Clinical Features of Borderline Ovarian Seromucinous Tumor.

BACKGROUND/AIM: Ovarian seromucinous tumor is a histological type of ovarian neoplasm. Although seromucinous borderline tumors (BSMT) are associated with endometriosis, the frequency of their occurrence is low, and many aspects of their behavior remain unclear. In this study, we aimed to clarify the clinicopathological factors of BSMT. PATIENTS AND METHODS: We retrospectively reviewed 32 patients with pathologically diagnosed BSMT who underwent surgery at Jikei University Hospital. The survey items were patient characteristics, such as age, initial symptoms, preoperative tumor markers, surgical procedure and stage of surgery, presence of endometriosis, and recurrence. RESULTS: The median age was 45 years. Lower abdominal pain was the most common chief complaint, about one-third of patients were asymptomatic; one-sixth were discovered during follow-up for endometriosis. The majority had a high serum CA19-9 level. Twenty-five patients (78.1%) had unilateral masses, whereas seven patients (21.9%) had bilateral masses. More than 90% of the cases had coexisting endometriosis histologically. Thirty cases (93.8%) were stage I, only two were stage II, and none were stage III or IV. Recurrence was observed in two cases: one was borderline malignant and the other was a carcinoma. CONCLUSION: BSMT is a rare form of borderline malignancy. Its preoperative diagnosis is often difficult because of various clinical findings, but a history of endometriosis and an elevated serum CA19-9 level may aid in some cases.

Paclitaxel sensitizes homologous recombination-proficient ovarian cancer cells to PARP inhibitor via the CDK1/BRCA1 pathway.

OBJECTIVE: An effective treatment strategy for epithelial ovarian cancer (EOC) with homologous recombination (HR)-proficient (HRP) phenotype has not been established, although poly (ADP-ribose) polymerase inhibitors (PARPi) impact the disease course with HR-deficient (HRD) phenotype. Here, we aimed to clarify the cellular effects of paclitaxel (PTX) on the DNA damage response and the therapeutic application of PTX with PARPi in HRP ovarian cancer. METHODS: Two models with different PTX dosing schedules were established in HRP ovarian cancer OVISE cells. Growth inhibition and HR activity were analyzed in these models with or without PARPi. BRCA1 phosphorylation status was examined in OVISE cells by inhibiting CDK1, which was reduced by PTX treatment. CDK1 expression was evaluated in EOC patients treated with PTX-based neoadjuvant chemotherapy. RESULTS: PTX suppressed CDK1 expression resulting in impaired BRCA1 phosphorylation in OVISE cells. The reduced CDK1 activity by PTX could decrease HR activity in response to DNA damage and therefore increase the sensitivity to PARPi. Immunohistochemistry showed that CDK1 expression was attenuated in samples collected after PTX-based chemotherapy compared to those collected before chemotherapy. The decrease in CDK1 expression was greater with dose-dense PTX schedule than with the conventional PTX schedule. CONCULSIONS: PTX could act synergistically with PARPi in HRP ovarian cancer cells, suggesting that the combination of PTX with PARPi may be a novel treatment strategy extending the utility of PARPi to EOC. Our findings provide cules for future translational clinical trials evaluating the efficacy of PTX in combination with PARPi in HRP ovarian cancer.

A case of relapsing aseptic meningitis under excellent tumor response to pembrolizumab in microsatellite instability-high recurrent endometrial cancer.

•This is the first report of aseptic meningitis due to immune checkpoint inhibitor treatment in endometrial cancer.•The meningitis was severe and relapsed multiple times unlike in other reported cases.•Oncologic outcome was excellent after overcoming this severe adverse event.

Interleukin-6 as an enhancer of anti-angiogenic therapy for ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with elevated interleukin-6 (IL-6) expression, resistance to chemotherapy, and increased mortality. Although bevacizumab (Bev) is a widely used anti-angiogenic agent for EOC, the efficacy of Bev and the role of IL-6 in modulating angiogenesis in OCCC are unknown. We performed tube formation assays using human umbilical vein endothelial cells (HUVEC) cultured in OCCC cell-conditioned medium and using cells directly co-cultured with OCCC cells. We observed that IL-6 inhibition significantly mitigated the ability of Bev to impede tube formation in both cases. Furthermore, IL-6 blockade disrupted the anti-angiogenic efficacy of Bev and its concomitant anti-tumor activity. In addition, IL-6 inhibition resulted in a significant increase in angiopoietin-1 (Ang1) secretion and decreased vascular endothelial growth factor (VEGF) expression. Clinical specimens also exhibited this reciprocal relationship between IL-6 and Ang1 expression. Finally, depletion of Ang1 abrogated the effects of IL-6 inhibition on Bev activity, demonstrating that IL-6 supports the anti-angiogenic activity of Bev by suppressing Ang1 expression and promoting dependence on VEGF for angiogenesis. Altogether, our data suggest that OCCC tumors with high IL-6 levels are candidates for Bev therapy.

Survival Following Chemotherapy in Ovarian Clear Cell Carcinoma Is Not Associated with Pathological Misclassification of Tumor Histotype.

PURPOSE: Although ovarian clear cell carcinomas (OCCC) are commonly resistant to platinum-based chemotherapy, good clinical outcomes are observed in a subset of patients. The explanation for this is unknown but may be due to misclassification of high-grade serous ovarian cancer (HGSOC) as OCCC or mixed histology. EXPERIMENTAL DESIGN: To discover potential biomarkers of survival benefit following platinum-based chemotherapy, we ascertained a cohort of 68 Japanese and Australian patients in whom progression-free survival (PFS) and overall survival (OS) could be assessed. We performed IHC reclassification of tumors, and targeted sequencing and immunohistochemistry of known driver genes. Exome sequencing was performed in 10 patients who had either unusually long survival (N = 5) or had a very short time to progression (N = 5). RESULTS: The majority of mixed OCCC (N = 6, 85.7%) and a small proportion of pure OCCC (N = 3, 4.9%) were reclassified as likely HGSOC. However, the PFS and OS of patients with misclassified samples were similar to that of patients with pathologically validated OCCC. Absent HNF1B expression was significantly correlated with longer PFS and OS (P = 0.0194 and 0.0395, respectively). Mutations in ARID1A, PIK3CA, PPP2R1A, and TP53 were frequent, but did not explain length of PFS and OS. An exploratory exome analysis of patients with favorable and unfavorable outcomes did not identify novel outcome-associated driver mutations. CONCLUSIONS: Survival benefit following chemotherapy in OCCC was not associated with pathological misclassification of tumor histotype. HNF1B loss may help identify the subset of patients with OCCC with a more favorable outcome.

Prognostic impact of interleukin-6 expression in stage I ovarian clear cell carcinoma.

OBJECTIVE: Ovarian clear cell carcinoma (OCCC) frequently presents at an early stage. In stage I OCCC, the prognosis differs according to substage. In particular, predictive biomarkers and new treatment strategies are needed for stage IC2/IC3 disease. We investigated tumor biology and prognostic factors for stage I OCCC from a clinicopathological perspective, including the expression of ARID1A and IL-6, which are considered critical for OCCC carcinogenesis. METHODS: A retrospective cohort study of 192 patients with stage I OCCC treated at a single institution was performed. We calculated overall survival (OS) with respect to 12 clinicopathological parameters that included the unique and diverse histological features of OCCC. RESULTS: The estimated 5-year OS rate in patients with all stage I OCCC was 88.9% during a median of 91months of follow-up. The multivariate analysis indicated that substage classification and IL-6 expression status were associated with poor OS (p=0.010 and p=0.027, respectively). Loss of ARID1A expression had no impact on survival; however, it was associated with substage (p=0.001), capsule rupture status (p=0.011), and ascites cytology (p=0.016). No clear association was found between ARID1A and IL-6 expressions. Histological findings, including the presence of endometriosis, adenofibroma, architectural pattern, and tumor cell type, showed no prognostic effects. CONCLUSIONS: Both substage classification and IL-6 expression status may be independent prognostic factors in stage I OCCC. Therefore, IL-6 molecular stratification may be crucial in optimizing therapeutic strategies for early stage OCCC to improve survival.

Stepwise increase of MIB-1 index in frequently relapsed malignant peritoneal mesothelioma.

We identified the stepwise increase of MIB-1 index in a long-surviving malignant peritoneal mesothelioma (MPM) patient with a history of frequent relapse. A 29-year-old Japanese woman showed upper abdominal induration with adnexal tumor. Imaging study with biochemical analyses strongly suggested peritoneal tumor. On primary surgery, all tumors were resected completely without any residual tumor. Histologically, the tumor was diagnosed as MPM, for which she received adjuvant chemotherapy containing platinum agent. Two years later, the tumor relapsed in her pelvic cavity, but was resected completely with hysterectomy and salpingo-oophorectomy. Histologically, the tumor was diagnosed as MPM relapse. She underwent intraperitoneal chemotherapy with cisplatin that achieved progression-free survival of 5 years. However, relapse was detected again in pelvic cavity without any dissemination in upper abdominal cavity. The tumors were completely removed and were revealed to be compatible with MPM. She received gemcitabine and carboplatin chemotherapy. However, 2 years later, the tumor relapsed again in left upper abdominal cavity, for which she wouldn't receive 4th treatment. To investigate the longevity of this patient in association with the histologic findings, the MIB-1 index was examined in the primary and relapse tumors. The rate of MIB-1 index positive cells was calculated by counting 500 cells. MIB-1 indices were 4.2 ± 1.1 (mean ± SE), 11.8 ± 2.3, and 37.3 ± 2.5 in primary, 1st- and 2nd-relapsed tumor, respectively, demonstrating stepwise increase of MIB-1 expression over the surviving time of more than 9 years. Increase in MIB-1 index was not associated with mitotic index but may be indicating drug sensitivity, resulting in >2-year progression-free interval in each relapse.

Ectopic pregnancy developing in a cyst of the canal of Nuck.

BACKGROUND: A cyst of the canal of Nuck is a rare cause of inguinal swelling in adult women. Ectopic pregnancies that implant to rare regions are sometimes challenging to diagnose. CASE: A 45-year-old woman presented with painful swelling in her right groin with a positive urine pregnancy test. Ultrasonography, magnetic resonance imaging, and the histopathologic result of dilation and curettage suggested ectopic pregnancy in the right inguinal canal. Exploratory laparotomy, extraction of the right inguinal mass lesion, and closure of the deep inguinal ring were performed. The mass lesion measured 4×3 cm, and the histopathologic finding revealed an unusual ectopic pregnancy in the cyst of the canal of Nuck. CONCLUSION: In women of reproductive age presenting with painful swelling of the groin, ectopic pregnancy in a cyst of the canal of Nuck should be ruled out.

Pemphigoid gestationis after spontaneous expulsion of a massive complete hydatidiform mole.

Pemphigoid gestationis (PG) is a rare, perinatal, autoimmune, and blistering dermatosis. Only few cases of PG involving hydatidiform moles have been reported. Complete hydatidiform moles are usually evacuated by dilatation and curettage. We report a patient with a massive complete hydatidiform mole that underwent spontaneous expulsion; she subsequently developed PG. A 19-year-old unmarried nulligravid woman was referred to our hospital following excessive vaginal bleeding after an uncertain amenorrheal period. The patient presented with preshock vital signs, severe anemia, and a positive urine pregnancy test. Imaging examinations revealed a massive intrauterine mass (19 × 15 × 10 cm), suggesting a complete hydatidiform mole. She was hospitalized and treated with blood transfusion. Sixteen hours after hospitalization, the massive molar mass underwent spontaneous expulsion and bleeding ceased. Three days after the expulsion, she developed pruritic skin lesions including papules, erythemas, and bullae, which spread over her entire body. Skin biopsy revealed PG and subepidermal blister formation and linear complement C3 deposition along the basement membrane zone, and the serum anti-BP180 antibody level was found to be high on measurement. She was effectively treated with 50 mg/day of oral prednisolone. Her skin lesions disappeared, leaving pigmentation.