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SYNCHRONOUS OVARIAN ENDOMETRIOID ADENOCARCINOMA AND ENDOCERVICAL MUCINOUS ADENOCARCINOMA

Yi-Duen Huang, Yao-Ching Hung, Lian-Shung Yeh, I-Ping Chiang1, Guan-Ching Zeng1, Wei-Chun Chang* Departments of Obstetrics and Gynecology, and 1Pathology, China Medical University Hospital, Taichung, Taiwan.

SUMMARY Objective: We report a rare case of synchronous consisting of ovarian endometrioid adenocarcinoma and endocervical mucinous adenocarcinoma. Related literature was reviewed and it appeared that no similar case had been reported previously. Case Report: A 30-year-old (gravida 1, para 1, abortus 0) woman complained of abdominal fullness, chest tightness and dyspnea on exertion of several days’ duration. Gynecologic sonography showed a right complex adnexal , 16 × 14 cm in size. Computed tomography showed an 18 × 16 cm right pelvic tumor, with both cystic and solid components, ascites and bilateral massive pleural effusion. Cytology of the pleural effusion showed no malignant cells. The patient underwent staging surgery. Histology showed moderately to poorly dif- ferentiated endometrioid adenocarcinoma of the right ovary with extensive lymphovascular permeation, as well as paraaortic and bilateral pelvic lymph node metastases. Extensive tumor thrombi were observed in the lym- phovascular channels of the left ovary, bilateral tubes and uterus. Endocervical adenocarcinoma, < 3 mm in depth, was also identified on the cervix. The final surgical-pathologic stage of ovarian endometrioid adenocar- cinoma was stage IIIc and of endocervical mucinous adenocarcinoma was stage IA1. Adjuvant chemotherapy with carboplatin and paclitaxel was prescribed postoperatively, but the malignancy was not controlled due to lung, brain and vulva metastases. The patient died of respiratory failure. Conclusion: The coexistence of primary in the ovary and cervix is rare. Diagnosis should be based on histologic examination and requires appropriate treatment for both tumors. [Taiwanese J Obstet Gynecol 2006; 45(3):264–267]

Key Words: endometrioid adenocarcinoma, mucinous adenocarcinoma, synchronous tumor

Introduction tumors. Synchronous tumors occur, or are diagnosed, at the same time; metachronous tumors occur at differ- Multiple primary cancer is a rare condition. The concept ent times. Moore et al introduced the concept of syn- of multiple malignant lesions has interested investiga- chronous tumors and defined them as secondary tors since 1889, when Billroth first described the condi- tumors that occur within 12 months [2]. If a new tumor tion [1]. Synchronous and metachronous are terms develops many years after the first, then the previously used to describe the occurrence of second primary administered radiotherapy or chemotherapy must be considered to be a possible . It is often pos- tulated that when two tumors occur in close succession, they may have been exposed to the same hormone or *Correspondence to: Dr Wei-Chun Chang, Department of Obstetrics carcinogen. The most common synchronous gyneco- and Gynecology, China Medical University Hospital, 2, Yuh-Der logic tumors are ovarian and endometrial; synchronous Road, Taichung 404, Taiwan. E-mail: [email protected] ovarian and endocervical tumors have rarely been Accepted: April 25, 2006 reported in the past.

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Case Report antigen (CEA) level was within the normal range. The results of preoperative examinations, including blood, A 30-year-old woman (gravida 1, para 1, abortus 0) urine, liver function, renal function, electrolytes, elec- with no significant past medical history visited our trocardiogram and chest X-ray, were all within normal outpatient department on January 4, 2005 with the ranges except for bilateral pleural effusion. complaints of chest tightness, dyspnea on exertion and The patient underwent laparotomy on January 7, orthopnea of several days’ duration. She had a non- 2005. Yellowish, watery ascites (~1,000 mL) was found tender abdominal mass, increased abdominal girth, in the abdominal cavity and was sent for cytologic exam- nausea and decreased appetite over the past month. ination. The cystic mass, 16 × 14 × 15 cm, had a dark red Gynecologic sonography showed a right complex adnexal smooth surface with no adhesions to the peritoneum or cyst, measuring 16 × 14 cm in size, with ascites and bilat- intestines. The internal content comprised fragile soft eral pleural effusion. She was admitted for further tissue soaked in a cola-like fluid and a small daughter evaluation the same day. Abdominal and pelvic com- cyst containing chocolate-like fluid. Frozen section of puted tomography (CT) showed a large tumor with the right ovary disclosed endometrioid adenocarcinoma both cystic and solid parts in the pelvis, mainly on the with papillary architecture and massive tumor necrosis. right side, ascites and massive bilateral pleural effusion The left ovary had a rough surface measuring about (Figure 1). Cytologic examination of the pleural effusion, 4.5 × 4 × 4 cm in size. The internal content was a performed twice, showed no malignant cells. The serum chocolate-like fluid. There was no enlargement of the CA-125 level was 702 U/mL but the carcinoembryonic retroperitoneal lymph nodes. Staging surgery was per- formed, including total abdominal hysterectomy, bilat- eral salpingo-oophorectomy, bilateral pelvic lymph node dissection, paraaortic lymph node sampling, bilat- eral infundibulopelvic ligament resection, appendec- tomy and omentectomy. In the final pathology report, the section of the right ovary mass showed a picture of grade 2/3 endometri- oid adenocarcinoma with tumor necrosis, papillary growth pattern, endometriosis and extensive lympho- vascular permeation (Figure 2). Metastatic adenocar- cinoma with tumor thrombus in the lymphovascular channels was found on the left ovary, bilateral tubes, uterus, cervix, bilateral pelvic lymph nodes and paraaortic lymph nodes. The cervix also presented with metastatic adenocarcinoma, about 18 mm in depth and 7 mm in width. Interestingly, according to the his- Figure 1. Computed tomography shows a large pelvic tumor tochemical studies, endocervical mucinous adenocar- with cystic and solid parts. cinoma was identified on the cervix (Figure 3), which

A B

Figure 2. (A) Ovarian endometrioid adenocarcinoma: complex, branching glands with focal tumor necrosis; glandular lesion showing irregular budding but smooth surface; tall columnar cells with central nuclei and nuclear stratification (hematoxylin & eosin, 100×). (B) Tumor cell nonreactive to carcinoembryonic antigen (CEA).

Taiwanese J Obstet Gynecol • September 2006 • Vol 45 • No 3 265 Y.D. Huang, et al

AB

Figure 3. (A) Cervical endocervical mucinous adenocarcinoma: tumor in the endocervical canal, about 3 mm in depth; glands with tall columnar cells containing basal nuclei and apical intracytoplasmic mucin; no focal adenocarcinoma found in situ (not shown here) (hematoxylin & eosin, 100×). (B) Diffuse positivity to carcinoembryonic antigen (CEA) (black arrows). was reactive for CEA and nonreactive for vimentin. The tumors derived from multiple tissues of origin, although lesion was < 3 mm in depth. The tumor on the ovary they were not divided into synchronous or metachro- was negative for CEA and vimentin. The cytology of the nous [3]. In 1984, the occurrence rate of synchronous ascites was negative for malignancy. The final surgical- gynecologic malignancies in patients with gynecologic pathologic stage of ovarian endometrioid adenocarci- tumors was 1.78%, and three cases of synchronous noma was stage IIIc and of endocervical mucinous invasive cervical cancer and ovarian tumor were found adenocarcinoma was stage IA1. among 2,362 patients by Axelrod et al in the Downstate After surgery, adjuvant chemotherapy with carbopla- Medical Center Tumor Registry [4]. In 1989, Eisner et al tin (area under the curve, 5) and paclitaxel (175 mg/m2) reviewed the histopathology of 3,863 patients with was prescribed monthly from January 14, 2005. female genital malignancies in the UCLA Tumor Registry Although CA-125 serum level declined to within the over a 30-year period [5]. Twenty-six patients (0.7%) normal range, multiple nodules in both lungs, prevas- with invasive synchronous primary were identi- cular and pretracheal spaces were present on CT 2 fied. The most frequent synchronous genital lesions were months later. Gemcitabine 800 mg/m2 was added. How- ovarian and endometrial cancer in 11 patients (0.3%), ever, tiny nodules were apparent on chest X-ray, when with only a single case of synchronous ovarian and cer- compared to previous X-rays, and the CA-125 level vical tumors (0.025%) [5]. In 1983, LiVolsi reported was slightly elevated from 9.06 U/mL to 43.7 U/mL. four cases of endocervical adenocarcinoma coexisting After finishing six courses of adjuvant chemotherapy, with ovarian mucinous adenocarcinoma [6]. In 2004, 18F-2-fluoro-2-deoxy-D-glucose positron emission tomo- two cases of synchronous ovarian and cervical cancer graphy (FDG-PET) was arranged and disclosed increas- were reported out of 861 women with gynecologic ing FDG uptake in both lungs, liver, paraaortic region tumors in Taiwan [7]. One of the cervical cancers was and pelvis, compatible with multiple metastases. Sal- squamous cell and the other was adenosqua- vage chemotherapy with pegylated doxorubicin HCl mous carcinoma. The ovarian cancers were both serous liposome was continued but progressive dyspnea and cystadenocarcinoma [7]. cachexia developed. She was transferred to a hospice Our patient presented with rare synchronous pri- ward on August 8, 2005 and died of respiratory failure mary gynecologic tumors of ovarian endometrioid and on September 1, 2005. endocervical mucinous adenocarcinomas. Distinction between endometrial and endocervical adenocarcino- mas may be made by using a small panel of antibodies, Discussion including CEA, estrogen receptor and vimentin [8]. Cells containing CEA are detected in approximately In 1961, Moertel et al described 1,909 patients who were 80% of endocervical adenocarcinoma and < 10% of found to have multiple primary malignant neoplasms out endometrial [9]. The cervical tumor in this of 37,580 patients with malignant neoplasms in a 10- case had diffuse positivity to CEA and the ovarian year period, which represented an overall occurrence rate tumor cells were nonreactive to CEA (Figures 2B and 3B). of 4.6% [3]. They also reported six cases of cervical and Recently, human papillomavirus (HPV) DNA was among 921 cases of double primary assessed to determine whether ovarian neoplasms were

266 Taiwanese J Obstet Gynecol • September 2006 • Vol 45 • No 3 Synchronous Ovarian and Endocervical Cancer metastatic or independent. The presence of HPV DNA 2. Moore R, Tsukada Y, Regelson W, Pickren JW, Bross ID. in ovarian tumors confirms that they are metastatic Synchronous tumors in patients with multiple primary endocervical adenocarcinomas [10]. cancers. Cancer 1965;18:1423–7. 3. Moertel CG, Dockerty MB, Baggenstoss AH. Multiple pri- Ovarian endometrioid carcinoma was reported to mary malignant neoplasms. Cancer 1961;14:221–30. have the highest incidence of multiple primary tumors 4. Axelrod JH, Fruchter R, Boyce JG. Multiple primaries among (21.3%) in 413 patients with primary ovarian tumors in gynecologic malignancies. Gynecol Oncol 1984;18:359–72. Silverman et al’s study [11]. Embryologic, hormonal, 5. Eisner RF, Nieberg RK, Berek JS. Synchronous primary neo- genetic or other phenomena may be associated with the plasms of the female reproductive tract. Gynecol Oncol 1989; development of malignancies arising simultaneously in 33:335–9. genital tissues [11–13]. Ovarian and endometrial can- 6. LiVolsi VA, Merino MJ, Schwartz PE. Coexistent endocervical cers are the most common synchronous primary tumors. adenocarcinoma and mucinous adenocarcinoma of ovary: a clinicopathologic study of four cases. Int J Gynecol Pathol Generally, synchronous double primary cancers have 1983;1:391–402. a more favorable prognosis than a tumor of a single 7. Wung RT, Su HY, Wu CC, Zhu BW, Yu MH. Synchronous metastatic lesion [7]. Patients with low stage and low primary gynecologic malignancy. Chung Hua Min Kao Fu Yen I grade synchronous ovarian and endometrial cancers have Hsueh Tsa Chih 2004;2:20–7. excellent prognoses. Detection at a relatively early stage 8. McCluggage WG. Recent advances in immunohistochemistry suggests diagnosis may be facilitated by early symptoms in gynaecological pathology. Histopathology 2002;40:309–26. from the endometrial carcinoma [5]. Our patient had 9. Crum CP, Nuovo GJ. The Cervix. In: Sternberg SS, Antonioli an advanced stage of ovarian cancer when diagnosed. DA, Carter D, Mills SE, Oberman HA, eds. Diagnostic Surgical Pathology, 2nd edition. New York: Raven Press, 1994:2083. In this case, the reaction or nonreaction of immuno- 10. Elishaev E, Gilks CB, Miller D, Srodon M, Kuman RJ, Ronnett histochemical stain to CEA on the tissue slides deter- BM. Synchronous and metachronous endocervical and ovar- mined the ovarian tumor cells from the endocervical ian neoplasms: evidence supporting interpretation of the ones. The treatment plan was mainly based on the ovarian neoplasms as metastatic endocervical adenocarci- protocol for advanced ovarian cancer since hysterec- nomas simulating primary ovarian surface epithelial neo- tomy is adequate treatment for cervical lesions. plasms. Am J Surg Pathol 2005;29:281–94. 11. Silverman BB, O’Neill RT, Mikuta JJ. Multiple malignant tumors associated with primary carcinoma of the ovary. Surg Gynecol Obstet 1972;134:244–8. References 12. Woodruff JD, Solomon D, Sullivant H. Multifocal disease in the upper genital canal. Obstet Gynecol 1985;65:695–8. 1. Billroth T. Die allgemeine chirurgische Pathologie und Therapie in 13. Hiroaki F, Toshiharu M, Manabu Y, et al. Genetics of syn- einundfünfzig Vorlesungen: ein Handbuch für Studirende und Aerzte, chronous uterine and ovarian endometrioid carcinoma: 14th edition. Berlin: Druck und Verlag von Georg Reimer, combined analyses of loss of heterozygosity, PTEN mutation, 1889:908. and microsatellite instability. Hum Pathol 2002;33:421–8.

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