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Case Report Primary Vaginal Clear Cell Adenocarcinoma Accompanied by Herlyn-Werner-Wunderlich Syndrome Without Prenatal Diethylstilbestrol Exposure: a Case Report

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Case Report Primary Vaginal Clear Cell Adenocarcinoma Accompanied by Herlyn-Werner-Wunderlich Syndrome Without Prenatal Diethylstilbestrol Exposure: a Case Report Int J Clin Exp Pathol 2020;13(11):2784-2787 www.ijcep.com /ISSN:1936-2625/IJCEP0117244 Case Report Primary vaginal clear cell adenocarcinoma accompanied by Herlyn-Werner-Wunderlich syndrome without prenatal diethylstilbestrol exposure: a case report Ling Mei1,2, Juan Zou2,3, Qijun Chen2,3, Wei Jiang2,3, Yueyue Chen1,2 1Department of Gynecology, West China Second Hospital of Sichuan University, Chengdu 610041, Sichuan, China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second Hospital of Sichuan University, Chengdu 610041, Sichuan, China; 3Department of Pathology, West China Second Hospital of Sichuan University, Chengdu 610041, Sichuan, China Received June 30, 2020; Accepted August 29, 2020; Epub November 1, 2020; Published November 15, 2020 Abstract: We report a rare case of a 40 years old woman with primary vaginal clear cell adenocarcinoma (CCA) ac- companied by Herlyn-Werner-Wunderlich syndrome (HWWS) and without any prenatal diethylstilbestrol exposure. Pathological results indicated that the CCA was surrounded by adenosis and that there was a benign to malignant transformation of several glands in the epithelium, so the CCA was believed to have arisen from the adenosis. The literature review disclosed that genitourinary anomalies might be associated with an increased risk of adenocarci- noma, but the mechanism was not clear. Keywords: Clear cell adenocarcinoma (CCA), diethylstilbestrol, genitourinary malformation, Herlyn-Werner-Wun- derlich syndrome, vaginal adenosis Introduction a blind hemivagina and ipsilateral renal agene- sis, and is responsible for 7.1% of all female Primary vaginal malignant tumors account for genital tract abnormalities [7]. Primary vaginal only 1% to 3% of all malignant tumors of the CCA accompanied by HWWS is rare and fewer female reproductive tract [1]. Primary vaginal than 5 cases have been reported [1, 8]. Here- adenocarcinoma is rare, and the most common in, we reported a case of primary vaginal CCA histologic type is clear cell adenocarcinoma accompanied by HWWS, which is considered (CCA) [2]. This tumor gained recognition in the to be derived from coexisting adenosis without 1970s because of its association with intra- intrauterine DES exposure. uterine exposure to diethylstilbestrol (DES) [3, 4]. Vaginal adenosis, defined as the develop- Case report ment of columnar epithelium in the vagina, is the most common anomaly in women exposed A 40-year-old Chinese woman with gravidity 1, to DES in utero. Currently, it is widely accepted parity 1 through Caesarean section complain- that adenosis is a precursor of CCA [5]. ed of abnormal vaginal bleeding for 4 years. The manifestation was the elongation of the Congenital malformations of the female genital menstruation period from 7 days to more than tract are defined as deviations from the normal 10 days and an increase in menstrual volume. anatomic structure due to embryological mal- A vaginal left oblique septum with a hole of ap- development of the Müllerian or parameso- proximately 1 cm in diameter was discovered nephric ducts. This is a very common benign upon inspection, and there was a little clear disease with a prevalence of 4% to 7% in the liquid flowing out of the hole. The right cervix general population [6]. Herlyn-Werner-Wunder- was smooth, but the cervix behind the oblique lich syndrome (HWWS) is a rare congenital septum could not be detected. Transvaginal ul- anomaly characterized by uterus didelphys with trasound revealed two uterine bodies and cer- A primary vaginal CCA accompanied by HWWS examination of the left uterine cervix indicated NILM, and biopsy of the endometrium from both uterine cavities re- vealed endometrium in the proliferative stage. The patient had no prenatal DES exposure. Three weeks later, radical hysterectomy, bilateral salpin- go-oophorectomy, and pelvic lymphadenectomy were per- formed based on a diagnosis of stage I vaginal CCA. Microscopically, CCA was fou- nd in the upper segment of the vagina and vaginal oblique septum. As shown in Figure 2, the CCA lesion was surround- ed by adenosis, and there was a benign to malignant trans- formation of several glands in the epithelium, so the CCA was considered to have arisen from the adenosis. The tumor invol- ved the vaginal cuff and the lymphovascular space. There was no tumor involvement in the parametrium, ovaries, fal- lopian tubes, pelvic lymph no- des, or lateral surgical borders. Figure 1. Schematic of the case. There was a fistula hole in the oblique Meanwhile, there was adeno- septum, which did not cause severe menstrual blood retention but resulted myosis in the left corpus uteri in prolongation of menstruation. but not in the right corpus uteri. Because of the positive vical canals. MRI detected two separate uter- vaginal cuff and lymphovascular space inva- ine bodies and cervical canals, and there were sion, adjuvant radiotherapy and chemotherapy no abnormalities in the uterine cavities and were administered. The patient is still alive at cervixes (Figures S1, S2 and S3). The upper 17 months after the surgery. segment of the left vagina was thickened, and the signal of left fornix was abnormal. The uri- Discussion nary tract ultrasound revealed agenesis of the left kidney. The cytologic examination of the In adult women, the incidence of non-DES-in- right uterine cervix was negative for intraepi- duced vaginal adenosis was about 10% [9]. In thelial lesions or malignancies (NILMs). The ini- addition to the toxicity of DES exposure, che- tial diagnosis was HWWS and abnormal uterine motherapeutic drugs such as 5-fluorouracil bleeding. might also promote the occurrence of vaginal adenosis and cancer [10, 11]. In our case, the During the oblique vaginal septum resection, patient had not been exposed to DES or any the left uterine cervix and a 2×1 cm rough chemotherapy, so it was hypothesized that the lesion in the left fornix were revealed. Pathologic adenosis might have arisen from maldevelop- diagnosis of the oblique septum and the ment of the Müllerian duct, but this speculation left fornix lesion found clear cell adenocarcino- lacked supporting evidence. Uehara et al. [1] ma. The schematic of the abnormalities reported a case of vaginal CCA with adenosis and lesions is shown in Figure 1. Cytological accompanied by a bicornuate uterus. There- 2785 Int J Clin Exp Pathol 2020;13(11):2784-2787 A primary vaginal CCA accompanied by HWWS Figure 2. Excision of vaginal lesions. The yellow arrows indicate the vaginal squamous epithelia, the blue arrows indicate the CCA lesions, the red arrows indicate the vaginal adenosis lesions, the green arrows indicate the atypi- cal vaginal adenosis, and the dark arrow indicates the area of transformation from atypical vaginal adenosis to CCA (hematoxylin and eosin staining). fore, it is necessary to further identify similar nary abnormalities. It was found that 69.4% of cases in order to investigate whether vaginal the analyzed patients with genitourinary tract adenosis coexists with or is caused by uro- malformations had adenocarcinoma of the genital abnormalities. Our patient received a lower genital tract. This suggested that geni- final diagnosis of genital tract malformation tourinary anomalies were associated with an and vaginal CCA approximately 4 years after increased risk of adenocarcinoma, but the the onset of symptoms, which lasted until the mechanism was not clear. A study [13] indicat- oblique septum was removed. Making the ed that teratogenic factors might make the correct diagnosis seemed more difficult in Müllerian epithelium more sensitive to a carci- women with reproductive tract abnormalities nogenic substance. than in those without such malformations. In our study, the follow-up time was not long First, irregular vaginal bleeding is a common enough. Another study found that the 5-year symptom of lower genital tract tumor and geni- survival rates in women with stage I and II tal tract abnormalities and the clinical mani- non-DES-associated vaginal adenocarcinoma festations might be atypical. Additionally, for were 80% and 25% respectively. These out- patients with HWWS, the gynecological exam comes were inferior to those of patients with usually cannot discover a tumor which is locat- DES-associated vaginal CCA [14]. ed in the blocked cervix or vaginal wall. Zong et al. [12] conducted a retrospective study of Disclosure of conflict of interest 36 women diagnosed with lower genital tract primary carcinoma accompanied by genitouri- None. 2786 Int J Clin Exp Pathol 2020;13(11):2784-2787 A primary vaginal CCA accompanied by HWWS Address correspondence to: Yueyue Chen, Depart- [7] Acien P and Acien M. The presentation and ment of Gynecology, West China Second Hospital of management of complex female genital mal- Sichuan University, Chengdu 610041, Sichuan, formations. Hum Reprod Update 2016; 22: 48- China; Key Laboratory of Birth Defects and Related 69. Diseases of Women and Children of Ministry of [8] Ahsan A. Vaginal clear cell adenocarcinoma with associated Müllerian duct anomalies, re- Education, West China Second Hospital of Sichuan nal agenesis and situs inversus: report of a University, Chengdu 610041, Sichuan, China. E-mail: case with no known in-utero exposure with di- [email protected] ethyl stilboestrol. J Pak Med Assoc 2009; 59: 568-570. References [9] Pang L, Li L, Zhu L, Lang J and Bi Y. Malignant transformation of vaginal adenosis to clear cell [1] Uehara T, Onda T, Sasajima Y, Sawada M and carcinoma without prenatal diethylstilbestrol Kasamatsu T. A case of vaginal clear cell ade- exposure: a case report and literature review. nocarcinoma complicated with congenital BMC Cancer 2019; 19: 798-805. anomalies of the genitourinary tract and meta- [10] Georgiev D, Karag’ozov I, Velev M and Makave- nephric remnant without prenatal diethylstil- eva V. Three cases of vaginal adenosis after bestrol exposure. J Obstet Gynaecol Res 2010; topical 5-fluorouracil therapy for vaginal HPV- 36: 681-685. associated lesions. Akush Ginekol (Sofiia) [2] Talia KL, Scurry J, Manolitsas T and McClug- 2006; 45: 59-61.
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