Long-term response of metastatic hereditary leiomyomatosis and renal cell carcinoma syndrome associated renal cell carcinoma to bevacizumab plus erlotinib after temsirolimus and axitinib treatment failures.

BACKGROUND: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare hereditary kidney cancer syndrome in which affected individuals are at risk of skin and uterine leiomyomatosis and kidney cancer. HLRCC-associated kidney cancer is a lethal disease with a highly aggressive behavior, and there is no standard treatment option for metastatic disease. CASE PRESENTATION: Here, we report a 29-year-old patient with a locally advanced HLRCC-assiciated RCC. He was administrated temsirolimus initially, then underwent surgical removal of kidney, retroperitoneal lymph nodes, inferior vena cava and tumor thrombi. Unfortunately, multiple liver metastases were confirmed 1 month after surgery, so axitinib was given but failed immediately. We tried bevacizumab plus erlotinib, which achieved long-term good response lasting more than 18 months. He is alive with disease and maintains bevacizumab plus erlotinib treatment. CONCLUSION: The promising results obtained in this patient suggest that combined bevacizumab plus erlotinib may offer a valid treatment option for advanced HLRCC-associated kidney cancer, even after failures of mTOR inhibitor and/or VEGFR TKI based therapies.

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.

Second primary uterine malignancies after radiation therapy for cervical cancer.

PURPOSE: Radiation exposure has long been established as a risk factor for cancer development. The purpose of this study is to assess the risk of uterine malignancy in patients previously treated for cervical cancer with radiation therapy. METHODS: A population-based cohort of 9092 patients diagnosed with cervical cancer who did not undergo surgery and received radiation therapy between 1973 and 2008 was identified from the Surveillance, Epidemiology and End Results Program database (SEER 9). Patients in this cohort who developed endometrial cancer after treatment of cervical cancer were identified. 55,140 patients with endometrial cancer were also identified. The distribution of the different histologic types of endometrial cancer was determined for each of these cohorts. RESULTS: 54 patients (0.6%) were diagnosed with an endometrial cancer more than 12 months after diagnosis of cervical cancer. The average latency to endometrial cancer diagnosis was 160 months, with a range of 14-374 months. The average age of cervical cancer diagnosis was 52 years and the average age at subsequent endometrial cancer diagnosis was 66 years. Only 40% of the endometrial cancers diagnosed following treatment of cervical cancer were endometrioid. The majority were clear-cell adenocarcinomas (42%), 9% were carcinosarcomas and 5.5% were leiomyosarcomas. Of the 55,140 endometrial cancer patients in the database, a vast majority were endometrioid adenocarcinomas (91%), and only 2.3% clear-cell adenocarcinoma, 2.3% carcinosarcoma and 0.5% leiomyosarcoma. The difference in histologic type distribution between these two cohorts is highly significant (p < 0.01). CONCLUSION: A small proportion of women who receive radiation for cervical cancer go on to develop endometrial cancer. These are predominantly of the more aggressive histologic types when compared to primary endometrial cancers. The latency from cervical cancer diagnosis to endometrial cancer diagnosis is over a decade. In a patient who still has a uterus after receiving pelvic radiation, vaginal bleeding should be investigated.

Malignant Female Adnexal Tumor of Probable Wolffian Origin: Case Report and Literature Review.

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.

Uterine metastasis of lung adenocarcinoma under molecular target therapy with epidermal growth factor receptor tyrosine kinase inhibitors: A case report and review of the literature.

A 63-year-old woman presented with abnormal vaginal bleeding. Her disease history was significant, and included advanced lung adenocarcinoma with a deletion mutation in exon 19 of the epidermal growth factor receptor (EGFR) gene, which was managed by concurrent chemoradiotherapy, followed by molecular targeted therapy with tyrosine kinase inhibitors (TKIs) for a two-year period. Contrast-enhanced computed tomography showed the enlargement of a previously suspicious myoma node, with peripheral enhancement. Hemorrhagic necrosis was also observed on magnetic resonance imaging. Transabdominal hysterectomy and bilateral salpingo-oophorectomy showed solitary intramyometrial metastatic lung adenocarcinoma with a second-site T790M gatekeeper mutation in exon 20 of the EGFR gene. In conclusion, uterine metastasis from lung adenocarcinoma can present a diagnostic challenge. The possibility of lung cancer metastasis should be considered when a uterine mass increases in size during treatment. Molecular analysis of the EGFR gene to detect mutations could provide useful information for planning the treatment strategy.

p40 in metastatic pulmonary trophoblastic tumour: potential diagnostic pitfall on histopathology.

p40, one of the two isomers of p63, is nowadays widely used for diagnosis of squamous cell carcinoma, especially in subtyping non-small cell carcinoma on lung biopsies. We describe a case in which lung tumour was misdiagnosed as squamous cell carcinoma due to p40 immunopositivity. A 36-year-old lady presented with cough and left sided chest pain of 2 months duration. Chest imaging revealed a lesion in left lower lobe of the lung and biopsy was suggestive of squamous cell carcinoma. However, past history revealed amputation of great toe for non-healing discharging ulcer which on histopathology was diagnosed as choriocarcinoma. She also had a history of hysterectomy five years ago, details of which were not available. Post-amputation ß-hCG levels were high and she had been treated with multimodality chemotherapy for choriocarcinoma. She had good response to chemotherapy initially, however became resistant later on. Review of the lung biopsy in the light of the past history along with extensive literature review led to the final diagnosis of metastatic trophoblastic tumour to lung. Hence, awareness that p40 immunopositivity can be seen in trophoblastic tumours is essential to avoid misdiagnosis, especially in sites like the lung where squamous cell carcinoma is common.

[A Hematogenous Metastasis from Scirrhous Gastric Cancer to the Uterus].

A 46-year-old woman was referred to our hospital because of nausea. Endoscopy revealed scirrhous gastric cancer, and abdominalcomputed tomography revealed peritonealdissemination. She was diagnosed with Stage IV gastric cancer and treated with S-1 plus CDDP combination chemotherapy. After 4 courses of chemotherapy, the primary tumor and peritoneal dissemination were considered clinically stable, but the uterus grew rapidly. She was diagnosed as having uterine metastasis based on cervicaland endometrialsmear class V cytology. As the chemotherapy was not effective for the uterine lesions, totalhysterectomy and bilateralsal pingo-oophorectomy were performed. Histological findings showed a poorly differentiated cancer with vascular emboli. Uterine metastases are an important consideration in women with scirrhous gastric cancer, and we recommend palliative hysterectomy for chemotherapy-resistant metastases if the primary tumor and other metastases are controlled.

[A Case of Uterine Body Metastasis from Sigmoid Colon Adenocarcinoma].

We report a case of metastatic carcinoma to the uterine body from a colorectal adenocarcinoma. A 73-year-old woman underwent laparoscopic sigmoidectomy for sigmoid colon carcinoma 2 years before. In the following study, her serum carcinoembryonic antigen level was elevated, and a uterine body tumor invading the rectal wall was detected via enhanced computed tomography. Colonoscopic examination revealed an elevated lesion at the rectum, which was diagnosed as an adenocarcinoma. Based on these results, we diagnosed the uterine tumor as metastatic tumor from the colon carcinoma. Immunostaining was negative for CK7, but positive for CK20. Thus, we confirmed metastasis of the sigmoid colon cancer to the uterus. Metastasis to the female genital tract from extragenital malignancies are rare, and the prognosis is extremely poor. However, some patients attain long-term survival by surgical intervention even in such cases.

Parasitic myoma after laparoscopic morcellation: a systematic review of the literature.

BACKGROUND: Laparoscopic morcellation is frequently used for tissue removal after laparoscopic hysterectomy or myomectomy and may result in parasitic myomas, due to seeding of remained tissue fragments in the abdominal cavity. However, little is known about the incidence and risk factors of this phenomenon. OBJECTIVES: To identify the incidence and risk factors for the development of parasitic myoma after laparoscopic morcellation. SEARCH STRATEGY: A systematic review of the literature in Pubmed (MEDLINE) and Embase was conducted. Reference lists of identified relevant articles were checked for missing case reports. SELECTION CRITERIA: Studies reporting on incidence or cases of parasitic myoma diagnosed after laparoscopic morcellation were selected. Studies were excluded when history of laparoscopic morcellation was lacking or final pathology demonstrated a malignancy or endometriosis. DATA COLLECTION AND ANALYSIS: Data were extracted and analysed on incidence of parasitic myomas and characteristics of case reports. MAIN RESULTS: Fourty-four studies were included. Sixty-nine women diagnosed with parasitic myomas after laparoscopic morcellation were identified. Mean age was 40.8 (± 7.5) years (range 24-57), median time between surgery and diagnosis was 48.0 months (range 1-192) and mean number of parasitic myomas was 2.9 (± 3.3) (range 1-16). The overall incidence of parasitic myomas after laparoscopic morcellation was 0.12-0.95%. CONCLUSION: Although the incidence is relatively low, it is important to discuss the risk of parasitic myoma after laparoscopic morcellation with women and balance towards alternative treatment options. The duration of steroid exposure after laparoscopic morcellation might be a risk factor for development of parasitic myomas. TWEETABLE ABSTRACT: Systematic review on the incidence and risk factors for parasitic myoma after laparoscopic morcellation.

A case report of benign metastasizing leiomyoma of the lung: FDG-PET-CT findings and the utility of uterine needle biopsy.

Benign metastasizing leiomyoma (BML) is a rare condition that affects other organs out of the uterus. Recently, a few case reports in which 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been used to distinguish the malignancy have been published. Here, the authors present a case of BML with metabolic activity on PET, in which needle biopsy of the uterus was efficient to make diagnosis.

[A Case of a Patient with Metastatic Rectal-Uterine Cancer from the Ascending Colon Who Underwent NOSE].

An 80-year-old woman had undergone a right hemicolectomy for ascending colon cancer 9 months prior to the current presentation. CT and PET-CT showed a solitary tumor measuring 55mm in diameter at the uterus and rectum. Three 5mm ports and two 12mm two ports were placed. The sigmoid colon was mobilized using a medial approach as usual in laparoscopic surgery. The rectum and uterus were mobilized and were resected. We inserted the End-catchTM in from the vagina and removed the specimen. The patient had no abdominal pain and was discharged from the hospital 9 days after the operation.

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.

Secondary Involvement of the Adnexa and Uterine Corpus by Carcinomas of the Uterine Cervix: A Detailed Morphologic Description.

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.

Incidental Finding of Metastatic Cutaneous Malignant Melanoma at Uterine Leiomyoma, A Thai University Hospital Experience: A Case Report.

BACKGROUND: Metastatic malignant melanomas to the uterus are extremely rare; to our knowledge, no more than 13 cases have been reported to date. CASE REPORT: A 44-years-old multigravida woman presented with a black and irregular surface mass at medial aspect of left thigh. There was also an enlarged left groin node. Wide excision with lymph node dissection revealed malignant melanoma. Further examination found a huge pelvic mass with left deep vein thrombosis consequent by pressure effect. Chest and complete abdominal computed tomography revealed an enlarged, fibroid uterus with pressure effect at left common iliac vein. A total abdominal hysterectomy and bilateral adnexectomy were performed. Intra-operative finding was scattered hyperpigment spots at surface of the uterus and its tumor Histopathological report showed metastatic malignant melanoma involving myometrium and uterine serosa. Diagnosis of stage IV malignant melanoma (uterine metastasis) was achieved. The patient was counseled about her diagnosis, stage, prognosis and further treatment. CONCLUSION: Uterine metastatic malignant melanoma was a rare condition. This report represents the first case of a cutaneous malignant melanoma involving a uterine leiomyoma in Thailand.

[Metastasizing Leiomyoma of the Lung Detected on Chest X-ray after Surgery for Breast Cancer；Report of a Case].

A 60-year-old postmenopausal woman presented with a lung nodule, which was detected on a chest X-ray 2 years after surgery for breast cancer. Pulmonary metastasis from the breast cancer was suspected and surgical resection was performed. On histopathological examination, the lung nodule showed a smooth muscle cell tumor, and immunohistochemical staining was positive for estrogen and progesterone receptors. As a mass in the uterine was detected by computed tomography images before surgical resection, benign metastasizing leiomyoma of the lung was suspected. Subsequently, the patient underwent hysterectomy and bilateral salpingo-oophorectomy. The pathological findings revealed that the mass in the uterine was atypical leiomyoma, which was consistent with the primary lesion of the lung metastasis. Atypical leiomyoma is classified as a benign tumor, but in this case, careful follow-up is required because of its clinical course and histological features.

[A Case of Sigmoid Colon Cancer with Metastasis to the Uterus].

A 65-year-old woman complaining of fetor ex vagina was diagnosed with endometrial adenocarcinoma of the uterus based on the pathological findings of an endometrial biopsy. Sigmoid colon cancer was found on a pre-operative CT scan. Diagnosis of double cancer was made and we performed sigmoidectomy and panhysterectomy with associated resection of both adnexa. Histopathological examination found that the tumor accounted for almost all of the uterine mucosa and over half of the muscular layer. Immunostaining showed CK7 (-), CK20 (+), CDX2 (+), ER (-), and PgR (-), and we diagnosed it as a metastasis to the uterus of the sigmoid colon cancer. The pathological diagnosis was a moderately differentiated adenocarcinoma, pT4b (SI: urinary bladder), pN0 (0/12), H0, P1,M1a (uterus), pStage Ⅳ. As adjuvant chemotherapy, she was administered XELOX for 6 months. Although colorectal cancer rarely metastasizes to the uterus, due to the increase in the prevalence of colorectal cancer, it may be also increase. To choose the best treatment course, it is necessary to diagnose whether it is a primary uterine cancer or a metastatic uterine cancer.

Case report: Renal cell carcinoma with metastasis to the myometrium.

Renal cell carcinoma (RCC) is well known for its ability to metastasize to different organs, but the involvement of gynecological organs is rare. Our case represents the first case of bilateral RCC with metastasis to the myometrium. The patient was a 60-year-old woman who underwent bilateral robotic partial nephrectomy surgeries for clear cell RCC, low-grade, low-stage with negative margins. Her 1-year postoperative computed tomography scan showed an enlarging necrotic uterine mass. She underwent a debulking excision, including hysterectomy, with pathology showing metastatic RCC to the uterus. The patient developed widespread metastatic disease, and died months later of metastatic RCC.

Massive perivillous fibrin deposition in the placenta and uterine metastasis of gastric adenocarcinoma during pregnancy.

The prognosis of gastric cancer during pregnancy is unfavorable because of delayed diagnosis and advanced stage. We present a case of gastric carcinoma metastasized to the placenta and uterus during pregnancy. Pathological examination revealed a poorly differentiated adenocarcinoma of the stomach with lymph node metastasis. After counseling, the patient decided to terminate the pregnancy and begin immediate treatment for gastric cancer. Hysterectomy and subtotal hysterectomy were performed because medical termination of the pregnancy was unsuccessful. Pathological examination of the placenta and uterus revealed metastases of gastric adenocarcinoma. All the uterine vessels were packed with tumor cells and the myometrium showed extensive coagulative necrosis. Moreover, microscopic findings of the placenta were consistent with massive perivillous fibrin deposition. Our case clearly suggests that massive perivillous fibrin deposition in the placenta can be associated with malignancy during pregnancy and that uterine metastasis of maternal malignancy may result in myometrial dysfunction unresponsive to uterotonics.

Papillary thyroid carcinoma with massive metastasis in the uterine corpus: a case report.

BACKGROUND: Distant metastases stemming from a papillary thyroid carcinoma (PTC) are quite rare. Here we report an exceptional case of PTC presenting with cervical lymphatic and uterine metastases. This is the first case report of a PTC with uterine involvement. CASE PRESENTATION: A 60-year-old Chinese woman came to our hospital complaining of discomfort in the throat that she had been experiencing for about half a month. PTC and cervical lymphatic metastasis were diagnosed after ultrasound examinations. A massive heterogeneous mass was found beside the uterus during the pre-operative checkup and a diagnosis of ovarian carcinoma was suspected after a thorough case discussion. However, it proved to be a metastasis from the PTC as determined by pathological and immunohistochemical examinations after the operation. The patient declined further treatments. She was followed for 22 months with no sign of recurrence detected. CONCLUSIONS: In this report, an unusual case of PTC was presented. The patient had not only regional lymphatic metastasis, but also had a massive metastasis in the uterine corpus, which was initially misdiagnosed as ovarian carcinoma. This case is of interest because of its rarity and exceptionally good prognosis. The reason for the misdiagnosis was attributed to overlooking the possibility of a distant metastasis coming from a PTC. This case raises the issue that completing an iodine-131 scan before operating on patients with PTC may be warranted.