Plasmacytoid Variant Of Urothelial Carcinoma Research Articles

Plasmacytoid urothelial carcinoma - A clinicopathological case series of an aggressive variant of urothelial cancer.

Many new morphological variants of urothelial carcinoma of urinary bladder have been described in the literature, plasmacytoid/signet ring cell/diffuse variant being one of the rare amongst these. Till date, no case series has been reported from India, describing this variant. We retrospectively analyzed the clinicopathological data of 14 patients diagnosed at our center with plasmacytoid urothelial carcinoma. Seven cases (50%) were pure forms while the remaining 50% of cases had a concurrent conventional urothelial carcinoma component. Immunohistochemistry was performed to rule out other mimickers of this variant. Treatment-related data were available for seven patients, while follow-up was available for nine cases. Overall, plasmacytoid variant of urothelial carcinoma is considered to be an aggressive tumor with poor prognosis.

Plasmacytoid variant urothelial carcinoma of the bladder: effect of radical cystectomy and chemotherapy in non-metastatic and metastatic patients.

Data about optimal management of plasmacytoid (PCV) bladder cancer patients are extremely scarce and limited by sample size. We focused on PCV bladder cancer patients to explore the effect of radical cystectomy (RC) and chemotherapy in non-metastatic (T 2-4N0-3M0), as well as in metastatic (TanyNanyM1) subgroups. Using the Surveillance, Epidemiology and End Results database (2000-2016), we identified 332 PCV patients with muscle-invasive disease or higher (≥ T2N0M0). Kaplan-Meier plots and Cox regression models addressed cancer-specific mortality (CSM). In 332 PCV patients, median age was 68years (Interquartile range [IQR]:58-76). Of those, 252 were non-metastatic patients (76%) vs 80 were metastatic patients (24%), at presentation. Of non-metastatic patients, 142 (56%) underwent RC and 131 (52%) underwent chemotherapy. Chemotherapy did not improve CSM in non-metastatic PCV. Conversely, RC was associated with lower CSM (hazard ratio [HR]: 0.51, p = 0.002). Median CSM-free survival was 48 vs 38 months for RC treated vs RC not treated. Of metastatic patients, 22 (28%) underwent RC and 42 (52%) underwent chemotherapy. Both chemotherapy and RC improved CSM in metastatic PCV. Median CSM-free survival was 12 vs 7 months for RC treated vs RC not treated (HR: 0.27, p < 0.001). Median CSM-free survival was 11 vs 4 months for chemotherapy exposed vs chemotherapy naïve (HR: 0.32, p = 0.002). Although RC resulted in lower CSM, chemotherapy failed to show that effect in non-metastatic PCV patients. Conversely, both chemotherapy and RC resulted in statistically significantly lower CSM in metastatic PCV patients.

Plasmacytoid Variant of Urothelial Carcinoma: Poor Prognostic Variant with High Expression of CDH1 Mutation

Plasmacytoid variant of urothelial carcinoma is a rare subtype of urothelial carcinoma that has poor prognosis. We describe two cases of patients with the plasmacytoid variant of urothelial carcinoma (PVUC) who had initial response to neoadjuvant chemotherapy followed by radical cystoprostatectomy and lymph node dissection but presented with early relapse and disease progression manifesting with intestinal obstruction and peritoneal carcinomatosis. Tumor genomic sequencing revealed mutations and alterations in ARID1A, CDH1, PIK3CA, RB1 loss, and TERT promoter, as well as tumor mutational burden of 10 Muts/Mb treated with pembrolizumab with a minimal response. A further review of the literature regarding this rare variant is discussed here.

Editorial Comment on Plasmacytoid Variant Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis of Clinicopathological Features and Survival Outcomes.

Editorial Comment on Plasmacytoid Variant Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis of Clinicopathological Features and Survival Outcomes.

Plasmacytoid Variant Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis of Clinicopathological Features and Survival Outcomes

The clinicopathological features and treatment outcomes of plasmacytoid variant-urothelial carcinoma of the bladder have not been fully understood. We evaluated the clinicopathological characteristics and survival outcomes of plasmacytoid variant-urothelial carcinoma of the bladder compared to conventional urothelial carcinoma of the bladder. A systematic review was performed following the PRISMA guideline. PubMed®/MEDLINE®, Embase® and Cochrane Library were searched up to June 2019. The differences in the clinicopathological features (stage pT3 or greater, lymph node metastasis, ureteral margin positive and perivesical soft tissue margin positive status) and survival outcomes (overall mortality and cancer specific mortality) between plasmacytoid variant-urothelial carcinoma of the bladder and conventional urothelial carcinoma of the bladder were compared. The GRADE approach was used for rating the certainty of evidence. Eight studies were included. Patients with plasmacytoid variant-urothelial carcinoma of the bladder had a higher frequency of stage pT3 or greater (OR 3.84, 95% CI 1.63-9.03, p=0.002) and risk of lymph node metastasis (OR 2.58, 95% CI 1.15-5.76, p=0.02), ureteral margin positive (OR 12.18, 95% CI 4.62-32.13, p <0.00001) and perivesical soft tissue margin positive (OR 12.31, 95% CI 5.15-29.41, p <0.00001) status after radical cystectomy than those with conventional urothelial carcinoma of the bladder. Although there was no difference in cancer specific mortality (HR 1.40, 95% CI 0.82-2.40, p=0.22) between plasmacytoid variant-urothelial carcinoma of the bladder and conventional urothelial carcinoma of the bladder, plasmacytoid variant-urothelial carcinoma of the bladder had worse survival outcomes (overall mortality) than conventional urothelial carcinoma of the bladder approaching the borderline of significance (HR 1.62, 95% CI 0.98-2.68, p=0.06) when adjusted for other clinicopathological characteristics. Plasmacytoid variant-urothelial carcinoma of the bladder was strongly associated with adverse clinicopathological features and worse overall mortality compared to conventional urothelial carcinoma of the bladder after adjusting for other clinicopathological parameters, and plasmacytoid variant histology of urothelial carcinoma of the bladder is an independent prognostic factor for overall survival.

Plasmacytoid variant urothelial carcinoma: Clinicopathologic outcomes and experience with neoadjuvant chemotherapy.

483 Background: Plasmacytoid variant histology is a rare variant that is often locally advanced at diagnosis. Data is limited to small series and the ideal treatment remains unknown. Here we report the clinicopathologic features and outcomes of 29 patients with plasmacytoid variant histology, including 12 patients treated with neoadjuvant chemotherapy (NAC) and 4 with adjuvant or salvage immunotherapy. Methods: All cystectomies performed from 2011-2018 at our institution were reviewed. Patients with plasmacytoid features on transurethral resection or cystectomy were included. Categorical variables were compared using chi-squared tests and survival outcomes were analyzed with log-rank analysis. Results: A total of 993 patients underwent cystectomy for malignancy. Of these, 29 patients (2.9%) had plasmacytoid variant features. At cystectomy, 65.5% were ≥ pT3, 48.2% were node positive, and 13.8% had positive soft-tissue margins. Twelve patients died during the observed period (41.4%), with a median time to death of 7.2 months. Among surviving patients, median follow-up was 21.9 months. Of the 4 patients with positive margins, survival was significantly worse than those with negative margins (p&lt;0.005); all 4 died with a median survival of 1.8 months. Cisplatin based NAC was given to 12 patients (41.4%). NAC was not associated with a survival benefit over cystectomy alone (median survival 27.7 and 51.9 months, respectively; p=0.07), complete response (pT0), or organ confined disease (&lt; pT3). Four patients (13.8%) received adjuvant or salvage checkpoint inhibitors; all surviving with a median follow-up of 28.7 months. Conclusions: Consistent with prior reports, plasmacytoid variants were uncommon and locally advanced. While our rate of positive margins was lower than in previous series, patients with positive margins universally did poorly. NAC was not associated with improved survival or pathologic outcomes. Our findings suggest plasmacytoid variants may not respond well to NAC, though no definitive conclusions can be drawn due to the small number of patients and retrospective design.

Targeted sequencing of plasmacytoid urothelial carcinoma reveals frequent TERT promoter mutations

Activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary tract. Although the cadherin 1 (CDH1) gene is commonly mutated in the clinically aggressive plasmacytoid variant of urothelial carcinoma (PUC), little is known about their TERT promoter mutation status. A retrospective search of our archives for PUC and UC with plasmacytoid and/or signet ring cell features (2007-2014) was performed. Ten specimens from 10 patients had archived material available for DNA analysis and were included in the study. Intratumoral areas of nonplasmacytoid histology were also evaluated when present. Samples were analyzed for TERT promoter mutations with Safe-SeqS, a sequencing error-reduction technology, and sequenced using a targeted panel of the 10 most commonly mutated genes in bladder cancer on the Illumina MiSeq platform. TERT promoter mutations were detected in specimens with pure and focal plasmacytoid features (6/10). Similar to conventional UC, the predominant mutation identified was g.1295228C>T. In heterogeneous tumors with focal variant histology, concordant mutations were found in plasmacytoid and corresponding conventional, glandular, or sarcomatoid areas. Co-occurring mutations in tumor protein p53 (TP53, 2 cases) and kirsten rat sarcoma (KRAS) viral proto-oncogene (1 case) were also detected. TERT promoter mutations are frequently present in PUC, which provides further evidence that TERT promoter mutations are common events in bladder cancer, regardless of histologic subtype, and supports their inclusion in any liquid biopsy assay for bladder cancer.

A Case of PT1 Plasmacytoid Variant Bladder Cancer Treated by Bladder Conserving Therapy

Plasmacytoid variant bladder cancer is a highly malignant subtype associated with a high propensity for invasion, metastasis and poor prognosis. Among approximately 100 reported cases, most were diagnosed at an advanced stage and only 10 were diagnosed at a non-muscle-invasive stage. Due to the limited data on clinical features of non-muscle-invasive plasmacytoid variant bladder cancer, its treatment has not been established. We report a long-surviving patient with pT1 plasmacytoid variant bladder cancer in whom the bladder was conserved after detailed pathological examinations of the transurethral resection (TUR) specimen and intensive follow-up. A 65-year-old man presented with macroscopic hematuria. Cystoscopy revealed a nodular tumor 11 millimeters in diameter and no metastasis was observed on computed tomography. The histopathological diagnosis of the TUR specimen was pT1 plasmacytoid variant urothelial carcinoma of the bladder. Microvascular invasion was not found by immunohistochemical staining and histopathological examination of the specimen from the second TUR indicated no residual cancer. The patient strongly desired bladder conservation and additionally underwent intravesical instillation therapy with 40 mg of mitomycin C weekly for 6 consecutive weeks. Follow-up cystoscopy demonstrated 3 small papillary tumors 12 months after intravesical instillation therapy, but histopathologically, the recurrent tumors were pTa with pTis urothelial carcinomas without plasmacytoid components. To treat pTis disease, he subsequently underwent intravesical BCG instillation therapy. The plasmacytoid variant bladder cancer has not recurred for 26 months since the initial diagnosis. Non-muscle-invasive and localized plasmacytoid variant bladder cancer may be treated with bladder conserving therapy.

Plasmacytoid Variant of Urothelial Carcinoma in Ureter

Plasmacytoid Variant of Urothelial Carcinoma in Ureter

Bladder cancer rapid autopsy: A mechanism for collecting metastatic tumor tissue and establishing xenograft models of metastatic disease.

478 Background: Patients with metastatic bladder cancer have a poor prognosis with a median survival of only 9-15 months. Understanding the biology of metastatic bladder cancer has been historically difficult due to a paucity of specimens and models that recapitulate human disease. We established a bladder cancer rapid autopsy program to systemically acquire metastases, and build patient-derived xenograft (PDX) and organoid models for biological studies. Methods: Patients with metastatic bladder cancer were consented and a rapid autopsy was performed 2-6 hours after death to allow acquisition of normal and metastasis specimens. Frozen and formalin-fixed and paraffin embedded specimens were collected and pathological evaluation was performed on each specimen. Additionally, tumors were implanted subcutaneously into SCID mice to establish PDXs. Once PDXs were developed, PDXs were dissociated for companion organoid culture. Clinical history and treatment information was documented for each patient. Results: We have performed 10 bladder cancer rapid autopsies to date, and have acquired 105 metastatic and 45 normal specimens. The pathological subtypes of patients include urothelial cell carcinoma (5/10), squamous cell carcinoma (3/10), and plasmacytoid variant of urothelial carcinoma (2/10). The cohort has been treated BCG only (1/10), chemotherapy (3/10), and chemotherapy and immune checkpoint inhibitors (6/10). The leading site of metastasis was the liver (7/10) and lung (7/10), followed by lymph node (5/10), bone (5/10), intestine (4/10), and omentum (2/10). Half (5/10) of the patients had extensive liver metastases that allow acquisition of multiple tumor foci. For the first time, PDX and organoids from two independent metastases (omentum – CoCaB 14.1 and liver –CoCaB 14.2) from the same patient were successfully developed. Conclusions: This bladder cancer rapid autopsy program provides an important volume of metastatic tumor specimens for study. Importantly, the first bladder cancer PDX derived from metastasis has been developed. The availability of metastatic bladder cancer specimens, PDXs, and organoids will allow biological studies of advanced disease.

The Impact of Plasmacytoid Variant Histology on the Survival of Patients with Urothelial Carcinoma of Bladder after Radical Cystectomy

BackgroundThe clinical significance of the plasmacytoid variant (PCV) in urothelial carcinoma (UC) is currently lacking. ObjectiveTo compare clinical outcomes of patients with any PCV with that of patients with pure UC treated with radical cystectomy (RC). Design, setting, and participantsWe identified 98 patients who had pathologically confirmed PCV UC and 1312 patients with pure UC and no variant history who underwent RC at our institution between 1995 and 2014. Outcome measurements and statistical analysisUnivariable and multivariable Cox regression and Cox proportional hazards regression to determine if PCV was associated with overall survival (OS). Results and limitationsPatients with PCV UC were more likely to have advanced tumor stage (p=0.001), positive lymph nodes (p=0.038), and receive neoadjuvant chemotherapy than those with pure UC (46% vs 22%, p<0.0001). The rate of positive soft tissue surgical margins was over five times greater in the PCV UC group compared with the pure UC group (21% vs 4.1%, respectively, p<0.0001). Median OS for the pure UC versus the PCV patients were 8 yr and 3.8 yr, respectively. On univariable analysis, PCV was associated with an increased risk of overall mortality (hazard ratio=1.34, 95% confidence interval: 1.02–1.78, p=0.039). However, on multivariable analysis adjusted for age, sex, neoadjuvant chemotherapy received, lymph node status, pathologic stage, and soft margin status, the association between PCV and OS was no longer significant (hazard ratio=1.06, 95% confidence interval: 0.78, 1.43, p=0.7). This retrospective study is limited by the lack of pathological reanalysis, and the impact of other concurrent mixed histology cannot be determined in this study. ConclusionsPatients with PCV features have a higher disease burden at RC compared with those with pure UC. However, PCV was not an independent predictor of survival after RC on multivariable analysis, suggesting that PCV histology should not be used as an independent prognostic factor. Patient summaryPlasmacytoid urothelial carcinoma is a rare and aggressive form of bladder cancer. Patients with plasmacytoid urothelial carcinoma had worse adverse pathologic features, but this was not associated with worse overall mortality when compared with patients with pure urothelial carcinoma.

Plasmacytoid urothelial carcinoma: a case report

The plasmacytoid variant of urothelial carcinoma is a rare entity with a very poor prognosis. The majority of patients present in advanced stages with extravesical disease. The awareness of this entity is important as the features can be confused with that of other malignancies. Accurate reporting is of critical importance due to the chemosensitve nature of this disease. We present a case of a 55-year-old who presented with left flank pain and who subsequently underwent CT which showed a thickened bladder wall. Urine cytology was positive for malignant cells. He went on to have a transurethral resection of the tumour with histological features of plasmacytoid urothelial carcinoma with muscle invasion. Immunohistochemical studies confirmed the diagnosis. Following a radiacal cystoprostatectomy, he was found to have extravesical fat involvement and adventitial tissue involvement around the resection margin of the left ureter. Regional lymph nodes were positive for small collections of malignant cells. This case report illustrates the very aggressive nature of this disease and the potential pitfalls in the diagnosis.

膀胱癌plasmacytoid variantを認めた1例

We reported the experience with a case of plasmacytoid variant of urothelial carcinoma of urinary bladder. A 75-year-old woman complained of gross hematuria. She was hospitalized to be diagnosed as the bladder tumor on abdominal CT. TUR-BT was performed and pathological finding was invasive urothelial carcinoma. But she refused radical cystectomy. 2 months later, she was hospitalized again with worsening hematuria. Simple cystectomy was performed. Histological examination revealed a plasmacytoid appearance of the infiltrating tumor cells. Immunohistochemical stains for lymphoid markers were negative. Those findings lead to the diagnosis of plasmacytoid variant of urothelial carcinoma. She died due to local recurrence for 1.5 months after simple cystectomy.

Plasmacytoid Urothelial Carcinoma, a Chemosensitive Cancer with Poor Prognosis, and Peritoneal Carcinomatosis

Plasmacytoid urothelial carcinoma is a rare variant histology with poorly defined clinical behavior. We report clinical outcome information on patients with predominant plasmacytoid urothelial carcinoma. We retrospectively analyzed treatments and outcomes in patients with predominant plasmacytoid urothelial carcinoma seen at our institution from 1990 through 2010. The Kaplan-Meier method was used to calculate overall and progression-free survival. We identified 31 patients with a median age of 63.5 years, of whom 83.3% were male. TNM stage was cT1N0 in 4 patients, cT2N0 in 7, cT3b-4aN0 in 5 and cT4b, N+ or M+ in 15. Median overall survival was 17.7 months (stage I-III vs IV 45.8 vs 13.3). Five of the 16 patients with potentially surgically resectable plasmacytoid urothelial carcinoma (pT4aN0M0 or less) received neoadjuvant chemotherapy, 10 underwent initial surgery and 1 was treated only with transurethral resection of bladder tumor. Despite pathological down staging in 80% of the patients who received neoadjuvant chemotherapy, relapses were common. There was no survival difference between patients treated with neoadjuvant chemotherapy or initial surgery, although 7 received adjuvant chemotherapy. Surgical up staging with positive margins was also common for surgery alone. The most common site of recurrence was in the peritoneum (19 of 23 patients) with relapses even in those with a pathological complete response at surgery. In patients who presented with metastatic disease and were treated with chemotherapy median survival was 12.6 months. Plasmacytoid urothelial carcinoma is an aggressive subset with overall poor outcomes. Although down staging is seen with neoadjuvant chemotherapy, there are few long-term survivors. There is a strong predilection for recurrence along the peritoneal lining.

Dysregulation of mammalian target of rapamycin pathway in plasmacytoid variant of urothelial carcinoma of the urinary bladder

Plasmacytoid urothelial carcinoma is a rare but aggressive variant of bladder cancer with no clear therapeutic guidelines. Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been linked to oncogenesis in conventional bladder cancer. Several antineoplastic agents targeting mTOR pathway are currently available. This study assesses mTOR pathway status as well as c-myc and p27 expression. We retrieved 19 archival cases of plasmacytoid urothelial carcinoma from two institutions. Whole tissue sections were evaluated for immunoexpression of phosphatase and tensin homolog (PTEN), phosphorylated mTOR, phosphorylated protein kinase B (AKT), phosphorylated S6, c-myc, and p27. We evaluated intensity (0 to 3+) and extent (0%-100%) of expression for all markers. An H score was calculated as the sum of products of intensity and extent for each marker and used during analysis. In addition, PTEN loss was defined as absence of expression in >10% of tumor cells. We encountered PTEN loss in 28%. Higher H score for nuclear phosphorylated AKT and a lower H score for phosphorylated S6 was encountered in muscle invasive tumors compared to non-muscle invasive tumors (P = .007 and P = .009, respectively). Although a trend for negative prognostic impact on overall survival for higher phosphorylated mTOR expression was noted (P = .051), markers expression levels failed to predict survival in our cohort. We found dysregulation of mTOR pathway members in urinary bladder plasmacytoid urothelial carcinoma, suggesting that the use of mTOR pathway inhibitors might be beneficial for patients with this aggressive tumor.

Plasmacytoid variant of urothelial carcinoma: A report of a rare case

Plasmacytoid variant of urothelial bladder carcinoma is rare. We report a case with a detailed discussion of features that help characterize this variant. A 50-year-old man originally presented with gross hematuria. Resections at that time revealed a grade I-II superficial urothelial carcinoma. He did not return for follow-up until recently, three years later, when he presented with recurrent gross hematuria. An extensive tumor was identified on cystoscopy. Resection revealed a high-grade non-invasive papillary urothelial carcinoma. CT scan revealed a large urinary bladder solid mass with bilateral hydronephrosis. Metastatic workup was negative. The patient underwent a radical cystectomy with creation of ileal conduit. Final pathology revealed plasmacytoid variant of urothelial carcinoma with extensive vascular invasion and extension to the perivesical adipose tissue. We present a rare variant of urothelial carcinoma with comprehensive analysis of the morphological and immunophenotypic clues that characterize this variant.

395 DYSREGULATION OF MTOR PATHWAY IN PLASMACYTOID VARIANT OF UROTHELIAL CARCINOMA OF THE URINARY BLADDER

You have accessJournal of UrologyUrothelial Cancer: Natural History & Pathophysiology/Marker1 Apr 2012395 DYSREGULATION OF MTOR PATHWAY IN PLASMACYTOID VARIANT OF UROTHELIAL CARCINOMA OF THE URINARY BLADDER Nilda Gonzalez-Roibon, Alcides Chaux, Adeboye O. Osunkoya, Turki Al-Hussain, Jessica Hicks, Jonathan I. Epstein, and George Netto Nilda Gonzalez-RoibonNilda Gonzalez-Roibon Baltimore, MD More articles by this author , Alcides ChauxAlcides Chaux Baltimore, MD More articles by this author , Adeboye O. OsunkoyaAdeboye O. Osunkoya Atlanta, GA More articles by this author , Turki Al-HussainTurki Al-Hussain Baltimore, MD More articles by this author , Jessica HicksJessica Hicks Baltimore, MD More articles by this author , Jonathan I. EpsteinJonathan I. Epstein Baltimore, MD More articles by this author , and George NettoGeorge Netto Baltimore, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.459AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Mammalian target of rapamycin (mTOR) pathway plays an important role in cell growth, migration, and proliferation. mTOR pathway dysregulation has been linked to oncogenesis in several malignancies, including conventional urothelial carcinoma of bladder. Several antineoplastic agents targeting mTOR pathway are currently available. Plasmacytoid variant of urothelial carcinoma (UC) is a rare but aggressive variant of bladder cancer. The current study assesses mTOR pathway status as well as c-myc and p27 expression, two markers known to interact with this pathway. METHODS Nineteen cases of plasmacytoid UC were retrieved from the surgical pathology files of our 2 institutions, including 12 cases from the consultation service of 2 of the authors. Whole sections were evaluated for immunoexpression of PTEN, phosphorylated mTOR (phos-mTOR), phosphorylated AKT (phos-AKT), phosphorylated S6 (phos-S6), c-myc, and p27. Antibody sources and IHC parameters were as previously described (Cancer 2010;116:5517). Cases with >10% loss of cytoplasmic PTEN expression were considered to show loss of PTEN. For the remaining markers, expression intensity (0 to 3+) and extent (0% to 100%) was evaluated in each tumor. An H-Score (Σintensity × percentage) was calculated. Pairwise correlation coefficients (CC) were estimated to assess relationship among markers expression. RESULTS PTEN loss was encountered in 5 cases (28%) of plasmacytoid UC. In contrast, high levels of phos-mTOR (mean 218, range 97 - 285), phos-AKT (mean 211, range 67 - 295) and phos-S6 (mean 248, range 164 - 298) were found. Low expression of c-myc (mean 51, range 0 - 223) and of p27 (mean 61, range 0 - 225) were noted. phos-AKT expression positively correlated with phos-mTOR (CC = 0.54, P = .02). phos-S6 expression negatively correlated with c-myc expression (CC = -0.67, P < .005). CONCLUSIONS We found dysregulation of the mTOR pathway in plasmacytoid urothelial carcinoma of the urinary bladder. These results suggest that the use of mTOR inhibitors might be beneficial for patients with this aggressive variant of urothelial carcinoma. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e162 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nilda Gonzalez-Roibon Baltimore, MD More articles by this author Alcides Chaux Baltimore, MD More articles by this author Adeboye O. Osunkoya Atlanta, GA More articles by this author Turki Al-Hussain Baltimore, MD More articles by this author Jessica Hicks Baltimore, MD More articles by this author Jonathan I. Epstein Baltimore, MD More articles by this author George Netto Baltimore, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Plasmacytoid Carcinoma of the Bladder: A Urothelial Carcinoma Variant With a Predilection for Intraperitoneal Spread

Bladder plasmacytoid carcinoma is an invasive urothelial carcinoma subtype that is emphasized for its morphological overlap with plasma cells and metastatic carcinoma. Our experience suggests frequent intraperitoneal spread that is not typical of conventional urothelial carcinoma. We identified cases of plasmacytoid urothelial carcinoma diagnosed on radical cystectomy. Patient age, gender, American Joint Committee on Cancer (7th edition) stage, metastatic spread/recurrence sites and clinical disease status at last followup were recorded. A total of 10 male and 5 female patients 42 to 81 years old were identified. One tumor was pT2, 11 pT3 and 3 pT4. Six of 15 patients (40%) presented with lymph node metastasis and 5 (33%) had intraperitoneal metastasis at cystectomy. These initial sites of metastatic spread included the prerectal space, ovary and vagina, ovary and fallopian tube, bowel serosa, and omentum and bowel serosa in 1 case each. Three patients had subsequent metastasis involving the prerectal space, pleural fluid and small bowel serosa, and bowel serosa in 1 each. Eight patients had followup information available, including 3 who died of disease, 3 with disease and 2 with no evidence of disease. Of the patients 33% with the plasmacytoid variant of urothelial carcinoma presented with intraperitoneal disease spread and 20% had subsequent metastasis involving serosal surfaces. The possibility of noncontiguous intraperitoneal spread involving serosal surfaces should be recognized to ensure proper intraoperative staging and clinical followup for patients with plasmacytoid carcinoma.

Two cases of plasmacytoid variant of urothelial carcinoma of urinary bladder: systemic chemotherapy might be of benefit

We report two cases of the plasmacytoid variant of urothelial carcinoma of urinary bladder in which systemic chemotherapy was effective. In the first case, a 76-year-old man presented with dysphasia. Magnetic resonance imaging (MRI) and computed tomography revealed a brain tumor and a bladder tumor. Resection of the brain tumor and transurethral resection of the bladder tumor were performed. The pathological diagnosis was plasmacytoid variant of urothelial carcinoma of urinary bladder with brain metastasis (pT1N0M1). Three cycles of adjuvant MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) chemotherapy were performed. He has no evidence of recurrence 96 months after resection of brain metastasis. In the second case, a 76-year-old man presented with hematuria. MRI revealed a bladder tumor with abdominal wall invasion, and a transurethral biopsy was performed. The pathological diagnosis was plasmacytoid variant of urothelial carcinoma of urinary bladder (cT4bN0M0). After three cycles of neoadjuvant GC (gemcitabine and cisplatin) chemotherapy, MRI demonstrated a complete response. Radical cystectomy was performed, and the pathological diagnosis was pT0pN0. Although there was no evidence of recurrence 9 months after radical cystectomy, he died from other causes. Our two cases suggest that systemic chemotherapy might be effective for the plasmacytoid variant of urothelial carcinoma.

Plasmacytoid urothelial carcinoma of the urinary bladder: clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis of a case series

A plasmacytoid variant of urothelial carcinoma has been recently recognized in the World Health Organization classification system. This is characterized by a discohesive growth of plasmacytoid cells with eccentric nuclei, extending in the bladder wall and often in the perivesical adipose tissue. Herein, we report the clinicopathologic, immunohistochemical, ultrastructural, and molecular features of a series of plasmacytoid urothelial carcinoma of the urinary bladder. Four bladder carcinomas characterized by epithelial cells with morphologic appearance resembling plasma cells were evaluated at the immunohistochemical, electron microscopic, and molecular genetic levels. Tumor cells stained with cytokeratins, epithelial membrane antigen, GATA-3 (endothelial transcription factor 3), CD15, p53, and p16. In addition, malignant cells strongly stained with CD138 in all the cases, whereas leukocyte common antigen and multiple myeloma 1/interferon regulatory factor 4 were completely negative, nor immunoreactivity was seen for either κ or λ light chains. The electron microscopic examination showed the presence of divergent squamous and glandular differentiation. At variance with conventional urothelial carcinoma, the analysis of exons 4-9 of TP53 gene revealed no alteration in all the 4 tumors tested, and this can be of value in choosing additional chemotherapy after surgery. Plasmacytoid carcinoma of the bladder is a tumor entity, which can be characterized by specific immunohistochemical markers, including positivity for GATA-3, and presents phenotypic and genotypic peculiarities.