Live births and maintenance with levonorgestrel IUD improve disease-free survival after fertility-sparing treatment of atypical hyperplasia and early endometrial cancer.

OBJECTIVE: Our objectives were to (1) compare different regimens of hormonal therapy (HT) in young women with atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC), (2) assess reproductive and oncologic outcomes and (3) explore possible predictors of complete response (CR) and disease free survival (DFS). METHODS: Reproductive age women with AEH and Grade 1-2 endometrioid EC with no or minimal myometrial invasion on MRI treated with different regimens of HT were prospectively analyzed. Treatment protocols included levonorgestrel intrauterine device (LNG IUD), gonadotropin-releasing hormone agonist (aGnRH) or high-dose oral medroxyprogesteron acetate (MPA) separately and in combinations. RESULTS: Total of 418 patients with AEH (n = 228) and EC (n = 190) aged 19-46 years received HT. Overall CR rate was 96% in AEH and 88% in EC patients (р < 0.001). None of the regimens used in AEH (LNG IUD + 2 D&C vs. LNG IUD + aGnRH vs. LNG IUD + 3 D&C) was found inferior to the others (CR of 98%, 95%, 100%, respectively, p > 0.05) except for MPA alone (CR 87%, р = 0.009). Out of four HT regimens used in EC LNG IUD + aGnRH+3 D&C was superior to all others (CR 96%, р = 0.026) where 2 D&Cs were performed or oral MPA was prescribed. The median follow-up for 339 patients was 33 months (range: 3-136), 68% of patients (n = 232) attempted conception, 38% (n = 89) of them used ART. The birth rate was 42% (n = 97). The rate of recurrence was 26% (50/196) in AEH group and 36% (51/143) in EC group (p = 0.05). Birth after treatment (HR = 0.24) or LNG IUD maintenance (HR = 0.18) were associated with superior DFS (p < 0.001 for both). ART use did not influence DFS. CONCLUSION: Hormonal therapy of AEH and early EC with LNG IUD is superior to MPA-containing regimens, however still carries high risk of recurrence. Post-treatment pregnancy rates are satisfactory and can be further improved by broader ART use which was proven safe. Initial diagnosis of AEH, post-treatment child birth and LNG IUD maintenance were associated with decreased rates of recurrence.

Non-Peutz-Jeghers syndrome associated ovarian sex cord tumor with annular tubules: a case report.

OBJECTIVE: Sex cord tumors with annular tubules (SCTAT) are a rare subtype of sex cord stromal tumor of the ovary. An evidence-based management plan with follow-up evaluations is difficult to outline because of the rarity of these tumors. We describe the case of a premenarcheal patient with a SCTAT. DESIGN: Case report. SETTING: The patient was encountered during routine patient care process. PATIENT(S): The patient presented with a pelvic mass and precocious puberty. Her condition was diagnosed as SCTAT. Her clinical presentation was consistent with an estrogen-secreting tumor, resulting in early menarche and premature breast development. Inhibin and estradiol levels were markedly elevated preoperatively and normalized 5 weeks after surgical removal of the tumor. The preoperative computed tomography scan demonstrated a 12-cm abdominopelvic mass, which appeared to be mostly cystic. INTERVENTION(S): The patient was treated surgically. She underwent laparotomy, right salpingo-oophorectomy, ipsilateral pelvic and paraaortic lymph node sampling, and partial omentectomy. Peritoneal biopsy samples were obtained from the abdomen and pelvis. MAIN OUTCOME MEASURE(S): The patient did well postoperatively. She is being observed with serial examinations and serum inhibin measurements. RESULT(S): Normalization of serum estradiol and inhibin along with cessation of menstruation were seen 5 weeks postoperatively, with persistence of morphologic signs of precocious puberty and advanced bone age at 11 months after the diagnosis. CONCLUSION(S): The diagnosis of SCTAT was established on final pathology examination based on morphologic features of the tumor microscopically and the marker expression profile on immunohistochemistry. Primary management was surgical.

Predictors of recurrence of ovarian granulosa cell tumors.

OBJECTIVE: The prognosis of granulosa cell tumors (GCTs) is overall favorable, but a proportion of patients will experience recurrence. We report one of the largest series of patients with GCT for whom clinical, morphologic, and immunohistochemical markers have been assessed for their roles as predictors of recurrence. METHODS: Patients with the diagnosis of GCT were identified at 2 hospitals from 1974 to 2004; a detailed chart analysis was performed. Tissue blocks were analyzed immunohistochemically for mitotic index, luteinization, inhibin staining, epidermal growth factor receptor, and Ki67 expression. Univariate and multivariate analyses were performed. RESULTS: Sixty-seven patients were identified. Follow-up data up to 30 years were available. The mean age at diagnosis was 48.1 years. Twenty-five patients experienced recurrence. A statistically significant correlation (P < 0.05) was observed for age at diagnosis, with earlier age being an adverse factor (43.6 vs 50.9, P < 0.01), and use of adjuvant chemotherapy postoperatively (24% vs 40% in the nonrecurrence group). Luteinization and the immunohistochemical markers, such as inhibin, Ki67, and epidermal growth factor receptor, seemed to significantly increase the risk of recurrence if expressed. A multivariate analysis model confirmed that younger age at diagnosis and higher expression of inhibin and Ki67 are significant risk factors of GCT recurrence. CONCLUSIONS: Identification of patients who are at a high risk for recurrence of GCT is critical. Routine treatment for all patients with cytotoxic chemotherapy is not justified. We report a set of predictors of recurrence for GCT that identified subsets of patients who may benefit from prolonged surveillance and/or adjuvant systemic chemotherapy.

Validation of serum biomarkers for detection of early-stage ovarian cancer.

OBJECTIVE: Ovarian cancer has the highest mortality of all the gynecologic malignancies with most patients diagnosed at late stages. Serum CA-125 is elevated in only half of patients with stages I-II. We identified 3 serum proteins (apolipoprotein A-1, transthyretin, and transferrin) for the detection of ovarian cancer and reported them combined with CA-125 to effectively detect early-stage mucinous tumors. The objectives of this study were to assess the effectiveness of the panel in detection of early-stage serous and endometrioid ovarian cancers. STUDY DESIGN: In all, 358 serum samples (control, benign adnexal masses, and early-stage and late-stage ovarian cancer) were obtained from the National Cancer Institute. The level of each marker was measured. Multiple logistic regression models were built to calculate sensitivity and specificity. RESULTS: When combined with CA-125, the panel detected early-stage cancer with a sensitivity of 96%. The highest sensitivity was seen for detection of endometrioid subtype of early-stage carcinomas (98%). CONCLUSION: A panel of 4 serum biomarkers effectively detected early-stage ovarian cancers with the highest reported overall sensitivity of 96%. Endometrioid tumors were detected at early stages with a sensitivity of 98%. Prospective clinical analysis of the panel is needed to validate it as an effective screening tool for early-stage ovarian cancer.