Long-term Outcomes of Local and Metastatic Small Cell Carcinoma of the Urinary Bladder and Genomic Analysis of Patients Treated With Neoadjuvant Chemotherapy.

INTRODUCTION: Small cell carcinoma of the bladder (SCCB) is a rare variant of bladder cancer with poor outcomes. We evaluated long-term outcomes of nonmetastatic (M0) and metastatic (M1) SCCB and correlated pathologic response with genomic alterations of patients treated with neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Clinical history and pathology samples from SCCB patients diagnosed at our institution were reviewed. RESULTS: One hundred and ninety-nine SCCB patients were identified. (M0: 147 [74%]; M1: 52 [26%]). Among M0 patients, 108 underwent radical cystectomy (RC) (NAC: 71; RC only: 23; adjuvant chemotherapy: 14); 14 received chemoradiotherapy; the rest received chemotherapy alone or no cancer-directed therapy. RC-only patients had a median follow-up of 9.1 years, and median disease-free survival (DFS) and overall survival (OS) were 1.1 and 1.2 years, respectively. NAC patients had pathologic response (

Incidentally found focal xanthogranulomatous pyelonephritis with extensive venous thrombus.

A 71-year-old woman with history of asthma presented with 2 months history of shortness of breath; on imaging an incidental left renal mass was noted. Subsequent renal protocol CT was obtained that showed a 4.5 cm left upper pole exophytic mass with renal vein thrombus extending into the inferior vena cava to the level of the caudate lobe concerning for renal cell carcinoma. She underwent an open left radical nephrectomy and IVC thrombectomy with subsequent postoperative pathology demonstrating xanthogranulomatous pyelonephritis without renal cell carcinoma.

Intraperitoneal Rupture of a Synovial Sarcoma of the Kidney.

Primary renal synovial sarcoma is an aggressive, extremely rare disease. Nearly all reported cases are characterized by SYT-SSX gene translocation (X;18)(p11;q11). We describe the case of a 43-year-old woman who presented with an intraperitoneal rupture of this rare sarcoma followed by a right radical nephrectomy. Follow-up imaging 1 month after surgery revealed peritoneal carcinomatosis. She began systemic chemotherapy with doxorubicin and dacarbazine, progressed after 3 months, and is currently receiving single-agent ifosfamide. Only one instance of intraperitoneal rupture has been reported previously. This case report contributes to the characterization of this rare disease.

Adenocarcinoma of the minor duodenal papilla and its precursor lesions: a clinical and pathologic study.

The minor duodenal papilla drains the accessory pancreatic duct of Santorini and lies proximal to the ampulla of Vater. Adenocarcinoma and its precursor lesions arising in the minor papilla are rare. Literature data thus far are limited to a few individual case reports, and the condition is consequently poorly defined. Our study cases were composed of carcinomas fulfilling all of the following criteria: location at 1.5 to 2.5 cm proximal to the major papilla; presence of associated submucosal pancreatobiliary-type ducts with periductal glands or acinar tissue; a predominant submucosal location of the tumor; and lack of an intestinal-type adenoma in the adjacent duodenal mucosa. Tumors were studied morphologically, immunohistochemically, and clinically. Nine cases fulfilling the inclusion criteria were identified. There were 5 men and 4 women with an age range of 50 to 76 years (median, 72 y). The tumor size ranged from 1.2 to 4.4 cm (median, 3 cm). The carcinomas were of colloid type (3 tumors), pancreatobiliary type (4), or nonmucinous intestinal type (2). Five cases were associated with an intraductal papillary mucinous neoplasm (IPMN)-like precursor lesion within the residual structures of the minor papilla in the duodenal submucosa. Immunohistochemically, the intestinal-type and mucinous-type tumors tended to be positive for CK20, CDX2, MUC2, and B72.3, and pancreatobiliary-type tumors tended to be positive for CK7, MUC1, B72.3, and CA125. Loss of DPC4 (Smad4) expression was found in the pancreatobiliary-type carcinomas only. Two tumors showed loss of DNA mismatch-repair protein expression, one losing MLH1 and PMS2 and the other losing MSH6. Both patients were older than 60 years, and neither had germline mutation testing. Follow-up information was available for 6 patients (median follow-up time, 67.5 mo): 3 of the 6 patients died of disease at 60, 75, and 85 months after surgery, respectively, and all 3 patients had an intestinal-type carcinoma (1 colloid and 2 nonmucinous). The patient whose tumor was MSH6 deficient was alive without evidence of disease 51 months after surgery. In conclusion, adenocarcinomas of the minor papilla are rare tumors occurring predominantly in the sixth to seventh decade. Some of them arise from IPMN-like precursors in the residual submucosal minor papilla tissue. Morphologically, immunohistochemically, and clinically they are similar to ampullary or IPMN-associated pancreatic carcinomas and can exhibit either an intestinal, colloid, or pancreaticobiliary phenotype. DNA mismatch-repair deficiency may occur. A careful gross and histologic examination is essential to accurately recognize the site of origin of minor papilla carcinomas.

Primary retroperitoneal lymph node dissection in low-stage testicular germ cell tumors: a detailed pathologic study with clinical outcome analysis with special emphasis on patients who did not receive adjuvant therapy.

OBJECTIVE: To evaluate, in detail, the histopathologic features of metastatic testicular germ cell tumors to retroperitoneal lymph nodes treated with primary retroperitoneal lymph node dissection (RPLND) and correlate the findings with patients' outcomes. MATERIALS AND METHODS: We studied 183 patients with documented pathologic stage II disease with or without elevated serum tumor markers, selected from 453 patients who underwent primary RPLND at our institution from 1989 to 2002. Tumor type(s), size and extent of disease, and amount of tumor necrosis were assessed and correlated with outcome. RESULTS: Embryonal carcinoma was the most common tumor type, present as the only component in 99 cases (54%) and the predominant tumor type (>50%) in 142 (78%). The number of positive lymph nodes ranged from 1 to 40 from a total of 2-80 lymph nodes examined (median, 28). Extranodal extension (ENE) was identified in 120 cases (66%). Among 73 patients followed up expectantly and with normal serum tumor markers, 19 experienced relapse, the probability of which was higher in patients with more positive nodes, larger metastases, and presence of ENE. However, none of these differences was statistically significant (all P >.2). The predominance of embryonal carcinoma and the presence of tumor necrosis were not significantly associated with outcome. CONCLUSION: In this cohort, most patients treated with primary RPLND and with positive lymph nodes also had ENE. We did not identify any variables to be significantly associated with relapse after RPLND in patients managed expectantly. Additional studies with more patients are needed to validate our findings.

Phase II trial of neoadjuvant docetaxel and CG1940/CG8711 followed by radical prostatectomy in patients with high-risk clinically localized prostate cancer.

BACKGROUND: Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP). METHODS: Patients received docetaxel administered at a dose of 75 mg/m(2) every 3 weeks for 4 cycles. GVAX was administered 2-3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10(8) cells. The subsequent boost immunotherapies consisted of 3×10(8) cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate. RESULTS: Six patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP. CONCLUSIONS: Neoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.

Laparoscopic resection of a gastric glomus tumor.

Surgeons are commonly asked to evaluate patients with subepithelial masses of the stomach. Glomus tumors are subepithelial mesenchymal tumors that are rarely included in the differential diagnosis when evaluating these patients. We present the case of 55-year old man with a gastric glomus tumor that was diagnosed preoperatively and removed by laparoscopic wedge resection. We review the preoperative evaluation and classic finding associated with this uncommon entity.

Testicular mixed germ cell tumors: a morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas.

Stem cell markers, OCT3/4, and more recently SOX2 and growth differentiation factor 3 (GDF3), have been reported to be expressed variably in germ cell tumors. We investigated the immunohistochemical expression of these markers in different testicular germ cell tumors, and their utility in the differential diagnosis of morphologically difficult-to-classify components of these tumors. A total of 50 mixed testicular germ cell tumors, 43 also containing difficult-to-classify areas, were studied. In these areas, multiple morphological parameters were noted, and high-grade nuclear details similar to typical embryonal carcinoma were considered 'embryonal carcinoma-like high-grade'. Immunohistochemical staining for OCT3/4, c-kit, CD30, SOX2, and GDF3 was performed and graded in each component as 0, negative; 1+, 1-25%; 2+, 26-50%; and 3+, >50% positive staining cells. The different components identified in these tumors were seminoma (8), embryonal carcinoma (50), yolk sac tumor (40), teratoma (40), choriocarcinoma (3) and intra-tubular germ cell neoplasia, unclassified (35). By immunohistochemistry, the staining patterns were OCT3/4 -3+, all seminomas, embryonal carcinomas and intra-tubular germ cell neoplasia; SOX2 -3+, all embryonal carcinomas and -2 to 3+, 11/14 (79%) primitive neuroectodermal components in immature teratomas; GDF3 -2 to 3+, all yolk sac tumors, seminomas and intra-tubular germ cell neoplasia and 1 to 2+, 40/50 embryonal carcinomas. A total of 34/43 (79%) of difficult-to-classify areas stained 3+ for OCT3/4, CD30, and SOX2, similar to embryonal carcinoma. Among these areas, only 'embryonal carcinoma-like high-grade' nuclear details were significantly associated with such an immunophenotype. Thus, SOX2 is expressed in embryonal carcinoma and primitive neuroectoderm of teratoma, and unlike OCT3/4, not in intra-tubular germ cell neoplasia and seminoma. Therefore, it may be useful in the distinction of seminoma from embryonal carcinoma, and potentially in diagnosing early carcinomatous differentiation in seminoma. GDF3 positivity, in the absence of OCT3/4 and CD30, combined with morphological features, is helpful in the diagnosis of yolk sac tumor. 'Embryonal carcinoma-like high-grade' nuclear details are the most important morphological criterion for the diagnosis of embryonal carcinoma in difficult-to-classify areas.

Urachal carcinoma: a clinicopathologic analysis of 24 cases with outcome correlation.

BACKGROUND: Urachal carcinomas occur mostly in the bladder dome, comprising 22% to 35% of vesical adenocarcinomas, and are generally treated by partial cystectomy with en bloc resection of the median umbilical ligament and umbilicus. Detailed pathologic studies with clinical outcome correlation are few. DESIGN: We reviewed histologic material and clinical data from 24 cases selected from a database of 67 dome-based tumors diagnosed and treated at our institution from 1984 to 2005. Follow-up information was available for all 24 patients. RESULT: The mean age at diagnosis was 52 years (range: 26 to 68 y). Fifteen patients were male and 9 were female. Location was the dome in 23 and dome and anterior wall in 1. Thirteen cases were pure adenocarcinoma, not otherwise specified, 9 were enteric type adenocarcinoma, and 2 were adenocarcinoma with focal components of lymphoepithelioma-like carcinoma and urothelial carcinoma with cytoplasmic clearing. Signet ring cell features were focally seen in 2 cases. Cystitis cystica and cystitis glandularis were seen in 4 and 2 cases, respectively. In all instances but 1, cystitis cystica/glandularis was focal and predominantly in the bladder overlying the urachal neoplasm. Urachal remnants were identified in 15 cases: the urachal epithelium was benign urothelial-type in 6 cases and showed adenomatous changes in 9. The overlying bladder urothelium was colonized by adenocarcinoma in 3 cases. In all 3, urachal remnants were identified and showed transition from benign to adenomatous epithelium. On immunohistochemistry, these tumors were positive for CK20 and variably positive for CK7 and 34BE12. The majority showed a cytoplasmic membranous staining pattern for beta-catenin, although in 1 case, focal nuclear immunoreactivity was identified. The Sheldon pathologic stage was pT1 in 0, pT2 in 2, pT3a in 8, pT3b in 11, pT3c in 1, pT4a in 1, and pT4b in 1 patient. One patient had a positive soft tissue margin. The mean follow-up period was 40 months (range: 0.3 to 157.6 mo). Seven of 24 (29%) cases recurred locally. The incidence of local recurrence was higher in patients who underwent a partial cystectomy alone (37.5%) versus those who had a more radical surgery (27%). Distant metastases occurred in 9 (37.5%) patients, 4 of whom had no prior local recurrence. Seven patients (29%) died of the disease. All cases with locally recurrent and metastatic disease belonged to stage pT3 or higher. CONCLUSIONS: Pathologic stage is an important prognostic factor in urachal carcinoma. Surface urothelial involvement by carcinoma and presence of cystitis cystica/glandularis do not necessarily exclude the diagnosis of urachal carcinoma. Immunostains do not unequivocally discriminate a urachal from a colorectal carcinoma, but diffuse positivity for 34BE12 would support, and diffuse nuclear immunoreactivity for beta-catenin would militate against, a diagnosis of urachal carcinoma. Local recurrence may be owing to seeding within the distal urothelial tract, particularly in tumors with a configuration that is polypoid and which open into the bladder cavity. The type of surgery performed may have an effect on local recurrence despite negative margins of resection.

Expression of prostate-specific membrane antigen in renal cortical tumors.

Prostate-specific membrane antigen is a type II membrane glycoprotein that is expressed in benign and neoplastic prostatic tissue and has been recently shown to be also expressed in the neovasculature of various solid malignant tumors including renal cell carcinoma. Renal cell carcinoma is a heterogeneous group of tumors with distinct morphologic and genetic characteristics and clinical behaviors. We performed immunohistochemical studies on formalin-fixed, paraffin-embedded archival material from 75 nephrectomies, using antibodies 13D6 against prostate-specific membrane antigen and CD31 against endothelial cells. The study included 30 clear cell renal cell carcinomas, and 15 of each of papillary and chromophobe renal cell carcinoma and oncocytoma. The extent and intensity of staining were assessed semiquantitatively. In all cases, immunoreactivity was detected only in the tumor-associated neovasculature and not in tumor cells. Clear cell renal cell carcinoma showed the most diffuse staining pattern, where 24/30 cases or 80% had >50% reactive vessels, followed by chromophobe renal cell carcinoma (9/15; 60%) and oncocytoma (5/15, 33%). No diffuse staining was detected in any of the papillary renal cell carcinomas and only focal staining was detected in 11 cases (11/15; 73%). Staining intensity was the strongest in clear cell renal cell carcinoma (25/30; 83%) followed by chromophobe renal cell carcinoma (9/15; 60%), oncocytoma (8/15, 53%) and papillary renal cell carcinoma (5/15; 33%). In summary, prostate-specific membrane antigen is expressed in tumor-associated neovasculature of the majority of renal cortical tumors and is most diffusely and intensely expressed in clear cell renal cell carcinoma and least in papillary renal cell carcinoma. The differences in the expression of prostate-specific membrane antigen in renal cell carcinoma subtypes provide further evidence of the biological diversity of these tumors, and diagnostic and therapeutic applications of such expression can be expanded to include subtypes of renal cell carcinoma.

Carbonic anhydrase IX expression in clear cell renal cell carcinoma: an immunohistochemical study comparing 2 antibodies.

Carbonic anhydrase IX (CAIX)-a protein maintaining intracellular and extracellular pH-reportedly also influences regulation of cell proliferation, oncogenesis, and tumor progression. Its expression is von Hippel-Lindau-hypoxia inducible factor pathway dependent. Immunohistochemical (IHC) studies show that CAIX is diffusely overexpressed in clear cell renal cell carcinoma (CRCC), making it a potentially important differential diagnostic marker. Prognostically, low CAIX expression reportedly indicates poor survival and low response to interleukin therapy in CRCC. Most IHC studies have used clone M75 as the primary antibody, which is not commercially available. We evaluated a new commercially available antibody (clone NB100-417) to assess its expression in CRCC and compared its results with M75. On a tissue microarray of CRCC, IHC staining was performed using both antibodies. The immunoreactivity was graded as 0; 1+, 1% to 25%; 2+, 26% to 50%; and 3+, >50% tumor cells immunoreactive. Ninety-one out of ninety-five (96%) cases showed similar staining grade with excellent agreement (kappa=0.65, weighted kappa=0.75). Grade 3+ expression of CAIX was observed in 89 (94%) cases each, with both antibodies. Both antibodies produced intense membrane-predominant expression, limited to tumor cells. More than 95% of the tumors with low nuclear grade, compared with 84% and 88% of tumors with high nuclear grade, showed 3+ expression using both antibodies. Thus, most CRCC show strong and diffuse expression of CAIX, and the expression is comparable using both antibodies. Therefore, similar to the clone M75, NB100-417 can be used as a diagnostic and potentially a prognostic marker in CRCC, with the advantage of its commercial availability.

Anterior-predominant prostatic tumors: zone of origin and pathologic outcomes at radical prostatectomy.

Aggressive screening and prostate needle biopsy protocols have been successful in early detection of low-volume posterior tumors. Consequently, we have observed an increased incidence of anterior-predominant prostate cancers. However, the zones of origin, patterns of spread, and patterns of extraprostatic extension of this group of tumors have not been well studied. Of 1312 radical prostatectomies performed at our institution over a span of 4.5 years, 197 had predominant (largest) tumors anterior to the urethra in whole-mounted radical prostatectomy specimens. Detailed histopathologic analysis of this cohort was undertaken emphasizing the variability in anterior prostatic anatomy from apex through base to determine zone of origin and pathologic staging. Using this approach, 97/197 (49.2%) anterior-predominant tumors (ATs) were assigned to the anterior peripheral zone (APZ), 70 (35.5%) to the transition zone (TZ), 16 (8.1%) were of indeterminate zone, and 14 (7.1%) were of both zones. Comparing APZ and TZ tumors, there were no significant differences in Gleason scores, incidence of extraprostatic extension, overall surgical margin positivity rate, or laterality. Involvement of the anterior fibromuscular stroma was significantly more likely in tumors of TZ origin (P< or =0.01), yet was observed in 50.5% of APZ tumors. Conversely, APZ tumors were more commonly localized within the apical one third of the prostate. Most of the prostates (91.4%) also showed additional PZ tumors, which were occasionally stage determining (7/197; 3.9%). In conclusion, ATs of APZ origin are more prevalent than those arising from the TZ. Contrary to previous reports comparing TZ tumors to all PZ tumors, ATs of both zones exhibit similar grading and staging parameters in this series. Given these similarities, long-term clinical outcomes and future molecular analyses will be necessary to assess whether true differences in biology and behavior exist between tumors of TZ and APZ origin.

Risk assessment of prostatic pathology in patients undergoing radical cystoprostatectomy.

OBJECTIVES: To determine the incidence and location of prostate adenocarcinoma (PCa) and prostatic urothelial carcinoma (PUC) for patients undergoing radical cystoprostatectomy (RCP) for bladder cancer and to ascertain what preoperative information may be useful in predicting PUC or PCa in patients who may be candidates for prostate-sparing cystectomy. METHODS: Between 2001 and 2004, 235 consecutive patients underwent RCP and had whole-mount sections of the prostate. We reviewed our prospective radical cystectomy database for preoperative clinicopathological information associated with each patient. The bladder and whole-mount prostate sections were re-reviewed to determine the location and depth of the bladder tumor as well as the presence of any associated PCa and PUC. RESULTS: We identified 113 of 235 (48%) and 77 of 235 (33%) men with PCa and PUC, respectively. Among patients with PCa, 33 (29%) had Gleason score of > or = 7, 25 (22%) had PCa tumor volume > 0.5 cc, and 15 (13%) had extracapsular extension. On multivariable analysis, only increasing age was significantly associated with PCa (odds ratio=1.3, p=0.046). Of the 77 with PUC, 28 (36%) had in situ disease only, while 49 (64%) had prostatic stromal invasion. Bladder tumor location in the trigone/bladder neck (p<0.001) and bladder carcinoma in situ (p<0.001) was strongly associated with PUC in the final specimen. Overall, 158 (67%) had either PCa or PUC in the prostate. CONCLUSIONS: PCa and/or PUC is present in a majority of RCP specimens. Current preoperative staging and tumor characteristics are not adequate for determining who can safely be selected for prostate-sparing cystectomy.

Estrogen and progesterone-receptor-positive stroma as a non-tumorous proliferation in kidneys: a possible metaplastic response to obstruction.

The presence of estrogen and progesterone-receptor-positive stroma is well known in renal mixed epithelial and stromal tumor, cystic nephroma, and angiomyolipoma with epithelial cysts. It has been suggested that the hormone receptor positivity in mixed epithelial and stromal tumor may be etiologically related to exogenous hormone intake-a phenomenon that has become more frequent in recent years. In the past few years, we have observed such stroma in some non-neoplastic kidneys, as well as in tumor-bearing kidneys away from the tumor. Herein we present our experience with 10 such cases. In a prospective manner, whenever we noted stroma resembling that in ovaries or müllerian organs (endometrial or cervical-like) in kidneys removed for any cause, immunohistochemical stains for estrogen and progesterone receptors were performed. There were eight males and two females among the group, with ages ranging from 11 months to 71 years. In six cases, the nephrectomies were performed for a non-functional kidney, and in three for tumors (one each of chromophobe, clear cell, and acquired cystic disease-associated renal cell carcinoma). One case was a partial nephrectomy for vesico-ureteric reflux, with upper pole hydronephrosis. Such stroma was present in nine cases as a non-mass forming proliferation around dilated, frequently inflamed pelvicalyceal system and collecting ducts. In one it was present at the periphery of an acquired cystic disease-associated renal cell carcinoma, as well as around non-tumorous cysts. The only common finding in all cases was a generalized or segmental hydronephrosis, or tumor compression-related focal obstruction. The stroma was positive for estrogen receptors in all 10 cases, and for progesterone receptors in seven. Thus, estrogen- and progesterone receptor-positive stroma can be present in the kidney, not only as a component of certain tumors, but also in association with non-neoplastic conditions. Its association with obstructive changes suggests that it may represent a metaplastic change in the renal interstitial cells surrounding these obstructed epithelial structures.

Nested variant of urothelial carcinoma.

Nested variant of urothelial carcinoma is a rare neoplasm that is histologically characterized by large numbers of small, closely packed, haphazardly arranged, poorly defined, confluent irregular nests of bland-appearing urothelial cells infiltrating the lamina propria and the muscularis propria. Due to the cells' deceptively bland appearance, the tumors are sometimes misdiagnosed as benign lesions, leading in some cases to a significant delay in establishing the correct diagnosis and thus contributing to this neoplasm's advanced stage. Nested variant of urothelial carcinoma must be differentiated from the benign proliferative lesions of urothelium, such as von Brunn nests, cystitis cystica, cystitis glandularis, nephrogenic adenoma, inverted papilloma, and paraganglioma.

Positive surgical margins in soft tissue following radical cystectomy for bladder cancer and cancer specific survival.

PURPOSE: We evaluated risk factors for positive soft tissue surgical margins and the impact of soft tissue surgical margins on metastatic progression and disease specific survival in patients treated with radical cystectomy for bladder cancer. MATERIALS AND METHODS: A total of 1,589 patients who underwent radical cystectomy for primary urothelial cancer at our institution were included in the study. Several variables were analyzed including gender, age, use of perioperative chemotherapy, tumor stage, tumor grade, presence of carcinoma in situ, pathological vascular invasion, bladder pathology, status of soft tissue surgical margins, lymph node status, number of lymph nodes removed and number of positive lymph nodes. End points were freedom from progression to metastases and disease specific survival. RESULTS: Positive soft tissue surgical margins were detected in 67 patients (4.2%). Risk factors for positive soft tissue surgical margins were female gender (p = 0.04), pathological stage, vascular invasion in the radical cystectomy specimen, lymph node metastases (all p < or = 0.001) and median number of positive lymph nodes (p = 0.002). In addition, nonpure transitional cell carcinoma histology (p = 0.001) was associated with positive soft tissue surgical margins. In the 5 years after cystectomy, rates of disease specific survival for the negative and positive soft tissue surgical margin groups were 72% (95% CI 69-75) and 32% (95% CI 19-54), respectively. On multivariate analysis disease specific death was associated with tumor stage, positive soft tissue surgical margins, vascular invasion, presence of positive lymph nodes, number of nodes removed and number of positive nodes. CONCLUSIONS: Risk factors for positive soft tissue surgical margins are female gender, locally advanced cancer, presence of vascular invasion and mixed histology. Patients with positive soft tissue surgical margins have poor prognosis, and positive soft tissue surgical margins were found to be independently associated with disease specific death.

Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum.

The recently recognized Xp11 translocation renal cell carcinomas (RCCs), all of which bear gene fusions involving the TFE3 transcription factor gene, comprise at least one-third of pediatric RCC. Only rare adult cases have been reported, without detailed pathologic analysis. We identified and analyzed 28 Xp11 translocation RCC in patients over the age of 20 years. All cases were confirmed by TFE3 immunohistochemistry, a sensitive and specific marker of neoplasms with TFE3 gene fusions, which can be applied to archival material. Three cases were also confirmed genetically. Patients ranged from ages 22 to 78 years, with a strong female predominance (F:M=22:6). These cancers tended to present at advanced stage; 14 of 28 presented at stage 4, whereas lymph nodes were involved by metastatic carcinoma in 11 of 13 cases in which they were resected. Previously not described and distinctive clinical presentations included dense tumor calcifications such that the tumor mimicked renal lithiasis, and obstruction of the renal pelvis promoting extensive obscuring xanthogranulomatous pyelonephritis. Previously unreported morphologic variants included tumor giant cells, fascicles of spindle cells, and a biphasic appearance that simulated the RCC characterized by a t(6;11)(p21;q12) chromosome translocation. One case harbored a novel variant translocation, t(X;3)(p11;q23). Five of 6 patients with 1 or more years of follow-up developed hematogenous metastases, with 2 dying within 1 year of diagnosis. Xp11 translocation RCC can occur in adults, and may be aggressive cancers that require morphologic distinction from clear cell and papillary RCC. Although they may be uncommon on a percentage basis, given the vast predominance of RCC in adults compared with children, adult Xp11 translocation RCC may well outnumber their pediatric counterparts.

Glomus tumor of the kidney: a report of 3 cases involving renal parenchyma and review of the literature.

Glomus tumor is a rare mesenchymal neoplasm affecting the subcutaneous tissue of the distal extremities in the majority of cases. It only rarely involves visceral organs. We report 3 cases of the glomus tumor family in the kidney, a solid glomus tumor, a glomangioma, and a glomangiomyoma. All 3 tumors involved the renal parenchyma and occurred in 3 men aged 36, 81, and 48 years, respectively. All 3 tumors were well-circumscribed and showed morphology otherwise identical to those seen in soft tissue. All 3 tumors were immunoreactive for actin and negative for desmin and S100 and only 1 tumor expressed CD34 in tumor cells. To date, all 3 tumors have followed a benign course without evidence of recurrence or metastasis. This report expands the spectrum of mesenchymal tumors of the kidney.

Immunohistochemical expression of hypoxia inducible factor-1alpha and its downstream molecules in sarcomatoid renal cell carcinoma.

PURPOSE: Sarcomatoid renal cell carcinomas, highly aggressive variants of renal cell carcinoma subtypes, often present with or develop metastases soon after the primary diagnosis. Most metastatic cases do not respond to immunotherapy or aggressive chemotherapy. Recently targeted therapies, particularly those targeting hypoxia inducible pathway molecules, have been tested clinically on metastatic clear cell renal cell carcinoma with promising initial results. No such studies are available on sarcomatoid renal cell carcinoma. We investigated the hypoxia inducible pathway marker immunohistochemical expression profile, and any potential therapeutic implications that such expression may have, in these tumors. MATERIALS AND METHODS: Immunohistochemical staining for hypoxia inducible factor-1alpha, glucose transporter 1, carbonic anhydrase IX and vascular endothelial growth factor was performed in 22 clear cell and 12 nonclear cell sarcomatoid renal cell carcinomas. The immunoreactivity in the tumors was graded from 0 to 3+ (0-no staining, 1+-1% to 25% cells positive, 2+-26% to 50% cells positive and 3+-greater than 50% cells positive). The results were then compared with various clinical parameters to assess for associations. RESULTS: Most clear cell renal cell carcinomas over expressed (2+ or 3+) hypoxia inducible factor-1alpha (in 59%), carbonic anhydrase IX (95%), glucose transporter 1 (91%) and vascular endothelial growth factor (95%). None of the nonclear cell sarcomatoid renal cell carcinomas showed 2+ or 3+ expression of hypoxia inducible factor-1alpha, carbonic anhydrase IX or glucose transporter 1, but 92% showed diffuse positivity for vascular endothelial growth factor. Over expression of carbonic anhydrase IX showed no association with survival, unlike that reported in (nonsarcomatoid) clear cell renal cell carcinoma. There was significant discordance in the staining grades among hypoxia inducible factor-1alpha, carbonic anhydrase IX and glucose transporter 1 in clear cell renal cell carcinoma, suggesting that mechanisms other than hypoxia inducible pathway may be involved in some sarcomatoid clear cell renal cell carcinoma. CONCLUSIONS: Hypoxia inducible pathway markers continue to be over expressed in sarcomatoid clear cell renal cell carcinoma, and can be of diagnostic usefulness in such high grade tumors. Over expression of vascular endothelial growth factor in the clear and nonclear cell groups raises the possibility that vascular endothelial growth factor targeted therapies may have a role in the management of sarcomatoid renal cell carcinoma, and deserve further investigation.