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Gastrointestinal adenocarcinoma arising in a mature cystic teratoma of the ovary
Gynecologic Oncology 94 (2004) 597 – 599 www.elsevier.com/locate/ygyno
Case Report
Gastrointestinal adenocarcinoma arising in a mature cystic teratoma of the ovary Douglas A. Levine, a,* Jeannine A. Villella, a Elizabeth A. Poynor, a and Robert A. Soslow b a
Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA b Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA Received 19 March 2004 Available online 2 July 2004
Abstract Background. Mature cystic teratoma of the ovary (MCTO) is the most common ovarian germ cell neoplasm and is usually diagnosed in early adulthood. Malignant transformation is rare, occurring in approximately 2% of all cases. Though malignant transformation can occur from any of the embryonic germ layers, the most common malignancy arising in these otherwise benign tumors is squamous cell carcinoma. Case. We present a patient with a MCTO where malignant transformation of gastrointestinal epithelium resulted in moderately differentiated adenocarcinoma. After 3 years of follow-up, she remains free of disease. Conclusion. Although gastrointestinal epithelium is often found in MCTOs, adenocarcinoma arising from this cell type is uncommon. This is the third reported case of adenocarcinoma arising in gastrointestinal epithelium of a MCTO. D 2004 Elsevier Inc. All rights reserved. Keywords: Cystic teratoma of the ovary; Dermoid cyst; Adenocarcinoma; Malignant transformation; Ovarian cancer
Introduction
Case presentation
Mature cystic teratoma of the ovary (MCTO), frequently called a dermoid cyst, is the most common of all ovarian neoplasm and represents the majority of benign ovarian neoplasms in women less than 30 years of age [1]. Malignant transformation of mature cystic teratoma of the ovary (MCTO) occurs in approximately 2% of all cases [2]. Patients found to have malignant transformation in a MCTO are likely to be post-menopausal. Squamous cell carcinoma accounts for 75– 85% of the malignant degeneration found in MCTO and adenocarcinoma has been reported to occur in 6.8% of cases [3,4]. To our knowledge, only two previous cases of adenocarcinoma arising in gastrointestinal epithelium of a MCTO have been reported in the English literature [5,6]. The case presented herein represents the rare occurrence of malignant transformation of gastrointestinal epithelium within a MCTO.
A 37-year-old woman presented to our service complaining of 3 months of lower abdominal and back pain, frequent urination and fatigue. Her past medical, surgical, gynecologic, and family histories were all unremarkable. She reported routine gynecologic care and denied ever having mammography or colonoscopy. Physical examination revealed a palpable solid abdominal mass extending to a point midway between the umbilicus and the pubic symphysis. Bimanual exam confirmed a mobile adnexal mass approximately 12 to 15 cm in greatest dimension. Computed tomography scan of the abdomen and pelvis with oral and intravenous contrast revealed a 12 12 10 cm complex right adnexal mass containing fat and other soft tissue (Fig. 1). The uterus and upper abdomen were within normal limits. The left ovary was not seen. Laboratory analyses revealed a CEA of 11.2 ng/ml (nl: 0– 5) and a normal CA-125, HCG and AFP. Serum electrolytes, liver function tests, and complete blood counts were unremarkable. After obtaining informed consent, the patient was scheduled for an exploratory laparotomy, unilateral salpingo-oophorectomy, and possible staging procedures.
* Corresponding author. Gynecology Service Academic Office, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room MRI-1027, New York, NY 10021. Fax: +1-212-717-3214. E-mail address: [email protected] (D.A. Levine). 0090-8258/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2004.05.045
598
D.A. Levine et al. / Gynecologic Oncology 94 (2004) 597–599
specimens were benign resulting in a completely resected FIGO stage IA, grade 2, adenocarcinoma of the right ovary. The patient’s postoperative course was complicated by severe Clostridium difficile colitis requiring readmission to the hospital for antibiotics and intravenous hydration. The patient recovered without any further sequelae. Postoperatively, the patient’s CEA returned to normal within 3 weeks of the operation. The patient also had a postoperative colonoscopy and upper endoscopy both of which were entirely within normal limits. The patient received no further treatment and remains free of disease 40 months after her initial cancer diagnosis.
Pathologic findings Fig 1. Computed tomography scan through the pelvis showing a large complex cystic mass with a fat-fluid level and soft tissue components.
During the surgical procedure, a 14-cm cystic right adnexal mass was found. Hair and other particulate matter were visible through the translucent cyst wall. There was a 2-cm cyst on the contralateral ovary. The uterus, other pelvic structures and the upper abdomen were all grossly normal. A right salpingo-oophorectomy was performed. An intraoperative pathologic analysis of the right adnexal mass revealed a focus of adenocarcinoma. Therefore, a modified staging procedure was performed including a bilateral pelvic and paraaortic lymphadenectomy, infracolic omentectomy and multiple peritoneal and diaphragmatic biopsies. Pelvic and peritoneal washings had been obtained when the abdomen was initially opened. A left ovarian cystectomy was also performed. A contralateral oophorectomy and hysterectomy were not performed based upon the patient’s age and desire to preserve the potential for future fertility. Final pathology confirmed a focus of moderately differentiated adenocarcinoma within the right cystic teratoma. All other
Fig 2. Photomicrograph at low-power magnification of the malignant gastrointestinal epithelial component of the cystic teratoma (H&E). This moderately differentiated gastrointestinal-type adenocarcinoma contains an entrapped hair (denoted by an asterisk), highlighting its origin in a mature cystic teratoma.
The main specimen consisted of a 15 12 11 cm cystic mass containing hair and keratinaceous debris. The cyst lining was thickened with a yellow, gritty surface. There were areas of hemorrhage and edema surrounding the cyst. Gross necrosis was not appreciated, although abundant debris was described. The histologic sections from the cyst wall disclosed a mature cystic teratoma that included ectodermal, mesodermal and endodermal elements. Sections from areas of wall thickening showed a 2-cm neoplasm composed predominantly of tubular glands arranged in a cribriform pattern. Neoplastic elements entrapped hair and keratinaceous debris (Fig. 2). Dirty necrosis of the type commonly found in colorectal adenocarcinomas was noted. Tumor cells possessed amphophilic cytoplasm with occasional intracytoplasmic mucin. Nuclei were enlarged and irregularly shaped and contained coarse chromatin and large nucleoli. Nonneoplastic colonic epithelium and adenomatous epithelium were noted at the periphery of the tumor. There was no lymphovascular space invasion appreciated. Adenocarcinoma was present within 1 mm of the uninvolved ovarian surface. Immunohistochemistry staining for cytokeratin 20 was strongly positive supporting the diagnosis of gastroin-
Fig 3. Photomicrograph at high-power magnification demonstrating a strongly positive cytokeratin 20 immunohistochemical stain and counterstained with hematoxylin.
D.A. Levine et al. / Gynecologic Oncology 94 (2004) 597–599
testinal adenocarcinoma (Fig. 3). The contralateral ovary contained a benign functional cyst. Twelve pelvic and six paraaortic lymph nodes were all within normal limits.
Discussion MCTO is the most common ovarian teratoma as well as the most common ovarian germ cell neoplasm. Fifteen percent of cases are bilateral. These tumors consist of maturely differentiated derivatives of all three germ cell layers, the ectodermal layer being most prominent. Though malignant transformation of the mature cystic ovarian teratoma can occur in 2% of all cases, there are no characteristic signs or symptoms [2]. Occasionally, patients will present with weight loss, a rapidly enlarging mass or changes in bowel habits; however, this is more the exception than the rule with malignant transformation of MCTO. Degenerative changes occur between the age of 30 and 70 years, with a higher incidence in post-menopausal patients [3]. Given the totipotent nature of these cells, they may undergo any type or any combination of malignant degeneration. Although many cell types have been described, squamous cell carcinoma is responsible for the majority of malignant transformations. The presence of gastrointestinal epithelium in MCTO is not rare, yet its malignant degeneration is uncommon. In 1957, Peterson [7] reviewed 15 adenocarcinomas and found that the histologic origins were from mammary, salivary, sebaceous, and thyroid gland epithelium, not gastrointestinal. Since then, there have been many reports of adenocarcinoma arising in MCTO, but only two cases showing gastrointestinal differentiation [5,6]. This case differs from the two previously reported cases of adenocarcinoma arising from the gastrointestinal epithelium of a MCTO. In the first reported case, the patient was postmenopausal (62 years of age), the tumor was huge (15 kg) yet confined to the ovary, the patient received adjuvant chemotherapy and had a favorable outcome (without evidence of disease 15 years after diagnosis) [6]. In the second reported case, the patient was pre-menopausal (38 years of age), had widely metastatic disease at diagnosis, received adjuvant chemotherapy, and succumbed to disease shortly after diagnosis [5]. The first case is similar to the case presented here in that the patient had both a favorable outcome and limited disease at diagnosis. It appears that in contrary to initial reports, patients with adenocarcinoma arising from a MCTO without spread beyond the ovary can have a favorable outcome. However, our case is similar to the second case in that the patient was diagnosed in her late 30s. Malignant degeneration of MCTO typically occurs in post-menopausal women, though diagnosis in pre-menopausal women is not extraordinary. However, nearly half of the recently reported cases of adenocarcino-
599
ma arising from glandular epithelium in MCTO have been under the age of 50. Serum markers are frequently measured in young patients with an adnexal mass and an unclear clinical picture. Interestingly in this case, the elevation of the carcinoembryonic antigen, common in mucinous carcinomas of the gastrointestinal tract, was unexpected and unexplained until the final diagnosis was returned. As with other malignant ovarian neoplasms, most recurrences reported to date in adenocarcinomas arising in MCTO have been detected within 2 years of diagnosis. The patient presented here has been free of disease for well over 3 years. For epithelial ovarian cancer not associated with a MCTO, conservative treatment and no adjuvant therapy are appropriate for selected patients with stage IA comprehensively staged disease. Adjuvant therapy is typically prescribed for patients with grade 3 tumors and withheld for patients with grade 1 tumors. The treatment of stage IA grade 2 tumors is controversial. In this case with limited disease, treatment options were discussed with the patient and withholding adjuvant therapy was felt to be appropriate. It appears that similar treatment paradigms to common epithelial ovarian cancer can be applied to adenocarcinoma arising in MCTO in regard to the extent of surgical resection and adjuvant therapy; however, our experience with these tumors is obviously very limited. For organ-confined adenocarcinomas arising in a MCTO without surface involvement, adjuvant therapy may be appropriate for larger, poorly differentiated tumors with lymphovascular space invasion. We are hopeful at this point that our patient has been cured of her disease, which had a remarkable histologic origin and was amenable to conservative therapy. References [1] Koonings PP, Campbell K, Mishell DR, Grimes DA. Relative frequency of primary ovarian neoplasms: a 10-year review. Obstet Gynecol 1989;74:921 – 6. [2] Talerman A. Germ cell tumors of the ovary. In: Kurman RJ, editor. Blaustein’s Pathology of the Female Genital Tract. New York (NY): Springer-Verlag; 1994. p. 883 – 4. [3] Templeman CL, Fallat ME, Lam AM, Perlman SE, Hertweck SP, O’Connor DM. Managing mature cystic teratomas of the ovary. Obstet Gynecol Surv 2000;55:738 – 45. [4] Powell JL, Stinson JA, Connor GP, Shiro BS, Mattison M. Squamous cell carcinoma arising in a dermoid cyst of the ovary. Gynecol Oncol 2003;89:526 – 8. [5] Fishman A, Edelstein E, Altaras M, Beyth Y, Bernheim J. Adenocarcinoma arising from the gastrointestinal epithelium in benign cystic teratoma of the ovary. Gynecol Oncol 1998;70:418 – 20. [6] Ueda G, Fujita M, Ogawa H, Sawada M, Inoue M, Tanizawa O. Adenocarcinoma in a benign cystic teratoma of the ovary: report of a case with a long survival period. Gynecol Oncol 1993;48:259 – 63. [7] Peterson WF. Malignant degeneration of benign cystic teratomas of the overy; a collective review of the literature. Obstet Gynecol Surv 1957; 12:793 – 830.
Case Report
Gastrointestinal adenocarcinoma arising in a mature cystic teratoma of the ovary Douglas A. Levine, a,* Jeannine A. Villella, a Elizabeth A. Poynor, a and Robert A. Soslow b a
Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA b Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA Received 19 March 2004 Available online 2 July 2004
Abstract Background. Mature cystic teratoma of the ovary (MCTO) is the most common ovarian germ cell neoplasm and is usually diagnosed in early adulthood. Malignant transformation is rare, occurring in approximately 2% of all cases. Though malignant transformation can occur from any of the embryonic germ layers, the most common malignancy arising in these otherwise benign tumors is squamous cell carcinoma. Case. We present a patient with a MCTO where malignant transformation of gastrointestinal epithelium resulted in moderately differentiated adenocarcinoma. After 3 years of follow-up, she remains free of disease. Conclusion. Although gastrointestinal epithelium is often found in MCTOs, adenocarcinoma arising from this cell type is uncommon. This is the third reported case of adenocarcinoma arising in gastrointestinal epithelium of a MCTO. D 2004 Elsevier Inc. All rights reserved. Keywords: Cystic teratoma of the ovary; Dermoid cyst; Adenocarcinoma; Malignant transformation; Ovarian cancer
Introduction
Case presentation
Mature cystic teratoma of the ovary (MCTO), frequently called a dermoid cyst, is the most common of all ovarian neoplasm and represents the majority of benign ovarian neoplasms in women less than 30 years of age [1]. Malignant transformation of mature cystic teratoma of the ovary (MCTO) occurs in approximately 2% of all cases [2]. Patients found to have malignant transformation in a MCTO are likely to be post-menopausal. Squamous cell carcinoma accounts for 75– 85% of the malignant degeneration found in MCTO and adenocarcinoma has been reported to occur in 6.8% of cases [3,4]. To our knowledge, only two previous cases of adenocarcinoma arising in gastrointestinal epithelium of a MCTO have been reported in the English literature [5,6]. The case presented herein represents the rare occurrence of malignant transformation of gastrointestinal epithelium within a MCTO.
A 37-year-old woman presented to our service complaining of 3 months of lower abdominal and back pain, frequent urination and fatigue. Her past medical, surgical, gynecologic, and family histories were all unremarkable. She reported routine gynecologic care and denied ever having mammography or colonoscopy. Physical examination revealed a palpable solid abdominal mass extending to a point midway between the umbilicus and the pubic symphysis. Bimanual exam confirmed a mobile adnexal mass approximately 12 to 15 cm in greatest dimension. Computed tomography scan of the abdomen and pelvis with oral and intravenous contrast revealed a 12 12 10 cm complex right adnexal mass containing fat and other soft tissue (Fig. 1). The uterus and upper abdomen were within normal limits. The left ovary was not seen. Laboratory analyses revealed a CEA of 11.2 ng/ml (nl: 0– 5) and a normal CA-125, HCG and AFP. Serum electrolytes, liver function tests, and complete blood counts were unremarkable. After obtaining informed consent, the patient was scheduled for an exploratory laparotomy, unilateral salpingo-oophorectomy, and possible staging procedures.
* Corresponding author. Gynecology Service Academic Office, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room MRI-1027, New York, NY 10021. Fax: +1-212-717-3214. E-mail address: [email protected] (D.A. Levine). 0090-8258/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2004.05.045
598
D.A. Levine et al. / Gynecologic Oncology 94 (2004) 597–599
specimens were benign resulting in a completely resected FIGO stage IA, grade 2, adenocarcinoma of the right ovary. The patient’s postoperative course was complicated by severe Clostridium difficile colitis requiring readmission to the hospital for antibiotics and intravenous hydration. The patient recovered without any further sequelae. Postoperatively, the patient’s CEA returned to normal within 3 weeks of the operation. The patient also had a postoperative colonoscopy and upper endoscopy both of which were entirely within normal limits. The patient received no further treatment and remains free of disease 40 months after her initial cancer diagnosis.
Pathologic findings Fig 1. Computed tomography scan through the pelvis showing a large complex cystic mass with a fat-fluid level and soft tissue components.
During the surgical procedure, a 14-cm cystic right adnexal mass was found. Hair and other particulate matter were visible through the translucent cyst wall. There was a 2-cm cyst on the contralateral ovary. The uterus, other pelvic structures and the upper abdomen were all grossly normal. A right salpingo-oophorectomy was performed. An intraoperative pathologic analysis of the right adnexal mass revealed a focus of adenocarcinoma. Therefore, a modified staging procedure was performed including a bilateral pelvic and paraaortic lymphadenectomy, infracolic omentectomy and multiple peritoneal and diaphragmatic biopsies. Pelvic and peritoneal washings had been obtained when the abdomen was initially opened. A left ovarian cystectomy was also performed. A contralateral oophorectomy and hysterectomy were not performed based upon the patient’s age and desire to preserve the potential for future fertility. Final pathology confirmed a focus of moderately differentiated adenocarcinoma within the right cystic teratoma. All other
Fig 2. Photomicrograph at low-power magnification of the malignant gastrointestinal epithelial component of the cystic teratoma (H&E). This moderately differentiated gastrointestinal-type adenocarcinoma contains an entrapped hair (denoted by an asterisk), highlighting its origin in a mature cystic teratoma.
The main specimen consisted of a 15 12 11 cm cystic mass containing hair and keratinaceous debris. The cyst lining was thickened with a yellow, gritty surface. There were areas of hemorrhage and edema surrounding the cyst. Gross necrosis was not appreciated, although abundant debris was described. The histologic sections from the cyst wall disclosed a mature cystic teratoma that included ectodermal, mesodermal and endodermal elements. Sections from areas of wall thickening showed a 2-cm neoplasm composed predominantly of tubular glands arranged in a cribriform pattern. Neoplastic elements entrapped hair and keratinaceous debris (Fig. 2). Dirty necrosis of the type commonly found in colorectal adenocarcinomas was noted. Tumor cells possessed amphophilic cytoplasm with occasional intracytoplasmic mucin. Nuclei were enlarged and irregularly shaped and contained coarse chromatin and large nucleoli. Nonneoplastic colonic epithelium and adenomatous epithelium were noted at the periphery of the tumor. There was no lymphovascular space invasion appreciated. Adenocarcinoma was present within 1 mm of the uninvolved ovarian surface. Immunohistochemistry staining for cytokeratin 20 was strongly positive supporting the diagnosis of gastroin-
Fig 3. Photomicrograph at high-power magnification demonstrating a strongly positive cytokeratin 20 immunohistochemical stain and counterstained with hematoxylin.
D.A. Levine et al. / Gynecologic Oncology 94 (2004) 597–599
testinal adenocarcinoma (Fig. 3). The contralateral ovary contained a benign functional cyst. Twelve pelvic and six paraaortic lymph nodes were all within normal limits.
Discussion MCTO is the most common ovarian teratoma as well as the most common ovarian germ cell neoplasm. Fifteen percent of cases are bilateral. These tumors consist of maturely differentiated derivatives of all three germ cell layers, the ectodermal layer being most prominent. Though malignant transformation of the mature cystic ovarian teratoma can occur in 2% of all cases, there are no characteristic signs or symptoms [2]. Occasionally, patients will present with weight loss, a rapidly enlarging mass or changes in bowel habits; however, this is more the exception than the rule with malignant transformation of MCTO. Degenerative changes occur between the age of 30 and 70 years, with a higher incidence in post-menopausal patients [3]. Given the totipotent nature of these cells, they may undergo any type or any combination of malignant degeneration. Although many cell types have been described, squamous cell carcinoma is responsible for the majority of malignant transformations. The presence of gastrointestinal epithelium in MCTO is not rare, yet its malignant degeneration is uncommon. In 1957, Peterson [7] reviewed 15 adenocarcinomas and found that the histologic origins were from mammary, salivary, sebaceous, and thyroid gland epithelium, not gastrointestinal. Since then, there have been many reports of adenocarcinoma arising in MCTO, but only two cases showing gastrointestinal differentiation [5,6]. This case differs from the two previously reported cases of adenocarcinoma arising from the gastrointestinal epithelium of a MCTO. In the first reported case, the patient was postmenopausal (62 years of age), the tumor was huge (15 kg) yet confined to the ovary, the patient received adjuvant chemotherapy and had a favorable outcome (without evidence of disease 15 years after diagnosis) [6]. In the second reported case, the patient was pre-menopausal (38 years of age), had widely metastatic disease at diagnosis, received adjuvant chemotherapy, and succumbed to disease shortly after diagnosis [5]. The first case is similar to the case presented here in that the patient had both a favorable outcome and limited disease at diagnosis. It appears that in contrary to initial reports, patients with adenocarcinoma arising from a MCTO without spread beyond the ovary can have a favorable outcome. However, our case is similar to the second case in that the patient was diagnosed in her late 30s. Malignant degeneration of MCTO typically occurs in post-menopausal women, though diagnosis in pre-menopausal women is not extraordinary. However, nearly half of the recently reported cases of adenocarcino-
599
ma arising from glandular epithelium in MCTO have been under the age of 50. Serum markers are frequently measured in young patients with an adnexal mass and an unclear clinical picture. Interestingly in this case, the elevation of the carcinoembryonic antigen, common in mucinous carcinomas of the gastrointestinal tract, was unexpected and unexplained until the final diagnosis was returned. As with other malignant ovarian neoplasms, most recurrences reported to date in adenocarcinomas arising in MCTO have been detected within 2 years of diagnosis. The patient presented here has been free of disease for well over 3 years. For epithelial ovarian cancer not associated with a MCTO, conservative treatment and no adjuvant therapy are appropriate for selected patients with stage IA comprehensively staged disease. Adjuvant therapy is typically prescribed for patients with grade 3 tumors and withheld for patients with grade 1 tumors. The treatment of stage IA grade 2 tumors is controversial. In this case with limited disease, treatment options were discussed with the patient and withholding adjuvant therapy was felt to be appropriate. It appears that similar treatment paradigms to common epithelial ovarian cancer can be applied to adenocarcinoma arising in MCTO in regard to the extent of surgical resection and adjuvant therapy; however, our experience with these tumors is obviously very limited. For organ-confined adenocarcinomas arising in a MCTO without surface involvement, adjuvant therapy may be appropriate for larger, poorly differentiated tumors with lymphovascular space invasion. We are hopeful at this point that our patient has been cured of her disease, which had a remarkable histologic origin and was amenable to conservative therapy. References [1] Koonings PP, Campbell K, Mishell DR, Grimes DA. Relative frequency of primary ovarian neoplasms: a 10-year review. Obstet Gynecol 1989;74:921 – 6. [2] Talerman A. Germ cell tumors of the ovary. In: Kurman RJ, editor. Blaustein’s Pathology of the Female Genital Tract. New York (NY): Springer-Verlag; 1994. p. 883 – 4. [3] Templeman CL, Fallat ME, Lam AM, Perlman SE, Hertweck SP, O’Connor DM. Managing mature cystic teratomas of the ovary. Obstet Gynecol Surv 2000;55:738 – 45. [4] Powell JL, Stinson JA, Connor GP, Shiro BS, Mattison M. Squamous cell carcinoma arising in a dermoid cyst of the ovary. Gynecol Oncol 2003;89:526 – 8. [5] Fishman A, Edelstein E, Altaras M, Beyth Y, Bernheim J. Adenocarcinoma arising from the gastrointestinal epithelium in benign cystic teratoma of the ovary. Gynecol Oncol 1998;70:418 – 20. [6] Ueda G, Fujita M, Ogawa H, Sawada M, Inoue M, Tanizawa O. Adenocarcinoma in a benign cystic teratoma of the ovary: report of a case with a long survival period. Gynecol Oncol 1993;48:259 – 63. [7] Peterson WF. Malignant degeneration of benign cystic teratomas of the overy; a collective review of the literature. Obstet Gynecol Surv 1957; 12:793 – 830.