Photodiagnosis and Photodynamic Therapy (2014) 11, 533—536
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/pdpdt
Fertility-sparing management combined with photodynamic therapy for endometrial stromal sarcoma: A case report Min Chul Choi a, Gwangil Kim MD b, Yoon Young Hwang a,∗ a
Comprehensive Gynecologic Cancer Center, Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea b Department of Pathology, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea Available online 11 August 2014
KEYWORDS Endometrial stromal sarcoma; Fertility sparing; Photodynamic therapy
Summary Background and objectives: Low-grade endometrial sarcoma (LGESS) has a favorable prognosis after standard surgical treatment. The conservative fertility-sparing treatments in young patients with LGESS have been reported; however, the role of conservative therapy is not well defined. Study design/patient and methods: A 31-year-old nulliparous woman was diagnosed with LGESS after resection of a cervical polyp with resection margin positive for malignancy. She underwent fertility-sparing surgery including laparoscopic pelvic lymph node dissection, hysteroscopic endometrial polypectomy, endocervical curettage, and photodynamic therapy (PDT) on the endometrium and uterine cervix. And she had received adjuvant therapy with a non-steroidal aromatase inhibitor. Results: She conceived by in vitro fertilization and delivered twins at 32 + 2 weeks gestation by Cesarean section 32 months after conservative treatment. She has no evidence of recurrence after 99 months of follow-up. Conclusion: Conservative management of LGESS may be attempted in selected patients who want to preserve fertility. Conservative surgery combined with PDT has shown effective results in long-term follow-up. © 2014 Elsevier B.V. All rights reserved.
Introduction
∗
Corresponding author at: CHA Bundang Medical Center, Yatapdong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea. Tel.: +82 31 780 6191; fax: +82 31 780 6194. E-mail address: [email protected] (Y.Y. Hwang). http://dx.doi.org/10.1016/j.pdpdt.2014.07.007 1572-1000/© 2014 Elsevier B.V. All rights reserved.
Endometrial stromal sarcoma (ESS) is a rare entity of uterine malignancy, accounting for 0.2% of all uterine cancers [1]. The standard treatment of ESS consists of surgery with hysterectomy and bilateral salpingo-oophorectomy. Generally, ESS occurs in perimenopausal women [2], and it
534
M.C. Choi et al.
Fig. 2 The main microscopic image shows endometrial stromal sarcoma with hematoxylin—eosin stain (×200). Immunostaining for CD10 was strongly positive (×200).
Fig. 1 Transvaginal sonography of the patient. (A) Protruding cervical mass to the upper vagina. (B) 0.9 cm × 0.5 cm sized endometrial mass.
rarely occurs before the age of 40 years. Standard surgery causes irreversible sterility in patients who have not yet had children. Low-grade (LG) ESS has a favorable prognosis compared to that for other uterine sarcomas, with a 5-year survival rate of 92% [3]. Therefore, the use of conservative fertility-sparing treatments in young patients with LGESS has been reported [4—7]. Here, we present a case of LGESS treated by conservative surgery combined with photodynamic therapy (PDT).
Case A 31-year-old woman (gravida 0) presented to our institution with 1 year history of menorrhagia. Medical and surgical histories were unremarkable. On pelvic examination, a 3 cm × 3 cm polypoid mass was detected at the external cervical os that appeared to be either cervical myoma or polyp. No adnexal mass was palpated. Ultrasound examination revealed a 2.9 cm × 3.1 cm pedunculated cervical polypoid mass and a 0.9 cm × 0.5 cm endometrial polyp (Fig. 1A and B). The cervical polypoid mass was removed at first visit without any difficulty. The pathologic result of the cervical mass revealed LGESS (2—3 mitoses/10 HPF) with focal extension to the resection margin (Fig. 2). Immunohistochemical analysis showed that the tumor cells were strongly positive for estrogen/progesterone receptor, and CD 10.
Diagnostic imaging studies included abdominal computerized tomography (CT), pelvic magnetic resonance imaging (MRI), chest X-ray, chest CT, and positron emission tomography (PET)-CT were performed. Pelvic MRI confirmed a small endoluminal nodule at the endometrial cavity and a 1.6 cm left obturator pelvic lymph node enlargement. There was no evidence of intra-peritoneal disease or metastases. Other imaging studies were unremarkable. Laboratory tests showed normal levels of serum tumor markers (CA 125, CA 19-9 and CEA). After discussions with the patient and her family, conservative management was planned because of the patient’s strong desire to preserve fertility and nulligravidity. After confirming that the pelvic lymph nodes harvested by laparoscopic lymph node dissection were negative for malignancy including enlarged left obturator node on pelvic MRI, the patient underwent hysteroscopic endometrial polypectomy, endocervical curettage, and PDT on the endometrium and cervical canal. The PDT procedures for endometrial cancer have been described previously [8]. Histological examination of the endometrial polyp was also revealed LGESS. No remaining malignancy was detected in other specimens. Because of the risk of recurrence, conservative surgery was followed by adjuvant therapy with a non-steroidal aromatase inhibitor (letrozole 2.5 mg, by mouth every day) for 6 months. In consecutive clinical examinations and radiographic studies, the patient has no evidence of recurrence for 99 months. After 32 months, a twin pregnancy was achieved by in vitro fertilization (IVF) because of male factor combined with female factor infertility. Preterm delivery occurred at 32 + 2 weeks of gestation by Cesarean section, and the patient gave birth to twin neonates (two boys weighing 2075 and 1755 g). The placental pathology during delivery showed no evidence of tumor. In consecutive clinical examinations and radiographic studies, the patient has no evidence of recurrence for 99 months.
PDT for endometrial stromal sarcoma Table 1
535
Results of conservative therapy for the young women with endometrial stromal sarcoma.
First author, year
N
Age
Grade
Conservative therapy
Adjuvant therapy
Pregnancy
Recurrence, monthsa
Current status, f/u (months)
Mansi et al. [4], 1990
2
24
LG
Polypectomy
—
N/A
+, 66
DOD, 120
Lissoni et al. [5], 1997
6
19 27 (18—36)
HG LG: 5
Myomectomy Myomectomy: 4 Transcervical myomectomy:2 Myomectomy
CYVADIC #11b —
N/A Abortion: 1
+, 29 −
AWD, 32 NED, 51 (12—84)
HG: 1
Stadsvold et al. [6], 2005 Koskas et al. [7], 2009 Yan et al. [2], 2010
1
16
LG
1
34
LG
1
25
HG
Present case
1
31
LG
HSCpolypectomy Myomectomy
Cervical polypectomy HSCpolypectomy LSC-PLND PDT
VD: 2
Megesterol acetate —c
N/A
−
NED, 21
VD at 39 weeks
+, 16
AWD, 24
Mifepristoned CDDP + VP16 #3e Letrozole
C/S at 39 weeks
−
NED, 60
C/S at 32 + 2 weeks
−
NED, 99
LG, low grade; HG, high grade; HSC, hysteroscopic; LSC-PLND, laparoscopic pelvic lymph node dissection; PDT, photodynamic therapy; N/A, non-available; VD, vaginal delivery; C/S, Cesarean section; DOD, death of disease; AWD, alive with disease; NED, no evidence of disease. a Duration from diagnosis to recurrence, if recurrent. b 11 cycles of chemotherapy with cyclophosphamide, vincristine, adriamycin, and dacarbazine. c Adjuvant therapy was performed with non-steroidal aromatase inhibitors (Letrozole) after multiple recurrent mass removal without hysterectomy. d Progesterone receptor antagonist. e Three cycles of chemotherapy with cisplatin and etoposide.
Discussion The outcomes of conservative therapy for ESS reported by previous studies and the present study are summarized in Table 1. Conservative treatment has been used in patients with LGESS and high grade (HG) ESS, with ages ranging from 16 to 34 years. Exploratory mass removal (myomectomy), cervical myomectomy (polypectomy), and hysteroscopic polypectomy have been performed. Some reports [2,4,6,7] have described the use of chemotherapy or hormonal treatment as postoperative adjuvant therapy, and successful pregnancies and deliveries have been reported [2,5,7]. In present case, no recurrence was observed during 5 years of follow-up after delivery. Some cases of no evidence of disease (NED) status have been reported, even in cases of HGESS after conservative therapy [2]. Recurrence in patient with LGESS has been reported, eventually leading to death [4]. The so-called favorable prognosis of LGESS patients does not mean a favorable clinical outcome in cases performing conservative treatment, but in cases after undergoing standard surgery. Furthermore, the follow-up period of NED cases were not sufficiently long [2,5,6]. In general, lymph node dissection (LND) is not routinely recommended in patients with early stage LGESS because LN
metastasis is rare in these cases [5]. However, the reported metastasis rate differs among studies [3]. In the present case, LND was performed for the differential diagnosis of a relatively enlarged pelvic LN found in the imaging study. Because the subsequent LN analysis showed negative results, a conservative operation was feasible in this patient. The present case showed a favorable clinical outcome, in which the NED status was maintained for 99 months. This could be the result of the combined multimodal treatments which were to treat conservatively by hysteroscopic and laparoscopic operations, to eradicate the potentially remaining tumor by PDT, and to suppress recurrence by adjuvant therapy. In the present case, the causes for infertility were present in both patient and her husband. Therefore, IVF was attempted, resulting in successful twin pregnancy on first trial. However, the causes for the preterm delivery are not clear. No signs of recurrence have been detected during the 8 years of follow-up. As evidenced by a number of previous reports, LGESS has a more indolent growth with a tendency for late recurrence. The reported time interval between treatment and recurrence varies from 3 months to 23 years [6]. Therefore, definitive surgery should be performed post-motherhood after sufficient patient
536 counseling, regardless of the presence or absence of recurrence. Considering the favorable prognosis of early stage LGESS, several authors have proposed conservative management to preserve fertility in young patients [4—7], even reported successful deliveries. The present case is distinct because of the use of PDT to eradicate tumor that might be left after conservative treatment. We described a case of successful delivery with long-term absence of recurrence after fertility-sparing therapy combined with PDT.
Conflict of interest The authors did not report any potential conflict of interest.
References [1] Echt G, Jepson J, Steel J, Langholz B, Luxton G, Hernandez W, et al. Treatment of uterine sarcomas. Cancer 1990;66:35—44. [2] Yan L, Tian Y, Fu Y, Zhao X. Successful pregnancy after fertilitypreserving surgery for endometrial stromal sarcoma. Fertil Steril 2010;93(269):e1—3.
M.C. Choi et al. [3] Shah JP, Bryant CS, Kumar S, Ali-Fehmi R, Malone Jr JM, Morris RT. Lymphadenectomy and ovarian preservation in low-grade endometrial stromal sarcoma. Obstet Gynecol 2008;112:1102—8. [4] Mansi JL, Ramachandra S, Wiltshaw E, Fischer C. Endometrial stromal sarcomas. Gynecol Oncol 1990;36:113—8. [5] Lissoni A, Cormio G, Perego P, Gabriele A, Cantu MG, Bratina G. Conservative management of endometrial stromal sarcoma in young women. Int J Gynecol Cancer 1997;7:364—7. [6] Stadsvold JL, Molpus KL, Baker JJ, Michael K, Remmenga SW. Conservative management of a myxoid endometrial stromal sarcoma in a 16-year-old nulliparous woman. Gynecol Oncol 2005;99:243—8. [7] Koskas M, Morice P, Yazbeck C, Duvillard P, Walker F, Madelenat P. Conservative management of low-grade endometrial stromal sarcoma followed by pregnancy and severe recurrence. Anticancer Res 2009;29:4147—50. [8] Choi MC, Jung SG, Park H, Cho YH, Lee C, Kim SJ. Fertility preservation via photodynamic therapy in young patients with early-stage uterine endometrial cancer: a long-term follow-up study. Int J Gynecol Cancer 2013;23:698—704.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/pdpdt
Fertility-sparing management combined with photodynamic therapy for endometrial stromal sarcoma: A case report Min Chul Choi a, Gwangil Kim MD b, Yoon Young Hwang a,∗ a
Comprehensive Gynecologic Cancer Center, Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea b Department of Pathology, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea Available online 11 August 2014
KEYWORDS Endometrial stromal sarcoma; Fertility sparing; Photodynamic therapy
Summary Background and objectives: Low-grade endometrial sarcoma (LGESS) has a favorable prognosis after standard surgical treatment. The conservative fertility-sparing treatments in young patients with LGESS have been reported; however, the role of conservative therapy is not well defined. Study design/patient and methods: A 31-year-old nulliparous woman was diagnosed with LGESS after resection of a cervical polyp with resection margin positive for malignancy. She underwent fertility-sparing surgery including laparoscopic pelvic lymph node dissection, hysteroscopic endometrial polypectomy, endocervical curettage, and photodynamic therapy (PDT) on the endometrium and uterine cervix. And she had received adjuvant therapy with a non-steroidal aromatase inhibitor. Results: She conceived by in vitro fertilization and delivered twins at 32 + 2 weeks gestation by Cesarean section 32 months after conservative treatment. She has no evidence of recurrence after 99 months of follow-up. Conclusion: Conservative management of LGESS may be attempted in selected patients who want to preserve fertility. Conservative surgery combined with PDT has shown effective results in long-term follow-up. © 2014 Elsevier B.V. All rights reserved.
Introduction
∗
Corresponding author at: CHA Bundang Medical Center, Yatapdong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea. Tel.: +82 31 780 6191; fax: +82 31 780 6194. E-mail address: [email protected] (Y.Y. Hwang). http://dx.doi.org/10.1016/j.pdpdt.2014.07.007 1572-1000/© 2014 Elsevier B.V. All rights reserved.
Endometrial stromal sarcoma (ESS) is a rare entity of uterine malignancy, accounting for 0.2% of all uterine cancers [1]. The standard treatment of ESS consists of surgery with hysterectomy and bilateral salpingo-oophorectomy. Generally, ESS occurs in perimenopausal women [2], and it
534
M.C. Choi et al.
Fig. 2 The main microscopic image shows endometrial stromal sarcoma with hematoxylin—eosin stain (×200). Immunostaining for CD10 was strongly positive (×200).
Fig. 1 Transvaginal sonography of the patient. (A) Protruding cervical mass to the upper vagina. (B) 0.9 cm × 0.5 cm sized endometrial mass.
rarely occurs before the age of 40 years. Standard surgery causes irreversible sterility in patients who have not yet had children. Low-grade (LG) ESS has a favorable prognosis compared to that for other uterine sarcomas, with a 5-year survival rate of 92% [3]. Therefore, the use of conservative fertility-sparing treatments in young patients with LGESS has been reported [4—7]. Here, we present a case of LGESS treated by conservative surgery combined with photodynamic therapy (PDT).
Case A 31-year-old woman (gravida 0) presented to our institution with 1 year history of menorrhagia. Medical and surgical histories were unremarkable. On pelvic examination, a 3 cm × 3 cm polypoid mass was detected at the external cervical os that appeared to be either cervical myoma or polyp. No adnexal mass was palpated. Ultrasound examination revealed a 2.9 cm × 3.1 cm pedunculated cervical polypoid mass and a 0.9 cm × 0.5 cm endometrial polyp (Fig. 1A and B). The cervical polypoid mass was removed at first visit without any difficulty. The pathologic result of the cervical mass revealed LGESS (2—3 mitoses/10 HPF) with focal extension to the resection margin (Fig. 2). Immunohistochemical analysis showed that the tumor cells were strongly positive for estrogen/progesterone receptor, and CD 10.
Diagnostic imaging studies included abdominal computerized tomography (CT), pelvic magnetic resonance imaging (MRI), chest X-ray, chest CT, and positron emission tomography (PET)-CT were performed. Pelvic MRI confirmed a small endoluminal nodule at the endometrial cavity and a 1.6 cm left obturator pelvic lymph node enlargement. There was no evidence of intra-peritoneal disease or metastases. Other imaging studies were unremarkable. Laboratory tests showed normal levels of serum tumor markers (CA 125, CA 19-9 and CEA). After discussions with the patient and her family, conservative management was planned because of the patient’s strong desire to preserve fertility and nulligravidity. After confirming that the pelvic lymph nodes harvested by laparoscopic lymph node dissection were negative for malignancy including enlarged left obturator node on pelvic MRI, the patient underwent hysteroscopic endometrial polypectomy, endocervical curettage, and PDT on the endometrium and cervical canal. The PDT procedures for endometrial cancer have been described previously [8]. Histological examination of the endometrial polyp was also revealed LGESS. No remaining malignancy was detected in other specimens. Because of the risk of recurrence, conservative surgery was followed by adjuvant therapy with a non-steroidal aromatase inhibitor (letrozole 2.5 mg, by mouth every day) for 6 months. In consecutive clinical examinations and radiographic studies, the patient has no evidence of recurrence for 99 months. After 32 months, a twin pregnancy was achieved by in vitro fertilization (IVF) because of male factor combined with female factor infertility. Preterm delivery occurred at 32 + 2 weeks of gestation by Cesarean section, and the patient gave birth to twin neonates (two boys weighing 2075 and 1755 g). The placental pathology during delivery showed no evidence of tumor. In consecutive clinical examinations and radiographic studies, the patient has no evidence of recurrence for 99 months.
PDT for endometrial stromal sarcoma Table 1
535
Results of conservative therapy for the young women with endometrial stromal sarcoma.
First author, year
N
Age
Grade
Conservative therapy
Adjuvant therapy
Pregnancy
Recurrence, monthsa
Current status, f/u (months)
Mansi et al. [4], 1990
2
24
LG
Polypectomy
—
N/A
+, 66
DOD, 120
Lissoni et al. [5], 1997
6
19 27 (18—36)
HG LG: 5
Myomectomy Myomectomy: 4 Transcervical myomectomy:2 Myomectomy
CYVADIC #11b —
N/A Abortion: 1
+, 29 −
AWD, 32 NED, 51 (12—84)
HG: 1
Stadsvold et al. [6], 2005 Koskas et al. [7], 2009 Yan et al. [2], 2010
1
16
LG
1
34
LG
1
25
HG
Present case
1
31
LG
HSCpolypectomy Myomectomy
Cervical polypectomy HSCpolypectomy LSC-PLND PDT
VD: 2
Megesterol acetate —c
N/A
−
NED, 21
VD at 39 weeks
+, 16
AWD, 24
Mifepristoned CDDP + VP16 #3e Letrozole
C/S at 39 weeks
−
NED, 60
C/S at 32 + 2 weeks
−
NED, 99
LG, low grade; HG, high grade; HSC, hysteroscopic; LSC-PLND, laparoscopic pelvic lymph node dissection; PDT, photodynamic therapy; N/A, non-available; VD, vaginal delivery; C/S, Cesarean section; DOD, death of disease; AWD, alive with disease; NED, no evidence of disease. a Duration from diagnosis to recurrence, if recurrent. b 11 cycles of chemotherapy with cyclophosphamide, vincristine, adriamycin, and dacarbazine. c Adjuvant therapy was performed with non-steroidal aromatase inhibitors (Letrozole) after multiple recurrent mass removal without hysterectomy. d Progesterone receptor antagonist. e Three cycles of chemotherapy with cisplatin and etoposide.
Discussion The outcomes of conservative therapy for ESS reported by previous studies and the present study are summarized in Table 1. Conservative treatment has been used in patients with LGESS and high grade (HG) ESS, with ages ranging from 16 to 34 years. Exploratory mass removal (myomectomy), cervical myomectomy (polypectomy), and hysteroscopic polypectomy have been performed. Some reports [2,4,6,7] have described the use of chemotherapy or hormonal treatment as postoperative adjuvant therapy, and successful pregnancies and deliveries have been reported [2,5,7]. In present case, no recurrence was observed during 5 years of follow-up after delivery. Some cases of no evidence of disease (NED) status have been reported, even in cases of HGESS after conservative therapy [2]. Recurrence in patient with LGESS has been reported, eventually leading to death [4]. The so-called favorable prognosis of LGESS patients does not mean a favorable clinical outcome in cases performing conservative treatment, but in cases after undergoing standard surgery. Furthermore, the follow-up period of NED cases were not sufficiently long [2,5,6]. In general, lymph node dissection (LND) is not routinely recommended in patients with early stage LGESS because LN
metastasis is rare in these cases [5]. However, the reported metastasis rate differs among studies [3]. In the present case, LND was performed for the differential diagnosis of a relatively enlarged pelvic LN found in the imaging study. Because the subsequent LN analysis showed negative results, a conservative operation was feasible in this patient. The present case showed a favorable clinical outcome, in which the NED status was maintained for 99 months. This could be the result of the combined multimodal treatments which were to treat conservatively by hysteroscopic and laparoscopic operations, to eradicate the potentially remaining tumor by PDT, and to suppress recurrence by adjuvant therapy. In the present case, the causes for infertility were present in both patient and her husband. Therefore, IVF was attempted, resulting in successful twin pregnancy on first trial. However, the causes for the preterm delivery are not clear. No signs of recurrence have been detected during the 8 years of follow-up. As evidenced by a number of previous reports, LGESS has a more indolent growth with a tendency for late recurrence. The reported time interval between treatment and recurrence varies from 3 months to 23 years [6]. Therefore, definitive surgery should be performed post-motherhood after sufficient patient
536 counseling, regardless of the presence or absence of recurrence. Considering the favorable prognosis of early stage LGESS, several authors have proposed conservative management to preserve fertility in young patients [4—7], even reported successful deliveries. The present case is distinct because of the use of PDT to eradicate tumor that might be left after conservative treatment. We described a case of successful delivery with long-term absence of recurrence after fertility-sparing therapy combined with PDT.
Conflict of interest The authors did not report any potential conflict of interest.
References [1] Echt G, Jepson J, Steel J, Langholz B, Luxton G, Hernandez W, et al. Treatment of uterine sarcomas. Cancer 1990;66:35—44. [2] Yan L, Tian Y, Fu Y, Zhao X. Successful pregnancy after fertilitypreserving surgery for endometrial stromal sarcoma. Fertil Steril 2010;93(269):e1—3.
M.C. Choi et al. [3] Shah JP, Bryant CS, Kumar S, Ali-Fehmi R, Malone Jr JM, Morris RT. Lymphadenectomy and ovarian preservation in low-grade endometrial stromal sarcoma. Obstet Gynecol 2008;112:1102—8. [4] Mansi JL, Ramachandra S, Wiltshaw E, Fischer C. Endometrial stromal sarcomas. Gynecol Oncol 1990;36:113—8. [5] Lissoni A, Cormio G, Perego P, Gabriele A, Cantu MG, Bratina G. Conservative management of endometrial stromal sarcoma in young women. Int J Gynecol Cancer 1997;7:364—7. [6] Stadsvold JL, Molpus KL, Baker JJ, Michael K, Remmenga SW. Conservative management of a myxoid endometrial stromal sarcoma in a 16-year-old nulliparous woman. Gynecol Oncol 2005;99:243—8. [7] Koskas M, Morice P, Yazbeck C, Duvillard P, Walker F, Madelenat P. Conservative management of low-grade endometrial stromal sarcoma followed by pregnancy and severe recurrence. Anticancer Res 2009;29:4147—50. [8] Choi MC, Jung SG, Park H, Cho YH, Lee C, Kim SJ. Fertility preservation via photodynamic therapy in young patients with early-stage uterine endometrial cancer: a long-term follow-up study. Int J Gynecol Cancer 2013;23:698—704.
