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A large cell neuroendocrine carcinoma of the ovary is presented because of tubal metastases with peculiar growth patterns: pagetoid and serous tubal intraepithelial carcinoma-like. The possibility that a tubal intraepithelial carcinoma could represent a metastasis should be considered by pathologists.

Seromucinous carcinoma of the ovary was a newly defined category in the revised 2014 World Health Organization Classification of Tumors of Female Reproductive Organs. It was defined as a carcinoma composed of predominantly of serous and endocervical-type mucinous epithelium. Foci containing clear cells, and areas of endometrioid and squamous differentiation are not uncommon. It is a rare entity with morphologic and immunophenotypic features overlapping other types of ovarian carcinoma. There are different opinions as to whether it is a distinct entity or a histologic variant of well-established entities. Subsequent, to the writing of this manuscript the WHO 2020 reclassified this tumor as a type of endometrioid carcinoma. Here we present a case of seromucinous carcinoma of bilateral ovaries that had variable differentiation and morphology at different sites. Tumor in the fallopian tubes, ovarian surfaces, omentum, and peritoneal surfaces displayed predominant features of low-grade serous carcinoma, while the tumor in the ovaries had predominant mucinous carcinoma morphology with a confluent/expansile growth pattern. The mucosal involvement of the fallopian tubes morphologically mimicked serous tubal intraepithelial carcinoma., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Purpose: A prior history of breast cancer is a risk factor for the subsequent development of primary peritoneal, epithelial ovarian, and fallopian tubal (POFT) cancers. This study aimed to estimate the incidence of secondary POFT malignancy in breast cancer patients and the clinical outcomes of primary and secondary POFT cancer., Materials and Methods: We searched the Korea Central Cancer Registry to find patients with primary and secondary POFT cancer who had breast cancer in 1999-2017. The incidence rate and standardized incidence ratio were calculated. Additionally, we compared the overall survival of patients with primary and secondary POFT cancer., Results: Based on the age-standardized rate, the incidence of second primary POFT cancer after breast cancer was 0.0763 per 100,000 women, which increased in Korea between 1999 and 2017. Among the 30,366 POFT cancer patients, 25,721 were primary POFT cancer only, and 493 had secondary POFT cancer after a breast cancer diagnosis. Second primary POFT cancer patients were older at the time of diagnosis (55 vs. 53, p < 0.001) and had a larger proportion of serous histology (68.4% vs. 51.2%, p < 0.001) than patients with primary POFT. There were no differences between the two groups in tumor stage at diagnosis. The 5-year overall survival rates were 60.2% and 56.3% for primary and secondary POFT cancer, respectively (p=0.216)., Conclusion: The incidence of second primary POFT cancer after breast cancer increased in Korea between 1999 and 2017. Besides, second primary POFT cancer patients were diagnosed at older ages and had more serous histology.

Background: The role of nicotinamide N-methyltransferase (NNMT) in ovarian cancer is still elusive. Our aim is to explore the expression of NNMT in ovarian cancer and to assess its association with patient prognosis and treatment response., Methods: We first analyzed the differential expression of NNMT among fallopian tube epithelium, primary ovarian cancers, metastatic ovarian cancers, and recurrent ovarian cancers using Gene Expression Ominus (GEO) database (GSE10971, GSE30587, GSE44104 and TCGA datasets). Then, we assessed the association of NNMT expression with clinical and molecular parameters using CSIOVDB database and GSE28739 dataset. Next, we evaluate the association of NNMT expression with the prognosis of ovarian cancer patients in both GSE9891 dataset and TCGA dataset. Finally, GSE140082 dataset was used to explore the association of NNMT expression with bevacizumab response., Results: NNMT expression was significantly elevated in lymphovascular space invasion (LVSI)-positive ovarian cancers compared with that in LVSI-negative ovarian cancers (TCGA dataset, P < 0.05), Moreover, increased expression of NNMT was associated with increased tumor stage, grade, and mesenchymal molecular subtype (CSIOVDB database). Survival analysis indicated that increased expression of NNMT was associated with a reduced OS in both GSE9891 dataset (HR: 2.28, 95%CI: 1.51-3.43, Log-rank P < 0.001) and TCGA dataset (HR: 1.55, 95%CI: 1.02-2.36, Log-rank P = 0.039). Multivariate analysis further confirmed the negative impact of NNMT expression on OS in ovarian cancer patients in those two datasets. Furthermore, the NNMT-related nomogram showed that NNMT shared a larger contribution to OS, compared with debulking status. More interestingly, bevacizumab conferred significant improvements in OS for patients with low NNMT expression (HR: 0.56, 95%CI: 0.31-0.99, Log-rank P = 0.049). In contrast, patients with high NNMT expression didn't benefit from bevacizumab treatment significantly (HR: 0.85, 95%CI: 0.48-1.49, Log-rank P = 0.561). NNMT expression was positively correlated with the expression of genes, LDHA and PGAM1, involved in Warburg effect., Conclusions: In conclusion, NNMT expression is associated with the aggressive behavior of ovarian cancer, correlates with a poor prognosis, and is predictive of sensitivity to bevacizumab treatment.

We report a 55-yr-old woman who presented with bilateral ovarian masses, 11 yr after hysterectomy for superficially invasive stage IA1 cervical adenocarcinoma of usual (human papillomavirus-associated) type. The bilateral ovarian tumors were composed of glands lined by malignant mucinous epithelium and these tumors were metastases from her previous cervical adenocarcinoma, based on morphology, immunophenotype, and positive in situ hybridization for human papillomavirus. In addition, there was extensive involvement of the mucosa of the left fallopian tube by malignant mucinous epithelium. The patient is alive and well 2 yr after the ovarian recurrence. The phenomenon of minimally invasive cervical adenocarcinoma metastasizing to the ovary has been described previously; the extrauterine disease is typically limited to the ovaries and associated with a relatively favorable prognosis. The presence of fallopian tube involvement by cervical adenocarcinoma has rarely been reported, and suggests transtubal spread of tumor. Unique to this case is the >11 yr interval between diagnosis of the cervical and ovarian disease, with previously described cases showing up to a 7 yr latency period. This case demonstrates that spread of cervical adenocarcinoma to the ovaries, via the fallopian tube lumen, can occur after a very long latent period and this possibility must be considered when examining adnexal mass(es) in women who have previously had a hysterectomy for cervical adenocarcinoma.

This review discusses select fallopian tube entities and their associated mimics. It first focuses on adenomatoid tumors, the most common benign tumor of the fallopian tube. High-grade serous carcinoma and its precursor, serous tubal intraepithelial carcinoma, are then addressed. Finally, attention is turned to endometrioid proliferations of the fallopian tube. A diagnostic approach is provided for these lesions, with an emphasis on differential diagnoses and situations in which a benign lesion may appear malignant, and vice-versa., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Intraperitoneal drug delivery in first-line treatment of advanced ovarian cancer have been widely studied. After a complete primary surgery or with residual disease<1cm, intraperitoneal chemotherapy significantly improves disease-free and overall survival (NP1), but with more local and systemic toxicities. Whenever this therapeutic option is under consideration, the ratio efficacy/toxicity must be carefully discussed. Intraperitoneal chemotherapy has to be considered after complete or optimal primary surgery in ovarian, tubal or primitive peritoneal carcinomatosis FIGO IIIC. This treatment must be performed by trained teams and after an assessment of the ratio efficacy/toxicity. In one randomized study, hyperthermic intraperitoneal chemotherapy (HIPEC) using cisplatinum at interval surgery demonstrated an improvement in recurrence free and overall survival compared to surgery alone, in patients initially not resectable and with residual tumor less than 1cm (complete or optimal surgery) (NP1). HIPEC has to be considered after a complete or optimal interval surgery (residu<10mm) in patients with ovarian, tubal or primitive carcinomatosis FIGO IIIC, initially not resectable (Grade B)., (Copyright © 2019. Published by Elsevier Masson SAS.)

Although most female adnexal tumors of probable Wolffian origin have a benign biologic behavior, occasional cases have exhibited malignant potential. We encountered a 50-yr-old woman with an uncommon female adnexal tumors of probable Wolffian origin, which involved bilateral ovaries, invaded the ipsilateral fallopian tube, and extended to the uterine serosa. The initial histopathologic presentation caused significant confusion in pathologic diagnosis. Multiple differential diagnoses including ovarian endometrioid carcinoma, Sertoli cell tumor, and metastasis from nongynecologic organs were considered. After careful examination of the histologic findings and a thorough investigation with multiple immunohistochemical stains, the diagnosis was ultimately established. A literature review on female adnexal tumors of probable Wolffian origin including a malignant form is presented.

Cervical gastric-type adenocarcinomas are aggressive non-human papillomavirus-related carcinomas with a propensity for extracervical spread, including unusual sites such as the omentum, peritoneum, and ovary. We report 7 cases of cervical gastric-type adenocarcinoma with fallopian tube involvement predominantly in the form of mucosal colonization without underlying invasion. As far as we are aware, this has not been previously described and this report adds to the literature regarding metastatic neoplasms, which may exhibit tubal mucosal involvement and mimic an in situ lesion at this site. In all cases, there was associated ovarian involvement and in 6 of 7 cases, there was endometrial colonization. We speculate that the fallopian tube (and ovarian) involvement is secondary to transuterine spread. Given the occasional occurrence of multifocal gastric-type glandular lesions (benign or malignant) involving different sites in the female genital tract, we discuss the distinction between synchronous independent and metastatic lesions.

We present here the first-reported case of tubal metastasis from colorectal cancer diagnosed by a preoperative pelvic ultrasound. A 53-year-old woman suffering from vaginal discharge was referred to us 2 years after she underwent a partial colectomy for adenocarcinoma. The pelvic ultrasound examination revealed a right pelvic mass of 52 × 24 × 38 mm, independent of the right ovary, which was apparently unaffected. A right salpingo-oophorectomy was performed and the definitive histopathology examination showed a recurrence of the initial adenocarcinoma with a right tubal metastasis. The eventuality of such an unusual site of metastasis should be remembered.

Context: - Nonuterine high-grade serous carcinomas (HGSCs) are believed to arise most often from precursors in the fallopian tube referred to as serous tubal intraepithelial carcinomas (STICs). A designation of tubal origin has been suggested for all cases of nonuterine HGSC if a STIC is identified., Objective: - To highlight that many different types of nongynecologic and gynecologic carcinomas, including HGSC, can metastasize to the tubal mucosa and mimic de novo STIC., Data Sources: - A mini-review of several recently published studies that collectively examine STIC-like lesions of the fallopian tube., Conclusions: - The fallopian tube mucosa can be a site of metastasis from carcinomas arising elsewhere, and pathologists should exercise caution in diagnosing STIC without first considering the possibility of metastasis. Routinely used immunohistochemical stains can often be used to determine if a STIC-like lesion is tubal or nongynecologic in origin. In the context of uterine and nonuterine HGSC, STIC may represent a metastasis rather than the site of origin, particularly when widespread disease is present.

This study was aimed at investigating the clinicopathological characteristics of tubal metastases originating from primary endometrial, cervical, and nongynecological malignancies. We performed a 4-year retrospective study in which fallopian tube tissues obtained from 60 patients with tubal metastases were examined. In addition, we compared the number of tubal metastasis cases detected during periods of representative or whole tubal sampling. Twenty-three and 37 tubal metastases were found in cases examined after representative and whole tubal sampling techniques, respectively. Four cases of microscopic tubal metastases were detected via whole sampling, whereas no microscopic lesions were identified via representative sampling. The metastatic lesions originated from 14 uterine (10, endometrium; 4, cervix) and 46 nongynecological tumors (21, colon; 15, stomach; 5, biliary; 3, appendix; 2, breast). Tumors were most commonly involved in the muscle and lamina propria (n = 17). We noted distinctive histopathological features according to the extent of mural involvement: fibromyxoid stromal reaction and lymphohistiocytic infiltration in tumors involving the muscle and subepithelial connective tissue, architectural alterations of plicae in those involving the subepithelial connective tissue, and intraluminal mucinous and inflammatory exudate adjacent to intraepithelial tumors. We observed distinctive histopathological features associated with tubal metastases according to the extent of mural involvement. In addition, we demonstrated that the sampling method used in the routine microscopic examination of the fallopian tube affects the detection of tubal metastases. Our data support the notion that it is more logical to thoroughly sample both the fimbrial ends and the nonfimbriated portions of fallopian tubes for all salpingectomy specimens in the setting of cancer surgery.

Epithelial ovarian cancer (EOC) is the most common and lethal cancer-related death among females in the world. Asparaginyl endopeptidase (AEP) is a member of C13 family peptidases and expressed in the extracellular matrix and tumor cells. The aim of this article is to explore the function of asparaginyl endopeptidase in epithelial ovarian cancer. The expression of AEP was examined in 20 EOC samples, 3 EOC metastasis samples, 6 fallopian tube metastasis samples, 4 peritoneum metastasis samples and 20 benign ovarian tumor samples by immunohistochemistry. The expression of AEP was also evaluated in serum and ascites of EOC patients by elisa. And we used a lentiviral vector to overexpress AEP in human epithelial ovarian cancer cell lines SKOV3ip and detected the function of AEP-SKOV3ip cells both in vitro and in vivo. The growth of AEP-SKOV3ip cells was observed by MTT, migration and tube formation assays in vitro. Additionally, the subcutaneous mice model was used to identify the tumor growth and metastasis in vivo. Mice tumors were stained for CD31 to determine the microvessel density (MVD). We demonstrated that AEP was highly expressed in the EOC patient tissues and ascites. The AEP transfected SKOV3ip cells could both promote tumor growth in vitro and in vivo. The MVD in AEP-SKOV3ip group was higher than that in NC-SKOV3ip group. Therefore, our results demonstrated that AEP could induce EOC growth and progressionboth in vitro and in vivo.

We investigated the frequency, histopathologic, and immunohistochemical characteristics of tubal involvement in uterine serous carcinoma (USC) and aimed to clarify the relationship between "serous tubal intraepithelial carcinoma (STIC)" and USC in these cases. Cases of USC with complete tubal examination were prospectively collected and reviewed for the presence of tubal involvement. Immunohistochemical analysis for p53 and WT1 was performed on the endometrial and tubal tumor in cases with tubal involvement. Of 161 USC cases (pure USC or a component of a mixed carcinoma or a carcinosarcoma), 32 (20%) showed tubal involvement (unilateral: n=19; bilateral: n=13). The uterine tumors in cases with tubal involvement showed a trend toward increased likelihood of deep myometrial and lymphovascular invasion (LVI) compared with those without tubal involvement. The tubal fimbriae were involved in 15/32 cases. Tubal involvement was mucosal in 30/32 cases, mural in 14/32, serosal in 5/32, invasive in 22/32, and there was LVI in the tube in 13/32. STIC-like features were seen in 17/32 cases (7 as the only pattern of involvement, 9 with associated invasive carcinoma, and 5 with LVI). Immunostaining showed complete concordance of p53 and WT1 between the endometrial and tubal tumors in 26/32 cases, the majority being WT1 negative or only focally positive (19/26), and all exhibiting mutation-type p53 staining. On the basis of the histologic and immunohistochemical features, the tubal tumor was considered to represent metastatic USC in 26/32 cases, most likely metastatic USC in 2/32 cases, an independent tubal primary tumor in 3/32 cases, and to be of uncertain origin in the 1 remaining case. STIC-like lesions were considered to represent metastatic USC in 12/17 cases, most likely metastatic USC in 2/17 cases, an independent tubal primary in 2/17 cases, and of uncertain origin in the 1 remaining case. Tubal involvement, including STIC-like lesions, is seen in one fifth of USC when the tubes are examined in their entirety. The tubal involvement is metastatic in the vast majority of cases. Immunohistochemical studies assist, in most cases, in confirming the metastatic nature of the tubal disease. Consideration should be given to completely examining the fallopian tubes in apparent stage I or II USCs, as this will result in upstaging in a significant minority of cases.

Renal cell carcinoma (RCC), the most common type of kidney cancer in adult, rarely metastasizes to the ovary or fallopian tube, and most cases published in the literature were case reports. Herein, we describe the clinicopathological features of 9 cases of RCC metastatic to the ovary (n = 8) or the fallopian tube (n = 1). The patients' age at the onset of primary renal tumor was available in 8 patients, ranging from 37 to 73 years (mean, 51 years; median, 50 years). Ovarian metastasis was detected prior to or concurrently with the primary renal tumors in 3 patients, and after the diagnosis of renal tumors in 6 patients. The histotypes of the RCCs were clear cell (n = 7), chromophobe (n = 1), and unclassified (n = 1). Immunohistochemical stainings were performed on the sections containing metastatic tumors in 4 cases. Interestingly, pagetoid intraepithelial spread in the tubal mucosa was observed in the case of RCC metastatic to the fallopian tube. Among the 8 patients with follow-up data, 5 died of disease and 3 were alive with disease, with a follow-up period ranging from 3.7 months to 17 years (mean, 77 months; median, 53 months) after the diagnosis of primary kidney tumors. Diagnostically, metastatic RCC may mimic primary ovarian tumors clinically, morphologically, or immunophenotypically. Pathologists should also keep in mind that both ovarian and kidney tumors express PAX8 and PAX2, the markers commonly used to diagnose metastatic RCC. In addition, chromophobe RCC only rarely metastasizes, but it can be a diagnostic challenge when it metastasizes to the ovary., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Importance: High-grade serous carcinoma (HGSC) is the most prevalent and lethal form of ovarian cancer. HGSCs frequently arise in the distal fallopian tubes rather than the ovary, developing from small precursor lesions called serous tubal intraepithelial carcinomas (TICs, or more specifically, STICs). While STICs have been reported to harbor TP53 mutations, detailed molecular characterizations of these lesions are lacking., Observations: We performed targeted next-generation sequencing (NGS) on formalin-fixed, paraffin-embedded tissue from 4 women, 2 with HGSC and 2 with uterine endometrioid carcinoma (UEC) who were diagnosed as having synchronous STICs. We detected concordant mutations in both HGSCs with synchronous STICs, including TP53 mutations as well as assumed germline BRCA1/2 alterations, confirming a clonal association between these lesions. Next-generation sequencing confirmed the presence of a STIC clonally unrelated to 1 case of UEC, and NGS of the other tubal lesion diagnosed as a STIC unexpectedly supported the lesion as a micrometastasis from the associated UEC., Conclusions and Relevance: We demonstrate that targeted NGS can identify genetic alterations in minute lesions, such as TICs, and confirm TP53 mutations as early driving events for HGSC. Next-generation sequencing also demonstrated unexpected associations between presumed STICs and synchronous carcinomas, providing evidence that some TICs are actually metastases rather than HGSC precursors.

Cervical carcinoma infrequently involves the uterine corpus or adnexa. Metastatic adenocarcinoma (AC) to the ovaries can be difficult to distinguish from primary ovarian tumors, and metastatic squamous cell carcinoma (SCC) to these sites has not been well described. Our aim was to provide a detailed description of the morphologic patterns of adnexal and corpus involvement by cervical carcinoma. Cases were identified over a 15-yr period and the following features were recorded: visible lesion, depth of invasion, lymphovascular invasion, and patterns of spread. Only usual human papillomavirus-associated tumors were included. Twenty cases with available slides were identified (2 in situ and 8 invasive SCC; 10 AC); 17 had visible lesions, usually with deep cervical and lymphovascular invasion. Sixteen involved the corpus (1 in situ, 7 SCC, 8 AC), all colonizing endometrium and 10 invading myometrium. SCC involved the ovary and fallopian tube in 4 and 6 cases, respectively, whereas AC involved the ovary in 4 (2 unilateral, 2 bilateral) and the tube in 8 cases. SCC in the ovary usually showed parenchymal invasion, and parenchymal and mucosal involvement in the tube. AC in the ovary ranged from small nodules to confluent expansile growth, whereas in the tube it often showed mucosal colonization mimicking a primary tubal process. Adnexal metastasis of cervical carcinoma is rare and usually coexists with endometrial and myometrial extension from the cervix. Both squamous and ACs can colonize tubal and endometrial mucosa; AC in particular can mimic primaries at those sites. Bilaterality is not a common feature of metastatic endocervical AC.

Background: A patient with early-stage endometrial cancer may possibly have microscopic metastasis in the omentum, which is associated with a poor prognosis. The purpose of this study was to identify risk factors for microscopic omental metastasis in patients with clinical stage I endometrial cancer to establish the indications for selective omentectomy., Methods: We searched the PubMed, EMBASE, and Cochrane Library databases for published studies from inception to August 2014, using terms such as 'endometrial cancer' or 'uterine cancer' for disease, 'omentectomy' or 'omental biopsy' for intervention, and 'metastasis' for outcome. Two reviewers independently identified the studies that matched the selection criteria. We calculated the pooled risk ratios (RRs) with 95 % confidence intervals (CI) of each surgicopathologic finding for microscopic omental metastases in clinical stage I endometrial cancer. We also calculated the prevalence of microscopic omental metastases., Results: Among 1163 patients from ten studies, 22 cases (1.9 %) of microscopic omental metastases were found, which accounted for 26.5 % of all omental metastases. Positive lymph nodes (RR 8.71, 95 % CI 1.38-54.95), adnexal metastases (RR 16.76, 95 % CI 2.60-107.97), and appendiceal implants (RR 161.67, 95 % CI 5.16-5061.03) were highly associated with microscopic omental metastases., Conclusions: Microscopic omental metastases were not negligible in patients with clinical stage I endometrial cancer. Those with a risk factor of microscopic omental metastases were recommended for selective omentectomy.

Objective: To exclude minimal residual disease in remaining ovarian tissue after harvesting the ovarian cortex for cryopreservation, by means of a tailor-made approach., Design: Retrospective case series., Setting: Hospital laboratory., Patient(s): We evaluated the ovarian and tubal tissue from 47 cancer patients (breast cancer, [non-]Hodgkin lymphoma; osteo-, Ewing, myxoid lipo-, and oropharyngeal synovial sarcoma; cervical, rectal, and esophageal cancer), who had stored ovarian tissue for fertility preservation., Intervention(s): Immunohistochemistry (IHC) with tumor-related antibodies and genetic mutation analysis were performed to detect micrometastases by multiple sectioning at three levels of the paraffin-embedded formalin-fixed material. Molecular assays were performed with the use of tissue between these three levels of sectioning., Main Outcome Measure(s): Detection of micrometastases in ovaries., Result(s): We analyzed 847 ovarian slides to detect isolated tumor cells (ITCs) or micrometastases by IHC. In only one case (1/47) were ITCs detected in the fallopian tube. That patient had an intra-abdominal metastatic esophageal carcinoma. Additional DNA analyses of breast and rectal cancer, Ewing sarcoma, and human papilloma virus in cervical patients did not show evidence of micrometastases in the ovarian tissue., Conclusion(s): The tailor-made approach consisted of patient-specific tumor markers which were used to search for ovarian micrometastases. We found evidence of metastatic disease within the fallopian tube of a patient with intraperitoneal metastatic esophageal adenocarcinoma., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Recent progress in the understanding of the molecular events in ovarian cancer has prompted the need for a revised International Federation of Gynecology and Obstetrics (FIGO) staging system that may provide more accurate prognostic information and more specific guidance on personalized management of ovarian cancer than the older staging system that was last revised in 1988. In particular, it is now realized that cancer of ovary, fallopian tube, and peritoneum share similar molecular characteristics and should be considered collectively. With that, a new FIGO staging guideline for cancer of the ovary, fallopian tube, and peritoneum was approved by the FIGO executive board in October 2012 and published in the International Journal of Gynecology Obstetrics [2014; 124:1-5]. Several revisions have been made to the older staging system that needs to be elucidated so that accurate and appropriate patient care may be practiced., Recent Findings: The standardization of the staging system allows for a smoother transition of patient care between institutions and overall better communication and continuity of management., Summary: Our article briefly reviews and discusses the differences between the new and the old staging system of 1988.

Mucosal alterations of the fallopian tube are generally thought to represent alterations of the native tubal mucosal epithelium, whether benign or malignant. The current paradigm implicating the fallopian tube fimbriae as the origin of most pelvic high-grade serous carcinomas (HGSCs) is based on the premise that HGSC growing within the tubal mucosa originated there. This has fueled proposals to redefine classification rules for assigning the primary site of origin on the basis of the presence or absence of HGSC in the tubal mucosa. The corollary is that it is unlikely for metastatic carcinoma to grow within fallopian tube mucosa. Evidence to support or refute this corollary is minimal, in part because the fallopian tubes historically have been ignored. This study reports the pattern and topography of 100 nongynecologic cancers that metastasized to the fallopian tubes. Most tumors were adenocarcinoma (87%), and the remainder included lymphomas, neuroendocrine tumors, and mesotheliomas. The most common primary origins of tumor were the colon (35%) and breast (15%). Gross evidence of a tubal nodule or mass was only seen in 35% of cases. Ovarian metastases were present in 95% of cases, although 23% did not exhibit gross evidence of metastasis. Tumor involved the fimbriae in 49% of cases, including 10% of cases in which the tumor was restricted to the fimbriae without involving the nonfimbriated portion of the tube. The anatomic distribution of metastases included the tubal mucosa (29%), submucosa (43%), muscularis (54%), serosa (76%), lymphovascular spaces (38%), intraluminal space (16%), and mesonephric remnants (39%). The most common architectural pattern of mucosal growth was a flat layer (22/29 cases), followed by varying degrees of stratification, tufting, and papillary growth. High-grade atypia was present in 18/29 cases of mucosal growth, resulting in patterns that resembled primary tubal HGSC. Accompanying growth in the tubal submucosa frequently produced a pseudoinvasive pattern mimicking invasive tubal HGSC. Immunohistochemical expression of p53 by 8/18 high-grade mucosal metastases further contributed to the resemblance to primary tubal HGSC. Bland cytology was present in 11/29 cases of mucosal growth, some of which also exhibited mucinous features, resulting in patterns that resembled either tubal mucinous metaplasia or nonmucinous tubal hyperplasia. Although uncommon, it is possible for metastases of nongynecologic cancers to grow within the mucosa of the fallopian tube and create a potential diagnostic pitfall. Intramucosal growth of a tumor in the fallopian tube is not pathognomonic of a primary tubal origin of the tumor. These findings may carry implications for proposed criteria using the status of the fallopian tube mucosa to assign primary origin of a gynecologic cancer.

Recently there have been numerous advances in understanding the genetic basis of cancer which have resulted in more appropriate treatments. In this paper we describe the experience of the Burzynski Clinic, involved in treatment of numerous patients based on personalized approach using novel combinations for difficult-to-treat malignancies, with gynecological cancers. This retrospective study was conducted by extracting data from Burzynski Clinic's medical records and comprehensive review. Among the advanced refractory ovarian cancers cases (N=33), an objective response (OR) was found in 42.4%. We anticipate that with improved technology and novel therapeutics this rate will increase and adverse events will be reduced.

Aims:   To determine the frequency and distribution of Fallopian tube involvement in patients with ovarian metastases of non-gynaecological origin., Methods and Results:   All Fallopian tube tissue was processed for histological examination in a consecutive series of 31 patients with ovarian metastases of non-gynaecological origin. The most common primary sites were appendix (n = 10) colon (n = 7), stomach (n = 6) and breast (n = 4). Twenty cases (65%) showed at least one type of tubal spread. Mural involvement was most common (14 cases) but serosal, intra-vascular, intra-epithelial and intra-lumenal spread were also identified in 12, 9, 8 and 11 cases respectively. Intra-epithelial involvement was restricted to the fimbrial epithelium and mimicked tubal carcinoma in situ (CIS) architecturally. Pagetoid invasion was noted in two of the cases., Conclusions:   The Fallopian tubes are commonly involved in patients who have neoplasms metastatic to the ovaries. Metastases may show a CIS-like pattern of intra-epithelial spread and therefore small serous CIS-type lesions may not represent proof of tubal tumour origin in patients who have high-stage pelvic serous carcinomas. The frequency of intra-lumenal tumour cells supports transtubal spread as a likely mechanism for mucosal involvement by metastatic tumours involving the lower genital tract., (© 2012 Blackwell Publishing Ltd.)

Objective: Patients with ovarian cancer may have occult metastasis at the time of surgery. Our purpose was to determine the prevalence and sites of occult metastasis in epithelial ovarian cancer grossly confined to the ovary and examine the significance of routine omentectomy and peritoneal biopsies as part of a comprehensive staging procedure., Study Design: Data were retrospectively abstracted from patients presenting to University of Texas Southwestern Medical Center Hospitals from 1993 through 2009 with ovarian cancer without gross spread beyond the ovary who underwent comprehensive surgical staging., Results: A total of 86 patients with ovarian cancer grossly confined to the ovary who underwent complete surgical staging were identified. Of patients, 29% were upstaged following comprehensive surgical staging; 6% had metastatic disease in uterus and/or fallopian tubes, 6% in lymph nodes, and 17% in peritoneal, omental, or adhesion biopsies., Conclusion: Patients with epithelial ovarian cancer should continue to undergo comprehensive surgical staging, since it identifies occult metastasis in a significant number of patients., (Copyright © 2012 Mosby, Inc. All rights reserved.)

A 40-year-old woman, gravida 2, para 2, with squamous cell carcinoma of the cervix, stage IIB, underwent ovarian transposition. Bilateral salpingectomy was performed as part of the operative technique. Histopathologic analysis revealed mucosal spread of the tumor to one of the fallopian tubes. The patient underwent radiation of the ovaries in their new location in addition to standard chemoradiotherapy to the pelvis. There has been no evidence of disease for more than 5 years. Inasmuch as performance of bilateral salpingectomy in ovarian transposition is not standard practice, the finding of fallopian tube metastasis presented a dilemma to the clinician. It remains to be proved whether the finding of metastasis to the fallopian tubes can be evidence for ovarian metastasis in grossly normal-appearing ovaries to validate this practice. Literature review demonstrates that fallopian tube metastasis is usually associated with endometrial involvement., (Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.)

We report a 48-year-old woman presenting with gastric adenocarcinoma metastatic only to the left fallopian tube. In addition to invasive, poorly differentiated adenocarcinoma, there were areas simulating intraepithelial carcinoma, suggesting a primary fallopian tube lesion. The differential diagnosis included a metastatic process, based on unusual morphologic patterns with occasional signet-ring cells, single-cell linear pattern of infiltration, and abundant lymphvascular space invasion. Metastasis from an upper gastrointestinal primary was confirmed by immunostains (cytokeratin 7, CDX-2, and p53 positive in the tumor cells and cytokeratin 20, WT-1, estrogen, and progesterone receptors negative). Imaging studies and a posterior biopsy demonstrated primary gastric adenocarcinoma with similar histology and immunoprofile. We report an unusual case of primary gastric adenocarcinoma presenting only in the fallopian tube and discuss its mimics and differential diagnosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Ovarian squamous cell carcinoma is a rare malignancy and its occurrence is commonly attributed to malignant transformation of a pre-existing mature cystic teratoma. The de novo occurrence of primary squamous cell carcinoma is extremely rare. Malignant transformation in a mature cystic teratoma is almost always unilateral; however, there have been isolated reports of an uncomplicated mature cystic teratoma in the contralateral ovary. We report here a case of a 40-year-old woman presenting with squamous cell carcinoma of both ovaries with antecedent dermoid cyst in the left ovary, along with involvement of the fallopian tubes, cervix and omentum., (© 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.)

Objective: To determine the incidence of adnexal and lymph node (LN) metastasis in newly diagnosed endometrial stromal sarcoma (ESS)., Methods: We identified all cases with a diagnosis of ESS evaluated at our institution from January 1, 1980 to October 31, 2009. All uterine pathology was reviewed at our center. High-grade or undifferentiated tumors and ESS arising in extrauterine sites were excluded. Pertinent clinical data were abstracted from electronic medical records. Appropriate statistical tests were performed using SPSS16.0., Results: We identified 94 cases of ESS. LN metastasis was identified in 7 (19%) of 36 patients who underwent LN evaluation. Six of the 7 cases with LN metastasis had lymphovascular invasion (LVI). LVI status was not reported in the other case. Five of the 7 patients with LN metastasis had grossly positive LNs with or without other gross extrauterine disease. Of 20 patients with disease grossly limited to the uterus and grossly normal LNs, 2 (10%) had LN metastasis. Both of these cases had LVI and extensive myoinvasion. Eighty-seven cases (93%) underwent salpingo-oophorectomy. Adnexal metastasis was identified in 11 (13%) of 87 cases, all manifested by gross adnexal tumor and occurring in patients with other gross pelvic extrauterine disease., Conclusion: The incidence of LN metastasis in ESS is commonly associated with gross extrauterine disease, extensive myoinvasion, and LVI. Since myoinvasion and LVI status often are not assessable at the time of hysterectomy, LN dissection remains a reasonable option at primary surgery. The rate of adnexal metastasis appears to be negligible in the absence of gross adnexal and extrauterine tumor., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Although the majority of metastatic ovarian tumors arise within the female genital tract, squamous cell carcinoma of the cervix is a rare form of metastases to the bilateral ovaries by endometrial and transtubal spreading., Case: A 53-year-old woman was referred to the oncology clinic with postmenopausal bleeding. On vaginal examination, a 3 cm tumor arising from the cervix was inspected. Multiple cervical biopsies and endocervical curettage revealed large cell, non-keratinized squamous cell cervix carcinoma. Radical hysterectomy and bilateral salpingo-oophorectomy were performed. Bilateral pelvic and para-aortic lymph nodes were also removed. The final pathology report revealed endometrial, focal myometrial, bilateral tubal mucosal, fimbrial and bilateral ovarian squamous cell carcinoma involvement. Pelvic and para-aortic nodes were free from metastases., Conclusion: Although the incidence of ovarian metastases of adenocarcinoma of the cervix is significantly higher, squamous cell carcinoma may also metastasize to the ovaries by endometrial and transtubal spreading in the absence of lymph node involvement. Especially in young patients for whom preservation of the ovaries is supposed, gross intraoperative inspection of the radical hysterectomy specimen and endometrium should be done and ovaries should be evaluated carefully.

Interpretation of the mucinous change in the fallopian tubes has been difficult because several reports consider this mucinous change as a metastasis from a mucinous tumor. To clarify this issue, we decided to retrospectively review salpingectomies from 3 institutions looking for mucinous change in the fallopian tubes and documented the clinical history of these patients. Twenty-three cases of fallopian tubes with mucinous changes were found, including 11 patients without evidence of malignancy, 4 patients with mucinous ovarian tumors, 5 patients with nonmucinous gynecologic tumors, 2 patients with mucinous appendiceal neoplasm, and 1 patient with colon carcinoma. As mucinous changes are seen in several patients who do not have a malignant tumor, we believe that these changes represent a metaplastic process. The mucinous changes are frequently seen with chronic inflammation and/or other metaplastic changes and without cytologic evidence of malignancy.

Objective: Information sheet about metastatic tumors of the female genital tract., Design: Literature review with case reports., Setting: Department of Gynaecology and Obstetrics, Faculty of Medicine, Masaryk's University and Fakulty Hospital, Brno., Methods: Literature review about metastatic tumors of the female genital tract with illustrative case reports., Conclusions: Secondary gynecological malignant tumors are much less common than primary tumors of the female genital tract with the exception cancer of the fallopian tube and the vagina. Primary malignant tumors of the fallopian tube and the vagina are rare, the primary location of the tumor usually is in other areas of the female genital tract and the tumor grows directly into the above-mentioned organs secondarily. There is talking about metastatic malignant tumors of the female genital tract in the strict sense in the case of extragenital primary origin the cancer. Metastases can be caused by direct penetration of the tumor from anatomically adjacent organs, particularly from the bladder and the rectum, or are going through the lymph or the blood vessels. The most common primary location of the tumor are the breast, the stomach and the bowel in this case. Secondary laesions of the female genital tract can be sometimes the first clinical manifestation of the primary extragenital malignant tumor, simultaneously represent clearly negative prognostic factor for the disease. Differential diagnostic algorithm for solving the secondary laesions of the female genital tract requires a multidisciplinary approach and cooperation with the pathologist and the clinical oncologist. Surgical treatment, the indication and extent based on adequately performed staging, is essential for the diagnosis of the primary tumor and is necessary as the palliative treatment for the elimination event, clinical symptoms and for the improving quality of the life.

Lymph node involvement (LNI) in ovarian serous tumors of low malignant potential (OSLMP) upstages 22% of patients. The origin of LNI has been a subject of debate in the literature. The purpose of this study was to investigate the role of nodal endosalpingiosis in the pathogenesis of this entity. We first examined the frequency of nodal endosalpingiosis in 30 OSLMP cases, 30 cervical adenocarcinoma cases, and 30 endometrial endometrioid adenocarcinoma cases. The rate of nodal endosalpingiosis was significantly higher in OSLMP cases (33%) compared with both cervical (0%, P<0.0001) and endometrial tumor cases (3%, P=0.0015). We then compared the frequency of nodal endosalpingiosis in 36 cases of OSLMP with LNI and 36 cases of OSLMP without LNI. The rate of nodal endosalpingiosis was significantly higher in OSLMP with LNI (66%) than in OSLMP without LNI (14%, P<0.0001). We further investigated the cohort cases of OSLMP with LNI by recording the presence of nodal endosalpingiosis and LNI in each individual lymph node in every case. This analysis revealed that nodal endosalpingiosis and LNI appear together in the same lymph nodes at a much higher rate than would be expected by random chance alone (OR=71.2, P<0.0001). Lastly, in OSLMP cases with LNI, we recorded the types of LNI patterns. We found that the intraglandular pattern was present in a higher percentage of cases with nodal endosalpingiosis (50%) than in cases without nodal endosalpingiosis (8%, P=0.0253). Overall, the intraglandular pattern of LNI appeared in 36% of OSLMP cases with LNI. In this study, we show that nodal endosalpingiosis not only occurs more commonly in OSLMP compared with other Müllerian malignancies, but also in OSLMP with LNI compared with OSLMP without LNI. For the first time, we demonstrate a statistically significant association between endosalpingiosis and the intraglandular pattern of LNI, and we propose that in up to a third of patients with OSLMP and LNI, nodal foci of serous tumor of low malignant potential may derive independently, from nodal endosalpingiosis. This result contributes to the understanding of the pathogenesis of extraovarian disease in cases of OSLMP and has important implications for patient management and follow-up.

Objectives: The feasibility, safety, and preliminary efficacy of a second-line combination therapy for oral topotecan and pegylated liposomal doxorubicin in patients with platinum-resistant or refractory epithelial ovarian, peritoneal, or tubal carcinoma were investigated in this phase I trial., Methods: A fixed dose of oral topotecan 2.3 or 1.53 mg/m(2) on days 1 through 5 and escalating doses of pegylated liposomal doxorubicin on day 1 of a 28-day cycle were administered. Dose-limiting toxicities and maximum tolerated doses were recorded. Safety was assessed by adverse event monitoring, and complete and partial responses were recorded., Results: Twenty-two patients received a total of 61 courses of therapy. The maximum tolerated dose of combination therapy was 1.53 mg/m(2) of topotecan on days 1 through 5 and 40 mg/m(2) of pegylated liposomal doxorubicin on day 1 of a 28-day cycle. Because of cumulative thrombocytopenia, the dose of topotecan was decreased by one-third from 2.3 to 1.53 mg/m(2) in an effort to increase the dose of pegylated liposomal doxorubicin. Only 5 patients completed >4 cycles of therapy. The most common grade 4 adverse events at dose level 4 were neutropenia (5/9 patients) and leukopenia (2/9 patients). Overall responses were observed in 2 of 22 patients., Conclusions: Oral topotecan and pegylated liposomal doxorubicin can be combined at doses that are active as monotherapies. However, the overall response rates after monotherapy in patients with platinum-resistant ovarian cancer are comparable to or higher than those observed in this phase I study of combination therapy.

Objective: The clinical significance and optimal management of patients with stage IIIA endometrial cancer are controversial. We sought to determine whether recurrence and survival of patients with stage IIIA endometrial cancer differ with surgical pathologic findings (positive peritoneal cytology versus positive adnexae or serosa) and adjuvant treatment., Methods: Retrospective single institution analysis of patients surgically staged for IIIA endometrial cancer at Duke University Medical Center from 1973 to 2002. Stage IIIA patients were stratified into positive cytology alone (group IIIA1, n=37) and positive adnexae or uterine serosa (group IIIA2, n=20). Comparison was made with previously reported group of 467 patients with surgical stage I/II disease. Recurrence and survival were analyzed using Kaplan-Meier estimations and Cox proportional hazards model., Results: Mean age of 57 patients with stage IIIA endometrial cancer was 63. Adjuvant therapies were administered to 89% patients (74% radiotherapy, 4% chemotherapy, 19% progestins). Five-year overall (OS) and recurrence-free disease-specific survival (RFDSS) were 64% and 76%, respectively. Survival was similar comparing IIIA1 (62%) and IIIA2 (68%, p=0.999). RFDSS by adjuvant therapy was: external beam radiotherapy 89% (n=10), intraperitoneal P32 84% (n=21), progestins 78% (n=9), none 75% (n=6). 61% recurrences included extrapelvic component. In multivariable analysis of stage I-IIIA patients (n=517), positive cytology but not adnexal/serosal metastasis was predictive of death (HR 1.70, 95% CI 1.06-2.73) and disease recurrence (HR 1.70, 95% CI 1.07-2.71)., Conclusion: Among patients with stage IIIA endometrial cancer, metastasis to adnexae or serosa does not appear to confer worse prognosis than positive cytology alone. Positive cytology is an independent predictor of prognosis among patients with stage I-IIIA endometrial cancer. While optimal adjuvant therapy for these groups remains unclear, recurrence patterns suggest that systemic therapies are appropriate.

Most endometrial carcinomas metastasize by invading myometrial lymphatics and spreading to regional lymph nodes. However, uterine serous carcinomas (USCs) metastasize frequently to peritoneal surfaces even when only minimally invasive. This study examines the methods of spread and the role of retrograde transtubal spread. Eighty-seven USCs treated by hysterectomy were identified. Primary peritoneal cases and cases with significant ovarian involvement were excluded. Eighty (92%) cases were pure serous, and the remainder had at least 25% serous histology. Fifty-four of 87 (62%) had extrauterine spread at hysterectomy, most commonly to peritoneal surfaces and sometimes to the pelvic lymph nodes. Twenty-six of 54 (48%) cases had no lymphatic/vascular (LV) invasion and 18/54 (33%) had no myometrial invasion. Eleven of these 54 (20%) patients with metastases lacked both myometrial and LV invasion, and the metastases involved the peritoneal surface more often than the lymph nodes (p<0.001). Three of the 11 cases had tumor clusters in the fallopian tube lumen. Another 13 cases also had clusters of tumor within the fallopian tube lumen, and all 16 cases had peritoneal spread (p<0.001). Extrauterine spread correlated highly with LV invasion (p<0.001) but not with the presence or depth of myometrial invasion. Retrograde transtubal implantation as well LV invasion are two important mechanisms by which USC spreads; all cases with tumor clusters in the fallopian tube lumen had peritoneal spread. This explains the phenomenon whereby patients with serous carcinomas confined to the endometrium and lacking LV invasion have widespread metastases to the peritoneum.

Background: Mesonephric adenocarcinoma of the vagina is exceedingly rare, with only one well-documented case in the literature. Little is known regarding clinical presentation, pathological characteristics, therapy, or prognosis of the vaginal mesonephric adenocarcinoma., Case: A 55-year-old woman presented with a polypoid mass at the right vaginal apex, extending to the right paravaginal tissue. The tumor was an adenocarcinoma with ductal and tubular pattern arising in a background of mesonephric remnants. Tumor cells showed immunoreactivity for pankeratin, epithelial membrane antigen (EMA), and calretinin. The right fallopian tube and one paravaginal lymph node were positive for metastases. The patient is disease-free 3 years after surgery, radiation therapy, and chemotherapy., Conclusion: We report the second case of mesonephric adenocarcinoma of the vagina with metastasis to the right fallopian tube and to one paravaginal lymph node.

A 76-year-old woman underwent surgery for pelvic mass, during which a 13 x 8-cm right ovarian tumor was discovered. On histopathological examination, she was diagnosed with an endodermal sinus tumor with right tubal metastasis. The patient was treated with four cycles of Bleomycin, Etoposide and Cisplatin. She died of disseminated disease four years later.

We report a malignant uterine paraganglioma in a 41-year-old woman who underwent a hysterectomy for meno-metrorrhagia. It was initially thought to be a leiomyoma in necrobiosis. The clinical outcome was characterized by an early regional recurrence (in the left Fallopian tube). Later, vertebral and lung metastasis occurred, leading to death 22 months after the initial diagnosis. Paragangliomas are uncommon neuroendocrine tumors, related to pheochromocytomas. They are mainly found in the para-aortic and retroperitoneal region, and less commonly in the pelvic area. Location in the uterus is extremely rare: 5 cases were previously reported and only one malignant.

A 55-year-old woman, who was found to have malignant squamous cells on a routine cervical smear, underwent a conization biopsy, followed by hysterectomy with bilateral salpingo-oophorectomy. No gross tumor was present in the uterus, but both ovaries, which were of normal size, contained multiple cysts filled with light brown, soft material. Microscopic examination showed squamous cell carcinoma in situ of the cervix with contiguous spread to the endometrium, fallopian tubes, and ovaries; squamous cell carcinoma extensively replaced the endometrial and tubal epithelium, focally invaded the wall of the fallopian tubes, and involved the parenchyma of both ovaries. Although an invasive cervical carcinoma occasionally spreads to the ovary, this case illustrates that exceptionally an in situ tumor spreads along the epithelium of the upper genital tract and the ovarian surface and invades the ovary and tubes. The detection of human papillomavirus DNA in the cervical, endometrial, tubal, and ovarian tumors by the polymerase chain reaction suggests a role for human papilloma virus infection in this case.

Radiation myelopathy is a severe consequence of radiation to the spinal cord which rarely occurs with standard doses of radiation. This entity commonly results in different degrees of sensory and motor deficits. Diagnosis of radiation myelopathy in women with gynecologic malignancies may increase with the concomitant use of chemotherapy and radiation therapy. This paper reports the effect of this combination therapy in a 60-year-old woman with fallopian tube carcinoma.

431 cone biopsy specimens referred for CIN2 and CIN3 between 1984 and 1993 were reviewed with a peculiar attention paid to the possible associated endocervical glandular changes. The following features could be demonstrated: microglandular hyperplasia (17 cases), tubal metaplasia (15 cases), mesonephric hyperplasia (10 cases), in situ adenocarcinoma (7 cases), tunnel clusters (5 cases), and ectopic endometrium (4 cases). Cervical glandular atypia could not be found. A classification of the glandular lesions in uterine cervix has been proposed for an accurate diagnostic approach of lesions who could simulate carcinomatous changes.

154 patients suffering from endometrial carcinoma who underwent CO2-hysteroscopy pretherapeutically, were examined as to whether hysteroscopy lead to tumour cell spread to the peritoneal cavity and worsened the prognosis of the patients. For that purpose, both fallopian tubes of 118 women were investigated thoroughly by histology for intratubarian spread of tumourous cells. Only in one of the 118 patients a single tumour cell complex was detected inside the ampullar part of a fallopian tube. Comparing the investigated patients with data from the literature in terms of five-year survival rates and frequency of relapses, our collective showed the same outcome as those from the literature. These results prove, that the prognosis of endometrial carcinoma is not worsened by CO2-hysteroscopy.

The prognostic significance of peritoneal cytology among 269 women with clinical stage I and II carcinoma of the endometrium was studied. All patients were surgically staged and had undergone selective pelvic and para-aortic lymphadenectomies. Patients with clear cell and papillary serous carcinomas were excluded from the analysis. Thirty-four (12.6%) patients had malignant cells in the peritoneal washings (positive peritoneal cytology). The effect of positive peritoneal cytology on survival depended upon the extent of disease present. If the disease was confined to the uterus, positive peritoneal cytology did not influence survival; if the disease had spread to the adnexa, lymph nodes, or peritoneum, positive peritoneal cytology had a significant adverse effect on survival, decreasing it at 5 years from 73 to 13%, all recurrences being at distant sites. These findings suggest that treatment specifically directed at positive peritoneal cytology is not warranted unless extrauterine disease is present, and when it is, systemic rather than intra-abdominal treatment will be required to affect survival.

Report about three patients which were operated on due to a suspicion of ovarian cancer. In all three cases we could observed metastases of a primary breast cancer. This could be confirmed clinically, mammographically and histologically. In this connection problems of early detection and differential diagnosis have been discussed.