Tumors Of Low Malignant Potential Research Articles

P-234 A SEER based analysis of clinical characteristics and survival in patients with functional endocrine tumors of gastrointestinal origin

Functional endocrine tumors (FETs) belong to the heterogeneous class of neuroendocrine tumors characterized by excess secretion of disease-specific hormones. These are uncommon tumors of low malignant potential, however, rarely these tumors can become metastatic. The main goals of treatment include amelioration of symptoms from the overproduction of hormones and to address tumor growth.

Dermatofibrosarcoma protuberance: a recrudescent dermal malignancy

Dermatofibrosarcoma protruberens is a rare soft tissue tumour of low malignant potential, commonly seen on the trunk and extremities. It is a slow growing sarcoma, with a tendency for recurrence. Rarely, it may be a high-grade tumour. It responds well to wide local excision. Radiotherapy is beneficial for margin positive and high-grade tumours. We present a case of a 22 years old male with a dermatofibrosarcoma protruberens presenting as a swelling over the left inguinal region since, 4 years, that was excised with a 2cm margin. Patient was followed up for six months without any recurrence.

Endocrine biomarkers in low-grade serous ovarian cancers (LGSC) and serous ovarian tumors of low malignant potential (LMP).

e18045 Background: LGSC and serous ovarian LMP tumors are rare entities along a disease continuum. Because they are relatively chemotherapy resistant, there is interest in targeted treatment, including endocrine therapy. In studies of endocrine agents for treatment of recurrent ovarian cancer, tumor estrogen receptor (ER) status alone does not effectively predict outcomes. The objective of this study is to utilize protein and gene expression from ER and downstream targets to identify signaling components that will act as prognostic and predictive biomarkers. Methods: A single institution tumor registry was queried for patients with LGSC or serous LMP tumors between 1993-2016. Formalin-fixed, paraffin embedded (FFPE) tissue was obtained. Clinicopathologic data was collected. Immunohistochemistry (IHC) was performed and scored as dichotomous (+/-) and continuous (H-score). NanoString nCounter platform was used for gene expression of a predesigned endocrine biomarker panel. Wilcoxon Rank Sum was used to compare mRNA and protein expression. Survival analyses were performed using Cox proportional hazard (PH) method with elastic net to fit the prediction model for the gene panel. Results: Tissue was analyzed from 23 LGSC, 71 serous LMP tumors, and 2 recurrences. At diagnosis, 86% of patients with LMP tumors had stage I disease vs 78% of patients with LGSC had stage III/IV disease. There were 7 (10%) LMP and 13 (56.5%) LGSC recurrences. Median initial PFS was 76 and 37 months and median OS was 88 and 82 months for LMP and LGSC, respectively. Fourteen received endocrine therapy; nine for treatment of recurrent LGSC. Median therapy was 21 months, with 3 complete responses, 2 partial responses and 1 stable disease. All tumors were ER+ (median H-score 210) and 89% were PR+ (median H-score 130). ER H-scores and ESR1 expression levels were not significantly different between LGSC and LMP tumors (p = 0.1942, p = 0.0893). PR H-scores were higher in LMP tumors (p < 0.00001) but PGR expression was not significantly different (p = 0.6581). In the Cox PH analysis, ER H-score was a significant predictor of both PFS and OS (p < 0.001, p = 0.004). The Cox model identified independent sets of gene expression associated with PFS and OS in both the LGSC and LMP cohorts (c-indices 0.679, 0.570, 0.626, 0.689). Conclusions: Endocrine therapy is an active area of interest in the treatment of ovarian neoplasms. ER H-score and gene expression of downstream ER targets could improve upon the use of hormone receptors to determine risk of recurrence and guide use of adjuvant endocrine therapy.

Factors affecting recurrence rates in women with borderline ovarian tumors.

e18055 Background: Borderline or low malignant potential tumors of the ovary (BOTs) make up approximately 15-20% of all ovarian neoplasms. These tumors are considered indolent and usually confer an excellent overall survival in women who are treated utilizing a conservative surgical approach. However, recurrence rates can approach 30%. The aim of this study was to compare the type and mode of surgery and its impact on outcomes in patients with BOTs. Methods: An Institutional Review Board approved, retrospective cohort study identified all patients at Long Island Jewish Medical Center, North Shore University Hospital and USC Medical Center with BOTs who underwent surgery between January 2008 and May 2018. Demographics and outcome measures were obtained from the medical records. Prognostic factors for disease recurrence were studied including histological subtypes type of surgical procedure, including minimally invasive or open ovarian cystectomy and oophorectomy. Results: 260 patients were identified. 226 of these women (88%) had stage I disease at the time of diagnosis. There were 26 recurrences noted in the cohort, a recurrence rate of 10 percent. The median age was 50 years old (range 16-86). 145 patients (56%) underwent minimally invasive surgical procedures compared to 115 (44%) who had open laparotomy. 30 (12%) of the women underwent an ovarian cystectomy and 230 (88%) had an oophorectomy. The median time to disease recurrence was 25 months (range 4-94 months). There was significant difference in the recurrence free survival between the patients who had minimally invasive procedures and those who had open laparotomy (hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.11-6.52). There was also significant difference in Recurrence Free Survival (RFS) and in those who underwent ovarian cystectomy and oophorectomy (HR 7.32, 95%CI 3.34-16.06). No difference in recurrence rates were noted between those with serous and mucinous histology. Conclusions: In this cohort of women with BOTs, the risk of recurrence was associated with minimally invasive surgery versus open laparotomy as well as ovarian cystectomy compared with oophorectomy. Conservative surgery for BOTs in young patients plays an important role for fertility preservation in these young women and can be curative. This study allows us to present additional information to address surgical approach and risk for disease recurrence in young women having fertility sparing and conservative surgery for BOTs.

The Diagnosis, Treatment, Prognosis and Molecular Pathology of Borderline Ovarian Tumors: Current Status and Perspectives.

Borderline ovarian tumors (BOTs) are a type of low malignant potential tumor that is typically associated with better outcomes than ovarian cancer. Indeed, its 10-year survival rate is as high as 95%. However, there is a small subset of patients who experience relapse and eventually die. It has been shown that the prognosis of BOTs was based on pathological diagnosis, the age at diagnosis, pre-operative carbohydrate antigen 125 level, invasive implants, and micropapillary patterns. Now the molecular-targeted therapy and molecular-genetic diagnosis have developed into a form of precision medicine. Recent studies on extensive molecular characterizations and molecular pathological mechanisms of BOTs have helped us understand the genomic landscapes of BOTs, and therefore BOTs could be reclassified into biologically and clinically more accurate and effective subtypes. The purpose of this review is to summarize current status for the diagnosis and treatment of BOTs and to describe the research progress on molecular pathologies, with a goal of providing a theoretical perspective for the diagnosis and treatment of BOTs.

Appraising the role of circulating concentrations of micro-nutrients in epithelial ovarian cancer risk: A Mendelian randomization analysis

To determine the causality of micro-nutrients concentrations and risk of ovarian cancer using the Mendelian randomization approach. Analyses were conducted using summary statistics data for SNPs robustly associated with concentrations of thirteen micro-nutrients (iron, copper, zinc, calcium, magnesium, phosphorus, selenium, vitamin A, β-carotene, vitamin B6, vitamin B12, vitamin E, folate). The corresponding data for ovarian cancer were obtained from the Ovarian Cancer Association Consortium (25,509 cases and 40,941 controls). In standard Mendelian randomization analysis, the odds ratios (OR) of invasive epithelial ovarian cancer were 0.14 (95% CI, 0.03–0.70; P = 0.02) per 0.1 mmol/L (about one standard deviation, SD) increase in genetically predicted magnesium concentration, 1.04 (95% CI, 1.00–1.09; P = 0.03) per 0.3 μmol/liter (about one SD) increase in genetically predicted β-carotene concentration. The OR of low malignant potential tumours were 0.82 (95% CI, 0.76–0.90; P = 1.01 × 10−5) per 0.3 μmol/liter (about one SD) increase in β-carotene concentration, 1.42 (95% CI, 1.21–1.68; P = 3 × 10−5) per 153 pmol/L (about one SD) increase in vitamin B12 concentration, 0.21 (95% CI, 0.06–0.76; P = 0.02) per 6 mg/L (about one SD) increase in vitamin E concentration. No significant associations of other micro-nutrients and ovarian cancer were observed. This study found that an increased risk of invasive epithelial ovarian cancer was observed with a genetically higher concentration of β-carotene, whereas a decreased risk of invasive epithelial ovarian cancer was found with a higher concentration of magnesium. As for low malignant potential tumours, increased concentration of vitamin B12 could increase the risk of low malignant potential tumours, while increased concentrations of β-carotene and vitamin E could lower the risk of low malignant potential tumours.

V03-05 ROBOTIC APPENDICEAL ONLAY URETEROPLASTY FOR RECURRENT LOW GRADE UROTHELIAL CARCINOMA

INTRODUCTION AND OBJECTIVE: We report the case of a 63 year-old male smoker with recurrent low grade urothelial carcinoma and papillary urothelial neoplasm of low malignant potential, refractory to multiple rounds of endoscopic management. He underwent successful robotic assisted mid-ureteral segmentectomy followed by augmented ureteroplasty with anterior onlay appendiceal flap. METHODS: After docking, the right ureter was mobilized and direct visual ureteroscopy helped delineate the margins of the tumor using precise suture ligation to sequester the tumorous segment. After specimen removal, the defect was assessed and residual tension due to retraction precluded a suitable primary ureteroureterostomy (UU). After consideration of the various reconstructive options, we decided upon an appendiceal interposition. The appendix had adequate length, and intravenous indocyanine green (ICG) with near-infrared fluoroscopy (NIF) showed good blood supply. Appendix amputation followed by cecopexy to the psoas muscle was performed to reduce pedicle tension. The proximal appendix was unexpectedly found to be obliterated and the plan was revised to perform an augmented ureteroplasty with appendiceal onlay flap. A double-J ureteral stent was placed, followed by the completion of the onlay. RESULTS: Estimated blood loss was minimal (100cc); console time was 219 minutes. There were no complications. The patient was discharged on post-operative day 1. Follow-up retrograde pyelogram showed prompt drainage of contrast and a patent ureter and the stent was removed 10 weeks after the surgery. CONCLUSIONS: The appendix can serve as a suitable ureteral substitution in situations unamenable to UU, given the need for additional length. A skilled reconstructive urologist needs to maintain a high level of intraoperative flexibility in the event that original plans change based on anatomic findings during the case. Additionally, adjuncts such as intraoperative ureteroscopy and the use of ICG/NIF can prove significantly useful during complex reconstructive cases. Source of Funding: None

Recent advances in pediatric bladder malignancies.

Urothelial pediatric neoplasms are relatively rare. Papillary urothelial neoplasms of low malignant potential (PUNLMPs) and rhabdomyosarcoma (RMS) are the most common bladder malignancies in the pediatric population. Clinical presentation encompasses macroscopic hematuria or lower urinary tract symptoms (or both) or is detected incidentally at imaging. Tumors arising from the bladder can originate from any of its four histological layers (urothelium, lamina propria, detrusor, and adventitia) and are divided into tumors that have an epithelial origin (arising from the urothelium) and those that have a non-epithelial origin (mesenchymal neoplasms). RMS is the most common malignant tumor of the urinary bladder in children younger than 10 years. Deriving from the embryonic mesenchymal cell, the histopathologic subtypes of RMS are embryonal RMS (>90%) and alveolar histology (<10%). Pre-treatment imaging should be carried out by computed tomography (CT) or at present is more likely with magnetic resonance imaging of the pelvis. Chest CT and bone scintigraphy are used to screen for metastases. In selected cases, a positron emission tomography scan may be recommended to evaluate suspicious lesions. The current prognostic classification considers age, histologic subtype, tumor site, size, and extent (nodal or distant metastases). Staging is based on pre-operative findings, group is based on intra-operative findings and pathology, and risk stratification is derived from both stage and group data. Pre-operative chemotherapy is the most common first-line intervention for bladder/prostate RMS, before surgery or radiation therapy. Collaborative groups such as the Soft Tissue Sarcoma Committee of the Children’s Oncology Group and the European Pediatric Soft Tissue Sarcoma Study Group endorse this therapy. PUNLMPs are generally solitary, small (1–2 cm), non-invasive lesions that do not metastasize. Therapy is usually limited to a transurethral resection of the bladder tumor. About 35% are recurrent and around 10% of them increase in size if they are not treated.

Vaginal estrogen use for genitourinary symptoms in women with a history of uterine, cervical, or ovarian carcinoma

ObjectiveMenopausal symptoms may adversely affect quality of life and health in women diagnosed with a gynecologic malignancy. The aim of this study was to determine the incidence of adverse outcomes,...

Transurethral en bloc resection of non-muscle invasive bladder cancer with holmium:YAG laser in pediatric patients: cases series and review of literatures

Urothelial bladder carcinoma frequently occurs in adults over 60 years of age; yet it affects only 0.1–0.4% of patients before the first 2 decades of life. We present two cases of transitional cell carcinoma in two young patients treated with holmium:YAG laser to demonstrate the effectiveness of this technique in pediatrics. Case study 1 During a routine abdomen ultrasound, a 14-year-old female showed a endoluminal formation about 10 × 6 × 10 mm of size, in the left paramedian site. There was an absence of meaningful vascular signs during color-Doppler. Physical examination and laboratory exams were all normal. Case study 2 A 12-year-old female presented with acute macroscopic haematuria. No other symptoms were associated. Bladder ultrasound revealed an irregular 15 mm intravesical endophytic lesion in the posterior-superior area. In both cases, treatment commenced with an en bloc enucleation. For the resections, a 272 µm holmium:YAG fiber laser was used through the 12 Ch cystoscopy working channel with an energy of 0.8–1 J/pulse and a frequency of 8–10 Hz. There was no haematuria after the procedure and the transurethral catheter remained for 12 h. The histological diagnosis was papillary urothelial neoplasm of low malignant potential. Cystoscopy was performed 3 and 9 months after the surgery and an ultrasound every 6 months, which all came back normal. The follow-up continued for each patient with a cystoscopy once a year, according to EAU guidelines. Based on the findings, holmium:YAG laser is a good alternative to treat superficial transitional cell carcinoma in pediatric patients.

The Association of A Number of Predictive Factors for The Recurrence of Papillary Urothelial Neoplasm of Low Malignant Potential: Prognostic Analysis From Multiple Academic Centers.

To identify clinically useful predictors for the recurrence of papillary urothelial neoplasm of low malignant potential (PUNLMP), we reviewed the clinical information of patients who were diagnosed and treated in multiple tertiary-care academic facilities. Between February 2007 and April 2015, 95 patients diagnosed with PUNLMP after transurethral resection of bladder (TURB) were included in this study. Age, gender, body mass index, smoking history, the presence or absence of previous history of urothelial neoplasm, the presence or absence of gross hematuria, cytological results at the time of diagnosis, tumor diameter, and multiplicity of tumor were estimated as variablesfor analysis. Cox regression tests were used for identifying predictive factors for recurrence of PUNLMP. Sixty-nine cases of PUNLMP were de novo primary bladder PUNLMPs without known urothelial lesions in the urinary tract, and 26 PUNLMPs were identified on surveillance biopsies of patients with a previous history of urothelial neoplasm. During the follow-up period, recurrences developed in 13 patients (13.7%). Recurrence rates were 4.2% and 9.5% at 12 and 24 months, respectively. On univariate and multivariate Cox regression analyses, previous history of urothelial neoplasm [95% confidence interval (CI): 0.057-0.604, hazard ratio (HR) = 0.185, P = .005] and multiplicity of tumors [95% CI = 0.064-0.584, HR = 0.193, P = .004] were identified as independent predictors for recurrence-free survival of patients with PUNLMP. Tumor multiplicity and previous history of urothelial neoplasm are independent prognostic factors forprediction of recurrence of PUNLMP. More careful and closer follow-up should be recommended for PULNMPpatients with tumor multiplicity or a previous history of urothelial neoplasm.

CT and MRI Findings of Glomangiopericytoma in the Head and Neck: Case Series Study and Systematic Review.

Glomangiopericytoma is a rare sinonasal mesenchymal tumor of borderline or low malignant potential. We reviewed the CT and MR imaging findings of head and neck glomangiopericytoma via a retrospective case series study and systematic review. Our study revealed that glomangiopericytoma is a well-defined lobulated avidly enhancing soft-tissue mass with erosive bony remodeling that is most commonly found in the sinonasal cavity. Typically, it is hyperintense on T2-weighted images with vascular signal voids, has a high mean ADC value, and a wash-in and washout pattern on dynamic contrast-enhanced MR imaging. Although the CT findings are nonspecific, typical MR imaging findings, including those on the ADC map and dynamic contrast-enhanced MR imaging, may be helpful for differentiating glomangiopericytomas from other hypervascular tumors in the head and neck.

Paravaginal female adnexal tumor of probable Wolffian origin mimicking vaginal spindle cell epithelioma on biopsy

Female adnexal tumor of probable wolffian origin (FATWO) is a tumor of low malignant potential that arises predominantly in the broad ligament, mesosalpinx, and ovarian hilus. The rarity of FATWO increases its susceptibility to misdiagnosis as other tumors, especially when it occurs at an unusual site. We report a 29-year-old woman with a 7.2 cm left paravaginal FATWO that invaded into the vaginal lumen. The initial biopsy demonstrated features suggestive of vaginal spindle cell epithelioma, but with increased Ki67 proliferation index. Pathologists should be aware that the common sieve-like architecture of FATWO may not be apparent on small biopsies, which by sampling error may demonstrate predominantly the less common spindle cell architecture. Awareness of FATWO in the differential diagnosis of paravaginal tumors may help to avoid misinterpretation as vaginal spindle cell epithelioma, a previously unappreciated pitfall in the diagnosis of FATWO.

Clinicopathologic study of 60 cases of urothelial neoplasms with inverted growth patterns: Reclassification by international consultation on urologic disease (ICUD) recommendations

BackgroundMost urothelial neoplasms of the bladder show an exophytic papillary pattern, but some show an inverted growth pattern. In 2004, the World Health Organization (WHO) released a detailed histologic classification system for papillary urothelial neoplasms, but not for inverted forms. The International Consultation on Urologic Disease (ICUD) recommendations of 2012 are applicable to inverted/endophytic papillary lesions as follows: 1) inverted papilloma (IP), 2) inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP), 3) inverted papillary urothelial carcinoma, low grade, non-invasive (IPUCLG-NI), 4) inverted papillary urothelial carcinoma, high grade, non-invasive (IPUCHG-NI), 5) inverted papillary urothelial carcinoma, high grade, invasive (IPUCHG-I). However, only atypical cellular morphology was considered for classification in the 2012 ICUD recommendations, and data to support to validate this new grading system are lacking. MethodsSixty cases of inverted urothelial papillary tumors were classified into 5 categories according to 2012 ICUD and 2016 WHO/ISUP recommendations to evaluate their clinical, pathological, and immunohistochemical characteristics. Two subgroups were defined as subgroup 1, IP and IPUNLMP, and subgroup 2, IPUCLG-NI, IPUCHG-NI, and IPUCHG-I. Clinical features (age, sex, history of urothelial carcinoma, smoking history, size, and multifocality) and histologic features (nuclear pleomorphism, mitotic count, mitosis level, apoptosis, luminal necrosis, trabecular thickening, anastomosing trabeculae, hypercellularity, loss of polarity, peripheral palisading, palisading with central streaming, and discohesiveness) were evaluated. Immunohistochemical stains for CK20, CD44, P53, p16, Ki-67, cyclin D1 and c-erbB2 were performed. ResultsA total of 60 cases were classified as 10 cases of IP, 29 cases of IPUNLMPs, 15 cases of IPUCLG-NI, 4 cases of IPUCHG-NI, and 2 cases of IPUCHG-I. Compared to subgroup 1, subgroup 2 showed larger tumor size, more nuclear irregularity, higher mitotic count (hot spot and per 10 high power fields), more upper level mitosis (>1/2), and more frequent apoptosis, luminal necrosis, surface papillary component, trabecular thickening, anastomosing irregular trabeculae, hypercellularity, loss of polarity, peripheral palisading with central streaming, and discohesiveness, and absence of umbrella cells and urothelial eddies. CK20, Ki67, and c-erbB2 were the only markers that were differently expressed in the two subgroups, with more expression in subgroup 2. ConclusionsThe 2012 ICUD recommendations are valid to classify inverted papillary urothelial tumors. However, other histologic features besides atypical cellular morphology should also be considered to distinguish subgroup 1 and subgroup 2 inverted papillary urothelial tumors.

Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019?

BackgroundPapillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. ObjectivesTo analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. Materials and methodsIndividual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. ResultsPUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990–2000) to 3.2% (2000–2010) and to 1.1% (2010–2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. ConclusionsThe proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas.

P119 - Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, non-invasive bladder tumors in 2019?

P119 - Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, non-invasive bladder tumors in 2019?

PRMT1 expression in renal cell tumors- application in differential diagnosis and prognostic relevance

BackgroundProtein arginine methyltransferase-1 (PRMT1) is associated with the progression of various tumor types and the process of epithelial to mesenchymal transition (EMT). However, the expression of PRMT1 in renal cell tumors (RCT) is unknown.MethodsWe evaluated PRMT1 immunohistochemical (IHC) expression on tissue microarray (TMA) of 208 specimens of RCT, including clear cell renal cell carcinomas (ccRCC), papillary RCC type I and II (pRCC I and II), chromophobe RCC (chRCC), renal oncocytomas (RO), collecting duct carcinomas - Bellini (CDC) and multilocular cystic renal cell neoplasms of low malignant potential (MLCRN-LMP). Moreover, a subset of ccRCC, pRCC, chRCC, RO were also studied using conventional sections. PRMT1 expression in tumor tissue was compared to the IHC expression of EMT-related transcription factors (ZEB1, RUNX1, and TWIST1) and cell surface markers (ß-catenin, N- and E-cadherin). Additionally, qRT-PCR expression of PRMT1 in ccRCC, pRCC, and chRCC was evaluated and the results were compared to the mRNA PRMT1 transcript profiling data in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) cohort.ResultsPRMT1 immunoreactivity was observed in the majority of ccRCC, RO, all MLCRN-LMP, but in a minority of chRCC (p = 0.044), and it was associated with low grade and low stage ccRCC (p = 0.014; p = 0.044, respectively). ZEB1 immunoreactivity was noted in all RO, in minority of chRCC and neither of MLCRN-LMP (p < 0.001). The majority of PRMT1-negative ccRCC was negative to ZEB1 and showed cytoplasmic expression of TWIST1 (p = 0.028; p < 0.001, respectively). PRMT1 positive ccRCC mostly expressed RUNX1 (p = 0.019). PRMT1 and ZEB1 expression were associated with better cancer-specific survival in patients with ccRCC (p = 0.029; p = 0.009, respectively). In multivariate analysis, ZEB1 expression was an independent prognostic factor for cancer-specific survival (hazard ratio [HR], 0.367; p = 0.026). Significant IHC heterogeneity was observed in PRMT1, ZEB1 and TWIST1 expression (p < 0.001). Homogenous loss of PRMT1 was associated with high grade and high stage ccRCC, while the homogenous loss of PRMT1 and ZEB1 was more frequent in patients who died of ccRCC (p = 0.017; p = 0.040; p = 0.044; p = 0.009, respectively). Relative mRNA-PRMT1 expression in both cohorts was down-regulated in tumor tissue compared to non-tumor parenchyma (p = 0.009). Unlike in our samples, mRNA-PRMT1 expression in the TCGA cohort was not correlated to ccRCC tumor stage or grade. PRMT1, ZEB1, and TWIST1 expression were not associated with EMT related aberrant ß-catenin expression, a gain of N-cadherin or loss of E-cadherin expression. Only RUNX1 was associated with a gain of N-cadherin (p = 0.003).ConclusionsIHC expression of PRMT1 may be characteristic for low grade and low stage ccRCC, while the homogenous loss of PRMT1 may be significant for high grade and high stage ccRCC. Both, PRMT1 and/or ZEB1 expression, could be associated with better survival of the patients with ccRCC.

Molecular Classification of Epithelial Ovarian Cancer Based on Methylation Profiling: Evidence for Survival Heterogeneity.

Ovarian cancer is a heterogeneous disease that can be divided into multiple subtypes with variable etiology, pathogenesis, and prognosis. We analyzed DNA methylation profiling data to identify biologic subgroups of ovarian cancer and study their relationship with histologic subtypes, copy number variation, RNA expression data, and outcomes. A total of 162 paraffin-embedded ovarian epithelial tumor tissues, including the five major epithelial ovarian tumor subtypes (high- and low-grade serous, endometrioid, mucinous, and clear cell) and tumors of low malignant potential were selected from two different sources: The Polish Ovarian Cancer study, and the Surveillance, Epidemiology, and End Results Residual Tissue Repository (SEER RTR). Analyses were restricted to Caucasian women. Methylation profiling was conducted using the Illumina 450K methylation array. For 45 tumors array copy number data were available. NanoString gene expression data for 39 genes were available for 61 high-grade serous carcinomas (HGSC). Consensus nonnegative matrix factorization clustering of the 1,000 most variable CpG sites showed four major clusters among all epithelial ovarian cancers. We observed statistically significant differences in survival (log-rank test, P = 9.1 × 10-7) and genomic instability across these clusters. Within HGSC, clustering showed three subgroups with survival differences (log-rank test, P = 0.002). Comparing models with and without methylation subgroups in addition to previously identified gene expression subtypes suggested that the methylation subgroups added significant survival information (P = 0.007). DNA methylation profiling of ovarian cancer identified novel molecular subgroups that had significant survival difference and provided insights into the molecular underpinnings of ovarian cancer.See related commentary by Ishak et al., p. 5729.

Ultrasound Imaging Characteristics of Breast Lesions Diagnosed During Pregnancy and Lactation.

Background and Objectives: The breast undergoes extensive physiologic changes during pregnancy/lactation. We aimed to review the ultrasound (US) imaging characteristics of breast lesions during pregnancy/lactation and to demonstrate ultrasonography as an excellent imaging modality in this patient population. Materials and Methods: We performed a retrospective study involving 195 patients with 206 pathologically confirmed breast lesions during pregnancy/lactation over the period of January 2010 to December 2018; 51 were diagnosed with breast cancer, including 50 invasive ductal carcinomas and 1 low malignant potential phyllodes tumor, whereas 144 were diagnosed with 155 benign lesions, including 103 mastitis/abscesses, 45 fibroadenomas, 2 intraductal papillomas, 2 sclerosing lesions, and 3 benign phyllodes tumors. The patients' age, lesion diameter, and US characteristics were analyzed. Results: The breast lesions of patients during pregnancy/lactation were compared with those during nonpregnancy/lactation. Patients with breast cancer or fibroadenomas during pregnancy/lactation were younger than those during nonpregnancy/lactation. The average lesion diameter was significantly higher among pregnant/lactating patients compared with controls of childbearing age for fibroadenomas, but not for malignant lesions. The fibroadenomas and mastitis/abscesses during pregnancy/lactation usually have higher BI-RADS categories than those during nonpregnancy/lactation. Conclusions: The imaging features of breast cancer during pregnancy/lactation did not differ much from those of nonpregnancy/lactation; however, some benign lesions had suspicious sonographic features, and US-guided core biopsies were necessary for differentiating benign from malignant lesions.

Female Adnexal Tumor of Probable Wolffian Origin: A Review.

Female adnexal tumor of probable Wolffian origin (FATWO) is an extremely rare gynecologic neoplasm of low malignant potential. Fewer than 90 cases of this entity have been described in the English-language literature. It is presumed to be derived from mesonephric (Wolffian) duct remnants in the upper female genital tract. We provide a literature review to increase awareness of this extremely uncommon entity. To review the clinical and pathologic findings of FATWO and to discuss common entities in the differential diagnosis. The study involved PubMed (National Center for Biotechnology Information, Bethesda, Maryland) searches, including multiple review articles, case reports, retrospective studies, selected book chapters, and University of Mississippi Medical Center cases. FATWO can affect patients from a wide age range and present with a nonspecific clinical presentation. It typically presents as solid tumors with occasional nodular, lobulated, or cystic appearances. FATWO can show a variety of histologic patterns which may result in diagnostic difficulties for pathologists. There is no single specific immunohistochemical stain for FATWO, and the pathogenesis and molecular alterations are not yet well understood. Although it is generally considered a benign entity, recurrent and metastatic cases have been reported. There are no current recommendations regarding the optimal clinical management of FATWO.