Transitional Cell Tumors Research Articles

Transitional Cell Carcinoma of the Ovary is Related to High-grade Serous Carcinoma and is Distinct From Malignant Brenner Tumor

Transitional cell tumors of the ovary include benign, borderline (atypically proliferating), and malignant Brenner tumors (BT), as well as transitional cell carcinoma (TCC). Some TCCs could conceivably be examples of malignant BT where the benign component has been overgrown. Our objectives were: (A) compare the immunophenotypes of BT and TCC and (B) examine a large cohort of ovarian carcinomas for cases with the immunophenotype of BT and transitional features but lacking a benign BT component. Seven BTs (3 benign, 3 borderline/atypically proliferating, 1 malignant) and 7 TCCs were stained for WT1, ER, p53, and p16(INK4a). The BTs were negative for WT1, p53 overexpression, ER (except for weak positivity in 1), and negative or weakly positive for p16(INK4a). In contrast, the TCCs stained as follows: 4/6 positive for WT1, 5/7 positive for ER, 2/7 strongly positive for p16(INK4a), and 6/7 showed abnormal p53, an immunophenotype resembling that of high-grade serous carcinoma. A database of 500 cases of ovarian carcinoma was searched and 116 showed an immunoprofile characteristic of BT: WT1 negative, ER negative, p16(INK4a) or weak positive, p53 negative (77 clear cell carcinoma, 14 endometrioid carcinoma, 12 mucinous carcinoma, 8 high-grade serous carcinoma). None of these tumors showed transitional features on review, indicating that if examples of malignant BT where there has been overgrowth of benign BT components exist, they are rare. Our results suggest that BT and TCC are unrelated, and should not be combined for classification purposes.

Diagnostic Potential of Urinary α1-Antitrypsin and Apolipoprotein E in the Detection of Bladder Cancer

The ability to reliably diagnose bladder cancer in voided urine samples would be a major advance. Using high throughput technologies, we identified a panel of bladder cancer associated biomarkers with potential clinical usefulness. In this study we tested 4 potential biomarkers for the noninvasive detection of bladder cancer. We examined voided urine specimens from 124 patients, including 63 newly diagnosed with bladder cancer and 61 controls. Concentrations of proteins were assessed by enzyme-linked immunosorbent assay, including α1-antitrypsin, apolipoprotein E, osteopontin and pentraxin 3. Data were compared to the results of urinary cytology and the BTA Trak® enzyme-linked immunosorbent assay based bladder cancer detection assay. We used the AUC of ROC curves to compare the usefulness of each biomarker to detect bladder cancer. Urinary levels of α1-antitrypsin, apolipoprotein E and bladder tumor antigen were significantly increased in subjects with bladder cancer. α1-Antitrypsin (AUC 0.9087, 95% CI 0.8555-0.9619) and apolipoprotein E (AUC 0.8987, 95% CI 0.8449-0.9525) were the most accurate biomarkers. The combination of α1-antitrypsin and apolipoprotein E (AUC 0.9399) achieved 91% sensitivity, 89% specificity, and a positive and negative predictive value of 89% and 90%, respectively. Multivariate regression analysis highlighted only apolipoprotein E as an independent predictor of bladder cancer (OR 24.9, 95% CI 4.22-146.7, p = 0.0004). Alone or in combination, α1-antitrypsin and apolipoprotein E show promise for the noninvasive detection of bladder cancer (OR 24.9, 95% CI 4.22-146.7, p = 0.0004). Larger, prospective studies including more low grade, low stage tumors are needed to confirm these results.

Changing treatment and outcome of children with hepatoblastoma: analysis of a single center experience over the last 20 years

Background/PurposeThe aim of the study was to analyze changing management and survival of children with hepatoblastoma (HBL) treated in one center. Materials and MethodsOver the last 20 years, 51 children with HBL were treated. Surgery was performed in 48 children (94.1%), conventional liver resection in 38 (of those, 2 received a rescue liver transplantation [LTx] for relapse), and total hepatectomy and primary LTx in 10 patients. The remaining 3 patients received only palliative treatment. Patient data were analyzed for survival with respect to PRETreatment EXTent of disease (PRETEXT), metastases, histopathology, conventional resection, and LTx. ResultsSurvival of children with HBL treated with liver resection is 71% and 80% for primary LTx. Favorable prognostic factors for patient survival was tumor histology as epithelial-fetal subtype and mixed epithelial and mesenchymal type, without teratoid features, and good response to chemotherapy (necrosis, fibrosis). Unfavorable prognostic factors were small cells undifferentiated, transitional liver cell tumor, α-fetoprotein level above 1,000,000 IU/mL and below 100 IU/mL at diagnosis, lung metastases, and local recurrence after initial resection. Survival was related to PRETEXT stage. However, among patients with PRETEXT III and IV, LTx resulted in better survival. ConclusionLiver transplantation is a good option for children with advanced HBL. Early referral of children with potentially unresectable tumors to centers where combined treatment (chemotherapy, surgery including LTx) is available is crucial.

Urothelial Tumors of the Urinary Bladder in Manipur: A Histopathological Perspective

To study the histomorphological pattern of urothelial tumors of the urinary bladder in Manipur and to evaluate whether any correlation exists between tumor grade and muscle invasion. A 10 year retrospective study of all consecutive cases diagnosed in the Department of Pathology RIMS - Imphal, between 1st January 2001 to 31st December 2010. The study included 26 cases of transitional cell tumors of urinary bladder. The male to female ratio was 1.5: 1 and the ages ranged from 38 years to 73 years (medians of 60 and 64 years, respectively). Of the total, 14 (53.9%) cases were low grade, 9 (34.6%) were high grade, 2 (7.7%) were papillomas and 1 (3.9%) was a papillary urothelial neoplasm of low malignant potential (PUNLMP). Pathological staging showed that 14 (53.9%) of the cases were stage PTa, four (15.4%) PT1, and eight (30.9%) PT2. Some 18.2% of low grade tumors and 75% of high grade tumors were invasive to the detrusor muscle layer. Bladder cancer is an uncommon disease, transitional tumors being the only histological type observed. It was more common in males than females, with peak incidence in seventh decade. Most of the tumors were non- invasive (PTa) and invasion to the detrusor muscle layer was seen in more than half of the high grade tumors. There is a definite correlation between advancing tumor grade and muscle invasion.

Activation of RAS Genes by Specific Point Mutations in Transitional Cell Carcinoma of Urinary Bladder in Kashmiri Population

Urinary bladder cancer is a common malignancy in the west and ranks 7th most cancer in this region. The primary aim of the study was to evaluate the incidence of specific RAS gene point mutations among a group of Kashmiri patients diagnosed with bladder cancer. We also explored the correlation of clinic-pathological status of the illness with these mutations.The paired tumor and adjacent normal tissue specimens of 65 consecutive patients were examined in Kashmiri population,India. The DNA preparations were evaluated for the occurrence of RAS gene mutations by PCR-SCCP and DNA sequencing.Overall somatic point mutations of all the forms of RAS genes aggregated to 21.5% . In total there were nine mutations in HRAS (three in codon 12, six in codon 61), five in NRAS (two in codon 12 and three in codon 61) and no mutation was found in KRAS gene. Overall RAS genes showed no association with any clinic-pathological parameters but when stratified alone the pattern ofHRAS mutation in this study showed a significant association with smoking in bladder tumors (p <0.05).Activation of RAS gene mutation plays a less frequent role than other genetic events in the development of the most transitional cell tumors of the bladder but contribute equally well to the development of both major tumor groups. JMS 2012;15(1):15-21

Water-electrolyte metabolism disorders in patients with urinary bladder cancer before and after radical surgical treatment

We have studied water-electrolyte metabolism indicators and its main hormones-regulators in 32 patients with transitional cell tumour of the urinary bladder of T2a—T2b stages before and after radical cystectomy with ileocystoplasty. The most significant changes in water-electrolyte metabolism indicators have been identified during studies on 24-hour urinary excretion: a significantly large preoperative potassium ion concentration was noted in patients with urinary bladder cancer. Following cystectomy, it decreased to 67%. Postoperative urine osmolarity decreased to 45%, excreting sodium fraction increased to 50% ( р < 0,05). Preoperative vasopressin concentration was higher than that in the control group while postoperative one increased to 22%. Following cystectomy, the adrenocorticotrophic hormone level decreased to 29%. Preoperatively, the hydrocortisone level in the basic group was higher than that in the control one. It decreased to 16%, postoperatively. Excretion disorders of osmotic active substances in patients with urinary bladder cancer are due to both reabsorption properties of the intestinal wall and disorders of synthesis and tissue effects of hormones regulating water-electrolyte metabolism.

Diffusion-weighted Imaging of a Malignant Brenner Tumor

Microscopically, ovarian malignant Brenner tumor shows components of malignant transitional cell tumor intermixed with benign and borderline elements. We report a case of this tumor with components that transition from benign to malignant on diffusion-weighted images (DWI) and in histologic findings. The benign component showed low signal intensity on T(2)-weighted images, whereas the malignant component showed high signal intensity on T(2)-weighted images and high signal intensity on DWI with low apparent diffusion coefficient (ADC) value.

An Investigation into the Cytotoxic Effects of 13-Acetoxysarcocrassolide from the Soft Coral Sarcophyton crassocaule on Bladder Cancer Cells

Active compounds from natural products have been widely studied. The anti-tumor effects of 13-acetoxysarcocrassolide isolated from Formosan soft coral Sarcophyton crassocaule on bladder cancer cells were examined in this study. An MTT assay showed that 13-acetoxysarcocrassolide was cytotoxic to bladder female transitional cancer (BFTC) cells. We determined that the BFTC cells underwent cell death through apoptosis by flow cytometry. Due to the highly-migratory nature of the BFTC cells, the ability of 13-acetoxysarcocrassolide to stop their migration was assessed by a wound healing assay. To determine which proteins were affected in the BFTC cells upon treatment, a comparative proteomic analysis was performed. By LC-MS/MS analysis, we identified that 19 proteins were up-regulated and eight were down-regulated. Seven of the proteins were confirmed by western blotting analysis. This study reveals clues to the potential mechanism of the cytotoxic effects of 13-acetoxysarcocrassolide on BFTC cells. Moreover, it suggests that PPT1 and hnRNP F could be new biomarkers for bladder cancer. The results of this study are also helpful for the diagnosis, progression monitoring and therapeutic strategies of transitional cell tumors.

Comparative Outcomes of Pure Squamous Cell Carcinoma and Urothelial Carcinoma With Squamous Differentiation in Patients Treated With Radical Cystectomy

We compared clinical outcomes, and identified predictors of cancer specific and overall survival after radical cystectomy in patients with urothelial carcinoma with squamous differentiation and those with pure squamous cell carcinoma. We reviewed data on 2,031 patients treated with radical cystectomy and pelvic lymph node dissection at a single high volume referral center. Of these patients 78 had squamous cell carcinoma and 67 had squamous differentiation. Survival estimates by histological subtype were described using Kaplan-Meier methods. Within histological subtypes pathological stage, nodal invasion, soft tissue margins, age and gender were evaluated as predictors of cancer specific survival and overall survival using univariate Cox regression. Median followup was 44 months. Of 104 patient deaths 60 died of their disease. We did not find a statistically significant difference between survival curves of patients with squamous cell carcinoma and squamous differentiation (log rank overall survival p = 0.6, cancer specific survival p = 0.17). Positive soft tissue margins were associated with worse cancer specific survival (HR 6.92, 95% CI 2.98-16.10, p ≤0.0005) and overall survival (HR 3.68, 95% CI 1.84-7.35, p ≤0.0005) in patients with pure squamous cell carcinoma. Among patients with squamous differentiation, pelvic lymphadenopathy was associated with decreased overall survival (HR 2.52, 95% CI 1.33-4.77, p = 0.004) and cancer specific survival (HR 3.23, 95% CI 1.57-6.67, p = 0.002). There appears to be no evidence of a difference in cancer specific survival or overall survival between patients with squamous cell carcinoma and those with squamous differentiation treated with radical cystectomy and pelvic lymph node dissection. Patients with squamous differentiation and tumor metastases to pelvic lymph nodes should be followed more closely, and adjuvant treatment should be considered to improve survival. Wide surgical resection is critical to achieve local tumor control and improve survival in patients with squamous cell carcinoma.

Role of Diffusion MRI and Apparent Diffusion Coefficient Measurement in the Diagnosis, Staging and Pathological Classification of Bladder Tumors

Objectives: Our aim was to investigate the role of simultaneous apparent diffusion coefficient (ADC) measurement and diffusion-weighted MRI (DWMRI) in the diagnosis and differentiation of bladder masses. Methods: Weexamined 45 patients presenting with hematuria by dynamic and diffusion MRI (at b100, b600, b1000 gradients) and cystoscopy. Thirty healthy volunteers without hematuria were also included in the study. Results from imaging techniques were compared to cystoscopic and histopathologic findings. The ADC values of benign and malignant bladder masses, and bladder tissue in healthy subjects were measured and compared with each other. Results: The mean ADC values of benign (n = 10) and malignant lesions (n = 35) were significantly lower than the mean ADC values of adjacent bladder walls and bladder walls of healthy subjects at all 3 gradients (p < 0.05). However, no significant difference was detected between benign and malignant lesions (p > 0.05). Mean ADC values of invasive tumors were significantly lower than superficial malignancies at b600 and b1000 gradients. The mean ADC values of transitional cell tumors were significantly higher than squamous cell tumors at b100 and b600 gradients. Conclusion: Simultaneous measurement ofADC and DWMRI provided useful information in the diagnosis, staging and histopathological classification of bladder tumors.

Glycosyl-phosphatidylinositol-anchored interleukin-2 expressed on tumor-derived exosomes induces anti-tumor immune response

To prepare IL-2-anchored and tumor-derived exosomes vaccine, and investigate the antitumor efficiency of the special cytotoxic T-lymphocytes induced by Ex/GPI-IL-2. To construct pEGFP-N1-IL2gpi plasmid coding a fusion gene of a DNA oligo encoding GPI-anchor signal sequence attaching to human IL-2 cDNA. Then T24 cell lines stably expressing GPI-IL-2 proteins (T24/GPI-IL-2) were established. Ex/GPI-IL-2 were isolated and purified by ultrafiltration and sucrose gradient centrifugation, and the morphology and molecule markers were analyzed. The mixed lymphocyte reaction study and cytotoxic study were performed to determine the proliferative effect of T lymphocytes and the cytotoxicity induced by Ex/GPI-IL-2. The pEGFP-N1-IL2gpi plasmid was successfully constructed, and cell lines stably expressing GPI-IL-2 fusion proteins were established. Ex/GPI-IL-2 were small vesicular and saucer-shaped in diameter of 30-90 nm, containing heat shock protein 70, intercellular adhesion molecule-1, MAGE-1 and GPI-IL-2. Ex/GPI-IL-2-pulsed could dendritic cells induce proliferation of T cells and cytotoxic immune response more efficiently (P<0.05). GPI-IL-2 gene-modified tumor cells can make the exosomes containing GPI-IL-2 with an increased anti-tumor effect. Our study provides a feasible approach for exosome-based tumor immunotherapy of bladder transitional cell tumors.

Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer—Shifting the paradigm

Recent morphologic, immunohistochemical, and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer based on a dualistic model of carcinogenesis that divides epithelial ovarian cancer into 2 broad categories designated types I and II. Type I tumors comprise low-grade serous, low-grade endometrioid, clear cell and mucinous carcinomas, and Brenner tumors. They are generally indolent, present in stage I (tumor confined to the ovary), and are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN, PIK3CA, ARID1A, and PPP2R1A, which target specific cell signaling pathways. Type I tumors rarely harbor TP53 mutations and are relatively stable genetically. Type II tumors comprise high-grade serous, high-grade endometrioid, malignant mixed mesodermal tumors (carcinosarcomas), and undifferentiated carcinomas. They are aggressive, present in advanced stage, and have a very high frequency of TP53 mutations but rarely harbor the mutations detected in type I tumors. In addition, type II tumors have molecular alterations that perturb expression of BRCA either by mutation of the gene or by promoter methylation. A hallmark of these tumors is that they are genetically highly unstable. Recent studies strongly suggest that fallopian tube epithelium (benign or malignant) that implants on the ovary is the source of low-grade and high-grade serous carcinoma rather than the ovarian surface epithelium as previously believed. Similarly, it is widely accepted that endometriosis is the precursor of endometrioid and clear cell carcinomas and, as endometriosis, is thought to develop from retrograde menstruation; these tumors can also be regarded as involving the ovary secondarily. The origin of mucinous and transitional cell (Brenner) tumors is still not well established, although recent data suggest a possible origin from transitional epithelial nests located in paraovarian locations at the tuboperitoneal junction. Thus, it now appears that type I and type II ovarian tumors develop independently along different molecular pathways and that both types develop outside the ovary and involve it secondarily. If this concept is confirmed, it leads to the conclusion that the only true primary ovarian neoplasms are gonadal stromal and germ cell tumors analogous to testicular tumors. This new paradigm of ovarian carcinogenesis has important clinical implications. By shifting the early events of ovarian carcinogenesis to the fallopian tube and endometrium instead of the ovary, prevention approaches, for example, salpingectomy with ovarian conservation, may play an important role in reducing the burden of ovarian cancer while preserving hormonal function and fertility.

A singular observation of a giant benign Brenner tumor of the ovary

Brenner tumors are rare transitional cell tumors of the ovary. They are usually benign neoplasms, of solid or solid-cystic structure and small size. We describe the case of a benign, predominantly cystic Brenner tumor measuring 39 cm in diameter. A 62-year-old woman presented to the outpatient visit complaining about vague abdominal symptoms such as constipation and meteorism. Ultrasonography and CT scan showed the presence of a voluminous cystic mass, with fluid content, displacing other intra-abdominal organs. The patient underwent elective surgical excision, and there were no complications. Definitive pathological examination showed a metaplastic benign Brenner tumor. The largest benign Brenner tumors reported in literature have been up to 30 cm in size, and greater size has been thought to be a predictor of malignancy. We have seen, however, that it is possible for larger lesions of this type to have a completely benign behavior; consequently, a benign nature should not be excluded even in the event of a large ovarian lesion.

Abstract 5354: Characterisation of the cell line HC-AFW1 derived from a paediatric hepatocellular carcinoma

Abstract Paediatric hepatocellular carcinoma (HCC) has an incidence of 1.5 cases per million children and is linked to viral hepatitis in endemic regions. In Europe childhood HCC mostly arises in otherwise healthy liver and has an unknown ethiology. Current treatment results of HCC are dissatisfactory due to advanced disease at diagnosis and lacking response to chemotherapy. To improve the research of childhood HCC and to address specific therapeutic approaches a preclinical model for childhood HCC is needed. So far, there has been one existing cell line, HepG2, which has lately been discussed controversially as being hepatoblastoma. We established a cell line HC-AFW1 from the tumor of a 5 year old boy. The original tumor histology was characteristic as transitional liver cell tumor including hepatoblastoma and HCC morphology. These histological findings were confirmed through several reference pathology laboratories worldwide. The cell line HC-AFW1 was established by xenotransplantation of original tumor into immuno-deficient mice and re-culturing in vitro. The cell line is in sable culture now for over 8 months with a doubling time of 40 h. Cultured cells present epithelial characteristics and express hepatoma proteins like AFP, glypican 3, E-cadherin, CD10, CD326, HepPar1, Vimentin and Desmin. Catenin beta shows a deletion of 49 amino acids in the exon 3 involving the phosphorylation sites of GSK3 and was detected in cell nuclei. Cytogenetic analysis revealed large anomalies in the chromosomal map. This involves chromosomal aberrations found in hepatoblastoma as well as in adult HCC. Several alterations of gene copy numbers were detected by genome wide SNP array. Among different tested drugs cisplatin and irinotecan showed an effective inhibition of tumor cell growth in an MTT assay at concentration below 5 µg/ml. Transplantation of HC-AFW1 cells into NOD/SCID mice resulted in fast growing dedifferentiated tumors with high levels of serum AFP. This xenotransplants as well as stable cultured cells solely consist of HCC components suggesting a selection of HCC and degeneration of formally hepatoblastoma tumor parts. Therefore, HC-AFW1 is the first paediatric HCC-derived cell line and represents a valuable tool to investigate the biology and therapeutic strategies in childhood HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5354. doi:10.1158/1538-7445.AM2011-5354

Tumor de Brenner benigno bilateral asociado a cistadenoma mucinoso. Una aproximación a los tumores de células transicionales del ovario

Los tumores de células transicionales del ovario constituyen un raro grupo de tumores epiteliales ováricos que, desde su primera descripción en 1932, han sido sujeto de numerosos trabajos para establecer su histogénesis y comprender su actividad endocrina. Comprenden dos categorías clínico-patológicas: los tumores de Brenner (benigno, borderline o proliferante y maligno) y el carcinoma de células transicionales . Presentamos un caso de tumor de Brenner benigno bilateral y de grandes dimensiones asociado a cistadenoma mucinoso en una mujer de 54 años con antecedentes de carcinoma de mama. Discutimos las principales características clínico-patológicas de este grupo de tumores epiteliales ováricos y su asociación con los tumores mucinosos. Transitional cell tumours constitute a rare group of ovarian epithelial neoplasms, first described in 1932 and still the subject of many studies to determine their histogenesis and endocrine activity. They are classified into two distinct clinicopathological categories: Brenner tumours (benign, borderline or proliferative and malignant) and transitional cell carcinoma. We report a case of a large, bilateral benign Brenner tumour associated with mucinous cystadenoma in a 54 year old woman with a history of breast carcinoma. The main clinical and pathological features of transitional cell ovarian tumours are described and their association with mucinous tumours is discussed.

Unusual Presentation of Benign Cystic Brenner Tumor With Exuberant Psammomatous Calcifications

Transitional cell tumors of the ovary comprise about 1% to 2% of all ovarian neoplasms. Most of these tumors are benign Brenner tumors and account for about 5% of benign surface epithelial-stromal tumors. Spicules of calcifications are found in the stroma of about 50% of benign Brenner tumors. Although diagnostic challenges might occur more frequently with either of the borderline or malignant Brenner tumors, this problem is not that common when diagnosing a benign Brenner tumor. This study reports a case of benign Brenner tumor with exuberant dystrophic calcifications that obscured most of the epithelium and posed a diagnostic challenge in differentiating it from the more common malignant counterparts such as serous carcinoma and specifically psammocarcinoma.

S148 ENDOSCOPIC URETERECTOMY DURING NEPHROURETERECTOMY FOR UPPER URINARY TRACT TRANSITIONAL CELL CARCINOMA

Introduction: Radical nephroureterectomy with resection of a bladder cuff remains the “gold standard” in the treatment of upper urinary tract transitional cell tumors. McDonald is the first to describe a ureteral stripping technique with subsequent endoscopic resection of the bladder cuff around the ureteral orifice during nephroureterectomy, which is called transurethral endoscopic ureterectomy and is a less invasive alternative of open surgical ureterectomy in patients with transitional cell renal pelvic carcinoma. Objective: To evaluate the clinical outcome of transurethral endoscopic ureterectomy during nephroureterectomy for transitional cell carcinoma of the renal pelvis and calyces.

Prognostic Relevance of Uncommon Ovarian Histology in Women With Stage III/IV Epithelial Ovarian Cancer

The prognostic relevance of uncommon epithelial ovarian cancer (EOC) histological subtypes remains controversial. The Gynecologic Cancer InterGroup (GCIG) initiated this meta-analysis to assess the relative prognosis of women with a diagnosis of rare EOC histologies from completed, prospectively randomized studies performed by cooperative GCIG study groups. Studies eligible for analysis included first-line treatment of at least 150 patients with stage III/IV EOC treated with a platinum/taxane-based regimen. Collaborating groups were to provide patient-level data. Serous acted as the reference histology, and a proportional hazards model was used to estimate the relative rate of progression or death. Data on 8704 women with stage III/IV EOC from 7 randomized trials were included in these analyses. Two hundred twenty-one patients (2.5%) had clear cell carcinoma; 264 (3.0%), mucinous; and 36 (0.4%), transitional cell. The mean age of patients with serous histology was greater than those with mucinous (4.1 years) and clear cell (2.6 years, P < 0.001). Mucinous, clear cell, and transitional cell tumors were more likely to be completely resected than serous (P < 0.05). When controlling for age and residual disease, mucinous and clear cell tumors had shorter times to progression (hazards ratio [HR], 2.1; 95% confidence interval [CI], 1.8-2.4 and HR, 1.6; 95% CI, 1.4-1.9, respectively) and death (HR, 2.7; 95% CI, 2.3-3.1 and HR, 2.2; 95% CI, 1.8-2.6, respectively) compared with serous. The median overall survival for serous, clear cell, mucinous, and endometrioid histologies were 40.8, 21.3, 14.6, and 50.9 months. Mucinous and clear cell carcinomas are independent predictors of poor prognosis in stage III/IV EOC. Studies targeting these rare histological subtypes are warranted and will require significant intergroup collaboration.

Transitional cell neoplasm of the nasolacrimal duct associated with human papillomavirus type 11

Tumors of the lacrimal sac are rare but noteworthy because of their significant potential to become malignant or life-threatening if treatment is delayed. Dermatologists may be the first to encounter such neoplasms. We report a case of a 53-year-old Caucasian woman who presented with a seven-year history of an asymptomatic, subcutaneous nodule near her right medial canthus. Histology of the lesion revealed transitional epithelium in a papillary growth pattern with numerous goblet cells, scattered mitoses and focal full-thickness atypia. The patient was diagnosed with transitional cell neoplasm (inverted papilloma-type) of the nasolacrimal duct. PCR evaluation identified HPV type 11 in the lesion. Our report is one of a growing number of case reports and series detecting HPV DNA in these tumors which further supports HPV as an etiologic agent in epithelial lacrimal sac tumors. We believe that dermatopathologists need to be aware of this entity, as dermatologists may be the first to encounter these neoplasms. The association of HPV with this tumor does not prove causality.

Tumor Characteristics of Urothelial Carcinoma on Multidetector Computerized Tomography Urography

We investigated the relationship between tumor characteristics of urothelial carcinoma and detectability on multidetector computerized tomography urography. We retrospectively reviewed all adult consecutive patients with hematuria who underwent multidetector computerized tomography urography during a 23-month period at our hospital. Patients with a final diagnosis of urothelial carcinoma verified by histological examination of surgical specimens were included in the study. The presence and location of urothelial carcinomas on multidetector computerized tomography urography without knowledge of final diagnosis were recorded. Tumor characteristics (location, size, histological classification and stage) were recorded based mainly on histological findings. The association between tumor characteristics and urothelial carcinoma detectability on multidetector computerized tomography urography was analyzed. A total of 70 patients who underwent multidetector computerized tomography urography had 87 verified urothelial carcinomas. Of these carcinomas 6 (6.9%) were undetectable by multidetector computerized tomography urography, including 5 ureteral and 1 bladder urothelial carcinoma. Size of detectable and nondetectable tumors on multidetector computerized tomography urography differed significantly (3.05 +/- 1.79 vs 0.65 +/- 0.99 cm, respectively, p = 0.001). Tumor location (p = 0.009), tumor size 1 cm or larger (p = 0.003) and noncarcinoma in situ tumors (p = 0.001) were significantly associated with multidetector computerized tomography urography detectability. Conversely organ confined disease had no association with multidetector computerized tomography urography detectability. Multivariate analyses showed that noncarcinoma in situ tumor was a significant predictor of multidetector computerized tomography urography detectability (p = 0.001). Multidetector computerized tomography urography is useful for detecting nearly all urothelial carcinomas in adults with hematuria. Careful assessment by multidetector computerized tomography urography is needed to detect small (less than 1 cm) or ureteral urothelial carcinomas. It remains a challenge to detect carcinoma in situ tumors by multidetector computerized tomography urography. Thus, negative results of urothelial carcinomas on multidetector computerized tomography urography do not exclude the presence of carcinoma in situ tumors.