Deep Phenotyping the Anterior Urethral Stricture: Characterizing the Relationship Between Inflammation, Fibrosis, Patient History, and Disease Pathophysiology.

PURPOSE: Anterior urethral stricture disease (aUSD) is a complex, heterogeneous condition that is idiopathic in origin for most men. This gap in knowledge rarely affects the current management strategy for aUSD, as urethroplasty does not generally consider etiology. However, as we transition towards personalized, minimally invasive treatments for aUSD and begin to consider aUSD prevention strategies, disease pathophysiology will become increasingly important. The purpose of this study was to perform a deep phenotype of men undergoing anterior urethroplasty for aUSD. We hypothesized that unique biologic signatures and potential targets for intervention would emerge based on stricture presence/absence, stricture etiology, and the presence/absence of stricture inflammation. MATERIALS AND METHODS: Men with aUSD undergoing urethroplasty were recruited from one of 5 participating centers. Enrollees provided urethral stricture tissue and blood/serum on the day of surgery and completed patient-reported outcome measure questionnaires both pre- and postoperatively. The initial study had 3 aims: (1) to determine pediatric and adult subacute and repeated perineal trauma (SRPT) exposures using a study-specific SRPT questionnaire, (2) to determine the degree of inflammation and fibrosis in aUSD and peri-aUSD (normal urethra) tissue, and (3) to determine levels of systemic inflammatory and fibrotic cytokines. Two controls groups provided serum (normal vasectomy patients) and urethral tissue (autopsy patients). Cohorts were based on the presence/absence of stricture, by presumed stricture etiology (idiopathic, traumatic/iatrogenic, lichen sclerosus [LS]), and by the presence/absence of stricture inflammation. RESULTS: Of 138 enrolled men (120 tissue/serum; 18 stricture tissue only), 78 had idiopathic strictures, 33 had trauma-related strictures, and 27 had LS-related strictures. BMI, stricture length, and stricture location significantly differed between cohorts (P < .001 for each). The highest BMIs and the longest strictures were observed in the LS cohort. SRPT exposures did not significantly differ between etiology cohorts, with > 60% of each reporting low/mild risk. Stricture inflammation significantly differed between cohorts, with mild to severe inflammation present in 27% of trauma-related strictures, 54% of idiopathic strictures, and 48% of LS strictures (P = .036). Stricture fibrosis did not significantly differ between cohorts (P = .7). Three serum cytokines were significantly higher in patients with strictures compared to stricture-free controls: interleukin-9 (IL-9; P = .001), platelet-derived growth factor-BB (P = .004), and CCL5 (P = .01). No differences were observed in the levels of these cytokines based on stricture etiology. However, IL-9 levels were significantly higher in patients with inflamed strictures than in patients with strictures lacking inflammation (P = .019). Degree of stricture inflammation positively correlated with serum levels of IL-9 (Spearman's rho 0.224, P = .014). CONCLUSIONS: The most common aUSD etiology is idiopathic. Though convention has implicated SRPT as causative for idiopathic strictures, here we found that patients with idiopathic strictures had low SRPT rates that were similar to rates in patients with a known stricture etiology. Stricture and stricture-adjacent inflammation in idiopathic stricture were similar to LS strictures, suggesting shared pathophysiologic mechanisms. IL-9, platelet-derived growth factor-BB, and CCL5, which were elevated in patients with strictures, have been implicated in fibrotic conditions elsewhere in the body. Further work will be required to determine if this shared biologic signature represents a potential mechanism for an aUSD predisposition.

Tumor to Tumor Metastasis: A Case Report of Metastatic Angiosarcoma to an Ovarian Brenner Tumor and Review of the Literature.

While angiosarcoma metastatic to the ovary is rare, metastatic angiosarcoma to an ovarian tumor has never been reported in the literature, so far. We report a case of a 61-yr-old postmenopausal woman with history of breast cancer, presenting with metastatic angiosarcoma to an ovarian Brenner tumor. Initially at the frozen section examination, on limited sampling, and without knowledge of the patient's history, a diagnosis of at least proliferating Brenner tumor was rendered. Upon review of permanent sections, an intermixed angiosarcoma component was identified within Brenner tumor. Tumor to ovarian tumor metastasis is a rare phenomenon, with only 18 cases reported in the last 50 yr. It poses diagnostic challenges during sampling and histopathologic interpretation. Detailed clinical history, careful gross examination and sampling are important to recognize the separate tumor components.

Biobehavioral factors predict an exosome biomarker of ovarian carcinoma disease progression.

BACKGROUND: Biobehavioral factors such as social isolation and depression have been associated with disease progression in ovarian and other cancers. Here, the authors developed a noninvasive, exosomal RNA profile for predicting ovarian cancer disease progression and subsequently tested whether it increased in association with biobehavioral risk factors. METHODS: Exosomes were isolated from plasma samples from 100 women taken before primary surgical resection or neoadjuvant (NACT) treatment of ovarian carcinoma and 6 and 12 months later. Biobehavioral measures were sampled at all time points. Plasma from 76 patients was allocated to discovery analyses in which morning presurgical/NACT exosomal RNA profiles were analyzed by elastic net machine learning to identify a biomarker predicting rapid (≤6 months) versus more extended disease-free intervals following initial treatment. Samples from a second subgroup of 24 patients were analyzed by mixed-effects linear models to determine whether the progression-predictive biomarker varied longitudinally as a function of biobehavioral risk factors (social isolation and depressive symptoms). RESULTS: An RNA-based molecular signature was identified that discriminated between individuals who had disease progression in ≤6 months versus >6 months, independent of clinical variables (age, disease stage, and grade). In a second group of patients analyzed longitudinally, social isolation and depressive symptoms were associated with upregulated expression of the disease progression propensity biomarker, adjusting for covariates. CONCLUSION: These data identified a novel exosome-derived biomarker indicating propensity of ovarian cancer progression that is sensitive to biobehavioral variables. This derived biomarker may be potentially useful for risk assessment, intervention targeting, and treatment monitoring.

Epithelial-mesenchymal transition polarization in ovarian carcinomas from patients with high social isolation.

BACKGROUND: Social isolation has shown robust associations with clinical outcomes in the general population and in patients with cancer. In patients with ovarian cancer, social isolation has been found to be related to decreased survival and multiple biomarkers supporting tumor progression. However, to the authors' knowledge, little is known regarding the relationship between social isolation and the molecular characteristics of ovarian tumors. Herein, the authors have used genome-wide transcriptional profiling to quantify associations between social isolation and epithelial-mesenchymal transition (EMT) polarization in ovarian tumors and transcriptome-driven, promoter-based bioinformatics analyses to identify gene regulatory pathways that may potentially underlie these changes. METHODS: Tumor was sampled during primary surgical resection and immediately frozen in liquid nitrogen. After RNA extraction, microarray analysis of the transcriptome was performed and samples were analyzed to assess associations between EMT-related gene transcripts and social isolation (as indicated by a Social Provisions Scale Attachment subscale score <15). Convergent validation was provided by a promoter-based bioinformatic analysis of transcription factor activity. RESULTS: Primary analyses of 99 women demonstrated a lower average expression of gene transcripts previously associated with epithelial differentiation in women with high social isolation (-0.143 ± 0.048 log2 mRNA abundance; P = .004), but no difference in mesenchymal differentiation as a function of social isolation (+0.007 ± 0.0064 log2 mRNA abundance; P = .900). Upregulated activity was shown for 3 of the 4 targeted EMT-related transcription factors, including GATA4 (P = .014); SMAD2, SMAD3, and/or SMAD4 (P < .001); and TWIST1 (P < .001). Analyses of SNAIL2/SLUG activity indicated a directional trend toward increased activity that did not reach statistical significance (P = .123). CONCLUSIONS: The findings of the current study demonstrated differential EMT polarization and EMT-related transcription factor activity according to social isolation, a known socioenvironmental risk factor. LAY SUMMARY: Social isolation has shown robust associations with clinical outcomes in the general population and in patients with cancer. Herein, the authors examined the relationship between social isolation and the molecular characteristics of ovarian tumors. The authors investigated the epithelial-mesenchymal transition (EMT), a process whereby tumor cells lose epithelial characteristics and become more embryonic (mesenchymal), thereby enhancing invasiveness. Primary analyses demonstrated lower expression of genes previously associated with epithelial differentiation and increased activity of specific EMT-related transcription factors in individuals with high social isolation, indicating increased EMT polarization in these patients. These findings extend the understanding of how socioenvironmental factors may modulate tumor growth.

Alpha-dystroglycan staining pattern and mortality in patients undergoing radical prostatectomy with lymph node positive prostate cancer.

INTRODUCTION: Dystroglycan (DG) is a cell surface receptor for extracellular matrix proteins involved in tissue mechanical stability and matrix organization. Initial work has demonstrated that alpha-DG expression is decreased in many types of adenocarcinoma, including prostate, and potentially associated with the development of metastatic disease. However, the consistency between prostate and lymph node alpha-DG staining has not been previously reported. In addition, identification of an immunohistochemical marker associated with prostate cancer grade, stage, need for adjuvant or salvage therapy and mortality would have potential clinical value. MATERIALS AND METHODS: Node positive, margin negative radical prostatectomy specimens at a single institution from 1982 to 2012 were reviewed and identified 35 prostate specimens, including 26 patients with available tissue from both the primary prostatectomy and lymph node specimens. The expression levels of the alpha-DG subunit were analyzed using immunohistochemistry and graded from 0 to 4. Survival was compared in different staining pattern groups. RESULTS: Strength of alpha-DG staining was found to be consistent between prostate and lymph node specimens (p < 0.004). The median overall survival was shorter in those without alpha-DG staining in the prostate compared to those with positive staining, but this difference was not statistically significant (13.2 years versus 19.4 years, p = 0.21). In addition, negative staining was associated with higher mean PSA, pathologic T stage, Gleason grade and the need for adjuvant or salvage therapy compared to positive group but none reached statistical significance (16.06 ng/mL versus 11.67 ng/mL, p = 0.79; 89% versus 68%, p = 0.38; 33.3% versus 23.1%, p = 0.66; 88.9% versus 76.9%, p = 0.44). CONCLUSIONS: DG expression by immunohistochemistry staining was consistent between prostate and metastatic lymph node specimens. In a small cohort of prostate cancer patients with margin negative but node positive disease, DG staining was not associated with Gleason grade or with overall mortality.

Life stress as a risk factor for sustained anxiety and cortisol dysregulation during the first year of survivorship in ovarian cancer.

BACKGROUND: Patients with ovarian cancer often report elevated anxiety at diagnosis that decreases posttreatment. However, a minority of patients experience sustained anxiety. Few studies have examined risk factors for persistent anxiety or its physiologic sequelae in ovarian cancer. Therefore, the authors investigated associations between prior life events, anxiety, inflammation (plasma levels of interleukin-6), and diurnal cortisol profiles in patients with ovarian cancer during the first year postdiagnosis. METHODS: Participants (n = 337) completed surveys and had blood and salivary sampling prediagnosis, postchemotherapy (6 months), and 12 months after diagnosis. The Life Events and Difficulties Schedule was administered to a patient subset (n = 127) within 1 month of diagnosis. Linear mixed-effects models were used to analyze relations between anxiety and biologic variables over time. Linear regression models assessed whether anxiety trajectories mediated associations between prior stress exposure and biologic variables. Age, chemotherapy at 1 year, and cancer stage were covariates. RESULTS: Decreased anxiety was associated with a more normalized cortisol slope over time (ß = 0.092; P = .047). Early life adversity was related to flatter cortisol slopes over time (ß = -0.763; P = .002); this relation was partially mediated by anxiety trajectory (P = .046). More danger-related events prediagnosis were associated with sustained anxiety (ß = 0.537; P = .019) and flatter cortisol slopes over time (ß = -0.243; P = .047); anxiety partially mediated the relation between danger and cortisol slope (P = .037). Neither anxiety nor prior stress exposure was related to levels of interleukin-6. CONCLUSIONS: Because dysregulated cortisol has been related to fatigue, poorer quality of life, and shorter survival in patients with ovarian cancer, those who have prior life events and chronic anxiety during the first year postdiagnosis may be at risk for more negative outcomes. Cancer 2018. © 2018 American Cancer Society.

Urethral lichen sclerosus under the microscope: a survey of academic pathologists.

INTRODUCTION: Given the poor understanding of the pathophysiology of genital lichen sclerosus (GLS) and a lack of accepted definitive diagnostic criteria, we proposed to survey pathologists regarding their understanding of GLS. We hypothesized that significant disagreement about GLS will exist. MATERIALS AND METHODS: All urologists participating in the Trauma and Urologic Reconstruction Network of Surgeons identified genitourinary (GUP) and dermatopathologists (DP) at their respective institutions who were then invited to participate in an online survey regarding their experience with diagnosing GLS, GLS pathophysiology and its relationship to urethral stricture disease. RESULTS: There were 23 (12 DP, 11 GUP) pathologists that completed the survey. The most agreed upon criteria for diagnosis were dermal collagen homogenization (85.7%), loss of the normal rete pattern (33.3%) and atrophic epidermis (28.5%). No pathologists believed GLS had an infectious etiology (19% maybe, 42% unknown) and 19% believed GLS to be an autoimmune disorder (42% maybe, 38% unknown); 19% believed LS to be premalignant, but 52% believed it was associated with cancer; 80% believed that LS could involve the urethra (DP (92%) versus GUP (67%); p = 0.272). Of those diagnosing urethral GLS, 80% of DUP believed that GLS must first involve the glans/prepuce before involving the urethra, while all GUP believed that urethral disease could exist in isolation (p = 0.007). CONCLUSIONS: There was significant disagreement in this specialized cohort of pathologists when diagnosing GLS. A logical first step appears to be improving agreement on how to best describe and classify the disease. This may lead to improve treatments.

Struma Ovarii With Malignant Transformation and Germline KIT Mutation: A Case Report With Review of the Literature.

Struma ovarii accounts for 5% of ovarian teratomas. Malignant transformation occurs in <0.3%, however, the underlying molecular mechanism is unknown. We report a patient with follicular variant and tall cell variant of papillary thyroid carcinoma (PTC) arising from struma ovarii and coexisting incidental PTC in the thyroid. Mutation analysis by next-generation sequencing identified a novel germline mutation, KIT p.V530I mutation in the tumors and normal ovarian and thyroid tissue. Immunohistochemical staining showed loss of KIT expression in the PTCs. Activating mutations in KIT play an important role in diagnosis and prognosis of multiple malignancies including mastocytosis, gastrointestinal stromal tumors, and a subset of melanoma and acute myeloid leukemia. The p.V530I mutation has only been reported in 3 previous cases: acute myeloid leukemia, aggressive fibromatosis, and adenocarcinoma of the colon. In the case of aggressive fibromatosis, the patient responded well to imatinib treatment. KIT mutations have never been reported in thyroid carcinomas. This is the first case of PTC-harboring KIT mutation. Although more work needs to be done to elucidate the significance of this germline mutation, the response of the fibromatosis patient to imatinib may shed light on targeted therapy in PTC harboring this mutation.

Eudaimonic well-being and tumor norepinephrine in patients with epithelial ovarian cancer.

BACKGROUND: The impact of psychological well-being on the physiologic processes involved in cancer progression remains unclear. Prior research has implicated adrenergic signaling in tumor growth and metastasis. Given that adrenergic signaling is influenced by both positive and negative factors, the authors examined how 2 different aspects of well-being (eudaimonic and positive affect) and psychological distress were associated with tumor norepinephrine (NE) in patients with ovarian cancer. METHODS: A total of 365 women with suspected ovarian cancer completed psychosocial assessments before surgery and clinical information was obtained from medical records. Study inclusion was confirmed after histological diagnosis. Tumor NE was measured in frozen tissue samples using high-performance liquid chromatography with electrochemical detection. Confirmatory factor analysis was used to model eudaimonic well-being, positive affect, and psychological distress, and structural equation modeling was used to examine associations between these factors and tumor NE. RESULTS: Eudaimonic well-being, positive affect, and psychological distress, modeled as distinct but correlated constructs, best fit the data (ie, compared with unitary or 2-factor models) (root mean square error of approximation, 0.048; comparative fit index, 0.982; and standardized root-mean-squared residual, 0.035). Structural equation modeling analysis that included physical well-being, stage of disease, histology, psychological treatment history, beta-blocker use, and caffeine use as covariates was found to have good model fit (root mean square error of approximation, 0.052; comparative fit index, 0.955; and standardized root-mean-squared residual, 0.036) and demonstrated that eudaimonic well-being was related to lower tumor NE (ß = -.24 [P = .045]). In contrast, no effects were found for positive affect or psychological distress. CONCLUSIONS: Eudaimonic well-being was found to be associated with lower tumor NE, independent of positive affect and psychological distress. Because adrenergic signaling is implicated in tumor progression, increasing eudaimonic well-being may improve both psychological and physiologic resilience in patients with ovarian cancer.

Sleep disturbance, distress, and quality of life in ovarian cancer patients during the first year after diagnosis.

BACKGROUND: Sleep disturbance is a common clinical complaint of oncology patients and contributes to substantial morbidity. However, because most sleep studies have been cross-sectional, associations between sleep quality and distress in patients with ovarian cancer over time remain unclear. This prospective longitudinal study examined rates of sleep disturbance; contributions of depression, anxiety, and medication use in sleep disturbance; and associations between sleep quality and quality of life (QOL) during the first year after diagnosis among women with ovarian cancer. METHODS: Women with a pelvic mass completed measures of sleep quality, depression, anxiety, and QOL before surgery. Those diagnosed with primary epithelial ovarian, fallopian tube, or peritoneal cancer repeated surveys at 6 months and 1 year after diagnosis. Mixed modeling was used to examine trajectories of psychosocial measures over time, as well as associations between changes in distress and sleep quality. Relationships between changes in sleep and QOL were also examined. RESULTS: The majority of patients reported disturbed global sleep (Pittsburgh Sleep Quality Index > 5) at all 3 time points. Medications for sleep and pain were associated with worse sleep at all time points. Greater increases in depression were associated with increased disturbances in sleep quality over time (P < .04). Worsening sleep was also associated with declines in QOL over time (P < .001). CONCLUSIONS: Sleep disturbance is common and persistent in women with ovarian cancer, and is linked to depressive symptoms and QOL. Pharmacologic treatment does not appear to adequately address this problem. Results highlight the need for ongoing screening and intervention for sleep disturbance in this population.

Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: relationships with depression, fatigue, and disability.

Elevations in the pro-inflammatory cytokine interleukin-6 (IL-6) and alterations in the anti-inflammatory hormone cortisol have been reported in a variety of cancers. IL-6 has prognostic significance in ovarian cancer and cortisol has been associated with fatigue, disability, and vegetative depression in ovarian cancer patients prior to surgery. Ovarian cancer patients undergoing primary treatment completed psychological self-report measures and collected salivary cortisol and plasma IL-6 prior to surgery, at 6 months, and at 1 year. Patients included in this study had completed chemotherapy and had no evidence of disease recurrence. At 6 months, patients showed significant reductions in nocturnal cortisol secretion, plasma IL-6, and a more normalized diurnal cortisol rhythm, changes that were maintained at 1 year. The reductions in IL-6 and nocturnal cortisol were associated with declines in self-reported fatigue, vegetative depression, and disability. These findings suggest that primary treatment for ovarian cancer reduces the inflammatory response. Moreover, patients who have not developed recurrent disease by 1 year appear to maintain more normalized levels of cortisol and IL-6. Improvement in fatigue and vegetative depression is associated with the normalization of IL-6 and cortisol, a pattern which may be relevant for improvements in overall quality of life for ovarian cancer patients.

Case report: Robotically visualized and biopsy-confirmed peritoneal carcinomatosis as initial identification of metastatic prostate adenocarcinoma in a patient with a history of prostatic urethral lift.

Background: Peritoneal carcinomatosis is a particularly rare presentation of prostate cancer. Here we report a rare clinical case of surgically identified peritoneal carcinomatosis at the time of a planned robotic prostatectomy in a patient with a history of prostatic urethral lift procedure. Case presentation: A 72-year-old man, with a history of urinary retention managed with tamsulosin, presented to his local urologist. Prostatic urethral lift procedures were performed for symptom management. After a definitive uptrend in his prostate-specific antigen (PSA) values, a biopsy was obtained, which demonstrated prostate adenocarcinoma. On presurgical multidisciplinary review, it was presumed that he had very high-risk localized prostate cancer. However, upon initiation of robotically assisted laparoscopic radical prostatectomy (RALP), he was noted to have numerous punctate white plaques on the peritoneum; biopsy of these lesions confirmed metastatic disease-for which the patient was starting on triple therapy per the PEACE-1 trial. The PSA level responded appropriately, decreasing from 16.8 to 0.08. Genetic testing was performed and returned negative for any clinically significant mutations. Conclusion: Our patient, diagnosed with peritoneal carcinomatosis during a planned RALP, highlights the importance of vigilant laparoscopic exam prior to this prostatectomy. Multidisciplinary discussion is crucial for individualized and optimal treatment planning.

Social isolation is associated with elevated tumor norepinephrine in ovarian carcinoma patients.

Noradrenergic pathways have been implicated in growth and progression of ovarian cancer. Intratumoral norepinephrine (NE) has been shown to increase with stress in an animal cancer model, but little is known regarding how tumor NE varies with disease stage and with biobehavioral factors in ovarian cancer patients. This study examined relationships between pre-surgical measures of social support, depressed mood, perceived stress, anxiety, tumor histology and tumor catecholamine (NE and epinephrine [E]) levels among 68 ovarian cancer patients. We also examined whether associations observed between biobehavioral measures and tumor catecholamines extended to other compartments. Higher NE levels were found in advanced stage (p=0.006) and higher grade (p=0.001) tumors. Adjusting for stage, grade, and peri-surgical beta blockers, patients with a perceived lack of social support had significantly higher tumor NE (ß=-0.29, p=0.012). A similar trend was seen for social support and ascites NE (adjusting for stage, peri-surgical beta blockers and caffeine: ß=-0.50, p=0.075), but not for plasma NE. Other biobehavioral factors were not related to tumor, ascites, or plasma NE (p values >0.21). Tumor E was undetectable in the majority of tumors and thus E was not further analyzed. In summary, these results suggest that tumor NE provides distinct information from circulating plasma concentrations. Tumor NE levels were elevated in relationship to tumor grade and stage. Low subjective social support was associated with elevated intratumoral NE. As beta-adrenergic signaling is related to key biological pathways involved in tumor growth, these findings may have implications for patient outcomes in ovarian cancer.

Comprehensive review of chromophobe renal cell carcinoma.

Chromophobe renal cell carcinoma (chRCC) is the third most common type of RCC with distinct biology compared to other kidney cancer subtypes. The heterogeneity between the RCC subtypes is associated with noticeable differences in tumor aggressiveness and risk for the development of metastatic disease. ChRCC is characterized by chromosomal aneuploidy, TP53, PTEN, and mitochondrial gene mutations. Though the therapeutic landscape of clear cell RCC (ccRCC) has significantly evolved over the past decade, limited progress has been seen in chRCC due to its infrequent incidence. In fact, the therapeutic approach for chRCC is often extrapolated from ccRCC treatments or studies that combine several forms of nccRCC subtypes. In the new era of genetic profiling of tumors and targeted therapeutics, this review describes the epidemiology, pathology, molecular characteristics, and current management with ongoing clinical trials for chRCC.

Mitochondria in epithelial ovarian carcinoma exhibit abnormal phenotypes and blunted associations with biobehavioral factors.

Malignant tumor cells exhibit mitochondrial alterations and are also influenced by biobehavioral processes, but the intersection of biobehavioral factors and mitochondria in malignant tumors remains unexplored. Here we examined multiple biochemical and molecular markers of mitochondrial content and function in benign tissue and in high-grade epithelial ovarian carcinoma (EOC) in parallel with exploratory analyses of biobehavioral factors. First, analysis of a publicly-available database (n = 1435) showed that gene expression of specific mitochondrial proteins in EOC is associated with survival. Quantifying multiple biochemical and molecular markers of mitochondrial content and function in tissue from 51 patients with benign ovarian masses and 128 patients with high-grade EOC revealed that compared to benign tissue, EOCs exhibit 3.3-8.4-fold higher mitochondrial content and respiratory chain enzymatic activities (P < 0.001) but similar mitochondrial DNA (mtDNA) levels (- 3.1%), documenting abnormal mitochondrial phenotypes in EOC. Mitochondrial respiratory chain activity was also associated with interleukin-6 (IL-6) levels in ascites. In benign tissue, negative biobehavioral factors were inversely correlated with mitochondrial content and respiratory chain activities, whereas positive biobehavioral factors tended to be positively correlated with mitochondrial measures, although effect sizes were small to medium (r = - 0.43 to 0.47). In contrast, serous EOCs showed less pronounced biobehavioral-mitochondrial correlations. These results document abnormal mitochondrial functional phenotypes in EOC and warrant further research on the link between biobehavioral factors and mitochondria in cancer.

Giant renal angiomyolipoma without fat density on CT scan: case report and review of the literature.

Giant renal angiomyolipomas have been reported, but typically have the pathognomonic finding of fat density on CT scan. We present the case of a 53-year-old male with a symptomatic, 35-cm, predominantly cystic renal mass without fat density on CT that on nephrectomy was found to be a fat-poor angiomyolipoma with predominantly epithelioid morphology weighing 17.9 kg. Giant renal angiomyolipoma without macroscopic fat density on CT scan is an exceedingly rare occurrence.

Hepatocellular carcinoma masquerading as a large renal mass with hepatic invasion.

Large masses are evaluated with imaging to assess primary origin and tumor spread. We present the unusual case of a 53-year-old male with a 17-cm right upper quadrant mass suspected to be renal or adrenal in origin based on radiographic findings. After surgical excision, the mass was subsequently discovered to be primary hepatocellular carcinoma with direct extension to the kidney and adrenal gland. A diagnosis of chronic hepatitis B was made postoperatively. Primary hepatocellular carcinoma with direct renal extension is an exceedingly rare occurrence based on our experience and review of the published literature.

Non-Muscle Invasive Papillary Urothelial Carcinoma Metastatic to the Mandible.

Urothelial carcinoma, the most common histologic subtype of bladder cancer in the United States, most frequently presents as non-muscle invasive disease. Initially, therapy involves transurethral endoscopic resection and subsequent intravesical therapies with extended surveillance for high-risk disease. Even with the best treatments, recurrence and progression can occur. However, metastasis of non-muscle invasive bladder cancer to distant sites without evidence of progression or regional metastasis is rare. In this article, we present the case of a patient with high-grade papillary urothelial carcinoma who developed an unusual metastasis to the mandible, confirmed by GATA-3 immunostaining, over 4 years after initial transurethral resection. Prior to the development of metastatic disease, this patient had no evidence of local recurrence during maintenance Bacillus Calmette-Guerin intravesical therapy and concurrent surveillance. Positron emission tomography-computed tomography taken after presentation with mandibular metastasis did not show any evidence of regional metastasis. This case highlights an unusual location for distant metastasis of urothelial carcinoma occurring in a patient without evidence of muscle invasive disease or regional metastasis. We additionally highlight the utility of GATA-3 immunostaining in identifying urothelial carcinoma histologically.