Pathological variants in genes associated with disorders of sex development and central causes of hypogonadism in a whole-genome reference panel of 8380 Japanese individuals.

Disorders of sex development (DSD) comprises a congenital condition in which chromosomal, gonadal, or anatomical sex development is atypical. In this study, we screened for pathogenic variants in 32 genes associated with DSDs and central causes of hypogonadism (CHG) in a whole-genome reference panel including 8380 Japanese individuals constructed by Tohoku Medical Megabank Organization. Candidate pathogenic (P) or likely pathogenic (LP) variants were extracted from the ClinVar, InterVar, and Human Gene Mutation databases. Ninety-one candidate pathological variants were found in 25 genes; 28 novel candidate variants were identified. Nearly 1 in 40 (either ClinVar or InterVar P or LP) to 157 (both ClinVar and InterVar P or LP) individuals were found to be carriers of recessive DSD and CHG alleles. In these data, genes implicated in gonadal dysfunction did not show loss-of-function variants, with a relatively high tendency of intolerance for haploinsufficiency based on pLI and Episcore, both of which can be used for estimating haploinsufficiency. We report the types and frequencies of causative variants for DSD and CHG in the general Japanese population. This study furthers our understanding of the genetic causes and helps to refine genetic counseling of DSD and CHG.

Isolated torsion of the fallopian tube in a menopausal woman and a pre-pubertal girl: two case reports.

INTRODUCTION: Isolated torsion of the fallopian tube without an ovarian abnormality is an uncommon event, with an incidence of approximately 1 in 1,500,000 females. Isolated torsion of the fallopian tube occurs mostly in reproductive-aged women, and is thus extremely rare in menopausal women and pre-pubertal girls. CASE PRESENTATIONS: In case 1, 63-year-old Japanese woman presented with a 2-day history of acute lower abdominal pain. Menopause occurred at 53 years of age. Pelvic ultrasonography showed an enlarged mass (73 × 47 mm) on the right side of her uterus. An urgent laparoscopy was performed based on a presumptive diagnosis of right ovarian tumor torsion. During the laparoscopy, we noted a black, necrotic, solid tumor arising from the distal end of her right fimbria. Her right fallopian tube was twisted with the tumor, but her right ovary was normal and not involved. A laparoscopic tumorectomy with a right salpingectomy was performed. Her post-operative course was uneventful. In case 2, a 10-year-old Japanese girl presented with a 1-day history of lower abdominal pain associated with nausea and vomiting. Menarche had occurred 2 months earlier. A computed tomography and magnetic resonance imaging examination demonstrated a dilated tubal cystic mass with a normal uterus and bilateral ovaries. An urgent laparoscopy was performed based on a presumptive diagnosis of right fallopian tube torsion. During laparoscopy, her right fallopian tube was noted to be dark red, dilated, and twisted several times. Her right fimbria was necrotic-appearing and could not be preserved. Therefore, a laparoscopic right salpingectomy was performed. A histologic examination revealed ischemic changes with congestion of her right fallopian tube, which was consistent with tubal torsion. She had an uncomplicated post-operative course. CONCLUSION: We have presented two very rare cases of isolated fallopian tubal torsion. Radiologic interventions, such as computed tomography and magnetic resonance imaging, in addition to ultrasonography, are helpful diagnostic tools. Isolated torsion of the fallopian tube should be considered in the differential diagnosis of lower abdominal pain with a cystic mass and a normal ipsilateral ovary in all female patients, regardless of age.

Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.

INTRODUCTION: Solitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma. CASE PRESENTATION: A 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause. Seven years prior to her presentation, she was diagnosed with breast cancer and underwent a partial resection of her right breast for stage IIA invasive lobular carcinoma. She underwent adjuvant chemotherapy, radiotherapy, and five years of anastrozole hormonal therapy. She presented with a growing uterine mass. Her tumor marker levels were markedly increased over the course of her follow-up, but a systemic examination revealed only a solitary uterine tumor. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A histopathological examination, including detailed immunohistochemistry, confirmed metastatic invasive lobular carcinoma, infiltrating both her uterine myometrium and fibroid tissue. CONCLUSION: We report a very rare metastatic pattern of invasive lobular carcinoma and demonstrate that gross cystic disease fluid protein-15 and mammaglobin are useful in the diagnosis of metastatic breast cancer.

Spontaneous retroperitoneal hemorrhage caused by rupture of an ovarian artery aneurysm: a case report and review of the literature.

INTRODUCTION: Spontaneous rupture of an ovarian artery aneurysm is extremely rare. Although a majority of these cases have been associated with pregnancy, there have been recent reports and reviews of rare cases that were not directly associated with pregnancy. Transcatheter arterial embolization is considered to be an alternative therapy to surgery. CASE PRESENTATION: A 44-year-old Japanese woman, gravida 3 para 3, presented to our emergency room complaining of intermittent right flank pain. She had undergone a cesarean section 2 years previously, and had no history of abdominal trauma. On admission, her blood pressure was 115/78 mmHg, pulse 70 beats per minute, and hemoglobin concentration 9.8 g/dL. Abdominal ultrasonography and contrast-enhanced dynamic computed tomography revealed a large retroperitoneal hematoma. Findings on three-dimensional computed tomography angiography suggested ruptured aneurysm of her right ovarian artery. A selective right ovarian artery angiogram revealed a tortuous aneurysm. Transcatheter arterial embolization using N-butyl-2-cyanoacrylate was performed. The aneurysm was successfully embolized, and her course after embolization was uneventful. She has remained symptom-free during 3 months of follow-up. CONCLUSIONS: This was a very rare case of a patient who had a retroperitoneal hemorrhage originating from an ovarian artery aneurysm. A review of published case reports found that contrast-enhanced computed tomography with reconstruction images is an excellent imaging tool. Diagnostic angiography and subsequent transcatheter arterial embolization are thought to be very effective for this condition.