Search

Background: The aim of this clinical trial was to compare Fluorescein-stained intraoperative confocal laser endomicroscopy (CLE) of intracranial lesions and evaluation by a neuropathologist with routine intraoperative frozen section (FS) assessment by neuropathology., Methods: In this phase II noninferiority, prospective, multicenter, nonrandomized, off-label clinical trial (EudraCT: 2019-004512-58), patients above the age of 18 years with any intracranial lesion scheduled for elective resection were included. The diagnostic accuracies of both CLE and FS referenced with the final histopathological diagnosis were statistically compared in a noninferiority analysis, representing the primary endpoint. Secondary endpoints included the safety of the technique and time expedited for CLE and FS., Results: A total of 210 patients were included by 3 participating sites between November 2020 and June 2022. Most common entities were high-grade gliomas (37.9%), metastases (24.1%), and meningiomas (22.7%). A total of 6 serious adverse events in 4 (2%) patients were recorded. For the primary endpoint, the diagnostic accuracy for CLE was inferior with 0.87 versus 0.91 for FS, resulting in a difference of 0.04 (95% confidence interval -0.10; 0.02; P = .367). The median time expedited until intraoperative diagnosis was 3 minutes for CLE and 27 minutes for FS, with a mean difference of 27.5 minutes (standard deviation 14.5; P < .001)., Conclusions: CLE allowed for a safe and time-effective intraoperative histological diagnosis with a diagnostic accuracy of 87% across all intracranial entities included. The technique achieved histological assessments in real time with a 10-fold reduction of processing time compared to FS, which may invariably impact surgical strategy on the fly., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Objectives: Intrapathology consultation is recommended for complex cases during frozen section (FS) as routine practice. In our institution, solicited second opinions were traditionally provided by in-person consultation (IPC). Whole-slide imaging (WSI) was implemented in 2018 as an alternative but replaced by videoconferencing in 2020. Here, we assess the accuracy of remote FS consultation using these digital modalities vs IPC., Methods: Gynecologic FS cases over a 4-year period overseen by 2 intraoperative consultants were grouped by consultation method: (1) IPC, (2) WSI, and (3) videoconferencing. Accuracy was determined by concordance between the FS and final report diagnoses. Turnaround time between the 3 groups was analyzed using SPSS statistical software (IBM)., Results: Using WSI and videoconferencing, 100% concordance was observed, while the IPC group had a 98.5% concordance rate. Videoconferencing, however, showed longer turnaround times (mean, 45.59 minutes) than IPC (mean, 33.36 minutes). Although turnaround time positively correlated with the number of FS specimens, blocks, and H&E slides per case, no statistically significant differences in the number of specimens, blocks, and H&E slides generated were found among the consultation methods., Conclusions: Even though turnaround time using videoconferencing is longer, the accuracy of WSI and videoconferencing for remote FS consultation is equivalent to IPC. It is therefore a safe method for conducting intrapathology FS consultation in challenging surgical cases., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Monitoring of frozen section diagnostic performance provides an important quality improvement measure., Methods: Surgical specimens involving a frozen section diagnosis over a 3-year period were retrospectively reviewed. Glass slides were reviewed on cases with discordance. Discordance and deferral rates were calculated., Results: Of 3,675 frozen section diagnoses included, 96 (2.7%) were discordant with the final diagnosis. Additionally, 114 frozen section diagnoses (3.1%) were deferred. The organ-specific discordance rates were lowest in breast and genitourinary specimens and highest for pancreas, lymph node, and gynecologic specimens. Deferral rates were highest in musculoskeletal, breast, and hepatobiliary cases and lowest in thyroid, parathyroid, and neuropathology cases. Discordance was explained by block-sampling error (45%), specimen-sampling error (27%), or interpretation error (27%). Discordant frozen section diagnoses from gynecologic specimens were responsible for 81% of specimen-sampling errors; frozen section diagnoses of lymph nodes, head and neck, and pancreas were responsible for 54% of interpretation errors; 51% of block-sampling errors involved lymph node evaluation for metastatic carcinoma., Conclusions: Careful gross evaluation and microscopic examination of multiple levels should minimize specimen-sampling error and block-sampling error, respectively. Periodic review of accuracy and deferral rates may help reduce errors and improve the overall performance of this essential procedure., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To determine outcomes following relocation of frozen section services (FSS) and the implementation of a dedicated gastrointestinal frozen service., Methods: We reviewed our FSS 6 months prior to and following FSS relocation. Satisfaction surveys were sent to surgeons and pathologists. Survey feedback resulted in a pilot of gastrointestinal subspecialist frozen section coverage., Results: There were 1,607 and 1,472 specimens from 667 and 602 patients pre- and post-FSS relocation, respectively. There was a decline in median specimen delivery time to pathology (12 vs 10 minutes, P < .001) and an increase in median time from receipt in pathology to intraoperative diagnosis (20 vs 22 minutes, P = .008) in cases with intrapathology consultation but no change without consultation (median, 19 minutes). Intrapathology consultation decreased from 19.7% (317/1,607) to 11.5% (169/1,472) (P < .001). Discordance rates between frozen section and permanent section remained low and similar (2.0% [33/1,607] vs 2.7% [40/1,472], P = .24). There was no significant change in discordance with dedicated gastrointestinal subspecialty frozen section interpretation., Conclusions: Relocation of FSS and dedicated subspecialty interpretation may improve surgeon satisfaction but can also create workflow challenges. Pathology departments need to achieve a balance between satisfaction and adequacy to establish best frozen section coverage models., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To evaluate the diagnostic performance of frozen section in thyroid nodules classified as follicular neoplasm., Methods: A diagnostic test meta-analysis was designed. Studies that assessed frozen section in patients with thyroid nodules and a fine-needle aspiration biopsy result of Bethesda IV were selected. The outcomes measured were the number of false- and true-positive and -negative results. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) instrument for methodological quality assessment and a bivariate mixed-effects regression framework and a likelihood-based estimation of the exact binomial approach., Results: Forty-six studies from 1991 to 2018 were included. Most studies had moderate methodological quality. The overall sensitivity and specificity were 43% (95% confidence internal [CI], 0.34-0.53) and 100% (95% CI, 0.99-1.00), respectively. The hierarchic summary receiver operating characteristic curve showed an area under the curve of 0.91 (95% CI, 0.80-0.97)., Conclusions: Frozen section demonstrates moderate diagnostic performance in patients with follicular neoplasm, and its utility for making intraoperative decisions is limited. Its routine use should be discouraged., (© American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To compare studies that used telepathology systems vs conventional microscopy for intraoperative consultation (frozen-section) diagnosis., Methods: A total of 56 telepathology studies with 13,996 cases in aggregate were identified through database searches., Results: The concordance of telepathology with the reference standard was generally excellent, with a weighted mean of 96.9%. In comparison, we identified seven studies using conventional intraoperative consultation that showed a weighted mean concordance of 98.3%. Evaluation of the risk of bias showed that most of these studies were low risk., Conclusions: Despite limitations such as variation in reporting and publication bias, this systematic review provides strong support for the safety of using telepathology for intraoperative consultations., (© American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

For squamous cell carcinoma (SCC) treated using Mohs micrographic surgery (MMS), interpretation of haematoxylin and eosin-stained frozen sections can be challenging. In these situations, ancillary use of immunostaining is a useful tool for the Mohs surgeon. However, use of immunostaining in MMS laboratories is limited, mainly because current manual immunostaining platforms are subject to operator error, and automated immunostaining, albeit accurate, is too slow for inclusion in MMS. In this report, we describe a novel 1-hour protocol for rapid frozen section immunocytochemistry, using the pancytokeratin markers AE1/AE3. This protocol has been specifically designed to integrate the speed of manual techniques and the accuracy of automated platforms, making it a valuable addition to the MMS laboratory. We propose that in selected or histologically challenging cases, there is a role for the use of this novel protocol, allowing the Mohs surgeon to more confidently declare tumour clearance, thus preventing further unnecessary surgery and preserving healthy tissue., (© 2018 British Association of Dermatologists.)

Objectives: There is little information regarding sentinel lymph node (SLN) frozen-section examination in patients with a history of ductal carcinoma in situ (DCIS). We evaluated the usage, clinical impact, and pathology resources used for SLN cryosectioning in mastectomy cases with a DCIS history., Methods: Mastectomies with SLNs submitted from 2012 to 2013 at a tertiary care center were analyzed. Medicare reimbursement was used to estimate pathology health care expenditures of intraoperative frozen sections., Results: There was no difference in the rate of SLN frozen-section examination or parts submitted, total blocks frozen, total blocks submitted, or total SLNs identified per case between the DCIS (n = 139) and invasive (n = 369) groups. Nine patients with DCIS had SLN metastases (three macrometastases, two micrometastases, and four isolated tumor cells), all of which were examined by frozen section. Only the macrometastases were identified by cryosectioning, which led to two synchronous axillary lymph node dissections that did not yield any additional positive nodes. A total of $19,313 was spent for pathology per DCIS patient with surgical management affected, whereas only $1,019 was spent per invasive carcinoma patient affected., Conclusions: Decreasing SLN frozen-section use in patients with a history of DCIS represents an opportunity for pathology cost containment., (© American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

The process of preparing endoscopic esophageal adenocarcinoma samples for next-generation DNA/RNA sequencing is poorly described. Therefore, we assessed the feasibility and pitfalls of preparing esophageal adenocarcinoma endoscopic biopsies toward DNA/RNA samples suitable for next-generation sequencing. In this prospective study, four tumor biopsy samples were collected from consecutive esophageal cancer patients during esophagogastroduodenoscopy and fresh-frozen in liquid nitrogen. DNA and RNA were isolated from samples with a tumor percentage of at least 50%. For next-generation sequencing, double-stranded DNA (dsDNA) is required and high-quality RNA preferred. The quantity dsDNA and RNA quantity and quality were assessed with the Nanodrop 2000 spectrophotometer (Thermo Fisher Scientific, Waltham, MA, USA) and Agilent 2100 Bioanalyzer (Agilent, Santa Clara, CA, USA). Biopsy samples of 69 consecutive patients with esophageal adenocarcinoma were included. In five patients (7%), the tumor percentage was less than 50% in all four biopsies. Using a protocol allowing simultaneous DNA and RNA isolation, the median dsDNA yield was 2.4 μg (range 0.1-12.0 μg) and the median RNA yield was 0.5 μg (range 0.01-2.05 μg). The median RNA integrity number of samples that were fresh-frozen within 30 minutes after sampling was 6.7 (range 4.2-8.9) compared with 2.5 (1.8-4.5) for samples that were fresh-frozen after 2 hours. The results from this study show that obtaining dsDNA and RNA for next-generation sequencing from endoscopic esophageal adenocarcinoma samples is feasible. Tumor percentage and dsDNA/RNA yield and quality emphasize the need for sampling multiple biopsies and minimizing the delay before fresh-freezing., (© 2015 International Society for Diseases of the Esophagus.)

Background: Mohs micrographic surgery offers high cure rates of nonmelanoma skin cancers with optimal sparing of normal tissue. However, it is generally more time-consuming and labour-intensive than traditional surgery. Optical coherence tomography (OCT) is an emergent technology that has the potential to diagnose basal cell carcinoma (BCC) in vivo., Objective: To compare the efficiency and accuracy of ex vivo OCT with frozen-section histology for identifying BCC in Mohs surgery., Methods: Thirty-eight patients were enrolled. After the stages were taken, images were captured with an OCT microscope and subsequently processed for standard frozen sections., Results: In total, 75 sections were scanned and the mean time to produce one OCT image was 7 min. In four of 26 positive haematoxylin-eosin sections and 23 of 49 negative sections, there was a good correlation with OCT images. The sensitivity and specificity were 19% and 56%, respectively., Conclusions: It is possible to identify BCC with ex vivo OCT and this is more rapidly obtained than with haematoxylin-eosin frozen sections. However, tumour visualization in OCT was disappointing. Practical benefit may be obtained by optimizing this technology and combining it with other new diagnostic tools., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Background: Sentinel lymph node biopsy (SLNB) reduces the morbidity of axillary clearance and is the standard of care for patients with clinically node-negative breast cancer. The ability to analyse the sentinel node during surgery enables a decision to be made whether to proceed to full axillary clearance during primary surgery, thus avoiding a second procedure in node-positive patients., Methods: Current evidence for intraoperative sentinel node analysis following SLNB in breast cancer was reviewed and evaluated, based on articles obtained from a MEDLINE search using the terms 'sentinel node', 'intra-operative' and 'breast cancer'., Results and Conclusion: Current methods for evaluating the sentinel node during surgery include cytological and histological techniques. Newer quantitative molecular assays have been the subject of much recent clinical research. Pathological techniques of intraoperative SLNB analysis such as touch imprint cytology and frozen section have a high specificity, but a lower and more variably reported sensitivity. Molecular techniques are potentially able to sample a greater proportion of the sentinel node, and could have higher sensitivity., (Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Acute fungal sinusitis is a life-threatening infection affecting immunocompromised patients. Historically, the most commonly recovered fungi are Aspergillus and Mucor. The extent of potentially disfiguring debridement surgery is grossly determined by the appearance of bleeding at the margins, signifying viable tissue and the absence of fungus. Requests for frozen section may concern the initial diagnosis and the intraoperative verification of margin status. In 12 patients with acute fungal sinusitis, frozen section was used in 8. Routine H&E stains demonstrated fungal hyphae in necrotic debris in 5 cases, often associated with vascular and perineural invasion. All patients underwent extensive sinus debridement, including orbital exenteration in 2 cases. All 12 patients died, 9 of fungal sepsis. Autopsy in 3 patients showed pulmonary involvement (2 cases), intracranial spread (1 case), and no residual fungus (1 case). Inexperience with organism recognition is surmountable. Frozen section has a role in the management of this devastating disease.

The distinction between primary lung adenocarcinoma and metastatic breast carcinoma in patients with a history of breast cancer is difficult by frozen section (FS) analysis. Our experience with 129 FSs from 121 patients with a pulmonary nodule and a history of breast cancer was reviewed. The pretest odds ratio of primary pulmonary carcinoma/metastatic breast carcinoma was 2.6. The incidence of 12 histopathologic features was assessed in a "training set" composed of 20 FSs, 10 with primary lung adenocarcinoma and 10 with metastatic breast cancer. A differential diagnosis model composed of significant pathologic features that favor the diagnosis of primary lung adenocarcinoma (acini, lepidic growth, nuclear pseudoinclusions, and scar) or metastatic breast carcinoma (comedonecrosis, solid nests, trabecular architecture, and cribriform growth) was identified. The external validity of this model was successfully tested by challenging 19 pathologists and trainees with a test set of 20 unknown FSs, supporting the clinical applicability of the diagnostic model.

There are technical difficulties in obtaining intact sections of cereal grains in which mature cells and their subcellular structures are well preserved. Here we describe a simple method for sectioning hard mature rice grains. It makes possible accurate localization of storage proteins in high-quality histological sections of rice endosperm.

The frozen section diagnosis of lung nodules is difficult because inflammatory atypia and histologic artifacts can simulate a malignancy. From a total of 2,405 frozen sections examined, 143 cases were misdiagnosed or deferred, including 65 with reactive atypia (RA) and 35 bronchioloalveolar carcinomas or well-differentiated adenocarcinomas (BAC-AC), resulting in deferral and error rates of 4.36% and 1.58%, respectively. The presence of 25 pathologic features was evaluated by using an evidence-based pathology (EBP) approach. Of the pathologic features, 11 were significant at a P value of less than .05 but exhibited variable incidence in AC and RA. Positive likelihood ratios allowed for identification of the 5 most useful pathologic features for the diagnosis of AC: multiple growth patterns, anisocytosis, atypia more than 75%, macronucleoli, and atypical mitoses. Granulomas favored the diagnosis of RA. An EBP approach is helpful to stratify pathologic features according to their clinical applicability.

To examine the use of acetone- or ethanol-fixed frozen tissue sections as the "gold standard" for immunohistochemical analysis, we evaluated frozen sections with various conditions of fixation and antigen retrieval (AR). Fresh human tissues were frozen in OCT. An adjacent tissue block was fixed in 10% neutral buffered formalin (NBF) and paraffin embedded (FFPE). Frozen sections were fixed by 6 protocols: acetone, ethanol, NBF (2 durations), and NBF + calcium chloride (2 durations). AR was used for all NBF-fixed sections. More than half of the antibodies (16/26 [62%]) showed immunohistochemical results indistinguishable between acetone- and NBF-fixed sections; 8 (31%) showed better immunohistochemical signals following NBF and AR; 2 gave better immunohistochemical results for acetone-fixed sections. Most cytoplasmic proteins (10/13) showed comparable immunohistochemical signals between acetone- and NBF-fixed sections. For nuclear proteins, NBF-fixed sections gave better immunohistochemical signals than did acetone-fixed sections. In most cases, NBF yielded stronger signals with less background and better morphology. The data do not support the use of acetone-fixed frozen tissue sections as the gold standard for immunohistochemical analysis. In evaluating new antibodies, a combination of acetone- and NBF-fixed frozen sections should be used, although in practice, FFPE tissue sections may serve as the standard for most antigens for immunohistochemical analysis.

Background: Intraoperative evaluation of mediastinal lymph nodes is a necessary step which helps us to decide whether or not to continue the operation of lung cancer. Imprint cytology (IC) can be used as an alternative method in staging. It is a more rapid and simpler procedure than frozen section (FS) analysis. Therefore, we compared the diagnostic accuracy of IC with permanent section on 1050 mediastinal lymph nodes., Methods: A total of 255 non-small cell lung cancer patients who underwent surgical procedure between January 1995 and April 2004 were included. There were 236 males and 19 females with a mean age of 54.2 years (range 26-79 years). In order to obtain lymph node samples mediastinoscopy was performed in 232 (91%), anterior mediastinotomy in 50 (20%) and video-assisted thoracoscopic surgery in 16 (6.3%) patients. During final pathological diagnosis, both imprint and permanent section slides were compared., Results: There were five false-positive and eight false-negative results. The sensitivity, specificity and the predictive values for positive and negative results were 93.1, 99.5, 95.6 and 99.1%, respectively. The overall efficiency was 98.8%., Conclusions: The diagnostic IC is an accurate, reliable, simple and less time-consuming method for evaluation of mediastinal lymph nodes in lung cancer, compared with FS method.

Background: Use of blue dye alone as a marker for sentinel lymph node (SLN) biopsy is effective, but combining it with isotope marking can improve the success rate. Use of the isotope adds extra cost and there are potential radiation hazards. The two techniques were compared in a randomized trial., Methods: Women with early breast cancer (less than 3 cm) and no palpable axillary nodes were recruited. Women older than 70 years with multicentric cancers or previous surgery to the breast or axilla were excluded. Patients were randomized to either blue dye alone or combined mapping for SLN biopsy. All women had a level I and II axillary dissection after the SLN biopsy., Results: A total of 123 patients were recruited, of whom five were excluded from analysis. Blue dye alone was used in 57 women and 61 had combined mapping. Baseline demographic data were similar in the two cohorts. The success rate of SLN biopsy was higher with combined mapping than with blue dye alone (100 versus 86 per cent; P = 0.002). The accuracy and false-negative rate were similar (accuracy 100 per cent for combined mapping versus 98 per cent for blue dye; false-negative rate 0 versus 5 per cent)., Conclusion: Combined mapping was superior to blue dye alone in identification of the SLN, but accuracy and false-negative rates were similar.

Background: The role of routine frozen section (FS) in the surgical management of thyroid nodules remains uncertain. This study reviewed the role of FS in the presence of an adequate fine-needle aspiration biopsy (FNAB)., Methods: FNAB and FS were evaluated in 206 patients who had surgery for a thyroid nodule. Cytological specimens were classified as benign, malignant or suspicious. The FS diagnoses were benign, malignant or deferred., Results: A cytological diagnosis was obtained in 93 nodules; the remaining 113 were classified as suspicious, of which 21 were malignant on definitive examination. The overall accuracy of FNAB was 53 per cent. FS evaluation identified 165 lesions as benign; the diagnosis was deferred until definitive histological evaluation in only eight. The overall accuracy, therefore, was 96 per cent. Routine use of FS was cost-effective; lowering the number of reoperations led to an estimated saving of about 40 per cent., Conclusion: These data suggest that FS remains an important tool in the surgical management of thyroid nodules and can reduce the number of patients requiring reoperation.

Recently there have been several editorials suggesting that breast biopsies with small or nonpalpable lesions should not be subjected to frozen section examination. In this study, the approach of routinely performing frozen sections on all breast biopsies was compared to the recommended approach of performing frozen sections only on cases with gross lesions < 1.0 cm. From July 1, 1992 through June 30, 1993, there were 444 breast biopsies submitted. Nearly all of these (98%) had frozen sections performed. Among these cases, there were 14 false-negative frozen section diagnoses equating to a frozen section sensitivity of 84%, and a frozen section false-negative rate of 3.3%. From July 1, 1994 through June 30, 1995, there were 601 breast biopsies submitted. Of these cases, 310 contained a gross lesion > 1.0 cm and were subjected to frozen section examination. The remaining 291 cases contained either no distinct lesion or a gross lesion < 1.0 cm. These cases were not frozen. Among the 310 cases that were frozen, there were 3 false-negative frozen section diagnoses equating to a frozen section sensitivity of 96%, and a frozen section false-negative rate of 1.0%. These findings indicate that careful gross examination combined with selective freezing of only cases containing a gross lesion > 1.0 cm improves frozen section accuracy. This study provides statistical support for previous recommendations that frozen section examination should be limited to cases with distinct gross lesions > 1.0 cm.

Fifty cases of non-Hodgkin's lymphoma (15 nodular and 35 diffuse) were studied to determine the sensitivity, specificity, and ease of several different immunoperoxidase methods. The methods included a rapid, simple one-step immunoperoxidase procedure on frozen sections compared with indirect immunoperoxidase technics on paraffin sections. The frozen-section immunoperoxidase technic stained 15 of 15 nodular lymphomas and 24 of 35 diffuse lymphomas for monoclonal light chain. The majority of the diffuse lymphomas that did not stain for light chains were morphologically and immunohistochemically consistent with T-cell lymphomas. The indirect method on B-5 and formalin-fixed tissues only rarely displayed monoclonal staining for nonplasmacytoid small cell lymphomas but did stain some large cell lymphomas and a majority of plasmacytoid lymphomas for monoclonal light chain. The frozen section technic presented in this report is sufficiently sensitive and reliable to detect immunoglobulins in any morphologic subtype of B-cell lymphoma, whereas paraffin-embedded tissues have only limited application.