Diagnostic accuracy of frozen section in ovarian masses: A single centre study

Background Ovarian mass is not an uncommon imaging finding in women of all age groups. Hence, frozen section plays a very important role in determining the nature of the mass and, thus, deciding the appropriate surgical procedure. In the present study, we aim to analyze the accuracy of frozen sections at our center in diagnosing benign, borderline, and malignant tumors.

A total data on 50 patients were collected who were operated between February 2020 and January 2022, and frozen sections were sent intraoperatively. The results were compared with the final histopathology report, and the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were analyzed for diagnosing benign, borderline, and malignant masses.

The accuracy of frozen section analysis at our center was 90.0%. The sensitivity for diagnosing malignant tumors was 89.4%, with a specificity of 100%. For benign tumors, the sensitivity and specificity were 96.2% and 86.9%, respectively. Borderline tumors had the lowest sensitivity of 50.0% with specificity of 95.6%.

Intraoperative frozen sections are a very good and necessary tool for the identification of ovarian tumors. It helps to prevent unnecessary extensive surgeries in benign tumors, especially in young patients, and complete surgery in one sitting in cases of malignancy.

Frozen section, Ovarian tumors, Benign, Borderline, Malignant

Ovarian tumors are a significant cause of morbidity and mortality in females of all ages. Ovarian cancer is one of the top 10 cancers in the United States with an estimated 22,530 new cases and 13,980 deaths in 2019.1 In India, ovarian cancer contributed to 45,701 new cases and 32,077 deaths, according to GLOBOCAN 2020 estimates. It is the third most common cancer in females after breast cancer and cervical cancer in India.2 Ovarian tumors are a heterogeneous group of lesions that may be benign, borderline, or malignant, and hence the surgical management varies accordingly. Preoperative diagnostic modalities like imaging and serum tumor markers have a limited role in determining the nature of the mass. Hence, intraoperative pathological diagnosis by frozen section helps in the identification of the nature of the mass, and thus helping the surgical approach.3 The rapid frozen section technique was first introduced by Welsh WM in 1891.4 The use of frozen section in ovarian masses was studied by Ilvan et al, in 2005, with an overall accuracy as high as 97%.5 It is important that the accuracy of frozen sections should be improved so as to avoid extensive surgery, and make decisions about fertility-preserving surgeries in young patients, and avoid incomplete surgery in malignant tumors.6 The present study was intended to determine the diagnostic accuracy of frozen sections and categorize them into benign, borderline, and malignant masses to determine further surgery and then compare with final histopathology.3

Study design This is a retrospective observational study conducted at a tertiary care center reviewing the case records of all patients who underwent surgery for ovarian masses in the gynecology department from February 2020 to January 2022. This study was done after getting approval from the institutional ethics committee and after taking the consent from patients. While doing this research, all good clinical practice guidelines as per Declaration of Helsinki were followed. The data were collected after reviewing the medical records. All the patients with unilateral or bilateral ovarian masses without any extraovarian disease were included in the study. The exclusion criteria were biopsy proven and extra-ovarian disease. The decision to send the ovarian tumor for frozen section analysis was made by the operating surgeon on the basis of radiological findings like size and radiological features. After the frozen section report alone, further decisions about surgery were made after communicating with the patient's relatives. The report was categorized as benign, borderline, and malignant. Frozen section analysis Intra-operatively, fresh tissue specimens were sent to the frozen section room along with a properly filled requisition form. On the basis of the gross and morphological features of the specimen, sections were taken relevant to the requisition. The samples were frozen on cryostat holders using freezing media and cooled to −28 °C. Once the sample was frozen, it was sectioned in the cryostat machine at a controlled temperature. After the gross examination of the tumor, sections were obtained from representative areas at the discretion of the pathologist. The number of sections varies from 1 to 5. The slides were stained with rapid hematoxylin and eosin stain. The pathologist studied the slides and conveyed the result to the operating surgeon via direct telephone call to the operation theater. The remaining tissue after frozen section reporting was fixed in formalin and processed for paraffin embedding. The turn-around time from retrieving the sample until informing the client of the result was around 30 min. The diagnoses were categorized as benign, borderline, or malignant. Benign cysts are lined by a single layer of tall, columnar, ciliated/mucinous cells (Fig. 1), borderline cases show hierarchically branching papillae lined by stratified, heterogeneous epithelium with up to moderate atypia without any invasion (Fig. 2). Adenocarcinomas show an invasive growth pattern (Fig. 3). All cases were reported by a single pathologist so as to avoid inter-observer bias or variation. A comparable result meant that the frozen section diagnosis and the final histopathology on formalin-fixed paraffin-embedded sections were identical. Non-comparable results were analyzed for the problems faced in technical and pathological aspects. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Statistical analysis For the statistical analysis, the final histopathology result was obtained and compared with the frozen report. The accuracy of the frozen section was calculated, which is defined as the percentage of concordance between the frozen and final histopathology. The sensitivity, specificity, positive predictive value PPV, and negative predictive value NPV were calculated using a standard 2 × 2 table.

A total of 50 patients were studied after removing the exclusion factors (Fig. 4). The mean age of the patients was 46.8 ± 14.8 years. Out of the 50 patients who were analyzed, 31 (62%) were premenopausal, out of which 7 (22.5%) were less than 30 years of age and presented with an ovarian mass. In this study, frozen section agreed with the final histopathology in 45 out of 50 patients, with an overall accuracy of 90.0%. Table 1 shows the association between frozen reports and final histopathology. As shown in Table 1, one patient who was reported as benign in a frozen section turned out to be malignant on final histopathological examination. She was reported as having a benign mature cystic teratoma on a frozen section, for which unilateral oophorectomy was done at that time as the mass was large. On final histopathological examination (HPE), it turned out to be an immature cystic teratoma of low grade. As she was a 29-year-old female, the decision to complete fertility-preserving staging was made. Table 1. | FROZEN | Final HPE | ||| |---|---|---|---|---| | Benign | Borderline | Malignant | Total | | | Benign | 26 | 2 | 1 | 29 | | Borderline | 1 | 2 | 1 | 4 | | Malignant | 0 | 0 | 17 | 17 | | Total | 27 | 4 | 19 | 50 | Out of 29 patients reported as benign on frozen, two patients were reported as borderline on final HPE. One patient was diagnosed with a papillary serous tumor with borderline changes, and hence completion surgery was done in the second sitting as she was 35 years old. Another patient was reported having a benign mucinous tumor on frozen, which later turned out to be borderline mucinous tumor. Total abdominal hysterectomy with B/L salpingo-oophorectomy with infracolic omentectomy was done for this patient on the basis of suspicion as the mass was very huge in size. After the final report, she was kept under observation with regular follow up. Out of four patients reported as borderline on frozen sections, one was reported as benign and one was reported as malignant on final HPE. One who was reported as benign was a 36-year-old female with a 13 × 9 cm cystic lesion on imaging. She was reported as having a cyst lined with serous epithelium and suspicious atypical glands. Hence, unilateral salpingo-oophorectomy with omental biopsy was done after explaining to the relatives. Later on, the final HPE was suggestive of a mature cystic teratoma with struma ovarii. Another patient was a 69-year-old female who was reported as having a borderline tumor but later turned out to have endometrioid adenocarcinoma. But complete staging surgery was done in the same sitting. The sensitivity, specificity, PPV, and NPV of frozen sections for malignant tumors at our center were 89.4%, 100%, 100%, and 93.93%, respectively as shown in Table 2. Table 2. | Benign (%) | Borderline (%) | Malignant (%) | | |---|---|---|---| | Sensitivity | 96.29 | 50 | 89.4 | | Specificity | 86.95 | 95.65 | 100 | | Positive predictive value (PPV) | 89.6 | 50 | 100 | | Negative predictive value (NPV) | 95.23 | 95.65 | 93.93 | The benign lesions diagnosed during frozen sections were mostly serous or mucinous cystadenomas, endometriosis, and cystadenofibromas of the ovary. Out of 50 patients, 31 were pre-menopausal, where ovarian and fertility preservation could be done without compromising oncologic principles.

Even with the current best available, radiological modalities like transvaginal ultrasound and MRI, sometimes it becomes very difficult to identify an ovarian mass as benign or malignant when the biochemical markers are also normal. Especially in young patients with early ovarian cancers or borderline tumors, tumor markers may not be elevated. Therefore, it becomes important to decide the extent of surgery and when fertility preservation is supposed to be done. Certain ovarian masses like hemorrhagic cysts or benign endometriomas can mimic malignant masses on imaging, and tumor markers are also elevated in such situations. Hence, intraoperative diagnosis via frozen section helps identify the ovarian mass and decide the extent of surgery. Although the term frozen section diagnosis is widely used, some authors suggested the term “intraoperative consultation”, because not all diagnoses require a frozen section.10 The goal of a frozen section of ovarian tumors is to discriminate benign, borderline, and malignant tumors for appropriate surgical management. Frozen section analysis has some limitations, due to which sometimes overdiagnosis can also lead to unnecessary extensive surgery and surgical morbidity for the patient. It can lead to underdiagnosis sometimes, which can be responsible for either the dilemma of a second surgery or the fear of incomplete surgery. Hence, it is very important to know about the reliability of frozen sections and to communicate to the patient prior of all the possibilities. As shown in Table 3, frozen section has a good sensitivity in diagnosing benign and malignant ovarian masses, which is comparable to our study also.3,6, 7, 8, 9 Table 3. | Subbian et al (7) (2004–2006) 135 cases (%) | Anupama et al(8) (2010–2014) 178 cases (%) | Arshad et al (6) (2018) 92 cases (%) | Piyanat et al, (9) (2019) 150 cases (%) | Nandyala R et al, (3) (2022), 289 cases (%) | Present study (2022) 50 cases (%) | | |---|---|---|---|---|---|---| | Overall accuracy | 84.25 | 93.8 | 83.6 | 93.3 | 87.89 | 90.0 | | Sensitivity | |||||| | Benign | 90.4 | 99 | 95.6 | 100.0 | 93.0 | 96.2 | | Borderline | 31.2 | 81.8 | 76.2 | 88.9 | 68.7 | 50.0 | | Malignant | 91.5 | 92.5 | 69.2 | 79.6 | 81.4 | 89.4 | | Specificity | |||||| | Benign | 82.6 | 86.8 | 85.1 | 94.3 | 91.4 | 86.9 | | Borderline | 94 | 99.4 | 88.7 | 95.0 | 91.8 | 95.6 | | Malignant | 98.2 | 100 | 100.0 | 100.0 | 96.8 | 100.0 | | PPV | |||||| | Benign | 74.5 | 90.9 | 86.0 | 97.0 | 93.1 | 89.6 | | Borderline | 45.4 | 94.7 | 66.7 | 55.3 | 51.1 | 50.0 | | Malignant | 98.1 | 100 | 100.0 | 100.0 | 93.0 | 100.0 | | NPV | |||||| | Benign | 93.9 | 98.5 | 95.2 | 100.0 | 92.1 | 95.2 | | Borderline | 89.6 | 96.2 | 92.7 | 99.3 | 95.9 | 95.6 | | malignant | 91.9 | 95.3 | 89.2 | 92.2 | 91.1 | 95.9 | The PPV of frozen sections in predicting malignant lesions was 100%, which was again comparable to various studies.6,8,9 Hence, none of the patients were subjected to increased surgical morbidity. In our study, three patients were missed on frozen sections with 96.29% sensitivity. The patient, who was diagnosed as having a benign mature cystic teratoma on frozen, turned out to have an immature cystic teratoma on final HPE as there was a very small focus of immaturity in the big mass, and another was also showing the limitation of frozen sections as it is not possible to sample the whole mass in multiple sections on frozen. Another patient was diagnosed as having a borderline mucinous tumor on final histopathology and was reported as having a benign mucinous tumor on frozen section analysis. But surgical morbidity was not increased as she had already undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy, hence, repeat surgery was not done. This is in concordance with the previous published studies, which have shown the accuracy rates for frozen sections ranging from 50 to 85%.8,10 But borderline masses are difficult to diagnose on a frozen section. PPV for the diagnosis of borderline tumors by frozen section has been documented at between 60 and 70%6, 7, 8, 9. as shown in Table 3 except in a study done by Anupama et al, PPV for borderline tumors was 94.7%, which is quite high.8 Two studies done by Subbian et al, and Yarandi et al. also showed that sensitivity was low for borderline tumors because of large mucinous tumors showing tumor heterogeneity.7,11 In our study, sensitivity and PPV for borderline tumors were also 50% which was comparable to the rest of the studies. Out of two patients diagnosed with borderline tumors on frozen sections, one turned out to be benign and the other be malignant. But again, surgical compromise was not done in any patient. Therefore, intraoperative frozen section is an important diagnostic tool and helps in intraoperative decision-making.

In conclusion, intraoperative frozen section examination is an excellent and necessary tool that act as a quick histological diagnosis, guiding the surgeon in planning the appropriate surgery for the patient. It helps in the determination of the malignant potential of the ovarian tumor. Therefore, the use of frozen sections could reduce radical surgeries in benign tumors, especially in young patients, thereby preserving their fertility. In cases of borderline or malignant conditions, frozen section helps prevent suboptimal surgery, reducing the morbidity of a second surgery. However, frozen section has its own limitations in cases of very large ovarian tumors and in borderline tumors, especially those of mucinous histology. Hence, in such cases, relevant clinical details should be provided to the pathologists, and there should be increased tissue sampling from the representative area to increase the accuracy of the frozen section. Moreover, in this study, 50 cases were taken for a duration of 2 years, out of which there were 19 malignant cases; the power of study is less, which is an important limitation of the study. So more such studies should be done with an increased number of cases, and freezing should be a mandatory part of the management of such ovarian masses. Patients/ Guardians/ Participants consent Patients informed consent was obtained. Ethical clearance Institute/hospital ethical clearance certificate was obtained. Source of support None. Disclosure of competing interest The authors have none to declare.

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