Proposal for individual treatment by tubal occlusion factor based on the results of salpingoscopic salpingoplasty.

AIM: As a treatment for tubal infertility, falloposcopic tuboplasty (FT) is one of the options for patients who wish to conceive naturally. Based on the results of FT, we propose an appropriate time of transitioning to assisted reproductive technology (ART) for tubal infertility. OBJECTS AND METHODS: We examined the outcomes of cases of tubal infertility during the period from June 1999 through March 2021 who were performed tuboplasty at our hospital using the FT catheter system under laparoscopy. RESULTS: The number of treated cases was 828. There were 243 cases of endometriosis and 119 cases of genital chlamydial infection. By FT, 712 cases (86.0%) were successfully recanalized. Of the 712 cases, 189 conceived naturally (26.5%) and miscarriages were 23 cases (12.2%), ectopic pregnancies were 8 cases (4.2%). The mean duration from FT to pregnancy was 6.5 months in natural pregnancy group, 90% of them were pregnant within 14 months. In endometriosis cases, the pregnancy rate after FT did not change significantly among clinical stage. CONCLUSIONS: Even when the fallopian tube was recanalized by FT, if the couple is unable to conceive naturally, they had better to consider switching to ART at about 14 months. When the couples with endometriosis consider switching to ART, we suggest deciding without considering the rASRM stage.

Ulipristal acetate simultaneously provokes antiproliferative and proinflammatory responses in endometrial cancer cells.

Ulipristal acetate (UPA), a selective progesterone receptor modulator, is used for the treatment of uterine fibroids and selectively inhibits the proliferation and inflammation of leiomyoma cells. As few studies have focused on the molecular biological mechanism of UPA in Ishikawa endometrial cancer cells, we aimed to identify the effects of UPA on these cells. Ishikawa cells were treated with different concentrations of UPA. Cell viability and colony formation assays were performed to assess the growth of cancer cells, whereas invasion and migration assays were used to measure cell motility and invasiveness. Western blotting, caspase 3/7 assay, TUNEL assay, and flow cytometry were performed to analyze apoptosis. Moreover, expression levels of the proinflammatory cytokines oncostatin M, its receptor, interleukin 6, and interleukin 8 were examined using quantitative real-time PCR. UPA decreased cell viability and growth, thereby inhibiting cell migration and invasion via induction of apoptosis. Contrary to expectation, stand-alone application of UPA increased the expression of the proinflammatory cytokines but concomitant use of UPA and the estrogen receptor antagonist ICI 182,720 decreased it. These data revealed a novel dual role of UPA: It could attenuate cell growth via activation of apoptosis while simultaneously provoking the activation of proinflammatory cytokines in endometrial cancer cells. These indicate that the combination of UPA and an estrogen receptor antagonist may be useful in suppressing the secretion of proinflammatory cytokines by UPA alone.

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-like Cells using the Three-dimensional Co-culture System, NICO-1.

Cancer stem cells (CSCs) reside in a supportive niche, constituting a microenvironment comprised of adjacent stromal cells, vessels, and extracellular matrix. The ability of CSCs to participate in the development of endothelium constitutes an important characteristic that directly contributes to the general understanding of the mechanisms of tumorigenesis and tumor metastasis. The purpose of this work is to establish a reproducible methodology to investigate the tumor-initiation capability of ovarian cancer stem cells (OCSCs). Herein, we examined the neovascularization mechanism between endothelial cells and OCSCs along with the morphological changes of endothelial cells using the in vitro co-culture model NICO-1. This protocol allows visualization of the neovascularization step surrounding the OCSCs in a time course manner. The technique can provide insight regarding the angiogenetic properties of OCSCs in tumor metastasis.

Effect of murine double-minute 2 inhibitors in preclinical models of advanced clear cell carcinomas originating from ovaries and kidneys.

Advanced clear cell carcinomas originating from both ovaries and kidneys with cancerous peritonitis have poor prognoses. Murine double-minute 2 (MDM2) is a potential therapeutic target for clear cell ovarian carcinomas with WT TP53. Herein, we characterized the antiangiogenic and antitumor effects of the MDM2 inhibitors DS-3032b and DS-5272 in 6 clear cell ovarian carcinoma cell lines and 2 clear cell renal carcinoma cell lines, as well as in clear cell ovarian carcinomas s.c. xenograft and ID8 (murine ovarian cancer cells with WT TP53) cancer peritonitis mouse models. In clear cell ovarian carcinoma s.c. xenograft mouse models, DS-3032b significantly reduced WT TP53 clear cell ovarian carcinoma- and clear cell renal carcinoma-derived tumor volumes. In ID8 mouse models, DS-5272 significantly inhibited ascites production, reduced body weight, and significantly improved overall survival. Additionally, DS-5272 reduced the tumor burden of peritoneal dissemination and decreased CD31+ cells in a dose-dependent manner. Furthermore, DS-5272 significantly decreased vascular endothelial growth factor concentrations in both sera and ascites. Combined therapy with MDM2 inhibitors and everolimus showed synergistic, and dose-reduction potential, for clear cell carcinoma treatment. Our findings suggest that MDM2 inhibitors represent promising molecular targeted therapy for clear cell carcinomas, thereby warranting further studies to evaluate the efficacy and safety of dual MDM2/mTOR inhibitors in clear cell carcinoma patients.

Liver disease in pregnancy.

Development of liver diseases during pregnancy is not uncommon. They are caused by either a disorder that is unique to pregnancy or an acute or chronic liver disease that already exists or coincidentally develops as a comorbidity of pregnancy. Liver diseases unique to pregnancy include hyperemesis gravidarum; hypertensive disorders of pregnancy, such as pre-eclampsia/eclampsia; hemolysis, elevated liver enzymes, and low platelet count syndrome; intrahepatic cholestasis of pregnancy; and acute fatty liver of pregnancy. Chronic liver diseases that affect pregnancy, or are affected by pregnancy, mainly include autoimmune liver diseases and non-alcoholic fatty liver disease. Prompt diagnosis and management of liver diseases in pregnancy, while very challenging, is extremely important, as they might cause adverse maternal and fetal outcomes. Therefore, a multidisciplinary, collaborative approach involving both hepatologists and obstetricians is required. In this review article, the up-to-date epidemiology, etiology, clinical features, and outcomes of liver diseases in pregnancy are discussed, to promote a deeper understanding among physicians, and subsequently improved outcomes.

Ovarian hyperstimulation closely associated with resumption of follicular growth after chemotherapy during tamoxifen treatment in premenopausal women with breast cancer: a multicenter retrospective cohort study.

BACKGROUND: We previously reported that tamoxifen (TAM)-induced ovarian hyperstimulation (OHS) is associated with high serum concentrations of estradiol in premenopausal women with breast cancer. To investigate risk factors for TAM-induced OHS, we performed a retrospective multicenter study. METHODS: Premenopausal patients who received surgical therapy for endocrine-dependent breast cancer (n = 235) were recruited in this study and classified into 4 groups: group A, treated with TAM alone; group B, TAM treatment after 2-year-combined therapy with a gonadotropin-releasing hormone (Gn-RH) agonist; group C, TAM treatment after chemotherapy; group D, 5-year-combined therapy with TAM and a Gn-RH agonist. A serum estradiol value of more than 300 pg/mL or mean follicular diameter of more than 30 mm was defined as OHS. RESULTS: The incidence of OHS in group A (n = 13/26, 50.0%) was significantly higher than those in group B (n = 17/63, 27.0%), group C (n = 20/110, 18.2%), and group D (n = 0/36, 0%). The incidence of OHS was significantly correlated with aging, and the median serum concentration of estradiol in the presence of OHS was 823.0 pg/mL. The incidence of OHS (less than 47 years old) was 62.5% in group A, 48.6% in group B, and 28.2% in group C, respectively. Notably, the incidence rate of OHS following amenorrhea in group C (n = 13/20, 65.0%) was significantly higher than that in group B (n = 1/17, 5.9%). CONCLUSIONS: These findings indicate that the onset of OHS following amenorrhea was common in the post-chemotherapeutic group, while its ratio was low in the group after Gn-RH analog treatment, suggesting that combined treatment-based management involving TAM therapy is necessary for premenopausal patients with breast cancer.

The combination of dibenzazepine and a DOT1L inhibitor enables a stable maintenance of human naïve-state pluripotency in non-hypoxic conditions.

Conventional human pluripotent stem cells (hPSCs), known for being in a primed state, are pivotal for both basic research and clinical applications since such cells produce various types of differentiated cells. Recent reports on PSCs shed light on the pluripotent hierarchy of stem cells and have promoted the exploration of new stem cell states along with their culture systems. Human naïve PSCs are expected to provide further knowledge of early developmental mechanisms and improvements for differentiation programmes in the regenerative therapy of conventionally primed PSCs. However, practical challenges exist in using naïve-state PSCs such as determining the conditions for hypoxic culture condition and showing limited stable cellular proliferation. Here, we have developed new leukemia inhibitory factor dependent PSCs by applying our previous work, the combination of dibenzazepine and a DOT1L inhibitor to achieve the stable culture of naïve-state PSCs. The potential of these cells to differentiate into all three germ layers was shown both in vitro and in vivo. Such new naïve-state PSCs formed dome-shaped colonies at a faster rate than conventional, primed-state human induced PSCs and could be maintained for an extended period in the absence of hypoxic culture conditions. We also identified relatively high expression levels of naïve cell markers. Thus, non-hypoxia treated, leukemia inhibitory factor-dependent PSCs are anticipated to have characteristics similar to those of naïve-like PSCs, and to enhance the utility value of PSCs. Such naïve PSCs may allow the molecular characterization of previously undefined naïve human PSCs, and to ultimately contribute to the use of human pluripotent stem cells in regenerative medicine and disease modelling.

Rikkunshito attenuates induction of epithelial-mesenchymal switch via activation of Sirtuin1 in ovarian cancer cells.

Rikkunshito, a traditional Japanese herbal medicine, improves appetite via activation of gastrointestinal hormone ghrelin pathway. The function of ghrelin is mediated by growth hormone secretagogue receptor (GHSR1a), and ghrelin has been known to possess diverse physiological functions including growth suppression of some cancer cells. Considering that increased ghrelin signaling by Rikkunshito could enhance sirtuin1 (SIRT1) activity in nervous system, we aimed to investigate the effect of Rikkunshito in ovarian cancer cells. Ovarian cancer cell lines were treated with Rikkunshito, and cellular viability, gene expressions and epithelial-mesenchymal transition (EMT) status were investigated. To investigate the involvement of SIRT1 by Rikkunshito in SKOV3 cancer cells, endogenous expression of SIRT1 was depleted using small interfering RNA (siRNA). Treatment with Rikkunshito elevated ghrelin, GHSR1a and SIRT1, while cellular viability was decreased. The treatment of Rikkunshito also inhibited cellular migration and invasion status in a dose-dependent manner, and these effects were translated to the enhanced EMT status, although the role of SIRT1 was not determined. Our study revealed a novel function of Rikkunshito in enhancing EMT status of ovarian cancer cells. Therefore, we would like to propose that Rikkunshito may be used as a novel adjunctive therapy in chemotherapy of ovarian cancer because platinum-based chemotherapy frequently used for the treatment of ovarian cancer inevitably impairs appetite.

Anti-Tumor Effect of Inhibition of DNA Damage Response Proteins, ATM and ATR, in Endometrial Cancer Cells.

: While the incidence of endometrial cancer continues to rise, the therapeutic options remain limited for advanced or recurrent cases, and most cases are resistant to therapy. The anti-tumor effect of many chemotherapeutic drugs and radiotherapy depends on the induction of DNA damage in cancer cells; thus, activation of DNA damage response (DDR) pathways is considered an important factor affecting resistance to therapy. When some DDR pathways are inactivated, inhibition of other DDR pathways can induce cancer-specific synthetic lethality. Therefore, DDR pathways are considered as promising candidates for molecular-targeted therapy for cancer. The crosstalking ataxia telangiectasia mutated and Rad3 related and checkpoint kinase 1 (ATR-Chk1) and ataxia telangiectasia mutated and Rad3 related and checkpoint kinase 2 (ATM-Chk2) pathways are the main pathways of DNA damage response. In this study, we investigated the anti-tumor effect of inhibitors of these pathways in vitro by assessing the effect of the combination of ATM or ATR inhibitors and conventional DNA-damaging therapy (doxorubicin (DXR), cisplatin (CDDP), and irradiation) on endometrial cancer cells. Both the inhibitors enhanced the sensitivity of cells to DXR, CDDP, and irradiation. Moreover, the combination of ATR and Chk1 inhibitors induced DNA damage in endometrial cancer cells and inhibited cell proliferation synergistically. Therefore, these molecular therapies targeting DNA damage response pathways are promising new treatment strategies for endometrial cancer.

The proteasome deubiquitinase inhibitor bAP15 downregulates TGF-ß/Smad signaling and induces apoptosis via UCHL5 inhibition in ovarian cancer.

The ubiquitin-proteasome pathway plays an important role in the regulation of cellular proteins. As an alternative to the proteasome itself, recent research has focused on methods to modulate the regulation of deubiquitinating enzymes (DUBs) upstream of the proteasome, identifying DUBs as novel therapeutic targets in breast, endometrial, and prostate cancers, along with multiple myeloma. bAP15, an inhibitor of the 19S proteasome DUBs UCHL5 and USP14, results in cell growth inhibition in several human cancers; however, the mechanism remains poorly understood in ovarian cancer. Here, we found that aberrant UCHL5 expression predicted shorter progression-free survival (PFS) in a cohort of 1435 patients with ovarian cancer described in the Gene Expression Omnibus and The Cancer Genome Atlas databases. The subgroup of patients with TP53 mutations was significantly more likely to exhibit poor PFS (p <0.001). Moreover, we found bAP15 could suppress TP53-mutant ovarian cancer cell survival by regulating TGF-ß signaling through inhibiting UCHL5 expression and dephosphorylating Smad2, consequently inducing apoptosis. bAP15 (2.5 and 5.0 mg/kg) also exerted significant anti-tumor effect on nude mice bearing subcutaneous SKOV3 xenografts. As activated TGF-ß signaling is involved in ovarian cancer progression, these findings suggest that UCHL5 inhibition offers potential opportunities for a novel targeted therapy against TGF-ß-activated ovarian cancer.

On-chip immunofluorescence analysis of single cervical cells using an electroactive microwell array with barrier for cervical screening.

Several specific tests for cervical screening have been developed recently, including p16/Ki67 dual immunostaining for diagnosing high-risk human papillomavirus positive squamous intraepithelial lesion in the cervix. However, manual screening of cells in an entire glass slide is currently a standard clinical procedure for quantification and interpretation of immunocytochemical features of the cells. Here, we developed a microfluidic device containing an electroactive microwell array with barriers (EMAB) for highly efficient single-cell trapping followed by on-chip immunofluorescence analysis with minimum loss of the sample. EMAB utilizes patterned electrodes at the bottom of cell-sized microwells to trap single cells using dielectrophoresis (DEP) and cell-holding structures behind the microwells to stabilize the position of trapped cells even without DEP. Using the device, we evaluated the performance of p16/Ki67 dual immunostaining of HeLa cells on the chip. The device shows 98% cell-trapping efficiency as well as 92% cell-holding efficiency against the fixed HeLa cells, and we successfully demonstrated high-efficiency on-chip immunofluorescence analysis with minimal loss of sample. p16/Ki67 dual immunostaining using EMAB may be useful for complementary tests for cervical screening in confirming the histopathological diagnosis.

Detection of HPV RNA molecules in stratified mucin-producing intraepithelial lesion (SMILE) with concurrent cervical intraepithelial lesion: a case report.

BACKGROUND: Stratified mucin-producing intraepithelial lesion (SMILE) is a rare precursor lesion in the uterine cervix that is considered a variant of adenocarcinoma in situ (AIS). Although human papillomavirus (HPV) is thought to be related to the development of SMILE, there is little information available on the detection of HPV integrated into the lesion. CASE PRESENTATION: A 30-year-old female underwent a routine uterine cervical cancer screening, and her Pap smear indicated the possible existence of atypical glandular cells. A cervical biopsy with endocervical curettage was performed. The histopathological analysis showed that she had SMILE and high-grade squamous intraepithelial lesion (HSIL) on her cervix. The lesion was found to be positive for HPV genotypes 52 and 68 by multiplex PCR. In situ hybridization with HPV RNA probes revealed that these HPV types were involved in the onset of HSIL and SMILE, respectively. CONCLUSIONS: Rare, high-risk HPV genotypes may contribute to the development of SMILE, and their detection can be useful for preventing the progression to carcinoma and ensuring adequate patient management.

Array comparative genomic hybridization analysis discloses chromosome copy number alterations as indicators of patient outcome in lymph node-negative breast cancer.

BACKGROUND: Patients with lymph node metastasis-negative (pN0) invasive breast cancer have favorable outcomes following initial treatment. However, false negatives which occur during routine histologic examination of lymph nodes are reported to underestimate the clinical stage of disease. To identify a high-risk group in pN0 invasive breast cancer, we examined copy number alterations (CNAs) of 800 cancer-related genes. METHODS: Using array-based comparative genomic hybridization (CGH) in 51 pN0 cases (19 relapsed and 32 non-relapsed cases), the positivities of specific gene CNAs in the relapsed and non-relapsed groups were compared. An unsupervised hierarchical cluster analysis was then performed to identify case groups that were correlated with patient outcomes. RESULTS: The cluster analysis identified three distinct clusters of cases: groups 1, 2, and 3. The major component was triple-negative cases (69%, 9 of 13) in group 1, luminal B-like (57%, 13 of 23) and HER2-overexpressing (26%, 6 of 23) subtypes in group 2, and luminal A-like subtype (60%, 9 of 15) in group 3. Among all 51 cases, those in group 1 showed significantly worse overall survival (OS) than group 2 (p = 0.014), and 5q15 loss was correlated with worse OS (p = 0.017). Among 19 relapsed cases, both OS and relapse-free survival (RFS) rates were significantly lower in group 1 than in group 2 (p = 0.0083 and 0.0018, respectively), and 5q15 loss, 12p13.31 gain, and absence of 16p13.3 gain were significantly correlated with worse OS and RFS (p = 0.019 and 0.0027, respectively). CONCLUSIONS: As the target genes in these loci, NR2F1 (5q15), TNFRSF1A (12p13.31), and ABCA3 (16p13.3) were examined. 5q15 loss, 12p13.31 gain, and absence of 16q13.3 gain were potential indicators of high-risk recurrence and aggressive clinical behavior of pN0 invasive breast cancers.

Elevated Expression of Vascular Adhesion Molecule-1, Plasminogen Activator Inhibitor-1, Cyclooxygenase-2, and Thrombomodulin in Human Umbilical Vein Endothelial Cells from Hospitalized Gestational Diabetes Mellitus Patients.

Protein expression in human umbilical vein endothelial cells (HUVECs) is a useful indicator of maternal condition and the intrauterine environment during pregnancy. Therefore, we investigated protein expression in HUVECs obtained from patients with gestational diabetes mellitus (GDM). HUVECs were prepared from the umbilical cords of GDM patients and controls who underwent planned cesarean section between 2013 and 2014 at Teikyo University Hospital (Tokyo, Japan). There were no differences in blood glucose levels between the GDM patients and controls at admission. However, pre-pregnancy body mass index (BMI) was higher in GDM patients, although the changes in gestational BMI were smaller during hospitalization. To evaluate the state of the endothelium, we examined the protein expression levels of vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, thrombomodulin (TM), endothelial nitric oxide synthase, plasminogen activator inhibitor-1 (PAI-1), cyclooxygenase-2 (COX-2), and VE-cadherin, which are altered by various factors in endothelial tissue. VCAM-1, PAI-1, and COX-2 expression was higher in HUVECs from patients with GDM than the controls. Because the pre-pregnancy BMI was higher in GDM patients, we examined the relationship between BMI and protein expression. However, the expression levels of these proteins were not correlated with pre-pregnancy BMI and were higher in HUVECs from BMI-matched GDM patients than from BMI-matched controls. Intriguingly, TM expression was also higher in HUVECs from BMI-matched GDM patients. Thus, expression of VCAM-1, PAI-1, COX-2, and TM may reflect certain factors in the intrauterine environment that are altered in hospitalized GDM patients with controlled body weight.

Descended marginal sinus of the placenta.

This is the first reported case of descent of the placental marginal sinus through the cervix to the external os. We think marginal sinus rupture does exist. The definition of placental edge should be the parenchyma in diagnosis of low-lying placentation. Clinically, however, the low-lying marginal sinus should be treated similar to low-lying placentation.

Expression of the glucagon-like peptide-1 receptor and its role in regulating autophagy in endometrial cancer.

BACKGROUND: A previous report showed that a glucagon-like peptide-1 receptor (GLP-1R) agonist (exenatide) induced apoptosis in endometrial cancer cells. However, the pathophysiological role of GLP-1R in endometrial cancer has not been fully elucidated. Here, we investigated the effects of the GLP-1R agonist liraglutide in endometrial cancer cells and examined the association between GLP-1R expression and clinicopathological characteristics in endometrial cancer patients. METHODS: Human Ishikawa endometrial cancer cells were treated with different concentrations of liraglutide. To assess the effects of liraglutide, cell viability, colony formation, flow cytometry, Western blotting, and immunofluorescence assays were performed. Autophagy induction was examined by analyzing LC3 and p62 expression and autophagosome accumulation. Moreover, using a tissue microarray, we analyzed GLP-1R expression in 154 endometrial cancer tissue samples by immunohistochemistry. RESULTS: In accordance with the previous report, liraglutide inhibited Ishikawa cell growth in a dose-dependent manner. Liraglutide significantly induced autophagy, and phosphorylated AMPK expression was elevated. Immunohistochemical analysis revealed that GLP-1R expression was associated with positive estrogen receptor and progesterone receptor status, and higher GLP-1R expression was significantly correlated with better progression-free survival. CONCLUSIONS: The use of liraglutide to target autophagy in endometrial cancer cells may be a novel potential treatment for endometrial cancer. Furthermore, higher GLP-1R expression may be associated with better prognosis in endometrial cancer patients.

Changes in uterine flexion caused by cesarean section: correlation between post-flexion and deficient cesarean section scars.

PURPOSE: To investigate changes in uterine flexion after cesarean delivery in comparison with vaginal delivery, and their relationship with the presence of deficient cesarean section scars. METHODS: In 147 women who had a vaginal delivery and 101 women who had a cesarean delivery, transvaginal ultrasonographic photographs of the uterus were obtained at the first trimester of pregnancy and at 1 month postpartum, and they were reviewed to determine changes in uterine flexion. The presence of a deficient cesarean section scar was also reviewed in women with a cesarean section. RESULTS: Changes in uterine flexion were observed more frequently among the woman with a cesarean delivery than in those with a vaginal delivery. The incidence of post-flexed uterus during puerperium tended to increase depending on the number of cesarean sections the woman had undergone. In the women with a cesarean section, changes in uterine flexion were more frequently observed in the women with a deficient cesarean section scar than in those without one. CONCLUSION: Changes in uterine flexion after birth occurred more frequently in the women who had a cesarean delivery than in those who had a vaginal delivery, especially in the presence of a deficient cesarean section scar.

Loss of the cell polarity determinant human Discs-large is a novel molecular marker of nodal involvement and poor prognosis in endometrial cancer.

BACKGROUND: Recent Drosophila studies showed that Discs-large (Dlg) is critical for regulation of cell polarity and tissue architecture. We investigated the possibility that loss of the human homologue of Drosophila Dlg (DLG1) is involved in endometrial carcinogenesis. METHODS: We analysed DLG1 expression in 160 endometrial cancers by immunohistochemical staining. Its expression was confirmed by quantitative real-time PCR (RT-PCR). We investigated the roles of DLG1 in growth and invasion by knockdown experiment in endometrial cancer cell lines. RESULTS: Human DLG1 localises at cellular membrane in normal endometrial tissues. Loss of DLG1 was observed in 37 cases (23.1%). Loss of DLG1 was observed in patients with advanced stage and high-grade histology. It was also observed in patients with nodal metastasis, deep myometrial invasion, and negative oestrogen and progesterone receptors. Patients with loss of DLG1 showed poorer overall survival (P=0.0019). Immunohistochemistry data correlated with RT-PCR data. Knockdown of Dlg1 in endometrial cancer cells resulted in accelerated tumour migration and invasion in vitro. CONCLUSIONS: Tissue polarity disturbance because of loss of DLG1 was shown to confer more aggressive characteristics to endometrial cancer cells. Our study revealed that DLG1 expression is a novel molecular biomarker of nodal metastasis, high-grade histology, and poor prognosis in endometrial cancer.

Case of minimal deviation adenocarcinoma: possible clinical link to lobular endocervical glandular hyperplasia as its origin.

Minimal deviation adenocarcinoma (MDA) is defined as an extremely well differentiated variant of endocervical adenocarcinoma. Several reports have stated that MDA associates with lobular endocervical glandular hyperplasia (LEGH). It is difficult to distinguish LEGH from MDA based on clinical and histologic similarities. There is no definite evidence proving that LEGH is a precursor lesion of MDA. A 45-year-old woman was admitted to our hospital for minute investigation of her neurological disorder. The multiple-cystic lesion at the uterine cervix was identified by magnetic resonance imaging. Based on her normal histological findings and severe underlying conditions, a careful follow-up strategy was adapted. Two years later, atypical glandular cells were observed and the multiple-cystic lesion had increased. Pathological diagnosis of a conization specimen was MDA. Radical hysterectomy was carried out. Pathological examination revealed coexistence of LEGH and MDA. Her clinical course and histological findings suggested the possibility that LEGH might be a precursor lesion of MDA.