between the frozen, positive intraoperative malignancy and the postoperative pathology malignancy. The frozen, negative intraoperative malignancy and postoperative safe surgical margin did not significantly differ., Conclusion: As a result of intraoperative frozen examination, we found conformity between the postoperative pathology results of patients with positive and negative surgical margins. Frozen section examination could be used safely to examine intraoperative surgical margins of oral squamous cell carcinoma.

Background: In 2021, there is an increased global trend for sending sentinel lymph node biopsy (SLNB) specimens for permanent section (PS) without intraoperative frozen sections (FS). This pilot study conducted in Thailand determines the re-operation rate for SLNB without FS., Method: We retrospectively reviewed 239 SLNB cases without FS at King Chulalongkorn Memorial Hospital from April 2016 to April 2021. The patients were diagnosed with primary invasive breast cancer with clinically negative nodes. The clinical nodal status was assessed from physical examination. The re-operation rate was determined by the number of positive SLNs; where 3 more nodal metastases were subjected to a second surgical procedure., Result: Between April 2016 and April 2021, 239 patients who had undergone SLNB in accordance with ACOSOG Z0011 criteria with PS alone was enrolled. A total of 975 SLNs were removed from these 239 patients, with an average of 4.15 nodes per patient. Out of 239 patients, 21 (8.8%) and 6 (2.5%) had metastatic disease in 1 and 2 nodes, respectively. The remaining 212 (88.7%) patients had no nodal metastasis. None of the patients were subjected to a second surgical procedure., Conclusion: We conclude that the implementation of SLNB with PS analysis alone in patients who satisfy the ACOSOG Z0011 criteria, with a re-operation rate of 0%, does not have outcomes that would be altered by the standard of care additional FS analysis. With ommision of FS analysis, operation cost, operative time and anesthetic side effects are projected to decrease., (© 2022. The Author(s).)

Context.—: Intraoperative consultation-frozen section diagnosis (FSD)-determines tumor pathology and guides the optimal surgical management of ovarian neoplasms intraoperatively., Objective.—: To evaluate the diagnostic accuracy of the FSD and analyze the discrepancy between the FSD and final diagnosis., Design.—: This is a retrospective study of 618 ovarian neoplasm FSDs from 2009 to 2018 at a tertiary health care center. The discrepant cases were reviewed and reevaluated by gynecologic and general surgical pathologists. The outcomes of interest were performing unnecessary procedure, returning for a second surgery, and 30-day postoperative mortality., Results.—: The sensitivity and the positive predictive value of the FSD were lower in borderline tumors than in benign and malignant epithelial ovarian tumors. Major and minor discrepancies were identified in 5.3% (33 of 618) and 12.3% of (76 of 618) cases, respectively. A root cause analysis of the major discrepant cases showed that sampling error accounted for 43% (14 of 33). The discrepancy distributions of gynecologic and general surgical pathologists were statistically similar in the overall cohort (P = .65). The overall κ for diagnostic agreement among gynecologic pathologists, general surgical pathologists, and final diagnosis was 0.18 (0.10-0.26, P < .001), implying only a slight overall agreement. Of the major discrepant cases, only 3 had a clinical implication. One overdiagnosed patient underwent an unecessary procedure, and 2 underdiagnosed patients were recommended to return for a second surgery. No patient had 30-day postoperative mortality., Conclusions.—: Frozen section diagnosis remains a definitive diagnostic tool in ovarian neoplasms and plays a crucial role in guiding intraoperative surgical management.

Photo-isolation chemistry (PIC) enables isolation of transcriptome information from locally defined areas by photo-irradiation. Here, we present an optimized PIC protocol for formalin-fixed frozen and paraffin mouse sections and fresh-frozen mouse sections. We describe tissue section preparation and permeabilization, followed by in situ reverse transcription using photo-caged primers. We then detail immunostaining and UV-mediated uncaging to the target areas, followed by linear amplification of uncaged cDNAs, library preparation, and quantification. This protocol can be applied to various animal tissue types. For complete details on the use and execution of this protocol, please refer to Honda et al. (2021)., Competing Interests: S.O. and Y.O. are involved in a pending patent related to PIC technology (application number, 2019-094216; patent office, Japan Patent Office; current status, patent pending). All the other authors declare no competing interests., (© 2022 The Author(s).)

Objective: A primary medical relevance of thyroid nodules consists of excluding thyroid cancer, present in approximately 5% of all thyroid nodules. Fine-needle aspiration biopsy (FNAB) has a paramount role in distinguishing benign from malignant thyroid nodules due to its availability and diagnostic performance. Nevertheless, intraoperative frozen section (iFS) is still advocated as a valuable tool for surgery planning, especially for indeterminate nodules., Methods: To compare the FNAB and iFS performances in thyroid cancer diagnosis among nodules in Bethesda Categories (BC) I to VI. The performance of FNAB and iFS tests were calculated using final histopathology results as the gold standard., Results: In total, 316 patients were included in the analysis. Both FNAB and iFS data were available for 272 patients (86.1%). The overall malignancy rate was 30.4%% (n = 96). The FNAB sensitivity, specificity, and accuracy for benign (BC II) and malignant (BC V and VI) were 89.5%, 97.1%, and 94.1%, respectively. For all nodules evaluated, the iFS sensitivity, specificity, and accuracy were 80.9%, 100%, and 94.9%, respectively. For indeterminate nodules and follicular lesions (BC III and IV), the iFS sensitivity, specificity, and accuracy were 25%, 100%, and 88.7%, respectively. For BC I nodules, iFS had 95.2% of accuracy., Conclusion: Our results do not support routine iFS for indeterminate nodules or follicular neoplasms (BC III and IV) due to its low sensitivity. In these categories, iFS is not sufficiently accurate to guide the intraoperative management of thyroidectomies. iFS for BC I nodules could be an option and should be specifically investigated.

Background: Pediatric central nervous system (CNS) tumors have a different histological spectrum as compared to adults with the infantile group having even more varied and distinct histological profiles. Intra-operative diagnosis is especially important as it guides the neurosurgeon to tailor an approach which is best suited for a particular case. The aim of the study was to evaluate the diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value of frozen section (FS) and squash cytology and to find out the degree of correlation (kappa value) between the two procedures., Materials and Methods: A prospective study was conducted on 55 pediatric patients with clinicoradiologically diagnosed CNS lesions for a period of 2.5 years. Intra-operative squash smears and FS were made and stained with hematoxylin and eosin stain. Diagnosis made subsequently on paraffin embedded sections was taken as the gold standard., Results: Although the specificity (90%) and positive predictive value (96%) were comparable between the two procedures, sensitivity (91.4%) and negative predictive value (75%) of FS was more as compared to squash cytology. Both the diagnostic modalities showed substantial agreement (k = 0.728)., Conclusion: Even though the histological spectrum of pediatric CNS tumors is more varied than adults, FS gives a reasonable intra-operative diagnosis and better results when compared to squash alone., Competing Interests: None

Background: Breast cancer is one of the most prevalent malignancies in women worldwide, and the rate of breast cancer is increasing among Iranian women. The purpose of this study is to determine the cost-effectiveness of intraoperative frozen section analysis in women with breast cancer., Methods: This study was a cost-effectiveness analysis, which was implemented as a cross-sectional study from a societal perspective. In this case, total direct and indirect costs were calculated, and the study outcome was involved in preventing reoperation. A data collection form has been used to collect the cost and effectiveness data. The sample size was comprised of all the patients referred to the hospitals of Shiraz University of Medical Sciences for breast cancer surgery in 2019. The patients were studied in two different groups, including individuals who received frozen counseling during surgery, and individuals who did not receive it. A one-way sensitivity analysis was performed for this case. Moreover, the Tree Age and Microsoft Excel Software were employed for analyzing processes., Results: The results demonstrated that the mean costs of frozen and non-frozen patients were 4168$ and 3843$ purchasing power parity (PPP), respectively. In addition, the effectivenesses were 0.996 for the former and 0.8 for the latter. Furthermore, the incremental cost-effectiveness ratio (ICER) was 1658.2 PPP$. This issue revealed that the frozen section procedure during surgery was more cost-effective than the other case. Because, the cost-effectiveness of this option was below the threshold. Besides, the one-way sensitivity analysis confirmed the robustness of the study results., Conclusion: The results showed that performing frozen sections during surgery in women with breast cancer was more cost-effective than ignoring them. Indeed, the frozen section can prevent the costs of subsequent reoperations., (Copyright: © Iranian Journal of Medical Sciences.)

Considering that every tissue/organ has the most suitable microenvironment for its functional cells, controlling induced pluripotent stem cell (iPSC) differentiation by culture on frozen sections having a suitable microenvironment is possible. Induced PSCs were cultured on frozen sections of the liver, the brain, the spinal cord, and cover glasses (control) for 9 days. The iPSCs cultured on the sections of the liver resembled hepatocytes, whereas those on sections of the brain and the spinal cord resembled neuronal cells. The percentage of hepatocytic marker-positive cells in the iPSCs cultured on the sections of the liver was statistically higher than that of those in the iPSCs cultured on the sections of the brain and the spinal cord or on cover glasses. In contrast, the iPSCs cultured on the sections of the brain and the spinal cord revealed a high percentage of neural marker-positive cells. Thus, iPSCs can be differentiated into a specific cell lineage in response to specific factors within frozen sections of tissues/organs. Differentiation efficacy of the frozen sections markedly differed between the iPSC clones. Therefore, our induction method could be simple and effective for evaluating the iPSC quality.

Fine-needle aspiration (FNA) biopsy reliably diagnoses parotid gland lesions preoperatively, whereas intraoperative frozen section (FS) has the additional benefit of assessing surgical margins and refining diagnoses; however, the role of FS in the setting of prior FNA diagnosis is not well established. Our aim was to determine whether FS should still be performed after a prior FNA/ CNB diagnosis. Parotid gland resections from January 2009 to January 2020 were identified; however, only patients who had both FNA and FS constituted our study population. For the purpose of statistical analysis, FNA diagnoses were classified into non-diagnostic (ND), non-neoplastic (NN), benign neoplasm (BN), indeterminate, and malignant. FS diagnoses were classified into benign, indeterminate, or malignant. Resections were dichotomized into benign and malignant and regarded as the gold standard to subsequently calculate diagnostic accuracy of FNA and FS. A total of 167 parotid gland resections were identified, but only 76 patients (45.5%) had both FNA and FS. In 35 cases deemed as benign preoperatively, three (8.6%) were reclassified as malignant on FS. Out of 18 lesions reported as malignant on FNA, four (22.2%) were interpreted as benign on FS, with three of these benign lesions confirmed on permanent slides. In addition, in patients with both FNA and FS, compared to FNA, FS was able to provide a definitive diagnosis in all five ND cases and in 61.1% (11/18) of indeterminate tumors. Intraoperative assessment provided a relative increase of 33.3% in specificity and 38.5% in positive predictive value when compared to preoperative FNA. The addition of FS to FNA was helpful to further refine the diagnoses of parotid gland lesions, which may provide better guidance for surgical intervention., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Acute invasive fungal rhinosinusitis (AIFRS) is a fulminant disease with a high mortality rate. Here, we review the clinical and pathologic features of AIFRS over a 30-year period at a tertiary-care academic center focusing on diagnostic practice, especially the use of intra-operative consultation (IOC). A 1-year trial of intraoperative staining with DiffQuik® (DQ) was also assessed. There were 202 cases from 104 patients with AIFRS. The incidence of AIFRS increased over time (6.8 per year in the past decade versus 1.9 before 2009) as did the number of IOCs per case (2.4 per case in the past decade versus 0.6 before 2009). Disagreement between final diagnosis and IOC was seen in 8.3 % of patients, and the block-by-block error rate was 14.9 %. Fusarium was the most common fungus identified. An attempt to categorize the fungal organism based on histopathology was performed in 85.6 % of patients, with 91 % agreement with microbial cultures or PCR. Fungal hyphae were subjectively easier to identify on DQ stained cryostat sections compared to on routine hematoxylin and eosin stained sections and hyphae were identified in all 5 blocks in which organisms were present. The increasing incidence of AIFRS and expanding use of IOC indicate a need to improve and standardize the diagnostic protocol. The use of DQ as visual aid in IOC for AIFRS may be useful., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Immunohistochemistry (IHC) using mouse retinal cryosections is widely used to study the expression and intracellular localization of proteins in mouse retinas. Conventionally, the preparation of retinal cryosections from mice involves tissue fixation, cryoprotection, the removal of the cornea and lens, embedding and sectioning. The procedure takes 1-2 days to complete. Recently, we developed a new technique for the preparation of murine retinal cryosections by coating the sclera with a layer of Super Glue. This enables us to remove the cornea and extract the lens from the unfixed murine eye without causing the eyecup to collapse. In the present study, based on this new technique, we move a step forward to modify the conventional protocol. Unlike in the conventional protocol, in this method, we first coat the unfixed mouse eyeball on the sclera with Super Glue and then remove the cornea and lens. The eyecup is then fixed, cryoprotected and sectioned. This new protocol for the preparation of retinal cryosections reduces the time for the procedure to as little as 2 h. Importantly, the new protocol consistently improves the morphology of retinal sections as well as the image quality of IHC. Thus, this new quick protocol will be greatly beneficial to the community of visual sciences by expediting research progress and improving the results of IHC.

Context.—: Acute invasive fungal rhinosinusitis (AIFRS) is an aggressive form of fungal sinusitis, which remains a significant cause of morbidity and mortality. Early diagnosis and intervention are keys to improving patient outcomes. Intraoperative consultation has shown promise in facilitating early surgical intervention, but the accuracy of frozen section has not been clarified in this setting., Objectives.—: To assess the accuracy of frozen-section diagnosis in patients with clinically suspected AIFRS., Design.—: All cases of clinically suspected AIFRS during a 10-year period (2009-2019) were retrospectively reviewed. The frozen-section results were compared with the final permanent sections as well as the tissue fungal culture results, following which the accuracy of frozen section was determined., Results.—: Forty-eight patients with 133 frozen-section evaluations for AIFRS were included in the study. Thirty of 48 patients and 61 of 133 specimens were positive for AIFRS on final pathology. Of 30 positive patients, 27 (90%) had at least 1 specimen diagnosed as positive during intraoperative consultation; among the 61 positive specimens, 54 (88.5%) were diagnosed as positive during intraoperative consultation. Of 72 negative specimens, all were interpreted as negative on frozen section. Thus, frozen sections had a sensitivity of 88.5% (95% CI, 0.78-0.97), specificity of 100% (95% CI, 0.94-1), positive predictive value of 100% (95% CI, 0.92-1), and negative predictive value of 90.6% (95% CI, 0.82-0.97)., Conclusions.—: This study represents the largest series assessing the diagnostic accuracy of frozen section analysis in AIFRS. These findings are useful in frozen section-informed intraoperative decision making.

Frozen section analysis is a frequently used method for examination of tissue samples, especially for tumour detection. In the majority of cases, the aim is to identify characteristic tissue morphologies or tumour margins. Depending on the type of tissue, a high number of misdiagnoses are associated with this process. In this work, a fast spectroscopic measurement device and workflow was developed that significantly improves the speed of whole frozen tissue section analyses and provides sufficient information to visualize tissue structures and tumour margins, dependent on their lipid and protein molecular vibrations. That optical and non-destructive method is based on selected wavenumbers in the mid-infrared (MIR) range. We present a measuring system that substantially outperforms a commercially available Fourier Transform Infrared (FT-IR) Imaging system, since it enables acquisition of reduced spectral information at a scan field of 1 cm 2 in 3 s, with a spatial resolution of 20 µm. This allows fast visualization of segmented structure areas with little computational effort. For the first time, this multiphotometric MIR system is applied to biomedical tissue sections. We are referencing our novel MIR scanner on cryopreserved murine sagittal and coronal brain sections, especially focusing on the hippocampus, and show its usability for rapid identification of primary hepatocellular carcinoma (HCC) in mouse liver.

We investigated the relationship between positive surgical margin (PSM)-related factors and biochemical recurrence (BCR) and the ability of intraoperative frozen sections to predict significant PSM in patients with prostate cancer. The study included 271 patients who underwent robot-assisted laparoscopic prostatectomy with bilateral nerve sparing and maximal urethral preservation. Intraoperative frozen sections of the periurethra, dorsal vein, and bladder neck were analyzed. The ability of PSM-related factors to predict BCR and significant PSM was assessed by logistic regression. Of 271 patients, 108 (39.9%) had PSM and 163 (60.1%) had negative margins. Pathologic Gleason score ≥8 (18.9% vs 7.5%, P = 0.015) and T stage ≥T3a (51.9%vs 24.6%, P < 0.001) were significantly more frequent in the PSM group. Multivariate analysis showed that Gleason pattern ≥4 (vs <4; hazard ratio: 4.386; P = 0.0004) was the only significant predictor of BCR in the PSM cohort. Periurethral frozen sections had a sensitivity of 83.3% and a specificity of 84.2% in detecting PSM with Gleason pattern ≥4. Multivariate analysis showed that membranous urethra length (odds ratio [OR]: 0.79, P = 0.0376) and extracapsular extension of the apex (OR: 4.58, P = 0.0226) on magnetic resonance imaging (MRI) and positive periurethral tissue (OR: 17.85, P < 0.0001) were associated with PSM of the apex. PSM with Gleason pattern ≥4 is significantly predictive of BCR. Intraoperative frozen sections of periurethral tissue can independently predict PSM, whereas sections of the bladder neck and dorsal vein could not. Pathologic examination of these samples may help predict significant PSM in patients undergoing robot-assisted laparoscopic prostatectomy with preservation of functional outcomes., Competing Interests: None

Background: When the resected specimen is sent for intraoperative margin assessment, all margins are grossly checked, and selected margins undergo a frozen section (FS) examination. Therefore, there is a possibility of sampling error. This study evaluated the effectiveness of using toluidine blue (TB) as an intraoperative triage screening tool to detect positive mucosal margins of the resected specimens of oral squamous cell carcinoma (OSCC) and serve as a guide for FS sampling., Methods: Surgical samples of 30 consecutive patients with biopsy-proven OSCC were included in the study. A total of 140 mucosal margins were analyzed intraoperatively by TB and FS, the results were compared with the final histopathology., Results: Of the 140 examined mucosal tumor margins, 14 stained positives with TB, six were true-positives, eight were false-positives, and there were no false-negatives, as confirmed by final histopathology of the same margins. The diagnostic performance measures were sensitivity 100.0%; specificity 94.0%; positive predictive value (PPV) 42.9%; negative predictive value (NPV) 100.0%; and accuracy 94.3% (95% CI: 89.0-97.5%). For FS, there were three true-positives, three false-negatives, and no false-positives. The diagnostic performance measures were sensitivity 50.0%; specificity 100.0%; PPV 100.0%; NPV 97.8%; and accuracy 97.9% (95% CI: 93.9-99.6%)., Conclusion: TB is less specific but more sensitive than FS for detecting positive mucosal margins of resected OSCC. Screening the tumor mucosal margins with TB before FS sampling may help identify more tumor-bearing margins., Trial Registration: This trial was registered at ClinicalTrials.gov. Registration number: NCT03554967 . Registration date: June 13, 2018.

The green fluorescent protein (GFP) is a powerful reporter protein that allows labeling of specific proteins or entire cells. However, as GFP is a small soluble protein, it easily crosses membranes if cell integrity is disrupted, and GFP signal is lost or diffuse if the specimen is not fixed beforehand. While pre-fixation is often feasible for histological analyses, many molecular biology procedures and new imaging techniques, such as imaging mass spectrometry, require unfixed specimens. To be able to use GFP labeling in tissues prepared for such applications, we have tested various protocols to minimize the loss of GFP signal. Here we show that, in cryocut sections of snap-frozen brain tissue from two GFP reporter mouse lines, leaking of the GFP signal is prevented by omitting the commonly performed drying of the cryosections, and by direct post-fixation with 4% paraformaldehyde pre-warmed at 30-37 °C. Although the GFP staining does not reach the same quality as obtained with pre-fixed tissue, GFP localization within the cells that express it is preserved with this method. This protocol can thus be used to identify GFP positive cells on sections originating from unfixed, cryosectioned tissue.

To maximize data obtainment from valuable cardiac tissue, we hypothesized that myocardium fixed in optimal cutting temperature (OCT) medium for histology could also be used to investigate the function of myofilament proteins in situ. We compared tissue prepared via conventional liquid nitrogen (LN) snap freezing with tissue fixed in OCT and then sectioned in fiber-parallel orientation. We found that actin-myosin Ca 2+ sensitivity, activation rate by Ca 2+ , cooperativity along the thin filament, as well as cross-bridge cycling rate were unaffected by OCT storage and could reliably be interpreted after sectioning. Absolute values in maximum force generation per cross-sectional area, as well as passive strain, are difficult to investigate after sectioning, as myofibrillar continuity along the preparation cannot be guaranteed. We have shown that myocardial tissue stored in OCT and sectioned before analysis is available for functional analysis, a valuable means of maximizing usage of precious cardiac biopsies. NEW & NOTEWORTHY Myocardial tissue in optimal cutting temperature (OCT) fixation and cryostat sectioning was tested as a means of storing and preparing tissue for myofilament function analysis in relation to conventional liquid nitrogen freezing and dissection. Actomyosin interaction, Ca 2+ force activation, and passive compliance were tested. The study concluded that OCT storage and cryostat sectioning do not interfere with the actomyosin cross-bridge dynamics or Ca 2+ activation but that absolute tension values suffer and may not be investigated by this method.

Background/aim: The aim of this study was to evaluate the current role of frozen section in identifying patients who could benefit from an immediate axillary lymph node dissection (ALND), following the criteria of the ASOCOG Z0011 and IBCSG 23-10 trials., Patients and Methods: A retrospective review was performed involving 2,079 patients with early breast cancer who underwent conservative surgery or total mastectomy with sentinel lymph node biopsy., Results: Sensitivity and diagnostic accuracy were 63.8% and 90.3%, respectively. Sensitivity was significantly higher (p<0.001) in finding macrometastases (81.8%) compared to micrometastases (11.9%). Frozen section was useful only in 7.7% of the patients who met the criteria of the IBCSG 23-01 and ACOSOG Z0011 trials., Conclusion: Frozen section continues to be very useful in the intraoperative assessment of the SLN, offering a high sensitivity and diagnostic accuracy. Omission of ALND in 24.4% of patients who met the ACOSOG Z0011 criteria would have resulted in their undertreatment., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: For early-stage lung adenocarcinoma, determining the extent of surgical resection and lymphadenectomy according to the invasion status of the tumour may be more reliable. Intraoperative frozen section (FS) is a potentially effective method to identify the invasion status while its accuracy is still unknown. This meta-analysis aimed to evaluate the accuracy of FS for the invasion status of lung adenocarcinoma., Methods: We conducted a systematic search of PubMed, Embase, Scopus and Cochrane Library databases (from inception to October 26, 2018) to identify studies investigating the accuracy of FS for the invasion status of lung adenocarcinoma. The accuracy of FS was evaluated by calculating the pooled concordance rates (CCR) between FS and final pathology and the pooled sensitivity, specificity, and other parameters of FS for discriminating pre-/minimally invasive adenocarcinoma from invasive adenocarcinoma (IAC). The negative predictive value (NPV) of FS for diagnosing IAC was also calculated to evaluate the chance of underestimation., Results: Six eligible studies were included. The pooled CCR for differentiating pre-invasive adenocarcinoma, minimally invasive adenocarcinoma and IAC was 88% (95% CI, 84%-93%). When pre-invasive adenocarcinoma and minimally invasive adenocarcinoma were classified as a group, the pooled CCR, sensitivity, specificity of FS for differentiating pre-/minimally invasive adenocarcinoma from IAC were 95% (95% CI, 94%-97%), 95% (95% CI, 92%-97%), 95% (95% CI, 80%-99%), respectively. The pooled NPV of FS for diagnosing IAC was 95% (95% CI, 92%-97%)., Conclusions: Intraoperative FS is reliable for identifying the invasion status of lung adenocarcinoma, with high diagnostic accuracy for differentiating pre-/minimally invasive adenocarcinoma from IAC., (Copyright © 2019 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: The accuracy of intra-operative decision in confirming ovarian tumor malignancy during the operation is vital. Frozen sections are an important intra-operative tool to determine the provisional diagnosis and appropriate treatment of a tumor., Study Design: All records of diagnosed ovarian tumor patients who underwent exploratory laparotomy with intra-operative frozen sections request at Bhumibol Adulyadej Hospital (BAH) between January 2016 and June 2018 were reviewed., Main Outcome Measures: Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of intra-operative frozen and permanent sections were evaluated., Result: A total of 150 cases were recruited in this study. The mean age was 45.4 years. The number of benign, borderline and malignant ovarian tumors in this study were 97, 9 and 44 cases, respectively. The overall accuracy was 93.3%. Percentage of accuracy, sensitivity, specificity, PPV and NPV for benign, borderline and malignancy were 98.0/94.7/94.0, 100/88.9/79.6, 94.3/95.0/100, 97.0/55.3/100 and 100/99.3/92.2, respectively., Conclusion: The frozen section results yielded accurate diagnosis for rapid intraoperative evaluation of ovarian tumors. Its high accuracy allows for an appropriate surgical plan to be made in a timely manner. Large sizes and suspected mucinous borderline ovarian tumors reduced accuracy factors of frozen sections.

Background: The aim of this study was to assess the agreement rate between intraoperative evaluation (IOE) and final diagnosis (FD) in a series of surgically resected endometrial carcinoma (EC), with a preoperative ambiguous or inconclusive diagnosis by endometrial biopsies and imaging., Methods: A retrospective study was performed selecting patients who underwent surgery with IOE for suspected EC at our institution from 2012 to 2018. A K coefficient was determined with respect to the histotype, tumor grade, myometrial infiltration and cervical involvement., Results: Data analysis has been performed on 202 women. The IOE evaluation was distributed as Endometrioid (n = 180) and Non-Endometrioid (n = 22). The comparison between the frozen section (FS) and the definitive histological subtype showed an overall agreement rate of 93,07% (k = 0.612) and an agreement of 97.2% for Endometrioid vs 59% for Non-Endometrioid tumors. The FIGO system grading was the same in 91,1% of patients, none was upgraded and in 8,9% downgraded. Observed agreements were 89,11% and 95,54% for myometrial and cervical involvement, respectively., Conclusions: The good agreement between intraoperative grading, myometrial invasion and their histological definition on permanent sections highlights that FS is a good predictor for surgical outcome, in particular in presence of a preoperative ambiguous or inconclusive diagnostic evaluation.

Objective: To determine the accuracy of frozen section diagnosis and factors associated with final pathological diagnosis upgrade in patients with mucinous ovarian tumors., Methods: This study included 1,032 patients with mucinous ovarian tumors who underwent frozen section diagnosis during surgery. Sensitivity, specificity, and diagnostic accuracy of frozen section diagnosis was calculated. Univariate and multivariate regression analyses were performed to determine factors associated with diagnosis upgrade in the final pathology report., Results: The sensitivity and specificity of frozen section diagnosis were 99.1% (95% confidence interval [CI]=98%-99.6%) and 82.2% (95% CI=77.9%-85.7%), respectively, for benign mucinous tumors; 74.6% (95% CI=69.1%-79.4%) and 96.7% (95% CI=95.2%-97.8%), respectively, for mucinous borderline ovarian tumors; and 72.5% (95% CI=62.9%-80.3%) and 98.8% (95% CI=97.9%-99.3%), respectively, for invasive mucinous carcinomas. The multivariate analysis revealed that mixed tumor histology (odds ratio [OR]=2.8; 95% CI=1.3-6.3; p=0.012), tumor size >12 cm (OR=2.5; 95% CI=1.5-4.3; p=0.001), multilocular tumor (OR=2.9; 95% CI=1.4-6.0; p=0.006), and presence of a solid component in the tumor (OR=3.1; 95% CI=1.8-5.1; p<0.001) were independent risk factors for final pathological diagnosis upgrade., Conclusions: Mixed tumor histology, tumor size >12 cm, multilocular tumor, and presence of a solid component in the tumor were independent risk factors for final pathological diagnosis upgrade based on frozen section diagnosis., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Context.—: In vivo microscopy (IVM) allows direct, real-time visualization of tissue histology in living patients without the need for tissue removal, processing, or staining. The IVM technologies in clinical use include confocal microscopy and optical coherence tomography. These technologies also show promise for use with pathology specimens (ex vivo microscopy [EVM]). However, few systems designed for EVM are commercially available, at least in part because of the lack of defined minimal functional requirements (FRs)., Objective.—: To develop minimal FRs for likely high-volume pathology applications of EVM., Design.—: The IVM Committee of the College of American Pathologists identified potential EVM pathology applications based on the published literature. A subcommittee of IVM and EVM early adopters and experts then defined FRs for the most likely EVM applications., Results.—: Potential EVM applications include assessment of margins, adequacy of needle biopsies and aspirates for diagnosis, and transplant tissues; selection of tissue for molecular studies or biorepository; and guidance in block selection from gross specimens. The first 3 applications were selected for development of FRs. The FRs were identified based on existing laboratory practices and guidelines and input from experts in the field and included device footprint and portability, specimen preparation, imaging time, field of view or resolution, morphologic diagnostic capability, yield, accuracy, ease of use, safety, and cost., Conclusions.—: Consensus was achieved on FRs that would accommodate the selected EVM applications. Publication and dissemination of those FRs will provide guidance to engineers, researchers, and vendors on how to optimally adapt IVM technologies for EVM for widespread adoption by pathologists.

Purpose: The optimal timing of reimplantation of two-stage exchange arthroplasty for periprosthetic joint infection remains unknown. The purpose of the study was to (1) evaluate performance of combination of serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and frozen section in predicting persistent infection at the time of second-stage hip reimplantation and (2) compare accuracies of 5 and 10 polymorphonuclear neutrophils (PMNs) per high power field (HPF) as the threshold of frozen section., Methods: We retrospectively reviewed 97 two-stage exchange hip arthroplasties from 2012-2016. Persistent infection at time of reimplantation was diagnosed using the Musculoskeletal Infection Society (MSIS) criteria. Two diagnostic models were developed. Model 1 utilized ESR, CRP, and > 5 PMNs/HPF on frozen section. Model 2 utilized ESR, CRP, and > 10 PMNs/HPF. Receiver operating characteristic (ROC) curves of the two models were generated, and areas under the curves (AUCs) were compared. A set of sensitivity analysis, using the Delphi-based consensus criteria for treatment success, was conducted to verify the accuracy of our models., Results: The overall rate of infection at reimplantation was 14.4%. AUCs for models 1 and 2 were 0.709 (95% confidence interval [CI], 0.557-0.852) and 0.697 (95% CI, 0.529-0.847), respectively. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 57.1%, 88.0%, 44.4%, and 92.4%, respectively, in model 1 and 42.9%, 96.4%, 66.7%, and 90.9%, respectively, in model 2. Models 1 and 2 had no significant difference in predictive values (p = 0.821). Results remained robust in the sensitivity analysis., Conclusions: This study reveals that the combination of serum ESR, CRP, and frozen section has limited diagnostic value in predicting persistent infection at reimplantation. Additionally, no significant difference in accuracies between 5 and 10 PMNs/HPF as the threshold of frozen section were found. There is a need for timely biomarkers with higher accuracy in diagnosing infection before reimplantation.

Background: Evaluation of core needle biopsies (CNB) is a standard procedure for the diagnosis of breast cancer. However, tissue processing and image preparation is a time- consuming procedure and instant on-site availability of high-quality images could substantially improve the efficacy of the diagnostic procedure. Conventional microscopic methods, such as frozen section analysis (FSA) for detection of malignant cells still have clear disadvantages. In the present study, we tested a confocal microscopy scanner on fresh tissue from CNB with intention to develop an alternative device to FSA in clinical practice., Patients and Methods: In 24 patients with suspicious breast lesions standard of care image-guided biopsies were performed. Confocal images have been obtained using the Histolog™ Scanner and evaluated by two independent pathologists. Hematoxylin-Eosin (H&E) histological sections of the biopsies were routinely processed in a blinded fashion with respect to the confocal images., Results: In total 42 confocal images were generated from 24 biopsy specimens, and available for analysis within a few minutes of taking the biopsy. This resulted in 2 × 42 = 84 pathologic evaluations. In four cases, a pathologic diagnosis was not possible with confocal microscopy. An exact correlation based on the B-classification was reached in 41 out of 80 examinations and in another 35 cases in a broader sense of correspondence definition (i.e. malignant vs. benign)., Conclusions: As a reliable on-site method, the Histolog™ Scanner provides a visualization of cellular details equivalent to the H&E standards, permitting rapid and accurate diagnosis of malignant and benign breast lesions. Furthermore, this device offers great potential for immediate margin analysis of specimen in breast conserving therapy.

Background and purpose - For decision-making (aseptic vs. septic), surgeons rely on intraoperatively available tests when a periprosthetic joint infection (PJI) cannot be confirmed or excluded preoperatively. We compared and evaluated the intraoperative performances of the frozen section and the alpha defensin lateral flow test in the diagnosis of PJI. Patients and methods - In this prospective study, consecutive patients with indicated revision surgery after arthroplasty were included. Patients were classified as having PJI using the MusculoSkeletal Infection criteria. The presence of alpha defensin was determined using the lateral flow test intraoperatively. During revision surgery, tissue samples were harvested for frozen and permanent section. Analysis of diagnostic accuracy was based on receiver-operating characteristics. Results - 101 patients (53 hips, 48 knees) were eligible for inclusion. Postoperatively, 29/101 patients were diagnosed with PJI, of which 8/29 cases were definitely classified as septic preoperatively. Of the remainder 21 septic cases, the intraoperative alpha defensin test and frozen section were positive in 13 and 17 patients, respectively. Sensitivities of the alpha defensin test and frozen section were 69% and 86%, respectively. The area under the curves of both tests showed a statistically significant difference (p = 0.006). Interpretation - The frozen section showed a significantly higher performance compared with the alpha defensin test and a near perfect concordance with the definitive histology, and therefore remains an appropriate intraoperative screening test in diagnosing PJI. Although the sensitivity of the alpha defensin test was lower compared with that of frozen section, this test is highly specific for confirming the diagnosis of PJI.

We wanted to discuss our experiences in the approach to borderline ovarian tumors, which constitute a group different from epithelial ovarian tumors with respect to their biological structure in line with retrospective information gathered from our cases. A total of 25 patients operated on for the indication of adnexal masses diagnosed as borderline ovarian tumors based on frozen section results were included in our study. Patient age, tumor diameter, tumor markers and surgeries performed were discussed in the light of the literature. Statistical analyses were performed using the SPSS software. The patient mean age was 43.84±11.34 years. The mass was localized in the right (n=13), left (n=11) or both (n=1) adnexal regions. The mean tumor diameter was 12.9±5.84 cm. Histopathologic examination established the diagnosis of serous borderline (n=14 patients) and mucinous borderline (n=11) ovarian tumors. Although the results of our study are consistent with current literature data, a greater number of current studies should be performed on borderline ovarian tumors, which are defined as a class of tumors different from epithelial ovarian tumors.

Background: Frozen section (FS) is often performed when histopathological evaluations are urgently required for implementation of therapeutic measures. In dermatology, this method is most commonly used to evaluate excision margins of tumors. FS are also routinely employed to differentiate toxic epidermal necrolysis from staphylococcal scalded skin syndrome. However, little is currently known about the performance of FS in the diagnosis of inflammatory dermatoses., Objectives: To compare histopathological diagnoses in a series of patients with a clinical diagnosis of an inflammatory dermatosis for which FS and paraffin-section (PS) specimens were obtained on the same day., Methods: We conducted a single-center retrospective analysis of 43 cases. All histological slides were reviewed by a single dermato-pathologist. Concordance was calculated between FS and PS., Results: Patients were divided into three groups according to diagnosis: papulosquamous diseases (group I), drug eruptions (group II), and a heterogeneous group (group III) that included cases of bullous vasculitis and Sweet syndrome. Among the three groups, the results of FS and of PS were discordant only in five cases (5/43, 11.6%). Compared to PS, FS had a sensitivity of 92.9% [95% confidence interval (95%CI) 64.17-99.63%] and a specificity of 100% in group I, sensitivity of 90.9% (95%CI 57.12-99.52%) and specificity of 100% in group II, and sensitivity of 83.33% (95%CI 60.78-94.16%) and specificity of 100% in group III. The degree of agreement between the results of the FS and of the PS was almost perfect (kappa = 0.95, 0.93 and 0.85 respectively)., Conclusions: This study suggests that FS is a valid approach for the rapid diagnosis of inflammatory dermatoses. This method is as specific as PS, although it is less sensitive.

Background: Routine use of frozen section (FS) is a costly procedure and sparsely available in resource poor countries. A proper cost benefit analysis may help to reduce its routine use and would empower surgeons to perform oral cancer surgeries without having FS facility. FS is performed to identify microscopic spread beyond gross disease that cannot be assessed clinically., Objective: Our primary aim was to determine the cost benefit analysis of FS in the assessment of margins in oral cavity squamous cell carcinoma (OSCC)., Materials and Methods: Retrospective study of prospectively collected data of 1311 consecutive patients who were operated between January 2012 and October 2013. The gross and microscopic margin status of each patient was extracted from the patient's chart. The cost estimates were performed to calculate the financial burden of FS as well as expenses incurred on adjuvant treatment resulting from inadequate margins., Result: Microscopic spread changed the gross margin status in 5.2% (65/1237) patients. Of this entire cohort of 1237 patients, FS helped 29 (2.3%) patients to achieve tumor free margin, and it changed the adjuvant treatment plan in 9 (0.7%) patients. The cost of FS for each patient was INR 11052. The cost-benefit ratio of FS was 12:1. Gross examination alone could have identified majority of the inadequate margins., Conclusion: Frozen section for assessment of margin status bears poor cost-benefit ratio. Meticulous gross examination of the entire surgical specimen is sufficient to identify majority of inadequate margins., Competing Interests: There are no conflicts of interest.

Rationale: Adenoid cystic carcinomas (ACCs) are malignant tumors and occur in the major and the minor salivary glands. ACCs are rare in the larynx., Patient Concerns: A 55-year-old female patient who presented with a 12 months history of paraesthesia pharynges and hoarseness for 4 months. Laryngoscopy showed an endophytic lesion in the right supglottic area with no laryngeal stenosis. And magnetic resonance imaging (MRI) confirmed the presence of a submucosal mass in the supglottic area. Supporting laryngoscope was performed under general anesthesia and a lesion biopsy obtained., Diagnoses: The lesion was sent for frozen-section biopsy, which shows the lesion was the epithelial-derived tumors of salivary gland, but it was impossible to identify the relationship between the tumor and the surrounding normal tissue, and to judge the nature of the tumor further. So, the lesion was sent for the second frozen-section biopsy, an ACC of the larynx was confirmed and margins were negative., Interventions: The patient underwent partial laryngectomy., Outcomes: The patient was doing well except hoarseness during the follow-up period with no evidence of disease recurrence or metastasis for 17 months post-operatively., Lessons: Laryngeal ACC is a rare entity. When the nature of lesion cannot be confirmed, multiple biopsies may be required for confirm the diagnosis of pathology. It not only reduces patient's waiting time for surgery, but also define the diagnosis and surgical removal of lesion through a single anesthesia.

BACKGROUND The aim of this study was to compare the clinical outcome in patients with pancreatic ductal adenocarcinoma who underwent frozen section and paraffin section histology of the surgical resection margins during pancreaticoduodenectomy. MATERIAL AND METHODS Frozen section and routine paraffin section histopathology were performed using the following categories: R0 (no tumor cells at the surgical resection margin), R1 (tumor cells at, or within 1 mm, of the surgical resection margin), and R2 (tumor seen macroscopically at the surgical resection margin). R1 and R2 patients underwent additional resection to achieve R0. RESULTS Of 346 patients who underwent pancreaticoduodenectomy, frozen section histology showed positive resection margins in 22 patients (9.2%) and paraffin section histology was positive in 20 patients (8.4%). The OS was nine months in frozen section-positive patients and 20 months in frozen section-negative patients (p=0.001). The OS rates were significantly different between the paraffin section-positive and paraffin section-negative patients (11 months vs. 21 months) (p=0.001). Univariate and multivariate analysis showed that increased tumor size, high tumor grade, lymph node metastases, a positive superior mesenteric artery and retroperitoneal margin, and a positive resection margin on frozen section were significantly correlated with reduced OS (p<0.05). Twenty-two patients with positive resection margins on frozen section histology underwent further resection; R0 was achieved in 14 patients, with no significant difference in OS. CONCLUSIONS For patients who underwent pancreaticoduodenectomy for pancreatic carcinoma with positive resection margins on frozen section, further surgical resection to achieve R0 had no significant positive impact on OS.

The number of released free cholesterol crystal emboli (fCCE) and their role during percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) have not been documented yet. Furthermore, fCCE manifesting in the coronary lumen following plaque rupture has been historically overlooked owing to the standard tissue preparation for light microscopy which uses ethanol as a dehydrating agent that can dissolve fCCE, leaving behind empty tissue. In this case report, we evaluated fCCE released during PCI for ACS and their relationship with myocardial injury and coronary artery obstruction on the H&E-stained sections by using polarised light microscopy. To our knowledge, there has been no mention of the visibility of fCCE on H&E-stained frozen polarised sections before., Competing Interests: Competing interests: KK, who is the president of Inter-tec Medicals, Co., developed non-obstructive angioscopy. SK is a technical consultant for Nemoto Kyorin-do Co., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Frozen section helps in rapid intra-operative diagnosis. It is commonly used during surgical procedures to detect malignancy so that modifications of surgery can be decided at the time of surgery on the table. Frozen section is also performed for evaluation of surgical margins and detection of lymph node metastasis. In addition it is applied for detection of unknown pathological processes.The objective of this study was to assess the accuracy of frozen section diagnosis in comparison to gold standard histopathological diagnosis and to find concordance and discordance rate of frozen section with histopathological report., Methods: This was a cross sectional study of 41 frozen section samples done in the department of pathology of BP Koirala Institute of Health Sciences from September 2014 to August 2015. All frozen section samples with their permanent tissue samples sent for final histopathological evaluation were included in the study., Results: The overall accuracy of frozen section diagnosis was 97%. The sensitivity was 94%, specificity was 87%, positive predictive value was 90% and negative predictive value was 93%. The concordance rate was 90.2% and the discordance rate was 9.8%., Conclusions: The results of frozen section varied in different organ systems and the common cause of discrepancy in our study were the gross sampling error and the interpretational error.

Background: Direct aspiration from suspected pathological tissue and rapid parathyroid hormone analysis may offer a reliable, cost effective alternative to currently used "gold standard" tests., Objectives: To validate the accuracy of intraoperative measurements of parathyroid hormone levels in parathyroid adenomas., Methods: A prospective study included 22 patients diagnosed with primary hyperparathyroidism who underwent parathyroidectomy due to an adenoma or hyperplasia. Aspirations of tissues extracted from three adjacent areas (the pathological parathyroid, thyroid, and muscle tissues) were sent for rapid parathyroid hormone analysis. The assay values of these tissue aspirates were compared to the results of the pathology report based on frozen section analysis and the final pathology report., Results: All assay results were significantly higher for parathyroid tissue 16,800 to 1,097,986 pmol/L (median 26,600), than for either thyroid 1.7 to 415 pmol/L (median 6.5), P < 0.001, or muscle tissue 1.1 to 1230 pmol/L, (median 11.3), P < 0.001. All tissues showing high parathyroid assay values were also verified by pathology examinations: 7 had adenomas and 15 had a differential diagnosis of adenoma or hyperplasia. The frozen section identified all but one (false negative). Rapid intraoperative parathyroid levels > 1500 predicted parathyroid tissue with a 99% level of confidence, while levels between 1000 and 1500 predicted it with 95% confidence. The intraoperative parathyroid hormone assay showed > 70% decrease in 15/21 cases., Conclusions: Rapid intraoperative parathyroid hormone analysis is a reliable and precise technique, equally accurate for frozen section analysis in predicting with high certainty intraoperative parathyroid tissue.

Frozen biopsies are frequently used for decision making during surgery. This study aimed to evaluate the efficacy of frozen biopsy for guiding decision making before laser excision of glottic premalignant lesions. One hundred patients with 119 laser excisions were included in this study and reviewed retrospectively. After frozen biopsy, type I or II cordectomy was performed and the frozen result and final pathology of the excisional specimen were compared. The positive predictive value of frozen biopsy when the diagnosis is benign or malignant was relatively high (80.8 and 88.9 %, respectively) but the positive predictive value of a dysplasia or carcinoma in situ result was quite low (18.2 and 16.7 %). Under-diagnosis was frequent for dysplasia or carcinoma in situ (69.7 and 83.3 %). In particular, for lesions with suspicious features, lesions with dysplasia or carcinoma in situ had a much higher rate of under-diagnosis (81.8 and 100 %). Frozen biopsy was not reliable because the overall coincidence rate between final pathology and frozen biopsy was 63 %. Although a frozen biopsy result of a benign or malignant result was reliable, a dysplasia or carcinoma in situ result on frozen biopsy had a high risk of being an under-diagnosis.

Context: - The Bethesda System for Reporting Thyroid Cytopathology recommends against the use of intraoperative frozen section (FS) during lobectomy of a thyroid nodule with a fine-needle aspiration (FNA) diagnosis of malignant. Bethesda recommendations for FS in the FNA category of suspicious for malignancy (SFM) is less well-defined. In some institutions in China, FS examination is performed during lobectomy even for FNA-proven malignant cases., Objective: - -To compare the efficacy of FNA versus FS in the evaluation of malignant thyroid lesions., Design: - A 3-year retrospective analysis from a single institution was performed on cases with an FNA diagnosis of SFM or malignant with subsequent FS examination during thyroidectomy. The results of FNA and FS findings were compared to the final thyroidectomy pathology., Results: - -A total of 5832 thyroidectomy procedures were performed: 1265 cases had FNA and FS results available. Fine-needle aspiration gave a diagnosis of SFM to 306 cases and a diagnosis of malignant to 821 cases. Of the SFM cases, 10.5% (32 of 306) had benign/indeterminate, 4.6% (14 of 306) suspicious, and 84.9% (260 of 306) malignant FS results. Final pathology showed 56.3% (18 of 32), 64.3% (9 of 14), and 100% (260 of 260) malignancy rates, respectively. For the malignant FNA group, 10.0% (82 of 821) had benign/indeterminate, 4.4% (36 of 821) suspicious, and 85.6% (703 of 821) malignant FS results. The final pathology showed 96.4% (79 of 82), 97.2% (35 of 36), and 99.9% (702 of 703) malignancy rates, respectively., Conclusions: - Frozen section should not be performed for the malignant FNA category because FS evaluation may result in 10% falsely negative findings. Performing FS for SFM may be better justified; however, more than half of FS cases read as benign in this category had malignant final pathology. Therefore, caution should be taken for FS results even in the SFM group.

Storage of tissue sections for long periods allows multiple samples, acquired over months or years, to be processed together, in the same reagents, for quantitative histochemical studies. Protocols for freezer storage of free-floating frozen sections using sucrose with different additives have been reported and assert that storage has no effect on histochemistry, but no quantitative support has been provided. The present study analyzed the efficacy of long-term storage of brain tissue sections at -80C in buffered 15% glycerol. To determine whether histochemical reactivity is affected, we analyzed 11 datasets from 80 monkey brains that had sections stored for up to 10 years. For processing, sections from multiple cases were removed from storage, thawed, and batch-processed at the same time for different histochemical measures, including IHC for neuronal nuclear antigen, parvalbumin, orexin-A, doublecortin, bromodeoxyuridine, the pro-form of brain-derived neurotrophic factor, and damaged myelin basic protein as well as a histochemical assay for hyaluronic acid. Results were quantified using stereology, optical densitometry, fluorescence intensity, or percent area stained. Multiple regression analyses controlling for age and sex demonstrated the general stability of these antigens for up to a decade when stored in 15% glycerol at -80C., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Antigen masking in routinely processed tissue is a poorly understood process caused by multiple factors. We sought to dissect the effect on antigenicity of each step of processing by using frozen sections as proxies of the whole tissue. An equivalent extent of antigen masking occurs across variable fixation times at room temperature. Most antigens benefit from longer fixation times (>24 hr) for optimal detection after antigen retrieval (AR; for example, Ki-67, bcl-2, ER). The transfer to a graded alcohol series results in an enhanced staining effect, reproduced by treating the sections with detergents, possibly because of a better access of the polymeric immunohistochemical detection system to tissue structures. A second round of masking occurs upon entering the clearing agent, mostly at the paraffin embedding step. This may depend on the non-freezable water removal. AR fully reverses the masking due both to the fixation time and the paraffin embedding. AR itself destroys some epitopes which do not survive routine processing. Processed frozen sections are a tool to investigate fixation and processing requirements for antigens in routine specimens., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.