Cell Biochem Biophys DOI 10.1007/s12013-014-0288-7
ORIGINAL PAPER
CT Diagnosis in the Thecoma–Fibroma Group of the Ovarian Stromal Tumors Zhixu Zhang • Yan Wu • Jianbo Gao
Ó Springer Science+Business Media New York 2014
Abstract The aim of this study was to investigate characteristic CT manifestations of the group of ovarian thecoma–fibroma. 24 patients (26 lesions) presenting with the ovarian thecoma–fibroma were analyzed retrospectively, and the diagnosis were confirmed by pathology after surgery. Our findings included: 22 patients were unilateral, while 2 were bilateral; 12 lesions were located in the right side of ovary, while 14 lesions were in the left side. Of the 26 lesions, there were ovarian thecoma (16 lesions), fibrothecoma (6 lesions), and fibroma (4 lesions). The largest diameters of tumor ranged from 37 to 231 mm with the mean value of 100 ± 44.29 mm. 14 patients were accompanied by ascites. All the tumors had well-defined borders. The shape of 22 lesions appeared round or oval, and 4 lesions were irregular. The tumors were solid in 19 lesions, cystic in 2 lesions, and mixed in 5 lesions. Most of the tumors were of heterogeneous density. There were no (20 lesions) or slight enhancement (6 lesions) after injection of the contrast medium. CT values of plain scan, arterial phase and venous among three groups had no significant difference. The enhancement were in the range of 0–5 HU in 10 lesions, and 6–17 HU in 16 lesions. In conclusion, the characteristic CT manifestations of the group of ovarian thecoma–fibroma were: often unilateral solid mass with the shape of oval and well defined border; no enhancement or slight enhancement; accompanied by small amount of ascites.
Zhixu Zhang and Yan Wu have contributed equally to this work. Z. Zhang Y. Wu J. Gao (&) Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of China e-mail: [email protected]
Keywords Ovarian thecoma Fibrothecoma Fibroma Tomography
Introduction Thecoma–fibroma is a group of benign ovarian tumor with sex cord-stromal origin. It has lower incidence and accounts for 4 % of all ovarian tumors [1] which are composed of varying amounts of theca cells and fibroblasts. According to the proportion of two-component or structure, ovarian thecoma– fibroma group is divided into three different subcategories: Thecoma: almost full of the theca cells, lipid-laden [2], without fibroblasts cells; ` Thecoma–fibroma: both theca cells and fibroblasts with different proportions can be found; and ´ Fibroma: almost entirely formed by fibroblasts without theca cells. Since there are overlapping multidirectional differentiation characteristics in histology and difficulties for precise classification in pathology, WHO suggested that they be called thecoma–fibroma [3]. This type of tumor group can occur at any age. Menopausal and postmenopausal women account for most of the cases, but it can also occur in young people; rare cases can be found in patients before menarche, and the average age is in the range of 55–60 years [4]. Patients usually have no fixed clinical symptoms. Common complaints are abdominal pain, abdominal distention, or abdominal masses. Since they are caused by functional ovarian tumors, patients can incur higher levels of estrogen, menstrual disorders, and irregular vaginal bleeding. Because of the low incidence and very few cases, there are only limited data of imaging features described in the literature [4–6], proper diagnosis remains elusive. Common diagnostic methods for this group of diseases include ultrasound, MRI, and CT. For suspicious ovarian lesions, ultrasound was the preferred screening method as it was
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cheap, convenient, and simple to use. Ultrasound can be used to judge the cystic or solid mass. In thecoma–fibroma group, ultrasound can detect equal or low echo and implicates the solid mass [4]. However, problems of ultrasound are as follows: it is hard to obtain qualitative diagnosis, and there are influenced by subjective factors of operators; it only provides poor image quality which limit its application for the exchange of information to other methods. MRI can be used for qualitative diagnosis of the tumor. Usually signal of T1WI is low or slightly lower in this group, whereas signal of T2WI is complicated: thecoma cells often show equal or higher signal, while fibroma usually shows low signal. Disadvantages of MRI inspection are that it take a long time, claustrophobic patients would not accept MRI examinations. and patients, who have metal implants in vivo, could not be subjected to MRI examination, particularly those female patients with intrauterine contraceptive ring; It also has been restricted use of MRI application in some patients with larger sizes of tumor because of narrow body coverage under MRI. Therefore, CT diagnosis and evaluation of the tumor become very important. Because of the low incidence, there are only a very few studies in the literature to report CT Imaging data of tumor, and so the lack of knowledge for the CT manifestation can often cause misdiagnosis or cannot be diagnosed before surgery. In order to improve the accuracy of preoperative CT diagnosis of the disease, in the present study, we retrospectively analyzed 24 cases of verified theca cell tumors in our hospital for evaluating their CT characteristics and the related clinical data.
complaints reported were pelvic masses for 17 patients with the longest history of 11 months. 7 patients complained abdominal pain and other 3 patients complained menstrual disorder. CT Procedure 24 patients underwent plain and contrast enhanced CT scan using GE Discovery CT750 HD and Toshiba Aquilion One 640 CT. Before scanning, patients drank 1500–2000 ml warm water to fill intestinal and the bladder located in lower abdomen area. Patients with supine position were asked to hold breath during scanning. Scanning was started from top of diaphragm plane to low margin of pubic joint at tube voltage of 120 kV, with auto current mode in the range of 200–500 mAs. With 5-mm layer thickness and a pitch of 1, enhancement was done with nonionic iodine contrast agent. After the patients completed the fast injection of contrast agents in elbow vein with high-pressure syringe at the dose of 1.5 ml/kg and speed of 3–4 ml/s, artery and vein doublephase scan were performed, by means of automatically triggered technology applied in artery phase, plus 30–35s duration of arteria phase for venous phase. CT images were processed in GE ADW4.4 Workstation and Toshiba Vitrea 6.3 workstation for coronal, sagittal, and oblique reconstructions; both reconstruction slice thickness and reconstruction interval were 3 mm. Tumor Markers Examination Among 24 cases, 5 cases were examined for tumor markers: CA125, CA199, AFP, and CEA.
Material and Method Pathology Examination General Information 24 cases of pathologically confirmed thecoma–fibroma tumors after surgery were considered in this study for analyzing their clinical and preoperative CT imaging data collected from November 2010 to May 2014, with prior consent and approval from the hospital medical imaging center. Ages of patients ranges from 14 to 78 years old: median age 56 years, 4 cases aged less than 30 years old, 3 cases in the age range of 31–40 years old, 3 cases in the age range of 41–50 years old, and 14 cases aged more than 51 years old. There were 15 cases of patients with menopause, among whom 3 cases were caused by uterine resection (2 cases due to uterine myoma, and 1 case due to mucinous cystadenoma). Two cases of patients (14 and 23 years old) were unmarried without sex history, and 2 cases of patients (24 and 28 years old) were married without pregnancy history. The remaining patients were married with pregnancy history. Main
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All cases of routine HE stains were obtained after patients’ surgical resection for pathology diagnosis. 14 cases of immunohistochemical staining were conducted for further diagnosis. Image Analysis CT imaging was analyzed by two radiologists (both are associate professors) who possessed expertise in abdominal images. Only settled opinions were used for final diagnosis, in case of disagreement. Observations were focused on following features: location (left or right); ` shape (round, oval, or irregular); ´ border (clear or not); and ˆ largest diameter after measure of sagittal, coronal and transverse plane, the largest diameter was selected for later analysis. Patients were divided into two groups according to menopause status and correlation between largest diameter and menopause was analyzed. Correlation of
Cell Biochem Biophys
largest diameter and ascites was also analyzed; ˜ Content (cystic, solid, or mixture); Þ Degree of enhancement (Degree of enhancement = venous phase CT value - average of CT-values, 0–10 HU for no enhancement, 10–20 HU for mild enhancement, and 20–40 HU for moderate enhancement, 40–60 HU for strong enhancement); and þ Effusion or no effusion in abdomen. Surgical, and pathological findings were referred for co-analysis. Largest diameter measurements: averaging three times measurement in the diameter of largest section; CT value measurement: solid part of tumor mass was further divided into three parts: top, middle, and bottom. Each part measured three areas of interest. Totally nine measurement per tumor were made. CT value was defined to the average of those nine measurements. The size of area of interest was around 30 mm2. For cystic-dominant tumor, only solid part of tumor was measured.
Statistics SPSS17.0 software was used for statistics analysis. Enumeration data (occurrence rate and incidence) were processed with percentage. Measurement data (CT value and the tumor largest diameter) were processed with mean ± SD values. The one-way ANOVA was used to compare the difference between CT values of plain, and artery phase, and vein phase. Wilcoxon rank test was used to determine the correlation of the tumor largest diameter with menopause or ascites relationship. P \ 0.05 was set as statistically significant.
Results CT Findings Among 24 patients, only 2 patients had lesions on both sides (8.3 %, 2/24) (Fig. 1). In total, there were 26 lesions in 24 patients. For primary CT diagnosis, there were 3 cases of sex cord-stromal tumors, 8 cases of unknown mass, 5 cases of leiomyoma of uterus, 5 cases of chocolate
cyst, 1 case cystadenoma, 1 case of cystadenocarcinoma, 1 case of dysgerminoma. Since, in this study 24 cases covered all of the three subtypes of the tumor, we analyzed their CT image characteristics together. There are 12 lesions in the right (46.15 %, 12/26), and 14 in the left (53.85 %, 14/26) among 26 lesions out of 24 cases; All tumor boundaries were clear. As for the shape, 22 lesions were oval or round, and 4 lesions were irregular. Largest diameter of tumors ranged from 37 to 231 mm with the average of 100 ± 44.29 mm. There were 14 cases associated with ascites (58.33 %, 14/24), among which 12 cases had only small amounts of ascites (200 ml), and 1 case also occurred with pleural effusion. There was no significant difference among tumor largest diameters between patients with and without menopause. However, statistically significant differences of tumor largest diameters were found between patients with and without ascites, and the largest diameter of tumor in patients with ascites were larger than the one in patients without ascites (Table 1). Among 26 lesions, there were 9 solid lesions and 4 solidcystic lesions which showed solid features, and there were two cystic lesions in which only a few solid features could be detected at the bottom of cyst cavity (Figs. 2, 3). 8 out of 26 lesions were homogeneous density, and one of them had the size of 95 mm 9 85 mm with 23.51 HU for plain CT, 27.54 HU for arterial phase and 7.86 for venous phase. This case was misdiagnosed by CT for chocolate cyst and the results of ultrasound indicated its solid mass feature (Fig. 4). Average of regular tumor CT values of 26 lesions was 40.93 ± 9.48 HU; arterial phase CT value was 43.15 ± 9.92 HU; and venous phase CT value was 47.61 ± 11.49 HU. Since regular, arterial phase, and venous phase CT values meet normal distribution, ANOVA with single factors variance was used for statistical analysis. F = 2.813, P = 0.066 (Table 2). The average of enhancement of tumors was 6.67 ± 4.22 HU. Largest enhancement was 17.0 HU. There were 20 cases with no enhancement or mild enhancement; 6 cases with moderate enhancement. The distributions of enhancement were 10 in 0–5 HU, 10 in 6–10 HU, and 6 in 11–17 HU, The levels of enhancement were all lower than those for normal uterine endometrium.
Fig. 1 Female, 53 years old with bilateral ovarian thecoma. a Venous phase, bilateral solid mass, nonhomogenous density. Enhancement was lower than that of uterine. b HE staining 9 100
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Cell Biochem Biophys Table 1 The comparisons of tumor largest diameters between patients with and without menopause or between patients with and without ascites Group
Tumor largest diameter (mm)
Z value
P value
-0.459
0.646
-2.402
0.016
Menopause With (17)
99.06 ± 49.85
Without (9) Ascites
102.78 ± 33.90
With (16) Without (10)
116 ± 44.57 74.80 ± 30.99
Bold value indicates statistical significance (p \ 0.05) Wilcoxon rank test
Tumor Marker Examination It was found that only 2 patients out of 4 patients were positive for tumor marker detection. Their values of CA125 were 138 and 227 u/ml, respectively (normal 0.01–35 u/ ml); CA199, AFP, and CEA values were all negative. Operation and Pathology Examination Surgery findings indicated that the shape and morphology of samples were mostly matching with CT findings: tumors were of porcelain white color, with smooth surface and
Fig. 2 Female, 39 years old, right-side ovarian thecoma. Solid mass located ahead of uterine with heterogeneous density. a Arterial phase, shadow of capillary vascular could be seen inside lesions. b Venous
Fig. 3 Female, 68 years old, right side of ovarian thecoma– fibroma, a venous phase, solid mass at right-side accessories, and necrosis area with a small patch low density can be observed after enhancement; b HE staining 9 100
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clear border; the sections of tumor were ash white in color, with tough and woven-like form. 24 samples were solid tumor, while 2 samples were cystic tumor (one for follicle thecoma with yellow pigment and another for ovarian fibroma as confirmed by pathology). During operation, there were 2 cases found to be of tumor pedicle reverse, which were not found during CT diagnosis. 24 cases of patients had 26 a lesions. Among them, there were 16 thecoma (two patients with lesions on both sides) (61.54 %, 16/26), 6 fibroma (23.08 %, 6/26), 4 fiber tumors (15.38 %, 4/26). The results of 14 cases by immunohistochemistry showed CK (-), inhinbin-a (-), S-100 (-), SMA (-), Desmin (-), CD68 (-), Vimentin (?), and Ki67 (\10 % ?). Vimentin, also called VIM, forming the cytoskeleton, is the mesenchymal cell surface marker.
Discussion Theca Cell Tumor–Fibroid Tumor: Clinical Features Theca cell tumor-fibroid tumor is ovarian neoplasm, some of which can secrete hormones. Patients can incur higher level of estrogen, menstrual disorder, and abnormal vaginal bleeding. In this study, 3 patients incurred menstrual disorders, but unfortunately there was no testing of sex
phase at coronal section; ovarian vascular pedicle sign in the right side indicated that tumor came from right accessories
Cell Biochem Biophys Fig. 4 Female, 56 years old, left side of ovarian thecoma. a Venous phase, homogenous low density mass in the left accessories, which was misdiagnosis for cystic lesions by CT. b Ultrasound, heterogeneous low echo for solid mass and clear border in the left accessories
Table 2 Comparison of CT values between regular, arterial, and venous phases
One-way ANOVA
Phase
CT value (HU)
Regular
40.93 ± 9.48
Arterial
43.15 ± 9.92
Venous
47.61 ± 11.49
F
2.813
P
0.066
hormones. Patients with this group tumor were accompanied by pleural effusion and ascites, called Meigs syndrome [7, 8]. In this study, there was only 1 case of Meigs syndrome, 4.12 % (1/24), which showed the low incidence. Yen et al. [4] also reported only 1 case of Meigs syndrome among a total of 5 years cases, 3.45 % (1/29). Similar results were reported by Agaba et al. [9] and Maccio` et al. [10]. Even in rare cases of Meigs syndrome, it was well known that it occurred in thecoma–fibroma associated with ascites, and pleural effusion (triple syndrome). After resection tumor, ascites and pleural effusion could disappear. The nature of effusion could be serous or bloody, but no tumor cell and the microbial. It might due to the failure of peritoneal absorption for heavy secretion from tumor surface or blockages of lymphangion and vein. The onset age of this group tumor for most of the patients was [40 years, accounting for 70.8 % (17/24). Median onset age was 56 years, which was consistent with the reported average age [4]. The reported earliest onset ages were 8 years [11] and 13 years [12] respectively. In our study, the earliest onset age was 14 years. In this tumor group, patients with menopause accounted for 62.5 % (15/ 24), and the menopausal age ranged from 39 to 56, with the average age of 50, among which 3 cases of menopause were due to uterine resection and their age were 39, 44, and 45, respectively. This study found that the size of tumor was not associated with menopause (P [ 0.05), which suggested that hormonal changes after menopause had little effect on tumor size. Generally, patients had no obvious symptoms. Bloating and abdominal masses were the most common complaints. Tumor often occurred as
unilateral. Only 2 cases occurred as bilateral in this study (8.33 %, 2/24), and both were theca cell tumor.
Characteristics of CT Based on our CT findings of 24 cases of thecoma–fibroma and the related reports, we summarize the following CT characteristics: Most of the tumors occurred as unilateral with clear borders and with round or oval shapes, which accounted for 84.62 % (22/26) in our study. ` Contents of tumors were mainly solid. Small tumors showed homogeneous density. Larger tumors often were heterogeneous, and cyst-like or patch-like low density areas could be found inside them. In our study, solid tumors were 19 (73.08 %, 19/26), and 18 (69.2 %, 18/26) were heterogeneous density. According to previous reports [13], small patches of low density within the tumor might be caused by tumor degeneration; when a tumor diameter is [60 mm, 93 % of the tumors might appear due to cystic degeneration and necrosis which can be detected for heterogenous MRI T2 signal. In our study, the largest diameter of 21 tumor are beyond 60 mm, and it seemed that tumor with low density had bigger size. ´ Tumors were short of blood supply. Our data indicated that there were no significant differences among CT values of regular, arterial, and venous phases (P [ 0.05), which suggested that enhancement were under detection. In this study, changes in CT value after enhancement were 0–5 in 10 lesions and 5–17 in 16 lesions (Fig. 2). Shadow of capillary vascular in arterial phase could be seen in 1 lesion. Basically, our findings on enhancement were consistent with the other reported data [4–6, 14]. Also our findings were supported by ultrasound data, which showed that tumors were lack of blood flow or low blood flow [4]. Ascites were the most common complications. In this study, there were 14 cases (58.33 %, 14/24), among which small amounts of ascites were found in 12 cases. Our results indicated that tumor largest diameter in patients with ascites was 116 ± 44.57 mm, while that in patients without ascites was 74.80 ± 30.99 mm; there were significant differences
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(P \ 0.05). Our findings supported that larger tumor was more apt to be associated with ascites. Differential Diagnosis and Misdiagnosis Analysis Thecoma–fibroma often needs differential diagnosis from the following kinds of tumors: Subserous myoma or broad ligament leiomyoma: It was difficult to determine the location of the tumor because of its large size, but it can be judged from the following two characteristics: enhancement response: after enhancement, CT values of uterine muscle tumor and uterine were both strongly strengthened at the same time, whereas no enhancement or delayed mild enhancement was found in this tumor because this tumor received short of blood supply and contained fat mass and the fiber components. ` Ovarian vascular pedicle sign [15, 16]: it is formed by access vascular of ovarian in anatomy and connected with pelvic mass. As regards the occurrence of ovarian tumor, multiplanar reconstruction of MSCT can provide more information in respect of the relationship between tumor and uterine and accessories, which can help us identify pelvic masses of ovarian or non-ovarian sources. Chocolate cyst: In this study, there were 5 cases of misdiagnosis for chocolate cysts, among which 1 case had homogeneous density and with slightly higher density than bladder, and no increase after enhancement. However, ultrasound data suggested the presence of solid mass with heterogeneous echo signals and dot vascular signal. Combination of ultrasound data could exclude chocolate cyst. In this group, 3 cases with slightly higher density caused misdiagnosis, and their regular CT values were 32.18, 37.07, and 60.46 HU, respectively, with enhancement being\10 HU. Also another case of misdiagnosis showed cystic-solid mixture combined with torsion at 3 weeks. The authors believed that another reason for misdiagnosis was that differential phase blood supply could also show on enhancement. In spite of high density of chocolate cysts, combination of ultrasonography for cystic or solid signal could basically exclude it. Ovarian granulosa cell tumor: It is the second most common sex cord-stromal tumors. The most common forms observed are multilocular cystic masses with combination of cystic and solid mixture. Solid part enhancements are stronger than for the tumors that we studied here [17]. Ovarian cystadenocarcinoma: Most of the cystadenocarcinomas showed multilocular shape with cystic-solid mass and nonhomogeneous thicknesses of cystic wall and septum. A few tumors are solid mass with multilocular shape. Strengthened enhancement can be seen in the solid parts of tumor and septum, which is similar to the enhancement of uterine muscle. The signal of enhancement of ovarian cystadenocarcinoma is higher than the tumor that we studied. Cystadenocarcinoma is also associated
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with a large amount of ascites, together with irregular or cake-like thicknesses of greater omentum and nodules attached to them or with abnormally increased thickness of peritoneal. All of these show malignant signs [18]. CA125 of cystadenocarcinoma is often obviously increased. However, the tumors under this study mostly showed small amounts of ascites and mild increase in CA125. Collectively, the group of ovarian thecoma–fibroma is often found in tumors of menopausal women. The characteristic CT manifestations of the group of ovarian thecoma–fibroma were: often unilateral solid mass with the shape of oval and well defined border; no enhancement or slight enhancement; acompanied by small amount of ascites. It should be considered this disease if the manifestation matches the above, but pathology examination is still needed for confirmation.
References 1. Imaoka, I., Wada, A., Kaji, Y., et al. (2006). Developing an MR imaging strategy for diagnosis of ovarian masses. Radiographics Journal, 26(5), 1431–1448. 2. Okajima, Y., Matsuo, Y., Tamura, A., et al. (2010). Intracellular lipid in ovarian thecomas detected by dual-echo chemical shift magnetic resonance imaging: Report of 2 cases. Journal of Computer Assisted Tomography, 34(2), 223–225. 3. Chen, V. W., Ruiz, B., Killeen, J. L., et al. (2003). Pathology and classification of ovarian tumors. Cancer, 97(10 Suppl), 2631–2642. 4. Yen, P., Khong, K., Lamba, R., et al. (2013). Ovarian fibromas and fibrothecomas: Sonographic correlation with computed tomography and magnetic resonance imaging: A 5-year singleinstitution experience. Journal of Ultrasound in Medicine, 32(1), 13–18. 5. Mak, C. W., Tzeng, W. S., Chen, C. Y., et al. (2009). Computed tomography appearance of ovarian fibrothecomas with and without torsion. Acta Radiologica, 50(5), 570–575. 6. Dai, J., Wu, H., Li, J., et al. (2000). CT diagnosis of fibrothecoma and fibroma of the ovary. Zhonghua Zhong Liu Za Zhi, 22(6), 504–506. 7. Nemeth, A. J., & Patel, S. K. (2003). Meigs syndrome revisited. Journal of Thoracic Imaging, 18(2), 100–103. 8. Riker, D., & Goba, D. (2013). Ovarian mass, pleural effusion, and ascites: Revisiting Meigs syndrome. Journal of bronchology & interventional pulmonology, 20(1), 48–51. 9. Agaba, E. I., Ekwempu, C. C., Ugoya, S. O., et al. (2007). Meigs’ syndrome presenting as haemorrhagic pleural effusion. West African Journal of Medicine, 26(3), 253–255. 10. Maccio`, A., Madeddu, C., Kotsonis, P., et al. (2014). Large twisted ovarian fibroma associated with Meigs’ syndrome, abdominal pain and severe anemia treated by laparoscopic surgery. BMC Surgery, 14(1), 38. 11. Troiano, R. N., Lazzarini, K. M., Scoutt, L. M., et al. (1997). Fibroma and fibrothecoma of the ovary: MR imaging findings. Radiology, 204(3), 795–798. 12. Howell, C. G, Jr, Rogers, D. A., Gable, D. S., et al. (1990). Bilateral ovarian fibromas in children. Journal of Pediatric Surgery, 25(6), 690–691. 13. Shinagare, A. B., Meylaerts, L. J., Laury, A. R., et al. (2012). MRI features of ovarian fibroma and fibrothecoma with histopathologic correlation. AJR, 198(3), W296–W303.
Cell Biochem Biophys 14. Li, X., Zhang, W., Zhu, G., et al. (2012). Imaging features and pathologic characteristics of ovarian thecoma. Journal of Computer Assisted Tomography, 36(1), 46–53. 15. Lee, J. H., Jeong, Y. K., Park, J. K., et al. (2003). ‘‘Ovarian vascular pedicle’’ sign revealing organ of origin of a pelvic mass lesion on helical CT. American Journal of Roentgenology, 181(1), 131–137. 16. Taranto, A. J., Lourie, R., Lau, W. F., et al. (2006). Ovarian vascular pedicle sign in ovarian metastasis arising from gall bladder carcinoma. Australasian Radiology, 50(5), 504–506.
17. Kim, S. H., & Kim, S. H. (2002). Granulosa cell tumor of the ovary: Common findings and unusual appearances on CT and MR. Journal of Computer Assisted Tomography, 26(5), 756–761. 18. Zhang, Z. X., Gao, J. B., Zhang, Y. G., et al. (2011). The diagnosis of ovarian cystadenoma and cystadenocarcinoma in 31 patients on mutislice-CT. Journal of Zhengzhou University (Medical Sciences), 46(1), 143–145.
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ORIGINAL PAPER
CT Diagnosis in the Thecoma–Fibroma Group of the Ovarian Stromal Tumors Zhixu Zhang • Yan Wu • Jianbo Gao
Ó Springer Science+Business Media New York 2014
Abstract The aim of this study was to investigate characteristic CT manifestations of the group of ovarian thecoma–fibroma. 24 patients (26 lesions) presenting with the ovarian thecoma–fibroma were analyzed retrospectively, and the diagnosis were confirmed by pathology after surgery. Our findings included: 22 patients were unilateral, while 2 were bilateral; 12 lesions were located in the right side of ovary, while 14 lesions were in the left side. Of the 26 lesions, there were ovarian thecoma (16 lesions), fibrothecoma (6 lesions), and fibroma (4 lesions). The largest diameters of tumor ranged from 37 to 231 mm with the mean value of 100 ± 44.29 mm. 14 patients were accompanied by ascites. All the tumors had well-defined borders. The shape of 22 lesions appeared round or oval, and 4 lesions were irregular. The tumors were solid in 19 lesions, cystic in 2 lesions, and mixed in 5 lesions. Most of the tumors were of heterogeneous density. There were no (20 lesions) or slight enhancement (6 lesions) after injection of the contrast medium. CT values of plain scan, arterial phase and venous among three groups had no significant difference. The enhancement were in the range of 0–5 HU in 10 lesions, and 6–17 HU in 16 lesions. In conclusion, the characteristic CT manifestations of the group of ovarian thecoma–fibroma were: often unilateral solid mass with the shape of oval and well defined border; no enhancement or slight enhancement; accompanied by small amount of ascites.
Zhixu Zhang and Yan Wu have contributed equally to this work. Z. Zhang Y. Wu J. Gao (&) Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of China e-mail: [email protected]
Keywords Ovarian thecoma Fibrothecoma Fibroma Tomography
Introduction Thecoma–fibroma is a group of benign ovarian tumor with sex cord-stromal origin. It has lower incidence and accounts for 4 % of all ovarian tumors [1] which are composed of varying amounts of theca cells and fibroblasts. According to the proportion of two-component or structure, ovarian thecoma– fibroma group is divided into three different subcategories: Thecoma: almost full of the theca cells, lipid-laden [2], without fibroblasts cells; ` Thecoma–fibroma: both theca cells and fibroblasts with different proportions can be found; and ´ Fibroma: almost entirely formed by fibroblasts without theca cells. Since there are overlapping multidirectional differentiation characteristics in histology and difficulties for precise classification in pathology, WHO suggested that they be called thecoma–fibroma [3]. This type of tumor group can occur at any age. Menopausal and postmenopausal women account for most of the cases, but it can also occur in young people; rare cases can be found in patients before menarche, and the average age is in the range of 55–60 years [4]. Patients usually have no fixed clinical symptoms. Common complaints are abdominal pain, abdominal distention, or abdominal masses. Since they are caused by functional ovarian tumors, patients can incur higher levels of estrogen, menstrual disorders, and irregular vaginal bleeding. Because of the low incidence and very few cases, there are only limited data of imaging features described in the literature [4–6], proper diagnosis remains elusive. Common diagnostic methods for this group of diseases include ultrasound, MRI, and CT. For suspicious ovarian lesions, ultrasound was the preferred screening method as it was
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cheap, convenient, and simple to use. Ultrasound can be used to judge the cystic or solid mass. In thecoma–fibroma group, ultrasound can detect equal or low echo and implicates the solid mass [4]. However, problems of ultrasound are as follows: it is hard to obtain qualitative diagnosis, and there are influenced by subjective factors of operators; it only provides poor image quality which limit its application for the exchange of information to other methods. MRI can be used for qualitative diagnosis of the tumor. Usually signal of T1WI is low or slightly lower in this group, whereas signal of T2WI is complicated: thecoma cells often show equal or higher signal, while fibroma usually shows low signal. Disadvantages of MRI inspection are that it take a long time, claustrophobic patients would not accept MRI examinations. and patients, who have metal implants in vivo, could not be subjected to MRI examination, particularly those female patients with intrauterine contraceptive ring; It also has been restricted use of MRI application in some patients with larger sizes of tumor because of narrow body coverage under MRI. Therefore, CT diagnosis and evaluation of the tumor become very important. Because of the low incidence, there are only a very few studies in the literature to report CT Imaging data of tumor, and so the lack of knowledge for the CT manifestation can often cause misdiagnosis or cannot be diagnosed before surgery. In order to improve the accuracy of preoperative CT diagnosis of the disease, in the present study, we retrospectively analyzed 24 cases of verified theca cell tumors in our hospital for evaluating their CT characteristics and the related clinical data.
complaints reported were pelvic masses for 17 patients with the longest history of 11 months. 7 patients complained abdominal pain and other 3 patients complained menstrual disorder. CT Procedure 24 patients underwent plain and contrast enhanced CT scan using GE Discovery CT750 HD and Toshiba Aquilion One 640 CT. Before scanning, patients drank 1500–2000 ml warm water to fill intestinal and the bladder located in lower abdomen area. Patients with supine position were asked to hold breath during scanning. Scanning was started from top of diaphragm plane to low margin of pubic joint at tube voltage of 120 kV, with auto current mode in the range of 200–500 mAs. With 5-mm layer thickness and a pitch of 1, enhancement was done with nonionic iodine contrast agent. After the patients completed the fast injection of contrast agents in elbow vein with high-pressure syringe at the dose of 1.5 ml/kg and speed of 3–4 ml/s, artery and vein doublephase scan were performed, by means of automatically triggered technology applied in artery phase, plus 30–35s duration of arteria phase for venous phase. CT images were processed in GE ADW4.4 Workstation and Toshiba Vitrea 6.3 workstation for coronal, sagittal, and oblique reconstructions; both reconstruction slice thickness and reconstruction interval were 3 mm. Tumor Markers Examination Among 24 cases, 5 cases were examined for tumor markers: CA125, CA199, AFP, and CEA.
Material and Method Pathology Examination General Information 24 cases of pathologically confirmed thecoma–fibroma tumors after surgery were considered in this study for analyzing their clinical and preoperative CT imaging data collected from November 2010 to May 2014, with prior consent and approval from the hospital medical imaging center. Ages of patients ranges from 14 to 78 years old: median age 56 years, 4 cases aged less than 30 years old, 3 cases in the age range of 31–40 years old, 3 cases in the age range of 41–50 years old, and 14 cases aged more than 51 years old. There were 15 cases of patients with menopause, among whom 3 cases were caused by uterine resection (2 cases due to uterine myoma, and 1 case due to mucinous cystadenoma). Two cases of patients (14 and 23 years old) were unmarried without sex history, and 2 cases of patients (24 and 28 years old) were married without pregnancy history. The remaining patients were married with pregnancy history. Main
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All cases of routine HE stains were obtained after patients’ surgical resection for pathology diagnosis. 14 cases of immunohistochemical staining were conducted for further diagnosis. Image Analysis CT imaging was analyzed by two radiologists (both are associate professors) who possessed expertise in abdominal images. Only settled opinions were used for final diagnosis, in case of disagreement. Observations were focused on following features: location (left or right); ` shape (round, oval, or irregular); ´ border (clear or not); and ˆ largest diameter after measure of sagittal, coronal and transverse plane, the largest diameter was selected for later analysis. Patients were divided into two groups according to menopause status and correlation between largest diameter and menopause was analyzed. Correlation of
Cell Biochem Biophys
largest diameter and ascites was also analyzed; ˜ Content (cystic, solid, or mixture); Þ Degree of enhancement (Degree of enhancement = venous phase CT value - average of CT-values, 0–10 HU for no enhancement, 10–20 HU for mild enhancement, and 20–40 HU for moderate enhancement, 40–60 HU for strong enhancement); and þ Effusion or no effusion in abdomen. Surgical, and pathological findings were referred for co-analysis. Largest diameter measurements: averaging three times measurement in the diameter of largest section; CT value measurement: solid part of tumor mass was further divided into three parts: top, middle, and bottom. Each part measured three areas of interest. Totally nine measurement per tumor were made. CT value was defined to the average of those nine measurements. The size of area of interest was around 30 mm2. For cystic-dominant tumor, only solid part of tumor was measured.
Statistics SPSS17.0 software was used for statistics analysis. Enumeration data (occurrence rate and incidence) were processed with percentage. Measurement data (CT value and the tumor largest diameter) were processed with mean ± SD values. The one-way ANOVA was used to compare the difference between CT values of plain, and artery phase, and vein phase. Wilcoxon rank test was used to determine the correlation of the tumor largest diameter with menopause or ascites relationship. P \ 0.05 was set as statistically significant.
Results CT Findings Among 24 patients, only 2 patients had lesions on both sides (8.3 %, 2/24) (Fig. 1). In total, there were 26 lesions in 24 patients. For primary CT diagnosis, there were 3 cases of sex cord-stromal tumors, 8 cases of unknown mass, 5 cases of leiomyoma of uterus, 5 cases of chocolate
cyst, 1 case cystadenoma, 1 case of cystadenocarcinoma, 1 case of dysgerminoma. Since, in this study 24 cases covered all of the three subtypes of the tumor, we analyzed their CT image characteristics together. There are 12 lesions in the right (46.15 %, 12/26), and 14 in the left (53.85 %, 14/26) among 26 lesions out of 24 cases; All tumor boundaries were clear. As for the shape, 22 lesions were oval or round, and 4 lesions were irregular. Largest diameter of tumors ranged from 37 to 231 mm with the average of 100 ± 44.29 mm. There were 14 cases associated with ascites (58.33 %, 14/24), among which 12 cases had only small amounts of ascites (200 ml), and 1 case also occurred with pleural effusion. There was no significant difference among tumor largest diameters between patients with and without menopause. However, statistically significant differences of tumor largest diameters were found between patients with and without ascites, and the largest diameter of tumor in patients with ascites were larger than the one in patients without ascites (Table 1). Among 26 lesions, there were 9 solid lesions and 4 solidcystic lesions which showed solid features, and there were two cystic lesions in which only a few solid features could be detected at the bottom of cyst cavity (Figs. 2, 3). 8 out of 26 lesions were homogeneous density, and one of them had the size of 95 mm 9 85 mm with 23.51 HU for plain CT, 27.54 HU for arterial phase and 7.86 for venous phase. This case was misdiagnosed by CT for chocolate cyst and the results of ultrasound indicated its solid mass feature (Fig. 4). Average of regular tumor CT values of 26 lesions was 40.93 ± 9.48 HU; arterial phase CT value was 43.15 ± 9.92 HU; and venous phase CT value was 47.61 ± 11.49 HU. Since regular, arterial phase, and venous phase CT values meet normal distribution, ANOVA with single factors variance was used for statistical analysis. F = 2.813, P = 0.066 (Table 2). The average of enhancement of tumors was 6.67 ± 4.22 HU. Largest enhancement was 17.0 HU. There were 20 cases with no enhancement or mild enhancement; 6 cases with moderate enhancement. The distributions of enhancement were 10 in 0–5 HU, 10 in 6–10 HU, and 6 in 11–17 HU, The levels of enhancement were all lower than those for normal uterine endometrium.
Fig. 1 Female, 53 years old with bilateral ovarian thecoma. a Venous phase, bilateral solid mass, nonhomogenous density. Enhancement was lower than that of uterine. b HE staining 9 100
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Cell Biochem Biophys Table 1 The comparisons of tumor largest diameters between patients with and without menopause or between patients with and without ascites Group
Tumor largest diameter (mm)
Z value
P value
-0.459
0.646
-2.402
0.016
Menopause With (17)
99.06 ± 49.85
Without (9) Ascites
102.78 ± 33.90
With (16) Without (10)
116 ± 44.57 74.80 ± 30.99
Bold value indicates statistical significance (p \ 0.05) Wilcoxon rank test
Tumor Marker Examination It was found that only 2 patients out of 4 patients were positive for tumor marker detection. Their values of CA125 were 138 and 227 u/ml, respectively (normal 0.01–35 u/ ml); CA199, AFP, and CEA values were all negative. Operation and Pathology Examination Surgery findings indicated that the shape and morphology of samples were mostly matching with CT findings: tumors were of porcelain white color, with smooth surface and
Fig. 2 Female, 39 years old, right-side ovarian thecoma. Solid mass located ahead of uterine with heterogeneous density. a Arterial phase, shadow of capillary vascular could be seen inside lesions. b Venous
Fig. 3 Female, 68 years old, right side of ovarian thecoma– fibroma, a venous phase, solid mass at right-side accessories, and necrosis area with a small patch low density can be observed after enhancement; b HE staining 9 100
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clear border; the sections of tumor were ash white in color, with tough and woven-like form. 24 samples were solid tumor, while 2 samples were cystic tumor (one for follicle thecoma with yellow pigment and another for ovarian fibroma as confirmed by pathology). During operation, there were 2 cases found to be of tumor pedicle reverse, which were not found during CT diagnosis. 24 cases of patients had 26 a lesions. Among them, there were 16 thecoma (two patients with lesions on both sides) (61.54 %, 16/26), 6 fibroma (23.08 %, 6/26), 4 fiber tumors (15.38 %, 4/26). The results of 14 cases by immunohistochemistry showed CK (-), inhinbin-a (-), S-100 (-), SMA (-), Desmin (-), CD68 (-), Vimentin (?), and Ki67 (\10 % ?). Vimentin, also called VIM, forming the cytoskeleton, is the mesenchymal cell surface marker.
Discussion Theca Cell Tumor–Fibroid Tumor: Clinical Features Theca cell tumor-fibroid tumor is ovarian neoplasm, some of which can secrete hormones. Patients can incur higher level of estrogen, menstrual disorder, and abnormal vaginal bleeding. In this study, 3 patients incurred menstrual disorders, but unfortunately there was no testing of sex
phase at coronal section; ovarian vascular pedicle sign in the right side indicated that tumor came from right accessories
Cell Biochem Biophys Fig. 4 Female, 56 years old, left side of ovarian thecoma. a Venous phase, homogenous low density mass in the left accessories, which was misdiagnosis for cystic lesions by CT. b Ultrasound, heterogeneous low echo for solid mass and clear border in the left accessories
Table 2 Comparison of CT values between regular, arterial, and venous phases
One-way ANOVA
Phase
CT value (HU)
Regular
40.93 ± 9.48
Arterial
43.15 ± 9.92
Venous
47.61 ± 11.49
F
2.813
P
0.066
hormones. Patients with this group tumor were accompanied by pleural effusion and ascites, called Meigs syndrome [7, 8]. In this study, there was only 1 case of Meigs syndrome, 4.12 % (1/24), which showed the low incidence. Yen et al. [4] also reported only 1 case of Meigs syndrome among a total of 5 years cases, 3.45 % (1/29). Similar results were reported by Agaba et al. [9] and Maccio` et al. [10]. Even in rare cases of Meigs syndrome, it was well known that it occurred in thecoma–fibroma associated with ascites, and pleural effusion (triple syndrome). After resection tumor, ascites and pleural effusion could disappear. The nature of effusion could be serous or bloody, but no tumor cell and the microbial. It might due to the failure of peritoneal absorption for heavy secretion from tumor surface or blockages of lymphangion and vein. The onset age of this group tumor for most of the patients was [40 years, accounting for 70.8 % (17/24). Median onset age was 56 years, which was consistent with the reported average age [4]. The reported earliest onset ages were 8 years [11] and 13 years [12] respectively. In our study, the earliest onset age was 14 years. In this tumor group, patients with menopause accounted for 62.5 % (15/ 24), and the menopausal age ranged from 39 to 56, with the average age of 50, among which 3 cases of menopause were due to uterine resection and their age were 39, 44, and 45, respectively. This study found that the size of tumor was not associated with menopause (P [ 0.05), which suggested that hormonal changes after menopause had little effect on tumor size. Generally, patients had no obvious symptoms. Bloating and abdominal masses were the most common complaints. Tumor often occurred as
unilateral. Only 2 cases occurred as bilateral in this study (8.33 %, 2/24), and both were theca cell tumor.
Characteristics of CT Based on our CT findings of 24 cases of thecoma–fibroma and the related reports, we summarize the following CT characteristics: Most of the tumors occurred as unilateral with clear borders and with round or oval shapes, which accounted for 84.62 % (22/26) in our study. ` Contents of tumors were mainly solid. Small tumors showed homogeneous density. Larger tumors often were heterogeneous, and cyst-like or patch-like low density areas could be found inside them. In our study, solid tumors were 19 (73.08 %, 19/26), and 18 (69.2 %, 18/26) were heterogeneous density. According to previous reports [13], small patches of low density within the tumor might be caused by tumor degeneration; when a tumor diameter is [60 mm, 93 % of the tumors might appear due to cystic degeneration and necrosis which can be detected for heterogenous MRI T2 signal. In our study, the largest diameter of 21 tumor are beyond 60 mm, and it seemed that tumor with low density had bigger size. ´ Tumors were short of blood supply. Our data indicated that there were no significant differences among CT values of regular, arterial, and venous phases (P [ 0.05), which suggested that enhancement were under detection. In this study, changes in CT value after enhancement were 0–5 in 10 lesions and 5–17 in 16 lesions (Fig. 2). Shadow of capillary vascular in arterial phase could be seen in 1 lesion. Basically, our findings on enhancement were consistent with the other reported data [4–6, 14]. Also our findings were supported by ultrasound data, which showed that tumors were lack of blood flow or low blood flow [4]. Ascites were the most common complications. In this study, there were 14 cases (58.33 %, 14/24), among which small amounts of ascites were found in 12 cases. Our results indicated that tumor largest diameter in patients with ascites was 116 ± 44.57 mm, while that in patients without ascites was 74.80 ± 30.99 mm; there were significant differences
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(P \ 0.05). Our findings supported that larger tumor was more apt to be associated with ascites. Differential Diagnosis and Misdiagnosis Analysis Thecoma–fibroma often needs differential diagnosis from the following kinds of tumors: Subserous myoma or broad ligament leiomyoma: It was difficult to determine the location of the tumor because of its large size, but it can be judged from the following two characteristics: enhancement response: after enhancement, CT values of uterine muscle tumor and uterine were both strongly strengthened at the same time, whereas no enhancement or delayed mild enhancement was found in this tumor because this tumor received short of blood supply and contained fat mass and the fiber components. ` Ovarian vascular pedicle sign [15, 16]: it is formed by access vascular of ovarian in anatomy and connected with pelvic mass. As regards the occurrence of ovarian tumor, multiplanar reconstruction of MSCT can provide more information in respect of the relationship between tumor and uterine and accessories, which can help us identify pelvic masses of ovarian or non-ovarian sources. Chocolate cyst: In this study, there were 5 cases of misdiagnosis for chocolate cysts, among which 1 case had homogeneous density and with slightly higher density than bladder, and no increase after enhancement. However, ultrasound data suggested the presence of solid mass with heterogeneous echo signals and dot vascular signal. Combination of ultrasound data could exclude chocolate cyst. In this group, 3 cases with slightly higher density caused misdiagnosis, and their regular CT values were 32.18, 37.07, and 60.46 HU, respectively, with enhancement being\10 HU. Also another case of misdiagnosis showed cystic-solid mixture combined with torsion at 3 weeks. The authors believed that another reason for misdiagnosis was that differential phase blood supply could also show on enhancement. In spite of high density of chocolate cysts, combination of ultrasonography for cystic or solid signal could basically exclude it. Ovarian granulosa cell tumor: It is the second most common sex cord-stromal tumors. The most common forms observed are multilocular cystic masses with combination of cystic and solid mixture. Solid part enhancements are stronger than for the tumors that we studied here [17]. Ovarian cystadenocarcinoma: Most of the cystadenocarcinomas showed multilocular shape with cystic-solid mass and nonhomogeneous thicknesses of cystic wall and septum. A few tumors are solid mass with multilocular shape. Strengthened enhancement can be seen in the solid parts of tumor and septum, which is similar to the enhancement of uterine muscle. The signal of enhancement of ovarian cystadenocarcinoma is higher than the tumor that we studied. Cystadenocarcinoma is also associated
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with a large amount of ascites, together with irregular or cake-like thicknesses of greater omentum and nodules attached to them or with abnormally increased thickness of peritoneal. All of these show malignant signs [18]. CA125 of cystadenocarcinoma is often obviously increased. However, the tumors under this study mostly showed small amounts of ascites and mild increase in CA125. Collectively, the group of ovarian thecoma–fibroma is often found in tumors of menopausal women. The characteristic CT manifestations of the group of ovarian thecoma–fibroma were: often unilateral solid mass with the shape of oval and well defined border; no enhancement or slight enhancement; acompanied by small amount of ascites. It should be considered this disease if the manifestation matches the above, but pathology examination is still needed for confirmation.
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