Daiki Ogishima

Placental pathology in systemic lupus erythematosus with antiphospholipid antibodies

Systemic lupus erythematosus (SLE) is associated with a poor pregnancy outcome. Antiphospholipid antibodies (APL), which include lupus anticoagulant (LAC) and anticardiolipin antibodies (aCL), are frequently found in patients with SLE, and their presence has been associated with fetal loss. To examine placental pathologic features of SLE patients with APL, we performed a pathologic study on 47 placental tissue samples from 47 pregnant SLE patients with APL (15 patients; four LAC single‐positive patients, seven aCL single‐positive patients, four LAC and aCL double‐positive patients) and without APL (32 LAC and aCL double‐negative patients). The incidence of extensive infarction, decidual vasculopathy, decidual thrombosis and perivillous fibrinoid change, which have been thought to be characteristic lesions of APL placenta, was significantly higher in the LAC and aCL double‐positive patients than in the patients without APL. Conversely, the above‐mentioned lesions between the LAC or aCL single‐positive patients and the APL negative patients did not differ significantly. Among the 15 patients with APL, two of the three patients with both decidual vasculopathy and thrombosis had extensive infarction associated with fetal death. Moreover, the patients having fetal death showed LAC and aCL double‐positivity. In conclusion, this study indicated that the LAC and aCL double‐positivity is an important factor for extensive infarction resulting from decidual vasculopathy and decidual thrombosis in the SLE placenta. Moreover, it was indicated that LAC and aCL double‐positivity is an important risk factor for fetal death in the SLE patient.

Transmission of the major skin microbiota, Malassezia, from mother to neonate.

Background:  Skin surface colonization starts after birth. It is thought that early microbial colonization affects the development of skin immune functions. Although Malassezia is the predominant fungus in the skin microbiota in healthy individuals, the microorganism is associated with atopic dermatitis and seborrheic dermatitis. In the present study, transmission of skin microbiota from mothers to their neonates was elucidated using the Malassezia microbiota as an indicator.

Uterine angiosarcoma associated with lymphangioleiomyomatosis in a patient with tuberous sclerosis complex: an autopsy case report with immunohistochemical and genetic analysis.

A 41-year-old woman carrying a germline tuberous sclerosis complex 2 (TSC2) mutation, whose regular medical follow-up for tuberous sclerosis complex and tuberous sclerosis complex-associated lymphangioleiomyomatosis had continued for 2 years, had uterine angiosarcoma concomitant with uterine lymphangioleiomyomatosis. Immunohistochemically, the uterine angiosarcoma cells showed an extremely skewed lymphatic differentiation; they were diffusely immunopositive for CD31 but negative for other vascular endothelial markers including factor VIII and CD34 yet strongly immunopositive for lymphatic endothelial markers including D2-40 and Prox-1. Loss of heterozygosity analysis demonstrated that not only lymphangioleiomyomatosis and renal angiomyolipoma but also the uterine angiosarcoma had loss of heterozygosity on TSC2. Furthermore, direct sequencing revealed a TP53 mutation in the uterine angiosarcoma. Collectively, the findings suggest that combined dysfunction of the p53 and TSC2 tumor suppressor proteins may contribute to the development of uterine angiosarcoma in this rare clinical setting.

Histopathological study of the spreading neoplastic cells in cervical glands and surface epithelia in cervical intra‐epithelial neoplasia and microinvasive squamous cell carcinoma: Ki‐67 immunostaining is a useful marker for pathological diagnosis from the gland involvement site

The purpose of the present study was to clarify the spreading status of neoplastic cells in the cervical glands and surface epithelia in cervical intra‐epithelial neoplasia (CIN) and microinvasive squamous cell carcinoma (MiSCC), and to evaluate the diagnostic usefulness of Ki‐67 immunostaining from the gland involvement (GI) site. Cervical conization samples from 120 patients, including 110 with CIN (CIN1, n = 2; CIN2, n = 21; CIN3, n = 87) and 10 patients with MiSCC, was examined using HE and Ki‐67 immunostaining. The linear extent, lateral extent in the surface epithelia and depth of GI were significantly increased from CIN1 to MiSCC. A significant correlation was found between the linear extent and lateral extent, between the linear extent and depth, and between the lateral extent and depth. These results indicated that the size of the surface epithelial lesion and the depth in CIN gradually increased in accordance with the grade of CIN, and that GI became deeper according to the increase in the size of the surface epithelial lesion. The Ki‐67 labeling index in the GI site gradually increased from CIN1 to MiSCC, which indicated that Ki‐67 immunostaining is a useful marker for the pathological diagnosis of CIN from the GI site.

Small cell carcinoma of the uterine cervix metastasizing to the bone marrow: A case report

We report a case of small cell carcinoma (SmCC) of the uterine cervix that metastasized to the bone marrow. A 60‐year‐old woman with stage IIB SmCC of the cervix was treated with three courses of neoadjuvant chemotherapy followed by radical hysterectomy. Because of the presence of a large residual tumor, the patient underwent postoperative adjuvant chemotherapy. Two months after the last course of chemotherapy, severe pancytopenia developed, and erythroblastic cells were found in the peripheral blood. The hematological disorder was shown to be secondary to bone marrow metastasis, and no other metastases were found. The patient died of the disease 8 months after the initial diagnosis. This case suggests that SmCC of the cervix can metastasize to bone marrow, that such metastasis can occur in isolation and lead to severe pancytopenia, influencing the clinical course of the disease.

Useful aspects of diagnosis of imprint cytology in intraoperative consultation of ovarian tumors: comparison between imprint cytology and frozen sections

In the intraoperative consultation of ovarian tumors, the histological diagnosis of frozen sections (FS) of large tumors is frequently difficult because of the limited number of tumor samples. The application of imprint cytology (IC), in which samples are obtained from wide areas of the tumors, is useful for intraoperative consultation. However, the useful aspects of IC have not been clearly defined. The present study is a detailed comparison of IC and FS that clearly defines the useful aspects of IC.

Culture Supernatants of Lactobacillus gasseri and L. crispatus Inhibit Candida albicans Biofilm Formation and Adhesion to HeLa Cells

PurposeVulvovaginal candidiasis (VVC) is a common superficial infection of the vaginal mucous membranes caused by the fungus Candida albicans. The aim of this study was to assess the mechanisms underlying the inhibitory effects of the culture supernatants of Lactobacillus gasseri and L. crispatus, the predominant microbiota in Asian healthy women, on C. albicans biofilm formation. The inhibition of C. albicans adhesion to HeLa cells by Lactobacillus culture supernatant was also investigated.MethodsCandida albicans biofilm was formed on polystyrene flat-bottomed 96-well plates, and the inhibitory effects on the initial colonization and maturation phases were determined using the XTT reduction assay. The expression levels of biofilm formation-associated genes (HWP1, ECE1, ALS3, BCR1, EFG1, TEC1, and CPH1) were determined by reverse transcription quantitative polymerase chain reaction. The inhibition of C. albicans adhesion to HeLa cells by Lactobacillus culture supernatant was evaluated by enumerating viable C. albicans cells.ResultsThe culture supernatants of both Lactobacillus species inhibited the initial colonization and maturation of C. albicans biofilm. The expression levels of all biofilm formation-related genes were downregulated in the presence of Lactobacillus culture supernatant. The culture supernatant also inhibited C. albicans adhesion to HeLa cells.ConclusionThe culture supernatants of L. gasseri and L. crispatus inhibited C. albicans biofilm formation by downregulating biofilm formation-related genes and C. albicans adhesion to HeLa cells. These findings support the notion that Lactobacillus metabolites may be useful alternatives to antifungal drugs for the management of VVC.

Loop-mediated isothermal amplification for the rapid detection of Gardnerella vaginalis : LAMP for rapid detection of G. vaginalis

The aim of this study was to develop a method for the rapid detection of Gardnerella vaginalis, which is proposed to play a key role in the pathogenesis of bacterial vaginosis. Specific loop‐mediated isothermal amplification (LAMP) primers were designed and used to detect target DNA within 45 min under isothermal conditions. Comparative screening indicated that the LAMP assay is superior to PCR in terms of rapidity, and is equivalent in sensitivity and specificity. This LAMP assay can be used for rapid screening and detection of G. vaginalis in vaginal samples; the limit of detection is 10 fg DNA.

Coexistence of Cervical Leiomyosarcoma and Gastric-Type Adenocarcinoma In Situ with Extensive Extension to the Endometrium and Fallopian Tube

Cervical leiomyosarcoma is known to be rare from the previous reviews of a large number of malignant cervical tumors. The patient was a 66-year-old woman with irregular vaginal bleeding. She underwent modified radical hysterectomy and bilateral salpingooophorectomy. Histopathologically, we diagnosed the coexistence of uterine cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ with endometrial lesions that had continuous and skip patterns and fallopian tubal lesions with a partial lesion. To the best of our knowledge, cases of synchronous leiomyosarcoma and cancers have not often been reported; only two cases of synchronous cervical leiomyosarcoma and cervical squamous cell carcinoma have been published. This case is the first presentation of coincidental primary cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ. Additionally, we considered cervical gastric-type adenocarcinoma in situ with continuous lesions on the endometrium and skip lesions on the left fallopian tube.

Long‐term efficacy and safety of aromatase inhibitor use for leiomyomatosis peritonealis disseminata

Leiomyomatosis peritonealis disseminata is a rare disease characterized by pelvic smooth‐muscle nodules of various sizes. It is sometimes misdiagnosed as ovarian or peritoneal carcinoma metastasis; therefore, surgical excision for pathological diagnosis is required. Treatment options include bilateral salpingo‐oophorectomy (BSO), gonadotrophin‐releasing hormone agonist therapy, and aromatase inhibitor therapy. All of these suppress estrogen levels, but a standard treatment has not been established. A 40‐year‐old woman had multiple pelvic tumors, suspicious for ovarian cancer. She underwent laparotomy, where frozen sections of the nodules revealed leiomyomatosis peritonealis disseminata. After she completed gonadotrophin‐releasing hormone agonist therapy, we performed a total abdominal hysterectomy and BSO with residual‐nodule resection, but the nodules recurred 6 months after surgery. We then started letrozole, and 3 years have now elapsed without nodule enlargement or development of new lesions. The long‐term use of aromatase inhibitor therapy is thought to be effective and safe for patients with recurrence after BSO.