MDA is a rare form of cervical adenocarcinoma with an incidence of 1–3%, accounting for only 0.15–0.45% of all cervical cancer [4]. The clinical manifestations of MDA were not typical. Li et al. [5] reported a meta-analysis of 347 cases of patients with MDA, 69.4% of patients appeared to have profuse mucoid or watery vaginal discharge, 50.0% of patients had contact or abnormal vaginal bleeding, pelvic pain, or urination obstacle existed in 24.5% of the MDA patients. In our case, her predominant clinical symptoms were pelvic pain and a 6-year history of cervical contact bleeding, gynecological inspection revealed cervical abnormalities, we highly suspect that this was a case of cervical cancer. These symptoms and signs guided us for further examination to confirm the diagnosis.
The preoperative methods for the screening and diagnosis of MDA were liquid-based cytology test, cervical biopsy, imaging technology, and immunohistochemical staining of biopsy tissue. MDA was extremely well-differentiated and lack of malignant cytological characteristics, this tumor could easily be diagnosed with the benign disease in biopsy [6]. In our case, no malignant was identified in multiple cytological tests and 6 cervical biopsies, the positive rate of cytology and biopsy were very low. Hence, accurate diagnosis of MDA previous to treatment was a very intractable problem. The optimally reliable criterium for assessing the malignant nature of MDA is the haphazard array of the glands, beyond the normal range of the endometrial glands (depth > 7 mm), and occasional the glandular epithelium shows mitotic figures [7]. Due to the infiltration depth of the gland is an essential histological feature of MDA, it was difficult to diagnose by biopsy specimens. The majority of cases were diagnosed by conization or hysterectomy. Itoh K et al [8]. believed that the depth of cervical biopsy greater than 5mm or cervical conization was more conducive to the explicit diagnosis of MDA.
It was difficult to diagnose MDA with cross-sectional imaging techniques due to this neoplasm resemble a benign histological appearance. Itoh et al. [8] reported MRI could inspect MDA more effectively compared with CT and transvaginal sonography. By magnetic resonance imaging (MRI), MDA manifested as multiple cavities lesions with solid components extending from the cervical glands to the depth of the cervix. The imaging features of MRI were with intermediate or long signal intensity on T1weighted images and high signal intensity on T2weighted images. T2-weighted MRI images showed more detailed features and reliable correlation with the histological findings [9–12]. In this case, The Irregular lumps displayed long intensity on T1weighted images and high intensity on T2weighted images and have penetrated the surrounding tissues when our patient was referred to our hospital. The detailed features of MRI provided a solid foundation for clinical diagnosis.
Immunostaining of tumor markers and pathology could distinguish benign proliferating diseases of the glands from MDA. Alcian blue pH 2.5/ periodic acid-Schiff staining (AB / PAS), Ki67, carcinoembryonic antigen (CEA), HIK1083 [13, 14], and smooth muscle actin (SMA) [15] helped to confirm the diagnosis of MDA. Isamu Hayashi et al. [16] reported MDA cells produced neutral mucoproteins, the cytoplasm was stained diffusely red by AB-PAS; in contrast, all unremarkable cervical glands and glandular hyperplasias created both acid and neutral mucins, the cytoplasm was stained blue or purple by AB-PAS. HIK1083 is a monoclonal antibody directed bonding gastric mucin, Li et al. [5] reported that Immunostaining for all specimens of MDA was positive for HIK1083 and therefore were positive for gastric mucin, and also showed positive staining of vimentin and proliferating cell nuclei Antigen (PCNA) with 100% sensitivity. Bei lin suggested that the positive rates for p53 and Ki67 in > 50% of the cell nuclei (Ki67/50+) were 88% and 64% in MDA respectively and CA 125 was 18% in MDA [17].
HPV infection is not considered to be associated with MDA because high-risk HPV (types 16 and 18) have found positive in more than 80% of cervical mucinous adenocarcinomas (MACs), but negative in all lobular endocervical glandular hyperplasias (LEGHs) and MDAs examined [18, 19].
Radical hysterectomy with pelvic lymphadenectomy should be performed in the early stage of MDA unless there were contraindications to surgery, otherwise, radiotherapy or chemotherapy should be given. All patients with advanced disease ought to be treated with synchronized radiotherapy or chemotherapy. Surgery alone was usually insufficient in patients with MDA lesions because of the low diagnosis rate of this neoplasm at an early stage.
The prognosis of MDA was controversial. Silverberg SG and colleagues believed that the survival rates of MDA were similar to invasive adenocarcinoma at the same clinical stages [2]. 26 cases of MDA reviewed by Gilks CB et al. proposed a poor prognosis of MDA [20]. They also considered that early diagnosis and treatment could improve the relatively good prognosis of MDA. Kuragaki et al. [21] confirmed that our patients who had minimal deviation adenocarcinoma with mutations in a serine-threonine kinase gene (STK11) had a poorer prognosis than those without mutations. Mucinous ovarian tumors or ovarian sex cord-stromal tumors often co-exist with MDA, Heinritz W et al. [6] also emphasized that ovarian tumors and Peutz-Jeghers syndrome had a certain impact on the progress of MDA. They also suggested that the expression level of p53 might be an indicator of the local progression of MDA. Li et al. [5] reported that the mean survival of MDA patients with stage I, stage II, stage III, stage IV were 5 years, 38.1 months, 22.8 months, and 5.4 months, separately.
In conclusion, MDA was a rarity in cervical adenocarcinoma. Early clinical manifestations of MDA were lack of specificity and frequently regarded as cervicitis, the effect of treatment was usually poor. The cytological characteristics of MDA were similar to the normal cervical endometrial glands. It was difficult to distinguish between MDA and benign endometrial lesions. Therefore, early diagnosis difficulties often lead to delayed diagnosis. The prognosis of advanced MDA was usually poor [7, 20]. The most reliable criteria for assessing the malignant nature of minimal deviation adenocarcinoma was the haphazard arrangement of the glandular clumps, beyond the normal range of the endometrial glands (depth > 7 mm), and the occasional mitotic figures of the glandular epithelium [7]. MDA cytological examination and biopsy positive rate were very low, while the gynecological examination was still a very significant means of inspection which could able to detect cervical abnormalities. The use of a disposable biopsy gun (Bard-Magnum Biopsy Instrument, USA) could puncture the deep cervical lesions and increase the depth of biopsy which was contributed to the diagnosis of MDA. Great attention must be paid to combining the clinical basic skills with modern imaging techniques, the use of appropriate diagnostic tools, along with multidisciplinary cooperation and exchange could confirm the diagnosis as early as possible and were the key to improve the prognosis and the survival rate of the patient.