Probable imaging diagnosis
Case 157
【Progress】
She was diagnosed as multiple myeloma (λ type M protein positive), inducing progressive anemia. She was scheduled to transport to the hospital where gynecologist and hematologist can serve the management together.
【Discussion】
Follicular stimulating hormone (FSH) and luteinizing hormone (LH) from anterior lobe of pituitary gland play a role of forming follicular cyst before ovulation and corpus luteum cyst after ovulation. It is reported that the maximum sizes of follicular cyst and corpus luteum cyst are approximately 35mm and 50mm, respectively (1, 2).
Granulosa cells exist surrounding oocytes and follicle, and theca cells exist such as capsule-like surrounding oocytes, follicle and granulosa cells. Theca cells create and secrete androgen precursor by stimulation of LH using cholesterol in blood. Granulosa cells create and secrete estrogen before ovulation and progesterone after ovulation by stimulation of FSH using androgen precursor from theca cells. After ovulation, granulosa cells also secrete inhibin which inhibits the secretion of FSH releasing factor (FSHRF) from hypothalamus (1, 2).
The latest ovarian cancer therapy focuses on the target to eradicate cancer stem cells. The idea of cancer stem cells is relatively new and getting acknowledged and prevailed. Ovarian cancer is composed of various kinds of cancer cells with high differentiated, moderate differentiated or poorly differentiated and cancer stem cells. Differentiated cancer cells are possibly able to function such as secretion of hormone. It is believed that radio-chemotherapy is effective for differentiated cancer cells but resistant for cancer stem cells (3, 4). The control or management for cancer stem cells are the future subject to be achieved. It is not clarified whether granulosa cell tumors include cancer stem cells but they are differentiated tumors and function to secret inhibin like normal granulosa cells to repress FSHRF secretion from hypothalamus.
Ovarian tumors are categorized into surface epithelial tumor, germ cell tumor, sex chord stromal tumor and metastatic tumors. Surface epithelial tumor is sub-categorized into serous cystic carcinoma, mucinous cystic carcinoma, endometrioid carcinoma and clear cell carcinoma. Germ cell tumor is categorized into teratoma, immature teratoma and dysgerminoma. Sex cohort stromal tumor is categorized into fibroma, granulosa cell tumor and theca cell tumor. Metastatic tumor is termed as Kruckenberg and primary tumors often come from gastric cancer or colon cancer (5).
Macroscopic findings of granulosa cell tumors show solid type, cystic type and mixed (solid + cystic) type. These types sometimes include hemorrhage. Granulosa cell tumor of the ovary occurs at any age. When it occurs before puberty, premature menstruation appears and when it occurs during mature adult, hyper menstruation appear and when it occurs at menopause, the intimal thickening of uterus appears (6 – 8).
In our case, CT showed inhomogeneous cystic tumor with slight high content inside, corresponded to the right ovary which is nonspecific for ovarian tumor, while her large uterus is large for a seventy seven-year old woman. It looks like a mature uterus and implyies the secretion of estrogen from the ovarian tumor, indicating estrogen-producing ovarian tumor. Granulosa cell tumor and thecoma are well-known estrogen-producing tumors and granulosa cell tumor secretes inhibin to inhibit FSHRF from hypothalamus (9, 10).
【Summary】
We present a seventy seven year-old female suffering from vomiting and anemia. Abdomen CT showed right ovarian tumor with enlarged uterus like a mature uterus. It is borne in mind that granulosa cell tumor and theca cell tumor are estrogen-producing tumors of the ovary. The maximum sizes of follicular cyst and corpus luteum cyst are approximately 35mm and 50mm, respectively. Granulosa cells secrete estrogen before ovulation and progesterone and inhibin after ovulation using androgen precursor secreted by theca cells. The cancer stem cells are contained in the differentiated cancer cells which sometimes remain the hormone-secrete function. They are radio-chemo resistant. Granulosa cell tumor is one of the sex chord stromal tumors and they appear macroscopically as solid type, cystic type and mixed type. When it occurs before puberty, premature menstruation appears and when it occurs during mature adult, hyper menstruation appear and when it occurs at menopause, the intimal thickening of uterus appears. Our case occurred when at menopause, inducing a large uterus like in a mature woman by estrogen producing.
【References】
1.Levine D, et al. Management of Asymptomatic Ovarian and Other Adnexal Cysts Imaged at US: Society of Radiologists in Ultrasound Consensus Conference Statement. 2010 Radiology. 256 (3): 943–954.
2.American College of Obstetricians and Gynecologists (2002). "ACOG Committee Opinion: Number 280, December 2002. The role of the generalist obstetrician-gynecologist in the early detection of ovarian cancer". Obstetrics and gynecology. 100 (6): 1413–1416.
3.Aleksandra Klemba, et al. Surface markers of cancer stem-like cells of ovarian cancer and their clinical relevance. Contemp Oncol (Pozn). 2018 Mar; 22(1A): 48–55.
4.Markowska A, et al. Ovarian cancer stem cells: A target for oncological therapy. Adv Clin Exp Med. 2018 Jul;27(7):1017-1020.
5.Jung SE, et al. CT and MR Imaging of Ovarian Tumors with Emphasis on Differential Diagnosis. RadioGraphics. 2002; 22: 1305 – 1325
6.Garzo, V. G.et al. Aromatase activity in human granulosa cells during follicular development and the modulation by follicle-stimulating hormone and insulin. American Journal of Obstetrics and Gynecology. 1984; 148 : 657–662.
7.Tanaka YO, et al. Functioning ovarian tumors: direct and indirect findings at MR imaging. RadioGraphics. 2004 ;24:S147-166.
8.Mom CH, et al. Granulosa cell tumors of the ovary: the clinical value of serum inhibin A and B levels in a large single center cohort. Gynecol Oncol. 2007 May;105:365-72.
9.Lappöhn RE, et al. Inhibin as a marker for granulosa cell tumor. Acta Obstet Gynecol Scand Suppl. 1992;155:61-5
10.Zhang, H, et al. MR findings of primary ovarian granulosa cell tumor with focus on the differentiation with other ovarian sex cord-stromal tumors. J Ovarian Res. 2018; 11: 46. Published online 2018 Jun 5. doi: 10.1186/s13048-018-0416-x
2019.8.14