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Low-Grade Ovarian Cancer in an Adolescent Patient
Gynecologic Oncology 80, 104 –106 (2001) doi:10.1006/gyno.2000.6020, available online at http://www.idealibrary.com on
CASE REPORT Low-Grade Ovarian Cancer in an Adolescent Patient Lynn P. Parker, M.D.,* Pedro T. Ramirez, M.D.,* Russell Broaddus, M.D.,† Sterling Sightler, M.D.,‡ and Judith K. Wolf, M.D.* ,1 *Department of Gynecologic Oncology and †Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; and ‡756 Colonial Drive, Suite A, Baton Rouge, Louisiana 70806 Received July 24, 2000; published online December 4, 2000
CASE REPORT
Background. Ovarian tumors in the pediatric population are most likely to be of germ cell origin. However, serous tumors have also been reported in adolescent patients. Case. A 14-year-old girl was diagnosed with stage IIIc lowgrade ovarian cancer. Her serum CA-125 was elevated preoperatively and was a marker for recurrence of disease. Five months after completing standard chemotherapy, she developed recurrent disease, which progressed despite hormonal therapy. She then developed toxicity on liposomal doxorubicin (Doxil) and is now receiving hospice care. Conclusion. Low-grade serous adenocarcinoma of the ovary can present as advanced disease and should be considered in the differential diagnosis of an ovarian mass in an adolescent patient. © 2001 Academic Press Key Words: ovarian cancer; serous adenocarcinoma; adjuvant chemotherapy.
INTRODUCTION
A 14-year-old girl, gravida 0, presented to her primary care physician in December 1998 with complaints of weight loss, fatigue, and abdominal pain since August 1998. She underwent an esophageal duodenoscopy that was negative, but a computed tomography (CT) scan done December 23, 1998, revealed a pelvic mass. Her serum CA-125 was elevated to 98.7 U/ml. On January 4, 1999, the patient underwent an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, rectosigmoid resection, low colorectal end-to-end anastomosis, upper abdominal tumor resection, appendectomy, omentectomy, and gastrostomy tube placement. Findings at the time of surgery were a large pelvic mass involving the sigmoid colon, diaphragmatic seeding less than 1 cm bilaterally, a 4 ⫻ 5-cm tumor in the gastrosplenic ligament, a 5 ⫻ 8-cm omental cake, and nodules measuring less than 1 cm throughout the small bowel, large bowel, peritoneal surfaces, and bladder peritoneum. The tumor was optimally debulked so that less than 1 cm of residual disease remained. The patient then received six cycles of paclitaxel (Taxol) at 175 mg/m 2 and carboplatin at doses adjusted to achieve an area under the concentration-versus-time curve (AUC) of 7.5. She completed these treatments in June 1999. In September 1999, CT was negative for disease. In November 1999, a repeat serum CA-125 measurement was 193.5 U/ml and repeat CT showed several loops of distended small bowel, rather than a cystic mass. On December 13, 1999, she underwent another exploratory laparotomy that revealed diffuse carcinomatosis coating the bowel and diaphragm that could not be debulked. On December 27, 1999, the patient presented at The University of Texas M. D. Anderson Cancer Center for further therapy. The pathology specimen was reviewed and was consistent with a low-grade papillary serous carcinoma (Fig. 1). She underwent hormonal therapy with leuprolide acetate (Depot-Lupron) at doses of 22.5 mg intramuscularly every 3 months. Her serum CA-125 had increased from 180 to 550 U/ml despite treatment, and CT on March 2, 2000, showed
An estimated 23,100 new cases of ovarian cancer will have been diagnosed in the year 2000. In the same year, approximately 14,000 women will have died of this disease [1]. Malignant ovarian tumors in adolescent patients are rare, accounting for only 1% of all cancers in patients under age 15 [2]. However, a pelvic mass in a pediatric patient is malignant in 16 to 55% of cases [3]. We present a case of an adolescent patient with an aggressive low-grade papillary serous carcinoma that progressed despite standard chemotherapy and hormonal therapy. Though unusual, this case reminds us to consider epithelial malignancies in the young patient presenting with a pelvic mass. 1
To whom correspondence should be addressed at Department of Gynecologic Oncology, Box 67, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Fax: (713) 792-7586. E-mail: [email protected]. 0090-8258/01 $35.00 Copyright © 2001 by Academic Press All rights of reproduction in any form reserved.
104
CASE REPORT
105
FIG. 1. Low-grade papillary serous carcinoma. The tumor is composed of sheets of well-differentiated epithelial cells with occasional psammoma bodies.
evidence of progression. The leuprolide acetate therapy was stopped, and chemotherapy with liposomal doxorubicin (Doxil) was begun. She received one cycle of liposomal doxorubicin on March 9, 2000, and developed a palmar/plantar erythrodesia. She then refused all chemotherapy and at this time is receiving hospice care. DISCUSSION This case report shows that low-grade serous carcinoma of the ovary can occur in adolescent patients and should be considered in the differential diagnosis of an ovarian mass in pediatric patients. Although most malignant ovarian tumors in adults are serous, germ cell tumors account for two-thirds of all malignant tumors of the ovary in the pediatric population [3– 6]. Epithelial tumors in the pediatric population are less common and have been reported to represent 17 to 22% of ovarian masses [5, 7, 8]. However, because most reports include benign serous cystadenomas, mucinous cystadenomas, or borderline tumors in addition to epithelial tumors, evaluation of treatment, survival rates, and recommended follow-up is difficult. Presenting symptoms for the adolescent with an ovarian mass include abdominal pain (50%), abdominal distention (18%), precocious pseudopuberty (18%), or an acute abdomen in the setting of torsion [2– 4, 9]. These cases are very often misdiagnosed as acute appendicitis [3, 4]. Evaluation of a suspected ovarian tumor in an adolescent patient should include assays for ␣-fetoprotein (AFP) and the -subunit of human chorionic gonadotropin (-HCG) to test for all tumor types, lactate dehydrogenase (LDH) to test
for germ cell tumors, inhibin to test for granulosa cell tumors, and serum CA-125 and carcinoembryonic antigen (CEA) to test for epithelial malignancies [3, 4]. However, it must be remembered that serum CA-125 can be elevated by benign entities such as pelvic inflammatory disease and endometriosis. Radiologic evaluation of an adolescent patient with a pelvic mass should include pelvic sonography to determine whether the lesion is solid or cystic. Solid ovarian masses are more likely to be malignant than are simple unilocular cysts [7]. For perimenarchal patients, Helmrath et al. recommends an algorithm of management that includes laparotomy or laparoscopy if the patient has a complex mass or a persistent cyst greater than 7 cm but considers observation acceptable in the patient with a cyst that is less than 7 cm and has a simple appearance [7]. CT or magnetic resonance imaging (MRI) of the abdomen and pelvis of patients with a solid mass should be performed to help with preoperative planning and to help determine the origin and extent of disease [2]. Surgical management of pediatric patients with an ovarian mass can be complex because of the concern to preserve fertility, the need for preoperative consent, the difficulty in making the diagnosis based on frozen sections of these rare tumors, and the surgeon’s degree of familiarity with the appropriate staging criteria in the event of the finding of malignancy. In formulating a management strategy, one should adopt the most conservative approach in an effort to preserve fertility. However, most published reports on the treatment of ovarian malignancies in pediatric patients focus on nonepithelial tumors, which allow a less aggressive surgical approach than required by epithelial tumors [2– 4, 6].
106
PARKER ET AL.
Given the progressive nature of the tumor of the patient described in this report, extensive surgical debulking was undertaken. Because so few cases of invasive serous carcinomas of the ovary in adolescent patients have been reported, there is no standard in the management of these patients. A retrospective review of ovarian cancer in young women reported by Koshiyama et al. included 10 epithelial tumors, but only 4 cases were stages II to IV [10]. Although the authors recommended combining conservative surgery with platinum-based chemotherapy, the small number of cases prevented them from drawing definite conclusions. We treated our case as we would have treated an adult with the same diagnosis, combining surgical debulking with chemotherapy. Regardless of the patient’s age, it appears that epithelial tumors have a high rate of recurrence despite adjuvant platinum-based chemotherapy. Our patient suffered a recurrence less than 6 months after completion of chemotherapy. Because of the low-grade nature of the tumor, we administered hormonal therapy. In a Gynecologic Oncology Group (GOG) protocol, Hatch et al. reported on 105 women with refractory ovarian cancer treated with tamoxifen. Ten women had a complete response, 8 had a partial response, and 40 had stable disease. The response rate overall was 17% [11]. The use of gonadotropin-releasing hormone (GnRH) analogues such as leuprolide acetate in patients with refractory ovarian cancer has yielded response rates of approximately 17% [12]. The use of leuprolide acetate concomitantly with tamoxifen resulted in a 12% response rate, a 29% rate of stabilization of disease, and a median survival time of 14.4 months [13]. Refractory ovarian tumors may prove more responsive to novel biologic therapies that are currently under investigation. Although rare in young patients, invasive ovarian cancer must be considered in the differential diagnosis of the adolescent patient with an ovarian mass. Therapies such as surgery
and chemotherapy should be individualized based on the histologic diagnosis, the prognosis, and the desires of the patient. REFERENCES 1. Greenlee RT, Murray T, Bolden S, Wingo PA: Cancer statistics, 2000. CA Cancer J Clin 50:7–33, 2000 2. Freud E, Golinsky D, Steinberg RM, Blumenfeld A, Yaniv I, Zer M: Ovarian masses in children. Clin Pediatr 38:573–577, 1999 3. Lovvorn HN, Tucci LA, Stafford PW: Ovarian masses in the pediatric patient. AORN 67:568 –576, 1998 4. Lazar EL, Stolar CJH: Evaluation and management of pediatric solid ovarian tumors. Semin Pediatr Surg 7:29 –34, 1998 5. Hassan E, Creatsas G, Deligeorolgou E, Michalas S: Ovarian tumors during childhood and adolescence: a clinicopathologic study. Eur J Gynaecol Oncol 20:124 –126, 1999 6. Garden AS: Paediatric gynaecology: an overview of current practice. Hosp Med 59:232–235, 1998 7. Helmrath MA, Shin CE, Warner BW: Ovarian cysts in the pediatric population. Semin Pediatr Surg 7:19 –28, 1998 8. Deprest J, Moerman P, Corneillie P, Ide P: Ovarian borderline mucinous tumor in a premenarchal girl: review of ovarian epithelial cancer in young girls. Gynecol Oncol 45:219 –224, 1992 9. Nelson L, Ekbom A, Gerdin E: Ovarian cancer in young women in Sweden, 1989 –1991. Gynecol Oncol 74:472– 476, 1999, doi:10.1006/ gyno.1999.5503 10. Koshiyama M, Yoshida M, Takemura M, Konishi M, Yura Y, Matsushita K, Hayashi M, Tauchi K: Management of malignant ovarian cancers in young women. Gynecol Obstet Invest 45:132–136, 1998 11. Hatch KD, Beecham JB, Blessing JA, Creasman T: Responsiveness of patients with advanced ovarian cancer to tamoxifen: a Gynecologic Oncology Group study of second-line therapy in 105 patients. Cancer 68: 269 –271, 1991 12. Kavanagh JJ, Roberts W, Townsend P, Hewitt S: Leuprolide acetate in the treatment of refractory or persistent epithelial ovarian cancer. J Clin Oncol 7:115–118, 1989 13. Lopez A, Tessadrelli A, Kudelka AP, Edwards CL, Freedman RS, Hord M, Kavanagh JJ: Combination therapy with leuprolide acetate and tamoxifen in refractory ovarian cancer. Int J Gynecol Cancer 6:15–19, 1996
CASE REPORT Low-Grade Ovarian Cancer in an Adolescent Patient Lynn P. Parker, M.D.,* Pedro T. Ramirez, M.D.,* Russell Broaddus, M.D.,† Sterling Sightler, M.D.,‡ and Judith K. Wolf, M.D.* ,1 *Department of Gynecologic Oncology and †Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; and ‡756 Colonial Drive, Suite A, Baton Rouge, Louisiana 70806 Received July 24, 2000; published online December 4, 2000
CASE REPORT
Background. Ovarian tumors in the pediatric population are most likely to be of germ cell origin. However, serous tumors have also been reported in adolescent patients. Case. A 14-year-old girl was diagnosed with stage IIIc lowgrade ovarian cancer. Her serum CA-125 was elevated preoperatively and was a marker for recurrence of disease. Five months after completing standard chemotherapy, she developed recurrent disease, which progressed despite hormonal therapy. She then developed toxicity on liposomal doxorubicin (Doxil) and is now receiving hospice care. Conclusion. Low-grade serous adenocarcinoma of the ovary can present as advanced disease and should be considered in the differential diagnosis of an ovarian mass in an adolescent patient. © 2001 Academic Press Key Words: ovarian cancer; serous adenocarcinoma; adjuvant chemotherapy.
INTRODUCTION
A 14-year-old girl, gravida 0, presented to her primary care physician in December 1998 with complaints of weight loss, fatigue, and abdominal pain since August 1998. She underwent an esophageal duodenoscopy that was negative, but a computed tomography (CT) scan done December 23, 1998, revealed a pelvic mass. Her serum CA-125 was elevated to 98.7 U/ml. On January 4, 1999, the patient underwent an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, rectosigmoid resection, low colorectal end-to-end anastomosis, upper abdominal tumor resection, appendectomy, omentectomy, and gastrostomy tube placement. Findings at the time of surgery were a large pelvic mass involving the sigmoid colon, diaphragmatic seeding less than 1 cm bilaterally, a 4 ⫻ 5-cm tumor in the gastrosplenic ligament, a 5 ⫻ 8-cm omental cake, and nodules measuring less than 1 cm throughout the small bowel, large bowel, peritoneal surfaces, and bladder peritoneum. The tumor was optimally debulked so that less than 1 cm of residual disease remained. The patient then received six cycles of paclitaxel (Taxol) at 175 mg/m 2 and carboplatin at doses adjusted to achieve an area under the concentration-versus-time curve (AUC) of 7.5. She completed these treatments in June 1999. In September 1999, CT was negative for disease. In November 1999, a repeat serum CA-125 measurement was 193.5 U/ml and repeat CT showed several loops of distended small bowel, rather than a cystic mass. On December 13, 1999, she underwent another exploratory laparotomy that revealed diffuse carcinomatosis coating the bowel and diaphragm that could not be debulked. On December 27, 1999, the patient presented at The University of Texas M. D. Anderson Cancer Center for further therapy. The pathology specimen was reviewed and was consistent with a low-grade papillary serous carcinoma (Fig. 1). She underwent hormonal therapy with leuprolide acetate (Depot-Lupron) at doses of 22.5 mg intramuscularly every 3 months. Her serum CA-125 had increased from 180 to 550 U/ml despite treatment, and CT on March 2, 2000, showed
An estimated 23,100 new cases of ovarian cancer will have been diagnosed in the year 2000. In the same year, approximately 14,000 women will have died of this disease [1]. Malignant ovarian tumors in adolescent patients are rare, accounting for only 1% of all cancers in patients under age 15 [2]. However, a pelvic mass in a pediatric patient is malignant in 16 to 55% of cases [3]. We present a case of an adolescent patient with an aggressive low-grade papillary serous carcinoma that progressed despite standard chemotherapy and hormonal therapy. Though unusual, this case reminds us to consider epithelial malignancies in the young patient presenting with a pelvic mass. 1
To whom correspondence should be addressed at Department of Gynecologic Oncology, Box 67, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Fax: (713) 792-7586. E-mail: [email protected]. 0090-8258/01 $35.00 Copyright © 2001 by Academic Press All rights of reproduction in any form reserved.
104
CASE REPORT
105
FIG. 1. Low-grade papillary serous carcinoma. The tumor is composed of sheets of well-differentiated epithelial cells with occasional psammoma bodies.
evidence of progression. The leuprolide acetate therapy was stopped, and chemotherapy with liposomal doxorubicin (Doxil) was begun. She received one cycle of liposomal doxorubicin on March 9, 2000, and developed a palmar/plantar erythrodesia. She then refused all chemotherapy and at this time is receiving hospice care. DISCUSSION This case report shows that low-grade serous carcinoma of the ovary can occur in adolescent patients and should be considered in the differential diagnosis of an ovarian mass in pediatric patients. Although most malignant ovarian tumors in adults are serous, germ cell tumors account for two-thirds of all malignant tumors of the ovary in the pediatric population [3– 6]. Epithelial tumors in the pediatric population are less common and have been reported to represent 17 to 22% of ovarian masses [5, 7, 8]. However, because most reports include benign serous cystadenomas, mucinous cystadenomas, or borderline tumors in addition to epithelial tumors, evaluation of treatment, survival rates, and recommended follow-up is difficult. Presenting symptoms for the adolescent with an ovarian mass include abdominal pain (50%), abdominal distention (18%), precocious pseudopuberty (18%), or an acute abdomen in the setting of torsion [2– 4, 9]. These cases are very often misdiagnosed as acute appendicitis [3, 4]. Evaluation of a suspected ovarian tumor in an adolescent patient should include assays for ␣-fetoprotein (AFP) and the -subunit of human chorionic gonadotropin (-HCG) to test for all tumor types, lactate dehydrogenase (LDH) to test
for germ cell tumors, inhibin to test for granulosa cell tumors, and serum CA-125 and carcinoembryonic antigen (CEA) to test for epithelial malignancies [3, 4]. However, it must be remembered that serum CA-125 can be elevated by benign entities such as pelvic inflammatory disease and endometriosis. Radiologic evaluation of an adolescent patient with a pelvic mass should include pelvic sonography to determine whether the lesion is solid or cystic. Solid ovarian masses are more likely to be malignant than are simple unilocular cysts [7]. For perimenarchal patients, Helmrath et al. recommends an algorithm of management that includes laparotomy or laparoscopy if the patient has a complex mass or a persistent cyst greater than 7 cm but considers observation acceptable in the patient with a cyst that is less than 7 cm and has a simple appearance [7]. CT or magnetic resonance imaging (MRI) of the abdomen and pelvis of patients with a solid mass should be performed to help with preoperative planning and to help determine the origin and extent of disease [2]. Surgical management of pediatric patients with an ovarian mass can be complex because of the concern to preserve fertility, the need for preoperative consent, the difficulty in making the diagnosis based on frozen sections of these rare tumors, and the surgeon’s degree of familiarity with the appropriate staging criteria in the event of the finding of malignancy. In formulating a management strategy, one should adopt the most conservative approach in an effort to preserve fertility. However, most published reports on the treatment of ovarian malignancies in pediatric patients focus on nonepithelial tumors, which allow a less aggressive surgical approach than required by epithelial tumors [2– 4, 6].
106
PARKER ET AL.
Given the progressive nature of the tumor of the patient described in this report, extensive surgical debulking was undertaken. Because so few cases of invasive serous carcinomas of the ovary in adolescent patients have been reported, there is no standard in the management of these patients. A retrospective review of ovarian cancer in young women reported by Koshiyama et al. included 10 epithelial tumors, but only 4 cases were stages II to IV [10]. Although the authors recommended combining conservative surgery with platinum-based chemotherapy, the small number of cases prevented them from drawing definite conclusions. We treated our case as we would have treated an adult with the same diagnosis, combining surgical debulking with chemotherapy. Regardless of the patient’s age, it appears that epithelial tumors have a high rate of recurrence despite adjuvant platinum-based chemotherapy. Our patient suffered a recurrence less than 6 months after completion of chemotherapy. Because of the low-grade nature of the tumor, we administered hormonal therapy. In a Gynecologic Oncology Group (GOG) protocol, Hatch et al. reported on 105 women with refractory ovarian cancer treated with tamoxifen. Ten women had a complete response, 8 had a partial response, and 40 had stable disease. The response rate overall was 17% [11]. The use of gonadotropin-releasing hormone (GnRH) analogues such as leuprolide acetate in patients with refractory ovarian cancer has yielded response rates of approximately 17% [12]. The use of leuprolide acetate concomitantly with tamoxifen resulted in a 12% response rate, a 29% rate of stabilization of disease, and a median survival time of 14.4 months [13]. Refractory ovarian tumors may prove more responsive to novel biologic therapies that are currently under investigation. Although rare in young patients, invasive ovarian cancer must be considered in the differential diagnosis of the adolescent patient with an ovarian mass. Therapies such as surgery
and chemotherapy should be individualized based on the histologic diagnosis, the prognosis, and the desires of the patient. REFERENCES 1. Greenlee RT, Murray T, Bolden S, Wingo PA: Cancer statistics, 2000. CA Cancer J Clin 50:7–33, 2000 2. Freud E, Golinsky D, Steinberg RM, Blumenfeld A, Yaniv I, Zer M: Ovarian masses in children. Clin Pediatr 38:573–577, 1999 3. Lovvorn HN, Tucci LA, Stafford PW: Ovarian masses in the pediatric patient. AORN 67:568 –576, 1998 4. Lazar EL, Stolar CJH: Evaluation and management of pediatric solid ovarian tumors. Semin Pediatr Surg 7:29 –34, 1998 5. Hassan E, Creatsas G, Deligeorolgou E, Michalas S: Ovarian tumors during childhood and adolescence: a clinicopathologic study. Eur J Gynaecol Oncol 20:124 –126, 1999 6. Garden AS: Paediatric gynaecology: an overview of current practice. Hosp Med 59:232–235, 1998 7. Helmrath MA, Shin CE, Warner BW: Ovarian cysts in the pediatric population. Semin Pediatr Surg 7:19 –28, 1998 8. Deprest J, Moerman P, Corneillie P, Ide P: Ovarian borderline mucinous tumor in a premenarchal girl: review of ovarian epithelial cancer in young girls. Gynecol Oncol 45:219 –224, 1992 9. Nelson L, Ekbom A, Gerdin E: Ovarian cancer in young women in Sweden, 1989 –1991. Gynecol Oncol 74:472– 476, 1999, doi:10.1006/ gyno.1999.5503 10. Koshiyama M, Yoshida M, Takemura M, Konishi M, Yura Y, Matsushita K, Hayashi M, Tauchi K: Management of malignant ovarian cancers in young women. Gynecol Obstet Invest 45:132–136, 1998 11. Hatch KD, Beecham JB, Blessing JA, Creasman T: Responsiveness of patients with advanced ovarian cancer to tamoxifen: a Gynecologic Oncology Group study of second-line therapy in 105 patients. Cancer 68: 269 –271, 1991 12. Kavanagh JJ, Roberts W, Townsend P, Hewitt S: Leuprolide acetate in the treatment of refractory or persistent epithelial ovarian cancer. J Clin Oncol 7:115–118, 1989 13. Lopez A, Tessadrelli A, Kudelka AP, Edwards CL, Freedman RS, Hord M, Kavanagh JJ: Combination therapy with leuprolide acetate and tamoxifen in refractory ovarian cancer. Int J Gynecol Cancer 6:15–19, 1996