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Combined Modality Treatment for Malignant Transformation of a Benign Ovarian Teratoma
Gynecologic Oncology 73, 319 –321 (1999) Article ID gyno.1999.5323, available online at http://www.idealibrary.com on
CASE REPORT Combined Modality Treatment for Malignant Transformation of a Benign Ovarian Teratoma J. E. Kurtz,* D. Jaeck,† F. Maloisel,* G. M. Jung,‡ M. P. Chenard,§ and P. Dufour* *Onco–Hematology Department, †Visceral and Transplantation Surgery Department, and §Pathology Department, Hoˆpitaux Universitaires, 67098 Strasbourg, France; and ‡Radiotherapy Department, Centre Paul Strauss, 3 rue de la Porte de l’Hoˆpital, 67000 Strasbourg, France Received July 31, 1998
Malignant transformation of a mature teratoma is a rare event. Patients often remain free of symptoms until the tumor burden makes the prognosis poor, due to pelvic and peritoneal metastases. We present a case of squamous cell carcinoma arising from a teratoma, with bowel and peritoneal invasion. The patient was treated by radical surgery followed by whole pelvic radiation and chemotherapy. This regimen, usually given for squamous cell tumors, such as cervical cancer, led to a 19-month persistant disease-free survival. © 1999 Academic Press Key Words: dermoid cyst; chemotherapy; radiotherapy.
INTRODUCTION Squamous cell carcinoma of the ovary is rare, and most cases develop within a mature cystic teratoma. The risk is reported to be between 0.5 and 2% of cases and usually arises in postmenopausal patients [1, 2]. Postoperative adjuvant therapy remains controversial. In locally advanced tumors, both radiation therapy and combination chemotherapy have been delivered in various schedules, but the overall survival is dismal. Patients with advanced disease have a dismal prognosis with a 2-year survival of 12% for stage III and 0% for stage IV [3]. We report a recent case and discuss the modalities of a combined modality treatment in the adjuvant setting. CLINICAL CASE A 34-year-old female was admitted for asthenia and leucocytosis (29.7 3 10 9/liter leucocytes with 22.3 3 10 9/liter neutrophils). She complained of thigh pain, mild fever, and night sweating for the previous 2 weeks. Two days prior to admission, her clinical status worsened; she had constipation alternating with diarrhea and complaints of diffuse arthralgias. At admission, temperature was 37°C, and the patient had a moderatly painful pelvic mass reaching the ombilicus. There was no palpable or visible ascites. Gynecologic examination revealed a left adnexal mass, consistant with a left ovarian
origin. Abdominal ultrasonography and abdominal CT scan showed a heterogenous tumor measuring 13 3 11 3 10 cm compressing the left ureter, bladder, and sigmoid colon. The tumor displayed various tissuler compounds, such as fat, liquid, and cystic parts. No particular feature was in favor of a malignancy. Barium enema was performed and showed a compressed sigmoid colon, with evidence of wall invasion. Standard blood chemistry was unremarkable, CA 125 was 116 U/liter. CEA, CA19-9, and B-HCG were normal, preoperative SCC antigen testing was not performed. Laparotomy was undertaken, and a large left ovarian tumor was found. Two metastatic peritoneal nodules were found as well, so the patient was staged IIIb in the FIGO classification. She underwent en-bloc tumor reductive surgery, resection of sigmoid bowel, omentectomy, and a total abdominal hysterectomy, with right salpingo-oophorectomy. Pathological findings revealed squamous cell carcinoma originating in a left ovarian dermoid cyst, with extension to the sigmoid wall (Fig. 1). A lymphadenectomy was not done at the time of surgery to assess whether pelvic or para-aortic lymphs nodes were involved. Postoperative lymphangiography was normal. Both adjuvant chemotherapy and radiotherapy were undertaken. Cisplatin (15 mg/m 2) was given as a continuous infusion days 1–5, 5-fluorouracil was given at 800 mg/m 2 days 1–5 every 3 weeks. External beam radiation was combined with chemotherapy, delivering 44 Gy (325 MeV; 5 3 1.8 Gy/week) to the whole pelvis and lomboaortic lymph nodes until the end of the second cycle of chemotherapy. Four additional chemotherapy courses were administered with acceptable tolerance. Six months after the completion of treatment the patient experienced constipation and abdominal pain. Abdominal CT scan and gastrointestinal contrast study revealed an ileal stenosis. Surgery was undertaken and revealed postradiation inflammation. The patient had removal of adhesions. Abdominal lymph nodes and peritoneal biopsies revealed no recurrent malignancy. The patient completely recovered from her abdominal symptoms and remains free of disease 19 months from diagnosis.
319
0090-8258/99 $30.00 Copyright © 1999 by Academic Press All rights of reproduction in any form reserved.
320
KURTZ ET AL.
FIG. 1. Invasion of the colonic wall by a squamous cell carcinoma of the left ovary. Note the colonic glands (G), the proliferation of neoplastic squamous cells (N), and the typical keratin pearls (arrow).
COMMENTARY Although a mature teratoma is the most common ovarian tumor among young women, its malignant transformation is a very rare event. Squamous cell carcinoma is the most frequent subtype of neoplasia in this setting, but other cancers have been reported, such as adenocarcinoma, melanoma, or carcinoid tumor. Squamous cell carcinomas usually develop from a mature teratoma in postmenopausal women, but are exceptional before the age of 30 [1, 4]. Clinical features include abdominal bloating or pain, constipation, and vaginal or rectal bleeding in cases of direct invasion. Radiological findings are those of large ovarian cystic masses, possibly a necrotic cavity, or mural thickening. The cyst walls may be adherent to adjacent structures (tubes, colon, bladder, or pelvic wall). Radiographic finding of either obvious capsular rupture or adjacent tissue invasion renders malignant transformation very likely. Surgery is essential, varying from salpingo-oophorectomy in stage I or II to total hysterectomy with bilateral salpingo-
oophorectomy, omentectomy, and sometimes segmental colectomy to obtain maximal tumor reduction in case of advanced disease [1, 4]. Due to its rarity, definitive or palliative therapy of squamous cell cancers arising from mature teratomas is not yet established. The question of whether pure stage I tumors require further therapy still remains questionable regarding their good prognosis after surgery alone [5]. Conversely, the tumor size was not a prognostic factor in a series of 24 patients [6]. In advanced tumors, radiation therapy has been delivered alone after surgery [1, 4, 6, 7] with inconstant results and serious adverse events (e.g., radiation enteritis) [5]. Multiagent chemotherapy has been delivered in advanced tumors with poor results [1, 3, 4]. It is noteworthy that some patients were treated with a PEB (cisplatin, etoposide, bleomycin) regimen, which is a standard for germ cells tumors, but is probably misadapted to squamous cell histology. A stage IIb patient was, however, treated with an adjuvant combination of doxorubicin vindesin, 5-fluorouracil, and cisplatin, remaining free of disease 3 years later [2]. Regimens designed for the treatment of squamous cell neoplasias (cervical cancer or head and neck cancer) are likely to be more adapted for squamous cell cancers arising from mature teratomas. In combined therapy for malignant transformation of mature teratomas, radiation therapy has been delivered both sequentially and concomitantly with various chemotherapy drugs and schedules [4, 7, 8]. Among these drugs, cisplatin and/or 5-fluorouracil are commonly used as radiosensitizers. Cisplatin 1 mg/kg weekly was delivered combined with a 50-Gy radiation therapy in squamous cell cancer arising from a mature teratoma patient, with an 8-month disease-free survival [5]. However, this patient experienced platinum-salt-induced neuropathy and radiation sigmoitidis. Sequential chemoradiation was reported in a stage II malignant squamous degeneration of a teratoma [8]. The patient received a pelvic external irradiation plus vaginal cesium insertion, for a total of 54 Gy, followed by a combination of methotrexate, bleomycin, and cisplatin. She died, free of cancer, 18 ½ months later. These combinations were based on the results of combined therapy for advanced cervical cancer, where radiosensitization with continuous 5-fluorouracil was shown to produce fewer complications compared to historical data with radiation therapy alone [9]. In patients with advanced squamous cell carcinoma of the cervix and vagina a combination of radiotherapy with cisplatin and 5-fluorouracil demonstrated a very high (89%) response rate [10]. The acute toxicity was mild and the delayed complications rate was consistent with prior reports of chemoradiation. As a consequence, we decided to undertake a combination of cisplatin and 5-fluorouracil with external radiation therapy to improve the local control of disease and perhaps survival in our patient. With regard to the reported outcome for stage III patients, it is noteworthy that at the time of report, our stage IIIb patient was free of disease 19 months after diagnosis.
CASE REPORT
REFERENCES 1. Beuzeboc P, Dorval T, Mathieu G, Garcia-Giralt E, Jouve M, Livartowski A, Palangie T, Scholl S, Pouillart P: De´ge´ne´rescence maligne e´pidermoı¨de des kystes dermoı¨des de l’ovaire. A propos de deux observations. Ann Chir 47(7):641– 644, 1993 2. Crouet H, De Ranieri E, De Ranieri J: Cance´risation secondaire des te´ratomes matures kystiques be´nins de l’ovaire (kystes dermoı¨des). Revue de la litte´rature a` propos d’un nouveau cas. J Gynecol Obstet Biol Reprod 15:1055–1066, 1986 3. Kashimura M, Shinohara M, Hirakawa T, Kamura T, Matsukuma K: Clinicopathologic study of squamous cell carcinoma of the ovary. Gynecol Oncol 34:75–79, 1989 4. Ribeiro G, Hughesdon P, Wiltshaw E: Squamous carcinoma arising in dermoid cysts and associated with hypercalcemia: a clinicopathologic study of six cases. Gynecol Oncol 29:222–230, 1988 5. Rose PG, Tak WK, Reale FR: Squamous cell carcinoma arising in a
6. 7.
8. 9.
10.
321
mature cystic teratoma with metastasis to the paraaortic nodes. Gynecol Oncol 50:131–133, 1993 Stamp GWH, Mc Connell EM: Malignancy arising in cystic ovarian teratomas. A report of 24 cases. Br J Obst Gyn 90:671– 675, 1983 Pins MR, Young RH, Daly WG, Scully RE: Primary squamous cell carcinoma of the ovary. Report of 37 cases. Am J Surg Pathol 20(7):823– 833, 1996 Seltzer V, Vogl S: Stage II benign cystic teratoma with malignant squamous degeneration. NY State J Med May:224 –225, 1985 Thomas G, Dembo A, Fyles A, Gadalla T, Beale F, Bean H, Pringle J, Rawlings G, Bush R, Black B: Concurrent chemoradiation in advanced cervical cancer. Gynecol Oncol 38:446 – 451, 1990 Roberts WS, Kavanagh JJ, Greenberg H, Bryson SCP, La Polla JP, Townsend PA, Hoffman MS, Cavanagh D, Hewitt S: Concomittant radiation therapy and chemotherapy in the treatment of advanced squamous carcinoma of the lower female genital tract. Gynecol Oncol 34:183–186, 1989
CASE REPORT Combined Modality Treatment for Malignant Transformation of a Benign Ovarian Teratoma J. E. Kurtz,* D. Jaeck,† F. Maloisel,* G. M. Jung,‡ M. P. Chenard,§ and P. Dufour* *Onco–Hematology Department, †Visceral and Transplantation Surgery Department, and §Pathology Department, Hoˆpitaux Universitaires, 67098 Strasbourg, France; and ‡Radiotherapy Department, Centre Paul Strauss, 3 rue de la Porte de l’Hoˆpital, 67000 Strasbourg, France Received July 31, 1998
Malignant transformation of a mature teratoma is a rare event. Patients often remain free of symptoms until the tumor burden makes the prognosis poor, due to pelvic and peritoneal metastases. We present a case of squamous cell carcinoma arising from a teratoma, with bowel and peritoneal invasion. The patient was treated by radical surgery followed by whole pelvic radiation and chemotherapy. This regimen, usually given for squamous cell tumors, such as cervical cancer, led to a 19-month persistant disease-free survival. © 1999 Academic Press Key Words: dermoid cyst; chemotherapy; radiotherapy.
INTRODUCTION Squamous cell carcinoma of the ovary is rare, and most cases develop within a mature cystic teratoma. The risk is reported to be between 0.5 and 2% of cases and usually arises in postmenopausal patients [1, 2]. Postoperative adjuvant therapy remains controversial. In locally advanced tumors, both radiation therapy and combination chemotherapy have been delivered in various schedules, but the overall survival is dismal. Patients with advanced disease have a dismal prognosis with a 2-year survival of 12% for stage III and 0% for stage IV [3]. We report a recent case and discuss the modalities of a combined modality treatment in the adjuvant setting. CLINICAL CASE A 34-year-old female was admitted for asthenia and leucocytosis (29.7 3 10 9/liter leucocytes with 22.3 3 10 9/liter neutrophils). She complained of thigh pain, mild fever, and night sweating for the previous 2 weeks. Two days prior to admission, her clinical status worsened; she had constipation alternating with diarrhea and complaints of diffuse arthralgias. At admission, temperature was 37°C, and the patient had a moderatly painful pelvic mass reaching the ombilicus. There was no palpable or visible ascites. Gynecologic examination revealed a left adnexal mass, consistant with a left ovarian
origin. Abdominal ultrasonography and abdominal CT scan showed a heterogenous tumor measuring 13 3 11 3 10 cm compressing the left ureter, bladder, and sigmoid colon. The tumor displayed various tissuler compounds, such as fat, liquid, and cystic parts. No particular feature was in favor of a malignancy. Barium enema was performed and showed a compressed sigmoid colon, with evidence of wall invasion. Standard blood chemistry was unremarkable, CA 125 was 116 U/liter. CEA, CA19-9, and B-HCG were normal, preoperative SCC antigen testing was not performed. Laparotomy was undertaken, and a large left ovarian tumor was found. Two metastatic peritoneal nodules were found as well, so the patient was staged IIIb in the FIGO classification. She underwent en-bloc tumor reductive surgery, resection of sigmoid bowel, omentectomy, and a total abdominal hysterectomy, with right salpingo-oophorectomy. Pathological findings revealed squamous cell carcinoma originating in a left ovarian dermoid cyst, with extension to the sigmoid wall (Fig. 1). A lymphadenectomy was not done at the time of surgery to assess whether pelvic or para-aortic lymphs nodes were involved. Postoperative lymphangiography was normal. Both adjuvant chemotherapy and radiotherapy were undertaken. Cisplatin (15 mg/m 2) was given as a continuous infusion days 1–5, 5-fluorouracil was given at 800 mg/m 2 days 1–5 every 3 weeks. External beam radiation was combined with chemotherapy, delivering 44 Gy (325 MeV; 5 3 1.8 Gy/week) to the whole pelvis and lomboaortic lymph nodes until the end of the second cycle of chemotherapy. Four additional chemotherapy courses were administered with acceptable tolerance. Six months after the completion of treatment the patient experienced constipation and abdominal pain. Abdominal CT scan and gastrointestinal contrast study revealed an ileal stenosis. Surgery was undertaken and revealed postradiation inflammation. The patient had removal of adhesions. Abdominal lymph nodes and peritoneal biopsies revealed no recurrent malignancy. The patient completely recovered from her abdominal symptoms and remains free of disease 19 months from diagnosis.
319
0090-8258/99 $30.00 Copyright © 1999 by Academic Press All rights of reproduction in any form reserved.
320
KURTZ ET AL.
FIG. 1. Invasion of the colonic wall by a squamous cell carcinoma of the left ovary. Note the colonic glands (G), the proliferation of neoplastic squamous cells (N), and the typical keratin pearls (arrow).
COMMENTARY Although a mature teratoma is the most common ovarian tumor among young women, its malignant transformation is a very rare event. Squamous cell carcinoma is the most frequent subtype of neoplasia in this setting, but other cancers have been reported, such as adenocarcinoma, melanoma, or carcinoid tumor. Squamous cell carcinomas usually develop from a mature teratoma in postmenopausal women, but are exceptional before the age of 30 [1, 4]. Clinical features include abdominal bloating or pain, constipation, and vaginal or rectal bleeding in cases of direct invasion. Radiological findings are those of large ovarian cystic masses, possibly a necrotic cavity, or mural thickening. The cyst walls may be adherent to adjacent structures (tubes, colon, bladder, or pelvic wall). Radiographic finding of either obvious capsular rupture or adjacent tissue invasion renders malignant transformation very likely. Surgery is essential, varying from salpingo-oophorectomy in stage I or II to total hysterectomy with bilateral salpingo-
oophorectomy, omentectomy, and sometimes segmental colectomy to obtain maximal tumor reduction in case of advanced disease [1, 4]. Due to its rarity, definitive or palliative therapy of squamous cell cancers arising from mature teratomas is not yet established. The question of whether pure stage I tumors require further therapy still remains questionable regarding their good prognosis after surgery alone [5]. Conversely, the tumor size was not a prognostic factor in a series of 24 patients [6]. In advanced tumors, radiation therapy has been delivered alone after surgery [1, 4, 6, 7] with inconstant results and serious adverse events (e.g., radiation enteritis) [5]. Multiagent chemotherapy has been delivered in advanced tumors with poor results [1, 3, 4]. It is noteworthy that some patients were treated with a PEB (cisplatin, etoposide, bleomycin) regimen, which is a standard for germ cells tumors, but is probably misadapted to squamous cell histology. A stage IIb patient was, however, treated with an adjuvant combination of doxorubicin vindesin, 5-fluorouracil, and cisplatin, remaining free of disease 3 years later [2]. Regimens designed for the treatment of squamous cell neoplasias (cervical cancer or head and neck cancer) are likely to be more adapted for squamous cell cancers arising from mature teratomas. In combined therapy for malignant transformation of mature teratomas, radiation therapy has been delivered both sequentially and concomitantly with various chemotherapy drugs and schedules [4, 7, 8]. Among these drugs, cisplatin and/or 5-fluorouracil are commonly used as radiosensitizers. Cisplatin 1 mg/kg weekly was delivered combined with a 50-Gy radiation therapy in squamous cell cancer arising from a mature teratoma patient, with an 8-month disease-free survival [5]. However, this patient experienced platinum-salt-induced neuropathy and radiation sigmoitidis. Sequential chemoradiation was reported in a stage II malignant squamous degeneration of a teratoma [8]. The patient received a pelvic external irradiation plus vaginal cesium insertion, for a total of 54 Gy, followed by a combination of methotrexate, bleomycin, and cisplatin. She died, free of cancer, 18 ½ months later. These combinations were based on the results of combined therapy for advanced cervical cancer, where radiosensitization with continuous 5-fluorouracil was shown to produce fewer complications compared to historical data with radiation therapy alone [9]. In patients with advanced squamous cell carcinoma of the cervix and vagina a combination of radiotherapy with cisplatin and 5-fluorouracil demonstrated a very high (89%) response rate [10]. The acute toxicity was mild and the delayed complications rate was consistent with prior reports of chemoradiation. As a consequence, we decided to undertake a combination of cisplatin and 5-fluorouracil with external radiation therapy to improve the local control of disease and perhaps survival in our patient. With regard to the reported outcome for stage III patients, it is noteworthy that at the time of report, our stage IIIb patient was free of disease 19 months after diagnosis.
CASE REPORT
REFERENCES 1. Beuzeboc P, Dorval T, Mathieu G, Garcia-Giralt E, Jouve M, Livartowski A, Palangie T, Scholl S, Pouillart P: De´ge´ne´rescence maligne e´pidermoı¨de des kystes dermoı¨des de l’ovaire. A propos de deux observations. Ann Chir 47(7):641– 644, 1993 2. Crouet H, De Ranieri E, De Ranieri J: Cance´risation secondaire des te´ratomes matures kystiques be´nins de l’ovaire (kystes dermoı¨des). Revue de la litte´rature a` propos d’un nouveau cas. J Gynecol Obstet Biol Reprod 15:1055–1066, 1986 3. Kashimura M, Shinohara M, Hirakawa T, Kamura T, Matsukuma K: Clinicopathologic study of squamous cell carcinoma of the ovary. Gynecol Oncol 34:75–79, 1989 4. Ribeiro G, Hughesdon P, Wiltshaw E: Squamous carcinoma arising in dermoid cysts and associated with hypercalcemia: a clinicopathologic study of six cases. Gynecol Oncol 29:222–230, 1988 5. Rose PG, Tak WK, Reale FR: Squamous cell carcinoma arising in a
6. 7.
8. 9.
10.
321
mature cystic teratoma with metastasis to the paraaortic nodes. Gynecol Oncol 50:131–133, 1993 Stamp GWH, Mc Connell EM: Malignancy arising in cystic ovarian teratomas. A report of 24 cases. Br J Obst Gyn 90:671– 675, 1983 Pins MR, Young RH, Daly WG, Scully RE: Primary squamous cell carcinoma of the ovary. Report of 37 cases. Am J Surg Pathol 20(7):823– 833, 1996 Seltzer V, Vogl S: Stage II benign cystic teratoma with malignant squamous degeneration. NY State J Med May:224 –225, 1985 Thomas G, Dembo A, Fyles A, Gadalla T, Beale F, Bean H, Pringle J, Rawlings G, Bush R, Black B: Concurrent chemoradiation in advanced cervical cancer. Gynecol Oncol 38:446 – 451, 1990 Roberts WS, Kavanagh JJ, Greenberg H, Bryson SCP, La Polla JP, Townsend PA, Hoffman MS, Cavanagh D, Hewitt S: Concomittant radiation therapy and chemotherapy in the treatment of advanced squamous carcinoma of the lower female genital tract. Gynecol Oncol 34:183–186, 1989