Objective: The aim of this work is to compare between intraoperative frozen section and scrape smear cytology in the diagnosis of ovarian neoplasm. Method: This study was performed between March 2011 and March 2012, on 50 patients presented with ovarian mass. Gross examination of the tumor removed was done by inspection and palpation. The specimen was then cut with a sharp knife into two halves. The area was scraped with a sharp scalpel or the end of a glass slide, depending upon the type of tissue. A semifluid drop thus obtained was spread over a glass slide. One to four slides per case were taken from different representative areas. The slides were labelled and immediately put into 95% ethyl alcohol and stained with hematoxylin-eosin. The specimens were then fixed in formalin. Paraffin blocks of the sections were processed in the routine way and sections were stained with hematoxylin and eosin (H and E). Assessment of the overall accuracy of the intraoperative diagnosis was classified as concordant or discordant. Results: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of scraping technique in the diagnosis of benign ovarian masses were 100%, 95.2%, 96.7%, 100% and 98% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of scraping technique in the diagnosis of border line ovarian masses were 100%, 93.4%, 25%, 100% and 94% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of scraping technique in the diagnosis of malignant ovarian masses were 80%, 100%, 100%, 88.2% and 92% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of frozen section in the diagnosis of benign ovarian masses were 100%, 100%, 100%, 100% and 100% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of frozen section in the diagnosis of borderline ovarian masses were 100%, 95.9%, 33.3%, 100% and 96% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of frozen section in the diagnosis of malignant ovarian masses were 90%, 100%, 100%, 93.8% and 96% respectively. Conclusion: Frozen section is more accurate than smear preparations in the intraoperative assessment of ovarian tumors in this study. However, the cytology preparations were helpful in supporting the histological diagnoses, and in some cases, provided additional useful information. Thus, cytology has a complementary role to frozen section in the intraoperative assessment of ovarian lesions. At the centers where the facilities of frozen section are not available, intraoperative scrape cytology is a useful tool for intraoperative diagnosis of tumor.
Ovarian neoplasms are a heterogeneous group of benign and malignant tumors of epithelial, stromal and germ- cell origin. Histopathology of a paraffin section remains the ultimate gold standard in tissue diagnosis [
Rapid diagnosis of surgically removed specimens has created many controversies and a single completely reliable method has not yet been developed. Frozen section is routinely used by the surgical pathology laboratories for intra-operative diagnosis [
Intra-operative cytology has high accuracy rates, excellent preservation of cellular details, and the possibility of identifying focal, macroscopically undetectable neoplastic lesion in large tissue fragments. The method is simple and inexpensive, not requiring special technique or instrument. The disadvantages of intraoperative cytology are very few and high accuracy rates can be achieved with experience. It is though not possible to distinguish in situ from infiltrating carcinoma and to evaluate the depth of invasion and/or margins of resection. Thus, apart from its diagnostic role, intraoperative cytology can become a very useful learning tool [
Scrape smear cytology is a modification of imprint cytology in which cells are harvested by scraping the cut surface of the specimen. It is an economical, simple and quick method of intra-operative diagnosis with acceptable sensitivity and high specificity, and does not alter the utility of the specimen for subsequent histopathology examination [
The aim of this work is to compare between intra-operative frozen section and scrape smear cytology in the diagnosis of ovarian neoplasm in Zagazig University Hospital.
This study was performed between March 2011 and March 2012, on 50 patients presented with ovarian mass recruited from the gynecology outpatient clinic. Patients with the following criteria were included: 1) clinically benign looking tumors (on preoperative radiology or intraoperative inspection) with raised CA 125; 2) adnexal mass in a patient with a past history of malignancy at another site; 3) young patients with ovarian neoplasms in whom fertility sparing surgery was planned; and 4) adnexal mass in any perimenopausal women.
The following was done for all selected patients: full history; full clinical examination and measurement of serum CA 125. The preoperative data studded were patient age, rapid weight loss, clinical examination, available imaging studies either ultrasonography, Computerized Tomography or both, level of the available tumor marker such as serum CA 125).
Patients with benign-appearing tumors at surgery underwent either cystectomy or salpingo-oophorectomy, depending on patient sand tumor characteristics. Patients with suspicious ovarian tumors underwent salpingo- oophorectomy. The intraoperative findings studded were presence of ascitis, adhesions to the adjacent structures, bilaterality, tumor implants on peritoneal surface, lymph node enlargement and gross picture of the tumor (e.g. tumor diameters, consistency, outer surface, cut surface, presence of necrotic areas and papillary structures within the cyst ).
The unfixed fresh specimen of the tumor was immediately delivered to Pathology Department―Faculty of Medicine―Zagazig University―with all the clinical details of the patient for evaluation. Gross examination of the tumor removed was done by inspection, palpation, The specimen was then cut with a sharp knife into two halves. The cut surface was wiped off the excess blood, if present, with the help of a filter paper. Again, reinspection and repalpation of the tumor was done. The most appropriate area thought to be representative of lesion was chosen.
The area was scraped with a sharp scalpel or the end of a glass slide, depending upon the type of tissue. A semifluid drop thus obtained was spread over a glass slide. One to four slides per case were taken from different representative areas. The slides were labelled and immediately put into 95% ethyl alcohol and stained with hematoxylin-eosin, then frozen sections was obtained from the same areas of the scraping.
The specimens were then fixed in formalin. Sections were taken from the same area from where scrapings were taken. Paraffin blocks of the sections were processed in the routine way and sections were stained with hematoxylin and eosin (H and E).
All the sections studied microscopically under low and high power and categorized according to the status of malignancy into benign, borderline and malignant tumor.
The diagnosis obtained by intraoperative scrape and frozen section based on cellularity and cell morphology were compared with final histopathological diagnosis in terms of diagnostic sensitivity, to differentiate between benign and malignant lesions.
Assessment of the overall accuracy of the intraoperative diagnosis was classified as follows:
・ Concordant. In these cases, the diagnosis was correct with regard to the major tumor category (benign, borderline, or malignant) and, in the case of malignant neoplasms, to tumor origin (primary vs metastatic).
・ Discordant. These were cases in which incorrect or equivocal assessment could have adversely affected intraoperative management, including the failure to identify the principle diagnostic category of surface epithelial tumors (benign, borderline, or malignant) or inaccuracy regarding the origin of malignant neoplasms (primary vs metastatic). Cases in which the major histological category of primary ovarian malignancy (carcinoma, sex cord stromal tumor, and germ cell tumor) was not recognized were also considered discordant because the optimal operative management of these cases may differ, particularly in the younger age group.
Statistical analysis was performed using STATA 11.0 (College Station, Texas, USA). Data were presented as a number (%) or mean ± standard deviation (SD)/median (range). The differences in Mean/Median values were measured by using Student’s t-test (normal data distribution)/Wilcoxon Ranksum Test (for categorical variables). p < 0.05 was considered to be statistically significant.
The study was approved by Zagazig University Medical Research Council Laboratories Joint Ethics Committee. All participants signed an informed consent. Rigorous confidentiality was maintained.
Different types of ovarian masses (benign, bordreline and malignant) shows statistical significant correlation with the age of the patient (p value: 0.03) while there is no significant association between parity and different types of ovarian masses (p value: 0.25) (
The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of scraping technique in the diagnosis of benign ovarian masses were 100%, 95.2%, 96.7%, 100% and 98% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of scraping technique in the diagnosis of border line ovarian masses were 100%, 93.4%, 25%, 100% and 94% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of scraping technique in the diagnosis of malignant ovarian masses were 80%, 100%, 100%, 88.2% and 92% respectively.
Benign (n = 29) | Borderline (n = 1) | Malignant (n = 20) | F | p | |
---|---|---|---|---|---|
Age (years) | |||||
Mean ± SD | 36.5 ± 17.7 | 43 ± 0 | 48.9 ± 12.7 | 3.57 | 0.03 |
Range | 11 - 70 | 19 - 77 | |||
Parity | |||||
0 | 13 (44.8%) | 1 (100%) | 6 (30%) | X2 = 5.06 | 0.28 |
1 - 3 | 7 (24.1%) | 0 (0%) | 10 (50%) | ||
> 3 | 9 (31%) | 0 (0%) | 4 (20%) |
Benign | Borderline | Malignant | X2 | p | ||||
---|---|---|---|---|---|---|---|---|
No | % | No | % | No | % | |||
Clinical | 21 | 42.0 | 0 | 0.0 | 29 | 58.0 | 0.04 | 0.8 |
Macroscopic and intraoperative picture | 20 | 40.0 | 0 | 0.0 | 30 | 60.0 | ||
Laterality | ||||||||
Unilateral | 20 | 69.0 | 1 | 100.0 | 6 | 30.0 | 8.1 | 0.017 |
Bilateral | 9 | 31.0 | 0 | 0.0 | 14 | 70.0 |
N B: | (%) | Number of cases | Histologic type |
---|---|---|---|
*3/8 complicated *5/8 noncomplicated *1/8 bilateral *1/3 complicated *2/3 non complicated *1/3 bilateral Unilateral | 16% 6% 2% | 8 cases 3 cases 1 case | A. Epithelial tumors: *Benign: Serous Mucinous Brenner. |
*4/12 Serouscyst adenoarcinoma, 3/4 bilateral. *8/12 papillary Serouscyst adenoarcinoma,6/8 bilat *3/6 bilateral | 24% 12% | 12 case 6 cases | *Malignant. Serouscyst adenoarcinoma Endometrioid adenocarinoma |
Unilat Unilat | 8% 2% | 4 cases 1 case | B. Sex-cord stromal neoplasm: Fibrothecoma Fibroma |
2/5 bilateral 1/2 bilateral | 10% 4% | 5 cases 2 cases | C. Germcell neoplasm: Teratoma Dysgerminoma. |
Bilateral | 2% | 1 case | D. Metastatic (Krukenberg): |
4/5 bilateral 1 non specific. 1 TB granuloma (bilateral) | 10% 4% | 5 cases 2 cases | E. Others: Endometrioti cyst Inflammatory cyst |
The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of frozen section in the diagnosis of benign ovarian masses were 100%, 100%, 100%, 100% and 100% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of frozen section in the diagnosis of borderline ovarian masses were 100%, 95.9%, 33.3%, 100% and 96% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of frozen section in the diagnosis of malignant ovarian masses were 90%, 100%, 100%, 93.8% and 96% respectively (Tables 4-7).
Paraffin section | Total | |||
---|---|---|---|---|
Benign | Borderline | Malignant | ||
Scraping | ||||
Benign | 29 | 0 | 1 | 30 |
Borderline | 0 | 1 | 3 | 4 |
Malignant | 0 | 0 | 16 | 16 |
Total | 29 | 1 | 20 | 50 |
Benign | Borderline | Malignant | |
---|---|---|---|
Sensitivity | 100.0 | 100.0 | 80.0 |
Specificity | 95.2 | 93.9 | 100.0 |
Positive predictive value | 96.7 | 25.0 | 100.0 |
Negative predictive value | 100.0 | 100.0 | 88.2 |
Accuracy | 98.0 | 94.0 | 92.0 |
Paraffin section | Total | |||
---|---|---|---|---|
Benign | Borderline | Malignant | ||
Frozen section | ||||
Benign | 29 | 0 | 0 | 29 |
Borderline | 0 | 1 | 2 | 3 |
Malignant | 0 | 0 | 18 | 18 |
Total | 29 | 1 | 20 | 50 |
Benign | Borderline | Malignant | |
---|---|---|---|
Sensitivity | 100.0 | 100.0 | 90.0 |
Specificity | 100.0 | 95.9 | 100.0 |
Positive predictive value | 100.0 | 33.3 | 100.0 |
Negative predictive value | 100.0 | 100.0 | 93.8 |
Accuracy | 100.0 | 96.0 | 96.0 |
Rapid intra-operative diagnosis of the nature of ovarian tumors is both interesting and challenging for effective planning of the surgical management of these tumors, particularly in a young woman as it can avoid unnecessary removal of contralateral ovary and helps preserve fertility [
Intraoperative frozen section for use in diagnosis of ovarian tumors is of great value. In some cases, it can help surgeons avoid under-treatment or overtreatment of patients. Frozen section is indicated to ensure that the tissue sampled adequate for diagnosis, to determine the nature of the disease process, to plan ancillary studies, to determine tumor spread, and to assess margins [
In this study, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of frozen section in the diagnosis of benign ovarian masses were 100%, 100%, 100%, 100% and 100% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of frozen section in the diagnosis of borderline ovarian masses were 100%, 95.9%, 33.3%, 100% and 96% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of frozen section in the diagnosis of malignant ovarian masses were 90%, 100%, 100%, 93.8% and 96% respectively.
In a systematic review of papers examining the use of intraoperative frozen section in predicting the final diagnosis of ovarian lesions, the sensitivity of frozen section was greater than 95% when benign tumors were compared with borderline and invasive carcinomas but just less than this when borderline and invasive carcinomas were compared. Specificity also exceeded 95% when benign and invasive carcinoma were compared but was less than this when borderline lesions were compared firstly with benign and secondly with invasive lesions. The positive and negative predictive values were also optimal when benign and invasive carcinomas were compared but reduced when either benign or invasive carcinomas were compared with borderline lesions [
Ilker et al., analyzed data of 266 patients with ovarian masses. The results of frozen sections were 235 (88.3%) benign, 11 (4.2%) borderline and 20 (7.5%) malignant. The sensitivity was 100% for the benign tumors, 77.8% for the borderline tumors and 71.4% for the malignant tumors. The specificity of frozen section was 83.8%, 98.4% and 100% for the benign, borderline and malignant tumors, respectively [
Wootipoom et al. concluded that intraoperative frozen section diagnosis is generally accurate and can be used as one piece of evidence for the surgeon to use in determining the type and extent of initial surgery to be performed. However, frozen section has limitations such as sampling error, deferred diagnosis and interpretation error. Good intraoperative communication between surgeons and pathologists and regular clinico-pathologic conferences, especially in cases with discordant diagnosis, can maximize accuracy and minimize limitations such as interpretation error and deferred diagnosis [
Commonly used methods for obtaining and preparing cells for cytological evaluation are touch preparation, fine needle aspiration cytology (FNAC) and scrape smear preparation [
Cytological evaluation provides a better morphological detail, and in experienced setup compares well with frozen section and subsequent formalin-fixed paraffin-embedded sections. In addition, cytological examination of surgical specimens has proved to be a valuable learning tool and has educational value. This significant educational value coupled with its intrinsic simplicity and rapidity and cost effectiveness will likely necessitate the widespread implementation of this diagnostic technique in the near future [
Scrape cytology could be preferred over touch preparation/ imprint cytology, as in most cases, the former technique would yield much more material than the latter. Further, its role as a potential tool in intra-operative consultation is more pertinent in institutions unequipped with frozen section facility. In these scenarios, in experienced hands, it not only offers a viable alternative, but also helps to reduce the overall cost and processing time, without compromising quality [
History of scrape cytology can be traced back to 1927 when Leonard S. Dudgeon and Vincent Patrick at the University of London raised the horizons of the rapid cytological diagnosis of freshly cut specimens with reliable accuracy rates. Following this, several studies done in the past have discussed the use of imprint and touch preparation, especially as a tool for intraoperative diagnosis [
We obtained very good results while using scrape cytology. In this study, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of scraping technique in the diagnosis of benign ovarian masses were 100%, 95.2%, 96.7%, 100% and 98% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of scraping technique in the diagnosis of border line ovarian masses were 100%, 93.4%, 25%, 100% and 94% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of scraping technique in the diagnosis of malignant ovarian masses were 80%, 100%, 100%, 88.2% and 92% respectively.
Shidham et al. [
Finally, we can conclude that frozen section proved to be more accurate than smear preparations in the intraoperative assessment of ovarian tumors in this study. However, the cytology preparations were helpful in supporting the histological diagnoses, and in some cases, provided additional useful information. Thus, cytology has a complementary role to frozen section in the intraoperative assessment of ovarian lesions. At the centers where the facilities of frozen section are not available, intraoperative scrape cytology is a useful tool for intraoperative diagnosis of tumor. It can be used to diagnose small tissue that can be preserved for permanent paraffin block method.