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[Frozen section examination in thyroid pathology. Technique and effective indications].

Frozen section examination for intraoperative diagnosis is often difficult in thyroid pathology. Fine-needle aspiration is widely used in the patients selection for surgery. Such a selection is accompanied by an increase in difficult frozen section cases, whose diagnosis is often differed to permanent sections. Thus, frozen section sensitivity is relatively low. In the era of cost containment, an increasing number of authors suggest that frozen section examination is unnecessary, and that surgical planning could rely on preoperative cytology only. Others consider fine-needle aspiration cytological evaluation and frozen section examination as complementary tools and recommend their association. The authors describe the technical aspects and difficulties of frozen section examination in thyroid pathology, and discuss its interest in surgical planning, in the light of preoperative cytology. Each team has to estimate local thyroid cytology development and accuracy, to define new indications for frozen section examination in thyroid pathology, according to local therapeutic choices. Such an approach could consistently reduce the number of intraoperative consultation for thyroid pathology, without prejudice for the patients.

Biopsy, Needle↗

A negative contrast stain for ultra-thin frozen sections.

Ultra-thin frozen sections are ideal substrates for immunolabelling in high resolution electron microscopy. However, visualization of subcellular structures is inferior to that obtained with corresponding plastic sections. Although negative staining is generally effective and even superior to positive staining, the accumulated stain is often too heavy, obscuring morphology and markers used for immunocytochemical localization of antigens. This paper describes the development of a modified negative contrast staining technique in which a high concentration of uranyl acetate is mixed with methyl cellulose at a low pH. Application of this stain to cryosections of cells and tissue resulted in improved visualization of morphological structures characterized by negative images of membranes and cell organelles. Use of this stain is advantageous for morphological and immunocytochemical studies involving ultra-thin frozen sections.

Adrenodoxin↗

Ureteral frozen section analysis during cystectomy: a reassessment.

PURPOSE: Frozen section analysis of the distal ureteral margins is commonly performed at cystectomy to exclude involvement of tumor in retained ureter. We reviewed our experience with 101 consecutive cystectomies to determine the contemporary incidence and clinical significance of the urothelial abnormalities detected by frozen section analysis performed at operation. METHODS AND MATERIALS: The pathology reports for 101 patients treated with nerve sparing cystectomy between 1982 and 1989 were reviewed. Frozen section and final ureteral analyses were compared. RESULTS: Of the patients 8% had evidence of a urothelial abnormality ranging from mild atypia to frank carcinoma in situ involving the distal ureters on frozen section. Only 4 patients had documented carcinoma in situ at the final margin and all 4 ultimately died of disease. The frozen section false-positive and false-negative rates were 2 and 6%, respectively. In 6 patients with ureteral urothelial abnormalities documented on frozen section ureterointestinal anastomosis was performed despite persistent abnormalities at the ureteral margins, frequently after multiple frozen analyses failed to clear the margins definitively. None of the 6 patients in this group experienced upper tract recurrence during a mean followup of 41 months. CONCLUSIONS: These data suggest that routine frozen section analysis of the ureteral margins at cystectomy may not be necessary for most patinets undergoing cystectomy.

Adult↗

Protocol for ultrarapid immunostaining of frozen sections.

Rapid immunostaining of frozen sections within a tolerable time span would be very helpful for intraoperative diagnosis. A protocol was therefore established using the enhanced polymer one-step staining (EPOS) system (Dako) with antibodies against leucocyte common antigen (LCA), cytokeratin (CK), and anti-melanoma (MEL). Best results with reliable and specific immunostaining and a labelling intensity comparable to standard immunostaining protocols were achieved with fixation of samples in 100% acetone for 20 seconds (CK, LCA) or two minutes (MEL), followed by incubation of the primary antibody and development of the chromogen reaction with 3,3'diaminobenzidine (DAB) for three and five minutes at 37 degrees C, respectively. The total procedure takes only 12 minutes, thus enabling rapid immunostaining on intraoperative frozen sections. Apart from its use in tumour classification, this method is especially useful in detecting tumour cells in sentinel lymph nodes.

Antigens, Neoplasm↗

Immunocytochemical staining of estrogen receptor in paraffin sections of human breast cancer by use of monoclonal antibody: comparison with that in frozen sections.

Estrogen receptor (ER) in human breast cancer tissues was demonstrated in paraffin sections as well as in frozen sections by immunoperoxidase methods using monoclonal antibody (H222) against ER. The avidin-biotin-peroxidase complex method was used for the paraffin sections fixed in cold buffered formalin, and the peroxidase-antiperoxidase method was used for the fixed frozen sections. The results were compared with the ER content in the respective tumor tissue determined by dextran-coated charcoal assay. The specific staining for ER was located exclusively in the nuclei of cancer cells in both paraffin and frozen sections. Differences in the intensity and distribution of nuclear staining within a section were often observed, suggesting heterogeneity of the ER content of individual breast cancer cells. In 24 breast cancer tissues studied simultaneously by both paraffin and frozen section methods, 21 (88%) showed similar evaluation of the presence of ER. The results of immunocytochemical staining agreed with those of the dextran-coated charcoal assay in 89 (82%) of the 109 paraffin-sectioned tumor tissues and in 24 (86%) of the 28 frozen-sectioned tissues, indicating that ER can be demonstrated immunocytochemically by use of paraffin as well as frozen sections.

Antibodies, Monoclonal↗

Large cell anaplastic lymphoma: evaluation of immunophenotype on paraffin and frozen sections in comparison with ultrastructural features.

Eleven cases of large cell anaplastic lymphoma (T type n = 5, B type n = 4, 0 type n = 2) were investigated using electron microscopy and immunophenotyping on formalin-fixed paraffin sections and frozen sections of fresh tissue, to determine whether morphological criteria exist for the discrimination of T, B, and 0 phenotypes. Tumour cell lineage could not be established from ultrastructural features. On paraffin material monoclonal B-cell markers Ki-B5 and L-26 served as reliable tools for recognizing the B phenotype of large cell anaplastic lymphomas (previously determined on fresh material). whereas monoclonal antibodies MT1 (CD43) and UCHL1 (CD45RO) were of limited value in lineage determination.

Adult↗

Surgical management of thyroid masses: assessing the need for frozen section evaluation.

OBJECTIVE/HYPOTHESIS: To determine the need for intraoperative frozen section to guide the extent of thyroid surgery in the presence of an adequate preoperative fine-needle aspiration (FNA) finding. METHODS: Charts of patients who presented from 1995 to 1998 to the two senior authors were reviewed. A total of 82 patients were found who satisfied the inclusion criteria of having both an adequate FNA and frozen section. The extent of surgery was based on the frozen section finding for all the patients in this study. The authors looked at the number of cases in which the surgical management would be changed if the frozen section was not obtained and the surgical decision was based only on preoperative FNA and intraoperative findings. RESULTS: FNA revealed papillary carcinoma in 18 patients that was confirmed by intraoperative frozen section and final pathology. In the remaining 64 patients, the FNA diagnosis was either benign or suspicious. When routine frozen section was done, 61 of these 64 patients were found to have either benign pathology or pathological diagnosis that was deferred to permanent section. Only three patients were found to have malignancy on frozen section that was missed by FNA. Of these three patients, two had obvious findings of malignancy at the time of surgery. This leaves only one patient with carcinoma that was missed by FNA and intraoperative findings but detected by the intraoperative frozen section. CONCLUSION: Of the 82 patients in this study, only one extra case of malignancy would be missed by elimination of the routine use of intraoperative frozen section. The authors conclude that the routine use of intraoperative frozen section may be unnecessary. The use of an adequate preoperative FNA together with sound clinical judgment at time of surgery can adequately guide the extent of surgical resection.

Adult↗

Accuracy, utility, and cost of frozen section margins in head and neck cancer surgery.

OBJECTIVES: Intraoperative frozen section analysis of surgical margins is widely used in head and neck cancer surgery. This study evaluates frozen section accuracy relative to permanent controls and final margins from the entire specimen, the rate at which frozen sections impact intraoperative management, and the resultant cost. STUDY DESIGN: Retrospective. METHODS: From 1997 to 1999 the frozen section results, permanent controls, and final tumor margins from 80 consecutive patients undergoing 420 intraoperative frozen section margins for head and neck malignancy were reviewed. RESULTS: A 98.3% accuracy rate (sensitivity, 88.8%; specificity, 98.9%) was found compared with permanent sections of the same tissue. However, 40% (8 of 20) of patients with positive final margins on the resection specimen, and 100% (15 of 15) with close (<5 mm) margins were not detected by frozen section analysis. The overall accuracy of frozen section in the evaluation of close or positive final margins was 71.3% (sensitivity, 34.3%; specificity, 100%). In addition, 5% (4 of 80) of patients potentially benefited from intraoperative frozen section by virtue of immediate margin revision. The estimated cost of intraoperative frozen section averaged as much as $3,123 per patient, with a cost-benefit ratio of 20:1. CONCLUSIONS: Intraoperative frozen section margins are accurate, but they are costly and cannot reliably eradicate positive final margins. Patients with early-stage lesions and those undergoing re-resection for recurrence or salvage surgery after radiation failure derived the greatest potential benefit from frozen section margins.

Cost-Benefit Analysis↗

Frozen section evaluation of cervical conization specimens.

Frozen section evaluation was done on 96 conization specimens. One patient had invasive carcinoma, which was correctly diagnosed on frozen section. No patient received inappropriate therapy on the basis of an erroneous diagnosis made from the evaluation of frozen sections. The mean time from initiation of surgery to the surgeon's receipt of the frozen section diagnosis was 0.9 hours. There was no significant increase in the blood loss or intraoperative complication rate when frozen conization was added to either abdominal or vaginal hysterectomy.

Biopsy↗

The accuracy of a frozen section diagnosis of borderline ovarian malignancy.

While the accuracy of frozen section in the diagnosis of invasive ovarian neoplasms has been previously addressed, the frozen section diagnosis of borderline ovarian tumors has been less well characterized. The distinction between benign and borderline lesions is critical to the proper operative management of these patients. The records of 48 patients that had a frozen section diagnosis of borderline ovarian malignancy during surgical exploration between 1986 and 1993 were reviewed. Thirty-one patients were Stage I, 2 patients were Stage II, 10 patients were Stage III, and 5 patients were unstaged. Clarifying phrases were used frequently in the frozen section report, and these terms were categorized as "rule out" borderline tumor, borderline tumor, and "at least" borderline tumor. Of 33 cases with a frozen section report of borderline or at least borderline malignancy, no case were subsequently found to be benign. Errors in the intraoperative management could have occurred in 3 of 48 cases (6.25%), when benign neoplasms were thought to be of borderline malignancy on frozen section. However, in each of these cases, the clarifying term rule out was used, indicating the equivocal nature of the frozen section findings. Thirteen of the 48 patients (27.1%) were found to have a focus of invasive cancer within a borderline tumor on final pathologic review; the primary tumors in these 13 cases ranged in maximal diameter from 5 to 26 cm and were of varying histologic types. The level of experience of the pathologist responsible for the frozen section did not influence the accuracy of frozen section determination noted in this study. A frozen section evaluation identifying a borderline ovarian malignancy is accurate in excluding the presence of benign pathology. It is crucial to understand the meaning of specific clarifying terms used in frozen section diagnoses.

Adult↗

Sensitivity of frozen section examination of pelvic lymph nodes for metastatic prostate carcinoma.

BACKGROUND: A Total Quality Improvement review of frozen section diagnoses yielded four sequential false-negative frozen section diagnoses in lymph nodes in the evaluation of metastases from prostate carcinoma. Because these results appeared to differ from the department's overall frozen section experience, frozen section diagnoses of pelvic lymph nodes in patients with prostate carcinoma were reviewed to benchmark the department's performance. METHODS: All 220 pelvic lymph node frozen section samples from 110 patients with prostate carcinoma from January, 1986 to July, 1993 at Bridgeport Hospital (BH) were reviewed, and the department's frozen section diagnostic efficiency was compared with: (1) all BH frozen section procedures performed during the same period; (2) pelvic lymph node frozen section analysis and (3) imaging techniques for prostate carcinoma from other institutions found in MEDLARS literature searches from 1973 to 1993. RESULTS: Frozen section diagnostic efficiency for patients with prostate carcinoma from BH was 93.6% (sensitivity 63.2%, specificity 100%) compared with (1) 98% for all BH frozen section analyses (sensitivity 99%, specificity 98%); (2) 90.1% for MEDLARS search pelvic lymph node frozen section prostate carcinoma analyses (sensitivity 66.5%, specificity 100%); and (3) 88% for MEDLARS search magnetic resonance imaging (MRI) pelvic lymph node prostate carcinoma (sensitivity 41%, specificity 97%). CONCLUSIONS: Frozen section diagnosis of pelvic lymph nodes approaches the overall diagnostic efficiency of frozen section analysis and is more sensitive for the diagnosis of prostate carcinoma in pelvic lymph nodes than is MRI because more than half of the metastases are smaller than the 1.0-cm resolution limit of the MRI. False-negative frozen section diagnoses (67% sensitivity) occur because of errors in sampling microscopic metastases.

Adenocarcinoma↗

Does frozen section have a role in the intraoperative management of thyroid nodules?

BACKGROUND: Frozen section in thyroid surgery is used to make an intraoperative pathological diagnosis of malignancy in a thyroid nodule at the time of hemithyroidectomy. A positive diagnosis allows completion of thyroidectomy, thus avoiding reoperation. However, the use of fine needle aspiration cytology in making a preoperative diagnosis of cancer has resulted in the lack of a defined role for frozen section. We examined the role of frozen section as an adjunct to fine needle aspiration cytology in determining which cytological subset will benefit from frozen section. METHODS: All patients who underwent thyroidectomy between 1992 and 2000 by a single endocrine surgeon were reviewed. RESULTS: Two hundred and nine frozen sections were performed, of which 144 underwent preoperative fine needle aspiration cytology. Frozen sections reported 135 benign nodules, 59 follicular neoplasms, five specimens with suspicious histology and 10 cancers. Ten out of 20 thyroid cancers were correctly identified by frozen section (sensitivity: 50%; specificity: 100%), eight cancers were reported on frozen section as indeterminate and two benign. Of 144 fine needle aspiration cytological procedures, frozen section on seven suspicious aspirates identified two cancers, and frozen section on 70 follicular aspirates identified four cancers, allowing intraoperative conversions to total thyroidectomy. Frozen section on seven malignant aspirates confirmed four cancers but resulted in reoperation for three because of the indeterminate frozen section reports. There were no cancers found on 135 benign aspirates. CONCLUSIONS: Frozen section on benign aspirates is unhelpful in the management of thyroid nodules. It need not be performed for cytologically proven malignant thyroid nodules. Selective use of frozen section complements fine needle aspiration cytology findings of suspicious or follicular lesions, especially in the subset with papillary cancer, allowing one-stage total thyroidectomy.

Adolescent↗

Discrepancies in frozen section mucosal margin tissue in laryngeal squamous cell carcinoma.

BACKGROUND: Head and neck surgeons commonly request frozen sections. Practice patterns vary from laboratory to laboratory on how the tissue is used in performing the frozen section. Some pathologists wish to see all the material submitted by consuming it completely during frozen section, whereas others reserve some for permanent section. We wished to determine whether knowledge of margin status was initially inaccurate because of reserving tissue for permanent section. METHODS: Sixty-five laryngectomies (total and partial) with margin assessment enhanced by frozen section evaluation were studied. Forty-five laryngectomy specimens, generating 249 frozen sections in which a permanent section was prepared from tissue remaining from frozen section examination, were studied. RESULTS: Five of the 249 frozen sections contained a discrepancy between the frozen section and permanent section because of insufficient leveling of the frozen section block. These five discrepancies were called negative on frozen section, but permanent section revealed dysplasia (two cases of mild dysplasia, one case with moderate dysplasia, and one case with severe dysplasia) or carcinoma in situ (one case). Twenty laryngectomies in which the frozen section tissue was consumed at the time of frozen section generated 103 frozen sections. In eight of the frozen sections involving six cases, the diagnostic tissue was not present on one or two of the frozen section levels examined. CONCLUSIONS: We conclude that in examining margins for laryngeal squamous cell carcinoma the frozen section tissue should be completely sampled by examining several levels at the time of frozen section. This requires consuming or exhausting the frozen section tissue rather than reserving any remaining frozen tissue for a paraffin-embedded permanent section.

Carcinoma, Squamous Cell↗

Local ampullary resection with careful intraoperative frozen section evaluation for presumed benign ampullary neoplasms.

BACKGROUND: Frozen section evaluation has been reported to be inaccurate in detecting foci of adenocarcinoma within adenomas of the ampulla of Vater, leading many authors to advocate pancreaticoduodenectomy as the method of treatment for these neoplasms. The authors hypothesized that (1) ampullary resection is less morbid than pancreaticoduodenectomy, and (2) frozen section evaluation following ampullary resection is accurate and allows for a selective application of pancreaticoduodenectomy to those with carcinoma or benign lesions too large to be locally resected. METHODS: A retrospective review of a single-surgeon experience was conducted. Thirty-eight patients who underwent ampullary resection and pancreaticoduodenectomy (39 procedures) for benign and malignant ampullary neoplasms were identified. Our technique of step-frozen section analysis is described. RESULTS: Twenty-one ampullary resections were performed for preoperative diagnoses of benign (16) and malignant (5) ampullary neoplasms. Frozen section evaluation accurately predicted the final histology in all patients undergoing ampullary resection. Ampullary resection (vs pancreaticoduodenectomy) was associated with a statistically lower operative time (169 minutes vs 268 minutes), estimated blood loss (192 mL vs 727 mL), mean length of stay (10 days vs 25 days), and overall morbidity (29% vs 78%). CONCLUSIONS: Frozen section evaluation of ampullary neoplasms is accurate. Because ampullary resection is less morbid than pancreaticoduodenectomy and frozen section evaluation is accurate, ampullary resection with frozen section evaluation is our current approach to the treatment of small benign ampullary neoplasms.

Adenocarcinoma↗

Origin of artifactual quantitation of electrolytes in microprobe analysis of frozen sections of erythrocytes.

Frozen sections of erythrocytes have been used to validate microprobe X-ray analysis of diffusible elements in biological samples. At this meeting last year we reported that intracellular Na concentrations measured by microprobe were much higher than those measured by bulk chemical methods. It was suggested that this might be due to the movement of extracellular material over the cells by microtomy. We now present evidence that such results are better explained by electron scattering within the sample during analysis. This evidence includes observations that the excess measured Na varies directly with section thickness and inversely with accelerating voltage. At 80 kV accelerating voltage there is excellent agreement between microprobe and chemical analysis. It may be concluded that specimen preparation techniques such as used in our laboratory are satisfactory for reliably localizing diffusible elements in small volumes, but that instrumental factors can seriously affect their quantitation.

Electron Probe Microanalysis↗

Rapid frozen section in pediatric pathology.

Frozen section examination in pediatrics differs from that in adult practice in two ways. First, there is a high proportion of undifferentiated small-cell cancers in which it it difficult to make a definitive diagnosis without additional information. Second, there are special categories of congenital disorders where one is seeking not neoplasia but the presence, absence, or size of normal structures. In 520 pediatric frozen sections, there was a comparatively high incidence of deferred (5.6%) or inaccurate diagnoses (3.5%). However, as there were 99 small-cell cancers, it is perhaps surprising that the number was not greater. In the nervous system (208 cases), it was sometimes difficult to distinguish between malignant ependymoma and medulloblastoma. In other neoplasms, e.g., soft tissues and bone, the most important requirement was adequate clinical and radiological information. In Hirschsprung's disease (132 cases), ganglion cell detection was 100% accurate. In measuring the diameter of bile ducts in the porta hepatis during surgery for biliary atresia (18 cases), it was sometimes difficult to recognize ducts that had lost their epithelial lining.

Bile Duct Diseases↗

Value of routine frozen section diagnosis of thyroid lesions.

OBJECTIVE: The value of routine frozen section examination for intraoperative diagnosis of thyroid cancer is controversial and needs to be evaluated on an institution to institution basis. This paper highlights the local experience with frozen section and analyses its role, accuracy and limitation in diagnosing thyroid cancer. METHODS: A retrospective study of 61 patients who underwent thyroidectomy with routine thyroid frozen section examination at King Fahd Hospital of the University, Al-Khobar, Kingdom of Saudi Arabia. Results were compared with the final diagnosis to evaluate its effectiveness in predicting malignancy. RESULTS: Frozen section diagnosis, proved to be benign in 44 (72%) specimens, malignant in 10 (16%) and the diagnosis deferred in 7 (11.5%) patients. After examination of the permanent sections of the specimens, 15 (28%) were found to be malignant including 3 (43%) out of 7 deferred cases. With an overall accuracy of >90% and a specificity of 100%, the sensitivity of frozen section diagnosis remains low. Only 60% of papillary carcinoma and 25% of follicular carcinoma were correctly diagnosed on frozen section. The low rate of diagnosis of follicular carcinoma is due to its encapsulated and minimally invasive nature. CONCLUSION: The inability to diagnose follicular carcinoma intraoperatively with frozen section is the most significant factor accounting for the relatively low sensitivity of frozen section diagnosis of thyroid malignant neoplasm. In our institution, frozen section is considered a complementary investigation to emerging fine needle cytopathology in the region.

Adenocarcinoma, Follicular↗