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Synchronous multiple malignant neoplasms of the female genital tract are rare, particularly in the uterus. We herein present the case of a patient with synchronous cervical squamous epithelial carcinoma and endometrial adenocarcinoma, and discuss the diagnosis, treatment and prognosis. The patient underwent a cervical biopsy and fractional curettage of the endometrium, followed by abdominal staging surgery, including radical hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy. The diagnosis was stage Ib1 cervical cancer and stage Ia endometrial cancer, without lymph node metastases. There has been no recurrence during 1 year of followup. Synchronous genital tract neoplasms are more clinically complex compared with single neoplasms and it is crucial to focus on the differential diagnosis between primary and metastatic tumors during the diagnostic process. The treatment of synchronous genital tract neoplasms also differs significantly from that of single neoplasms, although the prognosis of patients with synchronous gynecological malignancies does not appear to be worse.
Synchronous primary genital cancer is an uncommon occurrence. In a retrospective study of 3,863 patients with female genital malignancies, 26 (0.7%) patients with synchronous primaries were identified (
A 48-year-old Chinese female patient (body mass index, 26.8 kg/m2, gravida 2, para 2), who had a history of a sterilization operation, presented in July, 2013 at the First Affiliated Hospital of Xi'an Jiaotong University (Xi'an, China) with irregular vaginal spotting for 5 months. The patient's last menstrual period was on July 7, 2013. Other past history and family history were unremarkable. After attending a regional hospital for spotted vaginal bleeding, the patient underwent a cervical biopsy during colposcopy due to a 0.3-cm cauliflower-like lesion in the anterior cervical lip, and fractional curettage of the endometrium. The pathological examination of the bioptic material in our pathology department revealed a poorly differentiated squamous cell carcinoma in the cervix (
As the cervical cancer was at clinical stage Ib1 and the endometrial cancer was at stage Ia according to the International Federation of Gynecology and Obstetrics (FIGO) classification, the patient underwent abdominal staging surgery, including radical hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy. Macroscopically, the uterus was enlarged, measuring 12×8×6 cm3, with a minor ulcer-like lesion in the anterior lip of the cervix measuring 0.5 cm in greatest diameter. The adnexa and parametrium were unremarkable. A fungating tumor, sized 5×4.5×1 cm3, was identified in the uterine cavity, with superficial invasion of the myometrium. Hematoxylin and eosin-stained sections revealed poorly differentiated endometrial adenocarcinoma with superficial myometrial invasion (<50%) in the corpus uteri. No residual carcinoma cells were found in the resection margin of the vagina, and lymph node mapping revealed no metastasis. There was chronic cervicitis with local squamous metaplasia of the cervix and Naboth's cysts, bilateral hydrosalpinx and Graafian follicles in the bilateral ovaries. The results of the immunohistochemical examination of the carcinomas of the cervix and endometrium were as follows: Creatine kinase+ (
Synchronous tumors are defined as two or more tumors occurring in a patient simultaneously. In 1879, Billroth and Hackley were the first to report the development of different primary malignant tumors in the same patient (
Unlike the single aggressive ovarian cancers that usually remain asymptomatic until they reach an advanced stage, endometrial and cervical cancers usually produce earlier symptoms, such as abnormal vaginal bleeding. Therefore, the disease was stage I at diagnosis in the present case. The diagnosis of synchronous cancers generally relies on postoperative pathological examination, as the same pathological patterns may be considered as metastatic carcinoma. In the present case, the diagnosis of synchronous cancers was made prior to surgery, as the cancers were of different pathological type. In order to improve the accuracy of diagnosis of synchronous cervical and endometrial cancers, when contact bleeding is observed, the cervix and endometrium should be more closely inspected. Fractional curettage may be performed if necessary. When the diagnosis of endometrial cancer is confirmed, a Pap smear or ThinPrep cytological test should be performed to exclude cervical cancer. Biopsy is of the same diagnostic value as curettage in patients with endometrial cancer, particularly those with cancer of the cervical canal. Stage should be thoroughly evaluated pre- and postoperatively. Staging should be performed in combination with clinicopathological diagnosis in order to determine the treatment strategy. At present, none of the available staging systems is considered to be suitable and a new system of staging and treatment determination must be established. According to the results of diagnostic dilatation and curettage and colposcopic biopsy, some of the cases may be diagnosed preoperatively and the precise extent of the resection may be determined.
Radical hysterectomy is the recommended treatment for stage Ib1 cervical cancer. During the operation, resection of the sacral and main ligaments and vaginal and pelvic lymphadenectomy are crucial. For stage Ia poorly differentiated endometrial adenocarcinoma, hysterectomy may be sufficient, provided bilateral adnexectomy, pelvic and para-aortic lymphadenectomy are performed. For our patient, these two types of operations had to be combined. Radical hysterectomy with bilateral adnexectomy, pelvic and para-aortic lymphadenectomy were performed. Adjuvant concurrent chemoradiotherapy was deemed necessary based on postoperative FIGO staging. The treatment strategies for synchronous cancers depend on the established strategy for each individual cancer and, occasionally, both tumors may be treated simultaneously.
The prognosis of patients with synchronous primary cervical and endometrial cancers is associated with disease stage at the time of diagnosis. In general, synchronous cancers are often considered worse when compared with malignancies of a metachronous nature, but are associated with significantly higher survival rates compared with metastatic cases (
This case report has been approved by the Institutional Review Board of the First Affiliated Hospital of Xi'an Jiaotong University. Written informed consent was obtained from the patient for publication of the details of this case and any accompanying images.
Squamous carcinoma of the cervix. (A) Squamous carcinoma cells were arranged in sheets or clusters (arrow) [hematoxylin and eosin staining (H&E); magnification, ×100]. (B) The cytoplasm of the tumor cells was eosinophilic. Cells with vesicular nuclei (yellow arrow) and megakaryocytes (white arrow) were observed (H&E; magnification, ×400).
Adenocarcinoma of the endometrium. (A) Adenocarcinoma cells in acinar formations (arrow) [hematoxylin and eosin staining (H&E); magnification, ×200]. (B) The cell boundaries were indistinct, with a high nucleus:cytoplasm ratio. There was significant cellular atypia (arrow) and mitotic figures (H&E; magnification, ×400).
(A) Immunohistochemical staining of cervix for P16; Immunohistochemical staining of the endometrium for (B) creatine kinase and (C) vimentin revealed cytoplasmic positivity confined to the glands (original magnification, ×400). (D) Immunohistochemical staining for human epidermal growth factor receptor-2 (2+) revealed cell membrane positivity confined to the glands.
Immunohistochemical staining of the endometrium for (A) estrogen receptor (2+, 90%), (B) progesterone receptor (3+, 80%), (C) Ki-67 (80%) and (D) P53+ (80%) revealed nuclear positivity confined to the glands (original magnification, ×400).