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Advanced endocervical adenocarcinoma metastatic to the ovary presenting as primary ovarian cancer
Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 201e203
Contents lists available at ScienceDirect
Taiwanese Journal of Obstetrics & Gynecology journal homepage: www.tjog-online.com
Research Letter
Advanced endocervical adenocarcinoma metastatic to the ovary presenting as primary ovarian cancer Hsu-Dong Sun a, b, Sheng-Mou Hsiao a, Yi-Jen Chen b, c, Kuo-Chang Wen b, c, Yiu-Tai Li d, 1, Peng-Hui Peter Wang b, c, e, f, g, *, 1 a
Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital, New Taipei City, Taiwan Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan Division of Gynecology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan d Department of Obstetrics and Gynecology, Kuo General Hospital, Tainan, Taiwan e Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan f Department of Nursing, National Yang-Ming University School of Nursing, Taipei, Taiwan g Department of Medical Research, China Medical University Hospital, Taichung, Taiwan b c
a r t i c l e i n f o Article history: Accepted 21 October 2014
Dear Editor, Cervical squamous cell carcinoma (SCC) and adenocarcinoma may involve the ovary. Although it is not difficult to diagnose in most cases, on very rare occasions the presentation may show symptoms related to an ovarian mass, with the cervical cancer being undetected, especially endocervical adenocarcinoma [1,2]. This is important because the challenge of diagnosing primary endocervical adenocarcinoma occurs especially in women who show no symptoms, and have a grossly normal cervix and a negative Pap smear [3]. The spread of cervical malignancy (both SCC and adenocarcinoma) is often through lymphatic drainage or direct invasion [4]; except some reports show that endocervical adenocarcinoma carries a higher risk of ovarian metastases than SCC of the cervix [5]. There is an apparent difference in the treatment strategy for advanced cervical cancers and ovarian cancers [6,7]. Therefore, making an accurate diagnosis before planning therapy is of paramount importance. The following is a case report of advanced cervical adenocarcinoma metastatic to the ovary mimicking primary ovarian cancer.
* Corresponding author. Division of Gynecology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, 201, Section 2, Shih-Pai Road, Taipei, Taiwan. E-mail addresses: [email protected] (Y.-T. Li), [email protected], [email protected] (P.-H.P. Wang). 1 Drs. Li and Wang contributed equally to this article.
A 54-year-old menopausal woman (G3P3) visited the emergency room due to acute sudden onset of abdominal pain after several weeks of abdominal fullness. Her past medical history was unremarkable. She did not have any Pap smears since the birth of her last child (28 years previously). Physical examination revealed a protuberant and tense abdomen, but the cervix was essentially normal. Transvaginal ultrasound revealed a 15 cm complex cystic mass lesion located at the right adnexal area accompanied with massive ascites, but the uterus and the left ovary seemed to be normal. Computed tomography identified and confirmed the above finding (Fig. 1). Serum tumor markers, including CA 125, CA 199, and CEA were 286.0 U/mL, 209.0 U/mL, and 226.0 ng/mL, respectively. Other investigations, including hematological and biochemical tests, a chest X-ray, and upper and lower gastrointestinal (GI) tract evaluations were within normal limits. Under the diagnosis of ovarian malignancy, the patient underwent a laparotomy. During surgery, a right ovarian cystic complex mass with a mucinous component (Fig. 2) accompanied with massive ascites (7000 mL) and peritoneal carcinomatosis was found. The immediate frozen pathology report favored a diagnosis of adenocarcinoma-mucinous type. Therefore, the patient underwent an optimal debulking surgery, including total hysterectomy (Fig. 3), bilateral salpingo-oophorectomy, infracolic omentectomy and retroperitoneal lymph node sampling, and multiple biopsies. However, the final pathologic report was primary uterine endocervical adenocarcinoma. Pathologic features included hyperchromatic dysplasia of the mucinous glandular cells of the uterine endocervix; the mucinous tumor occupied the whole layer of the endocervix and extended to the lower segment of the uterine body. Other sections of the right ovary, appendix, omentum, abdominal wall, and mesentery all showed tumor metastases with floating mucinous tumor cells within an extensive mucin pool. The patient was treated with adjuvant systemic chemotherapy (8 cycles of topotecan [Hycamtin Injection, GlaxoSmithKline, San
http://dx.doi.org/10.1016/j.tjog.2014.10.005 1028-4559/Copyright © 2015, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.
202
H.-D. Sun et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 201e203
Fig. 3. Uterus specimen shows tumor invasion to the whole thickness of the uterine cervix.
Fig. 1. Computed tomography showing a 15 cm circumscribed, oval, and heterogeneously hypodense mass with a moderately enhancing solid component.
Polo di Torrile, Parma, Italy], plus cisplatin [Abiplatin Injection, Pharmachemie B.V. for TEVA Pharma B.V., Haarlem, The Netherlands]), and was still alive at 15 months after the initial operation. This case report is of educational value to clinicians, for the following reasons. Firstly, although secondary ovarian malignancies are not rare, the diagnosis is still challenging. The most likely metastatic tumors mimicking primary ovarian mucinous tumors are those of the GI, pancreatic or biliary tract, and endocervical adenocarcinomas [8,9]; our current case report fits into this grouping. The woman in the current case had no apparent symptoms and also had a negative cytological screening test (a negative Pap smear), all of which contributed to the delayed diagnosis. Secondly, it is widely accepted that a simple algorithm using tumor size and laterality (bilateral tumors of any size, or unilateral tumor <10 cm ¼ metastatic; unilateral tumor 10 cm ¼ primary)
Fig. 2. A complex cystic right ovarian mass with a mucinous component.
can accurately classify a substantial majority of tumors [8]. In addition, the concept is that gynecological organ-related diseases should always be kept in mind with women presenting with ascites and adnexa masses, regardless of size status, accompanied with massive ascites [10,11]; therefore, the tendency to diagnose primary ovarian cancer is always made, as with our current case, based on its relatively high prevalence compared with other possibilities. Yemelyanova and colleagues [12] reported that violations of these rules occurred most frequently with pancreatic, small and large bowel, and endocervical primary tumors, as these can give rise to metastatic tumors that are large, unilateral, and often cystic masses. Furthermore, a gross cystic, solid, or mixed cystic and solid appearance can be seen in borderline, primary mucinous carcinoma, and metastatic ovarian tumors and does not help to distinguish between them [8]. Thirdly, the extent of disease may be helpful in differentiating between primary and metastatic mucinous tumors [9]. Most primary mucinous ovarian carcinomas are usually early FIGO stage (I and II) at presentation [13,14]. Further information includes a smooth surface with no excrescences or surface implants [8]. Pathological features may be useful in making a distinction. Findings favoring a secondary ovarian tumor include: (1) an infiltrative invasion pattern; (2) small glands or tubules and single cells; (3) lymphovascular space invasion; (4) a nodular growth pattern of infiltrating tumor with intervening ovarian tissue containing normal ovarian structures, often with stromal desmoplasia; (5) hilar involvement; (6) microscopic surface invasion; and (7) the presence of signet ring cells [8]. By contrast, features favoring a primary ovarian tumor include: (1) an expansible invasion pattern with a back-to-back neoplastic gland without intervening stroma; (2) complex papillary patterns: (3) mural nodules with solid areas of a cyst wall containing an anaplastic carcinoma or sarcoma component; (4) background endometriosis; and (5) association with primary ovarian sex -cord or germ cell tumor [8]. Even with the assistance of pathologic evaluation, and especially during frozen pathology, many cases are still considered to be primary ovarian cancers. Recent evidence supports the possible role of informative immunohistochemistry in distinguishing primary from secondary mucinous ovarian cancers [15e17]. McCluggage [17] extensively reviewed the topic of the use of immunohistochemistry to distinguish between primary and metastatic ovarian mucinous neoplasms. Immunohistochemical analysis of primary ovarian
H.-D. Sun et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 201e203
203
Table 1 Frequently used immunohistocytologic markers of primary and secondary ovarian mucinous carcinomas. Tumors
Primary
Secondary
Markers
Intestinal
Mullerian
Colorectal
Pancreatic
Biliary
Gastric
Cervical
CK7 CK20 CDX2 CA 125 CA 19-9 CEA p16 ER DPC4 PAX8
þ/þþ þ/þþ þ Neg þþ þ/þþ Neg Neg þþ þþ
þþ Neg Neg þþ Neg/þ Neg Neg þþ þþ þþ
Neg þþ þþ Neg þþ þþ Neg/þ Neg þþ Neg
þ/þþ Neg/þ þ þ/þþ þþ þ/þþ Neg Neg þ/þþ Neg
þ/þþ Neg/þ þ þ/þþ þþ þ/þþ Neg Neg þ/þþ Neg
þ/þþ Neg/þ þ Neg þþ þ/þþ Neg Neg þþ Neg
þþ Neg/þ Neg/þ þþ Neg þ/þþ þþ Neg/þ þþ Neg/þ
þ ¼ focal positive; þþ ¼ diffuse positive; CK ¼ cytokeratin; CDX2 ¼ nuclear transcription factor CDX2; CA ¼ carbohydrate antigen; CEA ¼ carcinoembryonic antigen; DPC4 ¼ nuclear transcription factor DPC4; Neg ¼ negative; PAX8 ¼ paired box transcription factor 8.
mucinous neoplasms demonstrates CK7 reactivity, but metastatic ovarian tumor from the lower GI tract is often positive to CK20. In addition, since human papilloma virus (HPV) is absent or only rarely detected in primary ovarian neoplasia (more than 90% of cervical adenocarcinomas of “usual” histological type are HPV positive), if the diagnosis is challenged, a HPV test could be tried in our current case. Finally, we list the frequently used markers in Table 1, and these markers could provide additional information to help diagnosis. We may attempt to use tumor markers to distinguish primary from secondary, but the value is limited, since CA 125, CA 19-9, and CEA levels might be elevated in both conditions. A recent publication from Japan proposed new predictive algorithms for diagnosing primary and metastatic mucinous carcinomas of the ovary, including a combination of tumor size, patient age, serum CA19-9 and serum CA 125, which provided more accurate pre- and intraoperative diagnoses [18]; however, this approach also failed to help in our reported case. Radiological examinations, such as ultrasound and computed tomography, added little information about this patient, because she presented with an ovarian cystic mass lesion accompanied with massive ascites. Finally, our current patient could be considered as an accidental diagnosis of far-advanced cervical cancer (FIGO Stage IV). Although surgery might not be the treatment of choice, the patient was treated with immediate postoperative adjuvant systemic chemotherapy of eight cycles of topotecan plus cisplatin with a 15-month disease-free survival, suggesting that this strategy in the management of patients in a similar situation could be considered. However, a recent report from the University of Texas Southwestern Medical Center suggested that surgical evaluation of adnexal masses in patients with cervical cancer can be considered to optimize treatment outcomes, since the authors found that 23% of surgically managed patients and 57% of conservatively managed patients had disease recurrence (p ¼ 0.05), but the authors also suggested that patients with cystic masses less than 8 cm and complex masses less than 5 cm in size can be expectantly managed [19]. Our patient had a 15 cm adnexa mass, suggesting that this accidental removal of metastatic ovarian tumor secondary to endocervical adenocarcinoma was an acceptable choice, according to the above-mentioned report [19]. In conclusion, endocervical adenocarcinoma metastatic to the ovary mimicking a primary ovarian tumor is still a challenge. Based on this report, effort should be made to minimize the risk of a delayed diagnosis of primary endocervical adenocarcinoma. Conflicts of interest The authors have no conflicts of interest relevant to this article.
References [1] McCluggage WG, Wilkinson N. Metastatic neoplasms involving the ovary: a review with an emphasis on morphological and immunohistochemical features. Histopathology 2005;47:231e47. [2] Khor TS, Brennan BA, Leung YC, Sengupta S, Stewart CJ. Cervical adenocarcinoma metastatic to the ovary mimicking primary ovarian carcinoma. Pathology 2009;41:397e400. [3] Sun L, Wang PH, Lee CH, Fu TF, Chou MM, Ke YM, et al. Clinical parameters associated with absence of endocervical/transformation zone component in conventional cervical Pap smear. Taiwan J Obstet Gynecol 2015 [in press]. [4] Wang PH, Chang YH, Yang YH, Chang WH, Huang SY, Lai CR, et al. Outcome of patients with bulky IB ( 6 cm) cervical squamous cell carcinoma with and without cisplatin-based neoadjuvant chemotherapy. Taiwan J Obstet Gynecol 2014;53:330e6. [5] Elishaev E, Gilks CB, Miller D, Srodon M, Kurman RJ, Ronnett BM. Synchronous and metachronous endocervical and ovarian neoplasms: evidence supporting interpretation of the ovarian neoplasms as metastatic endocervical adenocarcinoma simulating primary ovarian surface epithelial neoplasms. Am J Surg Pathol 2005;29:281e94. [6] Huang BS, Sun HD, Hsu YM, Chang WH, Horng HC, Yen MS, et al. Clinical presentation and outcome of adult-type granulosa cell tumors: A retrospective study of 30 patients in a single institute. J Chin Med Assoc 2014;77:21e5. [7] Wiebe E, Denny L, Thomas G. Cancer of the cervix uteri. Int J Gynaecol Obstet 2012;119(Suppl. 2):S100e9. [8] Leen SL, Singh N. Pathology of primary and metastatic mucinous ovarian neoplasms. J Clin Pathol 2012;65:591e5. [9] Sun HD, Tsai CC, Hsiao SM, Wei MC, Wang KC, Wang PH. Primary gallbladder carcinoma presenting as advanced-stage ovarian cancer. Taiwan J Obstet Gynecol 2012;51:443e5. [10] Horng HC, Teng SW, Lai CR, Chang WH, Chang YH, Yen MS, et al. Prognostic factors of primary fallopian tube cancer in a single institute in Taiwan. Int J Gynecol Obstet 2014;127:77e81. [11] Lai CR, Yen MS, Wang PH. Neoplasm in the trocar site and peritoneal papillary serous cystadenocarcinoma. Taiwan J Obstet Gynecol 2014;53:139e40. [12] Yemelyanova AV, Vang R, Judson K, Wu LS, Ronnett BM. Distinction of primary and metastatic mucinous tumors involving the ovary: analysis of size and laterality data by primary site with reevaluation of an algorithm for tumor classification. Am J Surg Pathol 2008;32:128e38. [13] Wang PH, Yuan CC, Juang CM, Lai CR, Yen MS, Chao HT, et al. Primary epithelial ovarian carcinoma in Taiwanese women. Eur J Gynecol Oncol 2001;22:57e60. [14] Wang PH, Yuan CC, Shyong WY, Chiang SC, Chao JY, Yen MS, et al. Optimal debulking surgery seems to be an independent prognostic factor in patients with FIGO IIIC primary epithelial ovarian carcinoma. J Chin Med Assoc 2000;63:220e5. [15] Young RH. From Krukenberg to today: the ever present problems posed by metastatic tumors in the ovary. Part II. Adv Anat Pathol 2007;14:149e77. [16] Young RH. From Krukenberg to today: the ever present problems posed by metastatic tumors in the ovary: part I. Historical perspective, general principles, mucinous tumors including the Krukenberg tumor. Adv Anat Pathol 2006;13:205e27. [17] McCluggage WG. Immunohistochemistry in the distinction between primary and metastatic ovarian mucinous neoplasms. J Clin Pathol 2012;65: 596e600. [18] Maeda-Taniguchi M, Ueda Y, Miyake T, Miyatake T, Kimura T, Yoshino K, et al. Metastatic mucinous adenocarcinoma of the ovary is characterized by advanced patient age, small tumor size, and elevated serum CA125. Gynecol Obstet Invest 2011;72:196e202. [19] Nagel CI, Thomas SK, Richardson DL, Kehoe SM, Miller DS, Lea JS. Adnexal masses requiring surgical intervention in women with advanced cervical cancer. Gynecol Oncol 2014;134:552e5.
Contents lists available at ScienceDirect
Taiwanese Journal of Obstetrics & Gynecology journal homepage: www.tjog-online.com
Research Letter
Advanced endocervical adenocarcinoma metastatic to the ovary presenting as primary ovarian cancer Hsu-Dong Sun a, b, Sheng-Mou Hsiao a, Yi-Jen Chen b, c, Kuo-Chang Wen b, c, Yiu-Tai Li d, 1, Peng-Hui Peter Wang b, c, e, f, g, *, 1 a
Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital, New Taipei City, Taiwan Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan Division of Gynecology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan d Department of Obstetrics and Gynecology, Kuo General Hospital, Tainan, Taiwan e Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan f Department of Nursing, National Yang-Ming University School of Nursing, Taipei, Taiwan g Department of Medical Research, China Medical University Hospital, Taichung, Taiwan b c
a r t i c l e i n f o Article history: Accepted 21 October 2014
Dear Editor, Cervical squamous cell carcinoma (SCC) and adenocarcinoma may involve the ovary. Although it is not difficult to diagnose in most cases, on very rare occasions the presentation may show symptoms related to an ovarian mass, with the cervical cancer being undetected, especially endocervical adenocarcinoma [1,2]. This is important because the challenge of diagnosing primary endocervical adenocarcinoma occurs especially in women who show no symptoms, and have a grossly normal cervix and a negative Pap smear [3]. The spread of cervical malignancy (both SCC and adenocarcinoma) is often through lymphatic drainage or direct invasion [4]; except some reports show that endocervical adenocarcinoma carries a higher risk of ovarian metastases than SCC of the cervix [5]. There is an apparent difference in the treatment strategy for advanced cervical cancers and ovarian cancers [6,7]. Therefore, making an accurate diagnosis before planning therapy is of paramount importance. The following is a case report of advanced cervical adenocarcinoma metastatic to the ovary mimicking primary ovarian cancer.
* Corresponding author. Division of Gynecology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, 201, Section 2, Shih-Pai Road, Taipei, Taiwan. E-mail addresses: [email protected] (Y.-T. Li), [email protected], [email protected] (P.-H.P. Wang). 1 Drs. Li and Wang contributed equally to this article.
A 54-year-old menopausal woman (G3P3) visited the emergency room due to acute sudden onset of abdominal pain after several weeks of abdominal fullness. Her past medical history was unremarkable. She did not have any Pap smears since the birth of her last child (28 years previously). Physical examination revealed a protuberant and tense abdomen, but the cervix was essentially normal. Transvaginal ultrasound revealed a 15 cm complex cystic mass lesion located at the right adnexal area accompanied with massive ascites, but the uterus and the left ovary seemed to be normal. Computed tomography identified and confirmed the above finding (Fig. 1). Serum tumor markers, including CA 125, CA 199, and CEA were 286.0 U/mL, 209.0 U/mL, and 226.0 ng/mL, respectively. Other investigations, including hematological and biochemical tests, a chest X-ray, and upper and lower gastrointestinal (GI) tract evaluations were within normal limits. Under the diagnosis of ovarian malignancy, the patient underwent a laparotomy. During surgery, a right ovarian cystic complex mass with a mucinous component (Fig. 2) accompanied with massive ascites (7000 mL) and peritoneal carcinomatosis was found. The immediate frozen pathology report favored a diagnosis of adenocarcinoma-mucinous type. Therefore, the patient underwent an optimal debulking surgery, including total hysterectomy (Fig. 3), bilateral salpingo-oophorectomy, infracolic omentectomy and retroperitoneal lymph node sampling, and multiple biopsies. However, the final pathologic report was primary uterine endocervical adenocarcinoma. Pathologic features included hyperchromatic dysplasia of the mucinous glandular cells of the uterine endocervix; the mucinous tumor occupied the whole layer of the endocervix and extended to the lower segment of the uterine body. Other sections of the right ovary, appendix, omentum, abdominal wall, and mesentery all showed tumor metastases with floating mucinous tumor cells within an extensive mucin pool. The patient was treated with adjuvant systemic chemotherapy (8 cycles of topotecan [Hycamtin Injection, GlaxoSmithKline, San
http://dx.doi.org/10.1016/j.tjog.2014.10.005 1028-4559/Copyright © 2015, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.
202
H.-D. Sun et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 201e203
Fig. 3. Uterus specimen shows tumor invasion to the whole thickness of the uterine cervix.
Fig. 1. Computed tomography showing a 15 cm circumscribed, oval, and heterogeneously hypodense mass with a moderately enhancing solid component.
Polo di Torrile, Parma, Italy], plus cisplatin [Abiplatin Injection, Pharmachemie B.V. for TEVA Pharma B.V., Haarlem, The Netherlands]), and was still alive at 15 months after the initial operation. This case report is of educational value to clinicians, for the following reasons. Firstly, although secondary ovarian malignancies are not rare, the diagnosis is still challenging. The most likely metastatic tumors mimicking primary ovarian mucinous tumors are those of the GI, pancreatic or biliary tract, and endocervical adenocarcinomas [8,9]; our current case report fits into this grouping. The woman in the current case had no apparent symptoms and also had a negative cytological screening test (a negative Pap smear), all of which contributed to the delayed diagnosis. Secondly, it is widely accepted that a simple algorithm using tumor size and laterality (bilateral tumors of any size, or unilateral tumor <10 cm ¼ metastatic; unilateral tumor 10 cm ¼ primary)
Fig. 2. A complex cystic right ovarian mass with a mucinous component.
can accurately classify a substantial majority of tumors [8]. In addition, the concept is that gynecological organ-related diseases should always be kept in mind with women presenting with ascites and adnexa masses, regardless of size status, accompanied with massive ascites [10,11]; therefore, the tendency to diagnose primary ovarian cancer is always made, as with our current case, based on its relatively high prevalence compared with other possibilities. Yemelyanova and colleagues [12] reported that violations of these rules occurred most frequently with pancreatic, small and large bowel, and endocervical primary tumors, as these can give rise to metastatic tumors that are large, unilateral, and often cystic masses. Furthermore, a gross cystic, solid, or mixed cystic and solid appearance can be seen in borderline, primary mucinous carcinoma, and metastatic ovarian tumors and does not help to distinguish between them [8]. Thirdly, the extent of disease may be helpful in differentiating between primary and metastatic mucinous tumors [9]. Most primary mucinous ovarian carcinomas are usually early FIGO stage (I and II) at presentation [13,14]. Further information includes a smooth surface with no excrescences or surface implants [8]. Pathological features may be useful in making a distinction. Findings favoring a secondary ovarian tumor include: (1) an infiltrative invasion pattern; (2) small glands or tubules and single cells; (3) lymphovascular space invasion; (4) a nodular growth pattern of infiltrating tumor with intervening ovarian tissue containing normal ovarian structures, often with stromal desmoplasia; (5) hilar involvement; (6) microscopic surface invasion; and (7) the presence of signet ring cells [8]. By contrast, features favoring a primary ovarian tumor include: (1) an expansible invasion pattern with a back-to-back neoplastic gland without intervening stroma; (2) complex papillary patterns: (3) mural nodules with solid areas of a cyst wall containing an anaplastic carcinoma or sarcoma component; (4) background endometriosis; and (5) association with primary ovarian sex -cord or germ cell tumor [8]. Even with the assistance of pathologic evaluation, and especially during frozen pathology, many cases are still considered to be primary ovarian cancers. Recent evidence supports the possible role of informative immunohistochemistry in distinguishing primary from secondary mucinous ovarian cancers [15e17]. McCluggage [17] extensively reviewed the topic of the use of immunohistochemistry to distinguish between primary and metastatic ovarian mucinous neoplasms. Immunohistochemical analysis of primary ovarian
H.-D. Sun et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 201e203
203
Table 1 Frequently used immunohistocytologic markers of primary and secondary ovarian mucinous carcinomas. Tumors
Primary
Secondary
Markers
Intestinal
Mullerian
Colorectal
Pancreatic
Biliary
Gastric
Cervical
CK7 CK20 CDX2 CA 125 CA 19-9 CEA p16 ER DPC4 PAX8
þ/þþ þ/þþ þ Neg þþ þ/þþ Neg Neg þþ þþ
þþ Neg Neg þþ Neg/þ Neg Neg þþ þþ þþ
Neg þþ þþ Neg þþ þþ Neg/þ Neg þþ Neg
þ/þþ Neg/þ þ þ/þþ þþ þ/þþ Neg Neg þ/þþ Neg
þ/þþ Neg/þ þ þ/þþ þþ þ/þþ Neg Neg þ/þþ Neg
þ/þþ Neg/þ þ Neg þþ þ/þþ Neg Neg þþ Neg
þþ Neg/þ Neg/þ þþ Neg þ/þþ þþ Neg/þ þþ Neg/þ
þ ¼ focal positive; þþ ¼ diffuse positive; CK ¼ cytokeratin; CDX2 ¼ nuclear transcription factor CDX2; CA ¼ carbohydrate antigen; CEA ¼ carcinoembryonic antigen; DPC4 ¼ nuclear transcription factor DPC4; Neg ¼ negative; PAX8 ¼ paired box transcription factor 8.
mucinous neoplasms demonstrates CK7 reactivity, but metastatic ovarian tumor from the lower GI tract is often positive to CK20. In addition, since human papilloma virus (HPV) is absent or only rarely detected in primary ovarian neoplasia (more than 90% of cervical adenocarcinomas of “usual” histological type are HPV positive), if the diagnosis is challenged, a HPV test could be tried in our current case. Finally, we list the frequently used markers in Table 1, and these markers could provide additional information to help diagnosis. We may attempt to use tumor markers to distinguish primary from secondary, but the value is limited, since CA 125, CA 19-9, and CEA levels might be elevated in both conditions. A recent publication from Japan proposed new predictive algorithms for diagnosing primary and metastatic mucinous carcinomas of the ovary, including a combination of tumor size, patient age, serum CA19-9 and serum CA 125, which provided more accurate pre- and intraoperative diagnoses [18]; however, this approach also failed to help in our reported case. Radiological examinations, such as ultrasound and computed tomography, added little information about this patient, because she presented with an ovarian cystic mass lesion accompanied with massive ascites. Finally, our current patient could be considered as an accidental diagnosis of far-advanced cervical cancer (FIGO Stage IV). Although surgery might not be the treatment of choice, the patient was treated with immediate postoperative adjuvant systemic chemotherapy of eight cycles of topotecan plus cisplatin with a 15-month disease-free survival, suggesting that this strategy in the management of patients in a similar situation could be considered. However, a recent report from the University of Texas Southwestern Medical Center suggested that surgical evaluation of adnexal masses in patients with cervical cancer can be considered to optimize treatment outcomes, since the authors found that 23% of surgically managed patients and 57% of conservatively managed patients had disease recurrence (p ¼ 0.05), but the authors also suggested that patients with cystic masses less than 8 cm and complex masses less than 5 cm in size can be expectantly managed [19]. Our patient had a 15 cm adnexa mass, suggesting that this accidental removal of metastatic ovarian tumor secondary to endocervical adenocarcinoma was an acceptable choice, according to the above-mentioned report [19]. In conclusion, endocervical adenocarcinoma metastatic to the ovary mimicking a primary ovarian tumor is still a challenge. Based on this report, effort should be made to minimize the risk of a delayed diagnosis of primary endocervical adenocarcinoma. Conflicts of interest The authors have no conflicts of interest relevant to this article.
References [1] McCluggage WG, Wilkinson N. Metastatic neoplasms involving the ovary: a review with an emphasis on morphological and immunohistochemical features. Histopathology 2005;47:231e47. [2] Khor TS, Brennan BA, Leung YC, Sengupta S, Stewart CJ. Cervical adenocarcinoma metastatic to the ovary mimicking primary ovarian carcinoma. Pathology 2009;41:397e400. [3] Sun L, Wang PH, Lee CH, Fu TF, Chou MM, Ke YM, et al. Clinical parameters associated with absence of endocervical/transformation zone component in conventional cervical Pap smear. Taiwan J Obstet Gynecol 2015 [in press]. [4] Wang PH, Chang YH, Yang YH, Chang WH, Huang SY, Lai CR, et al. Outcome of patients with bulky IB ( 6 cm) cervical squamous cell carcinoma with and without cisplatin-based neoadjuvant chemotherapy. Taiwan J Obstet Gynecol 2014;53:330e6. [5] Elishaev E, Gilks CB, Miller D, Srodon M, Kurman RJ, Ronnett BM. Synchronous and metachronous endocervical and ovarian neoplasms: evidence supporting interpretation of the ovarian neoplasms as metastatic endocervical adenocarcinoma simulating primary ovarian surface epithelial neoplasms. Am J Surg Pathol 2005;29:281e94. [6] Huang BS, Sun HD, Hsu YM, Chang WH, Horng HC, Yen MS, et al. Clinical presentation and outcome of adult-type granulosa cell tumors: A retrospective study of 30 patients in a single institute. J Chin Med Assoc 2014;77:21e5. [7] Wiebe E, Denny L, Thomas G. Cancer of the cervix uteri. Int J Gynaecol Obstet 2012;119(Suppl. 2):S100e9. [8] Leen SL, Singh N. Pathology of primary and metastatic mucinous ovarian neoplasms. J Clin Pathol 2012;65:591e5. [9] Sun HD, Tsai CC, Hsiao SM, Wei MC, Wang KC, Wang PH. Primary gallbladder carcinoma presenting as advanced-stage ovarian cancer. Taiwan J Obstet Gynecol 2012;51:443e5. [10] Horng HC, Teng SW, Lai CR, Chang WH, Chang YH, Yen MS, et al. Prognostic factors of primary fallopian tube cancer in a single institute in Taiwan. Int J Gynecol Obstet 2014;127:77e81. [11] Lai CR, Yen MS, Wang PH. Neoplasm in the trocar site and peritoneal papillary serous cystadenocarcinoma. Taiwan J Obstet Gynecol 2014;53:139e40. [12] Yemelyanova AV, Vang R, Judson K, Wu LS, Ronnett BM. Distinction of primary and metastatic mucinous tumors involving the ovary: analysis of size and laterality data by primary site with reevaluation of an algorithm for tumor classification. Am J Surg Pathol 2008;32:128e38. [13] Wang PH, Yuan CC, Juang CM, Lai CR, Yen MS, Chao HT, et al. Primary epithelial ovarian carcinoma in Taiwanese women. Eur J Gynecol Oncol 2001;22:57e60. [14] Wang PH, Yuan CC, Shyong WY, Chiang SC, Chao JY, Yen MS, et al. Optimal debulking surgery seems to be an independent prognostic factor in patients with FIGO IIIC primary epithelial ovarian carcinoma. J Chin Med Assoc 2000;63:220e5. [15] Young RH. From Krukenberg to today: the ever present problems posed by metastatic tumors in the ovary. Part II. Adv Anat Pathol 2007;14:149e77. [16] Young RH. From Krukenberg to today: the ever present problems posed by metastatic tumors in the ovary: part I. Historical perspective, general principles, mucinous tumors including the Krukenberg tumor. Adv Anat Pathol 2006;13:205e27. [17] McCluggage WG. Immunohistochemistry in the distinction between primary and metastatic ovarian mucinous neoplasms. J Clin Pathol 2012;65: 596e600. [18] Maeda-Taniguchi M, Ueda Y, Miyake T, Miyatake T, Kimura T, Yoshino K, et al. Metastatic mucinous adenocarcinoma of the ovary is characterized by advanced patient age, small tumor size, and elevated serum CA125. Gynecol Obstet Invest 2011;72:196e202. [19] Nagel CI, Thomas SK, Richardson DL, Kehoe SM, Miller DS, Lea JS. Adnexal masses requiring surgical intervention in women with advanced cervical cancer. Gynecol Oncol 2014;134:552e5.