Clinical findings and pathologic diagnosis
Between June 2017 and June 2018, 591 consecutive women with adnexal tumours who underwent pre-operative ultrasound examinations were prospectively enrolled. The final cohort consisted of 486 women; 105 women met the exclusion criteria and were excluded from study. Figure 1 provides a detailed overview of the patients’ inclusion and exclusion from the study.
In the final analysis, 486 patients with 366 (75.3%) benign and 120 (24.7%) malignant adnexal masses were included. Table 1 presents the histological results. Endometriomas (19.8%, 96/486) and serous cystadenomas (13.4%, 65/486) were the most common benign diagnoses. Among the malignant masses, 7.0% (34/486) were BOTs, 4.9% (24/486) were stage I OCs, 9.7% (47/486) were stages II–IV OCs, and 3.1% (15/486) were metastases.
Table 1
Distributions of histology outcomes of 486 adnexal masses
Histological type of masses | n(%) |
Benign | 366 (75.3) |
Endometrioma | 96 (19.8) |
Serous cystadenoma | 65 (13.4) |
Teratoma | 46 (9.5) |
Mucinous cystadenoma | 34 (7.0) |
Hydrosalpinx | 32 (6.6) |
Fibrothecoma | 20 (4.1) |
Mesosalpinx cyst | 17 (3.5) |
Parovarian cyst | 14 (2.9) |
Cystadenofibroma | 6 (1.2) |
Fibroma | 6 (1.2) |
Adenofibroma | 4 (0.8) |
Brenner tumour | 4 (0.8) |
Peritoneal mesothelioma | 3 (0.6) |
Sertoli-Leydig cell tumour | 2 (0.4) |
Sclerosing stromal tumour | 1 (0.2) |
Tuberculosis | 1 (0.2) |
Other ovarian benign lesion | 15 (3.1) |
Borderline | 34 (7.0) |
Serous | 16 (3.3) |
Mucinous | 15 (3.1) |
Endometrioid | 3 (0.6) |
Primary ovarian malignant | 71(14.6) |
Serous adenocarcinoma | 42 (8.6) |
Clear cell carcinoma | 10 (2.1) |
Endometrioid adenocarcinoma | 6 (1.2) |
Mucinous adenocarcinoma | 3 (0.6) |
Sertoli-Leydig cell tumour | 2 (0.4) |
Carcinosarcoma | 2 (0.4) |
Granulosa cell tumour | 2 (0.4) |
Seromucinous adenocarcinoma | 1 (0.2) |
Diffuse large B cell lymphoma of ovary | 1 (0.2) |
Small cell neuroendocrine carcinoma | 1 (0.2) |
Strumal carcinoid of ovary | 1 (0.2) |
Metastasis | 15 (3.1) |
Gastric cancer | 6 (1.2) |
Appendiceal adenocarcinoma | 3 (0.6) |
Cholangiocarcinoma | 2 (0.4) |
Breast cancer | 2 (0.4) |
Pancreatic cancer | 2 (0.4) |
Table 2 summarises the patients’ clinical characteristics and data describing the ultrasound findings from the benign and malignant tumours. The patients with malignancies were older, were more likely to be post-menopausal and to have a family history of OC, and had higher CA125 levels than those with benign tumours (all P < 0.05). Regarding the ultrasound findings, the malignant tumours had significantly greater diameters, more solid tissue, wider solid tissue components, > 10-cyst locules, more papillary projections, and more ascites compared with the benign masses (all P < 0.001). None of the patients with malignant tumours had acoustic shadows.
Table 2
Results with regard to clinical characteristics and ultrasound features for 486 patients with adnexal mass
Characteristic | Benign (n = 366) | Malignant (n = 120) | P |
Age (years) | 41 (31–51) | 54 (42–63) | < 0.001a |
Menopausal status | | | < 0.001b |
Premenopausal | 275 (75.1) | 53 (44.2) | |
Postmenopausal | 91 (24.9) | 67 (55.8) | |
CA125 (U/mL) | 10 (11–38) | 54 (18–517) | < 0.001a |
Family history of OC | 0 (0.0) | 2 (1.7) | 0.013c |
Maximal diameter of lesion (mm) | 56 (44–72) | 78 (50–126) | < 0.001a |
Presence of solid tissue | 108 (29.5) | 107 (89.2) | < 0.001b |
Proportion solid tissue if present (mm) | 31 (17–46) | 44 (20–65) | < 0.001a |
Presence of papillary projections | 39 (10.7) | 46 (38.3) | < 0.001b |
0 | 327 (89.3) | 74 (61.7) | |
1 | 21 (5.7) | 13 (10.8) | |
2 | 6 (1.6) | 3 (2.5) | |
3 | 5 (1.4) | 5 (4.2) | |
༞3 | 7 (1.9) | 25 (20.8) | |
> 10-cyst locules | 11 (3.0) | 22 (18.3) | < 0.001b |
Acoustic shadows | 43 (11.7) | 0 (0.0) | < 0.001c |
Ascites | 2 (0.5) | 35 (29.2) | < 0.001b |
Data are given as n (%) for categorical data and median (interquartile range) for continuous data. aMann-Whitney U-test for continuous data, bChi-square test and cFisher’s exact test for categorical data. OC, ovarian cancer. |
Diagnostic performance of adnexal mass prediction models
Table 3 details the diagnostic performances of the adnexal mass prediction models regarding their discrimination between benign and malignant tumours. The AUCs for the ADNEX models for differentiating malignant tumours from benign tumours that did and did not account for the CA125 level were 0.94 (95% CI: 0.92–0.96) and 0.94 (95% CI: 0.91–0.96), respectively. At a cut-off of 10%, the performance of the prediction model that included CA125 was excellent, with a sensitivity of 0.93 (95% CI: 0.87–0.97), a specificity of 0.76 (95% CI: 0.72–0.81), and a DOR of 43.67, and the performance of the prediction model that did not include CA125 had a sensitivity of 0.93 (95% CI: 0.87–0.97), a specificity of 0.74 (95% CI: 0.69–0.79), and a DOR of 40.00.
Table 3
Diagnostic performance of the prediction models for discrimination between benign and malignant adnexal masses.
Assessment method | AUC | Sensitivity | Specificity | PPV | NPV | LR+ | LR- | DOR |
ADNEX125 | 0.94 (0.92–0.96) | 0.93 (0.87–0.97) | 0.76 (0.72–0.81) | 0.80 (0.75–0.84) | 0.92 (0.87–0.95) | 3.93 (3.20–4.72) | 0.09 (0.04–0.22) | 43.67 |
ADNEXN125 | 0.94 (0.91–0.96) | 0.93 (0.87–0.97) | 0.74 (0.69–0.79) | 0.78 (0.73–0.83) | 0.92 (0.87–0.95) | 3.60 (3.00-4.31) | 0.09 (0.05–0.20) | 40.00 |
SRs + BE | NA | 0.69 (0.60–0.77) | 0.96 (0.93–0.97) | 0.94 (0.90–0.97) | 0.76 (0.70–0.80) | 15.82 (9.66–25.93) | 0.32 (0.25–0.42) | 49.44 |
SRs + MAL | NA | 0.93 (0.86–0.97) | 0.86 (0.82–0.89) | 0.87 (0.82–0.91) | 0.92 (0.88–0.95) | 6.51 (5.04–8.42) | 0.09 (0.05–0.16) | 72.33 |
RMI-I | 0.87(0.83–0.90) | 0.55 (0.46–0.64) | 0.93 (0.90–0.96) | 0.89 (0.83–0.94) | 0.67 (0.62–0.72) | 8.05 (5.33–12.19) | 0.48 (0.43–0.59) | 16.77 |
RMI-II | 0.83 (0.80–0.86) | 0.61 (0.52–0.70) | 0.92 (0.89–0.95) | 0.89 (0.83–0.93) | 0.70 (0.65–0.75) | 7.95 (5.42–11.75) | 0.42 (0.33–0.52) | 18.93 |
RMI-III | 0.82 (0.78–0.86) | 0.53 (0.44–0.63) | 0.94 (0.91–0.96) | 0.90 (0.84–0.95) | 0.67 (0.62–0.72) | 9.30 (5.91–14.49) | 0.50 (0.45–0.63) | 18.60 |
Values in parentheses are 95% CI. Prediction models: ADNEX125, the Assessment of Different NEoplasias in the adneXa model with CA125 level; ADNEXN125, the Assessment of Different NEoplasias in the adneXa model without CA125 level; SRs + BE, International Ovarian Tumour Analysis simple ultrasound-based rules applied with inconclusive tumours (13.2%, 64/486 cases) being classified as benign; SRs + MAL, International Ovarian Tumour Analysis simple ultrasound-based rules applied with inconclusive results being categorised as malignant; RMI-I, RMI-II, RMI-III, three variants of the Risk of Malignancy Index. For ADNEX models, cut-off value of 10% was used and for the three variants of RMI model, cut-off value of 200 was used. AUC, area under receiver-operating characteristic curve; PPV, positive predictive value; NPV, negative predictive value; LR+, positive likelihood ratio; LR–, negative likelihood ratio; DOR, diagnostic odds ratio; NA, not applicable. |
The SRs model was applicable to 422 (86.8%) patients with adnexal tumours. Of the tumours with inconclusive diagnoses, 56.3% (36/64) were benign tumours, 20.3% (13/64) were BOTs, 14.1% (9/64) were stage I OCs, 4.7% (3/64) were stages I–IV OCs, 4.7% (3/64) were metastases, approximately 43.8% were malignant histologically, and most of the benign masses (75.0%, 27/36) presented with a solid component. When the masses with inconclusive diagnoses were classified as benign, the SRs model’s diagnostic performance had a sensitivity of 0.69 (95% CI: 0.60–0.77), a specificity of 0.96 (95% CI: 0.93–0.97), and a DOR of 49.44, and when they were categorised as malignant, the SRs model’s diagnostic performance had a sensitivity of 0.93 (95% CI: 0.86–0.97), a specificity of 0.86 (95% CI: 0.82–0.89), and a DOR of 72.33.
The three RMI variants with cut-offs of 200 showed poor diagnostic performances in relation to the adnexal masses. Regarding RMI variants I, II, and III, the AUCs for differentiating malignant tumours from benign tumours were 0.87 (95% CI: 0.83–0.90), 0.83 (95% CI: 0.80–0.86), and 0.82 (95% CI: 0.78–0.86), respectively, with sensitivities of 0.55 (95% CI: 0.46–0.64), 0.61 (95% CI: 0.52–0.70), and 0.53 (95% CI: 0.44–0.63), respectively, and specificities of 0.93 (95% CI: 0.90–0.96), 0.92 (95% CI: 0.89–0.95), and 0. 94 (95% CI: 0.91–0.96), respectively.
Figure 2 shows the ROC curves for the ADNEX model and the RMI variants for differentiating malignant and benign tumours. The ADNEX model with or without CA125 was superior to the RMI variants regarding the diagnosis of malignant and benign tumours. When the SRs model yielded inconclusive results that were classified as malignancies, the model’s diagnostic performance was good. Figure 3 (a, b) and Fig. 4 (a, b) present two case examples of the prediction models using in the clinical pactice.
Table 4 summarises the pairwise ROC curve comparisons of the ADNEX model with or without CA125 and the RMI, which are expressed as differences in the AUCs. The difference between the AUCs for the ADNEX model with or without CA125 was not significant (AUC difference: 0.0002; 95% CI: 0.01–0.02). Comparisons of the ADNEX model with or without CA125 and the three RMI variants revealed significant differences in the AUCs that ranged from 0.074 to 0.118 (all P < 0.0001). Comparisons of the ADNEX model with and without CA125 with RMI variant I showed the greatest differences in the AUC (AUC difference: 0.074; 95% CIs: 0.039–0.109 and 0.040–0.108, respectively; P < 0.0001). The diagnostic performances of the three RMI variants remained statistically significant for the pre-operative diagnosis of adnexal masses (AUC differences: 0.010–0.044; all P < 0.05).
Table 4
Pairwise ROC curve comparisons expressed as differences in AUC and P-values for the study.
d-AUC ( Pa ) | ADNEXN125 | RMI-I | RMI-II | RMI-III |
ADNEX125 | 0.0002 (-0.012-0.012) P = 0.977 | 0.074 (0.039–0.109) P < 0.0001 | 0.109 (0.066–0.151) P < 0.0001 | 0.118 (0.076–0.160) P < 0.0001 |
ADNEXN125 | / | 0.074 (0.040–0.108) P < 0.0001 | 0.108 (0.064–0.153) P < 0.0001 | 0.118 (0.073–0.163) P < 0.0001 |
RMI-I | / | / | 0.035 (0.010–0.060) P = 0.007 | 0.044 (0.017–0.071) P = 0.001 |
RMI-II | / | / | / | 0.010 (0.003–0.016) P = 0.002 |
aComparisons of area under the curves (AUCs) of prediction models using Delong’s test; methods in left column are used as reference standard for comparisons; d-AUC, differences in area under the curve. Prediction models: ADNEX125, the Assessment of Different NEoplasias in the adneXa model with CA125 level; ADNEXN125, the Assessment of Different NEoplasias in the adneXa model without CA125 level; RMI-I, RMI-II, RMI-III, three variants of the Risk of Malignancy Index. Values in parentheses are 95% CI. |