Frozen Section Evaluation Research Articles

Margin status and long-term prognosis of primary pancreatic neuroendocrine tumor after curative resection: Results from the US Neuroendocrine Tumor Study Group

BackgroundThe impact of margin status on resection of primary pancreatic neuroendocrine tumors has been poorly defined. The objectives of the present study were to determine the impact of margin status on long-term survival of patients with pancreatic neuroendocrine tumors after curative resection and evaluate the impact of reresection to obtain a microscopically negative margin. MethodsPatients who underwent curative-intent resection for pancreatic neuroendocrine tumors between 2000 and 2016 were identified at 8 hepatobiliary centers. Overall and recurrence-free survival were analyzed relative to surgical margin status using univariable and multivariable analyses. ResultsAmong 1,020 patients, 866 (84.9%) had an R0 (>1 mm margin) resection, whereas 154 (15.1%) had an R1 (≤1 mm margin) resection. R1 resection was associated with a worse recurrence-free survival (10-year recurrence-free survival, R1 47.3% vs R0 62.8%, hazard ratio 1.8, 95% confidence interval 1.2–2.7, P = .002); residual tumor at either the transection margin (R1t) or the mobilization margin (R1m) was associated with increased recurrence versus R0 (R1t versus R0: hazard ratio 1.8, 95% confidence interval 1.0–3.0, P = .033; R1m versus R0: hazard ratio 1.3, 95% confidence interval 1.0–1.7, P = .060). In contrast, margin status was not associated with overall survival (10-year overall survival, R1 71.1% vs R0 71.8%, P = .392). Intraoperatively, 539 (53.6%) patients had frozen section evaluation of the surgical margin; 49 (9.1%) patients had a positive margin on frozen section analysis; 38 of the 49 patients (77.6%) had reresection, and a final R0 (secondary R0) margin was achieved in 30 patients (78.9%). Extending resection to achieve an R0 status remained associated with worse overall survival (hazard ratio 3.1, 95% confidence interval 1.6–6.2, P = .001) and recurrence-free survival (hazard ratio 2.6, 95% confidence interval 1.4–5.0, P = .004) compared with primary R0 resection. On multivariable analyses, tumor-specific factors, such as cellular differentiation, perineural invasion, Ki-67 index, and major vascular invasion, rather than surgical margin, were associated with long-term outcomes. ConclusionMargin status was not associated with long-term survival. The reresection of an initially positive surgical margin to achieve a negative margin did not improve the outcome of patients with pancreatic neuroendocrine tumors. Parenchymal-sparing pancreatic procedures for pancreatic neuroendocrine tumors may be appropriate when feasible.

Testis-sparing surgery: Experience in 13 patients with oncological and functional outcomes.

We present oncological and functional outcomes of patients who underwent testis-sparing surgery (TSS). Overall, 13 patients were included. Mean patient age was 29.9±12.5 years. In five patients, TSS was performed for sequential bilateral testicular tumours. One patient underwent concurrent left radical orchiectomy and right TSS. In eight patients with normal contralateral testis, seven underwent left and one underwent right TSS. Mean pathological tumour size was 14.6±12.5 mm. Intraoperative frozen section evaluation of the mass was performed in eight patients that revealed benign lesions. No intraoperative tumour bed biopsies were taken in this patient group. Regarding the remaining five patients, intraoperative tumour bed biopsies were taken and testicular intraepithelial neoplasia (TIN) was reported in two (40%) patients; no local testicular radiotherapy was given postoperatively. Tumour pathology was malignant in all but one lesion, including Leydig cell tumour (n=1), seminoma(n=2), embryonal carcinoma (n=1), and adenomatoid tumour (n=1). During 47.2±22.5 months of followup, local recurrence was detected in one patient who underwent radical orchiectomy. No additional local recurrence or systemic metastasis was identified in other patients with malignant lesions. For patients with malignant tumours, of the three patients with a normal preoperative testosterone levels, testosterone level was normal in one patient (with no erectile dysfunction [ED]) and was decreased in two patients (with ED) following TSS. No ED was reported in the nine patients with benign lesions. In carefully selected cases, TSS appears to be a safe, feasible procedure with adequate cancer control that could preserve sexual function.

Frozen section evaluation via dynamic real-time nonrobotic telepathology system in a university cancer center by resident/faculty cooperation team

Frozen section telepathology interpretation experience has been largely limited to practices with locations significantly distant from one another with sporadic need for frozen section diagnosis. In 2010, we established a real-time nonrobotic telepathology system in a very active cancer center for daily frozen section service. Herein, we evaluate its accuracy compared to direct microscopic interpretation performed in the main hospital by the same faculty and its cost-efficiency over a 1-year period. From 643 (1,416 parts) cases requiring intraoperative consultation, 333 cases (690 parts) were examined by telepathology and 310 cases (726 parts) by direct microscopy. Corresponding discrepancy rates were 2.6% (18 cases: 6 [0.9%] sampling and 12 [1.7%] diagnostic errors) and 3.2% (23 cases: 8 [1.1%] sampling and 15 [2.1%] diagnostic errors), P = .63. The sensitivity and specificity of intraoperative frozen diagnosis were 0.92 and 0.99, respectively, in telepathology and 0.90 and 0.99, respectively, in direct microscopy. There was no correlation of error incidence with postgraduate year level of residents involved in the telepathology service. Cost analysis indicated that the time saved by telepathology was $19,691.00 over 1 year of the study period, whereas the capital cost for establishing the system was $8,924.00. Thus, real-time nonrobotic telepathology is a reliable and easy-to-use tool for frozen section evaluation in busy clinical settings, especially when frozen section service involves more than one hospital, and it is cost-efficient when travel is a component of the service.

Value and best way for detection of Sentinel lymph node in early stage endometrial cancer: Selective lymphadenectomy algorithm

IntroductionThe cornerstone of treatment for endometrial carcinoma is total abdominal hysterectomy and bilateral salpingo-oophoprectomy. Pelvic lymphadenectomy, with or without para-aortic lymphadenectomy, plays an important role in the surgical staging of endometrial carcinoma, and provides more accurate prognostic information. AimsWe aimed to evaluate the value and techniques for SLN mapping in early stage endometrial cancer with low risk for lymph node metastasis and whether selective or systematic lymphadenectomy is needed according to the results of proposed algorithm. MethodBetween June 2016 and June 2017, 120 patients with early stage endometrial cancer with low risk for nodal metastasis underwent surgical staging. Patients were classified equally according to SLN mapping technique used for injecting the methylene blue dye. Group A included hysteroscopic guided methylene blue injection, Group B included transcervical injection, Group C included subserosal uterine injection and Group D included combined transcervical and subserosal injection. Blue lymph nodes and enlarged suspicious whether stained or non stained ones were dissected for frozen section evaluation done then bilateral pelvic node dissection was done and tissues were sent for pathological examination. ResultsClinical and pathological SLN detection were more with hysteroscopic technique than others and pathological detection was lower than clinical detection in all techniques. Metastatic disease was more common in nodes with suspicious appearance. About 10% of negative suspicious and mapped nodes were associated with positive other nodes for metastasis. ConclusionSLN in endometrial cancer has a role in staging of endometrial cancer with best technique for detection, hysteroscopic guided blue dye injection. SLN can be used in patients with low risk for lymph node metastasis for selective lymphadenectomy. Blue dye labelling using methylene blue dye is good in low resource countries as it is cheap. We recommended the following algorithm for surgical staging in early endometrial cancer with better results than using SLN alone. Stage I type 1, grade 1,2 endometrial cancer should undergo surgical staging with initial evaluation of the peritoneum which if affected, it is stage III with no need for lymphadenectomy. Then, dissection of the blue and suspicious nodes which if any is positive on frozen section, selective same side pelvic and paraaortic nodal dissection should be done. If they are negative, no need for lymphadenectomy. This approach can help patients to avoid the side effects associated with a complete lymphadenectomy. The higher rate of detection using this algorithm is related to combining the suspicions nodes with the stained ones.

The Impact of Intraoperative Re-Resection of a Positive Bile Duct Margin on Clinical Outcomes for Hilar Cholangiocarcinoma.

The impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA. Patients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers. Short- and long-term outcomes were analyzed among patients stratified by margin status. Among 215 (83.7%) patients who underwent frozen-section evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary negative margin (secondary R0). There was no difference in morbidity, 30-day mortality, and length of stay among patients who had primary R0, secondary R0, and R1 resection (all p>0.10). Median and 5-year survival were 22.3 months and 23.3%, respectively, among patients who had a primary R0 resection compared with 18.5months and 7.9%, respectively, for patients with an R1 resection (p=0.08). In contrast, among patients who had a secondary R0 margin with re-resection of the bile duct margin, median and 5-year survival were 30.6 months and 44.3%, respectively, which was comparable to patients with a primary R0 margin (p=0.804). On multivariable analysis, R1 margin resection was associated with decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0-1.7; p=0.027), but secondary R0 resection was associated with comparable long-term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4-2.3; p=0.829). Additional resection of a positive frozen-section ductal margin to achieve R0 resection was associated with improved long-term outcomes following curative-intent resection of HCCA.

Role of frozen section in sentinel lymph node biopsy for breast cancer in the era of the ACOSOG Z0011 and IBCSG 23-10 trials

BackgroundIntraoperative frozen sections (FS) of sentinel lymph nodes (SLN) were evaluated to avoid the need for deferred axillary lymph node dissection (ALND) in patients with early breast cancer (EBC). However, FS has low sensitivity for detecting micro-metastases (<2 mm), resulting in patients who later undergo deferred ALND. The aim of the study was to determine the best clinical approach for selecting patients who would derive real benefit from ALND, as well as to minimize the functional and psychological damage caused by delayed surgery, and the risk of undertreating EBC patients. MethodsThis study evaluated 1453 patients with early breast cancer (EBC) who underwent SLN biopsy, FS and definitive evaluation. Causes of discrepancies between SLN biopsy and FS results and the need for further surgery were evaluated. ResultsA total of 1226 (86%) patients underwent FS; of these patients, 146 (11.9%) were false negatives. The global sensitivity of FS in detecting both macro and micrometastases was 53.7%. Although ACOSOG Z0011 criteria found that ALND could be avoided in 236 patients, 40 (17%) of these had >3 positive axillary lymph nodes. In contrast, application of the IBCSG 23-10 trial criteria, found that only three patients (3.1%) had >3 positive axillary lymph nodes. ConclusionsFS has a low sensitivity in detecting micrometastases (19%), but a reasonable sensitivity for macrometastases (75%). Most false negatives were smaller metastases (mean 2.1 mm) and more likely in patients with infiltrating lobular carcinoma. Retrospective modelling of the IBCSG 23-10 criteria reduced the percentage of patients requiring deferred surgery from 12% to 4%. Guidelines recommend irradiation of lymph node drainage stations in patients with ≥4 axillary metastatic lymph nodes. Omission of ALND from 40% of patients who met Z0011 criteria would have resulted in their undertreatment. This risk decreases to 3% by omitting axillary clearing only in patients with micrometastases.

An Evaluation of Frozen Section and Lymph Node Dissection Results for Mucinous Ovarian Tumors.

Intraoperative frozen section has greater than 90% accuracy for ovarian tumors; however, mucinous histology has been shown to be associated with increased frozen section inaccuracy. Recent data demonstrate that primary ovarian mucinous carcinomas have no lymph node involvement, even when extraovarian disease is present, and therefore may not require lymph node dissection. Our primary objective is to evaluate the accuracy of identifying mucinous histology on frozen section. A cross-sectional review of mucinous ovarian tumors in surgical patients at one institution from 2006 to 2016 was performed. Cases reporting a mucinous ovarian tumor on frozen section or final pathology were identified. Frozen section results were compared with final diagnosis to calculate concordance rates. Analyses with χ and t tests were performed to identify variables associated with pathology discordance. A total of 126 mucinous ovarian tumors were identified. Of these, 106 were reported as mucinous on frozen section and 103 (97.2%) were concordant on final pathology. Discordant cases included 2 serous and 1 clear cell tumor. Among the 103 mucinous tumors, classification as malignant, borderline, or benign was concordant in 74 (71.8%) of 103 cases, whereas 22 (21.4%) of 103 were discordant and 7 (6.8%) were deferred to final pathology. Lymph node dissection was performed in 33 cases; the only case with lymph node metastasis was a gastrointestinal mucinous adenocarcinoma. Discordance between frozen section and final pathology was associated with larger tumor size and diagnosis other than benign: discordant cases had a mean tumor size of 21.7 cm compared with 14.4 cm for concordant cases (P < 0.001), and 93.5% of discordant cases were borderline or malignant, compared with 30.5% of concordant cases (P < 0.001). Intraoperative identification of mucinous histology by frozen section is reliable with a concordance rate to final pathology of 97.2%. No lymph node metastases were present in any malignant or borderline primary ovarian cases.

Validation of Remote Digital Frozen Sections for Cancer and Transplant Intraoperative Services

Introduction: Whole-slide imaging (WSI) technology can be used for primary diagnosis and consultation, including intraoperative (IO) frozen section (FS). We aimed to implement and validate a digital system for the FS evaluation of cancer and transplant specimens following recommendations of the College of American Pathologists. Materials and Methods: FS cases were routinely scanned at ×20 employing the “Navigo” scanner system. IO diagnoses using glass versus digital slides after a 3-week washout period were recorded. Intraobserver concordance was evaluated using accuracy rate and kappa statistics. Feasibility of WSI diagnoses was assessed by the way of sensitivity, specificity, as well as positive and negative predictive values. Participants also completed a survey denoting scan time, time spent viewing cases, preference for glass versus WSI, image quality, interface experience, and any problems encountered. Results: Of the 125 cases submitted, 121 (436 slides) were successfully scanned including 93 oncological and 28 donor-organ FS biopsies. Four cases were excluded because of failed digitalization due to scanning problems or sample preparation artifacts. Full agreement between glass and digital-slide diagnosis was obtained in 90 of 93 (97%, κ = 0.96) oncology and in 24 of 28 (86%, κ = 0.91) transplant cases. There were two major and one minor discrepancy for cancer cases (sensitivity 100%, specificity 96%) and two major and two minor disagreements for transplant cases (sensitivity 96%, specificity 75%). Average scan and viewing/reporting time were 12 and 3 min for cancer cases, compared to 18 and 5 min for transplant cases. A high diagnostic comfort level among pathologists emerged from the survey. Conclusions: These data demonstrate that the “Navigo” digital WSI system can reliably support an IO FS service involving complicated cancer and transplant cases.

Frozen section evaluation of sentinel lymph nodes in breast carcinoma: a retrospective analysis

ObjectiveTo determine the false-negative rate, sensitivity, and diagnostic accuracy of the frozen section analysis of the sentinel lymph node (SLN) biopsy in early-stage breast cancer compared to the definitive section and to identify the factors that could be associated with the appearance of false-negative cases. Secondarily, to evaluate the pathological results of cases submitted to completion axillary lymph node dissection (ALND) for positive SLN.MethodsWe performed a five-year review of cases (2011–2015), including patients with early-stage breast cancer undergoing SLN biopsy, with frozen section evaluation and subsequent definitive pathological analysis. These results were compared to calculate the false-negative rate and the factors associated with it. The histopathological findings were also evaluated in patients submitted to completion ALND.ResultsA total of 281 patients were evaluated, identifying 18 cases with frozen section results as false negative (false-negative rate: 23.7%), and 55.5% of these cases were micrometastases. The false-negative rate in SLN with macrometastasis was 13.1% and for micrometastasis cases was 66.7% (p < 0.001). True-positive patients that were submitted to completion ALND had additional axillary lymph nodes with metastases in 28% of cases, whereas the group of false negatives had additional positive axillary lymph nodes in 40% of patients (p = 0.62).ConclusionFrozen section analysis had a false-negative rate acceptable in SLN biopsy in our institution, and the micrometastasis in the SLN was the most important factor associated with the appearance of this phenomenon.

Fine-Needle Aspiration Versus Frozen Section in the Evaluation of Malignant Thyroid Nodules in Patients With the Diagnosis of Suspicious for Malignancy or Malignancy by Fine-Needle Aspiration.

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

Surgeon performed continuous intraoperative ultrasound guidance decreases re-excisions and mastectomy rates in breast cancer

BackgroundIntraoperative ultrasound guided (IUG) breast conserving surgery (BCS) is being increasingly embraced by breast surgeons worldwide. We aimed to compare the efficacy of IUG-BCS for palpable and nonpalpable breast cancer with respect to margin status, re-excision rate, tissue sacrifice and cost-time analysis. MethodsIntraoperative localization protocol includes intraoperative ultrasound prior to excision to localize the lesion and guide the initial resection. The excised specimen was then examined visually and by palpation and the specimen and cavity was examined with ultrasound. Frozen sections were obtained routinely from a portion of all six faces of the resected specimen, and shaved cavity margins were sent for permanent histology. ResultsOf the 208 patients, 57.2% had nonpalpable tumors. The sensitivity of ultrasound localization was 100%. Negative margins were achieved in 92.43% of nonpalpable and 91.01% of palpable lesions at initial procedure. The involved margins were correctly identified by the surgeon via specimen sonography in 95.4% of cases. Final positive margin rate was 2.4%. Calculated resection ratio and time analysis revealed nothing significant. ConclusionIUG-BCS is an invaluable and effective modality for obtaining clear surgical margins with optimum resection volumes and reducing re-operations. Furthermore, by means of this algorithm, in case of shaving cavity margins of the tumor bed for permanent analysis, frozen section evaluation might be omitted.

Radiological diagnosis alone risks overtreatment of benign disease in suspected gallbladder cancer: A word of caution in an era of radical surgery

Incidental gallbladder cancer (iGBC) is on the rise world over. This may be a good scenario as we get to treat GBC in early stages. However, there is a practice of diagnosing patients based on clinicoradiological findings alone and subjecting them to a radical surgical procedure. This approach over-treats patient and has important implications for resource utilization. We performed a retrospective analysis of 284 consecutive patients undergoing upfront surgery for suspected GBC from January 2010 to December 2016. The study cohort was divided into two groups, group A - benign (n = 138, 48.6%) and group B - malignant (n = 146, 51.4%). Both groups were compared with respect to demographic characteristics, tumor marker levels, clinicoradiological features, and perioperative outcomes. Approximately 48.6% patients with clinicoradiological suspicion of GBC turned out to be benign on final histology as confirmed on frozen section evaluation (FS). Only 2 patients who were reported benign on FS required revision surgery for malignancy in the final histopathology report. Demographic and clinicoradiological characteristics in both groups were comparable. However, there was a significant difference in blood loss, postoperative hospital stay, and complications between the two groups (P < 0.005). Every other patient who presented to a tertiary cancer center with high index suspicion for malignancy, based on clinicoradiological findings, turned out to be benign on final histology. This emphasizes the fact that, as a norm, for radiologically suspected gallbladder malignancy, we need to have a confirmed histological diagnosis at least during surgery before proceeding to radical resection.

Is serum level of nestin useful in detecting epithelial ovarian cancer?

The aim of the present study was to evaluate the usefulness of nestin as a discriminative marker between benign and malignant ovarian tumors. During the 1 year from January 2015 through December 2015, a nonconsecutive series of 80 patients (40 malignant, 40 benign) who underwent surgery for an adnexal mass were enrolled in the study. Intraoperative frozen section evaluation was performed if there was a suspicion in diagnosis. Statistical analyses were performed using spss ver. 16.0, while clinicopathological variables, including the categorical data, were analyzed using the χ2 -test or Fisher's exact test. A P-value<0.05 was defined as statistically significant. Preoperative serum carbohydrate antigen (CA)-125, CA-15-3, and nestin levels were significantly higher in the malignant group compared to patients with benign ovarian tumors (P < 0.001, respectively). Serum nestin levels did not differ significantly on the basis of histologic subtypes. Serum nestin levels had specificity of 89.7%, which demonstrates nestin's sufficiency to distinguish benign from malignant epithelial ovarian tumors. The positive likelihood ratio of nestin was found to be superior to that of CA-125 and CA-15-3. The results obtained from our study suggest that measurement of nestin level, alongside physical examination, transvaginal ultrasound, and serum CA-125 and CA-15-3 levels, can help differentiate benign ovarian tumors from malignant epithelial ovarian tumors. The findings of our study need to be supported with additional studies.

KANKER OVARIUM DISGERMINOMA

Ovarian cancer is a female reproductive organ malignancy and the second most common gynaecological type cancers. World Health Organisation classifies ovarian cancer based on their origin: superficial stroma-epithelium tumour, cord-stroma sex tumour, and germ cell tumour originated from germinal cells (yolk sac). Epithelium type of ovarian cancer is common, while the germinal type is rare and can be found in teenagers and young women aged 16-20 years old. A case of suspected dysgerminomas ovarian cancer grade IIIA was reported in a 12 years old girl. The diagnosis was established by tumour markers, USG/CT Scan of abdomen, surgery, and frozen section evaluations. The reviewer expected better survival prognosis after surgery and three cycles of chemotherapy combinations were executed. The evaluations of when serial tumour markers CA-125 were suggested during chemotherapy to detect any recurrences factors possibility of the related cancer.

Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging.

BackgroundSurgical resection with microscopically negative margins remains the main curative option for pancreatic cancer; however, in practice intraoperative delineation of resection margins is challenging. Ambient mass spectrometry imaging has emerged as a powerful technique for chemical imaging and real-time diagnosis of tissue samples. We applied an approach combining desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with the least absolute shrinkage and selection operator (Lasso) statistical method to diagnose pancreatic tissue sections and prospectively evaluate surgical resection margins from pancreatic cancer surgery.Methods and FindingsOur methodology was developed and tested using 63 banked pancreatic cancer samples and 65 samples (tumor and specimen margins) collected prospectively during 32 pancreatectomies from February 27, 2013, to January 16, 2015. In total, mass spectra for 254,235 individual pixels were evaluated. When cross-validation was employed in the training set of samples, 98.1% agreement with histopathology was obtained. Using an independent set of samples, 98.6% agreement was achieved. We used a statistical approach to evaluate 177,727 mass spectra from samples with complex, mixed histology, achieving an agreement of 81%. The developed method showed agreement with frozen section evaluation of specimen margins in 24 of 32 surgical cases prospectively evaluated. In the remaining eight patients, margins were found to be positive by DESI-MSI/Lasso, but negative by frozen section analysis. The median overall survival after resection was only 10 mo for these eight patients as opposed to 26 mo for patients with negative margins by both techniques. This observation suggests that our method (as opposed to the standard method to date) was able to detect tumor involvement at the margin in patients who developed early recurrence. Nonetheless, a larger cohort of samples is needed to validate the findings described in this study. Careful evaluation of the long-term benefits to patients of the use of DESI-MSI for surgical margin evaluation is also needed to determine its value in clinical practice.ConclusionsOur findings provide evidence that the molecular information obtained by DESI-MSI/Lasso from pancreatic tissue samples has the potential to transform the evaluation of surgical specimens. With further development, we believe the described methodology could be routinely used for intraoperative surgical margin assessment of pancreatic cancer.

Diagnostic pitfalls of infarcted Warthin tumor in frozen section evaluation.

Warthin tumor (WT) is the second most common benign salivary gland neoplasm and has characteristic cytologic and histologic findings. Fine-needle aspiration is a common and useful preoperative diagnostic technique, which sometimes leads to ischemic injury resulting in the infarction of these lesions. Infarcted WT may demonstrate variable gross and histologic alterations that may render the diagnosis challenging, particularly during intraoperative frozen section evaluation. In this study, we collected 11 resection specimens from 9 patients with infarcted WT. Seven patients were men and 2 were women, ranging from 49 to 85 years (mean, 69). All the patients had fine-needle aspiration before the resection. Macroscopically, the tumors were tan-white and contained soft, yellow, exudative material. The histologic findings were variable and included necrosis, ghosts of papillae, squamous metaplasia, cholesterol clefts, foamy macrophages, multinucleated giant cell reaction, necrotizing granulomas, and fibrosis. Each case predominantly demonstrated 1 or 2 of these histomorphologic features. In the permanent sections, additional sampling revealed foci of residual viable WT in 8 cases. Three cases were completely infarcted; however, they all had ghost-like papillae in which the architecture of WT was evident. Infarcted WT may present a diagnostic challenge during intraoperative frozen section evaluation. Associated morphologic alterations may preclude a definitive diagnosis of WT and may mimic malignancy. Awareness of the gross and microscopic features associated with infarcted WT is important, particularly for accurate frozen section evaluation of these salivary gland tumors.

Frozen section evaluation of margins in radical prostatectomy specimens: a contemporary study and literature review.

The utility of routine frozen section (FS) analysis for margin evaluation during radical prostatectomy (RP) remains controversial. A retrospective search was conducted to identify RPs evaluated by FS over a 5-year period. The potential of FS to discriminate between benign and malignant tissue and to predict final margins was evaluated. During the study period, 71 (12.3%) of 575 cases underwent FS evaluation of margins, generating 192 individual FSs. There were 8 FSs diagnosed as atypical/indeterminate because of significant freezing, crushing, and/or thermal artifacts; 11 as positive for carcinoma; and 173 as benign. Two FSs classified as benign were diagnosed as positive for carcinoma on subsequent permanent section. Frozen sections' sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosis of prostatic adenocarcinoma were 85%, 100%, 100%, 99%, and 99%, respectively. Overall RP final margin predictive accuracy was 81%. Positive FS was significantly associated with perineural invasion on biopsy and extraprostatic extension and higher stage disease on RP, but not with the overall final margin status. The high FS accuracy supports its use to guide the extent of surgery. However, FS cannot be used to predict the overall final margin status. Recognition of the histological artifacts inherent to the FS procedure is important to ensure appropriate utilization.

Tissue requirements in lung cancer diagnosis for tumor heterogeneity, mutational analysis and targeted therapies: initial experience with intra-operative Frozen Section Evaluation (FROSE) in bronchoscopic biopsies.

Recent advances in lung cancer treatment have changed the requirement for the amount and quality of biopsy specimens needed to characterize the tumor and select the best treatment. One adjunct to guide the bronchoscopist on the quality and quantity of specimens during bronchoscopic biopsies for the diagnosis of lung cancer is rapid on-site evaluation (ROSE) of cytological specimens. This technique has been shown to add to the diagnostic yield of bronchoscopy when obtaining adequate specimens for molecular profiling in lung cancer. ROSE is not available at all medical centers. We describe our initial experience using intra-procedural Frozen Section Evaluation (FROSE) of bronchoscopic biopsy specimens as an alternative to ROSE. A retrospective analysis of all interventional pulmonology cases using FROSE between February and July 2015 was performed. Results analyzed to evaluate the success in obtaining adequate specimens for molecular profiling. A total of 88 interventional pulmonology cases employing a frozen section in at least one site were identified. In 94.3% of cases, a definitive diagnosis of benign or malignant was made. The concordance of frozen section diagnoses of benign or malignant was 100% with final diagnoses. Thirteen of the eighty-eight cases were ultimately sent for molecular analysis. Of these, twelve of thirteen (92.3%) cases were adequate to perform all ordered molecular testing. In all cases there was sufficient tissue to perform EGFR and ALK testing. In medical centers where ROSE may not be available, the use of FROSE by the local pathologist can be an effective technique to obtain adequate tissue and cytological samples for the diagnosis and molecular profiling of lung cancers. Further prospective study in bronchoscopic tissue sampling techniques to obtain the optimum quantity and quality of samples for molecular profiling of lung cancers for targeted treatments is needed.

Assessment of the Role of Intraoperative Frozen Section in Guiding Surgical Staging for Endometrial Cancer.

The aim of this study was to assess the role of intraoperative frozen section (FS) in guiding decision making for surgical staging of endometrioid endometrial cancer (EC). Medical records were collected retrospectively on 112 patients with endometrioid EC, who underwent total hysterectomy and bilateral salpingo-oophorectomy at the University of Arizona Medical Center from January 1, 2010, to December 31, 2014. Only patients with endometrioid adenocarcinoma, grade 1, less than 50% myometrial invasion, and tumor size less than 2 cm determined by intraoperative FS omitted lymphadenectomy; otherwise, surgical staging was performed with lymph node dissection. The FS results were compared with the permanent paraffin sections (PSs) to assess the diagnostic accuracy. The concordance rate of different variables between FS and PS in EC was 100%, 89.3% (100/112), 97.3% (109/112), and 95.5% (107/112), respectively, with respecting to histological subtype, grade, myometrial invasion, and tumor size. Diagnostic accurate rate of combined risk factors deciding surgical staging at the time of FS was 95.5% (107/112), and the discordance rate of all risk factors considered between FS and PS was 4.5%, resulting 3 cases (2.7%) undertreated and 2 cases (1.8%) overtreated. Despite nonideal FS evaluation, intraoperative FS diagnosis for EC is highly reliable by providing guidance for the intraoperative decisions of surgical staging at our institution, and such guidelines may be referenced by the institutions with sufficient gynecologic pathology expertise.

Accuracy of intraoperative frozen section for the evaluation of ovarian neoplasms: an institutional experience.

BackgroundOvarian neoplasms are a heterogeneous group of tumors including surface epithelial, germ cell and sex cord stromal tumors with a subset having low malignant potential (borderline tumors). While the surgical management plan differs in different categories of tumors, preoperative diagnosis is seldom available. In these circumstances, the role of frozen section becomes invaluable. In the current study, we aimed to evaluate the accuracy of the frozen section of ovarian tumors in our setup.MethodsIt was a retrospective study involving 141 cases of ovarian tumors undergoing surgical resection with frozen section evaluation from January 2009 to December 2014. After gross examination, one to five blocks were prepared on the frozen section depending upon the size of the specimen. After frozen section reporting, specimens were processed routinely for final paraffin section evaluation. Results of frozen and paraffin sections were categorized in benign, borderline, and malignant, and accuracy of frozen section was determined.ResultsOut of 141 cases, 107 were diagnosed as benign on final (paraffin) examination, while 6 were borderline and 28 were malignant. Out of 107 benign cases, 45 were non-neoplastic cystic lesions of the ovary including endometriotic, follicular, and corpus luteal cysts. The most common benign neoplastic tumor was mature cystic teratoma (20 cases) followed by mucinous cystadenoma (19 cases), serous cystadenoma (14 cases), sex cord stromal tumors (8 cases), and Brenner tumor (1 case). Among borderline cases, four cases were serous and two of mucinous neoplasms. The most common malignant neoplasm was serous carcinoma (11 cases) followed by mucinous carcinoma (6 cases). The overall accuracy of frozen section diagnosis is above 99 %. The sensitivity and specificity for benign tumors were found to be 100 and 97 %, respectively. The sensitivity and specificity for borderline tumors was 83 and 99 %, respectively, while for malignant tumors, it was 96 and 100 %, respectively.ConclusionsWe found a high sensitivity and specificity of frozen section for the diagnosis of ovarian tumors and to determine its malignant potential. Therefore, it should always be used when the preoperative diagnosis is not definite to govern extent of surgical resection. However, under-diagnosis can occur in tumors of borderline category which can be minimized by increased sampling on the frozen section.