International Journal of Gynecology & Obstetrics 72 Ž2001. 159᎐164
Article
Diagnostic accuracy of intraoperative imprint cytology in ovarian epithelial tumors Y. Nagai a,U , N. Tanakab, F. Horiuchi c , S. Ohki c , K. Seki b, S. Sekiyab b
a Second Department of Pathology, Chiba Uni¨ ersity, Chiba, Japan Department of Obstetrics and Gynecology, Chiba Uni¨ ersity, Chiba, Japan c Department of Clinical Pathology, Chiba Uni¨ ersity, Chiba, Japan
Received 29 March 2000; received in revised form 10 July 2000; accepted 27 July 2000
Abstract Objecti¨ e: To evaluate imprint cytology ŽIC. as the intraoperative pathological consultations for ovarian epithelial tumors ŽOET.. Method: We reviewed ICs obtained from 354 consecutive surgical specimens of OET. Cytological specimens were classified into five categories. Final pathological diagnoses were made according to the WHO classification. We performed logistic regression analysis, calculated the limits among benign, borderline, and malignant lesions, and analyzed the diagnostic accuracy. We also made receiver operating characteristic ŽROC. curves regarding IC. Results: The accuracies to differentiate benign and malignant lesions were 87.1 and 83.6%, respectively. In contrast, that of borderline lesions was 30.0%. The areas under ROC curves to diagnose benign, and malignant lesions were 0.888 Ž P- 0.05. and 0.951 Ž P- 0.05., respectively, that meant IC was significantly useful for diagnosis of malignancy. Conclusions: IC applied to OET was proved to be practically useful in establishing an intraoperative diagnosis by ROC curves. 䊚 2001 International Federation of Gynecology and Obstetrics. All rights reserved. Keywords: Ovarian tumors; Intraoperative cytology; Diagnostic accuracy; ROC curve
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[email protected] ŽY. Nagai.. 0020-7292r01r$20.00 䊚 2001 International Federation of Gynecology and Obstetrics. All rights reserved. PII: S 0 0 2 0 - 7 2 9 2 Ž 0 0 . 0 0 3 3 6 - 2
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1. Introduction The intraoperative pathological consultations are indispensable in determining malignancy, the surgical staging and the operating methods for ovarian tumors because of the difficulty of their preoperative or pathological examinations w1x. Although the frozen section is the gold standard in intraoperative diagnosis of malignant tumors, it seems unsuitable for ovarian tumors that are large in size and have various pathological patterns. Imprint cytology ŽIC. has been adopted as the chief intraoperative pathological consultations for ovarian tumors at Chiba University Hospital, because both the simplicity of producing many high-quality preparations and rapid results are an advantage of IC w2x. Although there have been several reports regarding the use of IC in ovarian tumors, its diagnostic accuracy has not been fully elucidated w3,4x. By ROC curves, we analyzed statistically diagnostic accuracy for differential diagnosis among benign ŽBe., borderline ŽBo., and malignant ŽM. lesions of ovarian epithelial tumors ŽOET. and demonstrated the usefulness of IC in diagnosing ovarian tumors.
2. Materials and methods We reviewed the IC smears of ovarian tumors from 576 consecutive surgical specimens obtained
Table 1 Histological distribution of intraoperative imprint cytology of common epithelial tumors of ovary Histological type
Number of cases
Common ‘epithelial’ tumors Sex cord stromal tumors Germ cell tumors Soft tissue tumors not specific to ovary Secondary Žmetastatic . tumors Tumor-like lesions Normal ovary
336 Ž58.3%.
Total
576
36 Ž6.3%. 89 Ž15.5%. 3 Ž0.5%. 18 Ž3.1%. 77 Ž13.4%. 16 Ž2.8%.
during the period between January 1978 and December 1998 at Chiba University Hospital. Of these, 354 were derived from epithelial origins ŽTable 1.. When surgical specimens were removed, cells derived from representative lesions of the cut surfaces were directly imprinted onto 5᎐10 slide glasses, fixed, and stained using the Papanicolaou procedure. We adopted a new classification by cytological features for diagnosis of IC and classified into five categories as shown in Table 2 ŽFigs. 1᎐5a,b.. The final pathological diagnoses were made based on the findings in permanent sections, and classified into three groups
Table 2 Characteristic features of cells in each class of imprint cytology of common epithelial tumors of the ovary Cytological diagnosis Žcategories.
Number of cells Type of cluster and polarity
1
2
3
4
5
Few Sheet
Žq. Small cell clusters Slightly overlapping Ž". y Žq.
Žq. y Žqq .
Žqq . Large cell clusters
Many
No overlapping Tumor diathesis Nuclear atypia
Žy. No atypia
Nuclear and cytoplasm
Small nuclei with abundant cytoplasm
Slightly enlarged nuclei with abundant cytoplasm
Overlapping and polarity Žq. y Žqq . Mild) moderate atypia Enlarged nuclei with intermediate cytoplasm
Žq. - Žqq . Moderate atypia Enlarged nuclei with scanty cytoplasm
Marked atypia
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Fig. 1. Ža. Imprint cytology of category 1 of mucinous cyst adenoma. Nuclear were slightly enlarged, but nuclear᎐cytoplasm ratio was small. Tumor cell overlapping and papillarity were not observed. Tumor diathesis was clear. Papanicolaou staining, =640. Žb. Permanent section of mucinous cyst adenoma from the same case as that of Fig. 1a. Hematoxylin and eosin staining, =640.
ŽBe, Bo, and M lesions. according to the WHO classification criteria w5x. To examine the accuracy of IC, we performed logistic regression analysis w6,7x and calculated the discrimination limits among Be, Bo, and M lesions. Furthermore, we established receiving operating characteristic ŽROC. curves in order to differentiate Be from Bo and M lesions, and M from Be and Bo lesions, according to the method of Hanley et al. w8x. The area under the ROC curve was analyzed and evaluated by z-test w9,10x and values of P- 0.05 were considered to be significant.
3. Results
Among 576 specimens there were 354 Ž61.4%. common and metastatic ‘epithelial’ tumors, 36 Ž6.3%. sex cord stromal cell tumors, 89 Ž15.5%. germ cell tumors, 3 Ž0.5%. soft tissue tumors not specific to ovary . There were 77 Ž13.4%. tumorlike conditions, and 16 Ž2.8%. normal ovaries ŽTable 1.. Imprint cytological and pathological diagnosis are shown in Table 3. The discrimination limit of IC in distinguishing Be lesions from Bo or M
Fig. 2. Ža. Imprint cytology of category 2 of mucinous cyst adenoma. Slight overlapping was observed. Nuclear was slightly enlarged but not atypical. Tumor diathesis was clear. Papanicolaou staining, =640. Žb. Permanent section of mucinous cyst adenoma from the same case as that of Fig. 2a. Hematoxylin and eosin staining, =640.
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Fig. 3. Ža. Imprint cytology of mucinous cyst adenoma of borderline malignancy. Nuclear atypia were mild, and tumor overlapping was moderately, so this case was cytologically diagnosed as category 3. Papanicolaou staining, =640. Žb. Permanent section of mucinous cystadenoma of borderline malignancy from the same case as that of Fig. 3a. Hematoxylin and eosin staining, =640.
Fig. 4. Ža. Imprint cytology of mucinous cystadenocarcinoma. Nuclear atypia were severe, and tumor overlapping was remarkable, so this case was cytologically diagnosed as category 4. Papanicolaou staining, =640. Žb. Permanent section of mucinous cystadenocarcinoma from the same case as that of Fig. 4a. Hematoxylin and eosin staining, =640.
Fig. 5. Ža. Imprint cytology of mucinous cystadenocarcinoma. Nuclear atypia were severe, tumor overlapping was remarkable, and tumor diathesis was severe, so this case was cytologically diagnosed as category 5. Papanicolaou staining, =640. Žb. Permanent section of mucinous cystadenocarcinoma from the same, case as that of Fig. 5a. Hematoxylin and eosin staining, =640.
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Table 3 Results of imprint cytological and pathological diagnosis Pathological diagnosis
Categories of imprint cytology 1 a
Benign Borderline Malignant Total a
22 1 1 24
2
3
4
5
86 11 5 102
10 9 15 34
4 6 20 30
2 3 159 164
124 30 200 354
The value was determined by number of specimens.
lesions was estimated to be 2.42 by logistic regression analysis, and categories 1 and 2 were consistent with Be lesions. The discrimination limit in distinguishing M lesions from Bo or Be lesions was 3.59, and categories 4 and 5 were consistent with M lesions. Consequently, category 3 was classified into Bo lesions. The sensitivity and specificity to discriminate M and Bo lesions from Be were 89.5 and 90.3%, respectively. Those to discriminate Be and Bo lesions from M were 87.1 and 92.2%, respectively. The accuracy, false positive rate and false negative rate of IC were 83.6, 7.1 and 9.3%, respectively. On the other hand, the values of the Bo lesions were 30.0, 30.0, and 40.0%, respectively ŽTable 4.. The ROC curves differentiating Be lesions from Bo or M lesions, and M lesions from Bo or Be lesions were shown in Fig. 6. The areas under the ROC curve in distinguishing Be lesions from Bo or M lesions, and M lesions from Bo or Be lesions were 0.888 Ž zs 12.6, P- 0.05., and 0.95
Ž zs 36.5, P- 0.05., respectively. The validation of IG in our study was proved to be statistically significant.
4. Discussions
In this study, we reviewed 354 IC of OET and evaluated the cytological data with our classifica-
Table 4 The diagnostic accuracy of intraoperative imprint cytology a Diagnostic accuracy
Benign Borderline Malignant Total
Accuracy
False positive rate
False negative rate
87.1% 30.0% 89.5% 83.6%
12.9% 30.0% ᎐ 7.1%
᎐ 40.0% 10.5% 9.3%
a Accuracy rate, false positive rate, and false negative rate were calculated according to the criteria that categories 1 and 2, category 3, and categories 4 and 5 were diagnosed as benign, borderline and malignant lesions, respectively.
Fig. 6. The receiver operating characteristic ŽROC. curves to distinguish benign lesions from borderline or malignant lesions Žclosed circle., and malignant lesions from borderline or benign lesions Žopened circle. and the areas under the curves were 0.888 Ž z s 12.6, P- 0.05. and, 0.951 Ž zs 36.5, P- 0.05., respectively.
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tion. There are few reports that the satisfactory number of cases was evaluated. Generally Papanicolaou classification has been adopted for the judgement of cytological specimens. Recently this classification might have been criticized, and be considered to be disused. In this study, we have adopted a new classification for IC, based on cytomorphologic features. Raab et al. w12,13x reported the usefulness of an ROC curve in pathology and cytology. However, in their study it was limited to distinguishing only between Be and M, and did not mention Bo lesions w12,13x. By describing two ROC curves, we tried to apply an ROC curve to ovarian tumors including the Bo lesion. In our study, the diagnostic accuracy of IC was 83.6% which was slightly lower than that of other reports w3,4x. However, its reliability was proved by ROC curves. In cytology of ovarian tumors, it has often been difficult to differentiate Bo lesions accurately from Bo and M w11x. Also, our criteria constituted the lowest accuracy level Ž30.0%. of borderline lesions. Even if borderline lesions were classified into serous and mucinous tumors, the accuracies of IC in both tumors were 28.6 and 30.4%, respectively. The difference of tumor subtypes did not account for the low accuracy level. These data might show the limitations of the cytological approach in the diagnosis of Bo lesions. The other pathological and clinical information Že.g. macroscopic findings, image data and tumor markers. will be useful for accurate diagnosis of Bo lesions.
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