Journal of Obstetrics and Gynaecology
ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: http://www.tandfonline.com/loi/ijog20
Clear cell adenocarcinoma in the uterine cervix associated with malformation of the uterus Y. Kawano, M. Nishida, K. Kai, T. Hirakawa, K. Nasu & H. Narahara To cite this article: Y. Kawano, M. Nishida, K. Kai, T. Hirakawa, K. Nasu & H. Narahara (2013) Clear cell adenocarcinoma in the uterine cervix associated with malformation of the uterus, Journal of Obstetrics and Gynaecology, 33:8, 914-915 To link to this article: http://dx.doi.org/10.3109/01443615.2013.830090
Published online: 12 Nov 2013.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijog20 Download by: [University of Birmingham]
Date: 06 November 2015, At: 03:42
914
Gynaecology Case Reports
Lee SM, Kang JH, Oh SY et al. 2005. A successfully treated case of primary tubal choriocarcinoma coexistent with viable intrauterine pregnancy. Gynecologic Oncology 97:671–673. Rotas M, Khulpateea N, Binder D. 2007. Gestational choriocarcinoma arising from a cornual ectopic pregnancy: a case report and review of the literature. Archives of Gynecology and Obstetrics 276:645–657.
accounts for only 4% of all uterine cervix adenocarcinomas. Cervical adenocarcinoma and genitourinary malformation are relatively common; however, their coexistence in patients is reportedly rare (Sporri et al. 2000). We present the case of a woman who had clear cell adenocarcinoma of the hemicervix with a rare uterine malformation.
Case report
Clear cell adenocarcinoma in the uterine cervix associated with malformation of the uterus Y. Kawano, M. Nishida, K. Kai, T. Hirakawa, K. Nasu & H. Narahara
Downloaded by [University of Birmingham] at 03:42 06 November 2015
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Yufu, Oita, Japan DOI: 10.3109/01443615.2013.830090 Correspondence: Y. Kawano, Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Yufu, Oita 8579-5593, Japan. E-mail: [email protected]
Introduction Clear cell adenocarcinomas of the uterine cervix are identified by cytological, histological and structural findings in the female genital tract, such as the vagina, endometrium and ovary. Clear cell adenocarcinoma of the uterine cervix is a rare disease, which
A 33-year-old woman, gravida 1, para 1, was admitted with the complaint of vaginal bleeding. An exophytic polypoid mass that involved the right part of the cervix was seen on vaginal examination. Rectal examination was normal, with no invasion to the uterosacral ligaments or parametrium. Pelvic magnetic resonance imaging (MRI), showed a solid tumour, about 2.5 cm in diameter. A bicornuate uterus with a double cervix was also shown (Figure 1a). No enlarged pelvic or para-aortic lymph nodes were detected. Histological diagnosis by punch biopsy was of clear cell adenocarcinoma of the uterine cervix. The patient’s mother was not aware of exposure to synthetic hormones, such as diethylstilboestrol, oestrogen or progesterone. Physical examination was otherwise normal and parameters from blood chemistry studies were within normal limits. Tumour makers such as SCC, CA125, and CA19-9 were within normal limits. The diagnosis was of clear cell adenocarcinoma of the uterine cervix IB1 (FIGO classification). Unilateral (right-side) renal agenesis was shown by intravenous urography. A modified radical hysterectomy with right salpingo-oophorectomy and bilateral pelvic lymphadenectomy was done. There was no apparent enlargement of pelvic lymph nodes at operation. Macroscopic findings were of a tumour, 3.2 ⫻ 2.5 cm in diameter, growing from the right side of the uterine cervix (Figure 1b). No malignant invasion
Figure 1. (a) Pelvic MRI showing a solid tumour, about 2.5 cm in diameter. (b) Frontal section of the resected specimen showing two separate uterocervical cavities, which were connected by an isthmic communication. Note the enlarged cervix with the exophytic tumour involving the left hemicervix. Two cervical canals are present, and the left one ends blindly. (c,d) Microscopic views of the hemicervix showing poorly-differentiated clear cell adenocarcinoma. So-called hobnail cells were prominent.
Gynaecology Case Reports 915 of the vaginal wall or the parametrium and no lymph node metastasis were found. In the histological findings, the clear cells were arranged into tubular, solid and papillary structures, and hobnail cells were also detected (Figure 1c,d). External-beam pelvic radiation (50 Gy) and six courses of chemotherapy (medication; cisplatin 75 mg/body, Adriamycin 30 mg/body, cyclophosphamide 500 mg/body) was given. Treatment was well tolerated and there has been no evidence of recurrence during more than 10 years of follow-up, after primary therapy.
Downloaded by [University of Birmingham] at 03:42 06 November 2015
Discussion This is a rare case of clear cell adenocarcinoma of the cervix that was associated with a rare congenital genito-urinary malformation, including unilateral renal agenesis. This occurrence has been reported in three other women (Nordqvist et al. 1976). Two had double uteri and vaginas with unilateral renal agenesis, and one had a bicornuate uterus. In addition, Sporri et al. (2000) also reported clear cell adenocarcinoma of the cervix in communicating uteri. It has been reported that the occurrence of vaginal clear cell adenocarcinoma in young women is linked to fetal exposure to diethylstilboestrol. However, it has also been reported that clear cell adenocarcinoma occurs in women never exposed to diethylstilboestrol (Seki et al. 2003). In the patients not exposed to diethylstilboestrol, it was indicated that clear cell adenocarcinoma was caused by a possible carcinogenic effect of alteration of the tumour suppression gene p53 and genomic integration of oncogenic human papilloma virus DNA type 31 (Waggoner et al. 1994). It is suggested that crucial prognostic features for survival in patients with clear cell adenocarcinoma are stage, histological growth pattern, grade of nuclear atypia and lymphatic invasion. In the present case, the tumour developed in the atretic hemicervix, which included glands with ciliated tubo-endometrial cells. These cells are of Müllerian origin and are believed to be the cells of origin for clear cell adenocarcinoma. Concerning the prognosis of these cases, it has been reported that clear cell adenocarcinoma has a greater tendency for delayed recurrence compared with that of squamous cell carcinomas (Jones et al. 1993). Several authors have speculated that the biological behaviour and prognosis of clear cell adenocarcinoma are poorer than those of squamous cell carcinomas and non-clear cell adenocarcinomas (Reich et al. 2000). In contrast to this speculation, in the largest study by Herbst et al. (1979), 5-year survival rates were reported as 91, 77 and 60% for stage I, IIA and IIB of clear cell adenocarcinoma, respectively. In our case, no infiltration of the uterine corpus was observed. Clear cell adenocarcinoma infiltrates the uterine corpus more often than other cervical carcinomas (Reich et al. 2000). The diagnosis of spread to the uterine corpus is important, because endometrial clear
cell adenocarcinoma with deep myometrial invasion has only a 15% 5-year survival rate (Abeler and Kjorstad 1991). In our case, cisplatin, adriamycin and cyclophosphamide were administrated as postoperative adjuvant therapy. It was reported that cisplatin or carboplatin and bleomycin were used in 15 cases of clear cell adenocarcinoma and the 5-year survival rate was 67% (Reich et al. 2000). Mitomycin, etoposide and carboplatin of intra-arterial injection as neoadjuvant chemotherapy were performed and no recurrence was detected in 3.5 years of follow-up (Seki et al. 2003). So far, standardised chemotherapy has not been established in clear cell adenocarcinoma. In order to investigate effective chemotherapy and improve the prognosis of clear cell adenocarcinoma, new drugs including molecular target therapy, should be developed from further studies. No findings suggesting recurrence were observed during 10 years of follow-up in this patient. Further clinical follow-up and biological investigation are mandatory for a better understanding of this rare disease. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Abeler VW, Kjorstad KE. 1991. Clear cell carcinoma of the endometrium: A histopathological and clinical study of 97 cases. Gynecologic Oncology 40:207–217. Herbst AL, Norusis MJ, Rosenow PJ et al. 1979. An analysis of 346 cases of clear cell adenocarcinoma of the vagina and cervix with emphasis on recurrence and survival. Gynecologic Oncology 7:111–122. Jones WB, Tan LK, Lewis JL. 1993. Late recurrence of clear cell adenocarcinoma of the vagina and cervix: a report of three cases. Gynecologic Oncology 51:266–271. Nordqvist SR, Fidler WJ, Woodruff JM et al. 1976. Clear cell adenocarcinoma of the cervix and vagina. Cancer 37:858–871. Reich O, Tamussino K, Lahousen M et al. 2000. Clear cell carcinoma of the uterine cervix: pathology and prognosis in surgically treated stage IB–IIB disease in women not exposed in utero to diethylstilbestrol. Gynecologic Oncology 76:331–335. Sporri S, Altermatt HJ, Dreher E et al. 2000. Clear cell adenocarcinoma of the cervix associated with a rare genitourinary malformation. Obstetrics and Gynecology 96:834–836. Seki H, Takada T, Sodemoto T et al. 2003. A young woman with clear cell adenocarcinoma of the uterine cervix. International Journal of Clinical Oncology 8:399–404. Waggoner SE, Anderson SM, Van Eyck S et al. 1994. Human papillomavirus detection and p53 expression in clear cell adenocarcinoma of the vagina and cervix. Obstetrics and Gynecology 84:404–408.
ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: http://www.tandfonline.com/loi/ijog20
Clear cell adenocarcinoma in the uterine cervix associated with malformation of the uterus Y. Kawano, M. Nishida, K. Kai, T. Hirakawa, K. Nasu & H. Narahara To cite this article: Y. Kawano, M. Nishida, K. Kai, T. Hirakawa, K. Nasu & H. Narahara (2013) Clear cell adenocarcinoma in the uterine cervix associated with malformation of the uterus, Journal of Obstetrics and Gynaecology, 33:8, 914-915 To link to this article: http://dx.doi.org/10.3109/01443615.2013.830090
Published online: 12 Nov 2013.
Submit your article to this journal
Article views: 36
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijog20 Download by: [University of Birmingham]
Date: 06 November 2015, At: 03:42
914
Gynaecology Case Reports
Lee SM, Kang JH, Oh SY et al. 2005. A successfully treated case of primary tubal choriocarcinoma coexistent with viable intrauterine pregnancy. Gynecologic Oncology 97:671–673. Rotas M, Khulpateea N, Binder D. 2007. Gestational choriocarcinoma arising from a cornual ectopic pregnancy: a case report and review of the literature. Archives of Gynecology and Obstetrics 276:645–657.
accounts for only 4% of all uterine cervix adenocarcinomas. Cervical adenocarcinoma and genitourinary malformation are relatively common; however, their coexistence in patients is reportedly rare (Sporri et al. 2000). We present the case of a woman who had clear cell adenocarcinoma of the hemicervix with a rare uterine malformation.
Case report
Clear cell adenocarcinoma in the uterine cervix associated with malformation of the uterus Y. Kawano, M. Nishida, K. Kai, T. Hirakawa, K. Nasu & H. Narahara
Downloaded by [University of Birmingham] at 03:42 06 November 2015
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Yufu, Oita, Japan DOI: 10.3109/01443615.2013.830090 Correspondence: Y. Kawano, Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Yufu, Oita 8579-5593, Japan. E-mail: [email protected]
Introduction Clear cell adenocarcinomas of the uterine cervix are identified by cytological, histological and structural findings in the female genital tract, such as the vagina, endometrium and ovary. Clear cell adenocarcinoma of the uterine cervix is a rare disease, which
A 33-year-old woman, gravida 1, para 1, was admitted with the complaint of vaginal bleeding. An exophytic polypoid mass that involved the right part of the cervix was seen on vaginal examination. Rectal examination was normal, with no invasion to the uterosacral ligaments or parametrium. Pelvic magnetic resonance imaging (MRI), showed a solid tumour, about 2.5 cm in diameter. A bicornuate uterus with a double cervix was also shown (Figure 1a). No enlarged pelvic or para-aortic lymph nodes were detected. Histological diagnosis by punch biopsy was of clear cell adenocarcinoma of the uterine cervix. The patient’s mother was not aware of exposure to synthetic hormones, such as diethylstilboestrol, oestrogen or progesterone. Physical examination was otherwise normal and parameters from blood chemistry studies were within normal limits. Tumour makers such as SCC, CA125, and CA19-9 were within normal limits. The diagnosis was of clear cell adenocarcinoma of the uterine cervix IB1 (FIGO classification). Unilateral (right-side) renal agenesis was shown by intravenous urography. A modified radical hysterectomy with right salpingo-oophorectomy and bilateral pelvic lymphadenectomy was done. There was no apparent enlargement of pelvic lymph nodes at operation. Macroscopic findings were of a tumour, 3.2 ⫻ 2.5 cm in diameter, growing from the right side of the uterine cervix (Figure 1b). No malignant invasion
Figure 1. (a) Pelvic MRI showing a solid tumour, about 2.5 cm in diameter. (b) Frontal section of the resected specimen showing two separate uterocervical cavities, which were connected by an isthmic communication. Note the enlarged cervix with the exophytic tumour involving the left hemicervix. Two cervical canals are present, and the left one ends blindly. (c,d) Microscopic views of the hemicervix showing poorly-differentiated clear cell adenocarcinoma. So-called hobnail cells were prominent.
Gynaecology Case Reports 915 of the vaginal wall or the parametrium and no lymph node metastasis were found. In the histological findings, the clear cells were arranged into tubular, solid and papillary structures, and hobnail cells were also detected (Figure 1c,d). External-beam pelvic radiation (50 Gy) and six courses of chemotherapy (medication; cisplatin 75 mg/body, Adriamycin 30 mg/body, cyclophosphamide 500 mg/body) was given. Treatment was well tolerated and there has been no evidence of recurrence during more than 10 years of follow-up, after primary therapy.
Downloaded by [University of Birmingham] at 03:42 06 November 2015
Discussion This is a rare case of clear cell adenocarcinoma of the cervix that was associated with a rare congenital genito-urinary malformation, including unilateral renal agenesis. This occurrence has been reported in three other women (Nordqvist et al. 1976). Two had double uteri and vaginas with unilateral renal agenesis, and one had a bicornuate uterus. In addition, Sporri et al. (2000) also reported clear cell adenocarcinoma of the cervix in communicating uteri. It has been reported that the occurrence of vaginal clear cell adenocarcinoma in young women is linked to fetal exposure to diethylstilboestrol. However, it has also been reported that clear cell adenocarcinoma occurs in women never exposed to diethylstilboestrol (Seki et al. 2003). In the patients not exposed to diethylstilboestrol, it was indicated that clear cell adenocarcinoma was caused by a possible carcinogenic effect of alteration of the tumour suppression gene p53 and genomic integration of oncogenic human papilloma virus DNA type 31 (Waggoner et al. 1994). It is suggested that crucial prognostic features for survival in patients with clear cell adenocarcinoma are stage, histological growth pattern, grade of nuclear atypia and lymphatic invasion. In the present case, the tumour developed in the atretic hemicervix, which included glands with ciliated tubo-endometrial cells. These cells are of Müllerian origin and are believed to be the cells of origin for clear cell adenocarcinoma. Concerning the prognosis of these cases, it has been reported that clear cell adenocarcinoma has a greater tendency for delayed recurrence compared with that of squamous cell carcinomas (Jones et al. 1993). Several authors have speculated that the biological behaviour and prognosis of clear cell adenocarcinoma are poorer than those of squamous cell carcinomas and non-clear cell adenocarcinomas (Reich et al. 2000). In contrast to this speculation, in the largest study by Herbst et al. (1979), 5-year survival rates were reported as 91, 77 and 60% for stage I, IIA and IIB of clear cell adenocarcinoma, respectively. In our case, no infiltration of the uterine corpus was observed. Clear cell adenocarcinoma infiltrates the uterine corpus more often than other cervical carcinomas (Reich et al. 2000). The diagnosis of spread to the uterine corpus is important, because endometrial clear
cell adenocarcinoma with deep myometrial invasion has only a 15% 5-year survival rate (Abeler and Kjorstad 1991). In our case, cisplatin, adriamycin and cyclophosphamide were administrated as postoperative adjuvant therapy. It was reported that cisplatin or carboplatin and bleomycin were used in 15 cases of clear cell adenocarcinoma and the 5-year survival rate was 67% (Reich et al. 2000). Mitomycin, etoposide and carboplatin of intra-arterial injection as neoadjuvant chemotherapy were performed and no recurrence was detected in 3.5 years of follow-up (Seki et al. 2003). So far, standardised chemotherapy has not been established in clear cell adenocarcinoma. In order to investigate effective chemotherapy and improve the prognosis of clear cell adenocarcinoma, new drugs including molecular target therapy, should be developed from further studies. No findings suggesting recurrence were observed during 10 years of follow-up in this patient. Further clinical follow-up and biological investigation are mandatory for a better understanding of this rare disease. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Abeler VW, Kjorstad KE. 1991. Clear cell carcinoma of the endometrium: A histopathological and clinical study of 97 cases. Gynecologic Oncology 40:207–217. Herbst AL, Norusis MJ, Rosenow PJ et al. 1979. An analysis of 346 cases of clear cell adenocarcinoma of the vagina and cervix with emphasis on recurrence and survival. Gynecologic Oncology 7:111–122. Jones WB, Tan LK, Lewis JL. 1993. Late recurrence of clear cell adenocarcinoma of the vagina and cervix: a report of three cases. Gynecologic Oncology 51:266–271. Nordqvist SR, Fidler WJ, Woodruff JM et al. 1976. Clear cell adenocarcinoma of the cervix and vagina. Cancer 37:858–871. Reich O, Tamussino K, Lahousen M et al. 2000. Clear cell carcinoma of the uterine cervix: pathology and prognosis in surgically treated stage IB–IIB disease in women not exposed in utero to diethylstilbestrol. Gynecologic Oncology 76:331–335. Sporri S, Altermatt HJ, Dreher E et al. 2000. Clear cell adenocarcinoma of the cervix associated with a rare genitourinary malformation. Obstetrics and Gynecology 96:834–836. Seki H, Takada T, Sodemoto T et al. 2003. A young woman with clear cell adenocarcinoma of the uterine cervix. International Journal of Clinical Oncology 8:399–404. Waggoner SE, Anderson SM, Van Eyck S et al. 1994. Human papillomavirus detection and p53 expression in clear cell adenocarcinoma of the vagina and cervix. Obstetrics and Gynecology 84:404–408.
