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Ovarian mature teratomas (OMTs) originate from post-meiotic germ cells. Malignant transformation occurs in approximately 1–2% of OMTs; however, sebaceous carcinoma arising from OMTs is rare. This is the first report of a detailed genomic analysis of sebaceous carcinoma arising from an OMT. A 36-year-old woman underwent evaluation for abdominal tumors and subsequent hysterectomy and salpingo-oophorectomy. Pathologically, a diagnosis of stage IA sebaceous carcinoma arising from an OMT was established. Eight months post-surgery, the patient was alive without recurrence. Immunohistochemically, the tumor was negative for mismatch repair proteins. A nonsense mutation in TP53 (p.R306*) and a deletion in PIK3R1 were identified. Single nucleotide polymorphisms across all chromosomes displayed a high degree of homozygosity, suggestive of uniparental disomy. Herein, the OMT resulting from the endoreduplication of oocytes underwent a malignant transformation to sebaceous carcinoma via TP53 as an early event and PIK3R1 as a late event. [ABSTRACT FROM AUTHOR]

Laparoscopic cystectomy for mature teratomas is associated with a high incidence of intraperitoneal spillage and tumor spread; however, extragonadal recurrence of this benign tumor is rare. We hereby present an additional case of extragonadal mature teratoma that recurred in the pouch of Douglas after ovarian cystectomy. A 43‐year‐old Japanese woman presented with atypical genital bleeding. A 7 cm mature teratoma was detected using transvaginal ultrasonography and magnetic resonance imaging. At 26 years old, she underwent bilateral cystectomy for bilateral mature teratoma of the ovary. During laparoscopic surgery, a cystic tumor appeared in the pouch of Douglas and was firmly adhered to the surrounding tissues. Both ovaries were normal. The resected tumor was diagnosed as extragonadal, benign, mature teratoma. To avoid the extragonadal recurrence of mature teratoma, removal of tumor contents from intraperitoneal spillage by lavage should be performed at the end of surgery. [ABSTRACT FROM AUTHOR]

Background: Tumor-to-tumor metastasis (TTM) is a rare but well-established phenomenon where histologically distinct tumors metastasize within each other. Here we report the first "known" case of follicular lymphoma that metastasized and extended to a mature ovarian teratoma. Case presentation: A 59-year-old Japanese postmenopausal woman visited our hospital for a detailed examination of an ovarian tumor. Clinical imaging suggested it to be either teratoma-associated ovarian cancer with multiple lymph node metastases, or tumor-to-tumor metastasis from malignant lymphoma to ovarian teratoma. A bilateral adnexectomy and retroperitoneal lymph node biopsy were performed. Lined with squamous epithelium, the cyst constituted a mature ovarian teratoma, and the solid part showed diffuse proliferation of abnormal lymphoid cells. Immunohistochemically, the abnormal lymphoid cells were negative for CD5, MUM1, and CyclinD1, and positive for CD10, CD20, CD21, BCL2, and BCL6. Genetic analysis using G-banding and fluorescence in situ hybridization identified a translocation of t(14;18) (q32;q21), and we diagnosed tumor-to-tumor metastasis from nodal follicular lymphoma to mature ovarian teratoma. Twelve months after surgery, the patient showed no progression without adjuvant therapy. Conclusions: The present case suggests that molecular approaches are useful in the diagnosis of TTM in mature ovarian teratomas when morphologic and immunohistochemical findings alone are insufficient for diagnoses. [ABSTRACT FROM AUTHOR]

Endometriosis is a common, estrogen-dependent benign tumor that affect 3–10% women of reproductive age, and is characterized by the ectopic growth of endometrial tissue, which is found primarily in the rectovaginal septum, ovaries, and pelvic peritoneum. To date, accumulating evidence suggests that various epigenetic aberrations, including the expression of aberrant microRNAs (miRNAs), play definite roles in the pathogenesis of endometriosis. This review summarizes the recent findings on the aberrantly repressed miRNAs, as well as their potential roles regarding the pathogenesis of endometriosis. [ABSTRACT FROM AUTHOR]

Little is known about the immune environment of ovarian clear cell carcinoma (OCCC) and its impact on various ethnic backgrounds. The aim of this OCCC immune‐related gene expression signatures (irGES) study was to address the interaction between tumour and immune environment of ethnically‐diverse Asian and Caucasian populations and to identify relevant molecular subsets of biological and clinical importance. Our study included 264 women from three different countries (Singapore, Japan, and the UK) and identified four novel immune subtypes (PD1‐high, CTLA4‐high, antigen‐presentation, and pro‐angiogenic subtype) with differentially expressed pathways, and gene ontologies using the NanoString nCounter PanCancer Immune Profiling Panel. The PD1‐high and CTLA4‐high subtypes demonstrated significantly higher PD1, PDL1, and CTLA4 expression, and were associated with poorer clinical outcomes. Mismatch repair (MMR) protein expression, assessed by immunohistochemistry, revealed that about 5% of OCCCs had deficient MMR expression. The prevalence was similar across the three countries and appeared to cluster in the CTLA4‐high subtype. Our results suggest that OCCC from women of Asian and Caucasian descent shares significant clinical and molecular similarities. To our knowledge, our study is the first study to include both Asian and Caucasian women with OCCC and helps to shine light on the impact of ethnic differences on the immune microenvironment of OCCC. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Background: In 2014, the World Health Organization (WHO) released a classification system introducing neuroendocrine neoplasms (NENs) of the female reproductive tract, excluding the ovaries. This study aimed to evaluate whether retrospective adaption of the gastroenteropancreatic (GEP)-NEN classification is feasible for ovarian NENs (O-NENs) and correlates with prognosis. Methods: Sixty-eight patients diagnosed with carcinoid, small cell carcinoma (pulmonary type), paraganglioma, non-small/large cell neuroendocrine carcinoma (NEC), mixed NEC, or undifferentiated carcinomas at 20 institutions in Japan were included in this retrospective cross-sectional study. We identified O-NENs through central pathological review using a common slide set, followed by reclassification according to WHO 2010 guidelines for GEP-NENs. A proportional hazards model was used to assess the association of prognostic factors (age, stage, performance status, histology, and residual disease) with overall survival (OS) and progression-free survival (PFS). Results: Of the 68 enrolled patients, 48 were eligible for analysis. All carcinoids (n = 32) were reclassified as NET G1/G2, whereas 14 of 16 carcinomas were reclassified as NEC/mixed adeno-NEC (MANEC) (Fisher's exact test; p < 0.01). The OS/PFS was 49.0/42.5 months and 6.5/3.9 months for NET G1/G2 and NEC/MANEC, respectively. Histology revealed that NEC/MANEC was associated with increased risk of death (HR = 48.0; 95% CI, 3.93–586; p < 0.01) and disease progression (HR = 51.6; 95% CI, 5.54–480; p < 0.01). Conclusion: Retrospective adaption of GEP-NEN classification to O-NENs is feasible and correlates well with the prognosis of O-NENs. This classification could be introduced for ovarian tumors. [ABSTRACT FROM AUTHOR]

Herein, we report magnetic resonance imaging (MRI) findings of a mucinous borderline tumor of the ovary, which we observed as a mainly solid tumor with large solid components in the lower pelvic cavity. The appearance of ovarian epithelial tumors on imaging is often complex. Cystic to solid appearing masses may be observed, and they often resemble epithelial carcinoma. Due to mucinous or hemorrhage components of packed small or microcystic components, MRI depicts slightly high signal intensity on T1-weighted images and low signal intensity on T2-weighted images. Mucinous borderline tumor of the ovary with a large solid component is very rare, but it is clinically important to recognize the possibility of mucinous borderline tumor to avoid unnecessary surgical intervention. [ABSTRACT FROM AUTHOR]

The cancer stroma serves an important role in tumour behaviours, including invasion, metastasis, and response to chemotherapy. The stroma of ovarian carcinoma is sometimes specialized, with luteinisation and/or hyperthecosis, and is designated as the 'functioning stroma' because it exerts endocrine function and produces sex steroid hormones. In the present study, 14 ovarian cancers with functioning stroma, comprising 7 endometrioid carcinomas and 7 clear cell carcinomas, were analysed to evaluate the molecular association of the functioning stroma with carcinoma cells. The median age of the patients was 67 years (range, 52–85 years); 13 patients were postmenopausal, and one was in perimenopause. Serum oestrogen values ranged from 10 to 129 ng/ml, with a median of 51 ng/ml. Sequence abnormalities in AT-rich interaction domain 1A (ARID1A), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA), Kirsten rat sarcoma viral proto-oncogene (KRAS) and phosphatase and tensin homolog (PTEN) were examined in whole tumours. For cancers positive for sequence abnormalities, their localization in carcinoma cells and/or stromal cells was examined. A total of 8 mutations - ARID1A (L2155L), PIK3CA (H1047R), KRAS (Q12V, E31K, Q61L), and PTEN (C105fs*8) - were identified in the whole tumours of 5 patients. Seven of these eight mutations were detected only in carcinoma cells. However, one case of endometrioid carcinoma had a KRAS (E31K) mutation in both carcinoma and stromal cells. In conclusion, although functioning stromal cells of ovarian cancer are usually thought to be non-neoplastic, some may share an origin with carcinoma cells. [ABSTRACT FROM AUTHOR]

Elderly patients with endometrial carcinoma (EMC) are considered to have a poor clinical outcome. The present study included 79 patients aged =70 years with EMC stage I or II according to the International Federation of Gynecology and Obstetrics classification, and it was conducted to analyse the clinicopathological significance of histological type (I or II), depth of myometrial invasion (<1/2 or =1/2), lymphovascular invasion (+ or -) and immunohistochemical profile. The aim of these analyses was to determine whether these factors may adversely affect the patient outcome and the underlying mechanisms. The immunohistochemical markers used were estrogen receptor (ER), Ki-67 and p53. The expression of these markers was evaluated as high (+) or low (-). Accordingly, the patients were divided into groups as follows: 54 cases type I vs. 25 cases type II; 48 cases with myometrial invasion <1/2 vs. 31 cases without myometrial invasion =1/2; 63 cases with lymphovascular invasion vs. 16 cases without lymphovascular invasion; 57 cases with ER (+) vs. 22 cases with ER (-); 24 cases with Ki-67 (+) vs. 55 cases with Ki-67 (-); and 29 cases with p53 (+) vs. 50 cases with p53 (-). In conclusion, close attention must be paid to elderly patients with EMC due to the tumor's intrinsic aggressiveness, which may include the ER (-) and p53 (+) pattern as an independent poor prognostic factor. [ABSTRACT FROM AUTHOR]

Histone deacetylase (HDAC) inhibitor is known to have a cytotoxic effect on ovarian cancer cell lines. The present study analyzed the association between immunohistochemical HDAC expression and clinicopathological findings, in particular, the association with histological type and effect of chemotherapy. The histology of the 201 ovarian cancers addressed was as follows: Serous carcinoma (SEC), 100 cases; clear cell carcinoma (CCC), 56 cases; endometrioid carcinoma (EMC), 36 cases; and mucinous carcinoma (MUC), 9 cases. Immunohistochemical analyses of HDACs 1, 2, 3, 4, 5, 6 and 7 expression levels were performed using tissue microarrays, composed of 201 primary tumors and 38 tumors following chemotherapy. Overexpression of HDAC1 was detected in the nucleus of all cases with MUC, followed by CCC (80%), SEC (73%), and EMC (53%). CCC specifically demonstrated HDAC7 expression in both the nucleus (27%) and the cytoplasm (54%), and HDAC6 expression in the nucleus (34%). The comparison between prior to and following chemotherapy revealed a nuclear expression increase in HDAC1 (76% vs. 92%; P=0.03) and HDAC7 (0.0 vs. 16%; P=0.01), and cytoplasmic expression increase in HDAC6 (40 vs. 74%; P=<0.01) and HDAC7 (16 vs. 66%; P=<0.01). HDAC1 nuclear expression adversely affected overall survival in SEC (P=0.02) and EMC (P=0.03), and HDAC7 cytoplasmic expression in CCC was associated with a poor prognosis (P=0.06). In multivariate analysis, HDAC6 nuclear expression was determined as a poor prognostic factor (hazard ratio=3.51; 95% confidence interval, 1.49 to 8.27, P=<0.01). In the subgroup analysis, HDAC6 nuclear expression was associated with a poor prognosis in CCC (P=0.07), International Federation of Obstetrics and Gynecology stage III/IV (P=0.07), and suboptimal surgery (P=<0.01). In conclusion, HDACs may be associated with the prognosis of ovarian cancers, depending on the histological subtypes, and upregulated following chemotherapy. HDAC1, 6 and 7 may therefor act as promising therapeutic targets in the future. [ABSTRACT FROM AUTHOR]

The present study presents a case of peritoneal malignant mesothelioma (PMM) following radiation therapy for cervical cancer. A 34-year-old Japanese woman, without asbestos exposure, was referred to the Department of Gynecologic Oncology, Saitama Medical University International Medical Center due to a cervical mass, and was diagnosed with cervical squamous cell carcinoma (SCC). The serum levels of tumor markers, including SCC antigen and cancer antigen 125 (CA125) were 229.0 ng/ml and 54.4 U/ml, respectively. The patient underwent concurrent chemoradiotherapy (CCRT), and a complete response was achieved. After 54 months, ascites was found at the rectouterine pouch, but peritoneal cytology suggested reactive mesothelial cell. After 62 months of CCRT, magnetic resonance imaging revealed masses in both the salpinges. The serum levels of SCC and CA125 were 0.9 ng/ml and 506.1 U/ml, respectively. Following this, left salpingectomy and peritoneal biopsy were performed laparoscopically. Histologic examination revealed atypical mesothelial cells with no continuity of background tubal epithelium. Immunohistochemistry showed positive staining for calretinin, thrombomodulin, mesothelin and glucose transporter 1. Based on these findings, the patient was diagnosed with PMM epithelioid type and underwent systemic chemotherapy; stable disease status has been obtained for 3 months. This case demonstrates the possibility of PMM occurrence within 10 years after radiotherapy, and indicates the importance of histological and immunohistochemical examination, particularly in cases of an atypical tumorigenesis pattern from the primary cancer. [ABSTRACT FROM AUTHOR]

Deep angiomyxoma is a rare, infiltrative, hormone-dependent, benign-mesenchymal neoplasm that occurs in the deep soft tissues of the perineal regions. In total, 33% females with newly diagnosed deep angiomyxoma will typically relapse within 5 years after the standard treatment of radical resection. Postoperative hormone therapy is frequently administered to prevent recurrence, but the role of prophylactic oophorectomy in premenopausal women remain to be fully elucidated. In the present report, a 42-year-old Japanese woman was referred for a refractory Bartholin's cyst that is 14 cm in diameter. Based on the results of imaging (unenhanced CT and MRI) and histopathology, deep angiomyxoma was suspected, but no definitive diagnosis was possible. Tumor resection and bilateral salpingo-oophorectomy were performed before the postoperative diagnosis was confirmed to be deep angiomyxoma. The patient received an aromatase inhibitor (2.5 mg letrozole daily) as adjuvant hormonal therapy. There was no evidence of recurrence at the 1-year postoperative follow-up. In conclusion, prophylactic oophorectomy and postoperative adjuvant therapy with aromatase inhibitors may be a promising treatment option for deep angiomyxoma to optimize the outcome of surgical treatment. Long-term follow-up is required to monitor for the late and/or local recurrence of deep angiomyxoma and possible adverse effects of adjuvant hormonal therapy. [ABSTRACT FROM AUTHOR]

Uterine fibroids are associated with heavy menstrual bleeding, abdominal discomfort, subfertility and a reduced quality of life. The present study reported a case series of life-threatening anemia with hemoglobin levels <2.0 g/dl caused by uterine fibroids and genital bleeding. Case 1 was of a 34-year-old woman who was transported to the emergency department of the Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University because of a decline in consciousness level. She had been experiencing excessive and prolonged menstruation for many years but had not sought medical help. A 5-cm uterine submucosal leiomyoma was detected and the patient underwent hysteroscopic myomectomy. Case 2 was of a 36-year-old woman with a history of blood transfusions owing to severe anemia who was presented with progressive dyspnea. Although it was repeatedly explained her that her condition was life threatening, she refused to be hospitalized. Her hemoglobin level was 1.7 g/dl. Multiple uterine fibroids and adenomyosis were detected and total hysterectomy was performed. Case 3 was of a 49-year-old woman who was transported to the emergency department of the Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University due to abdominal pain and severe anemia. Blood testing revealed a hemoglobin level of 1.9 g/dl. Multiple uterine fibroids with a maximum diameter of 8.5 cm were detected. However, the patient insisted on discharge because of lack of disease awareness. Total hysterectomy was performed. The present study is the largest case series showing a detailed clinical course of patients with life-threatening anemia with hemoglobin levels <2.0 g/dl. Additionally, Case 1 of the present series exhibited the lowest hemoglobin level (1.1 g/dl) reported to date. The present cases and a review of the literature suggested that the most important risk factors of life-threatening anemia are the patient's mental, social and personal factors, rather than the organic and functional abnormalities of the uterus. [ABSTRACT FROM AUTHOR]

Ovarian clear cell carcinoma (OCCC) is resistant to platinum-based chemotherapy. The use of immune checkpoint inhibitors is expected to be a new strategy for its treatment. Lymphocyte activation gene 3 (LAG-3), an immune checkpoint, is a poor prognostic factor and a new therapeutic target for several malignancies. In this study, we demonstrated a correlation between LAG-3 expression and the clinicopathological features of OCCC. We evaluated LAG-3 expression in tumor-infiltrating lymphocytes (TILs) by immunohistochemistry using tissue microarrays containing surgically resected specimens from 171 patients with OCCC. The LAG-3-positive cases were 48 (28.1%). The expression of LAG-3 significantly increased in patients with advanced stages (P = 0.036) and recurrence (P = 0.012). Using the Kaplan−Meier method, LAG-3 expression was observed to be correlated with poorer overall survival (P = 0.020) and progression-free survival (P = 0.019) than no expression. Multivariate analysis regarded LAG-3 expression (HR = 1.86; 95% CI, 1.00−3.44, P = 0.049) and residual tumor (HR = 9.71; 95% CI, 5.13−18.52, P < 0.001) as independent prognostic factors. In this study, it is clear that LAG-3 expression in patients with OCCC is a useful biomarker for predicting prognosis and may be a new therapeutic target. [ABSTRACT FROM AUTHOR]

The article presents a case study of 24-year-old primigravida with Long QT syndrome (LQTS) and symptoms of recurrent syncope. She was diagnosed with beta-blocker and mexiletine hydrochloride and epidural analgesia was used to prevent tachycardia associated with labour pain. She gave birth to a female who was diagnosed with LQTS and KCNH2 mutation and at age of 27 she gave birth to another baby who was also diagnosed with type 2 LQTS and both were treated with beta-blocker and mexiletine.