Development of an Algorithm to Differentiate Uterine Sarcoma from Fibroids Using MRI and LDH Levels.

BACKGROUND: This study aimed to establish an evaluation method for detecting uterine sarcoma with 100% sensitivity using MRI and serum LDH levels. METHODS: One evaluator reviewed the MRI images and LDH values of a total of 1801 cases, including 36 cases of uterine sarcoma and 1765 cases of uterine fibroids. The reproducibility of the algorithm was also examined by four evaluators with different imaging experience and abilities, using a test set of 61 cases, including 14 cases of uterine sarcoma. RESULTS: From the MRI images and LDH values of 1801 cases of uterine sarcoma and uterine fibroids, we found that all sarcomas were included in the group with a high T2WI and either a high T1WI, an unclear margin, or high LDH values. In addition, when cases with DWI were examined, all sarcomas had high DWI. Among the 36 sarcoma cases, the group with positive findings for T2WI, T1WI, margins, and serum LDH levels all had a poor prognosis (p = 0.015). The reproducibility of the algorithm was examined by four evaluators and the sensitivity of sarcoma detection ranged from 71% to 93%. CONCLUSION: We established an algorithm to distinguish uterine sarcoma if tumors in the myometrium with low T2WI and DWI are present.

A Case of Uterine Lymphangioleiomyomatosis Complicated by Tuberous Sclerosis Complex.

Lymphangioleiomyomatosis (LAM) is one of the presentations of perivascular epithelioid cell neoplasm that is frequently complicated by tuberous sclerosis complex (TSC). Here, we report an uncommon case of uterine LAM treated with everolimus, which is a mechanistic target of rapamycin (mTOR) inhibitor. A 42-year-old female patient (gravida 0) with a history of TSC presented with abdominal pain. Pelvic magnetic resonance imaging showed multiple masses in the uterine myometrium, suggesting tumors that may contain internal hemorrhagic components. The lesions were suspected as the root cause of her symptoms. After everolimus was administered for a previously diagnosed renal angiolipoma, her uterine tumors temporarily decreased in size. Subsequently, laparoscopic hysterectomy and bilateral salpingectomy were performed since she could not tolerate everolimus for a long period due to the medication's side effects. Furthermore, the patient was diagnosed with LAM through histopathological examination after surgical resection. Therefore, it is advisable to suspect and investigate uterine LAM when a patient with a history of TSC presents with irregular genital bleeding or abdominal pain. Moreover, mTOR inhibitors may be a treatment option, in addition to surgery, in cases of uterine LAM exacerbation.

Plasma Antithrombin Activity during Long-Term Magnesium Sulfate Administration for Preeclampsia without Severe Hypertension.

In preeclampsia, plasma antithrombin activity is decreased, which leads to exacerbation of the disorder. We previously showed that long-term magnesium sulfate (MgSO4) administration prolonged the pregnancy period and may be able to improve pregnancy outcomes for patients with severe preeclampsia. The present study aimed to investigate the changes in plasma antithrombin activity during long-term MgSO4 administration for patients without severe hypertension. This multicenter retrospective study included patients with preeclampsia and superimposed preeclampsia without severe hypertension at diagnosis. The participants were divided into two groups: MgSO4 nontreatment group (three institutions) and MgSO4 treatment group (one institution). Antithrombin activity from time of diagnosis to delivery were compared between the two groups. In the MgSO4 nontreatment group (n = 16), antithrombin activity prior to delivery was significantly lower than at time of diagnosis (p = 0.015). In three cases, antithrombin activity was less than 60%. On the other hand, in the MgSO4 treatment group (n = 34), antithrombin activity did not change until just before delivery (p = 0.74). There were no cases in which antithrombin activity was decreased below 60%. Long-term MgSO4 administration for preeclampsia without severe hypertension may prevent a decrease in antithrombin activity and improve the disease state of preeclampsia.

Imiquimod for vaginal intraepithelial neoplasia 2-3: A systematic review and meta-analysis.

OBJECTIVE: The treatment strategy for vaginal intraepithelial neoplasia (VaIN) 2-3 has not been established. This study aimed to investigate the efficacy of imiquimod in VaIN 2-3. METHODS: Electronic databases (PubMed, EMBASE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials) were searched from their inception until October 2019 and articles reporting imiquimod treatment for VaIN 2-3 were extracted. Additionally, the clinical records of women with VaIN 2-3 who had been treated with imiquimod in Shizuoka General Hospital from January 2016 to May 2020 were investigated. The data from the systematic search and the data from our hospital were analyzed, and a pooled complete response (CR) rate and response rate of imiquimod treatment for VaIN 2-3 were estimated. As a subgroup analysis, the CR rates and response rates were compared between women with and without a history of hysterectomy, and the rate ratio was calculated. RESULTS: Five articles described 28 women with VaIN 2-3 who underwent imiquimod treatment, and nine women with VaIN 2-3 were treated with imiquimod in our hospital. The discontinuation of the treatment was required in only one patient of the reported cases. The pooled CR rate and response rate of imiquimod, regardless of a history of hysterectomy, was 0.76 (95% CI, 0.59-0.87) and 0.89 (95% CI, 0.71-0.97), respectively. In the subgroup analysis, the CR rate in patients with hysterectomy was 0.98 (95% CI, 0.11-1.0) and in those without hysterectomy was 0.60 (95% CI, 0.30-0.84), and the rate ratio was 0.83 (95% CI, 0.48-1.19). The pooled response rates with and without a history of hysterectomy were not estimated, and the rate ratio was 0.83 (95% CI, 0.54-1.09). CONCLUSION: Imiquimod can be an effective treatment for vaginal intraepithelial neoplasia 2-3.

Recurrent vaginal intraepithelial neoplasia successfully treated with topical imiquimod: A case report.

Vaginal intraepithelial neoplasia (VAIN) is a rare disease associated with human papillomavirus infection. High-grade VAIN is typically treated with either excisional or ablative therapy. However, recurrent VAIN lesions are common and these treatments cause vaginal scarring. Recent studies have indicated that 5% imiquimod is an effective treatment for VAIN. The present report describes a case of a woman diagnosed with recurrent VAIN 3 who was treated with a 5% topical imiquimod cream and achieved a complete response after excision and CO2 laser vaporization. A 53-year-old, gravida 5, para 2 postmenopausal woman who was diagnosed with papillary squamous cell carcinoma by biopsy underwent conization, total abdominal hysterectomy and bilateral salpingo-oophorectomy. A histological examination revealed grade 3 cervical intraepithelial neoplasia with free surgical margins. At 3 years after the hysterectomy, the vaginal smear revealed atypical squamous cells, leading to a pathological diagnosis of VAIN 3. Partial vaginectomy was performed, and VAIN 3 was detected in the lesion with positive margins. At 4 months into follow-up, the vaginal smear revealed a high-grade squamous intraepithelial lesion (HSIL), and subsequent biopsy during colposcopy revealed a pathological diagnosis of VAIN 3. At 3 months after CO2 laser vaporization, the vaginal smear revealed HSIL with suspected recurrence and imiquimod treatment was initiated. One sachet of 5% imiquimod cream (0.25 g) was placed in the entire vagina three times per week for 14 weeks with no apparent complications. At 3 years after the treatment, there has been no recurrence. This case demonstrated that topical imiquimod with careful follow-up is an effective treatment for VAIN and is well-tolerated. Further clinical evidence of the effectiveness and safety of imiquimod in patients diagnosed with VAIN is required.

Invasive cervical cancer accompanied by IgG4-related disease.

IgG4-related disease (IgG4-RD) is a systemic disease that affects multiple organs and generates nodules or thickening. Discriminating these diseases from malignancy is important because glucocorticoid treatment is effective for patients with IgG4-RD. Coexistence of IgG4-RD with various malignant diseases has been reported, but there are few reports with regard to gynecologic malignant diseases. We encountered a case of invasive cervical cancer stage IIB accompanied by IgG4-RD. The patient was a 46-year-old woman. On pelvic magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography and computed tomography, systemic multiple lymph node swelling was seen, including in the neck and the mediastinum in addition to uterine cervix. Diagnosis (and hence, appropriate treatment choice) was achieved on pathology of the submandibular gland and uterus, and analysis of serum IgG4. IgG4-RD should be suspected in patients presenting with malignancy and unusual multiple lymph node swelling.

Pathways of metastases from primary organs to the ovaries.

To investigate the metastatic pathways from the primary organs to the ovaries, we examined the microscopic findings from 18 original and 18 metastatic ovarian tumors carefully. In addition, we examined the immunohistochemical findings (Victoria blue stain for vascular invasion and D2-40 expression for lymphangio invasion) of metastatic ovarian tumors carefully. There were 4 (57%) ovarian lymphangio invasion cases in the 7 gastric cancers, but there were no cases in the 6 colorectal cancers (P < 0.05). There were 4 (67%) ovarian vascular invasion cases and one (17%) liver metastasis case in the 6 colorectal cancers, while there were no ovarian vascular invasions (P < 0.05) or no liver metastases in the 7 gastric cancers. The patients with metastatic ovarian tumors originating from distant organs who were treated at the same time as the original cancers had a significantly poorer prognosis than the patients with ovarian tumors treated later (P < 0.05). The rate of lymphatic metastasis from the stomach to the ovary was significantly higher than from the colon to the ovary. In addition we hypothesized that the rate of intravascular metastasis from the colorectum to the ovary was relatively higher than from the stomach to the ovary.

Endometrial cancer implanted within a cesarean section scar.

Several reports have documented adenocarcinoma arising from endometriotic implants within cesarean section (C-S) scars on the serosal surface of the uterus; however, endometrial cancer invading the C-S scar from the uterine cavity has not been described. We report a case of a grade 1 endometrioid adenocarcinoma 'drop' lesion invading a previous C-S scar with resultant cervical stromal invasion. Using both MR images and a thorough review of the pathology, the tumor at the C-S scar was determined to be an implant derived from a primary lesion at the uterine fundus. With increases in the incidence of both endometrial cancer and births by C-S, it is likely we will encounter more cases of iatrogenic implants of endometrial cancers in C-S scars.

Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1.

Distinguishing primary mucinous ovarian cancers from ovarian metastases of digestive organ cancers is often challenging. Dipeptidase 1 was selected as the candidate novel marker of colorectal cancer based on an analysis of a gene expression microarray. Immunohistochemical analysis indicated that 13/16 ovarian metastases of colorectal cancers, but only 1/58 primary mucinous ovarian cancers, were dipeptidase 1-positive (threshold; ≧25% expression, P<0.0001). Next, five immunohistochemical markers (dipeptidase 1, estrogen receptor-α, cytokeratin 7, cytokeratin 20, and caudal type homeobox 2) were analyzed in combination. In a hierarchical clustering analysis, the mutually exclusive expression of cytokeratin 7 and dipeptidase 1 specifically identified the ovarian metastases of colorectal cancers (P<0.0001). In a decision tree analysis, cytokeratin 7, caudal type homeobox 2, and dipeptidase 1 classified primary mucinous ovarian cancers and ovarian metastases of digestive organ cancers with 90% accuracy. Finally, the five immunohistochemical markers were combined with six preoperative factors (patient's age, tumor size, laterality, serum CEA, CA19-9, and CA125) and combinations were analyzed. Of the 11 factors, 4 (dipeptidase 1, cytokeratin 7, caudal type homeobox 2, and tumor size) were used to generate a decision tree to classify primary mucinous ovarian cancers and metastases of digestive organ cancers with 93% accuracy. In conclusion, we identified a novel immunohistochemical marker, dipeptidase 1, to distinguish primary mucinous ovarian cancers from ovarian metastasis of colorectal cancers. The algorithm using immunohistochemical and clinical factors to distinguish metastases of digestive organ cancers from primary mucinous ovarian cancers will be useful to establish a protocol for the diagnosis of ovarian metastasis.

Retroperitoneal lipoma arising from the urinary bladder.

Retroperitoneal benign lipomas are extremely rare and represent about 2.9% of all primary retroperitoneal tumors. About 80% of the tumors in the retroperitoneal cavities are malignant neoplasms. We experienced a case of a retroperitoneal lipoma simulating an ovarian mature cystic teratoma. A diagnosis was correctly made by magnetic resonance imaging (MRI) prior to surgery, and a total tumorectomy was performed. The retroperitoneal lipoma was recognized to have arisen from the urinary bladder. Histological sections revealed a tumor consisting of typical adipose cells without atypia. These types of lipomas should be carefully followed-up because they often recur and undergo malignant transformations.