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Spread through air spaces (STAS) is reportedly associated with worse prognosis in sublobar resections of lung adenocarcinoma. Recently, it was proposed that STAS detected on frozen sections can be an indication for lobectomy instead of sublobar resection. We undertook this study to evaluate the reliability of STAS assessment on frozen sections compared to permanent sections, as well as the associations among STAS, tumor grade, and recurrence-free survival (RFS) after sublobar resection. A total of 163 stage I lung adenocarcinoma resections with frozen sections were identified retrospectively. For each case, and for frozen and permanent sections separately, the presence or absence of STAS, as well as the tumor grade, were recorded. Compared to permanent sections, STAS detection on frozen sections had low sensitivity (55%), low positive predictive value (48%), and fair agreement (K = 0.34), whereas there was higher specificity (80%) and negative predictive value (85%). Accuracy was 74%. Tumor grade assessment on frozen sections showed higher sensitivity (77%), positive predictive value (90%), agreement (K = 0.72), specificity (94%), and accuracy (87%), and the same negative predictive value (85%). High-grade histology on frozen sections was associated with shorter RFS (p = 0.02), whereas STAS on frozen sections was not (p = 0.47). Our results suggest that the intraoperative detection of STAS has low sensitivity and positive predictive value. False-positive results may lead to overtreatment of patients with lung cancer. The determination of tumor grade on frozen sections offers better sensitivity and specificity, plus it is associated with RFS, whereas STAS on frozen sections is not. Further study is needed to explore the utility of assessing tumor grade on frozen sections.

Objectives: To measure the diagnostic accuracy of intraoperative frozen section examination of sentinel lymph nodes (SLN) in vulvar cancer and to describe associated patient outcomes. Methods: This retrospective cohort study included patients with invasive squamous cell carcinoma of the vulva who underwent SLN biopsy with intraoperative frozen section at one cancer centre from Jan 2008 - Feb 2020. Exclusion criteria were tumor size >4cm, multifocal tumor, palpable groin lymph nodes and neoadjuvant therapy. The SLN procedure was performed by injection of the primary vulvar tumor or scar with technetium-99m, ICG and/or blue dye. We compared the intraoperative SLN frozen section diagnosis and the paraffin section report for concordance. Recurrence location was described and recurrence free survival (RFS) was compared using the Kaplan-Meier method. Results: A total of 173 patients (258 groins) met inclusion and exclusion criteria. On frozen section, there were 36/258 positive groins on frozen section and 222 negative groins. On final pathology, there were 39/258 positive groin nodes: 30 macro-metastases, 7 micro-metastases, 2 isolated tumor cells (ITCs). There were 219 negative groins. The sensitivity and specificity for frozen section detecting any metastatic disease compared to final pathology, was 89.7% and 99.5%, respectively. The positive-predictive value (PPV) was 97.2% and the negative-predictive-value (NPV) was 98.2%. There were 4 cases of false negative frozen section where final pathology revealed two cases of ITCs, 1 micro-metastasis and 1 macro-metastasis. A total of 30 patients (17.3%) underwent a full inguinal femoral lymphadenectomy during the same operation due to the frozen section results and avoided a second operation. A total of 2 patients (1.2%) required a second operation for lymphadenectomy due to false negative results on frozen section. Median (range) follow up was 38.0 (1-137.8) months. Median RFS was 14.9 (3.6 to 98.2) months. There were 46 recurrences in the study population, of which 29 were confined to the vulva, 9 groin recurrences and 8 distant recurrences. Among patients with a negative SLN biopsy on both frozen section and final pathology, there were 10 (3.9 %) groin and/or distant recurrences. A total of 6 nodal recurrences were ipsilateral, 1 was contralateral, 2 were bilateral and 1 recurrence was distant. After exclusion of patients with local recurrence only, the RFS at 3 years was 91.6% (95% CI 86.2-97.4%) for patients with negative SLN on frozen section and 64.6% (95% CI 46.5-89.7%) for positive SLN on frozen section. On final pathology, patients with negative SLN had a 3-year RFS of 91.7% (95% CI 86.3-97.4%), macro-metastases 58.4% (95% CI 38.5-87.7%), and micro-metastases/ITCs was 100%. Conclusions: Intraoperative frozen section of SLNs in vulvar cancer is an accurate intraoperative guide to determine if complete inguinal femoral lymphadenectomy should be performed. SLN biopsy reduced the need for a second surgical procedure and does not appear to compromise patient outcomes.

Purpose: 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 a reasonable option and should be specifically investigated.

Approximately 6% of deceased kidney donors (DKDs) are diabetic; their kidneys may be associated with worse allograft survival, but published studies suggest that recipient diabetes status has a greater impact on mortality and survival. Since biopsy findings are the most common reason for organ discard, we sought to understand histologic and clinical factors that influence graft survival in patients who receive a kidney from a diabetic DKD. We retrospectively reviewed our institutional experience from 2005 to 2019, and re-evaluated pre-implantation and earliest post-transplant biopsies. Histologic findings were compared against a control cohort of non-diabetic DKD. Of 829 adult DKD transplants, 37 (4.5%) came from diabetic donors. There was no significant difference in diabetic vs. non-diabetic DKD graft survival for all-comers; however, when stratified by duration of donor diabetes, donor diabetes ≥6 years was associated with graft failure. In 25 patients with post-transplant biopsies available, diabetic DKD allografts had significantly greater non-glomerular chronic injury than non-diabetic DKD allografts. Moderate arteriolar hyalinosis (in 24%), moderate tubular atrophy and interstitial fibrosis (IFTA, in 36%), and diabetic glomerulopathy (in 24%) on early post-transplant biopsy were associated with allograft failure. Pre-implantation frozen section discrepancies were more common in long-standing donor diabetes, and arteriolar hyalinosis and IFTA scores on frozen accurately prognosticated graft loss. There was no morphologic improvement in lesions of diabetic nephropathy on short-term follow-up. In conclusion, donor diabetes ≥6 years, and histologic findings on frozen section and early post-transplant biopsy are associated with diabetic DKD allograft loss.

Background Mohs micrographic surgery (MMS) has risen in popularity as a management option for treating lentigo maligna (LM) because of its ability to accurately detect subclinical spread while conserving tissue. The primary concern for opponents of MMS in melanoma remains the difficulty associated with interpretation of frozen sections compared with traditional paraffin sections; this has been made easier with the advent of immunostaining. Objective Our study aims to assess the concordance in clearance reporting of LM in immunostained frozen sections compared with permanent paraffin sections and hematoxylin and eosin staining. Methods We conducted a retrospective analysis of 38 LM cases treated by MMS between 2017 and 2020 in Melbourne, Australia. Immunostained frozen sections were assessed by a Mohs surgeon, whereas permanent paraffin sections were assessed by an external dermatopathologist. Results We report 86% agreement in reporting of LM in immunostained frozen sections compared with permanent paraffin sections. In 5/38 cases, permanent paraffin sections were reported as clear for LM, but the Mohs surgeon had detected positive margins, requiring further excision. Conclusion For LM treated with MMS, there is a high agreement of clearance reporting between immunostained stained frozen sections and permanent paraffin sections without immunostaining; however, immunostained frozen sections may be more sensitive.

Background Surgeons sometimes have difficulty determining which result to favor when preoperative results (MRI + preoperative endometrial biopsy [pre-op EB]) differ from intraoperative frozen section histology (FS) results. Investigation of how FS can complement ordinary preoperative examinations like MRI and pre-op EB in identification of patients at high risk of lymph node metastasis (high-risk patients) could provide clarity on this issue. Therefore, the aim of this study is to assess the utility of pre-op EB, MRI and FS results and determine how to combine these results in identification of high-risk patients. Methods The subjects were 172 patients with endometrial cancer. Patients with a histological high-grade tumor (HGT), namely, grade 3 endometrioid cancer, clear cell carcinoma or serous cell carcinoma, or with any type of cancer invading at least half of the uterine myometrium were considered high-risk. Tumors invading at least half of the uterine myometrium were classified as high-stage tumors (HST). We compared (a) detection of HGT using pre-op EB versus FS, (b) detection of HST using MRI versus FS, and (c) identification of high-risk patients using MRI + pre-op EB versus FS. Lastly, we determined to what degree addition of FS results improves identification of high-risk patients by routine MRI + pre-op EB. Results (a) Sensitivity, specificity, and accuracy for detecting HGT were 59.6, 98.4 and 87.8% for pre-op EB versus 55.3, 99.2 and 87.2% for FS (P = 0.44). (b) These figures for detecting HST were 74.4, 83.0 and 80.8% for MRI versus 46.5, 99.2 and 86.0% for FS (P < 0.001). (c) These figures for identifying high-risk patients were 78.3, 85.4 and 82.6% for MRI + pre-op EB versus 55.1, 99.0 and 81.2% for FS (P < 0.001). The high specificity of FS improved the sensitivity of MRI + pre-op EB from 78.3 to 81.2%, but this difference was not statistically significant (P < 0.16). Conclusion Frozen section enables identification of high-risk patients with nearly 100% specificity. This advantage can be used to improve sensitivity for identification of high-risk patients by routine MRI + pre-op EB, although this improvement is not statistically significant.

Preoperative diagnosis for suspected gallbladder cancers is challenging, with a risk of overtreating benign disease, for example, xanthogranulomatous cholecystitis, with radical cholecystectomies. We retrospectively evaluated the surgeon's intraoperative assessment alone, and with the addition of intraoperative frozen sections, for suspected gallbladder cancers from a tertiary hepatobiliary multidisciplinary team (MDT).MDT patients with complex gallbladder disease were included. Collated data included demographics, MDT discussion, operative details, and patient outcomes.A total of 454 patients with complex gallbladder disease were reviewed, 48 (10.6%) were offered radical surgery for suspected cancer. Twenty-five underwent frozen section that led to radical surgery in 6 (25%). All frozen sections were congruent with final histopathology but doubled the operating time (p 0.0001). Both the surgeon's subjective and additional frozen section's objective assessment, allowed for de-escalation of unnecessary radical surgery, comparing favourably to a 13.0% cancer diagnosis among radical surgery historically.The MDT process was highly sensitive in identifying gallbladder cancers but lacked specificity. The surgeon's intraoperative assessment is paramount in suspected cancers, and deescalated unnecessary radical surgery. Intraoperative frozen section was a safe and viable adjunct at a cost of resources and operative time.

Tailoring axillary surgery to disease burden has occurred for patients treated with breast-conserving surgery, but limited data exist for patients treated with mastectomy, thus most of these patients who are clinically node-negative but found to be pathologically node-positive are treated with axillary dissection. From 2295 clinically node-negative mastectomy patients treated at our institution 2008-2018, we studied 338 with 1-2 positive sentinel nodes. Patients with a positive sentinel node identified on intraoperative frozen section pathology had a higher nodal disease burden. 66 of 108 patients (61%) whose nodal disease was identified only on permanent section pathology were treated with sentinel node surgery without axillary dissection with no 5-year regional nodal recurrences. This approach permits tailoring axillary surgery in most clinically node-negative mastectomy patients whilst avoiding a second operation. Introduction : Controversy exists regarding optimal management of the axilla in clinically node-negative (cN0) mastectomy patients with 1-2 positive sentinel nodes (+SLNs). We evaluated the influence of frozen section pathology on axillary management and recurrence. Materials and Methods : We studied cN0 breast cancer patients treated 2008-2018 with mastectomy and SLN surgery with 1-2+SLNs. Patients with 1-2+SLNs identified on frozen section intraoperatively (FS+SLN) were compared to those with 1-2+SLNs not detected by frozen section (FS–SLN). Recurrence rates were estimated using the Kaplan-Meier method. Results : Of 2295 cN0 mastectomy patients, 338 had 1-2+SLNs: 108 (32%) FS-SLN and 230 (68%) FS+SLN. In FS+SLN cases, completion axillary dissection (cALND) was more frequent (97% versus 39%, p Conclusions : Mastectomy patients with 1-2 FS+SLNs have a higher nodal disease burden than FS-SLN patients. The majority of FS+SLN patients underwent cALND and 52% received PMRT with very low 5-year regional nodal recurrence rates. A substantial proportion of FS-SLN patients successfully avoided both cALND and PMRT. Frozen section pathology analysis can guide de-escalation of axillary management.

Evaluation of the resected margins of the frozen section during breast-conserving surgery can determine the presence of cancer cells in a short time and have a significant impact on the scope of surgery and the prognosis of the patient. However, breast tissue is composed of adipose tissue, which affects the accuracy of the test. In this study, a new method was applied to the resected surface of the frozen section in which wiping the surface of the frozen section block with alcohol was expected to expose the parenchyma to the surface as the adipose tissue would melt momentarily. Indeed, of the total of 98 cases, 37 cases showed a better exposure ratio of the parenchyma in the improved frozen section test than in the previous frozen section test. Of the 37 cases with increased visibility of parenchymal sections obtained by this method, two cases of ductal carcinoma in situ (DCIS) were detected. Although there are limitations such as turnaround time (TAT), the diagnostic accuracy of histopathologic examination of the frozen section may improve through this method and may have a direct impact on patient safety, and should therefore be researched further.

Background At present, lobectomy is still the standard treatment for lung cancer. Judging whether a lesion is invasive adenocarcinoma (IA) has important guiding significance for determining the scope of surgical resection. The commonly used methods are intraoperative frozen sections and computed tomography (CT) signs. There is still controversy about the accuracy of both in judging the invasiveness of ground‐glass nodules (GGNs). Methods The clinical data of patients with GGNs who underwent surgery were collected. According to the results of univariate analysis, the variables with statistical differences were selected and included in logistic regression multivariate analysis. The predictive variables were determined and the receiver operating characteristic (ROC) curve was drawn in order to achieve the area under the curve (AUC) value. Results According to the results of logistic regression analysis, the longest diameter and maximum CT value of nodules were independent risk factors for IA. The mathematical prediction model of CT signs was determined, and the ROC curves of CT signs and intraoperative frozen sections (FS) were drawn, respectively. The AUC values under the curves were calculated to be 0.873 and 0.807, respectively. The mathematical prediction model of intraoperative frozen section combined with CT signs was established. A ROC curve was drawn and the AUC was calculated to be 0.925. Conclusions The diagnostic accuracy of CT signs in judging whether nonbenign GGNs were IA was higher than that of intraoperative FS. Combined with CT signs and intraoperative FS to establish a mathematical prediction model, the diagnostic accuracy of judging whether nonbenign GGNs are IA is significantly improved., The receiver operating characteristic (ROC) curves for the mathematical prediction model (not included in the intraoperative frozen section). The area under the curve (AUC) value using the prediction model was 0.873.

Background Frozen section (FS) pathology has multiple limitations, and different institutions report variable experiences with the use of FS for diagnosis of tumor involvement. We aimed to compare the FS accuracy with that of permanent pathology (gold standard) regarding marginal involvement and lymph node status using data from the largest breast cancer registry in Iran. Methods In this retrospective study, women who had both FS and permanent pathology reports were included. The two pathology reports were cross compared with regard to the involvement of tumor margins and sentinel lymph nodes. Results Overall, 2786 patients entered the study. Mean age of patients was 48.96±11.44 years. A total of 1742 margins were analyzed. Accordingly, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FS pathology for detection of involvement of involved margins were 78.49%, 97.63%, 65.1%, and 98.7%, respectively. The accuracy and area under the curve (AUC) for FS pathology were 96.61% and 0.73 (95% CI: 0.64–0.831), respectively. A total of 1702 sentinel lymph node biopsies were assessed. Sensitivity, specificity, PPV, and NPV, of FS pathology for detection of lymph node involvement, were 87.1%, 98%, 95.5%, and 93.3%, respectively. Accuracy and AUC of FS for diagnosis of involved lymph nodes were 94.1% and 0.926 (95% CI: 0.909–0.942), respectively. Conclusion Frozen pathology is a suitable method for identifying involved sentinel lymph nodes in patients with breast cancer, but this method has a less than optimum efficacy for detecting and confirming marginal involvement.

Ovarian cancer is the seventh most common form of cancer among women worldwide. The aim of the study was to determine the accuracy of a frozen section and the factors affecting the accuracy of frozen diagnosis of ovarian neoplasms. This retrospective, cross-sectional study was conducted on 401 patients with ovarian masses with frozen section diagnosis in Shahid Faghihi Hospital affiliated to Shiraz University of Medical Sciences between 2014 and 2018. Each ovarian tumor sample was evaluated for histopathologic diagnosis using frozen and paraffin-embedded sections, which were reviewed by an expert gynecologic pathologist. Accuracy and diagnostic values were estimated by comparing the results of the 2 techniques, using the paraffin section as the gold standard. The overall accuracy of the frozen section was 94.5%. Its sensitivity was 85.3% for malignant, 88.2% for borderline, and 99.6% for benign tumors. Its specificity was also 99.7% for malignant, 98.0% for borderline, and 90.9% for benign tumors. The positive predictive value was 98.9% for malignant, 86.5% for borderline, and 94.6% for benign tumors. Most false negatives occurred in mucinous and borderline tumors. The sensitivity of malignant tumors of germ cell and sex cord-stromal cell types were 64.3% and 95.5%, respectively. The specificity of germ cell and sex-cord stromal tumors were 100% and 93.8%, respectively. Frozen section seems to be a precise technique for histopathologic diagnosis of ovarian tumors. However, borderline and mucinous tumors are the most problematic issues during frozen section diagnosis and malignant germ cell tumors have the lowest sensitivity.

Although there have been several reports of the diagnostic accuracy of frozen section biopsy (FSB) for parotid gland tumors, few studies have focused on its diagnostic accuracy for submandibular gland tumors.This study aimed to investigate the necessity of FSB with regard to its diagnostic accuracy for submandibular gland tumors (SGTs).About 42 SGT patients underwent both fine-needle aspiration cytology (FNAC) and FSB between 2005 and 2020. The results of FNAC and FSB were analyzed and compared with the final histological diagnoses.The respective sensitivity and specificity in detecting malignant tumors in 38 cases, excluding the four indeterminate FNAC cases, they were 0 and 97% for FNAC, and 100 and 97% for FSB. Considering the four indeterminate FNAC cases to be malignant, the respective sensitivity and specificity in detecting malignant tumors in the 42 cases were 50 and 92% for FNAC, and 100 and 95% for FSB.FSB may be useful for malignancy detection as a final histological diagnosis in cases that are diagnosed as benign or indeterminate by FNAC in SGTs.

Objective This study evaluated diagnostic accuracy of intraoperative sentinel lymph node (SLN) frozen section examination and scrape cytology as a possible solution for management of SLN positive patients. Study design Clinically early-stage endometrial cancer patients who underwent SLN algorithm and intraoperative SLN examination were analyzed. Findings were compared with final pathology results and diagnostic accuracy of frozen section and scrape cytology were evaluated. Results Of the 208 eligible patients, 100 patients (48 %) had frozen section examination and 108 (52 %) had scrape cytology of the SLN. Intraoperative examination and final pathology were negative for metastasis in 187/208 (90 %) cases. The rest 21 cases had metastatic SLNs according to final pathology. 12 of 21 (57 %) metastases were classified as macrometastasis. Intraoperative examination of SLNs correctly identified 13 cases (true positive) and missed 8 cases (false negative). Five of 8 false negative cases had micrometastasis or isolated tumor cells. Considering identification of macrometastasis, sensitivity and negative predictive value were 85.71 % and 98.94 %, respectively, for the frozen section and 60.00 % and 98.15 %, respectively, for the scrape cytology. Conclusion Frozen section examination of SLN has higher sensitivity in detecting macrometastasis compared to scrape cytology and it could help the surgeon in decision for further lymphadenectomy intraoperatively.

Background Surgeons utilize a combination of preoperative tests and intraoperative findings to diagnose periprosthetic joint infection (PJI); however, there is currently no reliable diagnostic marker that can be used in isolation. The purpose of our study is to evaluate the utility of frozen section histology in diagnosis of PJI. Methods Retrospective analysis of 614 patients undergoing revision total joint arthroplasty with frozen section histology from a single institution was performed. Discriminatory value of frozen section histology was assessed using univariate analysis and evaluation of area under the curve (AUC) of a receiver operating characteristic curve comparing frozen section histology results to the 2018 International Consensus Meeting (ICM) PJI criteria modified to exclude the histology component. Results The sensitivity of the frozen section histology was 53.6% and the specificity was 95.2%. There was 99.2% concordance between the permanent section and frozen section results. The receiver operating characteristic curve for frozen section yielded an AUC of 0.744 (95% confidence interval 0.627-0.860) and the modified ICM score yielded an AUC of 0.912 (95% confidence interval 0.836-0.988) when compared to the full score. The addition of frozen section histology changed the decision to infected in 20% of “inconclusive” cases but less than 1% of total cases. Conclusion In comparison to the modified ICM criteria, intraoperative frozen section histology has poor sensitivity, strong specificity, and acceptable overall discrimination for diagnosing PJI. This test appears to be of particular value for patients deemed “inconclusive” for infection using the remaining ICM criteria.

Purpose The interdisciplinary “Martinique-Principles” of four international professional societies concerned with the patient management of differentiated thyroid cancer (DTC) patients were agreed upon. Differences in perioperative diagnostics can lead to differences in clinical decision founding regarding the treatment of thyroid carcinoma. Our aim was to analyze the perioperative diagnostics of patients referred for postoperative I-131 therapy of DTC. Methods We retrospectively examined the data of 142 patients who were referred to our center for the first course of postsurgical I-131 therapy. We extracted data on perioperative diagnostics. Results Fine-needle biopsy (FNB) was performed in 27/142 patients. In 17 patients, FNB yielded findings suspicious of malignancy, in 3 patients a follicular lesion was reported. An intraoperative frozen section analysis was performed in 79/142 patients. 5/63 patients showed already a cytologically proven malignancy. In 10/79 patients, the frozen section had a nonmalignant result, although DTC was found on final assessment. In 2/79 patients, frozen section analysis was indecisive, although the final report confirmed DTC. In the remaining 67 patients, frozen section yielded DTC. Conclusions There is room for improvement in perioperative diagnostics surrounding thyroid surgery, currently many procedures are performed without adequate information on potential presence of thyroid cancer. More frequent use of FNB might be able to decrease the number of unnecessary thyroid surgeries, increased use of frozen section might decrease the number of second operations and might contribute to less discordance between experts in the field of DTC treatment.

At the time of intraoperative consultation, cytologic preparations including smears and imprints can be used in combination with frozen sections to increase diagnostic yield; however, these simple and rapid techniques are not adopted by all pathologists and their use varies considerably between institutions. In patients under investigation for suspected lymphoma, optimal triaging of tissue received fresh in pathology for lymphoma workup is paramount to maximize the odds of obtaining an accurate and clinically meaningful diagnosis and to avoid the need for additional procedures and delays in management, particularly in the current context in which core biopsies have become common practice as a first attempt to attain this goal. Imprint cytology is invaluable in this regard, also as these patients may not have a lymphoma but rather one of its clinical mimics. Herein, imprint cytology is used to approach fresh specimens received intraoperatively for lymphoma workup. More specifically, how these specimens are triaged for ancillary studies, such as flow cytometry, florescence in situ hybridization, or molecular analyses based on an interpretation of the touch imprints, is described. Detailed imprint cytological findings of typical benign and malignant lymphoid and nonlymphoid lesions are discussed and illustrated.

Keratin granulomas in the peritoneum are a rare finding with multiple etiologies and can be especially challenging for both the pathologist and the surgeon when these lesions are grossly visible. We report a case of a unique frozen section diagnostic scenario of evaluation of keratin granulomas in the peritoneum of a 47-year-old woman in the setting of multiple potential culprits: endometrial endometrioid adenocarcinoma following fertility sparing treatment, and a concurrent dermoid cyst. We discuss the various etiologies of keratin granulomas in the peritoneum, mechanism of their formation, diagnostic significance, as well as implications of fertility sparing treatments. To the best of our knowledge, this is the only case of keratin granulomas in the peritoneum with multiple distinct potential pathologic culprits as well the only case following fertility sparing treatment.

Background Achieving negative margins for melanoma in situ, lentigo maligna type can be challenging, particularly on cosmetically sensitive areas. Objective To assess the utility of intraoperative frozen section margin assessment using a teledermatopathology system in the treatment of head and neck lentigo maligna. Methods and materials Over a 6 year period, 96 patients with lentigo maligna had surgical excisions. The margins were assessed intraoperatively with frozen sections prepared in the manner used in Mohs surgery. The surgeon guided the frozen section slides around the margin while a dermatopathologist assessed the margin remotely. Results In 2/96 (2.1%) cases, the safety margin was positive (frozen sections were false negative). In 1 further case (1%) there was a recurrence of the melanoma 13 months following the excision. Conclusion The described method is effective in treating melanoma in situ, lentigo maligna type with clearance rates similar to previous studies for Mohs surgery.

Aims It can be extremely challenging to determine whether to perform reimplantation in patients who have contradictory serum inflammatory markers and frozen section results. We investigated whether patients with a positive frozen section at reimplantation were at a higher risk of reinfection despite normal ESR and CRP. Methods We retrospectively reviewed 163 consecutive patients with periprosthetic joint infections (PJIs) who had normal ESR and CRP results pre-reimplantation in our hospital from 2014 to 2018. Of these patients, 26 had positive frozen sections at reimplantation. The minimum follow-up time was two years unless reinfection occurred within this period. Univariable and multivariable logistic regression analyses were performed to identify the association between positive frozen sections and treatment failure. Results Treatment failure occurred in eight (30.77%) of the 26 PJI patients with positive frozen sections at reimplantation, compared with 13 (9.49%) of 137 patients with negative results. In the multivariate analysis, positive frozen section increased the risk of failure (odds ratio 4.70; 95% confidence interval (CI) 1.64 to 13.45). The mean number of months to reinfection was lower in the positive frozen section group than in the control group (p = 0.041). While there were nine (34.62%) patients with positive frozen section and 25 (18.25%) patients with negative frozen section who had prolonged antibiotic use (p = 0.042), the mean duration of antibiotic use was comparable in two groups. Synovial white blood cell count (p = 0.137) and polymorphonuclear leucocyte percentage (p = 0.454) were not associated with treatment failure in logistic regression model. Conclusion Positive frozen section at reimplantation was independently associated with subsequent failure and earlier reinfection, despite normal ESR and CRP levels pre-reimplantation. Surgeons should be aware of the risk of treatment failure in patients with positive frozen sections and carefully consider benefits of reimplantation. Cite this article: Bone Joint J 2021;103-B(5):916–922.

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 cm2 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.

Background The objective of this study was to evaluate the diagnostic value of intraoperative frozen section analysis (IFSA) of tumor bed margins in patients with oral squamous cell carcinoma (OSCC). Methods This retrospective study includes 194 primary OSCC cases. The impact of intraoperative information by IFSA on final margin status, local recurrence, and disease-specific survival were analyzed. Results IFSA revealed a 50% sensitivity and a 100% specificity, with a positive and negative predictive value of 100% and 89.1%, respectively. In 19 cases, margins were rated positive by IFSA and remained positive in eight cases (42.1%), despite immediate re-resection. This constellation led to higher recurrence and lower survival rates than in cases with consecutive R0 status (each p = 0.046). Positive margins in IFSA were associated with closer final margins (p = 0.022) and early recurrences (p = 0.050). Conclusions Achieving instant R0 status has a crucial impact on disease recurrence and patient survival. IFSA falls short to ensure secure definite surgical margins. Thus, improved intraoperative diagnostic information on the location and extent of OSCC could support patient treatment. Clinical relevance Considering that patient survival has not improved despite progress in surgical and adjuvant therapy, the process and outcome of IFSA was scrutinized as one part of the treatment concept.

Objective To summarize the diagnosis and treatment outcomes of basal cell adenocarcinoma (BCAC) of the parotid gland, a rare low-grade malignancy, at a single institution, and to investigate the treatment approach for this rare malignancy. Methods We conducted a retrospective analysis of 9 patients with BCAC during 20 years from September 1999 to December 2019. Forty-five patients with basal cell adenoma (BCA), who were treated during the same time period, were used for comparison. The clinical characteristics of BCAC, diagnostic imaging, the usefulness of fine-needle aspiration cytology (FNAC) and frozen section biopsy (FSB), histological assessment of malignancy, and treatment outcomes were investigated. Results There were no marked differences in sex, age, tumor diameter, or tumor location between BCAC and BCA cases. Among the 9 patients with BCAC, one patient was noted with pain/tenderness, and two patients were observed with adhesion to the surrounding tissues. Only one patient was diagnosed as malignant based on MRI/US. FNAC for BCAC was suspicious for malignancy in 6 of the 9 cases, which included one patient with the correct grade of malignancy, one patient with malignancy only, and 4 patients suspicious for malignancy. FSB was suspicious for malignancy in 8 of the 9 cases. Malignancy grade was determined based on infiltration to the surrounding tissues and expression of Ki-67, p53, and bcl-2. One patient with infiltration to the surrounding tissue was diagnosed as intermediate-grade malignancy, while the remaining 8 patients were diagnosed as low-grade malignancy. The BCAC cases included 7 patients with T2 and 2 patients with T1. Conservative resection was performed for all patients, and all cases are surviving cancer-free. Conclusion The malignancy of BCAC can be suspected before surgery based on symptoms/signs, diagnostic imaging, and FNAC. FSB enables the diagnosis of not only malignancy but also the grade of malignancy, which may help determine the appropriate surgical resection. Although all 9 patients with BCAC are surviving free from cancer, a long-term follow-up is warranted.

Oral leukoplakia (OL) is a potentially malignant oral disorder (PMOD) that sometimes trans-form into oral squamous cell carcinoma (OSCC). OL is one of the most frequent PMODs seen in the oral cavity. The global prevalence of OL is approximately 2.6%, with its worst prognosis of undergoing a malignant transformation. Leukoplakia is clinically divided into red zones (tongue and floor of mouth) and nonred zones (buccal mucosa, palate, and soft palate) areas. The red zone areas have more potency of transforming into malignancy. Hence, patients with red zone areas need to be followed up more frequently and treated appropriately. This case report signifies the importance of treating one such case of leukoplakia at red zone area.

For inconclusive testicular tumors with negative tumor markers, frozen section examination (FSE) during inguinal exploration is recommended. However, FSE is time-consuming and therefore often not requested. Furthermore, the exact diagnostic benefit remains poorly defined. We performed a systematic review and meta-analysis summarizing 12 published studies and our own series of FSE in patients with inconclusive testicular tumors, resulting in a cohort of 1052 FSEs. FSE showed sensitivity of 99% and specificity of 96% with a positive predictive value of 98% and a negative predictive value of 97%. Most importantly, one-third of all testicular tumors investigated were correctly identified as being suitable for testis-sparing surgery and orchiectomy could be avoided. For patients with inconclusive testicular tumors, FSE is useful for deciding whether testis-sparing surgery is an option or whether radical orchiectomy should be performed. Thus, these patients should be optimally treated in institutions where FSE is available. PATIENT SUMMARY: We found that intraoperative examination of a frozen section is useful in deciding on whether the entire or only parts of the testicle can be removed. We conclude that frozen section examination should be offered to men with small testicular lesions and negative tumor markers.

AimsAn increasing number of small pulmonary nodules are being screened by CT, and an intraoperative diagnosis is necessary for preventing excessive treatment. However, there is limited literature on the frozen diagnosis of small sclerosing pneumocytomas (SPs). In particular, tumours smaller than 1 cm are challenging for pathologists performing intraoperative frozen diagnosis.MethodsIn total, 230 cases of SP were surgically resected between January 2015 and March 2019 at Shanghai Chest Hospital, and of them, 76 cases were smaller than 1 cm. The histology and clinical information of these 76 cases (33.0%, 76/230) were reviewed retrospectively, 54 cases of which were diagnosed intraoperatively, and the pitfalls were summarised. All diagnoses were confirmed on permanent sections and immunohistochemical sections.ResultsHistologically, 78.9% (60/76) of the small SP was dominated by one growth pattern, and solid and papillary growth pattern were the most commonly misdiagnosed circumstances. The rate of intraoperative misdiagnosis of these SP smaller than 1 cm was 11.1% (6/54).ConclusionsThe main reason for misdiagnosis was failure to recognise the dual cell populations and the cellular atypia. Diagnostic clues include the gross morphology, the presence of dual-cell populations and a hypercellular papillary core, foam cell accumulation in glandular spaces and haemorrhage and haemosiderin on the periphery. In spite of awareness of pitfalls some cases may still be essentially impossible to diagnose on frozen section.

Objectives To report on the methods, peri-operative outcomes and histopathological concordance between frozen and final section from the NeuroSAFE PROOF feasibility study (NCT03317990). Patients and methods Between May 2018 and March 2019, 49 patients at two UK centres underwent robot-assisted radical prostatectomy (RARP). Twenty-five patient were randomized to NeuroSAFE RARP (intervention arm) and 24 to standard RARP (control arm). Frozen section was compared to final paraffin section margin assessment in the 25 patients in the NeuroSAFE arm. Operation timings and complications were collected prospectively in both arms. Results Fifty neurovascular bundles (NVBs) from 25 patients in the NeuroSAFE arm were analysed. When analysed by each pathological section (n = 250, average five per side), we noted a sensitivity of 100%, a specificity of 99.2%, and an area under the curve (AUC) of 0.994 (95% confidence interval [CI] 0.985 to 1; P ≤0.001). On an NVB basis (n = 50), sensitivity was 100%, specificity was 92.7%, and the AUC was 0.963 (95% CI 0.914 to 1; P ≤0.001). NeuroSAFE RARP lasted a mean of 3 h 16 min (knife to skin to off table, 95% CI 3 h 2 min-3 h 30 min) compared to 2 h 4 min (95% CI 2 h 2 min-2 h 25 min; P ≤0.001) for standard RARP. There was no morbidity associated with the additional length of operating time on in the NeuroSAFE arm. Conclusion This feasibility study demonstrates the safety, reproducibility and excellent histopathological concordance of the NeuroSAFE technique in the NeuroSAFE PROOF trial. Although the technique increases the duration of RARP, this does not cause short-term harm. Confirmation of feasibility has led to the opening of the fully powered NeuroSAFE PROOF randomized controlled trial, which is currently under way at four sites in the UK.

BACKGROUND The accuracy of diagnoses of acute invasive fungal rhinosinusitis (AIFRS) based on frozen sections has been questioned. METHODS PubMed, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, SCOPUS, and Google Scholar were used for data sources. True-positive, true-negative, false-positive, and false-negative data were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) Tool. RESULTS Nine prospective and retrospective studies were included. The diagnostic odds ratio of intraoperative frozen section in AIFRS was 124.4717 (95% confidence interval [CI], 75.5168-205.1623). The area under the summary receiver operating characteristic curve was 0.906. The sensitivity, specificity, and positive predictive value were 0.8337 (95% CI, 0.7962-0.8655), 0.9858 (95% CI, 0.9330-0.9971), and 0.9822 (95% CI, 0.8905-0.9973), respectively. The correlation between sensitivity and the false-positive rate was 0.437, indicating a lack of heterogeneity. In subgroup analysis, the "per patient" subgroup tended to show higher diagnostic accuracy than the "per specimen" subgroup. Regarding fungal species, the frozen biopsy of aspergillus showed higher sensitivity than that of mucor (0.8103 vs. 0.7544). CONCLUSION Positive frozen sections are reliable and facilitate early intervention in AIFRS. Collecting multiple specimens during surgery will decrease the rate of false-negative results.

BACKGROUND Appropriate surgical treatment of epithelial ovarian tumors is reliant on intraoperative diagnosis. A retrospective study to compare the diagnostic accuracies of imprint cytology (IC) with frozen section histology (FSH) in these tumors was performed. METHODS About 78 cases of IC-based and FSH-based diagnoses against the final histopathologic diagnoses in terms of both histologic subtype (serous, mucinous, endometrioid, or clear cell tumor) and behavioral type (benign, borderline, or malignant) were compared. The cytomorphologic features of the tumor cells (nuclear atypia, papillary clusters, adenoma cells, and necrosis) in relation to behavioral types were also evaluated. RESULTS While the diagnostic accuracy of IC and FSH were similar with respect to behavioral type (87% and 88%, respectively), the diagnostic accuracy of IC was superior to that of FSH with respect to histologic subtype (83% and 74%, respectively). Among histopathologically confirmed malignant tumors, the diagnostic accuracy of IC (62/64; 97%) was superior to that of FSH (58/64; 91%). The presence of necrosis and absence of adenoma cells were significantly more prevalent among malignant group than among borderline and benign groups (P

Background: Antibody validation for tissue staining is required for reproducibility; criteria to ensure validity have been published recently. The majority of these recommendations imply the use of routinely processed (formalin-fixed, paraffin-embedded) tissue. Materials & methods: We applied to lightly fixed frozen sections a panel of 126 antibodies validated for formalin-fixed, paraffin-embedded tissue with extended criteria. Results: Less than 30% of the antibodies performed as expected with all fixations. 35% preferred one fixation over another, 13% gave nonspecific staining and 23% did not stain at all. Conclusion: Individual antibody variability of the paratope's fitness for the fixed antigen may be the cause. Revalidation of established antibody panels is required when they are applied to sections whose fixation and processing are different from the tissue where they were initially validated. ispartof: BIOTECHNIQUES vol:70 issue:3 pages:137-148 ispartof: location:England status: published

Surgery consists the main treatment of endometrial cancer; however, decision of lypmhadenectomy is controversial. Intra-operative frozen section (FS) is commonly used in guiding surgical staging; nevertheless, there are different reports regarding its adequacy and reliability. Aim of this study is to assess accuracy of FS in predicting paraffin section (PS) results in patients with endometrium cancer. Data of 223 cases, who were operated for endometrial cancer at a tertiary hospital in 2012–2019, were analyzed retrospectively. Histological type, grade, tumor diameter, depth of myometrial invasion, and cervical and adnexal involvement in frozen and paraffin section were evaluated. Positive and negative predictive values and accuracy of frozen results in predicting paraffin results for each parameter was assessed. Statistical significance was taken as 0.05 in all tests. Accuracy of FS in predicting PS results were 76.23% for histology, 75.45% for grade, 85.31% for depth of myometrial invasion, and 95.45% for tumor diameter. Surgery, based on FS results, caused undertreatment in 4 patients, while metastatic lymph node ratios were found in only 35.3–50.0% of cases who had high risk parameters at FS. Our FS results have reasonable accuracy rates in predicting PS results, in comparison with the previous literature. However, even if the high risk parameters detected in FS predict PS accurately, absence of lymph node involvement in all cases with high risk parameters indicates that FS-based triage cannot prevent unnecessary lymphadenectomies.

Objective: Surgical margin is an important prognostic factor in solid cancer surgery. Frozen section (FS), the gold standard for intraoperative surgical margin evaluation, requires extensive waiting time and expensive FS devices. The purpose of this diagnostic study was to verify whether multi-staining (MS) method with acetic acid and iodine could be used to differentiate malignant and non-malignant lesions of solid tumor. Methods: The study was conducted on patients with solid tumor who underwent surgery in the Surgical Oncology Division of Dr. Cipto Mangunkusumo General Hospital from December 2017 to April 2018. Samples measuring less than 5 mm, necrotic tissue sample, and patients who did not agree to participate in the study were excluded. Every specimen was divided into two, one side as unstained control and the other side as MS samples. MS samples were sprayed with 10% acetic acid combined with iodine. MS samples and unstained controls were sent for histopathologic results and the pathologist was blinded to group assignment. Acetowhitening reaction in the sample was an indication of a positive MS result, and the presence of malignant foci in the histopathology examination was classified as positive pathological results. Results: Five-hundred-and-twenty samples were obtained from 150 patients. MS method was found to have sensitivity and specificity of 82%, and 63.5%, respectively. In subgroup analysis, we found that MS method has a sensitivity and specificity of 100% and 79.3%, respectively for epithelial breast tumor; 65.7% and 83.3%, respectively for thyroid nodules; and 94.1% and 33.3%, respectively for oral cavity tumors. MS method reacts positively to solid malignant tumor and negatively to benign tumor and normal tissue (from margin samples). Highest sensitivity was found for breast and oral cavity malignancy, and high specificity was found for thyroid cancers. Conclusion: This study provided an alternative staining method for intraoperative macroscopic surgical margin evaluation, especially for rural areas without frozen section facilities.

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

Treatment plan for ovarian neoplasms differs for benign, borderline and malignant tumors. With a turnaround time of 15-20 minutes, frozen section has become a reliable intraoperative diagnostic tool. The aim of this study is to correlate the frozen section diagnosis with subsequent histopathologic diagnosis and determine the accuracy of frozen section diagnosis. The study included 152 ovarian tumors, the overall accuracy of frozen section in diagnosing malignancy was 99.34%, whereas that for benign and borderline tumors were 97.37% and 96.71% respectively. However, the accuracy, sensitivity and specificity for borderline tumors and mucinous tumors were found to be low.

A histological diagnosis obtained from an intraoperative frozen section (FS) during biopsy confirms the adequacy of tumor tissue in the specimen. However, some cases show a discrepancy among the intraoperative FS diagnosis, permanent section (PS) diagnosis of the biopsy specimen, and the final diagnosis of the excised tumor specimen. In this study, we retrospectively investigated the diagnostic accuracy of the FS and PS for different types of bone tumors. This study included 377 patients with 411 bone tumors who underwent tumor excision after an open biopsy with intraoperative FS diagnosis. FS, PS, and final diagnoses of the patients were classified into benign tumors/tumor-like lesions, intermediate malignancies, and malignant tumors. To assess diagnostic accuracy, the histological grades in FS and PS diagnoses were compared with those in the final diagnoses. The overall diagnostic accuracies of FS and PS were 93% and 97%, respectively. The accuracy of FS and PS for histological grade was 84% and 93% for chondrogenic tumors, 90% and 96% for osteogenic tumors, 97% and 98% for osteoclastic giant cell-rich tumors, 100% and 100% for tumors of undefined neoplastic nature, and 95% and 99% for other bone tumors, respectively. These data suggest that surgical planning based on PS diagnosis is recommended for chondrogenic and osteogenic tumors.

Background The aim of this study was to investigate which histopathologic findings are most indicative for necrotizing soft tissue infections (NSTIs) in ambivalent cases. Methods Patients undergoing surgical exploration for suspected NSTIs with obtainment of incisional biopsies for histopathological assessment were included from January 2013 until August 2019. The frozen sections and formalin-fixed paraffin-embedded (FFPE) samples were retrospectively re-assessed. The primary outcome was the discharge diagnosis. Results Twenty-seven (69%) biopsies of the 39 included samples were from patients with NSTIs. Microscopic bullae (p = 0.043), severe fascial inflammation (p p n = 5), severe muscle inflammation (n = 5), muscle necrosis (n = 8), thrombosis (n = 10) and vasculitis (n = 5) were most frequently only seen in the NSTI group. In thirteen tissues samples, there were some discrepancies between the severity of findings in the frozen section and the FFPE samples. None of these discrepancies resulted in a different diagnosis or treatment strategy. Conclusion Microscopic bullae, severe fascial or muscle inflammation, fascial or muscle necrosis, muscle edema, thrombosis and vasculitis upon histopathological evaluation all indicate a high probability of a NSTI. At our institution, diagnosing NSTIs is aided by using intra-operative frozen section as part of triple diagnostics in ambivalent cases. Based on the relation between histopathologic findings and final presence of NSTI, we recommend frozen section for diagnosing NSTIs in ambivalent cases.

Summary Background Penoscrotal extramammary Paget's disease is a rarely found intraepithelial adenocarcinoma in older male patients. The challenge for surgeons to perform high-quality post-surgery reconstruction is mostly case-dependent. Here, we present a review of post-surgical reconstruction practice in 21 cases using various scrotal skin flaps. Methods During the 10-year study period (from 2008 to 2018), all 21 male patients diagnosed with penoscrotal extramammary Paget's diseases at Sun Yat-sen memorial hospital were enrolled in this study. All patients underwent expanding resections guided by frozen sections and penoscrotal reconstructions using various scrotal skin flaps alone or combined with pubic skin flaps and partial thickness skin graft depending on individual defects. The patient's clinical data, specifically the diagnosis, surgical outcome, and follow-up evaluation were retrospectively analyzed. Results The size of skin lesions ranged from 4 × 5 cm to 16 × 18 cm approximately. Out of 21 total cases, 13 patients received combined scrotal and pubic flaps, three patients received single scrotal flaps, and five patients received scrotal flaps and partial thickness skin grafts. Limited flap tip necrosis (two cases) and wound dehiscence (one case) were observed, and secondary resections were performed in four cases with positive post-operative pathological results. All patients experienced complete wound healing and had well-maintained penile morphology and function. Conclusion Various scrotal skin flaps alone or combined with pubic skin flaps designed for individual lesion conditions in patients with penoscrotal extramammary Paget's disease are efficient for scrotal reconstruction. A good match of the local skin texture helps to maintain the morphology and function of the penis and scrotum.

Objectives We aimed to assess the diagnostic value of frozen-section pathologic examination (FSE) of sentinel lymph nodes (SLN) in patients with early-stage cervical cancer. Methods Two French prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) were analysed. Patients with IA to IIA1 2018 FIGO stage, who underwent SLN biopsy with both FSE and ultrastaging examination were included. Results and discussion Between 2005 and 2012, 313 patients from 25 centers fulfilled the inclusion criteria. Metastatic involvement of SLN was diagnosed in 52 patients (16.6%). Macrometastases, micrometastases and isolated tumor cells (ITCs) were found in 27, 12 and 13 patients respectively. Among the 928 SLNs analysed, FSE identified 23 SLNs with macrometastases in 20 patients and 5 SLNs with micrometastases in 2 patients whereas no ITCs were identified. Ultrastaging of negative SLNs by FSE found macrometastases, micrometastases and ITCs in additional 7, 11 and 17 SLNs. Ultrastaging increased significantly the rate of patients with positive SLN from 7% to 16.6% (p The sensitivity and the negative predictive value of FSE were 42.3% and 89.7% respectively or 56.4% and 94.1% if ITCs were excluded. False-negative cases were more frequent with tumor size ≥ 20 mm (OR = 4.46, 95%IC = [1.45–13.66], p = 0.01) and preoperative brachytherapy (OR = 4.47, 95%IC = [1.37–14.63], p = 0.01) and less frequent with patients included in higher volume center (>5 patients/year) (OR = 0.09, 95%IC = [0.02–0.51], p = 0.01). Conclusions FSE of SLN had a low sensitivity for detecting micrometastases and ITCs and a high negative predictive value for SLN status. Clinical impact of false-negative cases has to be assessed by further studies.

Surgical staging in endometrial cancer has evolved and sentinel lymph node (SLN) mapping has replaced a full pelvic and paraaortic lymphadenectomy in several cases. An intraoperative evaluation of SLN might identify patients who could benefit the most from a full lymphadenectomy. The aim of this study is to evaluate the clinical relevance of frozen section of SLN. A retrospective analysis in patients with endometrial cancer who underwent SLN mapping with intraoperative evaluation at frozen section between February 2016 and September 2019 was performed. In case of metastatic involvement, a full lymphadenectomy was performed. Fifty-eight patients met the inclusion criteria. Clinical–pathologic characteristics of the patients and surgical data were analyzed. Overall, bilateral and unilateral detection rates were 100% (58/58), 89.7% (52/58), and 10.3% (6/58), respectively. Eight patients had a stage IIIC disease at permanent section. Frozen section detected SLN metastases in four of eight patients. Of these, two were micrometastases and two were macrometastases. At frozen section of the SLNs, no macrometastases were misdiagnosed. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of frozen section in detecting metastases was 50%, 100%, 93%, 100% and 92.6%, respectively. The intraoperative evaluation of SLN in endometrial cancer accurately identifies patients with macrometastases. This is the cohort that might benefit the most of a full lymphadenectomy for a higher risk of additional lymph node metastases.

For excised tumor specimens, histological grades can differ between the biopsy diagnosis and the final diagnosis. We retrospectively investigated the diagnostic accuracies of histological grades for frozen-section and permanent-section diagnoses from patients with soft-tissue tumors. Frozen-section, permanent-section, and final diagnoses were classified as benign tumors/tumor-like lesions, intermediate malignancies, or malignant tumors. Diagnostic accuracies of the histological grades from the frozen and permanent sections were evaluated by comparing the final diagnoses for the resected specimens. The diagnostic accuracies of the histological grades for the frozen- and permanent-section diagnoses were 95% (387/408 lesions) and 97% (395/408 lesions), respectively. Among the tumor types, the diagnostic accuracies of the histological grades for the frozen-section and permanent-section diagnoses were 84% and 87% for adipocytic tumors, 87% and 91% for fibroblastic/myofibroblastic tumors, 99% and 100% for nerve-sheath tumors, 98% and 98% for fibrohistiocytic tumors, 90% and 98% for tumors of uncertain differentiation, 100% and 100% for vascular tumors, and 97% and 98% for other tumors, respectively. Histological grades from frozen-section diagnoses yielded low diagnostic accuracies in adipocytic and fibroblastic/myofibroblastic tumors. Treatment should be planned based on permanent-section diagnosis and radiological findings for these tumors.

Background The possible benefit of frozen section (FS) analysis during (PD) for pancreatic ductal adenocarcinoma (PDAC) and of additional resection up to total pancreatectomy (TP) is debated. Aim of this work is to evaluate the prognostic role of positive FS analysis after PD for PDAC. Methods Multicentric retrospective analysis on prospective databases of three institutions. Based on FS analysis patients were classified as FS negative/FS positive. All positive FS patients underwent extended PD (EPD) or TP. Postoperative outcomes, disease-free (DFS) and disease-specific survival (DSS) were evaluated. Results Of 371 patients, 58 (16%) had positive FS. This resulted in 313 (84%) SPD (standard pancreatoduodenectomy), 22 (6%) EPD and 36 (10%) TP. Postoperative mortality was higher in patients undergoing TP (11% compared to 4.5% in EPD and 1% in SPD; p = 0.01). 26% of patients underwent neoadjuvant therapy, and it did not decrease the rate of positive FS. Systemic/local relapse rates were 59% and 41% in negative FS group, and 78% and 22% in positive FS group (p = 0.031). Median DFS and DSS were 20 and 37 months in negative FS group, and 12 and 23 months in positive FS patients (p = 0.001). Independent predictors of recurrence were G3, N1/N2 status and positive FS. R1 resection, G3, N1/N2 status, perineural invasion and positive FS were independent predictors of DSS. Conclusions Positive FS analysis is a poor prognostic factor after PD for PDAC. It is significantly associated with a high rate of R1 resection at final histology, PDAC recurrence and poor survival.

BACKGROUND Treatment of nonmelanoma skin cancer (NMSC) by Mohs surgery has traditionally relied on previous pathologic evaluation of paraffin-embedded tissue. Tissue processing by frozen sections allows for expedited diagnosis and treatment; however, data on its accuracy are limited. OBJECTIVE To measure the accuracy and outcomes of biopsy via frozen sections for clinical NMSC. METHODS Biopsies of clinical NMSCs processed via frozen sections with in-office diagnosis rendered by one Mohs surgeon were retrospectively reviewed by one board-certified dermatopathologist. Discordant diagnoses were re-read in blinded fashion by both physicians. If still discordant, final diagnosis was determined by consensus discussion. Inter-rater reliability was calculated using Cohen's kappa statistic. RESULTS Two hundred ninety-seven lesions from 208 patients were included. Correlation between in-office and final diagnosis was 0.876 indicating "almost perfect" concordance. Sensitivity and specificity of in-office diagnosis for detecting malignancy were 98.1% and 94.4%. Seven cases (2.0%) had a clinically relevant change in final diagnosis, but appropriate treatment had been rendered. Two benign lesions (0.7%) initially diagnosed as malignant underwent excision. CONCLUSION In-office biopsy via frozen sections is highly accurate in confirming NMSC. This practice may speed diagnosis and treatment thus improving outcomes and patient satisfaction.

Modified agarose cell-block (CB) technique can be effectively used to have the CB embedded in the OCT compound for the preparation of frozen CB (F-CB) sections in the same way as in the preparation of frozen sections from cryoembedded fresh tissue samples for the intraoperative consultation. In this report, we demonstrate the amenability of F-CB sections to the diagnostic immunocytochemistry. The pelleted cytologic material was at first compactly embedded in ultralow-gelling temperature agarose gel and then re-embedded in conventional agarose gel. The resulting agarose-embedded cell-pellet was cut in halves so that one half is embedded in OCT compound for cryosectioning on a cryostat, while the other half is reserved for the preparation of paraffin-embedded CB (P-CB). The F-CB sections were comparable to sections cut from the paraffin-embedded CB in terms of the quality of H&E-staining and immunocytochemistry. We suppose this method can also facilitate a rapid quantitative and qualitative assessment of the future P-CB. We have extended this technique to the cryo-embedded cell-block method, in which the compact agarose cell pellet is directly embedded in the OCT compound so that the frozen sections can be cut from the cryo-embedded cell block in the same way as in intraoperative frozen section analysis. In this technical report, we illustrate how the frozen cell blocks (F-CBs) can be effectively prepared not only from liquid-based cytology samples but also from conventional fine-needle aspiration cytology slides.

This study was conducted to determine whether establishing the proximal resection line using India ink tattooing can ensure safe resection margins during totally laparoscopic distal gastrectomy. This retrospective study included 81 patients who underwent totally laparoscopic distal gastrectomy for gastric cancer on the lower two-thirds of the stomach. The proximal resection margins were analyzed with respect to the macroscopic type and clinical T stage, and the intraoperative appearance of the stain on the serosa was classified by reviewing surgical videos. R0 resection was performed in all patients. The rates of the intended margins were 89.2% in patients without a frozen section diagnosis and 84.2% in patients with differentiated type lesions who underwent a frozen section diagnosis; however, most patients with undifferentiated advanced lesions failed to achieve the intended resection margins. Intraoperative appearance revealed that 85.2% of patients had localized type stains, whereas 11.1% had widespread-type stains. Our procedure to determine the proximal resection line in totally laparoscopic distal gastrectomy is oncologically safe. However, careful observation of the resected specimen and a frozen section analysis should be performed for undifferentiated advanced lesions.

Aims: To evaluate the accuracy of intraoperative frozen section histopathology for diagnosing periprosthetic joint infection (PJI) during hip revision surgery, both for patients with and without recent trauma to the hip. Patients and methods: The study included all revision total hip replacement procedures where intraoperative frozen section histopathology had been used for the evaluation of infection in a single institution between 2008 and 2015. Musculoskeletal Infection Society criteria were used to define infection. 210 hips were included for evaluation. Prior to revision surgery, 36 hips had a dislocation or a periprosthetic fracture (group A), and 174 did not (group B). Results: The prevalence of infection was 14.3% (5.6% in group A and 16.1% in group B). Using Feldman criteria, the sensitivity of histopathology was 50.0%, specificity 47.1%, positive predictive value 5.3% and negative predictive value 94.1% in group A. The sensitivity of frozen section histopathology was 75.0%, specificity 96.5%, positive predictive value 85% and negative predictive value 95.3% in group B. Conclusions: Intraoperative frozen section histopathology is reliable for the diagnosis of PJI if no dislocation or periprosthetic fracture has occurred prior to hip revision surgery.

Sentinel node biopsy (SNB) may be a decision-making tool for function preservation surgery, including radical trachelectomy and ovary preservation in the treatment of cervical and endometrial cancer. The intraoperative diagnosis is important for guiding treatment decisions for patients with these conditions. Three hundred seventy-one patients with cervical and endometrial cancer received SNB with an intraoperative frozen section analysis and imprint cytology. The sentinel node was cut in half, parallel to the longest axis, to obtain the maximum section area. After performing imprint cytology, one half was used to create a frozen section. The specimen was cut at 2-mm intervals into 5-μm-thick sections, which were subjected to hematoxylin and eosin staining. The diagnostic accuracy of intraoperative frozen section analyses and imprint cytology was compared to the final pathological diagnosis. Among 951 detected sentinel nodes, 51 nodes were found to be positive in the final pathological diagnosis. The sensitivity of a frozen section analysis, imprint cytology and the combination of the two modalities was 76.5%, 72.6%, and 92.2%, respectively. The specificity of a frozen section analysis and imprint cytology was 100%. The negative predictive value of a frozen section analysis and imprint cytology was 98.7% and 98.5%, respectively. In these settings, the accuracy of the frozen section analysis and imprint cytology in the evaluation of SNB specimens was considered acceptable; however, the sensitivity of the combined approach was higher in comparison to when a frozen section analysis or imprint cytology was performed alone.

Background Tissue harvesting for patients with a lung nodule is sometimes unsuitable due to the size and location of the nodule. In such cases, it is unclear whether it is acceptable to proceed to definitive lobectomy without intraoperative frozen section analysis. Methods We retrospectively reviewed patients who underwent definitive lobectomy or wedge resection for frozen section analysis at our institution between 2014 and 2018. The sensitivity, specificity, and accuracies of the clinical and frozen section diagnoses were evaluated against the final pathological diagnosis. Results There were 141 patients in the definitive lobectomy group and 58 patients in the frozen section analysis group, with the latter having smaller and less deep nodules and a lower rate of malignancy on clinical and final pathological diagnoses. The sensitivity, specificity, and accuracy of the clinical diagnosis were 100%, 82%, and 95%, respectively, in the frozen section analysis group and 99%, 67%, and 97%, respectively, in the definitive lobectomy group; values of frozen section diagnosis were 98%, 82%, and 93%, respectively. On subgroup analysis, all ground‐glass nodules clinically diagnosed as malignant had a final pathological diagnosis of malignancy. Conclusions The accuracy of the clinical diagnosis was high and was not inferior to the frozen section diagnosis. These data suggest that definitive lobectomy is an acceptable treatment option for carefully selected patients with large or deep nodules and ground‐glass nodules clinically diagnosed as malignant. To avoid unnecessary lobectomy, frozen section diagnosis should be considered for nodules likely to be benign. Key points Significant findings of the study The accuracy of the clinical diagnosis was high and was not inferior to the frozen section diagnosis. What this study adds Definitive lobectomy is an acceptable treatment option for carefully selected patients with large or deep nodules and ground‐glass nodules with a clinical diagnosis of malignancy.

Increasing studies have utilized mass spectrometry imaging (MSI) that is a label-free tool to investigate drug penetration and drug biotransformation in multicellular tumor spheroids (MCTS). Currently, the gelatin-assisted sectioning method is widely used to prepare frozen sections of MCTS for MSI. However, owing to the limited transparency of frozen gelatin, MCTS with diameters less than 500 μm that closely mimic solid tumors are difficult to be detected when cryosectioning. In order to identify the presence of MCTS, hematoxylin and eosin staining for frozen sections and dye pretreatment for MCTS were employed in previous works, which either increased the analytical time and cost in sample preparation or caused signal suppression in sample analysis. Herein, a new sectioning method was developed to prepare MCTS frozen sections. MCTS was coated with ice to ensure good visibility for small-size MCTS. The optimal cutting temperature compound was added around the ice block to assist the formation of frozen sections. A precast frozen mold was prepared to allow the acquisition of complete MCTS frozen sections. The developed method was applied to investigate lipid distribution in MCTS by using matrix-assisted laser desorption/ionization MSI. Compared to the gelatin-assisted sectioning method, our method did not cause signal suppression and analyte delocalization. Thus, this method provides an easy, universal, and innovative strategy to prepare MCTS frozen sections for further MSI analysis. Besides, we applied our method to investigate the penetration of bisphenol A in MCTS.

Histopathologic examination of the pathologic specimens using hematoxylin & eosin stains represents the backbone of the modern pathology. It is time-consuming; thus, “real-time” assessment of prostatic and periprostatic tissue has gained special interest in the diagnosis and management of prostate cancer. The current study focuses on the review of the different available techniques for “real-time” evaluation of surgical margins during radical prostatectomy (RP). We performed a comprehensive search of the Medline database to identify all the articles discussing “real-time” or intraoperative assessment of surgical margins during RP. Several filters were applied to the search to include only English articles performed on human subjects and published between January 2000 and March 2019. The search revealed several options for pathologic assessment of surgical margins including intraoperative frozen sections, confocal laser endomicroscopy, optical spectroscopy, photodynamic diagnosis, optical coherence tomography, multiphoton microscopy, structured illumination microscopy, 3D augmented reality, and ex vivo fluorescence confocal microscope. Frozen section represents the gold standard technique for real-time pathologic examinations of surgical margins during RP; however, several other options showed promising results in the initial clinical trials, and considering the rapid development in the field of molecular and cellular imaging, some of these options may serve as an alternative to frozen section.