Preoperative Differentiation of Benign and Malignant Non-epithelial Ovarian Tumors: Clinical Features and Tumor Markers.

OBJECTIVE: To evaluate the role of clinical features and preoperative measurement of cancer antigen 125 (CA125), human epididymis protein (HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. METHODS: One hundred and nineteen consecutive women with germ cell, sex cord-stromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. RESULTS: Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, among malignant, four were immature teratomas. The most common tumors in the sex cord-stromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign and malignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. CONCLUSION: Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant cases were diagnosed at initial stages with good prognosis. The measurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

OBJETIVO: Avaliar o papel das características clínicas e a medida pré-operatória dos níveis séricos de CA125, HE4, e CEA em mulheres com tumores de ovário não epiteliais benignos e malignos. MéTODOS: Cento e dezenove mulheres consecutivas com tumores ovarianos de células germinativas, do cordão sexual-estroma, e miomas ovarianos foram incluídas neste estudo. Os níveis pré-operatórios dos biomarcadores foram medidos, a cirurgia e a análise histopatológica foram realizadas. Informações sobre tratamento e recorrência da doença foram obtidas dos prontuários médicos das pacientes. RESULTADOS: Nossa amostra incluiu 71 mulheres com tumores de células germinativas (64 benignos e 7 malignos), 46 com tumores do cordão sexual-estroma (32 benignos e 14 malignos), e 2 com leiomiomas ovarianos. Entre os tumores benignos de células germinativas, 63 eram teratomas maduros, e, entre os malignos, quatro eram teratomas imaturos. Os tumores mais comuns do grupo do cordão sexual-estroma foram fibromas (benignos) e tumores de células da granulosa (malignos). Os níveis séricos dos biomarcadores não diferiram entre os tumores de ovário não epiteliais benignos e malignos. A cirurgia preservadora de fertilidade foi realizada em 5 (71,4%) mulheres com tumores malignos de células germinativas. Onze (78,6%) mulheres com tumores do cordão sexual-estroma malignos foram tratadas com cirurgia preservadora de fertilidade. Cinco (71,4%) mulheres com células germinativas e apenas 1 (7,1%) com tumor do cordão sexual-estroma foram tratadas com quimioterapia. Uma mulher com tumor de células germinativas recidivou e morreu da doença. Uma mulher com tumor do cordão sexual-estroma recidivou. CONCLUSãO: Os tumores de ovário não epiteliais foram benignos na maioria dos casos e os malignos foram diagnosticados em estágios iniciais, com bom prognóstico. A medida dos níveis séricos de CA125, HE4, e CEA não foram úteis no diagnóstico pré-operatório desses tumores.

Preoperative differentiation of benign and malignant non-epithelial ovarian tumors: clinical features and tumor markers / Diferenciação pré-operatória de tumores ovarianos não epiteliais benignos e malignos: características clínicas e marcadores tumorais

Abstract Objective To evaluate the role of clinical features and preoperativemeasurement of cancer antigen 125 (CA125), human epididymis protein(HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. Methods One hundred and nineteen consecutive women with germ cell, sex cordstromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. Results Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, amongmalignant, fourwere immatureteratomas. Themost common tumors in the sex cordstromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign andmalignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. Conclusion Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant caseswere diagnosed at initial stages with good prognosis. Themeasurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

Resumo Objetivo Avaliar o papel das características clínicas e a medida pré-operatória dos níveis séricos de CA125, HE4, e CEA em mulheres com tumores de ovário não epiteliais benignos e malignos. Métodos Cento e dezenovemulheres consecutivas comtumores ovarianos de células germinativas, do cordão sexual-estroma, e miomas ovarianos foram incluídas neste estudo. Os níveis pré-operatórios dos biomarcadores foram medidos, a cirurgia e a análise histopatológica foram realizadas. Informações sobre tratamento e recorrência da doença foram obtidas dos prontuários médicos das pacientes. Resultados Nossa amostra incluiu 71 mulheres com tumores de células germinativas (64 benignos e 7 malignos), 46 com tumores do cordão sexual-estroma (32 benignos e 14 malignos), e 2 com leiomiomas ovarianos. Entre os tumores benignos de células germinativas, 63 eram teratomas maduros, e, entre os malignos, quatro eram teratomas imaturos. Os tumores mais comuns do grupo do cordão sexual-estroma foram fibromas (benignos) e tumores de células da granulosa (malignos). Os níveis séricos dos biomarcadores não diferiram entre os tumores de ovário não epiteliais benignos e malignos. A cirurgia preservadora de fertilidade foi realizada em 5 (71,4%) mulheres com tumores malignos de células germinativas. Onze (78,6%) mulheres com tumores do cordão sexual-estromamalignos foram tratadas comcirurgia preservadora de fertilidade. Cinco (71,4%)mulheres com células germinativas e apenas 1 (7,1%) com tumor do cordão sexual-estroma foram tratadas com quimioterapia. Uma mulher com tumor de células germinativas recidivou e morreu da doença. Uma mulher com tumor do cordão sexual-estroma recidivou. Conclusão Os tumores de ovário não epiteliais foram benignos namaioria dos casos e os malignos foram diagnosticados em estágios iniciais, com bom prognóstico. A medida dos níveis séricos de CA125, HE4, e CEA não foram úteis no diagnóstico préoperatório desses tumores.

Sclerosing stromal tumor of the ovary in a postmenopausal woman with estrogen excess: A case report.

RATIONALE: Sclerosing stromal tumor (SST) of the ovary is rare. We describe the first case of ovarian SST with estrogen excess with both clinical and serological evidence in a postmenopausal woman. PATIENT CONCERNS: A 70-year-old female who referred menopause 14 years ago was admitted with postmenopausal bleeding for 3 months. Ultrasonography revealed thickened endometrium of 6 mm and no adnexal masses. An elevated serum estradiol level of 49.78 ng/L was revealed in laboratory examination with normal ranges less than 27.25 ng/L in postmenopausal women. DIAGNOSES: The final histology diagnosis is SST of left ovary and endometrial hyperplasia with polyps. INTERVENTIONS: Laparoscopic hysterectomy and bilateral salpingo-oophorectomy were performed and a solid tumor with a diameter of 3 cm × 2 cm from the left ovary was found intraoperatively. OUTCOMES: Three days after removal of the tumor, the serum estrogen level was decreased to normal which indicated the estrogen activity of the tumor. LESSONS: To the best of our knowledge, it is the first reported case of ovarian SST with estrogen excess with both clinical and serological evidence. The present case illustrates the necessity to consider the rare possibility of ovarian SST as a cause for estrogen excess leading to postmenopausal bleeding. Hormonal evaluation (estrogens, androgens) should be considered in women with postmenopausal bleeding regardless of imaging examination.

Endocrinological characterization of an ovarian sex cord-stromal tumor with a Sertoli cell pattern in a Japanese Black cow.

A Japanese Black cow was evaluated for prolonged post-partum anestrus and enlargement of the right ovary. Transrectal ultrasonography revealed that the right ovary was markedly enlarged and had a solid appearance, while the left ovary was small and inactive. The presumptive diagnosis was directed towards granulosa-theca cell tumour (GTCT) which was supported by markedly elevated plasma anti-Müllerian hormone (AMH; 332.0 ng/ml), oestradiol (E2 ; 103.3 pg/ml) and immunoreactive inhibin (ir-INH; 2.1 ng/ml) in comparison with the diagnostic cut-off points for bovine GTCTs. Since the cow had been infertile and had swelling of the udder, slaughter was chosen. Histopathological examination revealed that the tumour was an ovarian sex cord-stromal tumour (SCST) with a Sertoli cell pattern. These findings suggest that plasma AMH, ir-INH and E2 could be possible biomarkers for bovine ovarian SCST with a Sertoli cell pattern, whereas this case could not be distinguished from GTCTs based on endocrinological profile.

Prognostic significance of elevated pre-treatment serum CA-125 levels in patients with stage I ovarian sex cord-stromal tumors.

OBJECTIVE: To investigate the prognostic significance of elevated pre-operative serum CA-125 values for patients with early stage ovarian sex cord - stromal tumors (SCSTs). METHODS: Patients diagnosed between 2004 and 2015 with a SCST were drawn from the U.S National Cancer Database. Those with stage I disease, and normal or elevated CA-125 values were selected for further analysis. Overall survival (OS) was evaluated for patients diagnosed between 2004 and 2014 with Kaplan-Meier curves, and compared with the log-rank test. A multivariate Cox analysis was performed to control for known confounders. RESULTS: A total of 1156 patients met the inclusion criteria; 486 (42%) had elevated pre-treatment CA-125 values. Patients with elevated pre-treatment CA-125 (n = 417) had worse OS compared to those with normal values (n = 588), p < 0.001 from log-rank test; 5-yr OS rates were 86.8% and 94.8% respectively. After controlling for patient age (<50 vs > = 50 yrs), the presence of medical co-morbidities, tumor histology (granulosa vs non-granulosa), size (<10 vs > = 10 cm vs unknown) and the performance of lymphadenectomy, elevated pre-treatment CA-125 levels were associated with a worse survival (HR: 1.80, 95% CI: 1.15, 2.82, p = 0.01). CONCLUSIONS: In a large cohort of patients with early stage SCSTs elevated preoperative CA-125 levels were associated with worse survival.

Ovarian steroid cell tumor, not otherwise specified.

Ovarian steroid cell tumours are rare virilizing tumours. They are three types of tumours of ovary which are characterized by steroid cell proliferation : Leydig cell tumour, steroid cell tumour, Not Otherwise Specified (NOS) and stromal luteoma. Here we present a case of 36 year old female, who presented with history of weight loss since last two and half months. There is history of amenorrhoea and hirsuitism. Her CA was 125: 11.4 IU/ml (0-35 U/mL). Blood Testosterone levels was elevated with value of 150 ng/ml (5.71-77 ng/ml). Serum Inhibin A, Inhibin B, FSH, LH and prolactin were within normal limits. The steroid cell tumour, NOS are mostly benign but few of them behave in malignant fashion. Hayes and Scully gave few histopathological features which favour malignant behavior. These tumours should be differentiated from leydig cell tumour by lack of cytoplasmic Reinkes' crystals as well as from other neoplasms like primary clear cell carcinoma, metastatic clear cell renal cell carcinoma and adrenocortical tumour.

Case report: an identical twin with Sertoli-Leydig cell tumor.

Our report details the workup and management of a 43-year-old woman with an identical twin who presented with 2 years of virilization and secondary amenorrhea. Serum total testosterone was elevated. An MRI did not identify adnexal or adrenal pathology. Subsequent ovarian vein sampling demonstrated unilateral testosterone elevation. The patient underwent laparoscopic unilateral oophorectomy resulting in the diagnosis of Sertoli-Leydig cell tumor (SLCT). Although SLCT is a rare sex-cord ovarian tumor, it is associated with endometrial hyperplasia and malignancy. Our goals are to review the workup of androgen-secreting tumors and discuss the clinical importance of the DICER1 mutation in the context of SLCT. In this case, an identical twin underwent DICER1 testing which was one of the essential steps in her clinical management.

A case of postmenopausal androgen excess.

Ovarian steroid cell tumors are very rare but potentially life-threatening neoplasms. They represent less than 0.1% of all ovarian tumors, typically present in premenopausal women and frequently manifest with virilization. Signs of hyperandrogenism may appear in postmenopausal women due to tumorοus and non-tumorοus adrenal and ovarian causes as well due to the normal aging process. In any case, steroid cell tumor should be suspected in postmenopausal women who present with rapid progressive androgen excess symptoms. This report describes a case of a 67-year-old postmenopausal woman with signs of hyperandrogenism, where an ovarian steroid cell tumor was diagnosed and treated by laparoscopic bilateral salpingo-oophorectomy and synchronous hysterectomy.

Ginandroblastoma multiloculado, negativo para CD99 en una niña de 12 años: caso clínico / A twelve-years-old girl with multiloculated gynandroblastoma CD99 negative. Case report

Los ginandroblastomas son tumores del ovario extremadamente raros, los cuales comparten componentes de células de la granulosa y de células de Sertoli/Leydig. Se describe un caso de una niña de 12 años, quien presenta hemorragia uterina anormal y sensación de masa intraabdominal de crecimiento progresivo asociado a menorragia, niveles de CA-125 en 60,4 UI/mL y estudios de extensión que reportan masa quística en ovario izquierdo, manejada con ooforectomía. El estudio anatomopatológico muestra un tumor multiloculado lleno de material seroso, abundantes cuerpos de Call-Exner y 45% de células de Sertoli/Leydig. La inmunohistoquímica reveló inmunorreactividad para inhibina, calretinina y pCK, mientras que los marcadores CD99 y AE1/AE3 fueron negativos. Se trata del primer reporte de caso sobre un ginandroblastoma multiloculado, negativo para CD99 en una niña de 12 años, estudio que plantea un abordaje sistemático para los tumores de las células de los cordones sexuales.

The ginandroblastoma is an extremely rare ovarian tumor which shows components of granulosa cells and Sertoli/Leydig cells. We describe a case of a twelve-years-old girl who presented abnormal uterine bleeding and progressively growing intra- abdominal mass associated with menorrhagia, CA-125 60.4 UI/mL and extension studies reporting cystic mass in the left ovary. She underwent oophorectomy. Pathological study shows a multilocular tumor filled with serous material. Many Call-Exner bodies were observed in the histopathological analysis, 45% of Sertoli/Leydig cells. Immunohistochemistry was reactive for inhibin, calretinin and pCK while AE1/AE3 and CD99 markers were negative. This is the first case report about a multiloculated gynandroblastoma, negative for CD99 in a 12-years-old girl. Thus, the study of this clinical case represents a systematic approach for tumors of the sex cord cells.

[A twelve-years-old girl with multiloculated gynandroblastoma CD99 negative: case report]. / Ginandroblastoma multiloculado, negativo para CD99 en una niña de 12 años: caso clínico.

The ginandroblastoma is an extremely rare ovarian tumor which shows components of granulosa cells and Sertoli/Leydig cells. We describe a case of a twelve-years-old girl who presented abnormal uterine bleeding and progressively growing intraabdominal mass associated with menorrhagia, CA-125 60.4 UI/mL and extension studies reporting cystic mass in the left ovary. She underwent oophorectomy. Pathological study shows a multilocular tumor filled with serous material. Many Call-Exner bodies were observed in the histopathological analysis, 45% of Sertoli/Leydig cells. Immunohistochemistry was reactive for inhibin, calretinin and pCK while AE1/AE3 and CD99 markers were negative. This is the first case report about a multiloculated gynandroblastoma, negative for CD99 in a 12-years-old girl. Thus, the study of this clinical case represents a systematic approach for tumors of the sex cord cells.

Steroid cell tumor of the ovary in a pregnant woman whose androgenic symptoms were masked by pregnancy.

INTRODUCTION: Ovarian steroid cell tumors are very rare sex cord-stromal tumors, and most of them are unilateral and almost one-third of the cases are malignant. CASE REPORT: Here, we present a pregnant woman, who diagnosed with steroid cell tumor of the ovary and underwent surgical staging. DISCUSSION: We will discuss the clinical presentation of the case, management options and follow-up strategies.

Ovarian masses in children and adolescents - an analysis of 521 clinical cases.

OBJECTIVE: To analyze the clinical characteristics of ovarian masses in children and adolescents. MATERIALS AND METHODS: We performed a retrospective analysis of patients less than 20 years of age who were treated at the Obstetrics and Gynecology Hospital of Fudan University between March 2003 and January 2012. Medical records were reviewed for age at operation, including presentation of symptoms and signs; the levels of tumor markers; imaging examinations; pathologic findings; the size of masses; treatment; and outcome. Data management and descriptive analyses were performed using SPSS 16.0. RESULTS: A total of 521 patients were included in this study. Among them, 92 had non-neoplastic lesions, 382 had benign neoplasms, and 47 had malignant tumors. The mean age of the patients was 16.3 ± 2.2 years. The primary presenting symptoms and signs were abdominal pain (39.5%), menstrual disorder (31.1%), abdominal swelling (5.4%), and an enlarged abdominal perimeter (3.3%). Malignant tumors tended to be larger than benign neoplasms (17.3 ± 8.6 cm vs 9.0 ± 5.7 cm; P = .000). There was no age difference between patients with benign neoplasms (16.3 ± 2.1 y) and those with malignant tumors (15.7 ± 2.5 y). The operations included salpingo-oophorectomy, ovarian cystectomy, and oophorectomy. Two patients with malignant tumors had bilateral salpingo-oophorectomy, and 2 patients who had tumor metastasis underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Forty-one cases of malignant tumors received postoperative chemotherapy. CONCLUSIONS: Germ cell tumors are the most common malignancy, and mature teratomas are the most common benign neoplasms in children and adolescents. Abdominal pain and menstrual disorder are the main reasons for doctor's visit. Although examination by ultrasound is the preferred auxiliary in the diagnosis of ovarian pathology, it could not distinguish between benign and malignant tumors. However, tumor size and tumor markers are helpful to identify the properties of masses. Surgery is usually better for treatment, and it is preferable to attempt conservative, fertility-sparing surgery in adolescents. Postoperative chemotherapy is necessary for malignant tumors.

Efficacy and safety of bevacizumab in recurrent sex cord-stromal ovarian tumors: results of a phase 2 trial of the Gynecologic Oncology Group.

BACKGROUND: The Gynecologic Oncology Group conducted this phase 2 trial to estimate the antitumor activity of bevacizumab and to determine the nature and degree of toxicity in patients with recurrent sex cord-stromal tumors of the ovary. METHODS: A prospective, multi-institutional cooperative group trial was performed in women with recurrent, measurable ovarian stromal tumors. Patients were allowed to have unlimited prior therapy, excluding bevacizumab. Bevacizumab 15 mg/kg was administered intravenously on day 1 of every 21-day cycle until patients developed disease progression or adverse effects that prohibited further treatment. The primary endpoint was the response rate (RR). Inhibin A and B levels were measured before each cycle, and the values were examined in relation to response and progression. RESULTS: Thirty-six patients were enrolled, and all were eligible and evaluable. Patients received a median of 9 cycles of treatment (range, 2-37 cycles). Six patients (16.7%) had partial responses (90% confidence interval, 7.5%-30.3%), 28 patients (77.8%) had stable disease, and 2 patients (5.6%) had progressive disease. This met the criterion for declaring the regimen active. The median progression-free survival was 9.3 months, and the median overall survival was not reached in during reporting period. Two grade 4 toxicities occurred, including hypertension and proteinuria; and the most common grade 3 toxicities were hypertension (n = 5) and pain (n = 5). Inhibin A and B values were lower in patients who responded to treatment. CONCLUSIONS: Bevacizumab has activity in the treatment of recurrent sex cord-stromal tumors of the ovary, and its toxicity is acceptable. Further investigation is warranted.

[Sclerosing stromal tumor of the ovary associated with a Meigs' syndrome and pregnancy: a case report]. / Tumor estromal esclerosante de ovário associado à síndrome de Meigs e gestação: relato de caso.

The sclerosing stromal tumor of the ovary is an extremely rare benign tumor more common in young women and without specific symptoms in most cases. Less than 150 cases have been described, of which 8 were diagnosed during pregnancy. In this report, we describe the association between sclerosing stromal tumor of the ovary, Meigs' syndrome and elevated levels of CA-125 in term pregnancy.

Tumor estromal esclerosante de ovário associado à síndrome de Meigs e gestação: relato de caso / Sclerosing stromal tumor of the ovary associated with a Meigs' syndrome and pregnancy: a case report

O tumor estromal esclerosante de ovário é uma neoplasia benigna extremamente rara, mais frequente em mulheres jovens e sem sintomas específicos na maioria dos casos. Menos de 150 casos foram descritos, dos quais 8 diagnosticados durante a gestação. Neste relato, documentamos a associação entre tumor estromal esclerosante de ovário, síndrome de Meigs e elevação dos níveis de CA-125 em gravidez a termo.

The sclerosing stromal tumor of the ovary is an extremely rare benign tumor more common in young women and without specific symptoms in most cases. Less than 150 cases have been described, of which 8 were diagnosed during pregnancy. In this report, we describe the association between sclerosing stromal tumor of the ovary, Meigs' syndrome and elevated levels of CA-125 in term pregnancy.

Estrogen-producing endometrioid adenocarcinoma resembling sex cord-stromal tumor of the ovary: a review of four postmenopausal cases.

The 4 present cases with endometrioid adenocarcinoma (EMA) of the ovary were characterized by estrogen overproduction and resemblance to sex cord-stromal tumor (SCST). The patients were all postmenopausal, at ages ranging from 60 to 79 years (av. 67.5), who complained of abdominal discomfort or distention and also atypical genital bleeding. Cytologically, maturation of the cervicovaginal squamous epithelium and active endometrial proliferation were detected. The serum estrogen (estradiol, E2) value was preoperatively found to be elevated, ranging from 48.7 to 83.0 pg/mL (av. 58.4). In contrast, follicle stimulating hormone was suppressed to below the normal value. MR imaging diagnoses included SCSTs such as granulosa cell tumor or thecoma for 3 cases because of predominantly solid growth, and epithelial malignancy for one case because of cystic and solid structure. Grossly, the solid part of 3 cases was homogeneously yellow in color. Histologically, varying amounts of tumor components were arranged in solid nests, hollow tubules, cord-like strands and cribriform-like nests in addition to the conventional EMA histology. In summary, postmenopausal ovarian solid tumors with the estrogenic manifestations tend to be preoperatively diagnosed as SCST. Due to this, in the histological diagnosis, this variant of ovarian EMA may be challenging and misdiagnosed as SCST because of its wide range in morphology.

Meigs' syndrome with elevated serum cancer antigen 125 levels in a case of ovarian sclerosing stromal tumor.

OBJECTIVE: Meigs' syndrome presenting as an ovarian tumor with elevated serum cancer antigen 125 (CA 125) levels is unusual. Only 37 cases have been reported, including three cases of ovarian sclerosing stromal tumor (SCT). Many reports have suggested that the presence of ascites is the major factor inducing mesothelial expression of CA 125. CASE REPORT: An 18-year-old woman presented with massive ascites, elevated serum CA 125 levels, and radiographic evidence of ovarian tumor. The histological and immunohistochemical examinations revealed a benign SCT. CONCLUSION: SCT is a benign ovarian tumor and complete excision is curative. We also review all 37 cases and discuss possible mechanisms of Meigs' syndrome and elevated serum CA 125 level.