Spectrum of FDG PET/CT Findings of Uterine Tumors

Nuclear Medicine and Molecular Imaging Pictorial Essay Kitajima et al. FDG PET/CT of Uterine Tumors Nuclear Medicine and Molecular Imaging Pictorial Essay Downloaded from www.ajronline.org by 37.44.205.17 on 12/10/17 from IP address 37.44.205.17. Copyright RRS. For personal use only; all rights reserved Kazuhiro Kitajima 1,2 Koji Murakami 3 Yasushi Kaji 2 Kazuro Sugimura 1 Kitajima K, Murakami K, Kaji Y, Sugimura K Keywords: FDG PET/CT, MRI, oncologic imaging, uterine tumors, uterus DOI:10.2214/JR.09.4074 Received December 6, 2009; accepted after revision February 3, 2010. 1 Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan. ddress correspondence to K. Kitajima (kazu10041976@yahoo.co.jp). 2 Department of Radiology, Dokkyo University School of Medicine, Mibu, Japan. 3 PET Center, Dokkyo Medical University Hospital, Mibu, Japan. CME This article is available for CME credit. See www.arrs.org for more information. JR 2010; 195:737 743 0361 803X/10/1953 737 merican Roentgen Ray Society Spectrum of FDG PET/CT Findings of Uterine Tumors OJECTIVE. The purpose of this article is to review FDG PET/CT and MRI findings in a variety of benign and malignant tumors of the uterus and to become familiar with the wide variety of FDG PET/CT findings of this entity. CONCLUSION. enign uterine tumors generally have mild FDG uptake, and leiomyoma rarely shows high uptake. Uterine malignant tumors generally have intense FDG uptake, whereas malignant uterine tumors that are small or that have low cellular density often show minimal uptake. P ET/CT with 18F-FDG is increasingly being used for disease staging and restaging and for monitoring treatment of patients with various cancers. lthough FDG generally accumulates in malignant lesion because of high glucose metabolism, FDG can also accumulate in normal tissue, benign lesions, and tissues affected by inflammatory processes. Hence, knowledge of the wide variety of FDG PET/CT findings is important for the proper interpretation of FDG PET/CT scans. We illustrate the spectrum of FDG PET/CT findings in benign and malignant uterine tumors. Physiologic Endometrial Uptake Physiologic FDG endometrial uptake can be seen around the time of the first 3 days of menstruation and the ovulatory phase of the menstrual cycle in premenopausal women. Lerman et al. [1] reported that the mean endometrial standardized uptake values (SUVs) in premenopausal women were 5 ± 3.2 (SD) and 3.7 ± 0.9 during the menstruating and ovulating phases, respectively, and 2.6 ± 1.1 and 2.5 ± 1.1 during the proliferative and secretory phases, respectively. They also reported that the mean endometrial SUV of postmenopausal women receiving hormonal therapy was 1.7 ± 0.7 (range, 1.1 2.6) and that hormonal therapy in postmenopausal women was not associated with a significant alteration in endometrial FDG uptake. Increased FDG endometrial uptake in postmenopausal women may indicate malignancy. enign Tumors Uterine Leiomyoma Uterine leiomyomas usually show mild FDG uptake (Fig. 1) but sometimes show intense uptake (Fig. 2). Chura et al. [2] reported leiomyomas showing very high SUVs in three patients: One case was an ordinary leiomyoma of 13 mm (SUV = 16), the second was a cellular leiomyoma of 30 mm (SUV = 9.3), and the third was a stromomyoma (SUV = 6). lthough the exact mechanism responsible for high FDG uptake in leiomyomas is unclear, the phenomenon would be regulated by several factors including hormonal dependency, cellularity (the number of viable tumor cells), vascularity (microvessel density), tumor cell proliferation (the expression of growth factors such as basic fibroblast growth factor, transforming growth factor β, granulocyte-macrophage colony-stimulating factor, and Ki- 67 and their receptors), expression of glucose transporter 1 (GLUT-1) and hexokinase, the existence of endometrial tissue, and the presence of inflammatory cells [3, 4]. Leiomyomas with FDG uptake are more common in premenopausal women than postmenopausal women [3, 4]. Nishizawa et al. [3] reported that the incidence of FDG uptake in premenopausal women with leiomyomas (10.4% of 164 women) was higher than that in postmenopausal women with leiomyomas (1.2% of 338 women). They also showed that leiomyoma in premenopausal women tends to show higher uptake during a luteal phase than during menstrual flow and the follicular and periovulatory phases. lthough JR:195, September 2010 737

Kitajima et al. Downloaded from www.ajronline.org by 37.44.205.17 on 12/10/17 from IP address 37.44.205.17. Copyright RRS. For personal use only; all rights reserved they reported that degenerated leiomyomas showing high signal intensity on T2-weighted MR images (Fig. 3) tend to show higher FDG uptake than nondegenerated leiomyoma showing low signal intensity on T2-weighted MR images [3, 4], nondegenerated leiomyoma can often show high uptake (Fig. 2). denomyosis lthough adenomyosis generally shows mild FDG uptake (Fig. 4) in premenopausal women, it often shows higher uptake during the menstruating and ovulating phases. Endometrial Hyperplasia Endometrial hyperplasia mainly shows mild FDG uptake (Fig. 5). Tsujikawa et al. [5] reported that the mean SUV of endometrial cancer in nine patients was 9.6 ± 3.3 (SD) (range, 3.7 15.2) and that the mean SUV of endometrial hyperplasia in four patients was 1.7 ± 0.3 (range, 1.3 1.9). lthough the SUV values endometrial cancer and endometrial hyperplasia did not overlap, a study of larger sample size is warranted. Malignant Tumors Uterine Cervical Cancer lthough uterine cervical cancer generally shows intense FDG uptake (Fig. 6), small malignant tumors and malignant tumors with low cellular density may not show FDG uptake (Fig. 7) because of the limited spatial resolution of the PET machine (i.e., the partial volume effect). Kidd et al. [6, 7] reported that mean maximum SUV (SUV max ) of cervical cancer in 287 patients was 11.4 (range, 1 50.4). No correlation was noted between SUV max and International Federation of Gynecology and Obstetrics (FIGO) stage and tumor volume [6, 7]. Squamous cell carcinomas have been reported to tend to show higher SUV max values than nonsquamous cell carcinomas and poorly differentiated carcinomas have been reported to tend to show higher SUV max values than well- or moderately differentiated carcinomas [6]. Higher SUV max values were associated with an increased risk of lymph node metastasis [6, 7].Several authors have shown that FDG PET/CT of patients with uterine cervical cancer who have not yet received treatment to determine the SUV of the primary cancer, lymph node status, endometrial extension, and so on may be a sensitive biomarker of treatment response and prognosis [6 10]. Compared with MRI, PET/CT has a limited role for local staging of primary cancer (Fig. 6), whereas PET/CT is useful for assessing distant metastases throughout the whole body in a single examination in patients with advanced-stage disease. lthough PET/CT can detect normal-sized lymph node metastases from 5 to 9 mm, which conventional CT and MRI cannot diagnose, even PET/CT cannot detect micrometastases, the size of which is under a PET machine s sensitivity [11]. Minimal-deviation adenocarcinoma showed moderate FDG uptake (Fig. 8). lthough FDG PET could be used for the differential diagnosis of minimal-deviation adenocarcinoma from nabothian cyst, a study of larger sample size is warranted. Endometrial Cancer lthough endometrial cancer generally shows intense FDG uptake (Fig. 9), small malignant tumors or malignant tumors with low cellular density may not show uptake because of the limited spatial resolution of the PET machine. Kitajima et al. [12] reported that the mean SUV of endometrial cancer in 40 patients was 11.2 ± 5.9 (SD) (range, 2 25.6). Few reports discussing FDG PET/ CT of endometrial cancer are available to date in the medical literature. Compared with MRI, PET/CT has a limited role for local staging of primary cancer (Fig. 9), whereas PET/CT is a useful technique for assessing distant metastases throughout the whole body in a single examination in patients with advanced-stage disease. lthough PET/CT can often detect normal-sized lymph node metastases from 5 to 9 mm, which conventional CT and MRI cannot diagnose (Fig. 10), even PET/CT cannot detect micrometastasis, the size of which is under a PET machine s sensitivity [12]. Leiomyosarcoma Uterine leiomyosarcoma usually shows moderate to intense FDG uptake (Fig. 11). Umesaki et al. [13] reported that SUVs of uterine leiomyosarcoma in two patients were 3.0 and 3.9, and Tsujikawa et al. [5] reported that mean SUV of uterine leiomyosarcoma in four patients was 6.4 ± 4.3 (SD) (range, 2.4 10.2). ecause uterine leiomyoma rarely shows high FDG uptake (Fig. 2) and leiomyosarcoma rarely shows mild FDG uptake (Fig. 12), unfortunately FDG PET cannot be used to differentiate leiomyosarcoma from leiomyoma. Other Uterine Sarcomas Endometrial stromal sarcoma (Fig. 13) and uterine carcinosarcoma (Fig. 14) generally show intense FDG uptake. Ho et al. [14] reported that the mean SUV of uterine carcinosarcoma in 19 patients was 10.3 ± 5.5 (range, 3.1 22.4). Uterine Metastatic Tumor Uterine metastatic tumors generally show intense FDG uptake (Fig. 15). References 1. Lerman H, Metser U, Grisaru D, Fishman, Lievshitz G, Even-Spair E. Normal and abnormal 18 F-FDG endometrial and ovarian uptake in preand postmenopausal patients: assessment by PET/ CT. J Nucl Med 2004; 45:266 271 2. Chura JC, Truskinovsky M, Judson PL, Johnson L, Geller M, Downs LS. Positron emission tomography and leiomyomas: clinical analysis of 3 cases of PET scan-positive leiomyomas and literature review. Gynecol Oncol 2007; 104:247 252 3. Nishizawa S, Inubushi M, Kido, et al. Incidence and characteristics of uterine leiomyomas with FDG uptake. nn Nucl Med 2008; 22:803 810 4. Kitajima K, Murakami K, Yamasaki E, Kaji Y, Sugimura K. Standardized uptake values of uterine leiomyoma with 18 F-FDG PET/CT: variation with age, size, degeneration, and contrast enhancement on MRI. nn Nucl Med 2008; 22:505 512 5. Tsujikawa T, Yoshida Y, Mori T, et al. Uterine tumors: pathophysiologic imaging with 16α-[ 18 F] fluoro-17β-estradiol and 18 F-fluorodeoxyglucose PET initial experience. Radiology 2008; 248: 599 605 6. Kidd E, Spencer CR, Heuttner PC, et al. Cervical cancer histology and tumor differentiation affect 18 F-fluorodeoxyglucose uptake. Cancer 2009; 115:3548 3554 7. Kidd E, Siegel, Dehdashti F, Grigsby PW. The standardized uptake value for F-18 fluorodeoxyglucose is a sensitive predictive biomarker for cervical cancer treatment response and survival. Cancer 2007; 110:1738 1744 8. Singh K, Grigsby W, Dehdasht F, Herzog T, Siegel. FDG-PET lymph node staging and survival of patients with FIGO stage IIIb cervical carcinoma. Int J Radiat Oncol iol Phys 2003; 56:489 493 9. Hope J, Saha P, Grigsby PW. FDG-PET in carcinoma of the uterine cervix with endometrial extension. Cancer 2006; 106:196 200 10. Yen TC, See LC, Lai CH, et al. Standardized uptake in para-aortic lymph nodes is a significant prognostic factor in patients with primary advanced squamous cervical cancer. Eur J Nucl Med Mol Imaging 2008; 35:493 501 11. Sironi S, uda, Picchio M, et al. Lymph node metastasis in patients with clinical early-stage 738 JR:195, September 2010

FDG PET/CT of Uterine Tumors cervical cancer: detection with integrated FDG PET/CT. Radiology 2006; 238:272 279 12. Kitajima K, Murakami K, Yamasaki E, et al. ccuracy of FDG PET/CT in detecting pelvic and paraortic lymph node metastasis in patients with endometrial cancer. JR 2008; 190:1652 1658 13. Umesaki N, Tanaka T, Miyama M, et al. Positron emission tomography with 18 F-fluorodeoxyglucose of uterine sarcoma: a comparison with magnetic resonance imaging and power Doppler imaging. Gynecol Oncol 2001; 80:372 377 14. Ho KC, Lai CH, Wu TI, et al. 18 F-fluorodeoxyglucose positron emission tomography in uterine carcinosarcoma. Eur J Nucl Med Mol Imaging 2008; 35:484 492 Downloaded from www.ajronline.org by 37.44.205.17 on 12/10/17 from IP address 37.44.205.17. Copyright RRS. For personal use only; all rights reserved Fig. 1 45-year-old woman with leiomyoma showing imaging findings typical of leiomyoma., Ordinary nondegenerated leiomyoma measuring 5.5 cm shows homogeneous low signal intensity on T2-weighted MR image., On PET/CT image, leiomyoma shows faint FDG uptake with maximum standardized uptake value of 2.0. Fig. 2 47-year-old woman with leiomyoma showing unusual imaging findings., Ordinary nondegenerated leiomyoma (arrow) measuring 1.3 cm shows homogeneous low signal intensity on T2-weighted image., On PET/CT image, leiomyoma (arrow) shows uptake value of 8.5. Fig. 3 40-year-old woman with leiomyoma showing imaging findings typical of leiomyoma., Degenerated leiomyoma measuring 6.0 cm shows heterogeneous mixed low and high signal intensity on T2-weighted image., On PET/CT image, leiomyoma shows moderate FDG uptake with maximum standardized uptake value of 3.9. JR:195, September 2010 739

Kitajima et al. Fig. 4 45-year-old woman with diffuse adenomyosis., Diffuse adenomyosis shows low signal intensity with hyperintense tiny foci in enlarged myometrium on T2-weighted image., On PET/CT image, adenomyosis shows mild FDG uptake with maximum standardized uptake value of 2.5. Downloaded from www.ajronline.org by 37.44.205.17 on 12/10/17 from IP address 37.44.205.17. Copyright RRS. For personal use only; all rights reserved Fig. 5 42-year-old woman with endometrial hyperplasia., Endometrial hyperplasia shows thick endometrium on T2-weighted image., On PET/CT image, endometrial hyperplasia (arrow) shows faint FDG uptake with maximum standardized uptake value of 2.0. Fig. 6 32-year-old woman with advanced-stage uterine cervical cancer., Uterine cervical cancer shows heterogeneous high signal intensity invades right parametrium on T2-weighted image (International Federation of Gynecology and Obstetrics [FIGO] stage IIb)., On PET/CT image, uterine cervical cancer shows uptake value of 12.5. Whether there is invasion of parametrium is not clear on PET/CT. 740 JR:195, September 2010

FDG PET/CT of Uterine Tumors Fig. 7 62-year-old woman with early-stage uterine cervical cancer., Uterine cervical cancer (arrow) shows high signal intensity is localized in cervix (International Federation of Gynecology and Obstetrics stage Ib) on T2-weighted image., On PET/CT image, tiny uterine cervical cancer shows no abnormal FDG uptake. Downloaded from www.ajronline.org by 37.44.205.17 on 12/10/17 from IP address 37.44.205.17. Copyright RRS. For personal use only; all rights reserved Fig. 8 40-year-old woman with minimal-deviation adenocarcinoma., Minimal-deviation adenocarcinoma appears multilobulated and shows high signal intensity on T2- weighted image., On PET/CT image, minimal-deviation adenocarcinoma shows moderate FDG uptake with maximum standardized uptake value of 5.3. Fig. 9 64-year-old woman with endometrial cancer involving lymph node., Endometrial cancer shows heterogeneous high signal intensity invades myometrium on T2-weighted image (International Federation of Gynecology and Obstetrics stage Ib). MRI shows right internal iliac lymphadenopathy measuring 2.8 cm, suggesting presence of nodal cancer spread., On PET/CT image, endometrial cancer shows strong FDG uptake with maximum standardized uptake value of 15.0. Whether there is invasion of myometrium is not clear on PET/CT. PET/CT shows abnormal uptake corresponding to right internal iliac lymph node, clarifying presence of nodal cancer spread. JR:195, September 2010 741

Kitajima et al. Downloaded from www.ajronline.org by 37.44.205.17 on 12/10/17 from IP address 37.44.205.17. Copyright RRS. For personal use only; all rights reserved Fig. 10 55-year-old woman with bilateral internal lymph node metastases due to endometrial cancer., MR image shows two small lymph nodes measuring 7 mm in bilateral internal iliac areas (arrows), but it is difficult to diagnose lymph node metastases because of size criterion., PET/CT image shows abnormal uptake corresponds to two small lymph nodes (arrows), clarifying presence of nodal cancer spread. Histopathology results confirmed this imaging finding. Fig. 11 58-year-old woman with uterine leiomyosarcoma showing imaging findings typical of leiomyosarcoma., Huge uterine tumor shows heterogeneous high signal intensity with omentum involvement on T2- weighted image., On PET/CT image, huge uterine tumor shows uptake value of 15.7. Omental and peritoneal dissemination (arrows) also show strong FDG uptake. Fig. 12 51-year-old woman with uterine leiomyosarcoma showing unusual imaging findings., Huge uterine tumor shows heterogeneous high and low signal mixed intensity on T2-weighted image., On PET/CT image, huge uterine tumor shows moderate FDG uptake with maximum standardized uptake value of 6.5. 742 JR:195, September 2010

FDG PET/CT of Uterine Tumors Downloaded from www.ajronline.org by 37.44.205.17 on 12/10/17 from IP address 37.44.205.17. Copyright RRS. For personal use only; all rights reserved FOR YOUR INFORMTION This article is available for CME credit. See www.arrs.org for more information. Fig. 13 61-year-old woman with endometrial stromal sarcoma., MR image reveals hyperintense endometrial tumor showing extensive myometrial involvement with bands of low signal intensity on T2-weighted image. Tumor thrombus (arrow) in left ovarian vessel is suspected., On PET/CT image, huge uterine tumor shows uptake value of 8.2. Tumor thrombus (arrow) with intense uptake is seen in left ovarian vessel. Fig. 14 55-year-old woman with carcinosarcoma., Uterine polypoid mass in cavity of uterine body shows high and low signal intensity on T2-weighted image., On PET/CT image, uterine tumor shows strong FDG uptake with maximum standardized uptake value of 11.1. Fig. 15 53-year-old woman with uterine metastatic tumor from gastric cancer., Two masses in myometrium show heterogeneous low signal intensity on T2-weighted image., On PET/CT image, two uterine tumors show strong FDG uptake with maximum standardized uptake value of 13.4 and 15.2. JR:195, September 2010 743