Definitive radiotherapy for vaginal recurrence of early-stage endometrial cancer: survival outcomes and effect of mismatch repair status.

OBJECTIVE: To evaluate clinical outcomes, prognostic factors, and toxicity in patients with vaginal recurrence of early-stage endometrial cancer treated with definitive radiotherapy. METHODS: Retrospective review identified 62 patients with stage I-II endometrial cancer and vaginal recurrence treated with external beam radiotherapy and image-guided brachytherapy with definitive intent from November 2004 to July 2017. All patients had prior hysterectomy without adjuvant radiotherapy and >3 months follow-up. Mismatch repair (MMR) status was determined by immunohistochemical staining of the four mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6) when available in the pathology record. Rates of vaginal control, recurrence-free survival, and overall survival were calculated by Kaplan-Meier. Univariate and multivariate analyses were performed by Cox proportional hazards. RESULTS: Most patients had endometrioid histology (55, 89%), grade 1 or 2 tumor (53, 85%), and vaginal-only recurrence (55, 89%). With a median follow-up of 39 months (range, 3-167), 3- and 5-year rates of vaginal control, recurrence-free survival, and overall survival were 86% and 82%, 69% and 55%, and 80% and 61%, respectively. On multivariate analysis, non-endometrioid histology (HR 12.5, P<0.01) was associated with relapse when adjusted for chemotherapy use. Patients with non-endometrioid histology also had a 4.5-fold higher risk of death when adjusted for age (P=0.02). Twenty patients had known MMR status, all with grade 1-2 endometrioid tumors and 10 (50%) with MMR deficiency. The 3-year recurrence-free survival was 100% for MMR-proficient tumors and 52% for MMR-deficient (P=0.03). Late grade 2 and 3 gastrointestinal, genitourinary and vaginal toxicity was reported in 27% and 3%, 15% and 2%, and 16% and 2% of patients, respectively. CONCLUSION: Definitive radiotherapy with image-guided brachytherapy resulted in 5-year local control rates exceeding 80% and late severe toxicity rates were under 3%. Distant recurrence was common and highest for those with grade 3 or non-endometrioid tumors and MMR deficient grade 1-2 disease.

An isolated vaginal metastasis from intestinal signet ring cell carcinoma: a case report and literature review.

BACKGROUND: Isolated vaginal metastases from intestinal signet ring cell carcinoma are extremely rare. There are no reported cases in the domestic or foreign literature. The characteristics of such cases of metastasis remain relatively unknown. As a life-threatening malignant tumor, it is very important to carry out a systemic tumor examination and transvaginal biopsy, even though clinical symptoms are not typical and there is no systemic tumor history. CASE PRESENTATION: We present a case of an isolated vaginal metastasis from intestinal cancer in a 45-year-old female patient. The patient experienced a small amount of irregular vaginal bleeding and difficulty urinating. She had no history of systemic cancer. An early physical examination and transvaginal ultrasound (TVS) showed marked thickening of the entire vaginal wall. Pelvic nuclear magnetic resonance imaging (MRI) and a colposcopic biopsy were used to diagnose her with chronic vaginitis. An analysis of the vaginal wall biopsy showed signet ring cell carcinoma. Colorectal colonoscopy revealed advanced interstitial signet ring cell carcinoma as the primary source of vaginal wall infiltration. We review previous case reports of vaginal metastases from colorectal cancer and discuss the symptoms, pathological type, and outcomes. CONCLUSIONS: We hypothesize that vaginal wall thickening and stiffness accompanied by chronic inflammatory-like changes may be clinical features of a vaginal metastasis of signet ring cell carcinoma of the intestine. We also emphasize that it is very important to perform a systemic tumor examination in a timely manner when a patient has the abovementioned symptoms.

Presence of tumor cells in the vagina during surgical treatment could be the source of vaginal recurrence in patients with endometrial carcinoma - A pilot prospective study.

BACKGROUND: The commonest site of recurrence in endometrial cancer (EC) is the vagina, with a rate of 16%. The aim of this study was to determine if vaginal recurrences in EC patients could develop due to contamination of the vagina with glandular tumor cells dropping off on polypoid, large size EC or tumors involving the endocervix, through manipulation of the uterus during surgery. METHODS: This pilot prospective study included 10 consecutive patients with EC, surgically treated with hysterectomy and additional lymphadenectomy according to stage. In every case, 2 proximal vaginal smears were collected before and during the hysterectomy procedure. All smears underwent Papanicolaou staining and the presence of atypical glandular cells in the smears was correlated with clinico-pathological parameters. RESULTS: Residual tumor was identified on the surgical specimen in the 10 cases; the tumor characteristics were large size (median 6 cm), polypoid type (80%), infiltrating the cervix (70%), and infiltrating more than half of the myometrium (60%). The smears obtained from the vagina showed that five cases (50%) presented tumor cells of glandular type in all smears (before and during the surgery), while in 3 cases (30%) the smears were negative for tumor cells preoperatively, but positive in the perioperative smears. CONCLUSIONS: Our results suggest that the vagina is most often contaminated preoperatively due to bleeding; however, the vaginal wound may also be contaminated perioperatively. We propose a change in the surgical procedure, which is easy to perform and inexpensive compared to postsurgical vaginal radiotherapy.

Radical Cystectomy in Pathological T4a and T4b Bladder Cancer Patients: Is There Any Space for Sub Stratification?

INTRODUCTION: According to TNM staging, pathological T4ab are comprehensive of the invasion of prostate, seminal vesicles, uterus or vagina and pelvic or abdominal wall. However, few data are available on the perioperative and oncological outcomes of specific organ invasion. MATERIALS AND METHODS: A total of 917 consecutive bladder cancer (BCa) patients treated with radical cystectomy (RC) at a single institution between 1990 and 2015 were studies. Cox regression analyses were used to stratify pT4ab according to the site of invasion and survival. RESULTS: Overall, 176 (19.2%) and 40 (4.4%) patients harbored pT4a or pT4b disease. Specifically, 84 (9.2%) patients reported prostate and/or SVI invasion, 62 (6.8%) prostate only, 16 (1.7%) uterus, 14 (1.5%) vaginal, 24 (2.6%) pelvic wall, and 16 (1.7%) abdominal wall invasion. The median follow-up in pT4 patients was 48 months. The 1-year cancer-specific mortality (CSM) rates were 71, 65, 24, 50, 50, and 72%, for vaginal, uterus, prostate only, prostate and/or seminal vesicles, pelvic wall, and abdominal wall invasions, respectively. At multivariable Cox regression, the invasion of prostate only (hazard ratio [HR] 3.53), prostate and/or SVI (HR 4.98), uterus (HR 7.16), vagina (HR 6.12), pelvic (HR 11.81), abdominal (8.36) were associated with adverse CSM. CONCLUSIONS: Our study described the differences in survival related to invasion site in pT4 patients, confirming poor survival expectancies in this subgroup. Patients with prostate invasion only seem to be associated with better survival than those affected by concomitant invasion of seminal vesicles. Uterus and vaginal invasions were associated with poor survival outcomes. Patients Summary: In this study, we looked at the outcome of locally advanced invasive BCa (stage pT4) in patients treated with RC at a tertiary referral hospital. We analyzed the differences in survival related to the specific organ invasion. We confirmed poor survival in this subgroup of patients. Only patients who had prostate invasion only seem to have a better survival.

A Rare Case of Gestational Choriocarcinoma Presenting as Cornual Ectopic Pregnancy.

BACKGROUND: Choriocarcinoma associated with cornual pregnancy is extremely rare. To our knowledge, only three other cases have been reported in the literature. CASE: A 38-year-old woman was found to have a left cornual ectopic pregnancy on ultrasound after presenting with abdominal pain, irregular vaginal bleeding, and a positive pregnancy test. Laparoscopy confirmed the diagnosis and she underwent total abdominal hysterectomy. Three weeks later, she presented with vaginal bleeding. A solid ulcerating lesion was found arising from the vaginal wall and biopsy revealed metastatic gestational choriocarcinoma. CONCLUSION: Careful histopathological examination of the surgical specimen and diligent monitoring of ß-human chorionic gonadotropin to zero is crucial to prevent potentially missing this very malignant, but highly curable disease. Early systemic metastases are common and presentation can include bleeding from vaginal metastases.

Vaginal metastasis as the initial presentation of leiomyosarcoma: a case report.

BACKGROUND: Uterine leiomyosarcomas are very rare and highly aggressive tumors that have a high rate of recurrence and poor prognosis, even when early diagnosed. Due to their relative rarity, there is limited research on optimal management strategies. CASE PRESENTATION: A 60-year-old woman with a history of an asymptomatic uterine leiomyoma presented in October 2015 with postmenopausal bleeding and a friable vaginal cyst that bled when palpated. A partial cystectomy was performed, and malignant-like cystic and solid components were identified. Histopathology diagnosed an unclassifiable malignant epithelioid tumor. Subsequent imaging studies identified a malignant uterine tumor, a metabolically active vaginal lesion, and two benign leiomyomas. An anterior pelvic exenteration (colpectomy, hysterectomy, bilateral adnexectomy, total cystectomy, and cutaneous ureteroileostomy ad modum Bricker) were performed by laparotomy in March 2016. Examination of the surgical specimens identified a 75 × 75-mm leiomyoma, an 80 × 30-mm infiltrating mesenchymal uterine lesion with vascular invasion and tumor emboli, and a 60 × 30-mm perivascular vaginal tumor. Immunohistochemistry indicated a phenotypic transition from a uterine leiomyosarcoma to a vaginal epithelioid lesion; marker expression changed from the uterine tumor actin+/desmin+/caldesmon+/CD10- phenotype, through the tumor emboli, to an actin-/desmin-/caldesmon-/CD10+ phenotype in the vaginal lesion. A high-grade uterine mesenchymal tumor and vaginal metastasis were diagnosed. Adjuvant chemotherapy with docetaxel, gemcitabine, and doxorubicin commenced in May 2016 and treatment has been well tolerated. CONCLUSIONS: Differentiating leiomyosarcoma from leiomyoma is challenging and few tools other than microscopic evaluation are available. Vaginal compromise in leiomyosarcoma usually results from tumor extension, not hematogenous metastasis. A vaginal metastasis is a very rare initial presentation. We have found only two cases like this described on published literature. The atypical clinical and histological presentation in our case complicated diagnosis and delayed treatment. An early diagnosis and complete surgical clearance gives the best chance of survival, and imaging tools should be applied early in instances of new suspicious malignant lesions.

Vaginal metastasis of bladder urothelial carcinoma: Description of a case and revision of literature.

Vaginal metastases from urothelial cancer are a rare entity and in literature, few cases are described. We report a case of a 68 year-old woman with history of bladder urothelial carcinoma underwent to radical cystectomy who came in our department after 5 months for pelvic pain and vaginal bleeding. Objective examination revealed an ulcerative, solid vaginal lesion in the upper vaginal wall. We performed a vaginal biopsy that showed urothelial carcinoma compatible with the primitive bladder cancer. The patient underwent to surgery and was sent to oncological evaluation.

[A Case of Recurrence in the Posterior Wall of the Virginal after Radical Resection for Rectal Cancer Well Responded in a Long Period by Chemo-Radiotherapy].

We report a case of an advanced rectal cancer recurrence that responded completely to chemo-radiotherapy. The patient was an 80-year-old woman. Low anterior resection with D2(prxD3)lymph node dissection was performed. Sixteen months after operation, CEA level elevated but no recurrence foci were found in any image tests. Administration of TS-1 was initiated since recurrence was highly suspected. Twenty seven months after operation, PET-CT detected local recurrence in the posterior wall of the vagina. After construction colostomy, chemo-radiotherapy(60 Gy+oral UFT)was performed and CEA level dropped promptly to the normal value. No relapse was pointed out in CT scans or MRI tests. There were not any signs of recurrence through 112 months after chemo-radiotherapy.

[A Resected Case of the Vaginal Metastasis from Rectal Cancer].

The vaginal metastasis from colorectal cancer has rarely been reported. Here, we report a resected case of the vaginal metastasis from rectal cancer. A 51-year-old woman underwent radical hysterectomy and bilateral oophorectomy for uterus cancer. Five years after the operation, vaginal tumor was observed during an internal examination. Biopsy was positive for adenocarcinoma. Enhanced computed tomography demonstrated the wall thickening of the lower rectum and the mass of 20 mm at the inferior lobe of the left lung. Colonoscopy revealed the wall thickening of the lower rectum, and biopsy indicated a diagnosis of rectal cancer. We performed abdominoperineal resection and partial resection of the vagina. Pathological examination confirmed the vaginal metastasis from the rectal cancer.

Bladder cancer will grow anywhere: report of a urothelial carcinoma drop metastasis to the vagina and literature review.

Urothelial carcinoma is the 2nd most common cancer of the urinary tract and accounts for the majority of cases of bladder cancer. Metastases are not infrequently encountered, increasing with disease stage and are most commonly seen in the bones and lungs. Many other sites have been described including the omentum, liver, and ovaries. An extremely rare site of metastatic disease however is within the vagina. Here we present a case of a probable vaginal 'drop metastasis' from previously treated urothelial carcinoma in the ureter and bladder.

Vagina as a rare location of renal cell carcinoma metastasis.

INTRODUCTION: Metastatic renal cell carcinoma is often found in distant organs, including lung, bone, brain, and liver. Metastases to the vagina are extremely rare. CASE REPORT: The authors present a case of renal cell carcinoma metastasis to the anterior vaginal wall four months after nephrectomy in a 56-year-old patient. The vaginal lesions were excised. After two years the patient had no signs of recurrence or the disease progression. CONCLUSION: Vaginal metastases should be considered in differential diagnosis of female renal cell carcinoma patients presenting with vaginal bleeding of mass.

[The Vaginal Metastasis of Ureteral Carcinoma after Left Nephroureterectomy: A Case Report].

69-year-old woman underwent left nephroureterectomy for left ureteral cancer (urothelial carcinoma (UC), high grade, pT3pN0) in September 2013. She returned to our hospital presenting with asymptomatic macrohematuria in July 2014. Cystoscopy showed tiny papillary tumors in the bladder. We also found genital bleeding from multiple papillary tumors on the vaginal wall. We performed transurethral resection of the bladder tumor and a biopsy of the vaginal wall demonstrated non-invasive UC, high grade. Pelvic magnetic resonance imaging after the operation showed no infiltration outside the bladder wall and vaginal wall. Therefore, we performed endoscopic excision of the vaginal tumor. However we could not resect all vaginal tumors. Irradiation of the vagina and uterus was performed under the diagnosis of metastasis of UC tovagina. Vaginal UC is extremely rare and this is the 26th case report in the literature.

Adjuvant vaginal brachytherapy decreases the risk of vaginal recurrence in patients with stage I non-invasive uterine papillary serous carcinoma. A multi-institutional study.

OBJECTIVES: To investigate the impact of adjuvant vaginal brachytherapy on vaginal recurrence in stage I non-invasive uterine papillary serous carcinoma (UPSC). METHODS: This is a retrospective multi-institutional study from 2000-2012. 103 patients who underwent surgical treatment with non-invasive stage IA UPSC were included. RESULTS: 85% and 55% underwent staging lymphadenectomy and omentectomy respectively. 28.2% (29/103) developed recurrence. Vaginal, pelvic and extra-pelvic recurrences developed in 7.8% (8/103), 3.9% (4/103) and 16.5% (17/103) respectively. Among patients who were observed or received only chemotherapy, the rate of vaginal recurrence was 10.9% (7/64) compared to 2.6% (1/39) among those who received vaginal brachytherapy +/- chemotherapy (p=0.035). The rate of vaginal recurrence was not different between those who were observed and those who received only chemotherapy (9.3% vs. 14.3%, p=0.27). The 5-year progression free survival (PFS) and overall survival (OS) for the entire cohort were 88.3% and 90.6%. Patients who underwent surgical staging had longer PFS (p=0.001) and OS (p=0.0005) compared to those who did not. In multivariable analysis controlling for age, histology, chemotherapy, brachytherapy, and staging lymphadenectomy, only lymphadenectomy was an independent predictor of PFS (HR 0.28, 95% CI 0.11-0.71, p=0.0037) and OS (HR 0.27, 95% CI 0.10-0.71, p=0.0035). Neither chemotherapy nor brachytherapy were predictors of PFS or OS. CONCLUSIONS: This is the largest study reported in stage I non-invasive UPSC. The majority of recurrences were extra-pelvic. Vaginal brachytherapy has a significant role in reducing the risk of vaginal recurrence and surgical staging was the only predictor of outcome. Therefore, both should be considered in these patients.

Prognostic impact of infiltration of the vagina and/or uterus in women undergoing anterior pelvic exenteration for urothelial carcinoma of the bladder: results of a contemporary multicentre series.

PURPOSE: To evaluate for the first time the prognostic significance of female invasive patterns in stage pT4a urothelial carcinoma of the bladder in a large series of women undergoing anterior pelvic exenteration. PATIENTS AND METHODS: Our series comprised of 92 female patients in total of whom 87 with known invasion patterns were eligible for final analysis. Median follow-up for evaluation of cancer-specific mortality (CSM) was 38 months (interquartile ranges, 21-82 months). The impact on CSM was evaluated using multivariable Cox proportional-hazards regression analysis; predictive accuracy (PA) was assessed by receiver operating characteristic analysis. RESULTS: Vaginal invasion was noted in 33 patients (37.9 %; group VAG), uterine invasion in 20 patients (23 %; group UT), and infiltration of both vagina and uterus in 34 patients (39.1 %; group VAG + UT). Groups VAG and UT significantly differed from group VAG + UT with regard to the presence of positive soft tissue margins (STM) only. Five-year-cancer-specific survival probabilities in the groups VAG, UT, and VAG + UT were 21, 20, and 21 %, respectively (p = 0.955). On multivariable analysis, only STM status (HR = 2.02, p = 0.023) independently influenced CSM. C-indices of multivariable models for CSM with and without integration of invasive patterns were 0.570 and 0.567, respectively (PA gain 0.3 %, p = 0.526). CONCLUSIONS: Infiltration of the vagina, the uterus or both is associated with poor 5-year survival rates. With regard to CSM, no difference was detectable between patients with different invasion patterns, thus justifying further collectively including these invasive patterns as stage pT4a.

Pagetoid spread of bladder urothelial carcinoma to the vagina and vulva.

OBJECTIVE: To study the clinicopathologic features of a rare disease of pagetoid urothelial intraepithelial neoplasia (PUIN) in the vulva. MATERIALS AND METHODS: We reviewed a case of PUIN in a Chinese woman with a long history of bladder urothelial carcinoma. RESULTS: The patient presented with vulvar pruritus for more than 1 month. Gynecologic examination showed a red, thickened, eczematoid lesion in the bilateral labia minora and a palpable 4-cm mass between the middle part of the vagina and the urethral meatus. Microscopically, the neoplastic cells with clear or pale eosinophilic cytoplasm were distributed throughout the squamous epithelium, with a predilection for the middle and basal portion in the vulva. Acantholysis-related papillary formation and pagetoid spread pattern to the normal squamous epithelium were also present. Invasive carcinoma was found underneath the unremarkable squamous epithelium in the vaginal biopsy. Immunohistochemistry demonstrated that these cells were negative for mucin stain, carcinoembryonic antigen, and 34ßE12 and were strongly positive for cytokeratins 5/6, 7, 18, 19, and 20. CONCLUSIONS: This rare entity of PUIN was associated with metastatic urothelial carcinoma and should be discriminated from vulvar Paget disease and pagetoid squamous cell carcinoma in situ.

Magnetic resonance appearance of gastric-type adenocarcinoma of the uterine cervix in comparison with that of usual-type endocervical adenocarcinoma: a pitfall of newly described unusual subtype of endocervical adenocarcinoma.

OBJECTIVE: The aim of this study was to evaluate the characteristics of gastric-type adenocarcinoma (GAS) of the uterine cervix, compared with usual-type endocervical adenocarcinoma (UEA) and squamous cell carcinoma (SCC), using magnetic resonance (MR) imaging. MATERIALS AND METHODS: A total of 15 histopathologically defined GASs, 12 UEAs, and 40 SCCs were retrieved from archive files and were included for evaluation. Microscopic features, as well as topography and tumor growth pattern, and presence or absence of coexistence of cystic cavities were evaluated. Accuracy of evaluation for parametrial tissue and vaginal wall invasion was also evaluated by 2 diagnostic radiologists, independently, without clinical information on cases. RESULTS: Thirteen (86.70%) of the 15 cases of GAS exhibited tumors in the higher portion of cervical canal or the entire cervix. On the other hand, SCCs and UEAs were mainly located in the lower portion of cervical canal, at a frequency of 21 of 40 (52.5%) and 9 of 12 (75.0%), respectively. Involvement of the corpus was observed more frequently in cases of GAS with an occurrence of 8 of 15 (53.3%), whereas in all cases of UEA and in 5 of the 40 cases of SCC, the corpus was free of tumor. In GAS cases, the predominant pattern of growth was highly infiltrating and endophytic (14/15, 93.3%), whereas an exophytic growth pattern was observed in 31 (77.5%) of the 40 SCC cases and 11 (91.7%) of the 12 UEA cases. Cystic cavities associated with tumors were identified in only 1 case of SCC but occurred in 12 (80.0%) of the 15 GASs and 4 (33.3%) of the 12 UEAs. Diagnostic accuracies of more than 70% and more than 60% were reached in parametrial invasion and vaginal invasion, respectively, in GAS. CONCLUSION: Distinctive MR imaging features of GAS were infiltrating mass of endophytic growth, location in the upper cervical canal, and association with tiny cysts. This characteristic appearance can be a clue for the evaluation of extent of tumor based on MR imaging.

An isolated vaginal metastasis from rectal cancer: a case report.

INTRODUCTION: Vaginal metastasis from colorectal cancer is a rare occurrence, typically associated with other metastatic lesions. Isolated metastasis is exceedingly uncommon, with only a few cases documented in the literature. Vaginal involvement in colorectal cancer primarily results from direct contiguous spread from the primary tumor. CASE PRESENTATION: We present the case of a 70-year-old African woman diagnosed with adenocarcinoma of the middle rectum. She underwent chemotherapy, radiotherapy, and subsequent anterior resection. After 2 months, an isolated metastasis of rectal cancer was identified in the lower third of the left vaginal wall, confirmed by biopsy. Colonoscopy ruled out colorectal recurrence. Thoraco-abdominal computed tomography scan showed no distant metastases. The patient underwent abdominoperineal resection, removing the lateral and posterior vaginal wall with free macroscopic margins and a definitive colostomy. The final histopathological analysis confirmed the diagnosis of moderately differentiated adenocarcinoma of the vagina, measuring 5 × 4.5 cm. The rectal wall was extrinsically invaded by the tumor down to the muscularis propria while respecting the rectal mucosa. Resection margins were negative. The patient was discharged 1 week postoperation with no complications. Adjuvant chemotherapy was indicated, and the patient is currently tolerating the treatment well. CONCLUSION: Vaginal metastases from colorectal cancer are extremely rare. A vigilant gynecological examination is recommended during the follow-up of colorectal cancer patients. Diagnosis can be challenging, especially if the metastatic lesion is small and asymptomatic, even after standard radiological examination. Surgical resection followed by chemotherapy is a valid option for patients with early isolated metastases.

Three-dimensional transvaginal ultrasonography for locally advanced cervical cancer.

OBJECTIVE: The aim of the study was to evaluate the feasibility of using 3-dimensional transvaginal ultrasound (3D-TVUS) to diagnose the extent of invasive cervical cancer. METHODS: Using 3D-TVUS, we prospectively examined 24 patients diagnosed with locally advanced invasive cervical cancer before primary surgery. Parametrial, vaginal, bladder, and rectal invasion, alongside cancer staging, was evaluated in the orthogonal planes. We compared the preoperative clinical, magnetic resonance imaging (MRI), and ultrasonography findings with the histological results from surgery. RESULTS: With respect to cancer staging, accuracy was 62.5% with clinical examination, 40.9% with MRI, and 66.7% with TVUS. Magnetic resonance imaging demonstrated both low specificity (64.3%) and accuracy (68.2%) for nodal involvement. For the detection of parametrial invasion: sensitivity was 25% with clinical exanimation, 75% with MRI, and 75% with TVUS; specificity was 55.6% with MRI and 90% with TVUS; accuracy was 59% with MRI and 87.5% with TVUS. Although there was no case with bladder or rectal invasion, TVUS and MRI showed high specificity for the assessment of these. Clinical examination was useful for the detection of vaginal involvement. CONCLUSIONS: Preoperative 3D-TVUS may prove to be an excellent method for the evaluation of locally advanced cervical cancer. Transvaginal ultrasound also has advantages over MRI for the assessment of tumor volume and Doppler velocimetry and is a low-cost alternative. However, TVUS cannot identify nodal or distant metastasis.