Harumi Saeki

FOXA1 expression and its association with mucin expression and KRAS mutation in ovarian mucinous tumors: implications for tumor progression and differentiation

This study aimed to investigate forkhead box A1 (FOXA1) expression in ovarian mucinous tumors and its association with mucin expression and KRAS mutation status to clarify its role in tumor progression and differentiation. We analyzed 57 normal tissues or benign ovarian lesions, 110 mucinous ovarian tumors, including mucinous carcinomas, and 214 other ovarian epithelial carcinomas using immunohistochemistry for FOXA1, MUC2, MUC5AC, and MUC6. We also performed KRAS mutation analysis. Strong nuclear staining of FOXA1 was observed in Walthard nests, Brenner tumors, and fallopian tube ciliated epithelium. FOXA1 expression was significantly associated with mucinous histology in ovarian epithelial carcinomas (P < 0.001). In mucinous tumors, FOXA1 was expressed in 73.6% of cystadenomas, 91.4% of borderline tumors, 100% of borderline tumors with intraepithelial carcinomas, and 87.5% of carcinomas. MUC2 expression progressively increased from mucinous cystadenomas to borderline tumors (P < 0.050) and significantly correlated with FOXA1 expression (P = 0.024). The prevalence of KRAS mutations also tended to increase with the malignancy of mucinous tumors (P < 0.050); however, KRAS mutations were significantly enriched in FOXA1-negative cystadenomas compared with FOXA1-positive cystadenomas (P < 0.050). A stepwise increase was noted in the percentage of both KRAS mutations and FOXA1 expression from cystadenoma to carcinoma. Mucinous ovarian tumors commonly express FOXA1. The co-occurrence of KRAS mutations and FOXA1 expression may be important for driving the progression and intestinal differentiation of mucinous ovarian tumors.

Mixed Mesonephric-like Adenocarcinoma, Clear Cell Carcinoma, and Endometrioid Carcinoma Arising from an Endometriotic Cyst

Mesonephric-like adenocarcinoma is a rare neoplasm of the uterine corpus and ovary. Unlike prototypical mesonephric adenocarcinoma of the uterine cervix, which is considered of Wolffian origin, recent evidence suggests that mesonephric-like adenocarcinoma is a Mullerian tumor associated with endometriosis. We report here on a 48-year-old woman with a mixed carcinoma of the ovary that consisted of mesonephric-like adenocarcinoma, clear cell carcinoma, and endometrioid carcinoma, arising from an endometriotic cyst. The mesonephric-like adenocarcinoma consisted of cuboidal cells with vesicular nuclei presenting with a tubular, ductal, papillary, and solid architecture forming nodules. Each component showed distinct immunophenotypes that were consistent with their morphology. The mesonephric-like adenocarcinoma showed diffuse positive staining for paired box 8 and GATA binding protein 3, and negative staining for estrogen and progesterone receptors. A p53 stain exhibited wild-type immunoreactivity. A complete loss of AT-rich interactive domain-containing protein 1A (ARID1A) expression was suggestive of an ARID1A mutation. Manual macrodissection and Sanger sequencing revealed identical KRAS and PIK3CA mutations in all three components. To the best of our knowledge, this is the first report of mesonephric-like adenocarcinoma combined with a clear cell carcinoma and endometrioid carcinoma, which supports the hypothesis that mesonephric-like adenocarcinoma is an endometriosis-associated neoplasm. The report also highlights a potential pitfall in diagnosing mesonephric-like adenocarcinoma combined with clear cell carcinoma.

A case of transient hyperthyroidism induced by placental site trophoblastic tumor

AbstractWe report a case of placental site trophoblastic tumor (PSTT) with transient hyperthyroidism. A 29‐year‐old gravida 2 para 2 woman presented with abnormal genital bleeding 6 months after delivery. Endometrial histology suggested PSTT. Serum human chorionic gonadotropin (hCG) was 117 mIU/mL and serum estradiol (E2) were 51 pg/mL. She reported increased appetite, sweating, fatigue, and 7‐kg weight loss within 3 months. Blood samples showed a thyroid‐stimulating hormone (TSH) level &lt;0.01 μIU/mL, FT3: 24.3 pg/mL, FT4: 5.3 ng/mL. The patient was diagnosed with hyperthyroidism. After thyroid function normalized, laparoscopic hysterectomy and bilateral salpingectomy were performed. Two years postsurgery, there was no recurrence, and thyroid function improved. The hCG produced from gestational trophoblastic disease has stronger TSH activity than that from gestational trophoblasts. However, in PSTT, the E2 level, which increases thyroid‐binding proteins and suppresses elevated thyroid hormone levels, is low and may induce hyperthyroidism. In cases of suspected PSTT, thyroid function should be evaluated when hyperthyroid symptoms are present.