Alexiev BA, Tavora F
Histology and immunohistochemistry of clear cell adenocarcinoma of the urethra: histogenesis and diagnostic problems.
Virchows Arch. 2013; 462(2):193-201 [PubMed]

Clear cell adenocarcinoma (CCAC) of the urethra is a rare neoplasm, morphologically identical to its homologue arising in the female genital tract. The histogenesis of this neoplasm is uncertain. We present clinical, histopathologic, and immunohistochemical findings of four CCAC of the urethra and discuss the histogenesis and difficulties in diagnosis and differential diagnosis. CCAC of the urethra occurred in females (4/4). Two neoplasms were identified in urethral diverticulum; one of the two cases, in close proximity to a nephrogenic adenoma. CCAC exhibited tubulocystic, papillary, and diffuse/solid growth patterns. The neoplastic cells were cuboidal or columnar with eosinophilic or clear cytoplasm, and nuclear pleomorphism of at least moderate degree. Hobnail features and tumor necrosis were also observed. CCAC expressed p53 (4/4), AMACR (3/4), vimentin (3/4), PAX8 (2/4), CK7 (2/4), cytokeratin 34betaE12 (2/4), RCC (1/4), and CK20 (1/4) and were negative for PSA, WT1, ER, CA 125, uroplakin III, p16, and p63. The immunohistochemical profile supports a possible renal tubular cell differentiation/mesonephric origin for some urethral CCAC. Nephrogenic adenoma and metastatic clear cell carcinoma are the most important differential diagnostic considerations. Multicenter studies on more cases may improve our understanding of this malignancy.

Grivas PD, Davenport M, Montie JE, et al.
Urethral cancer.
Hematol Oncol Clin North Am. 2012; 26(6):1291-314 [PubMed]

Urethral carcinoma is a rare tumor with predominantly poor survival. Both the disease and its treatment can affect both sexual and urinary function. The natural history of urethral carcinoma varies, therefore the appropriate application of surgery, radiation, and chemotherapy remain unknown. Management of this disease remains driven by individual clinician experience and data derived from small case series. This article discusses the histology and anatomy of the male and female urethra, as well as their natural history. In addition, the epidemiology, clinical presentation, diagnosis, staging, treatment, and future directions of management of cancer arising in the urethra are addressed.

Champ CE, Hegarty SE, Shen X, et al.
Prognostic factors and outcomes after definitive treatment of female urethral cancer: a population-based analysis.
Urology. 2012; 80(2):374-81 [PubMed]

OBJECTIVE: To evaluate the prognostic factors and outcomes for a large observational cohort of female patients with urethral cancer in the Surveillance, Epidemiology, and End Results database.
METHODS: We identified 722 women diagnosed with urethral cancer from 1983 to 2008 in the Surveillance, Epidemiology, and End Results database. Descriptive statistics were used to explore the epidemiology, standard treatment practices, and tumor characteristics. A total of 359 women with nonmetastatic primary urethral cancer were identified for cancer-specific and survival analysis. Kaplan-Meier plots and log-rank tests were performed for each potential covariate. A multivariate Cox proportional hazards model was performed to evaluate age, demographic factors, T stage, nodal status, histologic findings, surgery, and radiotherapy.
RESULTS: The median overall survival time was 42 months (95% confidence interval 35-57), and the 5- and 10-year overall survival rate was 43% and 32%, respectively. The median cancer-specific survival (CSS) time was 78 months, and the 5- and 10-year CSS rate was 53% and 46%, respectively. On multivariate analysis, black race, Stage T3-T4 tumors compared with T1, node-positive disease, nonsquamous histologic features, and advanced age were associated with shortened CSS. Surgery was associated with longer CSS. Black patients presented with a statistically significant greater T stage.
CONCLUSION: Advanced age, T stage, node-positive disease, nonsquamous histologic features, and black race were associated with reduced CSS, and surgical resection was associated with longer CSS. We found that black patients present with more advanced tumors and have shorter CSS than white women with urethral cancer.

Gandhi JS, Khurana A, Tewari A, Mehta A
Clear cell adenocarcinoma of the male urethral tract.
Indian J Pathol Microbiol. 2012 Apr-Jun; 55(2):245-7 [PubMed]

We present a rare case of clear cell adenocarcinoma of the male bulbomembranous urethra. Mostly these tumors have been described in the female urethral tract with its possible origin from mullerian remnants, wolffian remnants or paraurethral glands. Histologically, these tumors have typically tubulocystic pattern comprising of hobnailed cells with clear glycogenated cytoplasm along with well-defined cytoplasmic membranes. This case is being presented due to its rarity, aggressive behavior and to discuss, trauma as its possible etiological factor.

Sidana A, Zhai QJ, Mahdy A
Nephrogenic adenoma in a urethral diverticulum.
Urology. 2012; 80(2):e21-2 [PubMed]

Nephrogenic adenoma (NA) is a rare benign metaplastic lesion of the urothelial tract that arises as a response to injury and chronic inflammation. Although the most common site for NA is the bladder, it can occur in any part of urinary tract lined by urothelium. NA can mimic minor variants of urothelial cancer, clear cell adenocarcinoma, and prostate adenocarcinoma, making a combination of histologic examination and immunohistochemistry essential for diagnosis. We hereby report a rare case of nephrogenic adenoma arising in a urethral diverticulum.

Zhang CT, Lu R, Lin YL, et al.
The significance of fragile histidine triad protein as a molecular prognostic marker of bladder urothelial carcinoma.
J Int Med Res. 2012; 40(2):507-16 [PubMed]

OBJECTIVES: The role and clinical significance of fragile histidine triad (FHIT) gene in the pathogenesis of bladder urothelial carcinoma (UC) and the potential of Fhit protein as a prognostic biomarker for UC were investigated.
METHODS: FHIT expression was determined according to semiquantitative immunohistochemical staining for Fhit protein levels in normal bladder and bladder UC tissues. Associations between FHIT expression, clinicopathological features and survival were evaluated.
RESULTS: This study evaluated 42 cases of normal bladder and 125 cases of bladder UC; bladder UC cases had a median follow-up of 53.5 months. Immuno histochemistry showed that 95.2% of normal cases and 47.2% of bladder UC cases, respectively, were positive for Fhit protein; this difference was statistically significant. There was a significant association between negative FHIT expression in bladder UC and advanced tumour stage, high pathological grade, large tumour size, tumour recurrence and reduced survival time, but no association with age, gender, tumour number or tumour shape.
CONCLUSIONS: The FHIT gene may have an important role in the pathogenesis of bladder UC and was expressed at lower levels in bladder UC compared with normal bladder tissue. Using Fhit protein as a biomarker could provide important information about patient prognosis.

Dudziec E, Gogol-Döring A, Cookson V, et al.
Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells.
PLoS One. 2012; 7(3):e32750 [PubMed] Free Access to Full Article

Epigenetic regulation of gene expression is commonly altered in human cancer. We have observed alterations of DNA methylation and microRNA expression that reflect the biology of bladder cancer. This common disease arises by distinct pathways with low and high-grade differentiation. We hypothesized that epigenetic gene regulation reflects an interaction between histone and DNA modifications, and differences between normal and malignant urothelial cells represent carcinogenic events within bladder cancer. To test this we profiled two repressive histone modifications (H3K9m3 and H3K27m3) using ChIP-Seq, cytosine methylation using MeDIP and mRNA expression in normal and malignant urothelial cell lines. In genes with low expression we identified H3K27m3 and DNA methylation each in 20-30% of genes and both marks in 5% of genes. H3K9m3 was detected in 5-10% of genes but was not associated with overall expression. DNA methylation was more closely related to gene expression in malignant than normal cells. H3K27m3 was the epigenetic mark most specifically correlated to gene silencing. Our data suggest that urothelial carcinogenesis is accompanied by a loss of control of both DNA methylation and H3k27 methylation. From our observations we identified a panel of genes with cancer specific-epigenetic mediated aberrant expression including those with reported carcinogenic functions and members potentially mediating a positive epigenetic feedback loop. Pathway enrichment analysis revealed genes marked by H3K9m3 were involved with cell homeostasis, those marked by H3K27m3 mediated pro-carcinogenic processes and those marked with cytosine methylation were mixed in function. In 150 normal and malignant urothelial samples, our gene panel correctly estimated expression in 65% of its members. Hierarchical clustering revealed that this gene panel stratified samples according to the presence and phenotype of bladder cancer.

Kanagarajah P, Ayyathurai R, Saleem U, Manoharan M
Small cell carcinoma arising from the bulbar urethra: a case report and literature review.
Urol Int. 2012; 88(4):477-9 [PubMed]

Primary neuroendocrine carcinomas of the genitourinary tract are rare and aggressive tumors carrying a bad prognosis. With squamous cell and transitional cell carcinoma being the most commonly reported urethral malignancies, primary small cell carcinoma (SCC) of the urethra is extremely rare. To date, only 5 cases have been reported in the literature. We present the first case of primary SCC occurring in the bulbar urethra in an 89-year-old male. We discuss the clinical, histological and immunohistochemical features of SCC of the urethra. Furthermore, we summarize the available literature and discuss the possible treatment options for this rare yet aggressive neoplasm.

Perugia G, Ciccariello M, Pirolli F, et al.
Paraurethral leiomyoma.
Urology. 2012; 79(4):e51-2 [PubMed]

Paraurethral leiomyoma is a rare, benign, hormone-dependent neoplasm of mesenchymal origin affecting women. The clinical evidence varies, but it tends to be asymptomatic or associated with the sensation of a foreign body; urinary symptoms are rarely described. The distinction among urethral, paraurethral, and anterior vaginal wall leiomyoma can be very difficult owing to their anatomic proximity. Excision of the mass is the recommended treatment, and the diagnosis is confirmed by the pathologic finding to rule out the presence of a sarcoma. A case of paraurethral leiomyoma associated with dysuria, dyspareunia, and obstructive voiding symptoms is reported.

Lu DY, Chang S, Cook H, et al.
Genital rhabdomyoma of the urethra in an infant girl.
Hum Pathol. 2012; 43(4):597-600 [PubMed]

Extracardiac rhabdomyomas are rare benign entities that usually occur in the head and neck region. Although genital rhabdomyoma is known to occur in the lower genital tract of young and middle-aged women, involvement of the anatomically adjacent urethra by rhabdomyoma is exceedingly rare. We present a case of genital rhabdomyoma arising from the urethra of an infant girl. The tumor was characterized by the submucosal presence of mature-appearing rhabdomyoblastic cells containing conspicuous cross-striations, with the cells set in a collagenous stroma. Necrosis and mitoses were absent. Skeletal muscle differentiation of the tumor cells was supported by positive immunohistochemical staining for desmin and myogenin. To our knowledge, this is the first case of urethral genital-type rhabdomyoma in a child.

Boorjian SA, Kim SP, Weight CJ, et al.
Risk factors and outcomes of urethral recurrence following radical cystectomy.
Eur Urol. 2011; 60(6):1266-72 [PubMed]

BACKGROUND: Conflicting data exist regarding predictors of urethral recurrence (UR) following radical cystectomy (RC) as well as variables associated with survival in patients who experience UR.
OBJECTIVE: To evaluate the incidence, risk factors, and outcomes of patients with UR.
DESIGN, SETTING, AND PARTICIPANTS: We reviewed 1506 patients who underwent RC to identify patients with UR. Median follow-up after RC was 13.5 yr (interquartile range [IQR]: 10.5-18.4).
INTERVENTION: Urethrectomy.
MEASUREMENTS: Cox proportional hazard regression models were used to analyze predictors of UR and evaluate factors associated with death from urothelial carcinoma (UC) in patients who experienced UR. Cancer-specific survival (CSS) for patients with UR, stratified according to the mode of diagnosis (abnormal urethral cytology vs symptoms), was estimated using the Kaplan-Meier method and compared with the log-rank test.
RESULTS AND LIMITATIONS: UR was identified in 85 patients (5.6%) at a median of 13.3 mo (IQR: 6.1-23.2) after RC, including 80 of 1243 (6.4%) who underwent cutaneous urinary diversion and 5 of 242 (2.1%) who received an orthotopic neobladder (p=0.002). On multivariate analysis, prostate involvement with UC (hazard ratio [HR]: 4.89; p<0.0001), bladder tumor multifocality (HR: 2.34; p=0.001), and orthotopic diversion (HR: 0.34; p=0.02) were significantly associated with the risk of UR. The 5-yr CSS after UR diagnosed by cytology was 80% versus 41% for patients who presented with symptoms (p<0.0001). Patients with symptomatic UR were noted to have significantly higher stage disease at urethrectomy (p=0.04) and tended toward an increased risk of death from UC (HR: 1.94; p=0.08). Limitations included retrospective study design.
CONCLUSIONS: Prostate involvement with UC, tumor multifocality, and type of urinary diversion are significantly associated with UR following RC. Although UR is relatively uncommon, the detection of asymptomatic UR was associated with significantly lower stage disease and improved patient survival, suggesting the importance of continued postoperative evaluation of the urethra.

Gourtsoyianni S, Hudolin T, Sala E, et al.
MRI at the completion of chemoradiotherapy can accurately evaluate the extent of disease in women with advanced urethral carcinoma undergoing anterior pelvic exenteration.
Clin Radiol. 2011; 66(11):1072-8 [PubMed]

AIM: To demonstrate the value of pelvic magnetic resonance imaging (MRI) in mapping tumour extension after chemoradiotherapy and before anterior pelvic exenteration in patients with primary carcinoma of the urethra.
MATERIALS AND METHODS: The Institutional Review Board approved and issued a waiver of informed consent for this retrospective study, which was compliant with the Health Insurance Portability and Accountability Act. Six women (median age 51 years, range 39-63 years) with histopathology-proven urethral carcinoma who underwent neoadjuvant chemoradiotherapy before anterior pelvic exenteration were included in the study. All had MRI performed at first presentation and after completion of chemoradiotherapy. MRI images were analysed by an experienced reader, who was blinded to the clinical data. The tumour location, signal intensity, size, local extension, and presence of enlarged lymph nodes were recorded for each patient at baseline and after chemoradiotherapy. Surgical histopathology constituted the reference standard.
RESULTS: All tumours were locally advanced (stage T3) at baseline MRI. The mean maximum diameter of the tumour at baseline MRI was 3.7 cm (range 2.4-5 cm). After chemoradiotherapy, the mean reduction in maximum tumour diameter on MRI was 44% (range 13-67%), but only three cases were down-staged. MRI was accurate in the evaluation of tumour extension after completion of chemoradiotherapy in all cases. Persistence of bladder neck and anterior vaginal wall invasion was correctly identified in three cases.
CONCLUSION: In women with advanced primary urethral cancer, MRI is an excellent tool for monitoring neo-adjuvant chemoradiotherapy changes and evaluating the extent of disease before exenterative surgery.

Downing R
A case report: veterinary palliative care and hospice for a west highland terrier with transitional cell carcinoma.
Vet Clin North Am Small Anim Pract. 2011; 41(3):677-81 [PubMed]

In providing palliative care and hospice in a veterinary outpatient primary care setting it is important to manage all aspects of the patient's needs as well as the primary disease process, and to understand that veterinary palliative care and hospice do not require a special degree or board certification. They only require compassion for the terminally ill patient and the human family members, a commitment to keeping patients united with their families for as long as they are comfortable, and a willingness to keep a comprehensive perspective on the patient's changing needs as death nears.

Raisi O, Magnani C, Bigiani N, et al.
The diagnostic reliability of urinary cytology: a retrospective study.
Diagn Cytopathol. 2012; 40(7):608-14 [PubMed]

The aim of this study was twofold. The first aim was to estimate the diagnostic reliability of urinary cytology for detection and management of urothelial neoplasms by using a specific preserving fluid for sample collection, and the liquid-based thin layer method for specimen preparation, the estimate was based on the correlation between the cytological findings of 10,000 non-hospitalized patients, and their histological diagnoses. A second aim was to compare the reliability of two instruments for thin-layer preparation, i.e., TP2000, TP3000, capable of processing the specimens at very different rates. The preservation of cell structure is ameliorated by the procedure of sample collection and treatment here described. This allows a more accurate reading of LBC slides as shown by: (a) the significant concordance between cytological and histological diagnosis (92%); (b) the significant number of low-grade urothelial carcinomas (20.5%) revealed by urinary cytology and validated by histologic diagnosis; (c) the low rate (8%) of misjudgement of cytological diagnosis reached in this study. The quality of performances of the two instruments tested for thin-layer preparation, i.e., TP2000 and TP3000, is statistically comparable. We recommend the procedure that makes use of preserving fluid for sample collection (cytolyt™) and treatment (preservcyt ™) as here described. We also recommend the use of thin-layer method for specimen preparation since it allows a more uniform distribution of the cells on the support with reduction of overlapping phenomena. Finally, economic considerations suggest the preferential use of Thin Prep 3000.

Brimo F, Herawi M, Sharma R, et al.
Hepatocyte nuclear factor-1β expression in clear cell adenocarcinomas of the bladder and urethra: diagnostic utility and implications for histogenesis.
Hum Pathol. 2011; 42(11):1613-9 [PubMed]

The histogenesis of clear cell adenocarcinoma of the bladder/urethra is uncertain. Hepatocyte nuclear factor-1β is a homeodomain protein that has been reported to be frequently overexpressed in ovarian clear cell adenocarcinoma in comparison with rare or no expression in other types of epithelial ovarian tumors. We assessed the expression of hepatocyte nuclear factor-1β in a series of 18 clear cell adenocarcinomas of the bladder and urethra and compared it with that of invasive high-grade transitional/urothelial carcinoma (n = 35); adenocarcinomas of the bladder, urethra, and paraurethral glands (n = 21); as well as nephrogenic adenomas of the bladder (n = 8). Staining intensity and extent were evaluated using a 4-tiered grading system (0-3). A case was considered positive for hepatocyte nuclear factor-1β if 10% or more of tumor cells showed at least weak nuclear staining or if any moderate or strong nuclear staining was observed. All 18 clear cell adenocarcinomas exhibited nuclear staining in at least 50% of tumor cells (16 strong, 1 moderate, and 1 weak with focal strong nuclear staining) in comparison with positive nuclear staining (moderate) in 1 of 21 bladder adenocarcinoma, 1 of 35 invasive high-grade transitional/urothelial carcinoma (weak to moderate staining), and 2 of 8 nephrogenic adenomas (1 weak and 1 moderate to strong staining). We concluded that hepatocyte nuclear factor-1β is a useful marker in differentiating clear cell adenocarcinomas of the bladder/urethra from invasive high-grade transitional/urothelial carcinoma and other types of bladder adenocarcinomas and to a lesser extent from nephrogenic adenomas. Hepatocyte nuclear factor-1β is of no diagnostic utility in discriminating primary bladder/urethral clear cell adenocarcinomas from metastatic clear cell adenocarcinomas of the female genital tract to the bladder/urethra. From a histogenesis standpoint, although the expression of hepatocyte nuclear factor-1β in both gynecologic and urologic tract clear cell adenocarcinomas may point to a Müllerian derivation/differentiation, this immunohistochemical evidence is insufficient to completely exclude an urothelial association.

Chen LP, Lin SJ, Fu TY, Yu MS
Locally advanced female urethral adenocarcinoma of enteric origin: the role of adjuvant chemoradiation and brief review.
Kaohsiung J Med Sci. 2011; 27(4):150-4 [PubMed]

Primary female urethral adenocarcinoma (FUA) is rare and has a poor prognosis. The common manifestations include urethrorrhagia, urinary frequency, dysuria, urethral obstructions, focal tenderness, and urinary tract infection. These symptoms are neither diagnostic nor pathognomonic; therefore, a delay in diagnosis and even a misdiagnosis is hardly uncommon. The histogenesis of FUAs may have derived from urethritis glandularis, Mullerian ducts, Skene's glands, or mixed origins. Tumors of different embryologic origins displayed heterogeneous pathological morphology and immunohistochemistical phenotypes. Because of its rarity and the lack of large-scale studies, there is no current consensus on the optimal treatment of urethral adenocarcinomas. Here, we report two cases of locally advanced FUA of enteric origin. They manifested as slightest warning symptoms of urinary tract infection and stress urinary incontinence, respectively. One patient died of disease progression 2 months after curative operation. The other patient underwent surgery followed by adjuvant irinotecan-containing chemoradiation, and the effect was at least modest. Hence, we recommend adjuvant chemoradiation in locally advanced FUA. Individualizing cancer care of chemoregimens in accordance with the tumor origins may probably be beneficial in FUAs.

Elshal AM, Barakat TS, Mosbah A, et al.
Complications of radical cysto-urethrectomy using modified Clavien grading system: prepubic versus perineal urethrectomy.
BJU Int. 2011; 108(8):1297-300 [PubMed]

OBJECTIVES: • To assess the impact of both prepubic and perineal urethrectomy on the complication rate and grade when cysto-urethrectomy is planned. • To review the perioperative complications of radical cysto-urethrectomy and grade them according to the modified Clavien classification system.
PATIENTS AND METHODS: • A total of 186 radical cysto-urethrectomies were performed between 1984 and 2008 • Patients' charts were retrospectively reviewed, focusing on operation duration, hospital stay and complications arising. • According to this new classification, perioperative complications were stratified into five grades.
RESULTS: • Prepubic urethrectomy was done in 71 patients (group I) while perineal urethrectomy was done in 115 patients (group II). • The mean operation duration was significantly lower in group I than in group II (173.8 and 208.9 min in groups I and II, respectively; P= 0.003). • There were a total of 46 perioperative complications in 186 (24.7%) patients, 21 (29.5%) in the prepubic group and 25 (21.1%) in the perineal group. • There were 19 (90.5%) and 18 (72%) low-grade (G1-3) complications in the prepubic and perineal groups, respectively, and two (9.5%) and seven (28%) high-grade (G4-5) complications in the prepubic and perineal groups, respectively (P= 0.033). • The mean hospital stay was significantly lower in group I than in group II (14.5 and 17.6 days in groups I and II, respectively; P= 0.047).
CONCLUSION: • The prepubic approach has a lower incidence of serious complications with shorter operation duration and shorter hospital stay.

Liu J, Wu H
Carcinosarcoma of female urethra with melanocytic differentiation.
Int J Clin Exp Pathol. 2011; 4(2):206-9 [PubMed] Free Access to Full Article

Carcinosarcoma arising from the female urethra is rare. We report an unusual case of urethral carcinosarcoma from a female patient with melanocytic differentiation. The tumor consists of a high-grade papillary serous carcinoma with psammoma bodies and a mesenchymal component with area of heterologous (cartilaginous) element. More interestingly, there are epithelioid tumor cells containing melanin pigment. On immunohistochemical stains, the epithelioid tumor cells are positive for S100, HMB45 and Mart-1, but negative for cytokeratin. This case represents an unusual carcinosarcoma with areas of melanocytic differentiation. Such rare tumors have been occasionally reported in the breast, uterus, kidney, and lung. These cases demonstrate the capacity of tumor cells to differentiate into divergent elements, supporting the concept of pluripotent tumor stem cells.

Ramakonar HH, Thomas A, Lind CR
Intramedullary conus medullaris metastasis of periurethral adenocarcinoma.
J Clin Neurosci. 2011; 18(4):567-9 [PubMed]

Intramedullary spinal cord metastasis to the conus medullaris is very rare. We report a 44-year-old woman with an intra-axial conus medullaris metastasis from periurethral adenocarcinoma. To our knowledge, this is the first report in the literature. We also discuss the clinical features, possible pathophysiological mechanisms and treatment options for intramedullary spinal cord metastasis to the conus medullaris.

Moon KS, Jung S, Lee KH, et al.
Intracranial metastasis from primary transitional cell carcinoma of female urethra: case report & review of the literature.
BMC Cancer. 2011; 11:23 [PubMed] Free Access to Full Article

BACKGROUND: Transitional cell carcinoma (TCC) of the female urethra is a rare urological malignancy, and intracranial metastasis of this cancer has not yet been reported in the literature. This review is intended to present a case of multiple intracranial metastasis in a female patient with a remote history of primary urethral TCC.
CASE PRESENTATION: A 49-year-old woman, presented with a prolapsed mass in urethral orifice that was diagnosed as primary urethral TCC with distant lung and multiple bone metastases. The patient subsequently underwent chemotherapy under various regimens. A year later, the patient developed headache and vomiting which as was found to be due to multiple intracranial metastasis. The patient underwent surgical resection of the largest lesion located on the cerebellum, and consecutively gamma knife radiosurgery was performed for other small-sized lesions. Pathological examination of the resected mass revealed a metastatic carcinoma from a known urethral TCC. Serial work-up of systemic metastasis revealed concomitant aggravation of lung, spleen, and liver metastasis. The patient died of lung complication 2 months after the diagnosis of brain metastasis.
CONCLUSION: To the best of our knowledge, this is the first reported case of cerebral metastasis from primary urethral TCC, with pathological confirmation. As shown in intracranial metastasis of other urinary tract carcinoma, this case occurred in the setting of uncontrolled systemic disease and led to dismal prognosis in spite of aggressive interventional modalities.

Ergün O, Koşar A, Ciriş IM
Urethral recurrence of bladder tumor occurring as a perineal mass 2 years after transurethral resection: a case report.
Kaohsiung J Med Sci. 2010; 26(11):624-7 [PubMed]

Transitional cell carcinoma can develop as a multifocal tumor in the urinary system, especially in the bladder. Here, we report a 69-year-old man who had undergone transurethral resection for bladder tumor and had urethral recurrence that presented as a perineal mass 2 years after treatment. However, he had obtained normal cystoscopy, ultrasonography and computed tomography results at follow-up examinations.

Ratanarapee S, Uiprasertkul M, Pradniwat K, Soontrapa S
Villous adenoma of the urinary bladder: a case report.
J Med Assoc Thai. 2010; 93(11):1336-9 [PubMed]

Villous adenomas of the urinary tract are rare, in contrast to urothelial neoplasms. Most reports were scattered individual cases. Only two case series of this entity have been published. The histopathology is identical to that of the much more common villous adenoma of the gastrointestinal tract. The authors reported a case of urinary bladder villous adenoma in a 41-year-old Thai patient who complained of hematuria for one day without any other symptom. Cystoscopic examination revealed a papillary growth at the bladder neck associated with marked degree of bullous edema and bilateral mild hydroureters. The clinical diagnosis was urothelial carcinoma. Transurethral resection was performed Histologic examination revealed typical features of villous adenoma. The tumor showed identical immunohistochemical profile to colonic villous adenoma. The patient has been well for more than a year after tumor removal.

Galsky MD, Hall SJ
Bladder cancer: current management and opportunities for a personalized approach.
Mt Sinai J Med. 2010 Nov-Dec; 77(6):587-96 [PubMed]

Urothelial carcinoma of the bladder exists as a spectrum of clinical states ranging from non-muscle-invasive to muscle-invasive to advanced/metastatic disease. Each clinical state is associated with a unique tumor biology, prognosis, and approach to treatment. The field of personalized medicine offers the promise to individualize therapeutic decisions in each clinical state with the goal of preventing or delaying progression to more advanced disease states while optimizing quality of life. This review will discuss bladder cancer as a paradigm for the development of personalized cancer medicine, focusing on recent efforts, current challenges, and future opportunities.

Ouzaid I, Hermieu JF, Dominique S, et al.
Management of adenocarcinoma of the female urethra: case report and brief review.
Can J Urol. 2010; 17(5):5404-7 [PubMed]

INTRODUCTION: We present a case of a differentiated adenocarcinoma of the female urethra, which caused dysuria and voiding dysfunction.
MATERIALS AND METHODS: A 54-year-old female presented with dysuria and the sensation of incomplete voiding.
RESULTS: An ultrasound-guided biopsy showed a urethral carcinoma. A magnetic resonance imaging (MRI) scan showed a high-stage tumor. The patient had a pelvic exenteration. The patient was free of disease after 2 years of follow up.
CONCLUSION: Urethral carcinoma is a rare malignancy. A biopsy is necessary to make a diagnosis. MRI is the best imaging for tumor staging. Small tumors are treated with a single modality option including sparing surgery or radiotherapy. Advanced disease should be treated with a multimodality of options including neoadjuvant radiotherapy given concomitantly with chemotherapy followed by surgery.

Korytko TP, Lowe GJ, Jimenez RE, et al.
Prostate-specific antigen response after definitive radiotherapy for Skene's gland adenocarcinoma resembling prostate adenocarcinoma.
Urol Oncol. 2012; 30(5):602-6 [PubMed]

OBJECTIVES: To assess prostate-specific antigen response after definitive radiotherapy in a patient with localized Skene's gland adenocarcinoma resembling prostate adenocarcinoma.
MATERIALS AND METHODS: A 71-year-old patient was evaluated for a 2 year history of painless hematuria and found to have a localized Skene's gland adenocarcinoma resembling prostate adenocarcinoma with a pre-therapy PSA of 54.52 ng/ul. She elected to undergo definitive radiotherapy holding radical surgery for salvage. She received 73.8 Gy of intensity modulated radiotherapy in 41 fractions. Serum PSA, imaging, and cystoscopy were followed at 6 month intervals for 2.5 years.
RESULTS: The PSA decreased to 0.65 ng/ul 32 months after treatment, her clinical symptoms resolved, and on imaging and exam she has no evidence of residual disease. The PSA half life was 6.16 months (r(2) = 0.97).
CONCLUSIONS: For this rare tumor we show that PSA is a reliable marker for disease response and also show that definitive radiotherapy can be an option for organ and functional preservation in patients with localized disease. Cases of periurethral adenocarcinomas should be pathologically screened to assess if they are of Skene's gland origin, as our results suggest a radiotherapy treatment paradigm may be appropriate management in a select subgroup of women with periurethral adenocarcinoma.

Lightner DJ, Bruner BC
Lower urinary tract leiomyoma: is excision necessary?
Can J Urol. 2010; 17(4):5278-82 [PubMed]

INTRODUCTION/OBJECTIVES: Our objective was to review our experience with lower urinary tract leiomyomata to determine if presentation, exam and imaging allows for stratification of the treatment of this rare lesion.
MATERIALS AND METHODS: A retrospective review of current practice was performed from the Mayo Clinic Rochester database identifying 13 female patients and 10 males from 1995-2008, focusing on the clinical presentation, cystoscopic findings, imaging and operative approaches.
RESULTS: Symptomatic patients had larger lesions, were more likely to be females, or had midline periurethral or bladder neck lesions. Cystoscopic findings were uniformly described as submucosal polypoid lesions without surrounding erythema or mucosal involvement, a hallmark in the differential. There were no cases of rapid growth of these lesions. There were no recurrences after complete excision with follow up ranging in some cases for up to 4 years.
CONCLUSIONS: Lower urinary tract urethral leiomyomata are benign lesions that can be clearly differentiated on the basis of modern imaging from malignant or other benign lesions. While these lesions can cause obstructive voiding symptoms, resection or excision is required only for relief of symptoms, and not for tissue confirmation. In comparison to the presentation of leiomyosarcoma, this benign mass presents with slowly progressive symptoms, is firm but with rounded contours on exam, mucosal ulceration is absent. Imaging confirms benign appearing, albeit, ectopic muscle tissue. Rare forms of metastatic uterine smooth muscle tumors are also easily differentiated from this lesion. Adoption of a conservative approach for the asymptomatic and benign appearing lesion appears prudent.

Trabulsi EJ, Hoffman-Censits J
Chemotherapy for penile and urethral carcinoma.
Urol Clin North Am. 2010; 37(3):467-74 [PubMed]

Although surgery is the mainstay of curative treatment of carcinomas of the penis and urethra, there is a role for systemic cytotoxic chemotherapy for locally advanced, unresectable, or metastatic tumors. Although this field is limited by a paucity of clinical trials or prospective data, the available single institutional retrospective reviews indicate that multi-agent cisplatin-based combination chemotherapy regimens have significant activity and may allow curative surgery for patients with otherwise unresectable tumors. Toxicity remains a concern in this typically older patient population, and clearly new regimens are necessary. This article reviews the available literature on chemotherapy for carcinoma of the penis and urethra in the neoadjuvant, adjuvant, and metastatic setting.

Koontz BF, Lee WR
Carcinoma of the urethra: radiation oncology.
Urol Clin North Am. 2010; 37(3):459-66 [PubMed]

Urethral cancer is a rare but aggressive neoplasm. Early-stage distal lesions can be successfully treated with a single modality. Results for definitive radiotherapy using either or both external beam radiation therapy and brachytherapy have shown excellent cure rates in men and women. The primary advantage of radiotherapy is organ preservation. Advanced tumors, however, have poor outcomes with single modality treatment. Results have been improved using a combination of radiotherapy and chemotherapy, chiefly 5-fluorouracil and mitomycin C. Although literature is limited to case reports because of the rarity of the disease, the markedly improved results compared with older results of surgery with or without radiation warrant consideration.

Karnes RJ, Breau RH, Lightner DJ
Surgery for urethral cancer.
Urol Clin North Am. 2010; 37(3):445-57 [PubMed]

Primary urethral cancers represent less than 1% of genitourinary malignancy. Given this is an uncommon disease, there are limited data to guide diagnostic and treatment strategies. Surgical extirpation remains the standard for most patients, with the addition of chemotherapy and radiation therapy in select patients. The surgical approach to urethral cancer depends largely on the location and extent of the tumor.

Stewart SB, Leder RA, Inman BA
Imaging tumors of the penis and urethra.
Urol Clin North Am. 2010; 37(3):353-67 [PubMed]

In penile and urethral cancers, imaging has come to play a crucial role in enhancing the precision of clinical staging and facilitating optimal surgical planning. Over the years, great improvements have occurred in imaging. High-resolution magnetic resonance imaging (MRI) now represents the gold standard for evaluating the primary tumor and its local extension. Lymphotropic nanoparticle-enhanced MRI, dynamic sentinel lymph node biopsy, and ultrasonography with fine-needle aspiration seem to be the superior modalities for detecting malignant regional lymph nodes. Positron emission tomography combined with computed tomography has shown great promise as a whole body screen for the detection of distant metastases. Ultimately, the ability of imaging to augment clinical evaluation and enhance the accuracy of staging penile and urethral cancers will translate into improved surgical decision making and overall superior patient outcomes.