Case Report
Laparoscopic Excisional Surgery for Growing Teratoma Syndrome of the Ovary: Case Report and Literature Review Naoya Shigeta, MD, Eiji Kobayashi, MD*, Kenjiro Sawada, MD, PhD, Yutaka Ueda, MD, PhD, Kiyoshi Yoshino, MD, PhD, Yumiko Hori, MD, PhD, and Tadashi Kimura, MD, PhD From the Department of Obstetrics and Gynecology (Drs. Shigeta, Kobayashi, Sawada, Yoshino, Kimura, and Ueda), and Department of Pathology (Dr. Hori), Osaka University Graduate School of Medicine, Osaka, Japan.
ABSTRACT Growing teratoma syndrome (GTS) is rare clinical phenomenon occurring as a sequelae of a malignant germ cell tumor. We present the case of a 20-year-old woman who developed GTS after undergoing fertility-sparing surgery and chemotherapy for an immature teratoma. She underwent left salpingo-oophorectomy, right ovarian cystectomy, and disseminated tumor reduction during her primary surgery. The postsurgical histology report identified the tumor as an immature teratoma, grade 3, International Federation of Gynecology and Obstetrics (FIGO) stage IIIb. She subsequently received 3 cycles of chemotherapy consisting of bleomycin, etoposide, and cisplatin. At 17 months after the chemotherapy, follow-up computed tomography (CT) scan revealed an enlarged mass in her right paracolic gutter and a small peritoneal lesion in the pouch of Douglas. Her serum alpha-fetoprotein level was not elevated. These findings were compatible with GTS, but it was difficult to rule out a recurrent immature teratoma. Diagnostic exploratory laparoscopic surgery revealed the enlarged tumors that had been detected by the CT scan. Although there were multiple tumors in the pouch of Douglas, we were able to resect all of them laparoscopically. Histological diagnosis of the surgically resected specimens was of a mature teratoma, and so we concluded that this tumor was a GTS. Our experience suggests that laparoscopic surgery is an effective alternative diagnostic and therapeutic approach in cases suspicious of GTS where the disease is disseminated to the peritoneum. Journal of Minimally Invasive Gynecology (2015) 22, 668–674 Ó 2015 AAGL. All rights reserved. Keywords:
DISCUSS
Growing teratoma syndrome; Laparoscopy; Ovarian; Peritonectomy
You can discuss this article with its authors and with other AAGL members at http://www.AAGL.org/jmig-22-4-JMIG-D-14-00605
Use your Smartphone to scan this QR code and connect to the discussion forum for this article now* * Download a free QR Code scanner by searching for ‘‘QR scanner’’ in your smartphone’s app store or app marketplace.
Growing teratoma syndrome (GTS) is rare clinical phenomenon occurring as a result of a malignant germ cell tumor [1]. The syndrome is defined as an increase in the size of a mature germ cell teratoma or the appearance of a new germ cell tumor mass, during or after chemotherapy, with any initially elevated tumor markers all remaining normal [2]. Although GTS is a histologically benign tumor, up to 3% of GTS cases can undergo malignant transformation [3]. Therefore, complete surgical resection of the tumor The authors declare no conflicts of interest. Corresponding author: Eiji Kobayashi, MD, Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: [email protected] Submitted December 7, 2014. Accepted for publication January 13, 2015. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ - see front matter Ó 2015 AAGL. All rights reserved. http://dx.doi.org/10.1016/j.jmig.2015.01.011
is desirable [4]. Here we report the results of laparoscopic excisional surgery for a case of GTS with multiple peritoneal dissemination within the pouch of Douglas and a peritoneal implant in the paracolic gutter. Owing to the rarity of GTS, there have been only 3 previous case reports of laparoscopic excisional surgery for GTS; our present case is the fourth. Case Report A 20-year-old woman (gravid 0, para 0) was referred to our hospital due to a large ovarian tumor, having complained of abdominal distention for 3 months. Her medical and gynecologic history was unremarkable. The physical examination was normal, except for a large abdominal mass. Trans-abdominal ultrasonography showed a 16-cm solid ovarian tumor and ascites fluid. Serum tumor marker
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Fig. 1 CT scan showing a pelvic tumor 17 cm in size originating from the left ovary (arrowheads) containing calcifications, fatty areas, and peritoneal nodules (arrows), implicating peritoneal dissemination.
analysis showed elevated alpha-fetoprotein at 96 ng/mL and elevated CA125 at 728 U/mL. Contrast-enhanced computed tomography (CT) revealed a 17-cm pelvic tumor containing calcifications and fatty areas; it originated from the left ovary and had peritoneal nodules, which implicated peritoneal dissemination (Fig. 1). A left salpingo-oophorectomy was performed, leaving 5 mm of residual disease on the pelvic and upper abdominal peritoneum. The final pathological analysis revealed a grade 3 immature teratoma of the left ovary, with features of immature tissue, skin, sebaceous glands, neural tissue, cartilage, bone, smooth muscle, and fatty tissue. Mature components and immature glial implants were microscopically revealed in the peritoneum implants (Fig. 2). The peritoneal washing was negative. She was diagnosed with an International Federation of Gynecology and Obstetrics (FIGO) stage IIIb immature teratoma.
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Postoperatively, the patient received 3 cycles of chemotherapy consisting of bleomycin, etoposide, and cisplatin. Her tumor markers returned to normal by 4 months after the operation. At 17 months after the primary surgery, a follow-up CT scan showed that the peritoneal lesions had grown to 1 cm and revealed a pelvic lesion of approximately 4 cm on the right paracolic gutter, with internal calcification, fatty areas, and a cystic component (Fig. 3). The tumor marker levels at regrowth were not elevated. A positron emission tomography–CT (PET-CT) scan showed uptake of fluoro-2-deoxy-D-glucose in the peritoneal lesion (SUV 2.5). Based on this limited information, we could not differentiate between a case of GTS and a recurrent immature teratoma. After thorough counseling, the patient consented to laparoscopic surgery and excision of the lesions. Laparoscopic surgery revealed a 5-cm-diameter tumor at the lateral edge of the ascending mesocolon and additional 0.5- to 1-cm nodules in the pouch of Douglas (Fig. 4A). The uterus, right ovary, and oviduct were normal. All of these lesions were resected laparoscopically (Fig. 4B). The histology report revealed that the largest tumor was composed of mature cartilage, neural tissue, skin, and sebaceous glands; thus, the tumor was diagnosed as a mature teratoma (Fig. 5). No immature elements or viable carcinoma were seen in any of the sections studied. The patient has been on follow-up every 3 months with imaging and tumor marker analysis. She resumed menstruation at 3 months after the operation, and has exhibited no subsequent evidence of disease for 12 months. Discussion GTS is a benign germ cell tumor that appears to be induced to grow after chemotherapy for a malignant tumor [5]. The pathogenesis of GTS has remained controversial. Two mechanisms have been proposed: (1) Chemotherapy induces the disappearance of any malignant cells, leaving behind the mature teratoma components, or (2) the benign
Fig. 2 Histological examination of the tumor of the first laparotomy showing immature teratomatous elements (arrow). (Hematoxylin and eosin; original magnification: A, 2!; B, 10!.)
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Fig. 3 (A) CT scan showing a recurrent peritoneal lesion growing to 1 cm (arrowhead). (B) CT scan showing an intra-abdominal tumor of 4 cm on the right paracolic gutter (arrow).
tumor is the result of chemotherapeutic-induced epigenetic retroconversion of the tumor cells [1]. These hypotheses have sometimes been considered synonymous [1,6]. Surgical resection is the cornerstone for the treatment of GTS. Complete resection of all GST is recommended because GTS can progress as GTS or undergo malignant transformation. Kikawa et al [4] reviewed 48 cases of ovarian GTS and also found that incomplete resection of the GTS was an important risk factor for the recurrence of GTS. They reported that 4 of 48 patients (8%) who did not undergo complete tumor resection experienced recurrence, and that recurrence was rare in patients with GTS who underwent complete resection. GTS has a small but real potential to undergo malignant transformation. According to our review, looking solely at ovarian GTS, GTS recurred in 12.7% of cases (7 of 55), and malignant transformation occurred in 5.4% of cases (3 of 55) (Table 2). If the residual teratoma components are related to chemotherapeutic retroconversion, it would make sense that they will retain a high level of histopathological genetic aneuploidy and thus malignant potential [7–9]. Therefore,
their complete surgical resection is a highly desirable treatment [10]. Recent advances in laparoscopic technology enable us to perform advanced laparoscopic surgical techniques. Laparoscopic surgery has many well-known advantages over laparotomy, including less blood loss, less pain, shorter recovery periods, and less adhesion formation [11,12]. Ovarian GTS is extremely rare, with only 55 cases reported in the English literature to date [1–6,10,13–38]. Only 3 of these 55 reported cases were managed laparoscopically [1,10,13]. These 3 laparoscopic cases are summarized in Table 1. Tumor recurrence did not occur after tumor resection in these 3 cases. Owing to the previous suboptimal surgery with advanced stage, we found the multiple tumors in the pouch of Douglas and the peritoneum of the deep pelvis. Compared with other patients treated laparoscopically for GTS, our case is the only one with residual multiple disseminations after the primary surgery. We needed to perform peritonectomy to completely resect the disseminated tumor. Kobayashi et al [39] presented a method of laparoscopic peritonectomy for ovarian cancer in which the tumor was
Fig. 4 Laparoscopic vision of lesions and the tumor. (A) Laparoscopic view of peritoneal tumor (arrow) in the pouch of Douglas. (B) Laparoscopic view after tumor resection of the pouch of Douglas.
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Fig. 5 Histological features of the tumor. (A) Mature cartilage (arrow). (B) Skin (arrow). (C) Sebaceous glands (arrow). (Hematoxylin and eosin; original magnification: A, 2!; B, 4!; C, 10!.)
adhered to the pelvic sidewall. In this method, after the Okabayashi perirectal space is opened, blunt dissection is used to identify the ureter. The ureter is separated from the retroperitoneum by resection of the remaining subperitoneal tissue. Finally, they resected the remaining retroperitoneum attached to the pelvic sidewall is resected, and the tumor is completely removed with the peritoneum.
We applied the Kobayashi technique and effectively resected the GTS tumors in the pouch of Douglas. Thus, we have shown that for multiple enlarged lesions located in the small pelvis in the pouch of Douglas, laparoscopy can serve as a curative method to treat GTS. In our review, we found that the median age at diagnosis of GTS of the ovary is roughly 20 years and that the median
Table 1 Summary of previous laparoscopic cases of GTS of the ovary Case
Matsushita et al [1]
First operation
RSO, POM, peritoneal LSO, RTFT, POM sampling (laparotomy) (laparotomy)
Histology Residual tumor at first operation Chemotherapy Time to GTS GTS site
IMT, G2, stage IIIa No residual mass
Mixed GCT, stage Ic No residual mass
Four cycles of BEP 92 mo 7-cm mass in superior pole of the right kidney
Four cycles of EP Three cycles of BEP 7 mo 24 mo umbilicus mass, ascites, 0.5- to 1-cm multiple cyst in sacrouterina ligaments and 1-cm mass in left pouch of Douglas vesicouterine plica
Follow-up duration from 6 mo surgery for GTS
Homs et al [10]
6 mo
Tzortzatos et al [13]
Present case
RTC (laparoscopy), RSO, POM, LTC, peritoneal sampling (laparotomy) IMT G2, stage Ic No residual mass
LSO (laparotomy), resection of disseminated tumors
5 yr
IMT, G3, stage IIIb Small disseminated mass Three cycles of BEP 11 mo Small peritoneal deposits, lesions in the pouch of Douglas, 4-cm mass on the right paracolic gutter 12 mo
RSO 5 right salpingo-oophorectomy; POM 5 partial omentectomy; RTC/LTC 5 right/left cystectomy; RTFT 5 right fallopian tube resection; IMT 5 immature teratoma; BEP 5 Bleomycin, etoposide, cisplatin; EP 5 Etoposide, cisplatin.
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Table 2 Growing teratoma syndrome of the ovary: review of the literature
Author
Age, yr
Matsushita et al [1] Lorusso et al [2] Andre et al [3]
30 33, 19 No data No data
Kikawa et al [4] Kattan et al [5]
Amsalem et al [6] Homs et al [10] Geisler et al [14]
No data 36 38
Laparoscopic management
Progression of malignancy/GTS
RFI of followup, mo
Recurrence site
Histology
1 2 3
Yes No No No
No No GTS GTS
6 6 No data 65
Peritoneum Peritoneum
Mature teratoma Mature teratoma; death secondary to small bowel necrosis and urinary fistula
No No No
No No GTS
No data 21 12
Pelvis
Mature teratoma, limited small bowel necrosis related to vascular compression
No Yes No No No No No No Yes No No No No No No No No No No No No
No No No No No No No No No No No No No No data No No No No No GTS GTS
24 6 17 28 1 36 60 9 72 60 11 72 132 No data 18–42 .12 8 36 24 3 48
Pelvis, anterior to the bladder Surface of the liver, around the spleen, right kidney Liver, right supraclavicular lymph nodes; metastasis to pulmonary parenchyma and mediastinal, periportal, and periaortic lymph nodes
Mature teratoma Mature teratoma
Liver metastasis
Spindle cell neoplasm
1 1
12 22 20 22 20 18 26 27 20 18 14 30 22 29 18–20 14 15 33 34 12 23
1 1 3
Jumean et al. [23]
30
1
No
Malignancy
84
Williams et al [24]
No data No data
6
No No
No Malignancy
21–108 120
Hariprasad et al [15]
Tzortzatos et al [13] Mrabti et al [16] Shibata et al [17] Kato et al [18] Panda et al [19] Disaia et al [20] Aronowitz et al [21] Moskovic et al [22]
3
1 1 1 2 1 3 2 4
Metastatic adenocarcinoma
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Number of cases
6 12 No No No Yes
Trabecular carcinoid tumor Intrahepatic mass, multiple small abdominal and pelvic nodules
No No No GTS No No GTS No No No No No Malignancy No No No No No No No No No No No No No
References
24 24 5 12 34 19 5 19 15 39 24 (mean) 12 38
26 20
David et al [25] Itani et al [26] Inaoka et al [27] Nimkim et al [28] Umekawa et al [29] Dewdney et al [30] Tangjitgamol et al [31] Lentini et al [32] Tonkin et al [33] Caldas et al [34] Tay et al [35] Zagame et al [36] Djordjevic et al [37]
Sengar et al [38] Present report
1 1 1 1 1 1 1 1 1 1 3 1 1
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recurrence-free interval (from final treatment of GTS to recurrent GTS) is about 24 months. These findings strongly indicate that there is a need for longer follow-up (.24 months) in GTS cases, and that there is a strong likelihood of repeat surgery during the remaining reproductive period. For the sake of any future pregnancy, laparoscopic surgery should play an important role in the surgical therapy for GTS, to minimize intra-abdominal adhesion formation and the risk of infertility [40]. In conclusion, it is quite reasonable to use a diagnostic exploratory laparoscopic surgery if a recurrent tumor cannot be confirmed as either a GTS or a recurrent immature teratoma. If there are multiple recurrent lesions, laparoscopy can be used as a curative method to treat GTS. Our experience suggests that laparoscopic surgery is an effective alternative diagnostic and therapeutic method for cases suspicious for GTS, even if there are multiple sites of disease.
1 1
Mature teratoma Upper abdomen
Laparoscopic Excisional Surgery for Growing Teratoma Syndrome of the Ovary
12 17 36 96 13 3.5 24 36 16 6 No data 165 60
Perihepatic mass
Mature teratoma
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1. Matsushita H, Arai K, Fukase M, et al. Growing teratoma syndrome of the ovary after fertility-sparing surgery and successful pregnancy. Gynecol Obstet Invest. 2010;69:221–223. 2. Lorusso D, Malaquti P, Trivellizzi IN, Scambia G. Unusual liver locations of growing teratoma syndrome in ovarian malignant germ cell tumors. Gynecol Oncol Case Rep. 2011;8:24–25. 3. Andre F, Fizazi K, Culine S, et al. The growing teratoma syndrome: results of therapy and long-term follow-up of 33 patients. Eur J Cancer. 2000;36:1389–1394. 4. Kikawa S, Todo Y, Minobe S, et al. Growing teratoma syndrome of the ovary: a case report with FDG -PET findings. J Obstet Gynaecol Res. 2011;37:926–932. 5. Kattan J, Droz JP, Culine S, et al. The growing teratoma syndrome: a woman with nonseminomatous germ cell tumor of the ovary. Gynecol Oncol. 1993;49:395–399. 6. Amsalem H, Nadjari M, Prus D, et al. Growing teratoma syndrome vs. chemotherapeutic retroconversion: case report and review of the literature. Gynecol Oncol. 2004;92:357–360. 7. Davey DD, Ulbright TM, Loehrer PJ, et al. The significance of atypia with teratomatous metastasis after chemotherapy for malignant germ cell tumor. Cancer. 1987;59:533–539. 8. Castoro SM, de Jong B, Ooterhuis JW, et al. Chromosomal changes in mature residual teratomas following polychemotherapy. Cancer Res. 1989;49:672–676. 9. Molenaar WM, Oosterhuis JW, Meiring A, et al. Histology and DNA contents of secondary malignancy arising in a mature residual lesion six years after chemotherapy for a disseminated nonseminomatous testicular tumor. Cancer. 1986;58:264–268. 10. Homs MY, Schreuder HW, Jonqes GN, et al. Clinical and radiologic signs of relapsed ovarian germ cell tumor: tissue is the issue. Case Rep Obstet Gynecol. 2013;2013:984524. 11. Jeong WK, Park JW, Choi HS, Jeong SY, Oh JH. Comparison of peristomal formation between laparoscopic and open low anterior resection of rectal cancer. World J Surg. 2013;37:2683–2687. 12. Yuen PM, Yu KM, Yip SK, Lau WC, Rogers MS, Chang A. A randomized prospective study of laparoscopy and laparotomy in the management of benign ovarian masses. Am J Obstet Gynecol. 1997;177:109–114. 13. Tzortzatos G, Sioutas A, Schedvins K. Successful pregnancy after treatment for ovarian malignant teratoma with growing teratoma syndrome. Fertil Steril. 2009;91:936.e1–936.e3. 14. Geisler JP, Goulet R, Foster RS, et al. Growing teratoma syndrome after chemotherapy for germ cell tumors of the ovary. Obstet Gynecol. 1994; 84:719–721.
674 15. Hariprasad R, Kumar L, Janqa D, et al. Growing teratoma syndrome of ovary. Int J Clin Oncol. 2008;13:83–87. 16. Mrabti H, El Ghissassi I, Sbitti Y, et al. Growing teratoma syndrome and peritoneal gliomatosis. Case Rep Med. 2011;2011:123527. 17. Shibata K, Kjiyama H, Kikkawa F. Growing teratoma syndrome of the ovary showing three patterns of metastasis: a case report. Case Rep Oncol. 2013;6:544–554. 18. Kato N, Uchigasaki S, Fukase M. How does secondary neoplasm arise from mature teratomas in growing teratoma syndrome of the ovary? A report of two cases. Pathol Int. 2013;63:607–610. 19. Panda A, Kandasamy D, Sh C, Jana M. Growing teratoma syndrome of ovary: avoiding a misdiagnosis of tumour recurrence. J Clin Diagn Res. 2014;8:197–198. 20. DiSia PJ, Saltz A, Kagan AR, et al. Chemotherapeutic retroconversion of immature teratoma of the ovary. Obstet Gynecol. 1997;49: 1346–1350. 21. Aronowitz J, Estrada R, Lynch R, et al. Retroconversion of malignant immature teratomas of the ovary after chemotherapy. Gynecol Oncol. 1983;16:414–421. 22. Moskovic E, Jobling T, Fisher C, et al. Retroconversion of immature teratoma of the ovary: CT appearances. Clin Radiol. 1991;43:402–408. 23. Jumean HG, Komorowski R, Mahvi D, et al. Immature teratoma of the ovary: an unusual case. Gynecol Oncol. 1992;46:111–114. 24. Williams SD, Blessing JA, DiSia PJ, et al. Second-look laparotomy in ovarian germ cell tumors: the Gynecologic Oncology Group experience. Gynecol Oncol. 1994;52:287–291. 25. David YB, Weiss A, Shechtman L, et al. Tumor chemoconversion following surgery, chemotherapy, and normalization of serum tumor markers in a woman with a mixed type germ cell ovarian tumor. Gynecol Oncol. 2002;84:464–467. 26. Itani Y, Kawa M, Toyoda S, et al. Growing teratoma syndrome after chemotherapy for a mixed germ cell tumor of the ovary. J Obstet Gynaecol Res. 2002;28:166–171. 27. Inaoka T, Takahashi K, Yamada T, et al. The growing teratoma syndrome secondary to immature teratoma of the ovary. Eur Radiol. 2003;13:2115–2118. 28. Nimkin K, Gupta P, McCauley R. The growing teratoma syndrome. Pediatr Radiol. 2004;34:259–262.
Journal of Minimally Invasive Gynecology, Vol 22, No 4, May/June 2015 29. Umekawa T, Tabata T, Tanida K, et al. Growing teratoma syndrome as an unusual cause of gliomatosis peritonei: a case report. Gynecol Oncol. 2005;99:761–763. 30. Dewdney S, Sokoliff M, Yamada SD, et al. Conservative management of chylous ascites after removal of a symptomatic growing retroperitoneal teratoma. Gynecol Oncol. 2006;100:608–611. 31. Tangjitgamol S, Manusirivithaya S, Leelahakorn S, et al. The growing teratoma syndrome: a case report and a review of the literature. Int J Gynecol Cancer. 2006;16:384–390. 32. Lentini JF, Love MB, Ritchie WG, et al. Computed tomography in retroconversion of hepatic metastases from immature ovarian teratoma. J Comput Assist Tomogr. 1986;10:1060–1062. 33. Tonkin KS, Rustin GJ, Wingnall B, et al. Successful treatment of patients in whom germ cell tumour masses enlarged on chemotherapy while their serum tumour markers decreased. Eur J Cancer Clin Oncol. 1989;25:1739–1743. 34. Caldas C, Sitzmann J, Trimble CL, et al. Synchronous mature teratomas of the ovary and liver: a case presenting 11 years following chemotherapy for immature teratoma. Gynecol Oncol. 1992;47:385–390. 35. Tay SK, Tan LK. Experience of a 2-day BEP regimen in postsurgical adjuvant chemotherapy of ovarian germ cell tumors. Int J Gynecol Cancer. 2000;10:13–18. 36. Zagame L, Pautier P, Duvillard P, Castaigne D, Patte C, Lhomme C. Growing teratoma syndrome after ovarian germ cell tumors. Obstet Gynecol. 2006;108:509–514. 37. Djordjevic B, Euscher ED, Malpica A. Growing teratoma syndrome of the ovary: review of literature and first report of a carcinoid tumor arising in a growing teratoma of the ovary. Am J Surg Pathol. 2007;31:1913–1918. 38. Sengar AR, Kulkarni JN. Growing teratoma syndrome in a postlaparoscopic excision of ovarian immature teratoma. J Gynecol Oncol. 2010;21:129–131. 39. Kobayashi E, Kanao H, Andou H. Laparoscopic adnexectomy with peritonectomy for an ovarian tumor adhered to the pelvic sidewall. Gynecol Obstet Invest. 2013;75:250–254. 40. Practice Committee of American Society for Reproductive Medicine, in collaboration with the Society of Reproductive Surgeons. Pathogenesis, consequences, and control of peritoneal adhesions in gynecologic surgery: a committee opinion. Fertil Steril. 2013;99:1550–1555.
Laparoscopic Excisional Surgery for Growing Teratoma Syndrome of the Ovary: Case Report and Literature Review Naoya Shigeta, MD, Eiji Kobayashi, MD*, Kenjiro Sawada, MD, PhD, Yutaka Ueda, MD, PhD, Kiyoshi Yoshino, MD, PhD, Yumiko Hori, MD, PhD, and Tadashi Kimura, MD, PhD From the Department of Obstetrics and Gynecology (Drs. Shigeta, Kobayashi, Sawada, Yoshino, Kimura, and Ueda), and Department of Pathology (Dr. Hori), Osaka University Graduate School of Medicine, Osaka, Japan.
ABSTRACT Growing teratoma syndrome (GTS) is rare clinical phenomenon occurring as a sequelae of a malignant germ cell tumor. We present the case of a 20-year-old woman who developed GTS after undergoing fertility-sparing surgery and chemotherapy for an immature teratoma. She underwent left salpingo-oophorectomy, right ovarian cystectomy, and disseminated tumor reduction during her primary surgery. The postsurgical histology report identified the tumor as an immature teratoma, grade 3, International Federation of Gynecology and Obstetrics (FIGO) stage IIIb. She subsequently received 3 cycles of chemotherapy consisting of bleomycin, etoposide, and cisplatin. At 17 months after the chemotherapy, follow-up computed tomography (CT) scan revealed an enlarged mass in her right paracolic gutter and a small peritoneal lesion in the pouch of Douglas. Her serum alpha-fetoprotein level was not elevated. These findings were compatible with GTS, but it was difficult to rule out a recurrent immature teratoma. Diagnostic exploratory laparoscopic surgery revealed the enlarged tumors that had been detected by the CT scan. Although there were multiple tumors in the pouch of Douglas, we were able to resect all of them laparoscopically. Histological diagnosis of the surgically resected specimens was of a mature teratoma, and so we concluded that this tumor was a GTS. Our experience suggests that laparoscopic surgery is an effective alternative diagnostic and therapeutic approach in cases suspicious of GTS where the disease is disseminated to the peritoneum. Journal of Minimally Invasive Gynecology (2015) 22, 668–674 Ó 2015 AAGL. All rights reserved. Keywords:
DISCUSS
Growing teratoma syndrome; Laparoscopy; Ovarian; Peritonectomy
You can discuss this article with its authors and with other AAGL members at http://www.AAGL.org/jmig-22-4-JMIG-D-14-00605
Use your Smartphone to scan this QR code and connect to the discussion forum for this article now* * Download a free QR Code scanner by searching for ‘‘QR scanner’’ in your smartphone’s app store or app marketplace.
Growing teratoma syndrome (GTS) is rare clinical phenomenon occurring as a result of a malignant germ cell tumor [1]. The syndrome is defined as an increase in the size of a mature germ cell teratoma or the appearance of a new germ cell tumor mass, during or after chemotherapy, with any initially elevated tumor markers all remaining normal [2]. Although GTS is a histologically benign tumor, up to 3% of GTS cases can undergo malignant transformation [3]. Therefore, complete surgical resection of the tumor The authors declare no conflicts of interest. Corresponding author: Eiji Kobayashi, MD, Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: [email protected] Submitted December 7, 2014. Accepted for publication January 13, 2015. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ - see front matter Ó 2015 AAGL. All rights reserved. http://dx.doi.org/10.1016/j.jmig.2015.01.011
is desirable [4]. Here we report the results of laparoscopic excisional surgery for a case of GTS with multiple peritoneal dissemination within the pouch of Douglas and a peritoneal implant in the paracolic gutter. Owing to the rarity of GTS, there have been only 3 previous case reports of laparoscopic excisional surgery for GTS; our present case is the fourth. Case Report A 20-year-old woman (gravid 0, para 0) was referred to our hospital due to a large ovarian tumor, having complained of abdominal distention for 3 months. Her medical and gynecologic history was unremarkable. The physical examination was normal, except for a large abdominal mass. Trans-abdominal ultrasonography showed a 16-cm solid ovarian tumor and ascites fluid. Serum tumor marker
Shigeta et al.
Laparoscopic Excisional Surgery for Growing Teratoma Syndrome of the Ovary
Fig. 1 CT scan showing a pelvic tumor 17 cm in size originating from the left ovary (arrowheads) containing calcifications, fatty areas, and peritoneal nodules (arrows), implicating peritoneal dissemination.
analysis showed elevated alpha-fetoprotein at 96 ng/mL and elevated CA125 at 728 U/mL. Contrast-enhanced computed tomography (CT) revealed a 17-cm pelvic tumor containing calcifications and fatty areas; it originated from the left ovary and had peritoneal nodules, which implicated peritoneal dissemination (Fig. 1). A left salpingo-oophorectomy was performed, leaving 5 mm of residual disease on the pelvic and upper abdominal peritoneum. The final pathological analysis revealed a grade 3 immature teratoma of the left ovary, with features of immature tissue, skin, sebaceous glands, neural tissue, cartilage, bone, smooth muscle, and fatty tissue. Mature components and immature glial implants were microscopically revealed in the peritoneum implants (Fig. 2). The peritoneal washing was negative. She was diagnosed with an International Federation of Gynecology and Obstetrics (FIGO) stage IIIb immature teratoma.
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Postoperatively, the patient received 3 cycles of chemotherapy consisting of bleomycin, etoposide, and cisplatin. Her tumor markers returned to normal by 4 months after the operation. At 17 months after the primary surgery, a follow-up CT scan showed that the peritoneal lesions had grown to 1 cm and revealed a pelvic lesion of approximately 4 cm on the right paracolic gutter, with internal calcification, fatty areas, and a cystic component (Fig. 3). The tumor marker levels at regrowth were not elevated. A positron emission tomography–CT (PET-CT) scan showed uptake of fluoro-2-deoxy-D-glucose in the peritoneal lesion (SUV 2.5). Based on this limited information, we could not differentiate between a case of GTS and a recurrent immature teratoma. After thorough counseling, the patient consented to laparoscopic surgery and excision of the lesions. Laparoscopic surgery revealed a 5-cm-diameter tumor at the lateral edge of the ascending mesocolon and additional 0.5- to 1-cm nodules in the pouch of Douglas (Fig. 4A). The uterus, right ovary, and oviduct were normal. All of these lesions were resected laparoscopically (Fig. 4B). The histology report revealed that the largest tumor was composed of mature cartilage, neural tissue, skin, and sebaceous glands; thus, the tumor was diagnosed as a mature teratoma (Fig. 5). No immature elements or viable carcinoma were seen in any of the sections studied. The patient has been on follow-up every 3 months with imaging and tumor marker analysis. She resumed menstruation at 3 months after the operation, and has exhibited no subsequent evidence of disease for 12 months. Discussion GTS is a benign germ cell tumor that appears to be induced to grow after chemotherapy for a malignant tumor [5]. The pathogenesis of GTS has remained controversial. Two mechanisms have been proposed: (1) Chemotherapy induces the disappearance of any malignant cells, leaving behind the mature teratoma components, or (2) the benign
Fig. 2 Histological examination of the tumor of the first laparotomy showing immature teratomatous elements (arrow). (Hematoxylin and eosin; original magnification: A, 2!; B, 10!.)
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Fig. 3 (A) CT scan showing a recurrent peritoneal lesion growing to 1 cm (arrowhead). (B) CT scan showing an intra-abdominal tumor of 4 cm on the right paracolic gutter (arrow).
tumor is the result of chemotherapeutic-induced epigenetic retroconversion of the tumor cells [1]. These hypotheses have sometimes been considered synonymous [1,6]. Surgical resection is the cornerstone for the treatment of GTS. Complete resection of all GST is recommended because GTS can progress as GTS or undergo malignant transformation. Kikawa et al [4] reviewed 48 cases of ovarian GTS and also found that incomplete resection of the GTS was an important risk factor for the recurrence of GTS. They reported that 4 of 48 patients (8%) who did not undergo complete tumor resection experienced recurrence, and that recurrence was rare in patients with GTS who underwent complete resection. GTS has a small but real potential to undergo malignant transformation. According to our review, looking solely at ovarian GTS, GTS recurred in 12.7% of cases (7 of 55), and malignant transformation occurred in 5.4% of cases (3 of 55) (Table 2). If the residual teratoma components are related to chemotherapeutic retroconversion, it would make sense that they will retain a high level of histopathological genetic aneuploidy and thus malignant potential [7–9]. Therefore,
their complete surgical resection is a highly desirable treatment [10]. Recent advances in laparoscopic technology enable us to perform advanced laparoscopic surgical techniques. Laparoscopic surgery has many well-known advantages over laparotomy, including less blood loss, less pain, shorter recovery periods, and less adhesion formation [11,12]. Ovarian GTS is extremely rare, with only 55 cases reported in the English literature to date [1–6,10,13–38]. Only 3 of these 55 reported cases were managed laparoscopically [1,10,13]. These 3 laparoscopic cases are summarized in Table 1. Tumor recurrence did not occur after tumor resection in these 3 cases. Owing to the previous suboptimal surgery with advanced stage, we found the multiple tumors in the pouch of Douglas and the peritoneum of the deep pelvis. Compared with other patients treated laparoscopically for GTS, our case is the only one with residual multiple disseminations after the primary surgery. We needed to perform peritonectomy to completely resect the disseminated tumor. Kobayashi et al [39] presented a method of laparoscopic peritonectomy for ovarian cancer in which the tumor was
Fig. 4 Laparoscopic vision of lesions and the tumor. (A) Laparoscopic view of peritoneal tumor (arrow) in the pouch of Douglas. (B) Laparoscopic view after tumor resection of the pouch of Douglas.
Shigeta et al.
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Fig. 5 Histological features of the tumor. (A) Mature cartilage (arrow). (B) Skin (arrow). (C) Sebaceous glands (arrow). (Hematoxylin and eosin; original magnification: A, 2!; B, 4!; C, 10!.)
adhered to the pelvic sidewall. In this method, after the Okabayashi perirectal space is opened, blunt dissection is used to identify the ureter. The ureter is separated from the retroperitoneum by resection of the remaining subperitoneal tissue. Finally, they resected the remaining retroperitoneum attached to the pelvic sidewall is resected, and the tumor is completely removed with the peritoneum.
We applied the Kobayashi technique and effectively resected the GTS tumors in the pouch of Douglas. Thus, we have shown that for multiple enlarged lesions located in the small pelvis in the pouch of Douglas, laparoscopy can serve as a curative method to treat GTS. In our review, we found that the median age at diagnosis of GTS of the ovary is roughly 20 years and that the median
Table 1 Summary of previous laparoscopic cases of GTS of the ovary Case
Matsushita et al [1]
First operation
RSO, POM, peritoneal LSO, RTFT, POM sampling (laparotomy) (laparotomy)
Histology Residual tumor at first operation Chemotherapy Time to GTS GTS site
IMT, G2, stage IIIa No residual mass
Mixed GCT, stage Ic No residual mass
Four cycles of BEP 92 mo 7-cm mass in superior pole of the right kidney
Four cycles of EP Three cycles of BEP 7 mo 24 mo umbilicus mass, ascites, 0.5- to 1-cm multiple cyst in sacrouterina ligaments and 1-cm mass in left pouch of Douglas vesicouterine plica
Follow-up duration from 6 mo surgery for GTS
Homs et al [10]
6 mo
Tzortzatos et al [13]
Present case
RTC (laparoscopy), RSO, POM, LTC, peritoneal sampling (laparotomy) IMT G2, stage Ic No residual mass
LSO (laparotomy), resection of disseminated tumors
5 yr
IMT, G3, stage IIIb Small disseminated mass Three cycles of BEP 11 mo Small peritoneal deposits, lesions in the pouch of Douglas, 4-cm mass on the right paracolic gutter 12 mo
RSO 5 right salpingo-oophorectomy; POM 5 partial omentectomy; RTC/LTC 5 right/left cystectomy; RTFT 5 right fallopian tube resection; IMT 5 immature teratoma; BEP 5 Bleomycin, etoposide, cisplatin; EP 5 Etoposide, cisplatin.
672
Table 2 Growing teratoma syndrome of the ovary: review of the literature
Author
Age, yr
Matsushita et al [1] Lorusso et al [2] Andre et al [3]
30 33, 19 No data No data
Kikawa et al [4] Kattan et al [5]
Amsalem et al [6] Homs et al [10] Geisler et al [14]
No data 36 38
Laparoscopic management
Progression of malignancy/GTS
RFI of followup, mo
Recurrence site
Histology
1 2 3
Yes No No No
No No GTS GTS
6 6 No data 65
Peritoneum Peritoneum
Mature teratoma Mature teratoma; death secondary to small bowel necrosis and urinary fistula
No No No
No No GTS
No data 21 12
Pelvis
Mature teratoma, limited small bowel necrosis related to vascular compression
No Yes No No No No No No Yes No No No No No No No No No No No No
No No No No No No No No No No No No No No data No No No No No GTS GTS
24 6 17 28 1 36 60 9 72 60 11 72 132 No data 18–42 .12 8 36 24 3 48
Pelvis, anterior to the bladder Surface of the liver, around the spleen, right kidney Liver, right supraclavicular lymph nodes; metastasis to pulmonary parenchyma and mediastinal, periportal, and periaortic lymph nodes
Mature teratoma Mature teratoma
Liver metastasis
Spindle cell neoplasm
1 1
12 22 20 22 20 18 26 27 20 18 14 30 22 29 18–20 14 15 33 34 12 23
1 1 3
Jumean et al. [23]
30
1
No
Malignancy
84
Williams et al [24]
No data No data
6
No No
No Malignancy
21–108 120
Hariprasad et al [15]
Tzortzatos et al [13] Mrabti et al [16] Shibata et al [17] Kato et al [18] Panda et al [19] Disaia et al [20] Aronowitz et al [21] Moskovic et al [22]
3
1 1 1 2 1 3 2 4
Metastatic adenocarcinoma
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Number of cases
6 12 No No No Yes
Trabecular carcinoid tumor Intrahepatic mass, multiple small abdominal and pelvic nodules
No No No GTS No No GTS No No No No No Malignancy No No No No No No No No No No No No No
References
24 24 5 12 34 19 5 19 15 39 24 (mean) 12 38
26 20
David et al [25] Itani et al [26] Inaoka et al [27] Nimkim et al [28] Umekawa et al [29] Dewdney et al [30] Tangjitgamol et al [31] Lentini et al [32] Tonkin et al [33] Caldas et al [34] Tay et al [35] Zagame et al [36] Djordjevic et al [37]
Sengar et al [38] Present report
1 1 1 1 1 1 1 1 1 1 3 1 1
673
recurrence-free interval (from final treatment of GTS to recurrent GTS) is about 24 months. These findings strongly indicate that there is a need for longer follow-up (.24 months) in GTS cases, and that there is a strong likelihood of repeat surgery during the remaining reproductive period. For the sake of any future pregnancy, laparoscopic surgery should play an important role in the surgical therapy for GTS, to minimize intra-abdominal adhesion formation and the risk of infertility [40]. In conclusion, it is quite reasonable to use a diagnostic exploratory laparoscopic surgery if a recurrent tumor cannot be confirmed as either a GTS or a recurrent immature teratoma. If there are multiple recurrent lesions, laparoscopy can be used as a curative method to treat GTS. Our experience suggests that laparoscopic surgery is an effective alternative diagnostic and therapeutic method for cases suspicious for GTS, even if there are multiple sites of disease.
1 1
Mature teratoma Upper abdomen
Laparoscopic Excisional Surgery for Growing Teratoma Syndrome of the Ovary
12 17 36 96 13 3.5 24 36 16 6 No data 165 60
Perihepatic mass
Mature teratoma
Shigeta et al.
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