Intraoperative Frozen Section Assessment Research Articles

Therapeutic mammoplasty: a "wise" oncoplastic choice-lessons from the largest single-center cohort from Asia.

The majority of breast cancer patients from India usually present with advanced disease, limiting the scope of breast conservation surgery. Therapeutic mammoplasty (TM), an oncoplastic technique that permits larger excisions, is quite promising in such a scenario and well suited to breast cancer in medium-to-large-sized breasts with ptosis and in some cases of large or multifocal/multicentric tumors. Here, we describe our TM cohort of 205 (194 malignant and 11 benign) patients from 2012 to 2019 treated at a single surgeon center in India, the largest Asian dataset for TM. All patients underwent treatment after careful discussions by a multidisciplinary tumor board and patient counseling. We report the clinicopathological profiles and surgical, oncological, cosmetic, and patient-related outcomes with different TM procedures. The median age of breast cancer patients was 49 years; that of benign disease patients was 41 years. The breast cancer cohort underwent simple (n = 84), complex (n = 71), or extreme (n = 44) TM surgeries. All resection margins were analyzed through intra-operative frozen-section assessment with stringent rad-path analysis protocols. The margin positivity rate was found to be 1.4%. A majority of the cohort was observed to have pT1-pT2 tumors, and the median resection volume was 180 cc. Low post-operative complication rates and good-to-excellent cosmetic scores were observed. The median follow-up was 39 months. We observed 2.07% local and 5.7% distal recurrences, and disease-specific mortality was 3.1%. At median follow-up, the overall survival was observed to be 95.9%, and disease-free survival was found to be 92.2%. The patient-reported outcome measures (PROMs) showed good-to-excellent scores for all types of TMs across BREAST-Q domains. We conclude that in India, a country where women present with large and locally advanced tumors, TM safely expands the indications for breast conservation surgery. Our results show oncological and cosmetic outcomes at acceptable levels. Most importantly, PROM scores suggest improved overall wellbeing and better satisfaction with the quality of life. For patients with macromastia, this technique not only focuses on cancer but also improves self-image and reduces associated physical discomfort often overlooked by women in the Indian setting. The popularization of this procedure will enable Indian patients with breast cancer to receive the benefits of breast conservation.

Intraoperative pathology consultation during urological surgery: Impact on final margin status and pitfalls of frozen section diagnosis.

Despite recent improvements in diagnostic and surgical techniques in urological oncology, positive resection margin remains a significant concern for surgeons. Meanwhile, intraoperative pathology consultation with frozen section assessment (FSA), particularly for histological diagnosis of the lesions incidentally found or enlarged or sentinel lymph nodes, generally provides critical information which enables immediate decision making for optimal patient care. The intraoperative evaluation of surgical margins is also often requested, although there are some differences in its application between institutions and surgeons. Importantly, it remains to be determined whether intraoperative FSA indeed contributes to reducing the risk of final positive margins and thereby improving long-term patient outcomes. This review summarizes available data indicating the potential impact of FSA at the surgical margins during urological surgeries, including radical or partial cystectomy, partial nephrectomy, radical prostatectomy, penectomy, and orchiectomy. The accuracy and pitfalls of the intraoperative consultation/FSA diagnosis are also discussed.

Intraoperative frozen section assessment of cavity shave margins in patients undergoing breast conservation surgery

Background: Surgical management of breast cancer has taken a paradigm shift from the early days of the radical Halstedian approach to a newer, relatively conservative approach. Breast conservation surgery (BCS) is the surgery of choice for early breast cancer (EBC). Pathological margin status is the single most important prognostic factor in patients undergoing BCS. Rates of margin positivity after BCS varies between 3- 20%. Multiple techniques have been applied to decrease margin positivity rates in BCS. We evaluated the impact of Intraoperative frozen section assessment of cavity shave margins (IFSA) in patients with EBC undergoing BCS

Investigation of the usefulness of fluorescein sodium fluorescence in stereotactic brain biopsy.

Intraoperative frozen section assessment, to confirm acquisition of pathological tissues, is used in stereotactic brain biopsy to minimise sampling errors. Limitations include the dependence on dedicated neuro-oncology pathologists and an increase in operative duration. We investigated the use of intraoperative fluorescein sodium, and compared it to frozen section assessment, for confirming pathological tissue samples in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. This prospective observational study consisted of 18 consecutive patients (12 men; median age, 63years) who underwent stereotactic biopsy of gadolinium-contrast-enhancing brain lesions with intravenous fluorescein sodium administration. Twenty-three specimens were obtained and examined for the presence of fluorescence using a microscope with fluorescence visualisation capability. Positive and negative predictive values were calculated based on the fluorescence status of the biopsy samples with its corresponding intraoperative frozen section and definitive histopathological diagnosis. Nineteen specimens (83%) were fluorescent and four (17%) were non-fluorescent. All 19 fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment and were suitable for histopathological diagnosis. Three of the non-fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment. One non-fluorescent specimen was non-diagnostic on frozen section and histological assessments. The positive predictive value was 100% and the negative predictive value was 25%. Fluorescein sodium fluorescence is as accurate as frozen section assessment in confirming sampling of pathological tissue in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. Fluorescein sodium fluorescence-guided stereotactic biopsy is a useful addition to the neurosurgical armamentarium.

Clinical benefits of frozen section assessment during urological surgery: Does it contribute to improving surgical margin status and patient outcomes as previously thought?

Despite significant advances in patient selection as well as surgical technique over the past few decades, it is still not uncommon for patients with urological malignancy and positive surgical margins to be observed. Meanwhile, intraoperative pathology consultation with frozen section assessment, which generally provides useful information for the optimal procedure, has been widely utilized for the assessment of surgical margins during urological surgeries. Thus, it remains unanswered whether intraoperative frozen section assessment has an impact on final surgical margin status as well as long-term oncological outcomes. The present review summarizes and discusses available data assessing the utility of frozen section assessment of the surgical margins during urological surgeries, such as radical prostatectomy, partial nephrectomy and radical cystectomy. The current findings suggest that select patients might benefit from the routine frozen section assessment.

The Role of Frozen-Section in the Surgical Management of Patients with Endometrial Intraepithelial Neoplasia.

Patients with endometrial intraepithelial neoplasia may have concurrent endometrial cancer if managed surgically or develop cancer in time if managed conservatively. Therefore, intraoperative assessment of the uterus may be helpful if a surgical approach is decided on. Our study aimed to investigate the role of frozen-section examination in patients with endometrial intraepithelial neoplasia. Patients with endometrial intraepithelial neoplasia who were subjected to hysterectomy with intraoperative frozen-section assessment were included. Main outcome measures were the rates of concurrent endometrial cancer and concurrent high-risk endometrial cancer as well as the efficacy of frozen-section in the detection of concurrent invasive disease and in the designation of low-risk and high-risk features. The study group consisted of seventy-three patients. Permanent pathology revealed endometrial adenocarcinoma in 19.2% whereas only one patient (1.4%) had high-risk disease necessitating surgical staging. Frozen-section diagnoses were consistent with final pathology in 93.2% of patients in terms of the presence or absence of co-existent carcinoma. When frozen-section reports were further evaluated in terms of the presence or absence of high-risk endometrial carcinoma, consistency with the final pathology was seen in 98.6% of patients. Co-existent endometrial cancer is not uncommon in endometrial intraepithelial neoplasia. Intraoperative frozen-section evaluation should therefore be considered whenever possible. Frozen-section is effective in the detection of coexistent invasive disease and in the designation of low-risk features. Although coexistent high-risk cancer is extremely rare, frozen-section assessment is not successful in determining high-risk features. Therefore, a re-staging surgery may be required on rare occasions.

Sertoli-Leydig cell tumor with unique nail findings in a post-menopausal woman: a case report and literature review

BackgroundSertoli-Leydig cell tumor (SLCT) is a rare sex-cord tumor that usually occurs unilaterally and accounts for < 0.5% of all ovarian tumors. SLCT is uncommon in post-menopausal women, with the average age of diagnosis being 25 years.CaseWe present a case of a 63-year-old post-menopausal woman presenting with progressive hirsutism, and male-pattern baldness. Unusual nail changes were also observed.MethodsHormonal profile of the patient revealed increased testosterone and estradiol levels, and a 3.5 cm left ovarian mass. The patient was evaluated and was not found to be anemic or iron-deficient. Intraoperative frozen section assessment during laparoscopic exploration revealed SLCT, which was confirmed subsequently by histopathological and immunohistochemical (IHC) examination. Nail bed tissues were collected from normal females and evaluated by IHC for the presence of androgen receptors (AR).ResultsThe patient had an excellent postoperative course and all her testosterone-related manifestations were reversed within one year of surgery. Following surgery, the patient’s unique nail abnormalities also resolved gradually. The IHC evaluation also confirmed the presence of AR in nail bed tissues of females.ConclusionSLCT, albeit rare, should be considered in post-menopausal women presenting with virilization and elevated androgen levels. Unusual nail signs may develop in response to increased androgen levels in these patients.

Evaluation of myometrial invasion in endometrial cancer: comparison of diffusion-weighted magnetic resonance and intraoperative frozen sections

To compare the diagnostic accuracy of diffusion-weighted magnetic resonance imaging (DWI) and frozen-section analysis in assessing myometrial invasion in endometrial cancer to guide surgery. In this prospective study, 51 women with diagnosed endometrial cancer were examined using magnetic resonance imaging (MRI) and subsequently underwent hysterectomy with intraoperative frozen-section assessment. The MRI protocol included T2-weighted images (T2WI), a dynamic T1-weighted post-gadolinium series, and DWI sequences acquired with b values of 0, 150, and 800s/mm(2). Apparent diffusion coefficient (ADC) maps were obtained in all the studies. Deep myometrial invasion was defined as involvement of ≥50% of the thickness of the myometrium. The final postoperative pathological evaluation was considered as the reference standard. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of DWI for detecting deep invasion of the myometrium were 90.2%, 77.8%, 97%, 93.3%, and 88.9%, respectively. For the intraoperative frozen section, these figures were 90.2%, 73.7%, 100%, 100%, and 86.5%. The precision for both tests was the same using McNemar's test (p=1). In assessing the depth of myometrial invasion, ADC maps show the same accuracy as intraoperative histological studies in endometrial cancers. They also allow for a more precise assessment than conventional MRI sequences. Frozen-section analysis can be avoided if the preoperative MRI study includes DWI sequences and ADC maps.

Sertoli-Leydig cell tumor with unique nail findings in a post-menopausal woman: a case report and literature review

BackgroundSertoli-Leydig cell tumor (SLCT) is a rare sex-cord tumor that usually occurs unilaterally and accounts for < 0.5% of all ovarian tumors. SLCT is uncommon in post-menopausal women, with the average age of diagnosis being 25 years.CaseWe present a case of a 63-year-old post-menopausal woman presenting with progressive hirsutism, and male-pattern baldness. Unusual nail changes were also observed.MethodsHormonal profile of the patient revealed increased testosterone and estradiol levels, and a 3.5 cm left ovarian mass. The patient was evaluated and was not found to be anemic or iron-deficient. Intraoperative frozen section assessment during laparoscopic exploration revealed SLCT, which was confirmed subsequently by histopathological and immunohistochemical (IHC) examination. Nail bed tissues were collected from normal females and evaluated by IHC for the presence of androgen receptors (AR).ResultsThe patient had an excellent postoperative course and all her testosterone-related manifestations were reversed within one year of surgery. Following surgery, the patient’s unique nail abnormalities also resolved gradually. The IHC evaluation also confirmed the presence of AR in nail bed tissues of females.ConclusionSLCT, albeit rare, should be considered in post-menopausal women presenting with virilization and elevated androgen levels. Unusual nail signs may develop in response to increased androgen levels in these patients.

Intraoperative frozen section assessment in the evaluation of axillary sentinel lymph node in breast cancer

INTRODUCTION: Intraoperative frozen section analysis has become a routine procedure to evaluate the status of axillary sentinel lymph nodes in breast cancer. OBJECTIVES: To evaluate the accuracy and sensitivity of FS in the detection of metastases in axillary sentinel lymph nodes and to investigate the predictive value of variables such as patients' age, tumor staging, histology, grade, and estrogen receptor expression. MATERIAL AND METHODS: We analyzed retrospectively the results of 177 FS procedures. The patients' age and tumor characteristics were organized in a database and the association with the presence of metastases was analyzed. RESULTS: Metastases were detected in 22 cases (12%). All macrometastases and one micrometastasis were detected by FS. Additional micrometastases were detected in post-operative analysis, from which five were determined by hematoxylin and eosin staining (H) and three by immunohistochemistry (IHC). FS diagnosis data proved to have an overall accuracy of 95%, sensitivity of 64%, and specificity of 100%. None of the analyzed variables showed significant association with lymph node metastases. CONCLUSION: Our results show that intraoperative FS is a highly accurate and sensitive method to detect macrometastases. However, it is inaccurate in the detection of micrometastases. The use of IHC improves the detection of micrometastases in postoperative analyses. The patient's age and tumor characteristics such as staging, histology, grade and estrogen receptor expression have low predictive value for lymph node metastasis in breast cancer.

Intraoperative frozen section assessment of pelvic lymph nodes during radical prostatectomy is of limited value

To evaluate the accuracy of frozen section (FS) assessment of pelvic lymph nodes (PLNs) during radical prostatectomy (RP) in a large contemporary cohort; and to analyse the contribution of FS to surgical decision making in this setting. During a 4-year period at a single institution, RPs with PLN dissection (PLND) were reviewed. The number and size of the PLNs, and the size of metastases were measured. FS was performed on 349 bilateral PLNDs. Overall, 28 (8%) cases were positive for metastasis, 11 of which were detected by FS (39%). The 17 false negatives, all of which contained metastases smaller than 5 mm, were due to failure to identify and freeze the positive PLNs (11), failure to section at the level of the metastatic tumour (four), or interpretative error (two). The sensitivity was not affected by the number of sampled nodes. The size of metastasis was the determining factor for the accuracy of FS, with metastases of ≥ 5 mm having a sensitivity of 100%, and metastases of < 5 mm having a sensitivity of 10%. Among the 11 true positives, RP was aborted in eight cases and continued in three. During the same period, 261 PLNDs were performed without FS, and 18 (6.9%) had metastases. FS is highly accurate in detecting large, grossly evident metastases, but performs poorly on micrometastases. It is recommended that a two-step approach applied to routine FS starting with a careful gross examination followed by FS for only grossly suspicious PLNs.

302 Is intra-operative frozen section assessment of sentinel lymph nodes worth our while?

302 Is intra-operative frozen section assessment of sentinel lymph nodes worth our while?

Intraoperative frozen section assessment of sentinel lymph nodes in the operative management of women with symptomatic breast cancer

BackgroundMaximisation of the potential of sentinel lymph node biopsy as a minimally invasive method of axillary staging requires sensitive intraoperative pathological analysis so that rates of re-operation for lymphatic metastases are minimised. The aim of this study was to describe the test parameters of the frozen section evaluation of sentinel node biopsy for breast cancer compared to the gold standard of standard permanent pathological evaluation at our institution.MethodsThe accuracy of intraoperative frozen section (FS) of sentinel nodes was determined in 94 consecutive women undergoing surgery for clinically node negative, invasive breast cancer (37:T1 disease; 43:T2; 14:T3). Definitive evidence of lymphatic spread on FS indicated immediate level II axillary clearance while sentinel node "negativity" on intraoperative testing led to the operation being curtailed to allow formal H&E analysis of the remaining sentinel nodal tissue.ResultsIntraoperative FS correctly predicted axillary involvement in 23/30 patients with lymphatic metastases (76% sensitivity rate) permitting definitive surgery to be completed at the index operation in 87 women (93%) overall. All SN found involved on FS were confirmed as harbouring tumour cells on subsequent formal specimen examination (100% specificity and positive predictive value) with 16 patients having additional non-sentinel nodes found also to contain tumour. Negative Predictive Values were highest in women with T1 tumours (97%) and lessened with more local advancement of disease (T2 rates: 86%; T3: 75%). Of those with falsely negative FS, three had only micrometastatic disease.ConclusionIntraoperative FS reliably evaluates the status of the sentinel node allowing most women complete their surgery in a single stage. Thus SN can be offered with increased confidence to those less likely to have negative axillae hence expanding the population of potential beneficiaries.

Transduodenal Resection of Peri‐Ampullary Lesions

Transduodenal resection (TDR) of lesions near the ampulla of Vater is an alternative to the Whipple pancreaticoduodenectomy. A retrospective analysis was performed to determine the long-term outcome and the utility of intraoperative frozen section examinations in aiding operative decision making in patients undergoing TDR. From 1992 to 2002, 19 patients with an average age of 64.2 years (range: 33-84 years) underwent a transduodenal resection of a peri-ampullary lesion; median follow-up was 47 months (range: 2-100 months). Pathology of the lesions was as follows: 11 with benign ampullary adenomas, including 4 with familial adenomatous polyposis (FAP); 7 with peri-ampullary adenocarcinomas; and 1 with a benign stricture. Survival for the entire cohort is 100%. In 12 cases an intraoperative frozen section was performed. The specificity and positive predictive value of the intraoperative histology were both 100%, and the sensitivity and negative predictive value were 57% and 38%, respectively. Three of the 4 patients with FAP have recurrent adenomatous change; 2 of the 7 with carcinoma have metastatic adenocarcinoma. Transduodenal resection of peri-ampullary lesions appears to be a safe alternative to radical resection for benign adenomas and selected carcinoma. Intraoperative frozen section assessment is recommended in cases of potential adenocarcinoma.

Intraoperative frozen section examination of axillary sentinel lymph nodes in breast cancer

The study presents the results from intraoperative frozen section assessment of axillary sentinel lymph nodes (SLNs) in breast cancer. Routine histological frozen sections from one level were used, two sections stained with haematoxylin and eosin. Immunohistochemistry for cytokeratins was applied to the permanent SLN paraffin sections only. Axillary dissection was performed on all SLN-positive cases regardless of the size of the metastatic deposits. With a detection rate of 83%, 272 patients entered the study over a period of 46 months. A total of 61 cases were SLN positive by frozen section analysis. The paraffin sections gave an additional 23 SLN-positive cases. The false-negative rate for frozen sections was then 27% (23/84). Micrometastases were found in 28 of 84 cases, and macrometastases in 56. The false-negative rate of frozen sections for micrometastases was 71% (20/28), and for macrometastases 5% (3/56). A total of 73% (61/84) of the patients underwent axillary surgery as a one-step procedure.

Frozen section analyses as predictors of lymphatic spread in patients with early-stage uterine cancer.

Many gynecologic oncologists use intraoperative frozen section (IFS) assessment of histologic grade and depth of myometrial invasion (DOI) as predictors of final grade and stage in women with endometrial cancer. This clinical decision method has never been critically examined. We retrospectively reviewed charts of patients with a preoperative diagnosis of uterine endometrioid adenocarcinoma and an intraoperative frozen section assessment of histologic grade and depth of myometrial invasion. Intraoperative predictors combining intraoperative frozen section assessment of histologic grade and depth of myometrial invasion were established and compared with final grade and surgical stage. We then modeled the risks of pelvic and paraaortic lymph node metastases for each predictor. There were 129 patients who met inclusion criteria. Thirty-six patients had the IAG1 predictor; 17 (47%) were stage IAG1 on final pathology. Ten patients had the IAG2 predictor; 3 (30%) were stage IAG2 on final pathology. Thirty-four patients had the IBG1 predictor; 18 (53%) were stage IBG1 on final pathology. Forty-nine patients had the IBG2 predictor; 34 (69%) were stage IBG2 on final pathology. Our decision models predict that the IAG1 predictor has a 1% risk of paraaortic and a 2% risk of pelvic lymph node metastases. The IAG2 and IBG1 predictors have a 2% risk of paraaortic and a 4% risk of pelvic lymph node metastases. The IBG2 predictor has a 2% risk of paraaortic and a 6% risk of pelvic lymph node metastases. The combination of intraoperative frozen section analysis for histologic grade and depth of myometrial invasion does not correlate well with final pathologic grade and stage. Data from our models suggest a significant risk of lymph node spread even for patients with seemingly low-risk disease. Until better markers of lymphatic spread exist, we recommend complete surgical staging of all patients with endometrial cancer.

Pattern of invasion and margin assessment in patients with oral tongue cancer.

Involvement of resection margins and the pattern of tumor invasion are reported to be important predictors of local recurrence and survival in surgically treated patients. In this study we have retrospectively assessed the significance of these two prognostic factors in a relatively homogeneous patient population. Patients and Methods This study was confined to 150 previously untreated patients who had surgery for squamous carcinoma of the oral tongue between 1987 and 1993. There were 82 men and 68 women who ranged in age from 25 to 89 years (median 60 years). Glossectomy was peroral in 129, whereas 8 and 13, respectively, had a cheek flap or mandibulotomy approach. Some form of lymphadenectomy was performed in 109 (73%), and 51 patients (34%) received postoperative radiotherapy. Histologic slides from each primary tumor were reviewed to verify the margin status. In addition, the pattern of invasion was evaluated and graded from 1 to 4, varying from a consistently well-defined, "pushing" border (Grade 1) to diffuse infiltration and cellular dissociation (Grade 4). Intraoperative frozen section assessment of margins was accurate, whether positive or negative, in 118 of 133 patients (89%). Positive or close margins (within one high-power field) and an endophytic growth pattern were associated with a significant increase in local recurrence (p <0.003 and <0.04, respectively). With higher grades of infiltration (Grade 3 or 4; 82 patients), the tumors tended to be larger and the patients younger. Although the likelihood of nodal involvement and subsequent distant metastasis was significantly greater in those with Grade 3 or grade 4 patterns (p <0.0003 and <0. 01, respectively), there was no impact on local recurrence. Cumulative survival was similar whether or not the surgical margins were involved, but was significantly reduced when the pattern of tumor invasion was of higher grade (p <0.01). Frozen section provided reasonably accurate information about margins in our patients, whether taken from the patient or the surgical specimen. Positive margins increased the likelihood of local recurrence, but did not impact on survival because subsequent surgery and/or irradiation controlled tumor recurrence in some patients. Grade 3 or 4 patterns at the tumor/host interface were associated with an increased incidence of nodal and distant metastasis, as well as a significant decrease in survival.