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Frozen section- frozen attitudes.

Patients with breast cancer who have clinically negative axillae, tumors 2 cm in diameter or less, and tumors with a moderate or low degree of anaplasticity are candidates for treatment by local excision and irradiation. A definitive histologic diagnosis should be made in all cases of breast cancer before a final treatment decision is made. This can be accomplished by needle or excisional biopsy. After a histologic diagnosis is established, the decision regarding treatment can be arrived at with the patient enering into the process. Those patients requiring mastectomy will be better able to cope with this, knowing why the operation was considered best for them. The elimination of frozen section diagnosis will free the patient from one of the great fears of the current treatment of breast cancer- subjecting herself to biopsy without knowing what the outcome will be. It will free the surgeon from the rigid sequence of frozen section followed by mastectomy and allow him to begin to rationally assign patients with proper criteria to conservative treatment, reserving mastectomy for those who do not meet these criteria.

Adult

In situ visualization of hemopoietic cell subsets and stromal elements in rat and mouse bone marrow by immunostaining of frozen sections.

We have developed a method to section frozen long bones of rat and mouse and stained bone marrow (BM) by (double) immunofluorescence and immunoperoxidase. Here we report this method and reveal the location of early hemopoietic progenitors (Thy-1) and myeloid cells (Mac-1) in mouse BM, and early hemopoietic progenitors and lymphoid cells (Thy-1), erythroid cells (HIS49), and macrophages (ED2) in rat BM. In mouse BM our new findings include (a) the scattered localization of early hemopoietic progenitors (Thy-1low) all over the marrow, and (b) the presence of Thy-1+ stromal cells, mainly subendosteally. In rat BM an important finding is that of (a) a subendosteal region of 12-14 hemopoietic cell layers characterized by an abundance of Thy-1 and the virtual absence of erythroid cells, and (b) the scattering of Thy-1very bright cells which are candidates for the earliest hemopoietic progenitors in this species. The results illustrate that the technique is an excellent tool for studying the topology of BM as an organ of hemopoiesis.

Animals

Evaluating cervical cone biopsy specimens with frozen sections at hysterectomy.

Frozen section evaluations of cervical cone biopsy specimens were performed at the time of hysterectomy to exclude invasive cervical cancer. During a two-year period we prospectively evaluated 43 cone biopsy specimens. We found all the diagnoses made with frozen sections to be accurate when compared with prospective permanent sections, and all patients received appropriate therapy. Thirty-eight cases showed no evidence of invasion. Two patients had invasive squamous cell cervical cancer, one had invasive cervical adenocarcinoma extending to the endometrial cavity, and two had microinvasion. All invasive cancers were diagnosed correctly with frozen sections and confirmed with permanent sections. When hysterectomy immediately followed conization, no complications occurred, and no significant increase in blood loss was noted. We found frozen section evaluation of a cone biopsy specimen at the time of hysterectomy to be a reliable procedure that saves time, eliminates the risk of additional anesthesia and decreases patients' costs.

Adult

Renal biopsy frozen section: a fluorescent study of hematoxylin and eosin-stained sections.

When frozen sections of kidney are stained with hematoxylin and eosin (H&E) and viewed by standard fluorescence microscopy, crisp detail of nephron and vascular basement membranes is revealed. We studied by H&E fluorescence, control kidneys, and 85 renal biopsies which span a broad range of renal disease. We found that H&E fluorescence provides useful initial orientation by revealing the presence of cortex or medulla and number of glomeruli and vessels. It also reveals major structural alterations of nephron and vascular basement membranes (sclerosis, disruption, atrophy) and heavy deposition of abnormal material (fibrin, immune deposits, paraprotein). When coupled with direct immunofluorescence, a much greater understanding of the disease process is possible, prior to review of permanent sections.

Benzopyrans

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

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

The accuracy of frozen section diagnosis of ovarian tumors.

We compared all frozen section examinations of ovarian tumors during a 6-year period in our institute with the final diagnosis from paraffin sections. In this period, 946 ovarian tumor specimens were removed for histologic assessment; 176 (18.6%) had frozen section examination. Final histological diagnosis was divided into benign (55.1%), borderline malignant (10.3%), and malignant (34.6%). Sensitivity of the frozen section method for malignant or borderline disease was 83.5% and specificity for a benign lesion, 92.8%. Predictive values and 95% confidence intervals were computed: 100% (93-100%) for malignancy, 62% (32-86%) for borderline malignancy, and 92% (85-96%) for a benign disease. Diagnostic problems occurred in large borderline tumors of mucinous cell type. Analysis of the 12 false negative diagnoses revealed that a sampling error was involved in 11 cases. A judgment error was made in the only false positive and in 1 out of 12 false negative frozen section diagnoses. It is concluded that when surgeons and pathologists are aware of the limitations of frozen section diagnosis of ovarian tumors, peroperative histologic examination can be worthwhile and prevent under- and overtreatment of gynecologic patients.

Adolescent

Oestrogen receptor staining of paraffin-embedded breast carcinomas following short fixation in formalin: a comparison with cytosolic and frozen section receptor analyses.

This paper describes an improved immunohistochemical method for demonstrating oestrogen receptor (OR) protein in paraffin-embedded sections of tissue fixed for 1.5 h in formalin. Thirty-two cases of infiltrating ductal breast carcinoma were stained with a monoclonal anti-OR antibody (H222), using a standard streptavidin-biotin method, following pretreatment with pronase. OR counts in paraffin sections were compared with those of frozen sections and with cytosolic values determined by a dextran-coated charcoal method. Twenty-seven of the carcinomas were OR-positive in paraffin sections. There was concordance between the paraffin section and the frozen section-determined receptor status in 30 cases (94 per cent) and a strong correlation was observed (r = 0.76; P less than 0.0001). Similarly, OR counts in paraffin sections correlated with cytosolic OR values (r = 0.60; P less than 0.001) and there was concordance in 97 per cent of cases. The percentage of positively-stained tumour cells in paraffin sections ranged from 0 to 94 per cent with staining intensities comparable to those seen in frozen sections. Staining of paraffin sections identified more OR-positive tumours than either frozen section staining or cytosolic assay. This study validates immunohistochemical OR analysis in formalin-fixed, paraffin-embedded breast carcinomas using a commercial anti-OR antibody.

Adult

The accuracy of frozen section in the diagnosis of ovarian neoplasms.

In a retrospective study to determine the accuracy of frozen section diagnoses in ovarian neoplasms, the results of consecutive frozen section diagnoses of 311 ovarian neoplasms from two institutions, New York University Medical Center and State University of New York Medical Center at Brooklyn, from 1980 through 1989 were compared with the final diagnosis results following extensive sampling on permanent sections. The final diagnosis was assumed to be correct for purposes of this study. Ovarian neoplasms were correctly diagnosed on frozen section as either benign or malignant in 292 patients (accuracy of 93.8%). Frozen section diagnoses were incorrect in 11 patients (3.5%). Frozen section diagnosis was deferred in 8 instances (2.6%). The positive predictive value was 100%. The negative predictive value was 95.3%, specificity 100%, and sensitivity 86%. There were no false positives. Of the 11 false negative frozen section diagnoses, 9 (82%) were due to limited sampling for frozen section. We therefore suggest that careful examination with sampling of any suspicious lesions be carried out at the time of surgery for patients with benign frozen section diagnosis, since this may avoid a second staging laparotomy, if the final diagnosis is malignant.

Carcinoma, Squamous Cell

Accuracy and pitfalls of frozen section during thyroid surgery.

The purpose of this study was to assess the accuracy of frozen sections performed during thyroid surgery and to define any pitfalls they may have. The material includes a series of 190 frozen section examinations of thyroid pathology. The overall accuracy of frozen section in this series was 95%. There were no false positives in our series and false negatives related to only follicular adenomas. In two patients, the report was deferred for permanent slide examination. Nine patients had lesions reported as malignant; however, the distinct cell type was not designated on frozen section. Eight specimens initially reported to have follicular adenoma on frozen section turned out to have angioinvasion or capsular invasion indicative of follicular carcinoma. Minor discrepancies between frozen and permanent sections in the types of benign disease were noted occasionally, but were not clinically significant. There was a discrepancy in the diagnosis of Hashimoto's thyroiditis on three occasions. The major discrepancy in patients with malignant pathology was related to the cell type. The diagnosis of anaplastic thyroid cancer, though suspected, was deferred for permanent sections in all cases. The diagnosis of medullary cancer of thyroid was difficult to make on frozen section. The major problem with frozen section was the diagnosis of follicular adenoma versus carcinoma. The benign diagnosis was changed in eight instances (out of 24 frozen sections) from follicular ademona to follicular carcinoma. Because of this experience, we do not provide the frozen section diagnosis to the patient and we wait until the final diagnosis is available.

Adenocarcinoma

Utility of frozen-section evaluation of lymph nodes in the staging of bronchogenic carcinoma at mediastinoscopy and thoracotomy.

We conducted a retrospective analysis of the utility of frozen-section diagnoses in determining lymph node status at mediastinoscopy in 122 consecutive patients with bronchogenic carcinoma. Thirty-five of 122 patients had one or more lymph nodes with frozen-section evaluation positive for metastatic carcinoma. Subsequent nodal sections not in the original frozen-section study revealed metastatic carcinoma in two additional patients. The false-negative rate was 1.6%. Sensitivity was 94.6%. Predictive value of negative frozen-section evaluation results was 97.7%. Because there were no false-positive frozen-section results, specificity and predictive value for positive results of frozen-section evaluation were 100%. The statuses of individual lymph nodes from these 122 patients were also evaluated. Six hundred twenty lymph nodes were sampled from the mediastinum at mediastinoscopy. Frozen-sections in 47 lymph nodes were positive. Subsequent nodal sections not in the original frozen-sections examination revealed metastatic carcinoma in four additional lymph nodes. The false-negative rate was 0.6%. Sensitivity was 92.2%. Predictive value of negative results from frozen-section evaluation was 99.3%. Because there were no false-positive frozen-section results, specificity and predictive value for positive results of frozen-section examination were 100%. We conclude that frozen-section evaluation of lymph nodes at mediastinoscopy reliably indicates lymph node status, thus enabling the physician to decide whether to proceed to thoracotomy. Thus staging of the carcinoma and definitive surgery can be accomplished during a single anesthetic procedure. Combining mediastinoscopy and thoracotomy with frozen-section diagnostic control also reduces both the length and cost of hospitalization.

Biopsy

Frozen section diagnosis of breast lesions. Recent experience with 556 consecutive biopsies.

Experiences with frozen sections performed on 556 consecutive breast biopsies were reviewed. There were no false positive reports among the 145 (26%) lesions interpreted as carcinoma. Among 381 (68.6%) biopsies in which no carcinoma was found on frozen section, eight proved to contain carcinoma in other areas. Seven of the false negatives contained noninvasive carcinoma (six--in situ lobular; 1--intraductal). A small infiltrating lesion was found in the eighth case. The diagnosis was deferred to paraffin section in 30 (5.4%) of biopsies. Ten lesions proved to be noninvasive carcinoma and one was an infiltrating lobular carcinoma. Frozen section diagnosis is a highly reliable procedure for the diagnosis of infiltrating breast carcinoma. Noninvasive carcinoma may be overlooked at frozen section because of the limitations of sampling. Consequently, patients should be cautioned to await the paraffin section report if the frozen section does not reveal carcinoma. A frozen section diagnosis of carcinoma does not necessarily commit the surgeon to further surgery at that time and the information obtained from the frozen section may be helpful in beginning to plan further treatment with the patient.

Biopsy

Accuracy of frozen section diagnosis of parotid lesions.

The accuracy of frozen section diagnosis was analyzed in a review of 132 parotid lesions. Of 107 benign lesions, 93% were correctly diagnosed on frozen section analysis, but of 25 malignant lesions, only 9 frozen sections were accurately interpreted. This study points out the difficulty encountered in using the frozen section technique when dealing with malignant parotid lesions and the importance of the surgeon's active participation in the analysis.

Biopsy

Imprints, smears, and frozen sections of brain tumors.

In this study, we compared the suitability and accuracy of imprints, smears, and frozen sections of suspected brain and spinal cord tumors of 150 patients. Eighty-six percent of the imprints, 91% of the smears, and 99% of the frozen sections were suitable for interpretation. Among the suitable preparations, 82% of the imprints, 92% of the smears, and 99% of the frozen sections agreed with our diagnosis on paraffin sections. Although frozen sections were clearly more accurate than imprints and smears, the latter two provided diagnoses in patients with acquired immunodeficiency syndrome where frozen sections were not done to avoid contaminating our cryostat and in a patient with an epidermoid cyst of the middle fossa that could not be adequately frozen sectioned. Our study shows that imprints and smears complement frozen sections in the intraoperative diagnosis of tumors of the central nervous system.

Biopsy

Use of aspiration cytology and frozen section examination for management of benign and malignant thyroid nodules.

Between January 1980 and December 1988, 161 patients underwent thyroidectomy with intraoperative frozen section consultation after fine-needle aspiration (FNA) of a thyroid nodule. The FNA were insufficient in 15 instances (9%) and in error in 39 (24%). In 15 cases, the incorrect aspiration diagnosis could have led to excessive surgery and in ten cases to delayed therapy if it had been the only guide for therapy. The diagnosis was deferred to permanent section analysis in 30 (19%) frozen sections. Twenty-two errors (14% of cases) were made in the interpretation of frozen section material, and in an additional 15 patients (9%), the diagnosis suggested (but deferred at frozen section) was in error. In one patient, this error could have led to more extensive surgery than necessary; in 21 patients, the frozen section error could have led to undertreatment. When frozen section results were combined with those of FNA, no therapeutically important false-positive diagnoses were made. In five patients, the combination of both FNA and frozen section results would not have identified a carcinoma which, in three cases, was a small occult papillary carcinoma not found in the index nodule.

Adenoma

Studies on the interaction and exchange of inhibitors and proteases on the surface of tumour cells in frozen sections.

We have used frozen sections of squamous cell carcinoma as a convenient source of a cell surface protease associated with tumour cells. This protease has been referred to as guanidinobenzoatase (GB) and is now known to be functionally identical to tissue plasminogen activator (t-PA). The use of a fluorescent competitive inhibitor of GB enabled the enzymic status of GB to be determined, i.e. was the enzyme active, latent or removed from our test system. The cell surface GB was then demonstrated to interact with extractable cytoplasmic inhibitors obtained from these sections. We then used a protected form of the GB in the absence of these internal inhibitors; such sections were used to transfer the GB to fibrin fibrils, thus exposing the presumptive receptor on the tumour cell surfaces. Texas red labelled t-PA was then shown to bind to the tumour cells in these pretreated sections from which the GB had previously been removed. We believe that the surface of tumour cells can be used to study the interaction of the naturally occurring inhibitors with GB and also that the cell surface receptors for GB can be used to study the binding of t-PA to cell surfaces.

Aminacrine

Interinstitutional comparison of frozen-section consultation. A College of American Pathologists Q-Probe study of 79,647 consultations in 297 North American institutions.

In 1989, the College of American Pathologists Q-Probes Quality Assurance Program studied intraoperative frozen-section consultations performed in 297 institutions with mean bed size of 316 (range, 0 to 1351 beds) in North America during 5 consecutive months. The aggregate database was composed of 933,751 surgical cases (mean, 3144 per institution); 52,464 frozen-section cases (mean, 177); and 79,647 individual frozen sections performed (mean, 268). The rate of frozen sections per all surgical case accessions was 5.6% (cases with frozen section) and 7.3% (individual frozen sections performed), with an average of 1.5 frozen sections per case. Frozen-section rate increased proportional to bed size, from less than 5% in institutions with bed size below 150 to 15% in institutions with bed size above 600. Of all frozen sections performed, 4.2% were deferred. Deferrals to paraffin sections in pathologists' opinions were 92.6% appropriate, 1.2% inappropriate, and 6.2% not stated. When frozen-section diagnoses were compared with permanent section diagnoses, there was a 98.3% diagnostic concordance, adjusted for deferred diagnoses, but including the performance of frozen sections on mammographically directed biopsy specimens with no gross abnormalities in 80% of institutions. This practice accounted for 11.8% of the discordant frozen-section diagnoses. The reasons for diagnostic discordances were gross tissue sampling (44.8%); misinterpretation (40%); sectioning (12.7%); inadequate history (5.6%); staining (1.5%); labeling (0.5%); and other (3%). Assessment of diagnostic discordance on patient outcomes by the reviewing pathologist showed that patient management was unaffected in 74%, minimally affected in 20%, and greatly affected in 2.5%.

Biopsy

Use of frozen section analysis in the treatment of basal cell carcinoma.

Frozen section margin verification has been used in the treatment of basal cell carcinoma at our institution for the past 13 years. A review of the last 450 cases has shown frozen section to be most helpful in treating recurrent tumors where microscopic tumor foci extend beyond clinical margins in 45% of cases. Frozen section analysis may be of value in selected patients with primary tumors, but its routine use is not indicated for the majority of these lesions, since complete excision is possible without relying on frozen section in 90% of cases.

Basal Cell Carcinoma