In this study, 63 married patients underwent transvaginal ultrasonography (TV US), one unmarried patient underwent transabdominal ultrasonography (TA US). Two-dimensional US showed an enlarged cervix, hypoechoic in most of CTCC and isoechoic in most of RTCC compared to adjacent normal cervical tissue, and CDUS showed abundant color flow signals in the lesions. Finally, 64 cases of cervical cancer were diagnosed through biopsy; the sensitivity and positive predictive value of ultrasound diagnosis was 95.31% (61/64) and 93.85% (61/65), respectively. The demographic characteristics (including age, sexual history, marital history) and tumor grade were not significantly different between RTCC and CTCC.
A recent study20 has shown that cervical cancer lesions are mostly hypoechoic; while isoechoic, hyperechoic and mixed echoic lesions are rare. In this study, total hypoechoic lesions accounted for 57.81% of the cases, lower than that reported in previous studies. However, in CTCC, hypoechoic lesions accounted for 74.51%, of the cases, which is consistent with previous studies; whereas in RTCC, the lesions were hypoechoic only in five cases (23.81%), with 13 cases (61.90%) showing isoechoic lesions, which is consistent with the study of Epstein.21 Furthermore, the echo of lesions was significantly different between the two groups; three of 13 cases with isoechoic lesions in RTCC were missed diagnosis by US, but CDUS showed slightly abundant color flow signals in these lesions, which showed that CDUS is helpful to diagnose RTCC. In addition, there were significant differences in the mean craniocaudal diameter, anteroposterior diameter, transverse diameter, and volume of cervical cancer between the two groups. Therefore, tumor size and the echo of lesions can be used to discover RTCC.
Uterine effusion is often caused by the accumulation of fluid secreted in the uterine cavity and the obstruction of the cervical canal by the lesion. In this study, five cases (23.81%) of RTCC had intrauterine effusion, while seven cases (16.28%) with uterine effusion were found in CTCC; however, there was no significant difference between the two groups. Therefore, uterine effusion cannot be used to differentiate RTCC from CTCC. In contrast, exophytic in CTCC and endophytic in RTCC accounted for 67.44% and 66.67%, respectively, the difference was significant between the two groups, which showed that RTCC often diffusely infiltrates the cervical stroma.12
Malignant tumors have the ability to metastasize distantly and infiltrate locally. Similarly, cervical cancer can infiltrate adjacent tissues or metastasize distantly after developing over time, and a large amount of neovascularization occurs in the involved tissues to promote tumor growth or ischemic necrosis of the tumor tissues. In this study, Color Doppler flow signals were found in all cases, as compared with normal cervical tissue in which virtually no detectable vascularization was found. Using these blood flow characteristics, we were able to use US to diagnose 27 cases of stage T1b1, seven of stage T1b2, five of stage T2a1, 13 of stage T2a2, three of stage T2b, one of stage T3a, and eight of stage T4. The consistency between preoperative US and TNM staging was 80% in CTCC and 87% in RTCC, which was higher than that shown in Byun et al. (62.5%), but the same as that demonstrated by Ghi et al. (85.71%).22,23 The deviation between these may be caused by local infection as a result of prolonged vaginal bleeding in patients with cervical cancer.
Cervical biopsy is the gold standard for the diagnosis of cervical cancer; however, ultrasonography is helpful for targeted cervical biopsy, especially for early diagnosis of RTCC. Although MRI has a high soft-tissue resolution and can be used for preoperative staging, it is contraindicated in certain circumstances: if metal parts are present in the body; in the presence of a pacemaker; or cochlear implants.17,19 With improvements in the resolution achieved by ultrasonic instruments and the accumulated experience of doctors, US can be used to observe whether the cervical line is interrupted or the cervical intima is thickened. Moreover, US is an economical and non-invasive technique that patients willingly accept, which has resulted in US becoming the preferred method for early diagnosis of cervical cancer. Specifically, TV US is a superior method for showing the detected site and the degree of infiltration in the adjacent tissues. Furthermore, TV US is superior to MRI in determining the scope of surgery, whether radiotherapy and chemotherapy are needed before surgery, as well as the size of the radiation field.18 However, ultrasonography has its limitations as it can only discover invasive cervical cancer. Pap smear is normally used for primary prevention to detect preinvasive lesions, however since recently it has been replaced by HPV test in many diagnostic procedures.15 Despite all these, the primary prevention of cancer, including HPV vaccines, were not 100% effective. In this study, 36 cases (83.72%) in CTCC had HPV infection, while 10 cases (47.62%) in RTCC had HPV infection, which showed that HPV vaccines were effective only for some RTCC cases.
CCCC is a rare type of adenocarcinoma; however, its incidence is increasing among young women, accounting for 4–9% of cervical adenocarcinoma.24 Spörri et al. believe that CCCC is related to genitourinary malformation and endometriosis of the cervix.25,26 Herbst27 discovered that the peak age of CCCC is about 20 years. However, Thomas et al. found that the median age of onset for CCCC is 53 years.28 In this study, a 23-year-old unmarried celibate woman presented with irregular but severe vaginal bleeding 3 years ago, leading to anemia. She was misdiagnosed with anovulatory dysfunctional uterine bleeding and treated wrongly for this condition in a local hospital. After being transferred to our hospital, TA US showed an enlarged and hypoechoic cervix; she was suspected to have cervical cancer and underwent cervical biopsy. Finally, according to microscopic morphological characteristics and positive immunohistochemical staining for Napsin A, HNF-1B, CK7, PAX, and P53, she was diagnosed with CCCC. She received preoperative paclitaxel combined with cisplatin chemotherapy, followed by radical laparoscopic hysterectomy + bilateral salpingoovariectomy + pelvic lymphadenectomy + paraaortic lymph node biopsy. Postoperative pathological report showed no cancer infiltration in other adjacent tissues and no metastasis in lymph nodes except left parauterine infiltration. No recurrence was found after 37 months. Therefore, pelvic US should be performed carefully when abnormal vaginal bleeding cannot be explained and treated in adolescent patients.
SCCC is a rare and highly malignant neuroendocrine neoplasm with rapid growth, a high recurrence rate, and poor prognosis, accounting for 1–3% of cervical cancer cases that occur either in celibate or sexually active women.29-31 In this study, four cases had SCCC, one of them with enlarged cervix and hypoechoic lesion was suspected by US; the other three with normal size cervix and isoechoic lesions were missed diagnosis by US, but had clinical symptoms, and they all underwent cervical biopsy. Finally, according to microscopic morphological characteristics and positive immunohistochemical staining for Syn, chromogranin A (CgA), neuron-specific enolase (NSE), Ki-67, carcinoembryonic antigen (CEA), and P16, these patients were diagnosed with SCCC and received preoperative paclitaxel combined with cisplatin chemotherapy, followed by radical laparoscopic hysterectomy + bilateral adnexectomy + pelvic lymphadenectomy. Postoperative pathological report of one case showed that the lesion infiltrated the whole wall of the cervix, and cancer could be seen on the serosal surface; metastases were also seen in the internal iliac and obturator lymph nodes, and intravascular cancer thrombus was found. In 6 months, multiple metastases to the liver and other organs occurred. The patient died 8 months after the surgery. Therefore, patients with RTCC had a worse prognosis than those with CTCC. Postoperative pathological report of one case demonstrated that the lesion infiltrated the deep fibromuscular layer of the cervical wall, and tumor thrombus could be seen in the vein. Postoperative pathological report of the other case showed no cancer infiltration in other adjacent tissues and no metastasis in lymph nodes except parauterine infiltration. At present, these patients undergo follow-up over 5 months after surgery.
Our study had some limitations. All patients were treated at our hospital; therefore, selection bias and errors in the analysis may have distorted our results. Thus, it is necessary to accumulate more cases from multiple centers and perform a multi-factor comprehensive analysis.