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Metastatic spread is the single most significant predictor of poor survival in breast cancer. Some of the most common metastatic sites are the bones, lungs, liver, brain, and peritoneal cavity. Clinically metastatic breast cancer to the gynecologic tract is usually asymptomatic and diagnosed as an incidental finding during a histologic examination of gynecologic specimens resected for other reasons. Cases of metastatic breast cancer to gynecologic organs diagnosed from August 1995 to January 2021 were retrieved from our institution's pathology databases, and their clinicopathologic features were reviewed. The most common site of metastasis was the ovary which was involved in about 79% (22 of 28 cases) of metastases to the gynecologic tract. Clinically, only 8 cases (36%) presented with ovarian mass detected in imaging studies and the rest of the cases were all incidental findings. Among ovarian metastasis, 59% of cases were invasive lobular carcinoma and 41% were invasive ductal carcinoma. In 5 cases, metastatic breast cancer was found in the endometrium, including 2 cases with endometrial metastasis only and 3 cases with multiple gynecologic organs involved. Metastatic breast cancer rarely involved the lower gynecologic tract, with only 7% vaginal metastasis and 4% found in the vulva. The absolute majority of metastatic breast cancer outside of the ovaries were lobular carcinoma (88%). Most of the metastatic breast carcinomas were positive for estrogen receptor on immunohistochemistry (27 of 28 cases, 96%). Her-2/neu immunostaining was positive in 4 cases only (14%). Metastatic breast cancer needs to be distinguished from gynecologic primary neoplasms and metastatic tumors from adjacent urinary and GI tracts. A careful review of the patient's history and adequate immunohistochemistry panel are helpful to render the diagnosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 by the International Society of Gynecological Pathologists.)

Recognising metastatic gastrointestinal and pancreatobiliary tumours to gynaecological sites may be challenging, as primary Müllerian tumours can demonstrate similar histological features. Endocervical adenocarcinomas can be of gastric and intestinal types, endometrial lesions may show gastrointestinal phenotype, and finally, mucinous tumours with secondary involvement of the ovaries may mimic primary neoplasms. The aim of this review is to address selected neoplastic entities of the gynaecological tract with gastric and intestinal differentiation and provide helpful clinical and pathological parameters for the diagnosis. A brief overview of metastatic tumours originating from the gastrointestinal and pancreaticobiliary tracts is also provided, including the most common pathological features., (Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Purpose: According to the American Urological Association/American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Urologic Oncology Guideline on treatment of nonmetastatic muscle invasive bladder cancer (MIBC), females requiring radical cystectomy (RC) should undergo concomitant anterior pelvic exenteration despite low rates of malignant involvement of gynecologic organs. We present the clinicopathological characteristics of patients with MIBC treated with neoadjuvant chemotherapy (NAC) and evaluate the impact of NAC on gynecologic organ involvement., Materials and Methods: An institutional review board approved review of patients with cT2-T3 MIBC treated with RC at our institution between 2005 and 2018 was performed. Patients were stratified by receipt of NAC., Results: A total of 186 females with cT2-T3 MIBC underwent RC during the study period, of whom 67.7% received NAC prior to RC. Patients who received NAC were more likely to have cT3 disease, preoperative hydronephrosis, and variant histology on transurethral resection (p <0.001, p=0.004, p=0.029, respectively). Rates of recurrence or metastasis were similar between groups (27.0% vs 26.7%, p=0.964). No patients had isolated genitourinary organ recurrence (median followup 32.1 months). Nine patients (5.7%) had gynecologic organ involvement (6 NAC vs 3 no NAC, p=0.978). Among those who underwent hysterectomy, 2 patients (3.1%) who received NAC had uterine involvement compared to none in the no NAC cohort (p=0.551). Rates of vaginal involvement were similar between the groups (4 NAC vs 3 no NAC, p=0.402). Additionally, 1 patient who received NAC had incidentally diagnosed localized endometrial cancer. No women had fallopian tube or ovarian involvement., Conclusions: Even among high risk patients with MIBC, gynecologic organ involvement of MIBC is rare, and organ preservation, especially of the ovaries, is likely safe.

Although the spread of extragenital tumors to individual female genital tract organs, particularly the ovary, has been much studied, histologic data with regard to secondary tumors involving the whole gynecologic tract are largely lacking. Thus, the aim of the study was to investigate the pathologic and clinical features of these tumors in order to better understand their features. This is a retrospective study of 196 secondary lesions involving the gynecologic tract. The parameters studied were the primary site, its histologic type and grade, the presence of mucous production, the type of secondary involvement, defined as distant metastasis, direct extension or locoregional recurrence, and the time to metastasis. Organs involved were the ovary (50%), the vagina (22%), the myometrium (10.7%), the cervix (10.2%), the endometrium (3.6%), the vulva (2%), and the Fallopian tube (1.5%). Most often, primary tumors were colorectal (39.8%), endometrial (15.3%), breast (12.7%), ovarian (10.7%), and gastric (5.6%). Secondary tumors were metachronous in 43.9% of the cases with a mean time to recurrence of 55.5 mo. Distant metastases were the most common type of secondary involvement (64.8%), followed by direct extension (19.9%) and local recurrence (15.3%). Gastrointestinal tumors involved mostly the ovaries, endometrial tumors the vagina, ovarian tumors the myometrium, and urothelial tumors the cervix/vagina (P<0.0001). Vaginal lesions endometrial origin presented with only superficial invasion (P=0.0002). The primary tumor's features dictate a different pattern of secondary involvement of the gynecologic tract. Endometrial tumors produce mostly superficial vaginal recurrences, mucus-producing gastrointestinal tumors present with ovarian metastases, whereas breast tumors affect the entire gynecologic tract and present the tumors with the most late recurrences.

Clear cell renal cell carcinomas (CCRCC) rarely metastasizes to the gynecologic tract. In this study, we analyzed a multi-institutional data set to provide insights into the clinical, morphologic, and immunophenotypic features of this phenomenon. Seventeen metastatic CCRCC involving the gynecologic tract [ovary/fallopian tube (n=9), vulva (n=2), uterine corpus (n=3), cervix (n=2), uterine serosa (n=1)] were analyzed. Mean patient age was 62 yr (range: 45-79 yr). Most cases (15/17) presented as a recurrence 6 to 72 mo postnephrectomy, 1 case was concurrently diagnosed, and 1 case (a cervical metastasis) was diagnosed prenephrectomy. In 10 cases, metastases to other locations were identified within 6 wk of the gynecologic tract lesion. The adnexa were the most common site of metastases and the mean tumor size of adnexal metastases was 3.7 cm; in only 2 of 9 cases were metastases bilateral and only 1 had external surface nodules. The morphologic and immunohistochemical features of metastatic CCRCC were compared with those of 102 müllerian clear cell carcinomas (müllerian CCC: 49 endometrial, 53 ovarian). Although CCRCC and müllerian CCC displayed extensive morphologic overlap, a higher mitotic index and a higher frequency of an alveolar pattern were seen in CCRCC, whereas diffuse hobnail cells, hyaline globules, tubulocystic pattern, or any papillary pattern were more frequently seen in müllerian CCC. CA-IX, CD10, and renal cell carcinoma antigen were more frequently expressed in CCRCC than müllerian CCC, whereas Napsin-A, CK7, and p504S showed the reverse. PAX8 and HNF1β did not significantly distinguish between the 2 groups. In summary, gynecologic tract metastases most often occur as a relapse of a previously resected CCRCC, and these relapses may occur many years postnephrectomy. Gynecologic tract metastases are often accompanied by concurrent metastases to other organs. The gross pathology of metastatic CCRCC in the ovary may potentially overlap with primary neoplasia. However, the expected morphology and immunophenotype of CCRCC are maintained in most gynecologic tract metastases. As such, although metastatic CCRCC and müllerian CCC may display significant overlap in pathologic features, several morphologic and immunophenotypic features are useful in their distinction.

Breast cancer survivors are at an increased risk of second primary cancers, and the risk factors for the latter may have clinical significance. The aims of our study were to evaluate the incidences and risk factors of second primary female genital cancers (corpus uteri, cervix uteri plus ovary) in a large cohort of breast cancer survivors. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined the standardized incidence ratio (SIR) and risk factors for second primary female genital cancers observed between 2000 and 2014. Breast cancer survivors had increased SIRs for second corpus uteri cancers and second ovarian cancers and a decreased SIR for second cervical cancers (SIR 1.17, 1.12, and 0.64, respectively). Risk factors of second corpus uteri cancers were the age at first cancer diagnosis, race (black vs. white, aHR = 1.142 95% CI 1.005-1.298), and progesterone receptor (PR) status (PR+ vs. PR-, aHR = 1.131 95% CI 1.004-1.273). In addition, the risk of second ovarian cancer was positively associated with age while inversely associated with race (black vs. white, aHR = 0.691 95% CI 0.555-0.859) and estrogen receptor (ER) status (ER+ vs. ER-, aHR = 0.655 95% CI 0.544-0.788). Age, race, and hormone receptor status are risk factors of developing second female genital cancers among breast cancer survivors. Older age, black race, and a PR+ status in survivors are associated with a higher risk of second corpus uteri cancers. Additionally, older age and an ER- status should increase vigilance for potential second ovarian cancers.

Study Objective: Laparoscopic port site metastases (PSMs) have an incidence of .5% to 2%. The management of an isolated PSM (iPSM), without evidence of recurrence elsewhere, remains unclear. The aim of this study was to elucidate practices regarding iPSMs., Design: A 23-item survey was created using commercially available survey software. Over the course of January 2016 the survey was e-mailed to the members of the Society of Gynecologic Oncology with 2 follow-up reminder e-mails. (Canadian Task Force classification III.) SETTING: Online survey., Measurements and Main Results: Of the 709 surveys sent, 132 were returned. Providers practicing for <5 years saw fewer PSMs and those who performed more minimally invasive surgeries (MISs) saw more PSMs. Comparing providers who have or have not seen PSMs, no differences in pneumoinsufflation pressure, the mode of delivery of the specimen, the use of local anesthesia at port site incisions, or the method of deflation were seen. If an iPSM was suspected, most providers indicated they would obtain imaging (computed tomography, 51%, or positron emission tomography/computed tomography, 43%) followed by an interventional radiology-guided biopsy (29%) or resection of the mass. Tendency for treatment is to surgically resect the lesion followed by adjuvant therapy., Conclusion: After controlling for time in practice, we did not find a strong risk factor for iPSMs other than performing >75% of oncologic surgeries by MIS. Most respondents performed imaging when suspecting iPSMs and use systemic adjuvant therapy after confirming iPSMs., (Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.)

Purpose: This study was carried out to assess the risk of gynecological malignancy in colorectal cancer survivors using a population-based retrospective cohort study., Method: Using the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 37,176 patients with colorectal cancer diagnosed in 1998-2009, aged 20 years and above, without other cancer history. We also randomly selected 148,700 women without any cancer in the comparison cohort, frequency matched by age and diagnosis date. Incidences and hazards of breast, cervix, endometrial and ovarian cancers were evaluated by 201l., Results: The overall incidence of the 4 types of gynecological cancer was 39.0% higher in colorectal cancer patients than in comparisons (2.99 vs. 2.14 per 1000 person-years) with an adjusted hazard ratio (HR) of 1.46 (95% confidence interval (CI) = 1.31-1.62). Breast cancer accounted for most subsequent cancer. The multivariable Cox method measured HR was the highest for endometrial cancer (3.40, 95% CI = 2.59-4.47) for the colorectal cohort relative to comparisons, followed by ovarian cancer and breast cancer, except cervix cancer. The risk of gynecological malignancies was apparently elevated for colorectal cancer survivors <50 years of age., Conclusions: Follow-up measures are suggested for women with colorectal cancer for early detection and prevention of the subsequent gynecological malignancy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To characterize the origin of nongynecologic pelvic masses., Study Design: Using a radiology database, women who underwent transvaginal ultrasound, CT scan, or MRI for the indication of pelvic mass or pelvic fullness were identified. Demographic information, radiologic data, and outcomes were reviewed., Results: A total of 450 women underwent imaging for the above indications been 2002 and 2012. Of those women, 347 had at least 1 pelvic mass; 3 women had both gynecologic and nongynecologic masses, and 13 women had 2 gynecologic masses. Forty women (12%) had nongynecologic pathology. Of the nongynecologic masses 13 were gastrointestinal in origin, 9 were urologic, and 9 were neuromuscular. Other etiologies included metastatic cancers, iatrogenic masses, and hematologic masses. Seventy-four women had malignant pathology (21%): 17/40 (43%) of nongynecologic pelvic masses and 57/320 (18%) of gynecologic masses (p < 0.05)., Conclusion: Compared to pelvic masses of gynecologic origin, nongynecologic pelvic masses are more likely to be malignant.

Lymph node dissection has been an integral part of the surgical treatment of gynecological malignancies for over a century. The significance of lymph node dissection in gynecological oncology is reviewed in the light of our current knowledge of tumor biology. The original 'centrifugal theory' of metastasis formation leading to the concept of 'radical' surgery has its limitations. Lymph node dissection will still be necessary in gynecological oncology until molecular diagnostics have developed sufficiently and efficacious systemic therapies are available., (© 2014 S. Karger GmbH, Freiburg.)

Background and Objectives: Robotic-assisted laparoscopic surgery is increasingly used for the management of patients with gynecologic malignancies. The rate of portsite metastases in patients undergoing these procedures is unknown., Methods: We conducted a retrospective cohort analysis of a prospective database. A total of 220 women underwent robotic-assisted surgery from 2007 through 2011. Malignancy was detected in 145 cases, and 142 met the inclusion criteria with histologically proven cancer and robotically completed surgery. All women who underwent surgical treatment for their malignancies were followed up at the study site for oncology treatments., Results: There were 710 potential port sites for metastasis. We found that 2 of 142 patients each had a single port-site metastasis, for an overall rate of 1.41%, or 0.28% per trocar site. Recurrent disease was not isolated in the two patients found to have port-site metastases because both had concurrent sites of pelvic recurrence., Conclusion: The rate of port-site metastases in patients undergoing robotic-assisted laparoscopic surgery for gynecologic malignancies is similar to the published rate in the literature for traditional laparoscopic oncology.

There remain no clear guidelines for the optimal management of patients with metastatic breast cancer. To better understand its natural history, we undertook a detailed examination of 197 autopsies performed on women who died of breast cancer. We reviewed clinical, treatment and pathological aspects of all cases and, additionally, pathological features and biomarker expression (ER, PgR, HER2, EGFR, p53, Ki67, c-Kit, CK AE1/AE3) were assessed in detail for the primary tumour and matched metastases for 55 of the cases. Genomes of the primary tumour and multiple metastases were analysed by array-based comparative genomic hybridization for six cases(##) . 945 metastatic deposits were identified, with a median of four/patient. The most common organs involved were lung/pleura (80%), bone (74%), liver (71%) and non-axillary lymph nodes (55%). Major findings included: (a) patients with CNS metastases were more likely to have bone metastases (p < 0.013); (b) younger age was associated with metastasis to the liver (≤ 49 years; p < 0.001) and to gynaecological organs (≤ 49 years; p = 0.001); (c) surgical excision of the primary tumour was associated with metastasis to the liver (p = 0.002); and (d) ER and PgR showed down-regulation during progression in a non-random manner, particularly in lung/pleura (ER; p < 0.001), liver and bone metastases. Genomic analysis revealed DNA copy number variation between the primary tumour and metastases (e.g. amplification of 2q11.2-q12.1 and 10q22.2-q22.3) but little variation between metastases from the same patient. In summary, the association of CNS and bone metastases, liver and gynaecological metastases in young women and the risk of liver metastases following surgery have important implications for the management of patients with breast cancer. Clonal heterogeneity of the primary tumour is important in developing metastatic propensity and the change in tumour phenotype during progression/colonization highlights the importance of sampling metastatic disease for optimal treatment strategies., (Copyright © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)

For many years hormonal treatment has played a role in the treatment of a selected group of patients with a variety of recurrent or metastatic gynaecological cancers, including ovarian and endometrial carcinomas, endometrial stromal sarcomas and granulosa cell tumours. Hormonal agents that are typically used include luteinizing-hormone-releasing hormone analogues, progestogens, selective oestrogen-receptor-modulating drugs such as tamoxifen, and more recently aromatase inhibitors. The rates of response to these drugs differ considerably depending on the tumour type, disease grade and stage as well as the type of drug used. Patients with granulosa cell tumours and endometrial stromal sarcomas have the highest response rates; owing to the rarity of these tumour types, the documented response rates are based on case reports and small series. Response rates in patients with recurrent and metastatic endometrial and ovarian carcinoma have been lower. It has been suggested that patients with well-differentiated and hormone-receptor-positive carcinomas are more likely to benefit from hormonal treatment. However, the data to support this are limited, and at times conflicting, with very few prospective studies to date. This review updates the evidence for the use of hormonal treatment in patients with potentially hormone responsive recurrent and metastatic gynaecological cancers.

Invasive extramammary Paget's disease (EMPD) is relatively rare and is reported to be highly metastatic to lymph nodes or even other organs, including bone. Histologically, EMPD shows significant numbers of lymphocytes around the tumor mass, suggesting the possible development of novel immunomodulatory therapy for EMPD by targeting these infiltrating lymphocytes. Previously, bisphosphonates (BPs) were administered for the treatment of malignancy, especially osteolytic bone disease. Recent reports also suggested that BPs might have a direct antitumor effect through several pathways beyond their beneficial effect on bone metastasis. Among them, the abrogation of immunosuppressive cells, myeloid derived suppressor cells (MDSC), by BPs might be one of the optimal methods to induce an antitumor immune response both locally and at sites remote from the tumor. In this study, we employed immunohistochemical staining for immunosuppressive macrophages and cytotoxic T cells in the lesional skin of patients with noninvasive EMPD and those with invasive EMPD.

Purpose: We evaluated pathological involvement of the reproductive organs in a cohort of female patients treated with anterior pelvic exenteration for invasive urothelial carcinoma of the bladder., Materials and Methods: A total of 2,098 patients with bladder cancer underwent cystectomy at our institution between 1971 and 2008, including 458 females, of whom 411 had urothelial carcinoma of the bladder. Median followup was 12.2 years (range 0.1 to 35.5). We reviewed the clinicopathological features of female patients treated with cystectomy who had pathological reproductive organ involvement. Recurrence-free and overall survival is reported using Kaplan-Meier survival curves., Results: Of 411 patients with urothelial carcinoma of the bladder 267 underwent reproductive organ removal with cystectomy. A total of 20 patients (7.5%) had reproductive organ involvement, including 10 (3.8%) with vaginal, 2 (0.7%) with cervical and 1 (0.3%) with uterine involvement only, while the remaining 7 (2.6%) had multiple reproductive organs involved. Median age was 71 years. Clinical stage T4a was diagnosed in 25% of cases. A palpable mass, hydronephrosis (each p <0.001) and positive lymph nodes at anterior pelvic exenteration (p = 0.001) were associated with reproductive organ involvement. Recurrence developed in 14 patients (70%) at a median of 7 months (range 1 to 22). Five-year recurrence-free and overall survival rates were 14.9% and 8.8%, respectively., Conclusions: The risk of reproductive organ involvement in female patients who undergo anterior pelvic exenteration for urothelial carcinoma of the bladder was about 7.5% with the vagina the most commonly involved organ. A palpable mass and hydronephrosis were among the preoperative clinical factors associated with reproductive organ involvement. The prognosis is poor in patients with reproductive organ involvement., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Cutaneous metastatic mammary carcinoma may occur in patients with a history of breast carcinoma. Cutaneous metastases typically present as firm papulonodules on the chest. We describe a rare case of cutaneous metastatic mammary carcinoma arising in a 45-year-old woman presenting as painful, indurated plaques with ulceration in the pelvic region.

The pathological analysis of cystectomy specimens from 360 female patients who underwent radical cystectomy for bladder cancer was retrospectively reported. The uterus was not available in 29 specimens, while one ovary was absent in 18 specimens and the two ovaries were absent in 20 specimens. Uterine involvement was observed in one case of transitional cell carcinoma, and benign uterine pathology was detected in 37 cases. All patients had normal ovaries, while the vagina was involved in 13 cases. A total of 12% of the patients had urethral involvement. None of the 29 patients, in whom the internal genitalia were totally or partially preserved, had late ovarian, vaginal or uterine recurrence at the last follow-up. Thus, the preservation of female internal genitalia in young patients undergoing radical cystectomy should be considered under strict criteria (low-grade, low-stage tumours away from the bladder neck). This will improve the quality-of-life (QoL) and the functional outcome without compromising cancer control.

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.

Introduction: Synchronous gynecological tumors are uncommon. Identifying the primary site of lymphatic spread may be difficult., Methods: Two women with synchronous squamous cervical and adenosquamous endometrial cancers (patient A) and squamous cervical and serous borderline ovarian tumors (patient B) entered retrospectively this study. Both patients had pelvic nodal metastases of unknown origin. Uterine cervix, endometrium, and lymph nodes were tested for human papillomavirus DNA using high-sensitive polymerase chain reaction, followed by oligonucleotide microarray for genotyping., Results: Human papillomavirus 16 DNA was extracted from portio vaginalis and pelvic nodes of both women. Viral homology between cervical and lymph nodal lesions helped to identify the primary metastasizing tumors in both patients., Conclusions: Human papillomavirus testing on pelvic lymphatic tissue represents a feasible tool to detect the primary site of lymphatic spread in synchronous gynecological malignancies, when uterine cervix is involved.

Objective: To estimate the safety and feasibility of extraperitoneal laparoscopic approach for the diagnosis and treatment of paraaortic lymph node recurrence in gynecologic cancers., Material and Methods: Between December 2002 and September 2009, 15 patients underwent extraperitoneal laparoscopic paraaortic lymphadenectomy for suspected isolated lymph node recurrence in the Gynecologic Oncology Unit of Hospital Vall d'Hebron. The suspected diagnosis of recurrence was performed with computed tomography scanning, 18F-fluorodeoxyglucose positron emission tomography scanning, or magnetic resonance imaging., Results: The median age of patients was 63 years (range 42-75). The median body mass index was 28.5 Kg/m(2) (range 18-38). The median operative time was 157.5 minutes (range 120-240). The median blood loss was 70 mL (range 30-150). The mean nodal yield was 7.7 +/- 5.3 (range 1-16). The median hospital stay was 2 days (range 2-13). There was 1 conversion to laparotomy. There was only 1 postoperative complication, a lymphorrhea that was resolved with drainage. Recurrence was confirmed in the pathologic study in 13 of the 15 patients., Conclusion: The extraperitoneal laparoscopic surgical approach is a feasible and safe procedure for the diagnosis of paraaortic lymph node recurrences of gynecologic cancers. The previous abdominal surgeries or treatment with chemotherapy or radiotherapy and high body mass index are not a problem. The low complication rate, low blood loss and low hospitalization allow a rapid recovery of the patients, which in turn, allows the rapid onset of adjuvant therapy. Complete debulking of suspicious lymphadenopathy offers an exact diagnosis of malignancy, and it may have a therapeutic benefit in the case of being positive., (Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.)

Aims: There is a high frequency of serous gynaecological and basal breast cancers in patients with germline BRCA1 mutations. These patients often undergo prophylactic salpingo-oophorectomies, where small tumours may be identified in which morphological distinction between primary serous and metastatic basal breast cancer may be problematic. These two cancer types share similar molecular genetics and have immunophenotypic overlap. We aimed to develop an immunohistochemical panel which could differentiate between these two tumour types., Methods: Immunohistochemistry was performed on a training set of 20 serous gynaecological and 20 basal breast cancers, from which a small differential panel was developed. This differential panel was tested in an additional validation set of serous and basal cancers., Results: WT1, ER and CK5/6 expression successfully differentiated serous gynaecological and basal breast cancers. WT1 and ER expression was significantly more common in serous cancers and CK5/6 expression more common in basal cancers., Conclusion: There is considerable genetic, morphological and immunophenotypic overlap between serous gynaecological and basal breast cancers. A limited panel of WT1, ER and CK5/6 was found to optimally differentiate these tumour types. Differences in the expression of these proteins appear to reflect the expression pattern of their cell of origin, rather than identify aberrant oncogenic pathways.

Purpose: To determine the value of diffusion-weighted imaging (DWI) in the evaluation of adnexal tumors, especially to distinguish between malignant and benign tumors. Materials and methods. Fifty-four patients with pelvic tumors (32 malignant and 22 benign) were referred for MRI of the pelvis. DWI was obtained in all patients. Histological correlation was available in all cases. The signal of solid and cystic tumor components was evaluated on T2W and b=1000 DWI, and ADC values were obtained., Results: T2W hypointensity or absence of hyperintense signal on b=1000 DWI sequences was suggestive of a benign tumor. Hyperintensity on b=1000 DWI sequences was strongly correlated with malignant lesions. ADC values did not appear to discriminate between malignant and benign tumors. Also, the signal intensity of cystic tumor components on DWI sequences was not helpful to distinguish between malignant and benign tumor., Conclusion: The evaluation of solid tumor components on DWI appears to be helpful for adnexal tumor characterization.

Radicality in primary surgical management in gynaecological cancers, especially in ovarian cancer, is the most important factor influencing patient survival. Postoperative residual tumour is one of the most important prognostic factors in ovarian cancer. Radical pelvic and paraaortic lymphadenectomy is recommended in cases of complete resection because of the high incidence of lymph node metastases, especially in the high paraaortic region. A multicenter, prospective randomised study of advanced ovarian cancer by the AGO Ovarian Cancer Study Group is planned to analyse the therapeutic impact of systematic lymphadenectomy in ovarian cancer.

For 20 years laparoscopic pelvic and para-aortal lymph node dissection has become increasingly popular as part of minimally invasive surgical treatment concepts for women suffering from gynaecological malignancies. Especially patients suffering from early-stage cervical or endometrial cancers can benefit from the general advantages of a minimally invasive procedure if a comparable degree of radical surgery is achieved. The feasibility and case-control studies published so far suggest comparable indicators of radicality, such as the number of dissected lymph nodes, but also demonstrate potential advantages like a lower intra-operative blood loss, shorter hospital stay and lower postoperative complication rate in comparison with the conventional approach. Regarding long-term survival, reliable data from prospective randomized studies are still lacking but can be expected to be available in the near future.

The presence of lymph node (LN) metastases has a major impact on the prognosis of women with endometrial cancer and compromises recurrence-free time. LN assessment has become the standard of care in the surgical staging of patients and plays a crucial role in decision making. Sentinel lymph node (SLN) detection improves the accuracy of lymphatic drainage mapping compared to pelvic node dissection used alone. Serial sectioning of SLNs followed by immunohistochemical examination with conventional histology improves accuracy of micrometastatic identification. In this review, we found a high incidence of micrometastases in endometrial cancer, reaching 25% depending on the stage and the techniques used for the node examination. Current data are insufficient to evaluate the prognostic impact of the presence of micrometastases, but it seems that more accurate detection of lymphatic spread will allow better stratification of intermediate risk patients. Ultimately, this will assist in tailoring adjuvant treatment.

Lymph node metastases is a recognized prognostic factor in women with cervical cancer. However, there is a need for consensual histological definition of micrometastases in this indication which could give rise to a classification system similar to that used in breast cancer. We thus conducted a MEDLINE and EMBASE database analysis to evaluate the concept of micrometastases in cervical cancer. Retrospective studies place the incidence of micrometastasis between 1.5 and 15% depending on the technique used to evaluate lymph node status. Sentinel lymph node biopsy with serial sectioning and immunohistochemical analysis appears to be the most accurate micrometastases detection technique. The value of RT-PCR in micrometastases detection remains to be clarified by further studies. From a clinical view point, few data are available to support the prognostic relevance of micrometastases. However, case control and longitudinal studies have underlined the risk of recurrence in women with micrometastases, raising the issue of a revision of adjuvant therapy indications in this specific population.

Emerging therapies and the growing number of therapeutic options available for some of the solid cancers have led to a large number of patients eligible for metastasectomy and cytoreductive surgery. It is likely that within the current health care structure, academic tertiary referral centers alone are not going to be able to accommodate the growing number of patients that are potential beneficiaries. Community-based practices will have to develop strategies to meet the demand for appropriate multimodality treatment teams to address the needs of these patients.

Introduction: The risk of endometrial cancer recurrence is estimated to be about 20%. In most cases, such situations are recognized in the first 3 years after the primary treatment. Early detection of such episodes leads to effective treatment. The aim of this study was to evaluate some histoclinical factors in the risk of recurrence., Material and Methods: Between the year 2001 and 2003, 203 from 243 patients with endometrial cancer underwent surgery. All procedures were performed in accordance with surgical-pathological staging system. The following histoclinical factors were taken into account: age, number of deliveries, BMI, use of estrogens, co-morbidity, histoclinical type, grading and the spread of cancer inside the uterus, pelvis and retroperitoneal space., Results: 29 recurrences (14.3%) were found in all analyzed groups. The mean time of follow-up was 43 months. The mean time of recurrences was 16 months (9-51 months). Lymph node metastases were recognized in 28 patients (13.7%). The most important factors in the multivariate analysis were: type of histology (serous or clear cell cancer) and lymph node involvement. Recognizing 2 or more metastatic lymph nodes significantly increased the risk of recurrences., Conclusion: In patients with endometrial cancer the risk of recurrences increases when lymph node metastases are recognized. This risk is 5 times higher when 2 or more lymph nodes are involved, comparing with patients with one node metastasis. Four times higher recurrence risk is observed in serous or clear cell cancer, comparing with other histological types.

Over the past two decades, immunohistochemical techniques have improved to such a degree that it is now a common adjuvant test to the traditional hematoxylin and eosin-stained histologic sections. It is used in most realms of surgical pathology and can often aid in final diagnosis and, in some cases, prognosis. However, immunohistochemistry (IHC) is not always helpful and many pitfalls to its use exist. Understanding the basics of IHC, its utility and difficulties will aid clinicians in better understanding how diagnoses are rendered. This study reviews the general principles of IHC and demonstrates its utility with several commonly encountered problematic areas in gynecological pathology.

In this review article, the application of sentinel lymph node (SLN) lymphoscintigraphy not only in breast cancer and melanoma but also in cancers of the genital organs and the lungs is described. After a brief historical background, including Virchow and Cabanas' views, a description of the basic technique and the sensitivity and specificity of this technique in identifying SLN in breast cancer and melanoma are presented. In cervical and vulvar cancer and also in lung cancer, special techniques are applied before and during surgery and evaluated after surgical operation. The advantages and disadvantages of using SLN lymphoscintigraphy are described. Finally, our experience from using SLN lymphoscintigraphy, especially in cervical cancer, is presented. The technique for SLN mapping may save the patient from extended surgical procedures, indicate the pathways of lymph drainage and identify skip metastases. Nevertheless, the sensitivity of this technique should improve more in order to provide information concerning the extent of surgical treatment.

This prospective, open-label, pilot phase 2 study examined the clinical and immunologic effects of oregovomab (OvaRex) in heavily pretreated patients with recurrent ovarian cancer (OC). Thirteen women were administered intravenous oregovomab (2 mg) at weeks 0, 2, 4, 8, and 12, followed by quarterly doses for up to 2 years or disease progression. Concomitant chemotherapy was not permitted. Eligibility criteria included recurrence after one or more platinum-based chemotherapy regimens, CA125 >35 U/mL, evaluable or measurable disease. Tumor burden was evaluated by physical or radiologic methods pretreatment, weeks 12, 24, and every 24 weeks thereafter. Immune responses, including antibodies and T cells to oregovomab and CA125, were demonstrated in over half the patients. Stabilization of disease and survival >2 years was observed in 3 of 13 patients and coincided with robust immune responses. Shrinkage of marker lesions was not observed; however, four patients showed decreases in CA125 levels. Treatment was well tolerated without serious adverse events or discontinuations due to therapy. This pilot study supports immunologic activity and safety of oregovomab in recurrent OC. Further study of this agent in the consolidation and adjuvant setting is ongoing to establish its clinical utility.

The utility of lymphatic mapping and sentinel lymph node biopsy in malignancies of the female lower genital tract-- vulvar, vaginal, and cervical cancers--is being explored in multiple centers internationally. For patients with these tumors, lymphatic mapping with sentinel lymph node biopsy holds the promise of increasing the identification of microscopically metastatic disease while decreasing the morbidity of complete lymphadenectomy. In this review article we present the published data on mapping techniques and discuss the advantages and pitfalls of these procedures.

Purpose: This study evaluated the diagnostic role and accuracy of positron emission tomography (PET) using 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) for the detection of tumor foci in patients with suspected recurrent or metastatic lesions of gynecologic cancers., Materials and Methods: FDG PET imaging was performed on 51 patients with a previous history of gynecologic cancer who were referred for a clinical suspicion of recurrent disease. PET acquisition was started 50-60 min after the intravenous injection of 5-6 MBq/kg FDG in all patients. The PET images were interpreted visually, and tracer uptake was quantitated as the standardized uptake value adjusted to body weight (SUV) in the lesions showing FDG uptake. The accuracy of the PET results was assessed by a consensual verdict based on histology, cytology, other imaging and clinical follow-up., Results: FDG PET correctly diagnosed 33 of 36 patients with recurrent disease and 12 of 15 patients without recurrence. On patient-based analysis, the sensitivity, specificity and accuracy of FDG PET were 91.7%, 80.0% and 88.2%, respectively, depending on the selected scheme for visual scoring of the lesions. The area index in receiver-operating characteristic analysis was 0.95 for patient detection. Malignant lesions accumulated significantly more FDG than the benign ones (the mean SUVs were 3.7 +/- 1.9 and 1.6 +/- 1.1, respectively, p = 0.004). The sensitivity and specificity in correct identification of tumor recurrence or metastases using a threshold SUV 1.9 were 88.8% and 66.7% in contrast to the visual analysis (sensitivity 96.4%, specificity 50%) on a lesion-based analysis. The partial volume effect of SUV in a few small lesions and the presence of bone lesions in which FDG uptake was relatively low might be the reason for the lower sensitivity in SUV analysis. FDG PET was valuable when CT/MRI was negative or inconclusive, and in patients with elevated tumor marker levels as well as with normal tumor marker levels when recurrence was suspected clinically. However, PET failed to visualize some small metastatic lesions in lung and bone, and showed falsely high FDG uptake in some benign lesions., Conclusion: The results indicated that FDG PET is a reliable and accurate diagnostic method for detecting recurrent or metastatic gynecologic cancer particularly lymph node metastases. Although the sensitivity of PET for detecting small metastases was relatively limited, the overall sensitivity of FDG PET was significantly higher than morphologic imaging.

The purpose of this study was to assess the accuracy of MRI in the staging of intra-abdominal tumor seeding of ovarian carcinoma. Fifty-seven patients with suspected primary or recurrent ovarian carcinoma were included in this study. All patients received laparotomy within 8 weeks after MRI. The MRI protocol included fat-saturated T1-weighted spin-echo (SE) sequences pre- and post i.v. application of gadopentetate dimeglumine. The criteria for tumor manifestation was contrast enhancement of intra-abdominal soft tissue lesions or peritoneum. The image review was performed by a blinded radiologist, a specialist in gynecological and abdominal MR imaging. Results were compared with findings during laparotomy. Sensitivity, specificity, positive and negative predictive values, and corresponding 95% confidence intervals were calculated for single intra-abdominal locations and for groups of locations defined according to surgical strategies for intra-abdominal cytoreduction. Laparotomy and histopathology confirmed 251 abdominal tumor locations. Sensitivity was high in lower pelvis locations (73-83%) except for ureter or bladder infiltration (40%). Bowel or mesentery locations displayed sensitivity values from 73 to 77%. Sensitivity was very low for pelvic lymph nodes (28%), greater omentum (38%), and lesser sac (43%). Magnetic resonance imaging based on contrast-enhanced fat-saturated T1 SE sequences improves planning of cytoreduction preceding chemotherapy in advanced primary or relapsed ovarian carcinoma.

The authors present data on 13 patients operated on for the treatment of locally advanced colorectal cancer infiltrating the adjacent parts of the urinary tract. Based on prior diagnostic evidences, every surgical intervention has been indicated as an expected curative resection. All patients of this study underwent a curative resection. The origin of the advanced cancer was in 9 cases the sigmoid colon, in 3 cases the rectum and in 1 case the ascending colon. Beside the resection of the tumorous colon or rectum, a resection of the urinary bladder has been performed in 9, a nephrectomy in 3 and the resection of the ureter in 2 cases. An additional gynecological resection was made in 4 cases for tumors infiltrating the female internal genitals. No mortality and no serious complication needing reoperation occurred in these series. Based on their experiences of a series of 13 radically operated cases, the authors suggest extended multiple organ resection for the treatment of advanced colorectal cancer infiltrating the urinary tract.

Objective: The purpose of our study was to assess the usefulness of imaging-guided catheter drainage and talc sclerotherapy in patients with metastatic gynecologic malignancies and symptomatic pleural effusions and to assess the affect of ascites on the success rate of this treatment., Materials and Methods: Twenty-five patients (mean age, 63 years) with metastatic gynecologic malignancies who had 26 symptomatic effusions treated at our institution over a 4-year period with imaging-guided catheter drainage and talc sclerotherapy were included in this study. Response to treatment was assessed by comparing pre-, immediate post-, and 30-day postsclerotherapy chest radiographs. Response to the treatment was graded as complete (no reaccumulation), partial (accumulation above immediate post- but below presclerotherapy level), or no response (reaccumulation to or above the presclerotherapy level). The presence of ascites on CT (n = 23), sonography (n = 1), direct intraoperative visualization (n = 1), or at physical examination (n = 1) was also noted., Results: Of the 25 patients, 13 patients with 14 treated malignant effusions survived at least 30 days after sclerotherapy and formed the final study group. The remaining patients either died (n = 11) or were lost to follow-up (n = 1). At 30 days, 12 of the 14 treated effusions showed complete responses and one showed a partial response. The overall response rate was 86%. Abdominal ascites was present at the time of treatment in 11 patients (79%) and did not affect the success rate (p > 0.999)., Conclusion: Imaging-guided catheter drainage and talc sclerotherapy are an effective treatment for symptomatic pleural effusions in patients with metastatic gynecologic malignancies. Ascites does not adversely affect the response to pleurodesis.

Purpose: Historically anterior pelvic exenteration has been the recommended treatment for invasive urothelial carcinoma in women undergoing radical cystectomy. We evaluated the pathological features of reproductive organs removed during exenteration to determine the incidence of malignant pathology in these organs and the need for removal., Materials and Methods: We reviewed the records of all patients who underwent radical cystectomy between January 1994 and December 2000. Of these 382 patients, we identified 68 females who underwent radical cystectomy for urothelial carcinoma. We reviewed preoperative, operative and pathological findings, including bladder, lymph nodes, uterine and adnexal pathology, in these female patients., Results: Median patient age was 64 years (range 35 to 86). Gynecologic organs were present in 40 of the 68 surgical specimens (59%). The reasons for absent gynecologic pathology were previous hysterectomy in 26 cases and the preservation of organs during orthotopic urinary diversion creation in 2. Malignancy was identified in 3 specimens, including invasive urothelial carcinoma in 2 (5%). In these 2 cases invasion was clearly identified intraoperatively. Low grade stromal sarcoma of the uterus was present in 1 specimen (2%)., Conclusions: In the absence of clinical suspicion radical hysterectomy at cystectomy rarely improves cancer control. Furthermore, secondary malignancies are rare. The functional impact of preserving gynecologic organs is a subject of ongoing study.

Objective: To investigate the malignant potential of positive peritoneal cytology in endometrial cancer., Methods: Fifty patients with clinical stage I-II endometrial cancer in whom the disease was completely surgically resected and positive peritoneal smears were found at surgery formed the study population. In these patients, a tube for cytologic analyses was inserted into the peritoneal cavity when closing the abdomen. The peritoneal cavity was irrigated with physiologic saline, and washings were obtained through the tube 7 and 14 days after the operation., Results: Persistence of positive peritoneal cytology was observed in four of seven patients with adnexal metastasis, zero of nine patients with nodal disease, and one of 34 patients with disease confined to the uterus, for a total of 10% (5 of 50). In the remaining 45 (90%) patients, no malignant cells were found in any of the washings., Conclusion: The current series suggests that endometrial cancer cells found in the peritoneal cavity usually disappear within a short time and seem to have a low malignant potential. It also seems that only malignant cells from special cases, such as adnexal metastasis, may be capable of independent growth, and are possibly associated with intraperitoneal recurrence.

Background: Complete surgical removal of cancer tissue is a goal in modern cancer treatment, and this is one of the arguments for total lymphadenectomy in gynaecologic cancer surgery., Material and Methods: Review of the literature identified through limited searches on Medline, Cochrane, Bibsys and the Internet., Results: Lymphadenectomy improves the staging and represent advanced surgical treatment with considerable complication rates, related to the surgeon's experience. It is likely that lymphadenectomy directly influences survival for vulva and cervical cancer. The effect on survival among endometrial and ovarian cancer patients is unsettled, but prospective randomized trials are ongoing., Interpretation: Correct staging is especially important in randomized trials of treatment alternatives, and it is the basis for individualised treatment. However, the effect of available treatment is not always well documented, hence the mortality and complication rates related to the procedure should be considered in relation to the potential benefit from the relevant treatment in each patient. Special training in the surgical technique is necessary. For rare conditions, this implies centralization. There are promising new approaches like the sentinel node and laparoscopic techniques, and studies of prognostic tumour markers, that may partially replace total lymphadenectomy in the future.

Objective: To review the experimental studies on laparoscopy and cancer and to propose guidelines for the clinical management of gynecologic cancer., Methods: The literature in MEDLINE was searched from January 1992 to December 1998 using the terms 'cancer', 'laparoscopy' and 'experimental or animal study'. Cross-referencing identified additional publications. Abstracts and letters to the editor were excluded. All the relevant papers were reviewed., Results: Depending on the model used, controversial results have been reported on the incidence of trocar site metastasis when comparing CO(2) laparoscopy and laparotomy. In contrast, the following conclusions can be proposed: (i) tumour growth after laparotomy is greater than after endoscopy; (ii) tumour dissemination is worse after CO(2) laparoscopy than after laparotomy; (iii) some of the disadvantages of CO(2) laparoscopy may be treated using local or intravenous treatments or avoided using other endoscopic exposure methods, such as gasless laparoscopy., Conclusions: The laparoscopic treatment of gynecologic cancer has potential advantages and disadvantages, and may only be performed in prospective clinical trials. The risk of dissemination appears high when a large number of malignant cells are present. Adnexal tumours with external vegetations, and bulky lymph nodes should be considered as contra-indications to CO(2) laparoscopy.

Objective: The objective of our study was to describe the accuracy of intraoperative frozen-section diagnosis of carcinoma metastatic to the adnexa in women with a history of breast or colorectal carcinoma., Methods: We conducted a retrospective chart review of all patients with a history of breast or colorectal carcinoma who developed histologically proven pelvic or abdominal metastases between 1988 and 1995. In those patients whose final histologic review revealed carcinoma metastatic to the adnexa, the accuracy of the intraoperative frozen-section diagnosis of the adnexal tumor was compared to the final diagnosis., Results: Forty-three patients were identified and in 36 patients the frozen section was obtained from the adnexa. Twenty-one patients (58.3%) had metastatic breast carcinoma and 15 (41.7%) had metastatic colorectal carcinoma to the adnexa. Carcinoma in the adnexa was correctly diagnosed by frozen section in 35 of 36 patients (97.2%). Metastatic carcinoma was identified at frozen section in 17 of 21 patients (81%) with metastatic breast cancer and 13 of 15 patients (86.7%) with metastatic colorectal cancer. In 3 of 21 patients (14.3%) with metastatic breast cancer and in 2 of 15 patients (13.3%) with metastatic colorectal cancer, the frozen-section diagnosis was carcinoma of uncertain origin. One patient had a false-negative frozen section because the small focus of metastatic breast cancer was not sampled at the time of frozen section., Conclusion: Intraoperative frozen-section evaluation correctly diagnosed carcinoma in the adnexa in 97% of patients, and in over 80% of cases, the carcinoma was diagnosed as being metastatic in origin., (Copyright 1999 Academic Press.)

Management of patients with advanced stage cervical carcinoma remains suboptimal. Primary radiation therapy has been the standard treatment for years. Despite some changes in radiation technique, cure rates for advanced stage cervical cancer remain disappointing. Radiation complications in those patients can also be severe. We report here a case of a patient who presented with renal failure from bilateral ureteral obstruction from stage III-B cervical squamous carcinoma. The patient underwent a primary total pelvic exenteration with low rectosigmoid reanastomosis, urinary conduit construction, and cecal neovagina construction as definitive treatment. She was found to have metastasis to the broad ligament, ovary, and fallopian tube. Surgical margins and lymph nodes were negative. The patient did not receive any radiation therapy or chemotherapy. The patient is alive, healthy, and without evidence of disease 8 years following treatment., (Copyright 1998 Academic Press.)

Clear cell adenocarcinomas of the vagina, cervix, endometrium, and ovaries show very similar histological features. Several other tumors and tumor-like lesions of the female genital tract may also contain clear cells and may occasionally be misinterpreted as clear cell adenocarcinomas. These conditions include microglandular hyperplasia, mesonephric hyperplasia, Arias-Stella change, smooth muscle tumors containing clear cells, dysgerminoma, yolk sac tumor, metastatic renal cell carcinoma, steroid cell tumors, hepatoid carcinomas, signet-ring-cell stromal tumors, and trophoblastic tumors. This review discusses the histological features of all of these lesions, emphasizing the morphological aspects that are essential to accurate differential diagnosis.