Transitional cell carcinoma of the ovary: A case–control study

Objectives

The aim of this study is to compare response to chemotherapy and survival between patients with transitional call carcinoma of the ovary (TCCO) and papillary serous ovarian cancer (PSOC).

Methods

We identified women with both pure and mixed TCCO who were treated between 2000 and 2010. Each case was matched to two women with PSOC by age, grade, stage, and year of diagnosis. Correlation between categorical variables was assessed with chi square test. The Kaplan–Meier survival analysis was used to generate overall survival data (OS). Factors predictive of outcome were compared using the log-rank test and Cox proportional hazards model.

Results

Eighty-one women diagnosed with TCCO were selected as cases and compared to 162 controls. Women with TCCO had a lower rate of platinum resistance compared to controls (9% vs. 25%; p = 0.01). When multivariate logistic regression was used to control for other factors independently associated with platinum resistance, patients with TCCO had a significantly lower risk of platinum resistance compared to PSOC. Median progression-free survival was not significantly different (27 months vs. 22 months; p = 0.15) for women with TCCO and PSOC, respectively. Median OS, however, was significantly different at 83 months vs. 52 months for the TCCO and PSOC groups, respectively (p = 0.01). A Cox proportional hazards model identified optimal cytoreduction, transitional cell histology, age, stage, and platinum and paclitaxel chemotherapy as independent predictors of OS.

Conclusions

Patients with TCCO are less likely to demonstrate resistance to platinum chemotherapy and have improved overall survival when compared to patients with PSOC.     

Sertoli–Leydig cell tumor presenting hyperestrogenism in a postmenopausal woman: A case report and review of the literature

ObjectiveSertoli–Leydig cell tumor (SLCT) accounts for <0.5% of all ovarian tumors, which is unusual in postmenopausal women. Postmenopausal women with SLCT usually become virilized. We report a postmenopausal woman with SLCT presenting with hyperestrogenism.Case ReportWe report a rare case of SLCT in a postmenopausal woman aged 61 years, who presented with postmenopausal bleeding, endometrial hyperplasia and mucous polyp, elevated estradiol, and decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) values, all suggesting hyperestrogenism. Transvaginal ultrasound revealed several small cyst locules, detected inside the right ovary, with a maximum diameter of 7 mm. The diagnosis was delayed because of the atypical clinical manifestation and negative serum tumor markers. The frozen section investigation revealed SLCT intraoperatively, which was confirmed by histopathological and immunocytochemical examination. The tumor was positive for inhibin-alpha, pancytokeratin, and p53 and in isolated tumor cells, positive for Ki-67.ConclusionThis case of SLCT suggests the existence of a new specific type of endocrine complex disease.     

Sertoli–Leydig cell tumor: A rare ovarian neoplasm. Case report and review of literature

Background.?Sertoli–Leydig cell tumor is a gonadal tumor of the sex cord–stromal type. It is a rare tumor comprising 0.1 to 0.5% of all ovarian tumors. Management of these cases poses a difficult therapeutic challenge.

Case.?A 13-year-old girl presented with acute urinary retention, excessive hair growth and deepening of the voice. A mass the size of a 28-week gravid uterus was arising from the pelvis. Serum testosterone level was raised to 145.2 ng/dl. Computed tomography revealed a heterogeneously hypoechoic, solid cystic mass arising from the left adnexa. Left salpingo-oophorectomy was done. A histopathological diagnosis of Sertoli–Leydig cell tumor (intermediate, Meyers type II) was given.

Conclusion.?Patients with Sertoli–Leydig cell tumors present with signs of defeminization followed by masculinization. Age of the patient, stage of the disease and degree of tumor differentiation based on morphology are the most important factors to consider in the management of the case.     

Germ cell tumors of the ovary: Is there a role for aggressive cytoreductive surgery for nondysgerminomatous tumors?

Abstract. Bafna UD, Umadevi K, Kumaran C, Nagarathna DS, Shashikala P, Tanseem R. Germ cell tumors of the ovary: Is there a role for aggressive cytoreductive surgery for nondysgerminomatous tumors?
Thirty-three patients with germ cell tumor of the ovary were seen at Kidwai Memorial Institute of Oncology (KMIO), Bangalore, between 1996 and 1999. Twelve patients had endodermal sinus tumor (EST), 11 dysgerminoma, seven mixed germ cell tumor, and three immature teratoma. Thirteen patients had bulky residual disease of>10 cm after the primary surgery. All but one patient received a combination of bleomycin, etoposide, and cisplatin (BEP) either as neoadjuvant (NACT, 3 cases) or as adjuvant therapy (28 cases). In the present study, all 11 patients with dysgerminoma achieved sustained complete remission (CR), irrespective of the size of residual disease at the time of chemotherapy. Four out of six cases (66.6%) with bulky nondysgerminomatous tumor achieved CR, which was sustained in three cases and one recurred. Fifteen of the remaining 16 (93.7%) nonbulky, nondysgerminomatous tumors achieved CR, which was sustained in 14 cases and recurred in one. This study indicates that there may be a role for aggressive cytoreductive surgery, either primary/interval or at the time of second-look laparotomy, in selected patients with nondysgerminomatous germ cell tumor of the ovary.     

Surgical margin status and recurrence pattern in invasive vulvar Paget’s disease: A Japanese Gynecologic Oncology Group study

ObjectiveTo examine the association between surgical margin status and recurrence pattern in invasive vulvar Paget’s disease.MethodsThis is a preplanned secondary analysis of a previously organized nationwide retrospective study in Japan (JGOG-1075S). Women with stage I-IV invasive vulvar Paget’s disease who received surgical treatment from 2001-2010 were examined (n=139). Multivariable analysis was performed to assess local-recurrence, distant-recurrence, and all-cause mortality based on surgical margin status.ResultsThe median age was 70 years. The majority had stage I disease (61.2%), and the median tumor size was 5.0cm. Nodal metastasis was observed in 15.1%. Simple vulvectomy (46.0%) was the most common surgery type followed by radical vulvectomy (28.1%). More than half received vulvar reconstructive surgery (59.0%). Positive surgical margin was observed in 35.3%, and close margin <1cm was observed in 29.5%. Vulvectomy type was not associated with surgical margin status (P=0.424). The median follow-up was 5.8 years. Positive surgical margin was associated with increased local-recurrence (5-year cumulative rates for positive versus negative margin: 35.8% versus 15.0%, P=0.010) but not distant-recurrence (18.3% versus 16.0%, P=0.567). Positive surgical margin was also associated with increased all-cause mortality (5-year overall survival rates for positive versus negative margin: 72.6% versus 88.2%, P=0.032). In multivariable analysis, positive surgical margin remained an independent factor associated with increased risk of local-recurrence (hazard ratio 2.80, 95% confidence interval 1.18-6.63) and all-cause mortality (hazard ratio 2.87, 95% confidence interval 1.20-6.83).ConclusionPositive surgical margin appears to be common in invasive vulvar Paget’s disease that is associated with increased local-recurrence and all-cause mortality risks. Role of alternative surgical technique or adjuvant therapy merits further investigation to improve local disease control.     

Malignant mixed müllerian tumors of the ovary

PURPOSE OF REVIEW: Müllerian mixed malignant tumors of the ovary constitute an infrequently encountered group of malignant ovarian neoplasms, which are highly aggressive and respond poorly to treatment. The relatively low number of reported cases and the difficulty of preoperative diagnosis make it difficult to ascertain the biology of these tumors. RECENT FINDINGS: These are mixed, mostly monoclonal tumors, and the predominance of the stromal component aggravates the prognosis. The clinical presentation of these tumors is similar to that of epithelial ovarian tumors, although they tend to manifest themselves at later stages of disease. There are no useful biochemical markers: imaging diagnostic methods (ultrasound, computed tomography, magnetic resonance imaging) do not provide specific data. The staging and primary treatment are always surgical. Survival improves when cytoreduction is satisfactory. Chemotherapy (platinum) can prolong survival, but there are no effective second-line treatments. Radiotherapy is of no help. The prognosis of this cancer is always guarded. Genetic and molecular techniques will be very important in advancing our knowledge of tumoral biology. In order to improve therapeutic results, it will be necessary to design multicenter, cooperative studies including larger numbers of patients. SUMMARY: In clinical practice, treatment options for these tumors are few; a rapid downhill course is the rule rather than the exception.     

Sertoli–Leydig cell tumor in a 12-year-old girl: a review article and case report

Background

The Sertoli and Leydig cell tumor is an unusual neoplasm that belongs to the sex cord-stromal tumors. Generally these tumors are associated with good prognosis. These tumors usually present virilizing symptoms such as oligomenorrhea or amenorrhea, hirsutism, voice raucity, laryngeal protuberance and clitoromegaly.

Case presentation

A 12 year old girl referred acute abdominal pain with no other clinical manifestations. An abdominal ultrasound showed a semisolid mass suggestive of ovarian tumor. The diagnosis was confirmed by a computed tomography. A unilateral salpingo oophorectomy was performed and the pathologist reported a Sertoli-Leydig tumor with intermediate differentiation. The outcome was excellent.

Conclusions

These tumors represent a rare condition in children. However, they can occur at any age, therefore it is important to acknowledge the clinical manifestations, diagnostic approach and therapeutic options. In this case the patient presented unusual symptoms which makes it more interesting.     

Virilising Sertoli–Leydig cell tumour associated with thyroid papillary carcinoma: case report and general considerations

We present a case of a Sertoli–Leydig cell tumour manifested with progressive hirsutism, frontal alopecia and secondary amenorrhea in a 46-years-old female, evolving for 6 years until presentation. Serum testosterone level was 8.01 ng/ml and gonadotropic hormones were LH 8.57 mIU/ml and FSH 9.52 mIU/ml. Computed tomography revealed a dense, solid, heterogeneous mass of 3.5/2.8?cm in the right ovary. Bilateral ovariectomy and hysterectomy were performed. The histopathological report mentioned a Sertoli-Leydig cell tumor with intermediate grade of differentiation. Immunohistochemical stains showed positive reaction for α-inhibin, calretin and for progesterone receptor. The testosterone levels dramatically decreased after surgery (0.31 ng/ml) while levels of gonadotropes increased: LH 40.98 mIU/ml and FSH 50.41 mIU/ml. At 6 months follow-up the diagnosis of a left lobe thyroid nodule leaded to fine needle aspiration biopsy with suspicion of papillary carcinoma. Total thyroidectomy established the diagnosis of thyroid papillary carcinoma (2.17/2.18?cm) T2N0M0, stage II, followed by radioiodine administration. This is to our knowledge the first presented case of ovarian Sertoli–Leydig cell tumour associated with papillary thyroid carcinoma. This could suggest a common genetic background.     

A phase II trial of intraperitoneal EGEN-001, an IL-12 plasmid formulated with PEG–PEI–cholesterol lipopolymer in the treatment of persistent or recurrent epithelial ovarian,fallopian tube or primary peritoneal cancer: A Gynecologic Oncology Group study

Objective

The purpose of this phase II trial was to evaluate the toxicity and antitumor activity of EGEN-001 in platinum resistant recurrent ovarian cancer.

Methods

Eligible patients had weekly IP infusion of EGEN-001 at a dose of 24 mg/m². Toxicity and antitumor activity were evaluated using CTCAE and RESIST criteria, respectively. Co-primary endpoints were tumor response and survival without progression (PFS) for at least 6 months. Survival without progression before going onto a subsequent therapy (EFS) for at least six months was also considered.

Results

A total of 58 EGEN-001 cycles were administered to 20/22 enrolled patients (median 2 cycles, range 1–9). The most frequently associated adverse events related specifically to EGEN-001 treatment were grade 1/2 fatigue, fever, chills, abdominal pain, nausea, vomiting, anemia, thrombocytopenia, and leukopenia. Three of 20 EGEN-001 treated patients evaluable for toxicity elected to withdraw from the study motivated in part by grade 1 treatment related toxicities. There were no patients with partial or complete response (0%; 90% CI 0–10.9%). Seven (35%) of 16 patients evaluable for response had stable disease, and 9 (45%) had progressive disease. Six (30%) patients had a PFS of greater than six months, although three had gone off study and onto other therapies before six months. The estimated six-month EFS was 15%. The median PFS and OS were 2.89 and 9.17 months, respectively.

Conclusion

EGEN-001 at the dose and schedule evaluated was associated with some but limited activity and was seemingly less tolerated in platinum resistant recurrent ovarian cancer patients.     

Granulosa cell tumors of the ovary: Do they have any unique ultrasonographic and color Doppler flow features?

Abstract. Sharony R, Aviram R, Fishman A, Cohen I, Altaras M, Beyth Y, Tepper R. Granulosa cell tumors of the ovary: Do they have any unique ultrasonographic and color Doppler flow features?
The aim of this study was to describe the ultrasonographic and Doppler flow attributes of granulosa cell tumors (GCT) of the ovary and to compare these attributes to those of epithelial tumors of the ovary. Among 13,475 gynecological patients who were scanned in our ultrasound unit between 1992 and 1996, seven patients had GCT. The final diagnosis was confirmed, postoperatively, by pathologic examination and by applying the WHO classification. The ultrasonographic findings of the GCT patients were compared to those recorded in a second group of 29 patients who had been diagnosed with epithelial tumor of the ovary. The sonographic appearance of GCT of the ovary was semi-solid and the endometrium was thick in six of the seven patients. Doppler flow studies of vessels within or in the contour of the lesions showed the resistive index (RI) to be 0.448 ± 0.018. The epithelial tumors had a similar appearance and flow pattern except for the presence of ascites in one-third of the patients. Ultrasound scanning, including color Doppler flow, did not contribute data that could assist in differentiating between GCT and epithelial tumors of the ovary.     

Are borderline tumors of the ovary safely treated by laparoscopy?

OBJECTIVES: To evaluate the risk of the laparoscopic approach to patients with borderline ovarian tumors compared to the laparotomic management. METHODS: We treated or followed in our institution 479 women with borderline ovarian tumor. Sixty-two patients had fertility-sparing surgery followed by restaging or follow-up intervention: 30 operated by laparoscopy, 32 by laparotomy. Restaging surgery was performed in five cases and second-look surgery in 57. RESULTS: The diameter of the cyst is significantly lower in patients treated by laparoscopy, especially in women who underwent cystectomy (4.7 cm) compared to oophorectomy (10 cm, P = 0.008). Rupture of the cyst and stage IC were more frequent in the laparoscopic group. After a median follow-up of 61 months for the laparoscopic group and 77 months for the laparotomic group, we observed 11 patients (37%) with persistent disease after primary laparoscopy (adnexa, five cases; peritoneal implants, three cases; both patterns, three cases). After primary laparotomy, no patients showed early persistence of tumor, and ovarian relapses were diagnosed in seven women (22%) 33-138 months after laparotomy. The univariate analysis for the risk of neoplastic persistence after primary laparoscopy shows that patients with cysts greater than 5 cm have a higher risk (odds ratio 9.7, P = 0.02) compared to smaller cysts. No other factors proved significant, but the odds ratios for patients with serous tumor (5.8), stage IC (2.0), and those undergoing cystectomy (1.9) suggest a relationship to the probability of persistence. CONCLUSION: Laparoscopic treatment in borderline ovarian tumors should be reserved to masses not greater than 5 cm. When conservative therapy is desired, the entire affected ovary should be removed. If the neoplasia is bilateral, cystectomy could be allowed in women who wish to preserve fertility, although they are at high risk of relapse.     

Chemotherapy for malignant mixed Müllerian tumors of the ovary

OBJECTIVE: The aim of this study was to review the chemotherapy experience at Magee-Womens Hospital for malignant mixed müllerian tumor (MMMT) of the ovary. Patients were treated with either paclitaxel/carboplatin (PC) outpatient chemotherapy or platinum/ifosfamide (PI) inpatient chemotherapy as first- or second-line therapy. METHODS: Thirteen patients diagnosed with MMMT of the ovary after complete surgical staging from 1990 to 1999 were studied retrospectively. Six patients received PC combination chemotherapy, of which 3 patients received PC as first-line treatment. The other 3 patients received PC as second-line therapy. Eight patients were treated with PI. Demographic data, pathology, cytoreductive surgery, treatment, and survival rates were reviewed. Complete clinical response (CR) was defined as the disappearance of all measurable disease or normalization of elevated CA 125 level after chemotherapy. Kaplan-Meier analysis was used for survival analysis. RESULTS: The median survival time of patients receiving PC was 19 months. One patient, after receiving PC as first-line treatment, demonstrated a CR and is free of disease beyond 33 months. The median survival time of patients managed with PI was 23 months. Three patients with suboptimal disease demonstrated CR after receiving PI. CONCLUSIONS: Optimal chemotherapy regimen for MMMT of ovary remains to be determined. Platinum-based chemotherapy in combination with ifosfamide or paclitaxel may be active against this rare malignancy.     

Should stage IIIC ovarian cancer be further stratified by intraperitoneal vs. retroperitoneal only disease?: a Gynecologic Oncology Group study

Objective

To examine whether clinical outcomes varied with intraperitoneal (IP) and/or retroperitoneal (RP) involvement in stage IIIC epithelial ovarian cancer (EOC) patients with microscopic residual disease after cytoreduction.

Methods

Retrospective review was performed for EOC patients enrolled in Gynecologic Oncology Group (GOG)-182 who underwent primary cytoreduction to microscopic residual disease. Patients were divided into 3 groups: stage IIIC by lymphadenopathy with < 2 cm IP spread (RP); > 2 cm IP spread and negative nodes (IP/RP−); and > 2 cm IP dissemination and positive lymphadenopathy (IP/RP+). Product-limit and multivariate proportional hazards modeling were used.

Results

Analyses included 417 stage IIIC women who underwent primary cytoreduction with lymphadenectomy to microscopic residual. There were 203, 123, and 91 in the RP, IP/RP−, and IP/RP+ groups, respectively. IP/RP+ and IP/RP− were associated with worse progression-free survival (PFS) (Hazard Ratio (HR) 1.68, 95% confidence interval (CI) 1.23-2.30; HR 1.38, 95% CI 1.04-1.84) vs. RP only. IP/RP+ was associated with worse overall survival (OS) (HR 1.79, 95% CI 1.24-2.57) while IP/RP− trended towards worse OS (HR 1.21, 95% CI 0.85-1.73) vs. RP only. Median PFS for IP/RP+ and IP/RP− groups was 21 and 29 months, respectively, vs. 48 months in the RP group (p = 0.0007) and median OS of 63 and 79 months vs. “not reached,” respectively (p = 0.0038).

Conclusions

Among EOC patients surgically cytoreduced to microscopic residual disease, those upstaged to IIIC by retroperitoneal involvement demonstrated significant improvement in PFS and OS compared to patients with intraperitoneal tumor, suggesting that these women may represent a unique subset of FIGO stage IIIC patients.     

Is bilateral lymphadenectomy for midline squamous carcinoma of the vulva always necessary? An analysis from Gynecologic Oncology Group (GOG) 173

ObjectiveTo determine which patients with near midline lesions may safely undergo unilateral groin dissection based on clinical exam and lymphoscintigraphy (LSG) results.MethodsPatients participating in GOG-173 underwent sentinel lymph node (SLN) localization with blue dye, and radiocolloid with optional LSG before definitive inguinal–femoral lymphadenectomy (LND). This analysis interrogates the reliability of LSG alone relative to primary tumor location in those patients who had an interpretable LSG and at least one SLN identified. Primary tumor location was categorized as lateral (> 2 cm from midline), midline, or lateral ambiguous (LA) if located within 2 cm, but not involving the midline.ResultsTwo-hundred-thirty-four patients met eligibility criteria. Sixty-four had lateral lesions, and underwent unilateral LND. All patients with LA (N = 65) and midline (N = 105) tumors underwent bilateral LND. Bilateral drainage by LSG was identified in 14/64 (22%) patients with lateral tumors, 38/65 (58%) with LA tumors and in 73/105 (70%) with midline tumors. At mapping, no SLNs were found in contralateral groins among those patients with LA and midline tumors who had unilateral-only LSGs. However, in these patients groin metastases were found in 4/32 patients with midline tumors undergoing contralateral dissection; none were found in 27 patients with LA tumors.ConclusionThe likelihood of detectable bilateral drainage using preoperative LSG decreases as a function of distance from midline. Patients with LA primaries and unilateral drainage on LSG may safely undergo unilateral SLN.