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(1) Background/Aim: In clinical practice, uterine lipoleiomyomas are variants of uterine leiomyomas that are often found incidentally and do not require surgical treatment unless the patient is symptomatic. Therefore, these should be clinically differentiated from lesions that need surgical treatment. Conversely, hemangiomas, or blood vessel benign tumors, rarely develop in the uterus; however, many clinical complications such as abdominal pain and excessive vaginal bleeding result from a uterine hemangioma. Hemangiomas can occur at any age and primarily affect pregnant women. (2) Materials and Methods: The oncological properties of uterine lipoleiomyoma and hemangioma in adults were investigated using molecular pathological examination on tissue excised from patients with a uterine tumor. (3) Results: Through molecular pathological studies, which included potential biomarkers for uterine mesenchymal tumors, a differential diagnosis was established for a case of mesenchymal tumor. Herein, we report a 54-year-old non-pregnant woman who presented with vaginal bleeding and underwent hysterectomy after detection of a 140 × 100 mm intramural mass diagnosed as a concurrent uterine hemangioma and lipoleiomyoma after molecular histopathologic examinations. (4) Conclusion: As far as we know, our case is the first patient of concurrent uterine hemangioma and lipoleiomyoma. Hence, the possibility of several types of mesenchymal tumors must be considered in the differential diagnosis of patients with abnormal vaginal bleeding. As such, molecular pathological examination and close monitoring of the MRI results should be conducted by medical staff while considering the patient's desire for pregnancy, including surgical treatment options for uterine hemangioma. [ABSTRACT FROM AUTHOR]

Serous carcinoma of the uterus (USC) is a pathological subtype of high-grade endometrial cancers, with no effective treatment for advanced cases. Since such refractory tumors frequently harbor antitumor immune tolerance, many immunotherapies have been investigated for various malignant tumors using immuno-competent animal models mimicking their local immunities. In this study, we established an orthotopic mouse model of high-grade endometrial cancer and evaluated the local tumor immunity to explore the efficacy of immunotherapies against USC. A multivariate analysis of 62 human USC cases revealed that the tumor-infiltrating cell status, few CD8+ cells and abundant myeloid-derived suppressor cells (MDSCs), was an independent prognostic factor (P < 0.005). A murine endometrial cancer cell (mECC) was obtained from C57BL/6 mice via endometrium-specific deletion of Pten and Tp53 , and another high-grade cell (HPmECC) was established by further overexpressing Myc in mECCs. HPmECCs exhibited higher capacities of migration and anchorage-independent proliferation than mECCs (P < 0.01, P < 0.0001), and when both types of cells were inoculated into the uterus of C57BL/6 mice, the prognosis of mice bearing HPmECC-derived tumors was significantly poorer (P < 0.001). Histopathological analysis of HPmECC orthotopic tumors showed serous carcinoma-like features with prominent tumor infiltration of MDSCs (P < 0.05), and anti-Gr-1 antibody treatment significantly prolonged the prognosis of HPmECC-derived tumor-bearing mice (P < 0.05). High CCL7 expression was observed in human USC and HPmECC, and MDSCs migration was promoted in a CCL7 concentration-dependent manner. These results indicate that antitumor immunity is suppressed in USC due to increased number of tumor-infiltrating MDSCs via CCL signal. [ABSTRACT FROM AUTHOR]

Background/Aim: Patients with uterine sarcoma comprise 2–5% of all patients with uterine malignancies; however, the morbidity of uterine sarcoma is low compared with that of other gynecological cancers. For many cases, malignant uterine tumors are diagnosed during follow-up of benign uterine leiomyoma. Of the uterine sarcomas, rhabdomyosarcoma is considered a mixed tumor containing components of epithelial cells and mesenchymal cells. Therefore, the onset of primary uterine rhabdomyosarcoma during follow-up of uterine leiomyoma is extremely rare. Rhabdomyosarcoma is a relatively common malignant tumor in children, but rhabdomyosarcoma in adults is extremely rare, accounting for approximately 3% of all patients with soft tissue sarcoma. Rhabdomyosarcoma in children is highly sensitive to chemotherapy and radiation therapy; however, the response to chemotherapy and radiation therapy in adult rhabdomyosarcoma is low and survival in adult rhabdomyosarcoma with metastatic lesions to other organs is approximately 14 months. We experienced a case of pleomorphic rhabdomyosarcoma during the follow-up of a uterine leiomyoma. Materials and Methods: We examined the oncological properties of uterine rhabdomyosarcoma in adults using molecular pathological techniques on tissue excised from patients with uterine leiomyoma. Result: A differential diagnosis was made for this case by molecular pathology, which included candidate biomarkers for uterine smooth muscle tumors. The oncological nature of uterine rhabdomyosarcoma was found to be similar to the oncological properties of uterine leiomyosarcoma. However, in uterine rhabdomyosarcoma, LMP2/β1i-positive cells were clearly observed. Conclusion: It is expected that establishing a diagnostic and treatment method targeting characteristics of mesenchymal tumor cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis. [ABSTRACT FROM AUTHOR]

Mesonephric‐like adenocarcinoma (MLA) is a rare tumor that occurs in the uterine endometrium and ovary. It morphologically and immunohistochemically resembles cervical mesonephric adenocarcinoma (MA). Here, we present a case of MLA of the ovary along with a literature review. An asymptomatic 84‐year‐old woman presented with a pelvic mass, detected by computerized tomography. Magnetic resonance imaging demonstrated a polycystic mass with a solid component in the left adnexal region. The solid component showed low signal intensity on T2‐weighted imaging and high signal intensity on diffusion‐weighted imaging. We strongly suspected an ovarian malignant tumor; therefore, surgical resection of the uterus and adnexa was performed. Macroscopically, the tumor was predominantly solid with yellowish‐tan cut surface. Microscopically, it showed a tubular pattern with intraluminal colloid‐like material resembling MA. The tumor cells were negative for estrogen receptor, calretinin, and CD10 and positive for PAX8 and TTF‐1. These findings are consistent with those of MLA. [ABSTRACT FROM AUTHOR]

Lymphoepithelioma‐like carcinoma of the uterine cervix is a rare variant of squamous cell carcinoma. Herein, we describe three cases of lymphoepithelioma‐like carcinoma of the uterine cervix and review relevant literature. All three patients initially presented with postmenopausal bleeding. Gross appearances were endophytic with ulcerated mucosa in case 1, exophytic with polypoid morphology in case 2, and unremarkable even using colposcopy and hysteroscopy in case 3. Magnetic resonance imaging demonstrated well‐demarcated cervical masses with high‐intermediate intensity on T2‐weighted images and high intensity on diffusion‐weighted images in all three cases. In case 3, biopsy referring to local information from magnetic resonance images was required for preoperative diagnosis. We reviewed the literature of 59 lymphoepithelioma‐like carcinoma cases in 19 papers published between 2001 and 2020. Preoperative diagnosis of lymphoepithelioma‐like carcinoma is sometimes challenging, although magnetic resonance imaging findings may help determine the location of the tumor and obtain a successful biopsy. [ABSTRACT FROM AUTHOR]

Diagnosis by biopsy is difficult in the ovary since it is located deep in the abdomen. As a result, ovarian cancer is mostly found insidiously during exploratory laparotomy. Consequently, the early diagnosis of ovarian cancer is often difficult. The likelihood of peritoneal dissemination increases with the progress of ovarian cancer. With further progression, ovarian cancer metastasizes to the momentum, retroperitoneal lymph nodes, large intestine, small intestine, diaphragm, spleen, and other organs. Ovarian cancer has been considered a tumor that has a favorable response to chemotherapy, but more effective treatments are still being explored. Tumors use their own immune escape mechanism to evade host immunity. The immune checkpoint (IC) mechanism, one of the immune escape mechanisms, is established by programmed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) communication. It has been shown that inhibiting PD-1/PD-L1 communication in various malignancies produces antitumor effects. However, the antitumor effect of ICI monotherapy on ovarian cancer is limited in actual clinical practice. In this review, we describe a novel cancer immunotherapeutic agent that targets myeloid-derived suppressor cells (MDSCs). [ABSTRACT FROM AUTHOR]

Background: Uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) is a predictive biomarker for the side-effects of irinotecan chemotherapy, which reduces the volume of tumors harboring UGT1A1 polymorphisms. We aimed to determine whether UGT1A1 polymorphisms can predict progression-free survival in patients with local cervical cancer treated with irinotecan chemotherapy.Methods: We retrospectively analyzed the data of 51 patients with cervical cancer treated at a single institution between 2010 and 2015. All patients were diagnosed with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IB1, IB2, IIA, or IIB squamous cell carcinoma, underwent radical hysterectomy, and received irinotecan chemotherapy as neoadjuvant and/or adjuvant treatment. All patients were examined for irinotecan side effects using UGT1A1 tests. Conditional inference tree and survival analyses were performed considering the FIGO stage, age, the UGT1A1 status, and the number of metastatic lymph nodes to determine primary factors associated with progression-free survival.Results: The tree-structured survival model determined high recurrence-risk factors related to progression-free survival. The most relevant factor was ≥2 metastatic lymph nodes (p = 0.004). The second most relevant factor was UGT1A1 genotype (p = 0.024). Among patients with ≤1 metastatic lymph node, those with UGT1A1 polymorphisms benefited from irinotecan chemotherapy and demonstrated significantly longer progression-free survival (p = 0.020) than those with wild-type UGT1A1.Conclusions: Irinotecan chemotherapy might be beneficial in patients with cervical cancer, UGT1A1 polymorphisms, and ≤ 1 metastatic lymph nodes. [ABSTRACT FROM AUTHOR]

Immunohistochemically p16 (CDKN2A)‐negative uterine cervical squamous cell carcinoma (SCC) is uncommon, and there are few reports about its pathological features. This study explored the causes of p16 negativity in such cases. We analyzed diagnostic tissue samples of five cases of p16‐negative cervical SCC among 107 patients who underwent hysterectomy at Kyoto University Hospital between January 2010 and December 2015. The samples were subjected to immunohistochemical staining, in situ hybridization and a genetic analysis. Two of five cases were positive for human papilloma virus (HPV) by genotyping. One was positive for HPV56 with promoter hypermethylation of CDKN2A and co‐existing Epstein–Barr virus infection. Another was positive for HPV6 categorized as low‐risk HPV with condylomatous morphology. Among the remaining three cases, one had amplification of the L1 gene of HPV with promoter hypermethylation of CDKN2A and TP53 mutation, and one of the other two HPV‐negative cases had a homozygous CDKN2A deletion, while the other was positive for p53 and CK7. p16‐negativity of cervical SCC is often associated with an unusual virus infection status and CDKN2A gene abnormality. [ABSTRACT FROM AUTHOR]

Uterine serous carcinoma (USC) is a highly aggressive histological subtype of endometrial cancers harboring highly metastatic and chemoresistant features. Our previous study showed that STAT1 is highly expressed in USC and acts as a key molecule that is positively correlated with tumor progression, but it remains unclear whether STAT1 is relevant to the malicious chemorefractory nature of USC. In the present study, we investigated the regulatory role of STAT1 toward platinum‐cytotoxicity in USC. STAT1 suppression sensitized USC cells to increase cisplatin‐mediated apoptosis (p < 0.001). Furthermore, phosphorylation of STAT1 was prominently observed on serine‐727 (pSTAT1‐Ser727), but not on tyrosine‐701, in the nucleus of USC cells treated with cisplatin. Mechanistically, the inhibition of pSTAT1‐Ser727 by dominant‐negative plasmid elevated cisplatin‐mediated apoptosis by increasing intracellular accumulation of cisplatin through upregulation of CTR1 expression. TBB has an inhibitory effect on casein kinase 2 (CK2), which phosphorylate STAT1 at serine residues. Sequential treatment with TBB and cisplatin on USC cells greatly reduced nuclear pSTAT1‐Ser727, enhanced intracellular accumulation of cisplatin, and subsequently increased apoptosis. Tumor load was significantly reduced by combination therapy of TBB and cisplatin in in vivo xenograft models (p < 0.001). Our results collectively suggest that pSTAT1‐Ser727 may play a key role in platinum resistance as well as tumor progression in USC. Thus, targeting the STAT1 pathway via CK2 inhibitor can be a novel method for attenuating the chemorefractory nature of USC. What's new? The molecular mechanisms underlying chemoresistance in uterine serous carcinoma (USC), a rare but highly aggressive subtype of endometrial cancer, remain unclear. This study shows that the prognostic outcome for USC patients with high STAT1 expression is poor and STAT1 is involved in platinum resistance. Mechanistically, cisplatin‐induced STAT1 Ser727 phosphorylation alters cellular platinum accumulation to promote resistance and CK2 inhibitors can suppress STAT1 Ser727 phosphorylation. The results suggest that STAT1 could serve as a biomarker to predict tumor chemoresponse, and premedication with a CK2 inhibitor may represent a potent strategy to increase the efficacy of platinum‐based chemotherapeutics in STAT1‐high USC patients. [ABSTRACT FROM AUTHOR]

Aim: To examine the hysteroscopic morphological features in each histological grade of endometrial cancer, and to distinguish high‐ and low‐grade cancer and low‐grade cancer and atypical endometrial hyperplasia (AEH), using hysteroscopy. Methods: In total, 135 patients who underwent hysterectomy after hysteroscopy were analyzed. They were divided into four categories: benign lesion; AEH; low‐grade cancer, including endometrioid carcinoma grades 1 and 2 (G1/2); and high‐grade cancer, including endometrioid carcinoma grade 3 and other high‐grade carcinomas (G3/others). Three blinded gynecologic oncologists independently evaluated hysteroscopic video images for abnormal vessels, surface smoothness, papillary structure and polypoid structure. Prevalence rates of each finding were compared between the four categories. The accuracy of blind biopsy in outpatient settings and hysteroscopic endometrial biopsy in the four categories were also investigated. Results: The number of patients with benign lesions, AEH, G1/2 and G3/others was 8, 7, 84 and 36, respectively. Patients with G3/others exhibited more polypoid (86% vs 61%, P = 0.0095) and less papillary (59% vs 80%, P = 0.023) structures than those exhibited by patients with G1/2. AEH and G1/2 were indistinguishable using hysteroscopy. Hysteroscopic biopsy was more accurate than outpatient biopsy in patients with G3/others (84% vs 52%, respectively, P = 0.010). Both biopsies were not sufficiently accurate to diagnose AEH (outpatient; 0%, hysteroscopic; 57%). Conclusion: Hysteroscopic papillary and polypoid structures can help distinguish between high‐ and low‐grade cancer. Hysteroscopic differentiation between AEH and low‐grade cancer is difficult. These findings are considerable in preoperative assessment to determine adequate surgical strategies. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumors (SFT) rarely arise in the pelvis. Here, we report two cases of SFT arising from the pelvic retroperitoneum. The first case involves a 64‐year‐old woman diagnosed with a 5‐cm pelvic mass. Magnetic resonance imaging revealed a solid and cystic mass with marked enhancement, but limited water restriction. During surgery, intraligamental tumor arising near the round ligament was resected. Pathologically, the tumor comprised dilated vessels and spindle‐shaped cells positive for STAT6 and CD34. The second case involves a 53‐year‐old woman diagnosed with a 4.5‐cm pelvic mass through computed tomography. Magnetic resonance imaging demonstrated a solid mass with multiple cysts with strong enhancement and slight water restriction. During surgery, the tumor was found in the retroperitoneum. Pathologically, spindle‐shaped tumor cells positive for STAT6 and CD34 had proliferated around the prominent hyalinized vessels. Although rare in the pelvis, SFT should be suspected when a mass with strong enhancement is found. [ABSTRACT FROM AUTHOR]

We report a case of aggressive adult granulosa cell tumor (AGCT) of the ovary. On presentation, the tumor was localized in the right ovary; a total abdominal hysterectomy, bilateral salpingo‐oophorectomy and partial omentectomy were performed. While some areas of the tumor represented typical AGCT, other areas showed enlarged and hyperchromatic nuclei with numerous mitoses (>10/high‐power field) with marked necrosis. The results of immunohistochemical analysis were compatible with AGCT, except that, in the necrotic portion, p53 was strongly positive, and the Ki‐67 index was high. Four months after laparotomy, recurrent tumors developed in the bones, liver, lungs and dura mater. The patient responded well to chemotherapy consisting of five cycles of paclitaxel and carboplatin, but later, the tumors rapidly proliferated, and the patient died of disease 11 months after laparotomy. FOXL2 examination demonstrated that both portions of the primary tumor did not have a point mutation (402C→G) specific to AGCT. [ABSTRACT FROM AUTHOR]

Mucinous adenocarcinoma, gastric type (GAS) is difficult to diagnose and shows poor prognosis. Trastuzumab, an anti-human epidermal growth factor type 2 (HER2) monoclonal antibody, is effective in HER2-positive stomach cancer. The objectives of this study were to identify the clinicopathological characteristics of GAS and to evaluate HER2 expression in GAS. We retrospectively reviewed 322 cervical cancer cases diagnosed at the Kyoto University Hospital from 2010 to 2016. The incidence, clinical factors including age, stage, and lymph node status, tumor markers, immunoreactive expression of MUC6, HIK1083, and HER2, and HER2 amplification were evaluated. Of the 322 cases of cervical cancer, 13 cases of the adenocarcinoma cases were diagnosed as GAS. Watery discharge, lower abdominal pain, CA19-9 elevation, and lymph node metastasis were frequently observed in GAS (p = 0.0226, p = 0.0400, p = 0.0346, and p = 0.0274, respectively). Immunohistochemistry showed positive MUC6 status in all 13 cases and positive HIK1083 status in 8 cases. The HER2 expression status was equivocal in six cases by immunohistochemistry and HER2 amplification was identified in one case. GAS exhibits frequent lymph node metastasis and clinical symptoms such as watery discharge and lower abdominal pain, high levels of CA19-9. In addition, some parts of GAS exhibit HER2 amplification. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Objectives: The aim of this study was to assess the prognostic and incremental value of pretreatment apparent diffusion coefficient (ADC) values of tumors for the prediction of tumor recurrence after complete resection of the tumor in patients with endometrial cancer. Methods: This study enrolled 210 patients with stages IA to IIIC endometrial cancer who had undergone complete resection of the tumor and pretreatment magnetic resonance imaging. The minimum and mean ADC values (ADCmin, ADCmean) of tumors and normalized ADC (nADCmin, nADCmean) were calculated from magnetic resonance imaging. The primary outcome was recurrence-free survival (RFS). Receiver operating characteristic analysis was performed to compare the diagnostic performance of ADC values of 4 types. The Kaplan-Meier method, log-rank tests, and Cox regression were used to explore associations between recurrence and the ADC values with adjustment for clinicopathological factors. Results: In receiver operating characteristic curve analysis, the areas under the curve were significant for ADCmean and nADCmean predicting tumor recurrence but were not significant for ADCmin and nADCmin. Regarding univariate analysis, ADCmean and nADCmean were significantly associated with increased risk of recurrence. Multivariate analysis showed that ADCmean and nADCmean remained independently associated with shorter RFS. In the high-risk group, the RFS of patients with lower ADC values (ADCmean and nADCmean) was significantly shorter than that of patients in the higher ADC value group. Conclusions: Pretreatment tumor ADCmean and nADCmean were important imaging biomarkers for predicting recurrence in patients after complete resection of the tumor. They might improve existing risk stratification. [ABSTRACT FROM AUTHOR]