Rare Gynecological Malignancy Research Articles

Significance of lymph node metastasis on survival of women with uterine adenosarcoma

ObjectiveUterine adenosarcoma (UAS) is a rare gynecologic malignancy and the significance of lymph node metastasis on survival has not been well studied. MethodsA retrospective study was performed utilizing the Surveillance, Epidemiology, End Results Program to examine UAS (n=994), endometrial stromal sarcoma (ESS, n=2910), and uterine leiomyosarcoma (LMS, n=5506) diagnosed between 1973 and 2013. The impact of lymph node metastasis on cause-specific survival (CSS) was cross-compared by multivariable analysis. Systematic literature review was conducted to examine the impact of nodal metastasis on progression-free survival (PFS) in UAS. ResultsUAS had the lowest incidence of lymph node metastasis among the sarcoma subtypes examined (UAS 2.9%, LMS 3.4%, and ESS 6.6%, P<0.001). Lymph node metastasis was independently associated with decreased CSS in all three tumor types (all, P<0.01); however, magnitudes of statistical significance of lymph node metastasis for CSS were similar across the three tumor types: adjusted-hazard ratio (aHR) for UAS 2.34, ESS 2.43, and LMS 2.10. Systematic literature review identified 230 unique cases of surgically treated UAS. On multivariable analysis, lymph node metastasis (aHR 4.72) had the greatest degree of significance for PFS compared to other tumor factors including sarcomatous overgrowth (aHR 2.88), heterologous elements (aHR 2.08), and deep myometrial invasion (aHR 1.51). Large tumor, deep myometrial invasion, and sarcomatous overgrowth were associated with increased risk of lymph node metastasis (all, P<0.05). ConclusionWhile uterine adenosarcoma had a low incidence of lymph node metastasis, the impact of lymph node metastasis on survival was comparable to ESS or LMS.

Primary Vaginal Melanoma, A Rare and Aggressive Entity. A Case Report and Review of the Literature

Primary malignant vaginal melanoma is a rare but aggressive melanoma that affects women in their 6th and 7th decade of life. The tumor appears as a dark node or spindle but can also be amelanotic. The size of the tumor is indicative of the prognostic factors. Surgery seems to be the only efficient treatment. Postoperative adjuvant therapy might help in preventing recurrence of the tumor. The survival rate is largely dependent on nodal and distant metastasis of the disease after initial tumor resection. There is a dire need to form a proper therapeutic regime to control this disease.

Vulvar Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is a rare gynecologic malignancy. Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)-dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up.

Ovarian Sex Cord-Stromal Tumors: The Challenge of Rare Gynecologic Malignancies.

Ovarian Sex Cord-Stromal Tumors: The Challenge of Rare Gynecologic Malignancies.

Carcinoma of The Fallopian Tubes A Rare Case Report And Revi ew of Literature.

Primary fallopian tube cancer (PFTC) is a rare gynecological malignancy and has similar clinical pr esentations like epithelial ovarian cancers (EOC).Treatment comprised multimodality approach using surgery, chemotherapy and radiotherapy. Surgery remains the mainstay of the treatment of PFTC. When considered inop erable neoadjuvant chemotherapy is used for down staging. Postoperative adjuvant chemotherapy improved loc al control in patients with adverse prognostic factors. Adjuvant radiotherapy improves outcome in patients with adverse factors.

Hormonal therapy of advanced or relapsed ovarian granulosa cell tumor

Ovarian granulosa cell tumor is a rare gynecologic malignancy with hormonal activity. Surgical excision is the standard treatment for this disease. Most patients present excellent short term prognosis, however, late relapse often occurs, even after many years. Viable treatments of advanced or relapsed granulosa cell tumor are still limited, and the optimal therapy method has not been established. Compared with chemotherapy and radiotherapy, hormonal therapy is a well-tolerated treatment which can be administrated over a long period of time without serious side effects, and the combined application of hormones may achieve a better outcome. Therefore, hormonal therapy has been suggested as a potential treatment option for patients with advanced or relapsed granulosa cell tumor, and to extend the tumor-free interval and attenuate the disease progression. Future researches should be focused on the identification of the hormonal therapy which may provide the greatest clinical benefit, comparing and analyzing the effects of different combined therapeutic regimens of hormone drugs, and on the synthesis of drugs highly activating estrogen receptor β expressed in the granulosa cell tumor cells.

HER2/neu, p53, MIB1 and PAX8 immunoexpression in Primary Serous Fallopian Tube Carcinomas

BackgroundCarcinoma of the fallopian tube is a rare gynecological malignancy. A previous review of Primary Fallopian Tube Carcinoma (PFTC) from a multi-institutional study identified several poor prognosis indicators, including the depth of invasion, advanced stage disease, tumor grade and the presence of lymph node metastases. The detection of the malignant lesion at an early stage and the identification of biomarkers with prognostic significance are the major concerns of recent studies. AimsIn this study, we have investigated the immunohistochemical expression of 4 proteins in cases of low-grade (n:5) and high-grade (n:65) serous PFTC to determine their role in PFTC prognosis. Material and methodsHER2/neu, p53, PAX8 and MIB-1 were evaluated using immunohistochemistry on a tissue microarray of 70 serous PFTC and the expression was correlated to the following clinico-pathologic variants: age, grade, lymph node metastases, stage and survival. ResultsHER2/neu oncoprotein overexpression was demonstrated in 20 of 65 (31%) high-grade serous fallopian tube carcinomas. p53 was demonstrated in more than 50% (3+) of the tumor in 59 (90.7%) high-grade serous FTCs, while eight cases (12%) were moderate or weakly positive (2+). The expression of PAX8 was positive in 55 (78.5%) cases, the remaining 15 (21%) cases being negative. The outcome of the disease for patients with tumors showing HER2/neu overexpression was worse (p:0.0001). p53, MIB-1 or PAX8 failed to have a predictive value in disease outcome. ConclusionThe potential prognostic relevance of HER2/neu in tubal cancer and its potential role in the selection of patients for targeted therapy should be investigated further.

The effect of distance traveled on disease outcomes in gestational trophoblastic neoplasia

Gestational trophoblastic neoplasia is a rare gynecological malignancy often treated at tertiary referral centers. Patients frequently travel long distances to obtain care for gestational trophoblastic neoplasia, which may affect cancer outcomes in these patients. We examined the association between distance traveled to obtain care and disease burden at time of presentation as well as recurrence. We performed a retrospective cohort analysis of all patients diagnosed with gestational trophoblastic neoplasia from January 1995 to June 2015 at a high-volume tertiary referral center. Patients were included if they met International Federation of Gynecologyand Obstetrics 2000 criteria for postmolar gestational trophoblastic neoplasia or had choriocarcinoma, placental-site trophoblastic tumor, or epithelioid trophoblastic tumor. Sixty patients were identified. Disease burden at presentation was examined using both the World Health Organization prognostic score and International Federation of Gynecology and Obstetrics. Patients who traveled more than 50 miles were considered long-distance travelers based on previous literature on the effect of distance traveled on cancer outcomes.Demographic, clinical, and pathological data were obtained by chart review. Bivariable comparisons were performed using the χ(2) test or Fisher exact test for categorical variables. The t test or Wilcoxon rank-sum test was used to compare continuous variables when normallyor not normally distributed. Most patients presented at stage I (61%) with low-risk gestational trophoblastic neoplasia (70%). Median distance to care was 40 miles (range, 4-384). Eighteen patients (30%) had no insurance and 42 (70%) had either private or public insurance. Patients traveling more than 50 miles for care were more likely to have high-risk gestational trophoblastic neoplasia (46% vs 19%, P= .03), but there was no differencein recurrence (13% vs 11%, P= .89). Patients with high-risk gestational trophoblastic neoplasia lived 63miles farther (92 vs 28 miles, P < .001) than patients with low-risk gestational trophoblastic neoplasia. Long-distance travelers had a longer period between antecedentpregnancy and gestational trophoblastic neoplasia diagnosis (10 weeks vs 4.5 weeks, P= .009) and were more likely to receive multiagent chemotherapy (86% vs 61%, P=.03). In this cohort, long distance traveled to obtain care for gestational trophoblastic neoplasia was associated with an increased risk of presenting with high-risk disease and requiring multiagent chemotherapy for treatment. Patients with high-risk gestational trophoblastic neoplasia traveled nearly 100 miles to obtain care. There may be a delay in diagnosis in women traveling more than 50 miles to obtain care; however, we found no difference in recurrence risk for long-distance travelers.

Primary mucinous adenocarcinoma of the vulva: A case report and review of the literature.

Primary vulvar cancer is a rare disease with an incidence of 2-3 per 100,000 women. The vast majority of vulvar carcinomas are of the squamous cell type (90%). Primary vulvar adenocarcinomas rank among the rare gynecological malignancies. We herein present a case of a vulvar mass near the vaginal orifice, the biopsy of which revealed a mucinous adenocarcinoma. Local excision was performed, followed by postoperative chemotherapy. The patient was asymptomatic and developed no recurrence during the 2 years of follow-up after surgery and chemotherapy. We consider local excision, with or without chemotherapy, to be an effective therapeutic approach to this type of tumor. However, further studies are required to support our conclusions for early-stage vulvar mucinous adenocarcinoma.

Genetic Investigation of Uterine Carcinosarcoma: Case Report and Cohort Analysis

Uterine carcinosarcoma, a rare gynecological malignancy, often presents at the advanced stage with a poor prognosis because current therapies have not improved rates of survival. Genetic characterization of this tumor may lead to novel, specifically targeted drug targets to provide better treatment options for patients with this malignancy. We present a case of a woman aged 61 years with uterine carcinosarcoma and retrospectively analyzed 100 study patients with uterine carcinosarcoma. From this group, 9 study patients underwent targeted sequencing of 1,321 genes. All 9 study patients had at least 1 mutation in JAK2, KRAS, PIK3CA, CTNNB1, PTEN, FBXW7, TP53, and ERBB2; of these, TP53 was the most frequently mutated gene (6/9). In addition, ARID1A and KMT2C, which have been described and identified as part of a set of chromatin-remodeling genes, were also found in our analyses. From our 100-person cohort clinical analyses, study patients with stage 1 cancer had a median survival rate of 33 months (95% confidence interval, 19-109) compared with a median survival rate of 6 months (95% confidence interval, 3-12) in those with stage 4 disease. Disease stage alone predicted the rate of clinical survival. Up to 50% in the study group were identified at having early stage disease (stage 1/2), indicating improved rates of overall detection compared with previously reported data. Our mutational analysis findings add to the number of tumors in which these mutations have been found and suggest that chromatin-remodeling dysregulation may play a role in the tumorigenesis of carcinosarcoma.

Anterior pelvic exenteration for pre-chemo-irradiated locally invasive vulvar cancer

Vulvar carcinomas are rare gynecologic malignancies. In cases presenting local invasion oncologic treatment such as chemo-irradiation might be performed. However complete remission is achieved in rare cases, most of the patients necessitating an aggressive surgical therapy such as pelvic exenteration. We present the case of a 78 year old patient who was diagnosed with a poorly differentiated squamous cell vulvar cancer with urethral invasion in whom a total vulvectomy en bloc with anterior pelvic exenteration, pelvic, para-aortic and inguinal lymph node dissection was performed.

Abstract POSTER-CTRL-1206: The mutational landscape of fallopian tube carcinoma

Abstract Fallopian tube (FT) carcinoma is a rare gynecological malignancy, whose incidence is most likely underestimated due to misdiagnoses as ovarian cancer. Recent advances in pathology with more thorough serial sectioning techniques have led to better identification. We undertook to define germline and somatic mutations in 98 FT carcinoma cases enrolled at diagnosis in IRB-approved studies at the University of Washington, excluding cases with carcinoma identified at the time of risk-reducing surgery. We sequenced DNA from blood and neoplastic tissue using BROCA, a targeted capture and massively parallel genomic sequencing approach that detects all classes of mutation in 64 genes. The fraction of all primary ovarian, peritoneal and FT carcinoma defined as a FT primary increased over time in our tissue bank: FT diagnoses accounted for 23% of cases in the past five years compared to 5% in the previous 10 years (p=0.002). Of 98 subjects with FT carcinoma, 32 (33%) had loss of function germline mutations in 9 genes. Mutations in BRCA1 were identified in 18 (19%), making up the largest number of germline mutations, and in BRCA2 in 4 (4%). Germline mutations were also identified in 6 other known breast and/or ovarian cancer susceptibility genes including 2 in BRIP1 (2%), 2 in CHECK2 (2%), and 1 each in BARD1, BLM, MRE11A, and ATM (1%). One mutation was found in the FA gene FANCL. Additionally, we found 1 mosaic mutations in TP53 (1%) and 2 in PPM1D (2%). Together germline and mosaic mutations were identified in 34 (35%) of cases. We sequenced neoplastic DNA with BROCA in 30 FT carcinomas and found 27 somatic mutations in TP53 (90%), 1 in PTEN (3%) and 1 in CHEK2 (3%). The germline mutation rate was higher in FT carcinoma compared to our previous studies in ovarian carcinoma (35% versus 22%), though the identified genes were similar. Recently identified ovarian cancer susceptibility genes such as BRIP1, BARD1, and PPM1D are also associated with hereditary fallopian tube cancer. Known breast cancer genes (i.e. CHEK2, MRE11A, ATM) and other cancer associated genes (BLM, FANCL) require further study to prove their association with FT or ovarian cancer risk. An increased pathological recognition of the FT as a primary site of disease is changing the relative distribution of FT, ovarian, and peritoneal carcinoma in some centers. Citation Format: M.I. Harrell, T. Walshb, K.J. Agnew, B. Norquist, M.K. Lee, S. Bernards, K.P. Pennington, E.M. Swisher. The mutational landscape of fallopian tube carcinoma [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-CTRL-1206.

Fallopian tube cancer incidentally diagnosed during laparoscopy for metastatic adenocarcinoma of unknown primary lesion

Abstract Primary fallopian tube cancer is a rare gynecological malignancy. We report a case of fallopian tube cancer that was incidentally diagnosed during laparoscopy for metastatic adenocarcinoma of unknown primary lesion. A 60-year-old woman had two intraperitoneal calcific masses, which a biopsy revealed to be a metastatic malignancy with an unknown primary site. She was asymptomatic, and the primary site was not identified in imaging evaluations such as transvaginal ultrasonography. A diagnostic laparoscopy was performed and revealed papillary tumor-like lesions in the right fallopian tube. The laparoscopy was immediately converted to laparotomy. Total hysterectomy, bilateral salpingo-oophorectomy, and an omentectomy were also performed. The histopathologic diagnosis was primary serous adenocarcinoma of the fallopian tube. The patient received adjuvant chemotherapy. At 8 months postoperatively, there were no signs of recurrence. In this patient, the diagnostic laparoscopy was more useful for detecting the primary small-volume fallopian tube cancer, compared with ultrasonography, computed tomography (CT), magnetic resonance imaging, and positron emission tomography–computed tomography (PET-CT). Laparoscopy may be a tool for revealing an obscure primary lesion in the abdominal cavity.

Identifying actionable mutations in uterine leiomyosarcoma.

5586 Background: Uterine leiomyosarcoma (uLMS) is a rare gynecologic malignancy affecting 2000 women annually in the United States. Little is known about the genomic basis of uLMS and there are no ...

Multimodal treatment with doxorubicin, cisplatin, and ifosfamide for the treatment of advanced or metastatic uterine leiomyosarcoma: a unicentric experience.

Uterine leiomyosarcoma (ULMS) is a rare gynecologic malignancy characterized by a poor prognosis due to a high rate of local and metastatic recurrences. Chemotherapy with doxorubicin or ifosfamide or both is associated with a 10% to 30% objective response rate. We report a monocentric experience with doxorubicin, cisplatin, and ifosfamide (API) combination in the setting of multimodal treatment of advanced or metastatic ULMS. This monocentric retrospective study included patients with metastatic or locally advanced ULMS with a physiological age younger than 65 years treated in first line with a multimodal aggressive approach with API chemotherapy. Treatment consisted of doxorubicin 50 mg/m2 d1, ifosfamide 3 g/m2 per day d1d2 plus mesna, cisplatin 75 mg/m2 d3, plus G-CSF; every 3 weeks up to 6 cycles. Surgery, radiation therapy, or radiofrequency ablation therapy of metastatic sites was associated whenever possible. Thirty-eight patients received API for metastatic or locally advanced ULMS. Median age was 51 years (40-64 years); 4 (11%) patients were treated for a locally advanced disease and 34 (89%) for metastatic disease. Sixteen patients responded (4 complete responses+12 partial responses) among 33 evaluable patients (objective response rate, 48%); 8 and 9 patients had, respectively, stable and progressive disease. Twelve patients had surgeries with 9 surgical complete responses and 3 surgical partial responses. Median progression-free and overall survival in the whole population were 9.8 and 27 months, respectively. Main grade 3-4 toxicities in 38 patients were neutropenia (74%), thrombocytopenia (60%), anemia (55%), fatigue (18%), and vomiting (13%). Febrile neutropenia was observed in 37% of patients. Despite the toxicity observed, API is an effective treatment which compares favorably with other first-line therapies for patients with metastatic or advanced ULMS.

Juvenile granulosa cell ovarian tumor- a rare presentation

Juvenile granulosa cell tumor is a rare gynecologic malignancy. A fourteen year old girl was brought to the emergency with acute abdominal pain with distension of abdomen and admitted in surgical unit, clinically suspected perforation of gut. Transabdominal ultrasonography revealed a right adenexal irregular mass with a moderate amount of ascitic fluid. On laparotomy, it was suspected malignant ovarian tumor stage Ic, and then ipsilateral salphingoophorectomy was done considering the age of the patient. It was juvenile Granulosa cell tumor which confirmed by histo-pathologically. The epidemiology, natural history, presentation, histological and imaging appearances, prognosis and treatment of this malignancy were reviewed. DOI: http://dx.doi.org/10.3329/mediscope.v1i1.21636 Mediscope Vol. 1, No. 1: 2014, Pages 36-39

Genetic and epigenetic variation in vulvar cancer: current research and future clinical practice.

Vulvar cancer is a relatively rare gynaecological malignancy, the treatment of which is associated with significant patient morbidity. With reports that the incidence of vulvar cancer is increasing, there is a rising need for improved preventive, diagnostic and therapeutic tools. Recent advances within genetics and epigenetics present possible approaches for addressing this need, by contributing to the clarification of the aetiology of this disease, identifying screening and drug targets and introducing the potential for personalised treatments. This paper reviews the genetic and epigenetic research undertaken to date within vulvar cancer, evaluates its potential for clinical application and identifies directions for future research.

Molecular mechanisms of endometrial stromal sarcoma and undifferentiated endometrial sarcoma as premises for new therapeutic strategies

Endometrial stromal sarcoma (ESS) and undifferentiated endometrial sarcoma (UES) are very rare gynecologic malignancies. Due to the rarity and heterogeneity of these tumors, little is known about their epidemiology, pathogenesis, and molecular pathology. Our previous studies have described deregulation of histone deacetylases expression in ESS/UES samples. Some of these enzymes can be inhibited by substances which are already approved for treatment of cutaneous T-cell lymphoma. On the basis of published data, they may also provide a therapeutic option for ESS/UES patients. Our review focuses on molecular mechanisms of ESS/UES. It describes various aspects with special emphasis on alteration of histone deacetylation and its possible relevance for novel therapies.

Management of squamous cell vulvar cancer: a review.

Squamous cell vulvar cancer is a rare gynecologic malignancy. Standard treatment for early stage disease consists of wide radical excision of the primary tumor with inguinal-femoral lymphadenectomy or sentinel lymph node mapping/biopsy. Because of the general paucity of patients with advanced vulvar cancer, there is no standard therapy for advanced disease and therefore treatment should be individualized. Intergroup trials are needed to clarify the value of chemoradiation, neoadjuvant chemotherapy and targeted therapy in patients with advanced squamous cell cancer of the vulva to identify modalities with the best therapeutic index and lowest morbidity.

Primary Fallopian-Tube Carcinoma

Background: Primary Fallopian tube carcinoma (PFTC) is a rare tumor in postmenopausal women, which clinically and histologically resembles surface epithelial ovarian carcinoma (SEOC). PFTC has a worse prognosis than SEOC as it is not routinely suspected; therefore, treatment may be delayed. Case: The case of a 48-year-old postmenopausal woman who presented with gradually increasing lower abdominal pain is reported. Ultrasound revealed a mass of left tubo-ovarian origin, with the possibility of an ovarian tumor. Results: Total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) was performed, and histologic findings established PFTC. The patient was followed-up for 2 years and remained free of disease. Conclusions: PFTC is a rare gynecologic malignancy. Histopathologic confirmation is mandatory for diagnosis and management of such patients of this condition. (J GYNECOL SURG 30:111)