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Plasmacytoid Urothelial Carcinoma
Abstract
The plasmacytoid variant of urothelial carcinoma is rare, of which less than 40 cases have been reported in the English language literature. Herein we report the largest series to date of 17 cases of urothelial carcinoma with plasmacytoid features and report the associated clinicopathologic findings. The architectural pattern of the tumor varied from cells arranged in cords and single cells (35%), small nests (17%), solid sheetlike growth (29%), and diffuse discohesive patternless architecture (23%). The plasmacytoid component varied from 15% to 100% of the specimen analyzed; in 12 cases the plasmacytoid component composed greater than 50% of the tumor. The individual tumor cells had striking morphologic overlap with plasma cells with an eccentrically placed nucleus and abundant amphophilic to eosinophilic cytoplasm. The nuclei were of low to intermediate nuclear grade with minimal nuclear pleomorphism. Thirteen of 17 cases (76%) were associated with conventional high-grade invasive urothelial carcinoma and 9 cases showed very focal intracytoplasmic vacuoles mimicking signet ring cells. One case also showed sarcomatoid dedifferentiation. The tumor cells were positive for cytokeratin 7 (94%) and cytokeratin 20 (31%); CD138 was positive in 94% of cases. All cases were invasive -- 7 into at least the lamina propria, 7 into at least the muscularis propria, and 3 into perivesical fat. Follow-up information was available in 16 cases (range: 2 wk to 43 mo; mean 10 mo; median 5.5 mo). Eleven patients died of disease and 5 patients were alive with disease. Plasmacytoid variant of urothelial carcinoma is an aggressive subtype associated with poor prognosis. In limited samples, it may be misdiagnosed as chronic cystitis or plasmacytoma, a pitfall further compounded by CD138 expression. Distinction from metastatic carcinoma from other primary sites such as stomach and breast is critical due to differing therapeutic implications.
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ABSTRACT Invasive urothelial carcinoma is the most frequent type of bladder cancer and may occur in pure or classical form or with the presence of variant or subtype histology and/or evidence of divergent morphology such as squamous, glandular, or trophoblastic differentiation. Increasingly, it is recognized that certain subtypes impact patient prognosis and outcome hence the need to correctly recognize and document their presence. Certain subtypes and divergent features correlate with the emerging molecular bladder cancer subtypes, which can also influence patient management decisions. The pathologist therefore plays a crucial role in providing clinically relevant information, mostly derived from hematoxylin and eosin slides, which will guide urologists and oncologists in terms of risk stratification and treatment planning.
Colorectal carcinoma with noncohesive tumor cells has been described in tumors with signet ring cells (mucinous adenocarcinoma and signet ring cell adenocarcinoma) and rhabdoid feature (carcinoma with sarcomatoid component). Cases of carcinoma with plasmacytoid morphology are rare in the gastrointestinal tract, and a single case of plasmacytoid colorectal carcinoma has been reported. We report the case of a 37-year-old woman who presented with urinary symptoms, hematuria, and abdominal pain. Imaging studies showed segmental sigmoid wall thickening with pericolic infiltration and focal bladder wall thickening. The cystoscopy with transurethral resection of bladder tumor revealed muscle invasion, dis-cohesive carcinoma with plasmacytoid morphology, which was initially misdiagnosed as the plasmacytoid urothelial carcinoma. Immunohistochemical stains showed the tumor cells to be positive for CDX2, CK20, and SATB2 and negative for p63, GATA3, CK7, and Uroplakin II, indicating the colorectal origin of the tumor. The subsequent colonic wall biopsy showed the same tumor. Molecular studies identified BRAF V600E, SMAD4, and p53 mutations associated with aggressive colorectal adenocarcinoma with mucinous/signet ring cell features. Further whole-exome sequencing and whole transcriptome analysis confirmed the colorectal origin of the tumor. This rare colorectal adenocarcinoma with the plasmacytoid feature may represent the signet ring cell adenocarcinoma lacking extracellular mucin or intracellular vacuole. Diagnosis of this rare histological subtype of colorectal carcinoma is important, particularly in the unusual presentation of this aggressive tumor.
Purpose
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.
Methods
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).
Results
In 332 PCV patients, median age was 68 years (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).
Conclusions
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.
Urothelial carcinoma is characterized by the presence of a wide spectrum of histopathologic features and molecular alterations that contribute to its morphologic and genomic heterogeneity. It typically harbors high rates of somatic mutations with considerable genomic and transcriptional complexity and heterogeneity that is reflective of its varied histomorphologic and clinical features. This review provides an update on the recent advances in the molecular characterization and novel molecular taxonomy of urothelial carcinoma and variant histologies.
Histopathological evaluation of bladder lesions represents one of the more challenging areas of pathology. In part, this reflects both the plasticity of the urothelium and the variety of processes that can affect the bladder. The frequent lack of objective ancillary markers to confirm or exclude a diagnosis contributes to the additional complexity to the analysis of bladder biopsies or resections. In this Chapter, we will outline common lesions that affect the bladder and highlight various challenges in their diagnosis.
Plasmacytoid urothelial carcinoma (PUC) is a rare, aggressive histologic variant of urothelial cancer characterised by a diffuse growth pattern and CDH1 mutation. We studied the efficacy of preoperative platinum-based chemotherapy in nonmetastatic PUC and immune checkpoint inhibitors (ICIs) in advanced PUC.
Cases of nonmetastatic PUC and advanced PUC treated with ICIs at our institution were identified. Outcomes were compared to those of a published cohort of patients with urothelial carcinoma not otherwise specified.
We identified 81 patients with nonmetastatic PUC. Of the patients with localised disease who underwent neoadjuvant chemotherapy, pathologic complete response and downstaging rates were 12 and 21%, respectively. Pathologic downstaging was not associated with significant improvement in clinical outcomes. Up to 18% of localised disease and 28% of locally advanced cases had unresectable disease at the time of surgery. ICI-treated advanced PUC (N = 21) had progression-free and overall survival of 4.5 and 10.5 months, respectively, and a 38% response rate. FGFR3 and DNA damage response gene alterations were observed in 3 and 15% of cases, respectively.
PUC is associated with high disease burden and poor chemosensitivity. Increased awareness and recognition of this disease variant will allow for new treatment strategies.
Background:
The tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E-box-binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial-mesenchymal transition, is involved in tumor transformation.
Case presentation:
The patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E-cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E-cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells.
Conclusion:
We suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E-cadherin in a plasmacytoid urothelial carcinoma.
Introduction
Despite significant advances in the treatment of metastatic urothelial carcinoma, including the advent of immune checkpoint inhibitors, this disease is still challenging to treat and associated poor outcomes remain. Genomic characterization of advanced-stage urothelial carcinoma is widening the field of potential treatments due to the identification of novel biologic drivers.
Areas covered
In this review, we explore the role of PARP, HER-2, and mTOR inhibitors in the therapeutic scenario of advanced urothelial carcinoma, as these pathways are frequently altered in urothelial carcinoma. We report ongoing clinical trials involving these agents, either in monotherapy or in combination with other compounds, highlighting the dynamic scenario of metastatic urothelial carcinoma treatment.
Expert opinion
Several challenges need to be faced in the development of new potential therapeutic strategies, such has inter/intratumoral heterogeneity and the lack of validated biomarkers.
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.
Patient: Female, 64-year-old
Final Diagnosis: Plasmacytoid urothelial carcinoma of the bladder
Symptoms: Nausea • vomiting
Medication:—
Clinical Procedure: Cystoscopy
Specialty: Oncology
Objective
Rare disease
Background
Plasmacytoid urothelial carcinoma (PUC) is a rare and aggressive variant of urothelial cancers. Herein, we report a patient with CDH-1 mutated PUC who presented with disseminated peritoneal metastasis and high levels of CA 19-9.
Cases Report
A 65-year-old female presented to the hospital with vomiting, obstructive jaundice, and acute renal failure. Imaging studies showed bilateral hydronephrosis, bladder wall thickening without masses, and dilation of both common bile and pancreatic ducts without pancreatic masses. Carbohydrate antigen (CA) 19-9 was elevated at >17 000 U/mL. Repeated cystoscopies demonstrated no masses within the bladder, but with nodularity and inflamed mucosa, and random biopsies were obtained and showed PUC. Ascitic fluid cytology revealed meta-static PUC. A targeted exome next-generation sequencing (NGS) revealed pathogenic mutations in TP53, CDH-1, RB1, and ARIDA1A. The patient was debilitated, and hospice care was recommended. She passed away after 2 months of her initial presentation.
Conclusions
PUC is a rare and aggressive histological variant of bladder cancer. Advanced stage at diagnosis and high relapse rates after treatment with cytotoxic regimens are common. At the molecular level, somatic alterations in cadherin-1 (CDH-1) gene seem to be characteristic. Exploring the molecular sphere of this disease is prudent to identify possible new therapeutic targets.
Histological and molecular analyses of urothelial carcinoma often reveal intratumoural and intertumoural heterogeneity at the genomic, transcriptional and cellular levels. Despite the clonal initiation of the tumour, progression and metastasis often arise from subclones that can develop naturally or during therapy, resulting in molecular alterations with a heterogeneous distribution. Variant histologies in tumour tissues that have developed distinct morphological characteristics divergent from urothelial carcinoma are extreme examples of tumour heterogeneity. Ultimately, heterogeneity contributes to drug resistance and relapse after therapy, resulting in poor survival outcomes. Mutation profile differences between patients with muscle-invasive and metastatic urothelial cancer (interpatient heterogeneity) probably contribute to variability in response to chemotherapy and immunotherapy as first-line treatments. Heterogeneity can occur on multiple levels and averaging or normalizing these alterations is crucial for clinical trial and drug design to enable appropriate therapeutic targeting. Identification of the extent of heterogeneity might shape the choice of monotherapy or additional combination treatments to target different drivers and genetic events. Identification of the lethal tumour cell clones is required to improve survival of patients with urothelial carcinoma.
Bladder cancer is a heterogenous disease that is associated with tangible mortality in muscle invasive disease. The WHO 2016 classification of urothelial tumours reflects the contemporary approach towards histological variants in bladder cancer, including variants of urothelial carcinoma and non-urothelial variants. This review focuses on variant histology in urothelial carcinoma, and discusses the importance of accurate histological diagnosis, and subsequent risk stratification and therapeutic decision making based on proper variant recognition. Most urothelial variants are associated with poorer outcomes compared to conventional urothelial carcinoma, although some perform reasonably better. However, high quality evidence detailing optimal treatment and survival outcomes are still lacking in literature, due to the rarity of these cases.
Urothelial carcinoma is the most common histologic subtype of bladder cancer, accounting for approximately 90%. We herein report a case of a 78-year-old man with an unusual association of bladder stones with an aggressive plasmacytoid variant of urothelial cancer. Initially he presented in 2009 with a very large bladder stone and was treated by an open cystolithotomy. Histology from a bladder biopsy at that time was benign. He failed to attend follow-up appointments but subsequently he attended in 2016 with a recurrent urinary tract infection and an acute kidney injury. A CT scan showed multiple bladder stones. The cause of our patients' multiple bladder stones is unclear and unusual. He then underwent a further open cystolithotomy according to our multidisciplinary team recommendation. Post-operatively he unfortunately developed a non-healing vesicocutaneous fistula for which he was performed cystoscopy and biopsy but ended with transurethral resection due to the extent of abnormal/necrotic tissue. Histology confirmed a plasmacytoid variant of urothelial cancer. To our knowledge, this is the first case of an association of bladder stones with a plasmacytoid variant of urothelial cancer.
Purpose of Review
Urothelial carcinomas (UC) are characterized by variant morphologies. However, the diagnosis of these variants can be challenging, in part due to their evolving diagnostic criteria. This review discusses the diagnostic criteria, molecular features, and prognostic implications of the UC variants. Evolving subtypes of UC are also briefly discussed.
Recent Findings
The WHO 2016 classification of tumors of the urinary system has refined the morphologic criteria for the diagnosis of UC variants. Many of these follow a more aggressive clinical course, but conclusive data on their effect on survival are lacking. The molecular alterations characteristic of some of these variants may be amenable to targeted therapies.
Summary
Accurate identification of variant histology in UC has important implications for patient management. Despite identification of distinct molecular alterations in some of these variants, current molecular classifiers of invasive UC have not been significantly analyzed in these subtypes, opening up areas of future research.
Background:
Rapid ("warm") autopsies of patients with advanced metastatic cancer provide important insight into the natural history, pathobiology and histomorphology of disease in treatment-resistant tumors. Plasmacytoid urothelial carcinoma (PUC) is a rare variant of urothelial carcinoma characterized by neoplastic cells morphologically resembling plasma cells. PUC is typically aggressive, high-stage at presentation, and associated with poor outcomes. Recurrence is common in PUC, with the majority of recurrences occurring in the peritoneum.
Case presentation:
Here, we report rapid autopsy findings from a patient with recurrent PUC. The patient had persistent pain after cystoprostatectomy, although initial post-operative imaging showed no evidence of disease. Imaging obtained shortly before his death showed only subtle growth along vascular tissue planes; however, extensive disease was seen on autopsy. Plasmacytoid tumor cells formed sheets involving many serosal surfaces. Molecular interrogation confirmed a mutation in CDH1 exon 12 leading to early truncation of the CDH1 protein in the tumor cells.
Conclusions:
The sheet-like growth pattern of PUC makes early phases of disease spread much more difficult to capture on cross-sectional imaging. Alternative forms of surveillance may be required for detection of recurrent PUC, and providers may need to treat based on symptoms and clinical suspicion.
Urothelial carcinoma is a morphologically and genomically heterogeneous disease that exhibits a wide spectrum of morphologic features and molecular alterations and subtypes. Classic urothelial carcinoma (not otherwise specified) is the most common tumor type that develops in the urinary bladder but many, well-documented, variant histologies are commonly encountered in approximately one-third of invasive urothelial carcinoma, including squamous, glandular, micropapillary, sarcomatoid, small cell/neuroendocrine, clear cell, lymphoepithelioma-like, and plasmacytoid types, among others. In this review, we provide an update on the molecular advances in urothelial carcinoma and some of its variant histologies.
Plasmacytoid and rhabdoid variants of urothelial carcinomas (UCs) of the urinary bladder have been described in humans with plasma cell–like or rhabdoid cellular appearance and aggressive clinical outcome. Canine UC of the bladder is generally classified as papillary/nonpapillary and infiltrating/noninfiltrating with limited information regarding other histological patterns. We report 3 cases of UC of the urinary bladder showing a unique discohesive cellular morphology with malignant behavior resembling the human plasmacytoid and rhabdoid variants of UC, which may raise some difficulties in diagnosis. Epithelial-mesenchymal transition and reduced E-cadherin expression were revealed by immunohistochemistry in 2 cases, possibly explaining the discohesive and invasive behavior of the tumor cells. The findings broaden the morphological spectrum as well as the distinct clinical features of canine UC of the urinary bladder.
Carcinoma of the urinary bladder exhibits a wide spectrum of morphologies that is characteristic of this disease. Urothelial carcinoma (UCa) represents the most common tumor that develops in the urinary bladder and it is well established that there is remarkable propensity for divergent differentiation in this disease. A number of well-documented variant histologies are commonly encountered in approximately one third of invasive UCa (Amin, Mod Pathol 22: S96–S118, 2009; Linder, et al., J Urol 190: 1692–6, 2013; Shah, et al., Urol Oncol 31: 1650–5, 2013; Moch, et al., World health organization classification of tumours, 2016). These include squamous, glandular, micropapillary, sarcomatoid, small cell/neuroendocrine, clear cell, lymphoepithelioma-like, and plasmacytoid types among others. Pure squamous cell carcinoma and adenocarcinoma can also occur in the bladder but are generally rare. In this chapter we will provide an update on the recent molecular developments with particular focus on those related to the variant histologies of bladder cancer.
Objective: The aim of the present study was to emphasize the critical importance of the clinician’s awareness of signet-ring cell carcinoma (SRCC) of the urinary bladder, a rare and aggressive disease entity.
Materials and methods: A review of the current literature was conducted and a classic case of advanced SRCC of the urinary bladder is reported, clearly demonstrating the severity of this disease and the imperative need for standardized recommendations for the diagnostic work-up and management of urinary bladder SRCC.
Results: The prognosis for patients with SRCC of the urinary bladder is poor, attributed to presentation at advanced stages following asymptomatic progression, inefficacy of multimodality therapy and possibly an aggressive underlying biological phenotype. Treatment options are limited and not well studied.
Conclusion: Given the rarity of SRCC, multi-institutional clinical trials and international cooperation are mandatory to improve survival for patients with primary SRCC of the bladder.
Micropapillary, sarcomatoid and small cell carcinoma are uncommon variants of invasive urothelial carcinoma that show aggressive behavior. These may occur in the context of high-grade papillary urothelial carcinoma or urothelial carcinoma in situ. Of these, only small cell carcinoma is effectively treated with currently available systemic therapy, with recent evidence suggesting a role for neoadjuvant chemotherapy. While pure adenocarcinoma and squamous cancers can also arise from the urothelium, neither is as sensitive to chemotherapy as conventional urothelial cancer. In contrast, the dominant lymphoepithelioma-like variant has a favorable prognosis. The plasmacytoid variant, which also appears chemosensitive, has very few long-term survivors despite downstaging with neoadjuvant chemotherapy. Urachal cancers require preoperative recognition for optimal surgical management, and are being shown to be somewhat responsive to regimens useful in colon cancer. Mesenchymal tumors are exceedingly rare and are treated like other pelvic sarcomas.
Background
Plasmacytoid urothelial carcinoma (PUC) is a distinct variant of urinary bladder cancer, with a high propensity for invasion and poor prognosis. These tumors occur most commonly in male patients with the age of reported cases ranging from 46 to 87 years.
Case report
We present a case of a 74-year-old male patient having massive ascites and bilateral lower leg edema. Colonoscopy showed a 3-cm lesion in the sigmoid colon and an edematous nonpapillary tumor was found by cystoscopy in the bladder. Histopathology analysis of the biopsies showed adenocarcinoma of colon and PUC of bladder. The diagnosis of PUC with peritoneal carcinomatosis was then confirmed by immunohistochemical stain.
Conclusion
The diagnostic dilemmas of the unusual variant of urothelial malignancy, the origin of peritoneal metastasis, and its clinical impact are discussed in the present case.
Plasmacytoid urothelial carcinoma (PUC) of the urinary bladder is a rare and aggressive subtype of urothelial carcinoma. Its deceptive morphology is characterized by a discohesive growth of cells with plasmacytoid morphology. Since this tumor might be confused with plasmacytoma, lymphoma, or carcinoma variants, appropriate diagnosis in small biopsy samples could be challenging. This study reports the case of a 53-year-old man who presented with frequent nocturnal urgency, without hematuria. A transurethral bladder and a prostate resection specimen displayed infiltration of neoplastic cells in a spray-like discohesive pattern with occasional formation of small irregular nests and cord-like arrangements. The basic morphology of the tumor cells was plasmacytoid, with eccentric nuclei and eosinophilic cytoplasm. Tumor cells grew through the lamina muscularis mucosae, with splintering of the bladder wall musculature and infiltration of prostatic tissue. They displayed strong and diffuse nuclear reactivity for p53 and GATA3. Eight months after surgery, the patient experienced upper abdominal discomfort. A duodenal biopsy showed infiltration of plasmacytoid atypical cells strongly immunoreactive for GATA3, consistent with the previously diagnosed PUC. The patient died eleven months after the primary diagnosis of his PUC of tumor cachexia losing about 50% of his original body weight, furthermore, with ascites and intraperitoneal tumor spread.
Introduction:
Plasmacytoid urothelial carcinoma (PUC) is a high-grade variant of conventional urothelial cell carcinoma. This study is the first to describe the imaging findings of PUC, which are previously unreported, using clinical and histopathological correlation.
Methods:
With internal review board approval, we identified 22 consecutive patients with PUC from 2007-2014. Clinical parameters, including age, gender, therapy, surgical margins, and long-term outcome, were recorded. Baseline imaging was reviewed by an abdominal radiologist who evaluated for tumour detectability/location/morphology, local staging, and presence/location of metastases. Pelvic peritoneal spread of tumour (defined as >5mm thick soft tissue spreading along fascial planes) was also evaluated. Followup imaging was reviewed for presence of local recurrence or metastases.
Results:
Median age at presentation was 74 years (range 51-86), with only three female patients. Imaging features of the primary tumour in this study were not unique for PUC. Muscle-invasive disease was present on pathology in 19/22 (86%) of tumours, with distant metastases in 2/22 (9%) at baseline imaging. Pelvic peritoneal spread of tumour was radiologically present in 4/20 (20%) at baseline. During followup, recurrent/residual tumour was documented in 16/22 (73%) patients and 7/16 (44%) patients eventually developed distant metastases. Median time to disease recurrence in patients who underwent curative surgery was three months (range 0-19).
Conclusions:
PUC is an aggressive variant of urothelial carcinoma with poor prognosis. Pelvic peritoneal spread of tumour as thick sheets extending along fascial planes may represent a characteristic imaging finding of locally advanced PUC.
Bladder cancer (BC) is a frequent type of carcinoma with an estimated incidence of approximately 100,000 men and women each year in the European Union (EU) with an associated mortality of 30,000 of these patients. In more than 70% the disease is diagnosed in a non-muscle invasive stage with the chance of minimally invasive, local treatment only, which might be required repetitively due to high rate of recurrence. In contrast, muscle invasive or metastatic stages need multimodal treatment strategies including surgical treatment and chemotherapy (CTX) in neoadjuvant (NAC), adjuvant, or palliative settings. Therapy recommendations and guidelines mainly refer to the most common histological type of BC, pure urothelial carcinoma (UC). However, BC can be classified as urothelial and non-UC. Non-urothelial BC and variants of UC account for up to 25% of all BCs. Further discrimination can be made into epithelial and non-epithelial non-UC. Most of the non-UCs are of epithelial origin (approximately 90%) including squamous-cell carcinoma, adenocarcinoma and small-cell carcinoma. Non-epithelial tumors are rare and include variants as sarcoma, carcinosarcoma, paraganglioma, melanoma and lymphoma. Even though it is unclear whether the prognosis of non-urothelial cancer truly differs from that of UC, there is evidence that additional variant histology might prognosticate an impaired prognosis. Accordingly, aggressive behavior and often advanced stages at primary presentation are frequently observed in non-UC arguing for radical and sometimes different treatment strategies as compared to pure UC. This review aims to summarize the available data for the most common histological variants of non-urothelial BC.
Plasmacytoid urothelial carcinoma (PUC) is an extremely rare and aggressive variant of urothelial carcinoma. We report a case of a 62-year-old male who presented with a rapid spread of PUC to involve his entire scrotal wall after failed surgery and chemotherapy. The second course of chemotherapy was effective in providing symptom control. We believe this is the first case report of PUC causing such rapid and extensive scrotal invasion. This case highlights the important features of PUC including the pattern of tumor spread along fascial planes, the tendency for initial understaging, and the rapid recurrence after initially response to chemotherapy.
CD138 (syndecan-1) immunoexpression has been reported to be specific for the plasmacytoid variant of urothelial carcinomas (UCs). The aim of this study was to examine the utility of CD138 immunohistochemistry for diagnosing the plasmacytoid variant of UCs. The extent and intensity of CD138 immunostaining were evaluated in 22 infiltrating UCs, 2 other infiltrating carcinomas, 15 noninvasive urothelial lesions, 3 other benign lesions, and perilesional normal tissues. CD138 immunostaining of the normal urothelial epithelium was universally diffuse and strong. In addition, all 42 cases of urinary tract lesions exhibited positive CD138 immunostaining; however, 1 of 3 plasmacytoid variants exhibited focal CD138 expression. The frequency of CD138 positivity in plasmacytoid variants may be relatively low, compared with that observed in the conventional types and other variants; thus, it is not appropriate to assume that CD138 expression in UCs is specific for plasmacytoid variants.
Bladder cancer imposes a considerable burden on patients and health care systems around the world. Estimates predict more than 70,000 new cases of bladder cancer and more than 14,000 deaths in 2010 in the USA [1]. Bladder cancer is three times more common in men than in women and roughly twice as common in Caucasians as African-Americans. For unknown reasons, relative mortality rates are lower for men and for Caucasians [2, 3]. The risk of bladder cancer increases with age, peaking between the sixth and eighth decades of life, creating unique challenges in treatment related to existing comorbidities [4, 5]. At the time of diagnosis, 75 % of patients present with nonmuscle-invasive bladder cancers (NMIBC); 70–80 % are limited to the mucosa (Ta, Tis) and the remaining 20–30 % invade the lamina propria (T1) [6].
During these past few decades, several uncommon and unique variants of urothelial carcinoma have been described. These variants’ morphologies constitute < 5 % of bladder carcinomas and may occur in pure form, or more often, are admixed with conventional urothelial carcinoma. Most tumors are recognized descriptively according to their unique histo- or cyto-morphology such as nested, microcystic, micropapillary, plasmacytoid, clear cell, and lymphoepithelioma-like carcinoma variants. Awareness of these variants is important as some are suggested to have an aggressive behavior and differing therapeutic response when compared to conventional urothelial carcinoma. Some may also have a unique presentation and pattern of tumor spread. Further, since these variants have distinct morphology from conventional urothelial carcinoma, they may histologically resemble benign processes or tumors of other organ primaries. Diagnosis of urothelial carcinoma variants may pose a challenge particularly in bladder biopsies or at metastatic sites.
Das Kapitel bietet eine umfassende Darstellung der neoplastischen Erkrankungen der Harnblase und der ableitenden Harnwege. Auf der Basis der WHO-Klassifikation und ihrer Modifikationen wird zu den häufigen wie auch zu den seltenen Tumoren Stellung genommen und ihre prognostische Bedeutung herausgestellt. Die Morphologie der Tumoren wird durch generelle Informationen zur Epidemiologie und Genetik ergänzt. Hervorgehoben wird die Differentialdiagnose der Tumoren, insbesondere unter Anwendung immunhistochemischer Marker. Makroskopie und Histologie der Tumoren werden durch repräsentatives Bildmaterial verdeutlicht.
It has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours. Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 WHO classification. In most cases, it represents intraductal spread of aggressive prostatic carcinoma and should be separated from high-grade prostatic intraepithelial neoplasia. New acinar adenocarcinoma variants are microcystic adenocarcinoma and pleomorphic giant cell adenocarcinoma. Modifications to the Gleason grading system are incorporated into the 2016 WHO section on grading of prostate cancer, and it is recommended that the percentage of pattern 4 should be reported for Gleason score 7. The new WHO classification further recommends the recently developed prostate cancer grade grouping with five grade groups. For bladder cancer, the 2016 WHO classification continues to recommend the 1997 International Society of Urological Pathology grading classification. Newly described or better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential, which is frequently identified in patients with a prior history of urothelial carcinoma. Invasive urothelial carcinoma with divergent differentiation refers to tumours with some percentage of “usual type” urothelial carcinoma combined with other morphologies. Pathologists should mention the percentage of divergent histologies in the pathology report.
Patient summary
Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 World Health Organization classification. Better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential.
Aim
. HER2 overexpression has been reported in a minority of urothelial carcinomas, but little is known about HER2 protein expression and gene alterations in plasmacytoid urothelial carcinoma, a rare and aggressive variant. The aim of this study was to clarify the HER2 status in plasmacytoid urothelial carcinomas.
Methods
. Six cases of plasmacytoid urothelial carcinoma were included, in which we evaluated HER2 protein expression by immunohistochemistry (IHC) and
HER2
gene amplification by fluorescence
in situ
hybridization (FISH).
Results
. The patients’ ages ranged from 57 to 83 years (mean age, 71 years). Five patients were male and one was female. The ratio of the plasmacytoid component ranged from 30% to 100% (mean, 77%). HER2 expression score was 3+ in 4 cases, 2+ in one case, and negative in one case. HER2 gene amplification was positive in 3 cases, of which 2 cases showed a 3+ HER2 IHC score but one case was negative for HER2 IHC. Another 2 cases showed equivocal HER2 FISH results, and one remaining case was negative for HER2 FISH.
Conclusion
. Our observation that plasmacytoid urothelial carcinomas frequently demonstrated HER2 protein overexpression provides supporting evidence that HER2 may be a potential therapeutic target for plasmacytoid urothelial carcinoma.
Plasmacytoid bladder cancer is an aggressive histologic variant with a high risk of disease-specific mortality. Using whole-exome and targeted sequencing, we find that truncating somatic alterations in the CDH1 gene occur in 84% of plasmacytoid carcinomas and are specific to this histologic variant. Consistent with the aggressive clinical behavior of plasmacytoid carcinomas, which frequently recur locally, CRISPR/Cas9-mediated knockout of CDH1 in bladder cancer cells enhanced cell migration.
Urothelial carcinoma can be subdivided primarily into conventional and nonconventional subtypes. Conventional urothelial carcinoma comprises the vast majority (>90 %) of all forms of urinary tract cancer and arises from either papillary or flat in situ lesions. In contrast, nonconventional carcinoma of the urinary tract includes squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, which are discussed in individual chapters within the text.
The plasmacytoid variant of urothelial carcinoma (UC) is a rare histological variant, with a small number of cases described in the literature. A 70-year-old man was referred to our hospital because of pain during urination and macroscopic hematuria. Cystoscopy revealed a massive nodular tumor in the bladder. Transurethral resection provided evidence for the diagnosis of UC with plasmacytoid morphology. After two cycles of neoadjuvant MEC (Methotrexate, Etoposide and Cisplatin) chemotherapy, cystectomy was performed. The pathological examination revealed plasmacytoid variant of UC (pT2b, grade 3, pNO). No adjuvant chemotherapy was initiated. In the eighth months since the cystectomy, abnormally high levels of serum alkaline phosphatase were noted. Computed tomography led to a diagnosis of multiple bone metastasis. After three cycles of MVAC (Methotrexate, Vinblastine, Doxorubicin and Cisplatin) chemotherapy, neither obvious exacerbation of the bone metastasis nor neopathy was recognized. Later, his clinical condition rapidly deteriorated and the patient died 13 months after the cystectomy.
The majority (more than 90%) of malignant neoplasms arising in the bladder are pure urothelial (transitional cell) carcinomas, and the rest (less than 10%) consist of histological variants of bladder cancer, including urothelial carcinoma admixed with other histologic patterns (squamous/glandular differentiation, nested, microcystic, clear cell, plasmacytoid, lymphoepithelioma-like, micropapillary, sarcomatoid variants, etc.) and pure forms of non-urothelial carcinoma (squamous cell carcinoma, adenocarcinoma, small cell carcinoma, etc.). These histological variants of bladder cancer have been described in a number of case series for several years and have been recognized in the 2004 World Health Organization Classification of urothelial cancers. These histological variants of bladder cancer have clinical significance at various levels, including diagnostic, that is, recognition of the morphological variant is necessary in order to avoid diagnostic misinterpretations; prognostic for patient risk stratification; and therapeutic, where a diagnosis of a particular variant may be associated with the administration of a therapy distinctive from that used in conventional urothelial carcinoma. In this article, we will chiefly review the literature on the histological variants of urothelial carcinoma with a focus on the prognostic and therapeutic implications of histological variants for the management of patients with bladder cancer.
A case of combined micropapillary and plasmacytoid urothelial carcinoma (UC) of the urinary bladder is presented for a 74-year-old male who was admitted to the hospital with gross hematuria and multifocal papillary bladder tumors. Abdominal computed tomography showed a large enhancing mass on the left lateral and anterior wall of the urinary bladder, which was highly suspicious for extravesicular extension and focal extension of the anterior lesion to the pubic bone. In voided urine, cancer cells were scattered as micropapillae or nests as well as single cells on the low power view. On a higher power view, micropapillae or nests were composed of pleomorphic, high grade tumor cells with an inverted nuclear arrangement and with acinar structures occasionally identified. Single cells were discohesive and large with a thick cytoplasm and eccentrically located nuclei. Histologically, the tumor from the resected bladder showed diffusely infiltrating micropapillae or nests with a surrounding halo and dense singly-scattered plasmacytoid cells. Immunohistochemically, the cancer cells were positive for cytokeratin-7 and cytokeratin-20 but negative for S-100, leukocyte common antigen, and vimentin. At the time of radical cystectomy, severe adhesions and peritoneal metastases were found and the surgery was discontinued. The patient received systemic chemotherapy, but died of bladder cancer 14 months after surgery. Diagn. Cytopathol. 2015. © 2015 Wiley Periodicals, Inc.
Plasmacytoid carcinoma of the urinary bladder or plasmacytoid urothelial carcinoma (PUC) is rare and only recently described a histological variant of transitional cell carcinoma. The morphological resemblance of PUC to other malignancies is a source of diagnostic dilemmas and often misdiagnosis. Immunohistochemistry plays a pivotal role in narrowing the differential diagnosis and reaching to a conclusive diagnosis. A diagnosis of PUC usually carries a dismal prognosis. Hence, correct diagnosis is important. We report here a 52-year-old male with a plasmacytoid variant of urothelial carcinoma.
Introduction :: Le carcinome urothélial plasmocytoïde est une variante histologique rare du carcinome urothélial. Seule une centaine de cas ont été décrits dans la littérature. Dans cette étude, nous faisons état de deux nouvelles observations. En combinant nos résultats à ceux des différentes séries décrites dans la littérature, nous tentons de définir les caractéristiques cliniques et pathologiques ainsi que l’approche thérapeutique de cette pathologie.
Observations :: Deux nouveaux cas de carcinome urothélial plasmocytoïde ont été diagnostiqués et pris en charge dans notre établissement. Les 2 patients étaient des hommes de 76 ans en moyenne. L’hématurie était le principal symptôme. Les deux patients ont subi une résection transurétrale de la vessie. Le stade tumoral au moment du diagnostic était avancé dans les deux cas (respectivement T3N0M0 et T3N1M0). Les deux patients ont été traités par cystoprostatectomie. L’analyse histologique de la pièce opératoire, complétée par une étude immunohistochimique, a confirmé le diagnostic de carcinome urothélial plasmocytoïde. Le premier patient est décédé un mois plus tard des suites d’une embolie pulmonaire. Le deuxième patient est décédé au bout de deux mois après avoir reçu deux cycles de chimiothérapie adjuvante. Les données recueillies sur les différentes séries décrites dans la littérature vont dans le même sens que nos données, à savoir un stade avancé au moment du diagnostic et un pronostic sombre.
Conclusion :: Le carcinome urothélial plasmocytoïde est une variante histologique rare et agressive du carcinome urothélial. Le diagnostic se fait souvent à un stade avancé, et le pronostic est peu encourageant. Le traitement repose le plus souvent sur une cystectomie, suivie d’une chimiothérapie adjuvante à base de cisplatine. L’intérêt d’une chimiothérapie néo-adjuvante n’a pas encore été établi.
The aim of this study was to report a small series of fine-needle aspiration (FNA) cytology of the plasmacytoid variant of urothelial carcinoma (PVUC).
A computerized search of our laboratory information system was performed for the 5-year period between January 2008 and January 2013 to identify all FNA cases in which the corresponding surgical pathology cases were diagnosed as PVUC.
The 4 cases identified were from 2 men (aged 56 and 64 years) and 2 women (aged 72 and 46 years). The FNA smears demonstrated low-to-moderate cellularity and consisted predominantly of single and dyshesive, medium-sized tumor cells with eccentrically located nuclei and a moderate-to-abundant dense cytoplasm. The nuclei were oval with slightly irregular nuclear membranes and contained coarse granular chromatin with inconspicuous or small nucleoli. There was moderate nuclear variation in size. The nuclear-to-cytoplasmic ratio ranged from <1 to 3. Binucleation, cytoplasmic vacuoles, and perinuclear hof were occasionally seen.
FNA cytology of PVUC shares features with plasma cell neoplasms, lobular carcinoma of the breast, and signet ring cell carcinoma of the stomach. Being aware of the patient's clinical history and the potential diagnostic pitfall of this rare variant of urothelial carcinoma is important for an accurate diagnosis on FNA biopsy. © 2015 S. Karger AG, Basel.
Biopsies from the urinary bladder are challenging and it may be difficult to differentiate normal from benign or reactive processes, and even from low-grade neoplastic processes. This chapter addresses these common problems by profiling immunohistochemical stains that change their patterns of expression from that of normal urothelium, including both the cellular layers and cellular compartments in which markers are expressed. Morphologic patterns of urothelial carcinoma that cause diagnostic dilemmas are also included, such as glandular lesions of both primary and metastatic origin, and lesions with variant histologic growth patterns. Staining patterns of urachal neoplasms and their differential diagnoses are addressed. Nephrogenic adenomas of the urothelial tract and their mimics are covered. Although uncommon, the differential diagnosis of spindle cell lesions is also addressed.
Sarcomatoid urothelial carcinoma is a dedifferentiated biphasic tumor that exhibits morphological and/or immunohistochemical evidence of epithelial and mesenchymal differentiation. In this series, we analyzed the clinicopathologic features of this rare variant of urothelial carcinoma.
A search was made through our surgical pathology files and consultation files of the senior author for cases of sarcomatoid urothelial carcinoma of the bladder from 2005-2014. All the slides were retrieved and re-reviewed, and clinical data was also obtained including follow up.
Thirty-seven cases of sarcomatoid urothelial carcinoma of the bladder were identified. Mean patient age was 71 years (range: 51 to 88 years). Twenty-six of 37 (70%) patients were male and 11/37 (30%) patients were female. Twenty-five cases were from cystectomy/cystoprostatectomy specimens, 8 cases from transurethral resection of bladder tumor specimens and 4 cases were from biopsy specimens. The mean tumor size was 5 cm (range: 1.4 cm to 13.0 cm). Four of 37 (10%) cases had focal heterologous components; 1 case with both chondroid and osteoid, 2 cases with chondroid and 1 case rhabdoid elements. Twenty-one of 37 (56%) patients died within a year of presentation.
Sarcomatoid urothelial carcinoma of the bladder is more prevalent in males, with the mean age of 71 years in our series. Smoking is an important risk factor. Sarcomatoid urothelial carcinoma is an aggressive variant of urothelial carcinoma which commonly presents at an advanced stage, and over 50% of patients in our series died of disease within 1 year of presentation.
Urothelial carcinoma has numerous histological variants, and these variants may coexist in a single case. Here, we present a case of a 70-year-old man with urothelial carcinoma of the bladder with a maximal diameter of 5 mm that involved micropapillary and plasmacytoid variants, with villoglandular differentiation. The presence of these variants was confirmed by pathological examination of a transurethral resection specimen, and high-grade urothelial carcinoma was found as a minor component. Although this bladder carcinoma was classified as pT1, cystoprostatectomy, urethrectomy, and lymphadenectomy were performed due to the presence of the micropapillary and plasmacytoid variants, which are known to be aggressive. Examination of a surgically resected specimen revealed no carcinoma. A transition between urothelial carcinoma in situ and non-invasive micropapillary carcinoma was found to be a pivot point connecting the diverse morphologies of this bladder carcinoma, from which there existed two pathways. One pathway was from urothelial carcinoma in situ to the plasmacytoid variant through invasive high-grade urothelial carcinoma, and the other was from non-invasive micropapillary carcinoma to urothelial carcinoma with villoglandular differentiation or to the micropapillary variant. This is the 16th reported case of urothelial carcinoma with villoglandular differentiation in the literature. As urothelial carcinoma with villoglandular differentiation is often associated with aggressive variants, as shown in our case, it should be reported whenever encountered in routine pathological practice.
We report two cases of urinary bladder urothelial carcinoma (UC). In both, histological examination of a transurethral resection specimen of the bladder tumor revealed UC with plasmacytoid and micropapillary differentiations. In Case 1, residual plasmacytoid UC deeply invaded the extravesical fat tissue of the radical cystectomy specimen, and metastatic carcinoma was found in almost all the dissected lymph nodes. Despite adjuvant chemotherapy and radiotherapy, the patient died 25 months postdiagnosis. Elevated serum carbohydrate antigen 19-9 (CA19-9) returned to near normal levels after radical cystectomy, but they increased shortly before death. In Case 2, no residual carcinoma was found in the radical cystectomy specimen or lymph nodes. Postoperative serum CA19-9 was maintained at normal levels, and the patient remains alive without recurrence or metastasis. Although plasmacytoid and micropapillary UC are known aggressive variants of UC, plasmacytoid UC may be more aggressive. Serum CA19-9 could serve as a useful biomarker to monitor progression of plasmacytoid UC.
© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
Micropapillary, sarcomatoid, and small cell carcinoma are uncommon, aggressive variants usually encountered in the evolution of high-grade nonpapillary transitional cell carcinoma. Of these, only small cell is effectively treated with currently available systemic therapy, with recent evidence suggesting a role for neoadjuvant chemotherapy. While adenocarcinoma and squamous cancers can also arise from the urothelium, neither is as sensitive to chemotherapy as conventional transitional cell carcinoma. Dominant lymphoepithelioma has a favorable prognosis. Urachal cancers require preoperative recognition for optimal surgical management, and are being shown to be somewhat responsive to regimens useful in colon cancer. Mesenchymal tumors are exceedingly rare and are treated like other pelvic sarcomas.
Invasive urothelial carcinoma with chordoid features has not been reported since being first documented in 2009. Here we report a further case of it, involving an 85-year-old man with a papillary tumor of the urinary bladder, measuring 3 cm in diameter. This case is unique in that an epithelial-mesenchymal transition was suspected to have occurred in the transformation of a conventional urothelial carcinoma to a sarcomatoid variant, with invasive urothelial carcinoma with chordoid features acting as an intermediate stage. Based on this finding, we recommend that the presence of invasive urothelial carcinoma with chordoid features should be reported as it may predict the coexistence or future development of an aggressive sarcomatoid variant.
Context:
Tumors of the genitourinary tract can be diagnostically challenging, particularly in core biopsies and cystoscopic biopsies with limited material. Immunohistochemistry is a valuable tool to use when morphology alone is insufficient for diagnosis.
Objectives:
To review tumors and benign lesions of the kidney, urinary bladder, prostate gland, testis, and paratesticular structures with an emphasis on difficult differential diagnoses, as well as staining patterns in normal tissue. Recommended immunohistochemical stain panels are discussed that can assist in the diagnostic workup.
Data sources:
Review of current literature.
Conclusions:
Immunohistochemistry is a valuable tool, assisting in the diagnosis of problematic tumors and benign lesions of the genitourinary tract.
Background:
CD138/Syndecan-1 (Sdc-1) is expressed on the tumor and stromal cells of invasive bladder carcinoma. CD138/Sdc-1 shedding from the cell surface is associated with the invasive phenotype in lung and breast cancers.
Patients and methods:
Soluble CD138/Sdc-1 was measured in the sera of 86 bladder cancer patients and 57 healthy individuals by a commercial ELISA assay.
Results:
Soluble Sdc-1 was increased in the sera of patients with bladder cancer (138.42 ± 81.85 vs. 86.48 ± 82.58 ng/ml, p = 0.0003). Patients aged over 70 years had higher levels of CD138/Sdc-1 in their sera (159.7 ± 15.77 vs. 124.5 ± 9.99 ng/ml, p = 0.025), and soluble Sdc-1 levels were higher in the sera of patients with moderately differentiated tumors compared to poorly differentiated ones (170.47 ± 85.06 vs. 101.79 ± 68.24 ng/ml, p = 0.01). The soluble Sdc-1 level was higher in muscle-invasive (154.45 ± 83.60 vs. 89.9 ± 55.02 ng/ml) but not lymphatic-invasive (106.25 ± 52.10 vs. 123.43 ± 63.76 ng/ml) tumors (p = 0.027 and 0.45, respectively). A non-significant trend of soluble Sdc-1 increase in the sera of male patients compared to female patients was observed (145.38 ± 85.47 vs. 110.20 ± 59.04 ng/ml, p = 0.054).
Conclusion:
The elevated levels of soluble CD138/Sdc-1 in older bladder cancer patients and those with muscular invasion sheds some light on the mechanisms of the disease invasion.
Primary signet-ring cell carcinoma is an uncommon malignancy arising in the urinary bladder. The authors report 12 cases collected at their institution. Median age for the ten men and two women was 58 years; the most frequent presentation was hematuria. In two of nine cases no mucosal lesion was cystoscopically visible. Eleven tumors were of nonurachal origin and one of urachal. At diagnosis, one tumor was stage B, two stage C, seven stage D, and two stages unknown. Nine of 12 patients were dead of disease (range, 1-16 months; median, 9 months), 1 alive with metastatic disease, 1 alive and well, and 1 dead of an unrelated cause. From a literature review, the authors accepted 35 cases that met their criteria and combined them with their 12 cases for statistical analysis. Prognosis was worse with a pure diffuse versus a mixed tumor (P = 0.004) and for nonurachal versus urachal origin (P = 0.005). The difference in five-year survival rates between stages B and D disease (P less than 0.05) was also statistically significant.
Most papillary transitional cell carcinomas (TCC) are characterized architecturally by an exophytic growth of fingerlike papillae, but some exhibit a prominent endophytic growth pattern resulting in considerable difficulty in assessing invasion. We report on 18 cases of TCC (17 urinary bladder, one pelvicalyceal system) in which endophytic growth was evident either as interanastomosing cords and columns of urothelium, often with a striking resemblance to inverted papilloma (inverted papilloma-like pattern), or as broad, pushing bulbous invaginations into the lamina propria (broad-front pattern). The mean age of the patients was 68 years (range, 32-94 years), with a male preponderance (3.5:1). In four cases, the endophytic pattern was exclusively inverted papilloma-like, 10 cases had only the broad-front pattern, and four cases showed both patterns. Exophytic papillary TCC of the usual type was present in all but two cases, varying from focal (five cases) to moderate (five cases) to extensive (six cases). In spite of the extensive incursion into the lamina propria resulting from the inverted growth, only nine cases (50%) had unequivocal destructive invasion (lamina propria invasion, eight cases; muscularis propria invasion, one case). Follow-up data, available in 14 cases (1-48 months; mean, 15.5 months), revealed one patient alive with disease, 11 patients with no evidence of disease, and two patients dead of other causes. The limited follow-up does not permit evaluation of the impact of the endophytic patterns on outcome. Because the phenomenon of endophytic growth in TCC has received little attention, we present detailed morphologic descriptions of our cases and review the problems associated with assessment of invasion and the different patterns of invasion by TCC.
Osteoclast-like giant-cell neoplasms of the urinary tract are rare. They are composed of ovoid or spindle-shaped mononuclear cells with evenly spaced osteoclast-like giant cells. Terminology, histogenesis, and biologic behavior of these tumors remain controversial. Six cases of osteoclast-like giant-cell neoplasms of the urinary tract were identified from the consultation files of two of the authors. Patients were all male and elderly (range 65-82), with the exception of one 39-year-old male. In all, 3/6 tumors developed in the bladder and 3/6 in the renal pelvis. Size ranged from 5 to 11 cm. One bladder and three renal pelvis tumors were high stage (pT3) at time of presentation. Adjacent to the osteoclast-like giant-cell neoplasm in the same specimen, all patients had urothelial carcinoma in situ and/or high-grade papillary urothelial carcinoma. Multinucleated cells had identical morphological and immunohistochemical properties of osteoclasts; positive for CD-68, LCA, CD51 and CD54, and negative for cytokeratins and EMA. Varying percentages of mononuclear cells expressed alpha-smooth muscle actin (4/6), desmin (1/6), S-100 (4/6), LCA (2/6) and CD68 (6/6). However, mononuclear cells were also positive for epithelial markers in 4/6 tumors (cytokeratins AE-1/AE-3, Cam 5.2, CK7 and/or EMA). p53 stained mononuclear tumor cells in three cases, paralleling the staining on the accompanying urothelial carcinoma. Ki-67 stained mononuclear tumor cells, but not osteoclast-like giant cells. Follow-up data were available in five cases. One patient developed recurrence of noninvasive urothelial carcinoma and is still alive. Four patients were dead due to disease within 15 months, three with distant metastases. The intimate association of these tumors with urothelial carcinoma along with their immunohistochemical profile supports an epithelial origin for the mononuclear cells and non-neoplastic reactive histiocytic lineage for the osteoclast-like giant cells.
We studied 28 cases of lymphoepithelioma-like carcinoma of the bladder, one case in the renal pelvis, and one in the urethra. The mean age of the patients was 67.6 years with 21 (70%) males. Seventeen cases (56.7%) were pure with the remaining mixed with other patterns of carcinoma, including invasive urothelial carcinoma (n=10), invasive adenocarcinoma (n=3), and squamous cell carcinoma (n=2). The surface demonstrated carcinoma in situ (CIS) in six cases, noninvasive high-grade papillary urothelial carcinoma in three cases, and in situ adenocarcinoma in one case. In 19/30 (66%) cases, there was a heavy lymphocytic infiltrate and in the remaining 11/30 (34%) cases a mixed inflammatory infiltrate. None of the 26 cases labeled for EBV-encoded RNA by in situ hybridization. Tumor stages at presentation were: seven cases T1 (23%); 14 cases T2 (47%); seven cases T3 (23%); and two cases T4 (7%). Treatment consisted of radical cystectomy in 13/30 cases (43%); partial cystectomy in 4/30 cases (13%); nephrectomy in one case (3%), and transurethral resection often followed by radiation or chemotherapy in 12/30 (40%) cases. The mean follow up for patients without progression was 31 months. Eight of 27 cases with follow-up (30%) cases had tumor recurrence, with seven patients having metastases. In cases treated with cystectomy, the 5-year actuarial recurrence-free risk was 59% (62 and 57%, for pure and mixed cases, respectively). Lymphoepithelioma-like carcinoma, whether in pure or mixed form, has a similar prognosis to ordinary urothelial carcinoma when treated by cystectomy. Of the three pure cases treated by chemotherapy, two were free of disease at 4 and 65 months and the third had recurrent disease at 17 months. Given the association of lymphoepithelioma-like carcinoma with urothelial carcinoma in 47% of our cases and its propensity for multifocality, partial cystectomy would typically be ill advised for lymphoepithelioma-like carcinoma.
Primary plasmacytoma of the bladder is extremely rare, with only 10 cases reported in the literature. We report on a patient who was treated unsuccessfully with radiation and subsequently underwent anterior exenteration with ileo-conduit construction.
Most papillary transitional cell carcinomas (TCC) are characterized architecturally by an exophytic growth of fingerlike papillae, but some exhibit a prominent endophytic growth pattern resulting in considerable difficulty in assessing invasion. We report on 18 cases of TCC (17 urinary bladder, one pelvicalyceal system) in which endophytic growth was evident either as interanastomosing cords and columns of urothelium, often with a striking resemblance to inverted papilloma (inverted papilloma-like pattern), or as broad, pushing bulbous invaginations into the lamina propria (broad-front pattern). The mean age of the patients was 68 years (range, 32-94 years), with a male preponderance (3.5:1). In four cases, the endophytic pattern was exclusively inverted papilloma-like, 10 cases had only the broad-front pattern, and four cases showed both patterns. Exophytic papillary TCC of the usual type was present in all but two cases, varying from focal (five cases) to moderate (five cases) to extensive (six cases). In spite of the extensive incursion into the lamina propria resulting from the inverted growth, only nine cases (50%) had unequivocal destructive invasion (lamina propria invasion, eight cases; muscularis propria invasion, one case). Follow-up data, available in 14 cases (1-48 months; mean, 15.5 months), revealed one patient alive with disease, 11 patients with no evidence of disease, and two patients dead of other causes. The limited follow-up does not permit evaluation of the impact of the endophytic patterns on outcome. Because the phenomenon of endophytic growth in TCC has received little attention, we present detailed morphologic descriptions of our cases and review the problems associated with assessment of invasion and the different patterns of invasion by TCC.
BACKGROUND: Plasmacytoid carcinomas are rare variants, and there are only a few reported examples of plasmacytoid carcinoma of the urinary bladder in the English-language literature. We now report another such case and the first in which there was examination of urinary cytology. CASE: A 79-year-old, Caucasian woman who presented with gross hematuria follow-ing a revascularization procedure on the right arm was found to have an extensive, diffuse carcinoma of the bladder. On biopsy, there were single, round and polygonal tumor cells with a striking plasmacytoid appearance infiltrating diffusely throughout the edematous lamina propria. Immunocytochemical stains confirmed an epithelial classification, and carcinoma in situ was demonstrated in the contiguous urothelium. Voided urine cytology before and after cystoscopy and biopsy demonstrated large, dyshesive tumor cells with plasmacytoid features. CONCLUSION: A case of plasmacytoid variant of urothelial carcinoma of the bladder is reported, with the first description of its urinary cytology.
Background Plasmacytoma of the bladder is an extremely rare tumor, with all information concerning this neoplasm derived from case reports. It can be a major diagnostic pitfall on both histology and urine cytology. Case A 95-year-old woman presented with gross hematuria and a large bladder mass detected by ultrasound. The case was initially misdiagnosed as a high grade urothelial carcinoma. Since the urine cytology did not show the classical cytologic features of urothelial carcinoma, the histologic sections were reviewed and immunohistochemical staining performed. The final diagnosis was plasmacytoma of the bladder. Subsequently the patient underwent a skeletal survey and bone scan, which did not reveal any lesion suspicious for multiple myeloma. The patient was scheduled for radiotherapy. Conclusion In this case of bladder plasmacytoma, urine cytology provided a clue to the diagnosis. Urine cytology can be a diagnostic tool to help make this diagnosis in the case of poorly differentiated bladder neoplasm, especially in a patient with a known history of multiple myeloma.
Adenocarcinomas represent approximately 2% of primary bladder epithelial malignancies. Of these, the signet ring-cell variant is the rarest form. We report such a case, with the unusual presentation of oliguria, including radiologic and histopathologic findings. The current literature is reviewed. J. Surg. Oncol. 1999:70:64–67. © 1999 Wiley-Liss, Inc.
The case of a 63-year-old man with a previously undescribed morphologic variant of transitional cell carcinoma of the urinary bladder is reported. The patient initially presented with multiple lytic bony metastases of the ribs and skull. Aspiration biopsy of one of the lytic lesions of the skull showed tumor cells with a striking plasmacytoid appearance, similar to the plasma cells seen in myeloma, leading to an initial observer's diagnosis of multiple myeloma. Subsequently, a bladder tumor with the same cytomorphology was found; immunohistochemical and ultra structural studies performed on the aspirated material and on the bladder biopsy specimen clearly established the epithelial nature of this neoplasm.
We report five carcinomas of the urinary bladder, four of them transitional cell carcinomas and one undifferentiated carcinoma, with unusual features that have received little or no comment in the literature and may be the cause of diagnostic difficulty because of their possible confusion with malignant lymphoma. Four patients were male and one female. They ranged from 61 to 76 years of age. Three tumors from these patients had a prominent (2 cases) or massive (1 case) lymphoid infiltrate that partially obscured the invasive carcinoma in two cases and largely obscured it in the third case, which closely resembled a lymphoepithelioma. The diagnosis of malignant lymphoma was only excluded with confidence in the last case after thorough immunohistochemical study. The lymphoid infiltrate was composed of numerous T-cells (UCHL-1 and Leu 22 positive) and polytypic plasma cells with admixed eosinophils; occasional germinal centers were present in one case. The tumors were deeply invasive in two patients, one of whom is alive with no evidence of disease 4 years after treatment with chemotherapy and radiation therapy; the other two cases are too recent for meaningful follow-up. Two other transitional cell carcinomas had diffuse patterns that simulated lymphoma or plasmacytoma. Recognition of these patterns of vesical carcinoma is important in order to avoid the misdiagnosis of the very rare malignant lymphoma of the urinary bladder.
Breast carcinoma metastatic to the bladder and presenting initially with urinary tract symptoms has been reported only sporadically. Two cases, one unique in that the bladder was the sole site of metastasis, are reported herein, along with a review of the literature.
Eighteen cases of transitional cell carcinoma (TCC) of the urinary bladder containing a micropapillary component (MPC) (> 90%, three cases; 50-90%, nine cases; < 50%, six cases) are presented. The patients' mean age was 66.6 years (range, 47-81 years) with a male predominance (male-to-female ratio of 5:1). The MPC was part of the surface noninvasive TCC in 16 cases and part of the invasive portion of the TCC in all 18 cases. Eight patients had metastases, each with a predominant (> or = 50%) MPC in the metastases; local recurrence was documented in one case, and the tumor was locally invasive into pelvic structures in three cases. Histologically, the surface MPC comprised slender, delicate filiform processes or small papillary clusters of tumor cells, whereas the deep MPC was composed of infiltrating tight clusters of micropapillary aggregates that were often present within lacunae. Vascular-lymphatic invasion was consistently present in the micropapillary areas. The cytologic features of the MPC were those of grade 3 TCC. A concurrent TCC in situ was identified in 10 cases, noninvasive papillary TCC component in all cases, and glandular differentiation of the invasive TCC in five cases. The initial stage at presentation was usually high stage: one patient with stage A, nine with stage B, six with stage C, and two with stage D. Follow-up data (mean, 44.8 months; range, 6-96 months) indicated that four patients were alive with disease, seven patients were dead of disease, and there was no evidence of disease in seven patients. In five cases, DNA ploidy analyzed by static image analysis showed nondiploid indices within the micropapillary TCC component, and in three cases the DNA index of the MPC (noninvasive, invasive, or at metastatic site) exceeded the DNA index of the noninvasive papillary TCC. In conclusion, the presence of a MPC in TCC is associated with high-grade and high-stage TCC with a tendency to vascular invasion. Our data suggest that a surface MPC in bladder biopsy specimens is a poor prognostic histologic feature and, if the biopsy does not contain muscularis propria, deeper biopsies should be recommended to determine the presence of muscle invasion.
We report the cases of 11 patients who were treated for undifferentiated carcinoma of the urinary bladder with a prominent lymphoid stroma (lymphoepithelioma-like carcinoma [LELC]). The chief complaint of all 11 patients was hematuria. Their ages ranged from 52 to 79 years (mean of 67). All tumors except one invaded the muscle wall and showed the typical syncytial growth pattern of undifferentiated cells with ill-defined cytoplasmic borders, prominent nucleoli, and numerous mitoses. A significant lymphocytic reaction was an essential component of all these tumors. There were three pure LELC tumors without concurrent invasive transitional-cell carcinoma (TCC) or TCC in situ; these cases morphologically simulated large-cell lymphoma. The remainder were mixed TCC and LELC (five predominant and three focal LELC). The tumor cells were immunoreactive for keratin and showed negative results for leukocyte common antigen. The lymphoid population was an admixture of T cells and B cells with a predominance of T cells. Seven patients (four with predominant and three with focal LELC) were treated with various therapeutic methods. Four patients (three with pure and one with predominantly LELC) received only chemotherapy after transurethral resection of the tumor, and follow-up found no evidence of disease for 9-72 months (mean of 38 months). Awareness of an LELC component in a urinary bladder tumor is also important in order to avoid misinterpreting these tumors as malignant lymphoma or severe chronic cystitis. Our data suggest that the pure LELC tumor appears to be morphologically and clinically different from TCC and that it merits recognition as a separate clinicopathologic entity. In addition, there is strong suggestive evidence that it responds to chemotherapy and therefore there is the potential of salvaging bladder function.
Primary plasmacytoma of the bladder is extremely rare, with only 10 cases reported in the literature. We report on a patient who was treated unsuccessfully with radiation and subsequently underwent anterior exenteration with ileo-conduit construction.
The nested variant of transitional cell carcinoma (TCC-NV) is a rare neoplasm; only eight cases have been described. This report reviews the clinicopathologic features of 16 additional examples. The cases were collected from consultations received during a 13-year period. In most instances, a consultation was sought because the histologic features suggested an atypical proliferation of Brunn's nests or a lesion similar to the previously published examples of TCC-NV. Clinical data were gathered and tissues were studied to exclude prostatic cancer and adenocarcinoma. TCC-NV is characterized by the presence of irregular nests and/or tubules of transitional cells infiltrating the lamina propria without surface involvement. Neoplastic cells tend to have innocuous features but at least a few cells in every case are cytologically anaplastic. There is a marked male predominance. Synchronous or metachronous TCCs of more usual histologic make-up may occur. After a follow-up averaging 16.6 months, only three patients are known to be alive with no evidence of disease. Clinicopathologic information from our 16 cases combined with the 8 previously reported examples confirms that TCC-NV is a persistent and aggressive neoplasm notable for its innocuous appearance in histologic preparations.
The microscopic appearances of carcinomas of the urinary bladder are reviewed, with emphasis on patterns that have been highlighted only recently or account for major problems in differential diagnosis. Approximately 80% of bladder cancers are of urothelial (transitional cell) type. The major new information pertaining to that category is the appreciation of the extent to which they may have unusual patterns that, on occasion, lead to their misinterpretation as benign. The homology between some of these variants and benign epithelial abnormalities is emphasized and helps in understanding them: nested carcinomas and von Brunn's nests, small tubules and nephrogenic adenoma, carcinomatous glands and cystitis glandularis, cystic carcinomas and cystitis cystica. Other peculiar patterns seen in urothelial carcinoma include silt-like spaces, clefts, and angulated nests with spikes. Differences in opinion have been apparent in recent contributions concerning carcinomas of the bladder with a prominent component of spindle cells (sarcomatoid carcinomas) and whether they represent a category distinct from carcinosarcoma. Irrespective of this academic distinction, the potential for some epithelial-derived tumors of the bladder to be dominated by or even have an exclusive component of spindle cells is important. Three other major categories of primary bladder cancer are squamous cell carcinoma, adenocarcinoma, and undifferentiated carcinoma. The differences in the frequency of subtypes of adenocarcinoma originating in the bladder mucosa and urachus has recently been emphasized, as has the spectrum of undifferentiated carcinomas. In some bladder cancers, the stroma has unusual features. These are carcinomas with pseudosarcomatous stroma, osseous or cartilaginous metaplasia, or osteoclast-type giant cells. The diversity of appearances of bladder cancer has important implications in differential diagnosis.
We performed a critical analysis of the different prognostic factors affecting survival among patients with carcinoma of the bladder for whom cystectomy was indicated. The different patient and tumor characteristics were correlated to survival data by a univariate as well as multivariate analysis.
Between 1969 and 1990, 764 men and 262 women, average age plus or minus standard deviation 43 +/- 8 years, with invasive carcinoma of the bladder were eligible for 1-stage radical cystectomy and urinary diversion. Patients were followed regularly and examined signs for and location of treatment failure. Followup ranged from 0 to 24.2 years, with a median plus or minus standard deviation of 4.05 +/- 4.16 years.
Postoperative mortality was 4%. Most of the patients presented with advanced stage (greater than P3) disease. Squamous tumors accounted for 59% of cases, transitional carcinoma 22% and adenocarcinoma 11%. Bilharzial eggs were seen in 85% of the specimens. Regional lymph nodes were involved in 18.3% of the cases. The 5-year survival rate was 48%. The survival estimate was correlated to patient and tumor characteristics by univariate and multivariate analyses. Only tumor stage and grade, and lymph node status had a significant impact on survival.
Contemporary cystectomy with continent diversion for muscle invasive disease provides minimal morbidity, offers good locoregional disease control and results in acceptable quality of life. The presence of positive regional lymph nodes is not a contraindication to this therapy.
Plasmacytoid carcinomas are rare variants, and there are only a few reported examples of plasmacytoid carcinoma of the urinary bladder in the English-language literature. We now report another such case and the first in which there was examination of urinary cytology.
A 79-year-old, Caucasian woman who presented with gross hematuria following a revascularization procedure on the right arm was found to have an extensive, diffuse carcinoma of the bladder. On biopsy, there were single, round and polygonal tumor cells with a striking plasmacytoid appearance infiltrating diffusely throughout the edematous lamina propria. Immunocytochemical stains confirmed an epithelial classification, and carcinoma in situ was demonstrated in the contiguous urothelium. Voided urine cytology before and after cystoscopy and biopsy demonstrated large, dyshesive tumor cells with plasmacytoid features.
A case of plasmacytoid variant of urothelial carcinoma of the bladder is reported, with the first description of its urinary cytology.
The morphology of urothelial carcinomas, particularly when poorly differentiated or in metastatic sites, is not distinctive and overlaps significantly with other poorly differentiated nonurothelial carcinomas. Currently, there is no widely used single marker or panel of markers to confirm urothelial origin. We evaluated a panel consisting of antibodies to uroplakin III (UROIII), thrombomodulin (THR), high molecular weight cytokeratin (HMWCK), and cytokeratin 20 (CK20) in a wide range of urothelial tumors. Immunohistochemistry was performed on 112 paraffin-embedded urothelial neoplasms: 14 low malignant potential, 16 low-grade noninvasive, 16 high-grade noninvasive, 36 invasive, and 25 metastatic and 5 small cell carcinomas of the urinary bladder. Tissue microarray analysis was used to examine 498 tissue cores of nonurothelial tumors and normal tissue using antibodies to UROIII, THR, and HMWCK. Overall positive staining results in all urothelial tumors are as follows: UROIII, 64 of 112 (57.1%); THR, 77 of 112 (68.8%); HMWCK, 88 of 110 (80%); and CK20, 53 of 110 (48.2%). The expression of the four markers varied with tumor grade and stage. All small cell carcinomas were negative for all markers. Variant morphologic subtypes showed similar staining as conventional urothelial carcinomas. Tissue microarray analysis showed no UROIII immunoreactivity in tissue cores of nonurothelial tumors. THR was expressed by a limited number of nonurothelial cores (10 of 37 [27%] non-small cell lung carcinomas, 2 of 36 [5.6%] lymphomas). HMWCK was expressed by 43.8% of non-small cell lung carcinomas and essentially absent in other nonurothelial tumor cores. Based on the results of the study, the expression of UROIII in a tumor is essentially diagnostic of urothelial origin; however, it is expressed in only slightly more than half of urothelial tumors. The coexpression of THR, HMWCK, and CK20 strongly suggests urothelial origin. The coexpression of two of three non-UROIII markers (THR, HMWCK, CK20) suggests urothelial origin but requires clinicopathologic correlation. The results of the study indicate a role for an antibody panel that includes UROIII, THR, HMWCK, and CK20 in the diagnosis of urothelial tumors.
Multiple myeloma is characterized by neoplastic proliferation of a single clone of plasma cells engaged in the production of a monoclonal protein. This condition affects mainly the bone marrow, but extramedullary manifestations can be seen in any organ. Urinary bladder involvement is extremely rare, with only 14 cases reported in the literature to our knowledge. Herein, we report a large extramedullary bladder plasmacytoma arising in a patient with history of multiple myeloma. A 78-year-old woman with history of multiple myeloma, currently in remission, presented with a large intravesical tumor. Because the tumor was considered to have characteristics of anaplastic neoplasm from transitional cell origin with evidence of deep muscular invasion, a radical cystectomy was performed. A subsequent microscopic evaluation of the cystectomy specimen revealed round cells with an eccentric cartwheel-like nucleus suggestive of plasmacytoma. The diagnosis was further confirmed with immunohistochemical studies. It is difficult, according to the literature, to distinguish bladder plasmacytoma from anaplastic transitional cell tumors. It is important to provide the pathologist with an appropriate history and to have a high index of suspicion for bladder plasmacytoma in patients with previous diagnosis of multiple myeloma and bladder mass.
We report a case of an 83-year-old man with a high-grade carcinoma of the urinary bladder who underwent cystoprostatectomy. The invasive carcinoma showed mixed, morphologically distinct patterns consisting of conventional high-grade urothelial carcinoma, glandular differentiation resembling enteric type adenocarcinoma, and acinar/tubular type differentiation, morphologically similar to Gleason grade 3 prostatic adenocarcinoma. Immunohistochemical studies revealed the acinar/tubular component of the tumor to be negative for prostate-specific antigen and prostatic acid phosphatase, but positive for cytokeratin 7, cytokeratin 20, high molecular weight cytokeratin (34 beta E12), and thrombomodulin, consistent with origin from the bladder rather than the prostate. Although bladder carcinomas composed of mixed morphologic patterns are not uncommon, to our knowledge, the presence of acinar/tubular type features simulating prostatic adenocarcinoma in such tumors has not been described elsewhere.
To describe a series of 10 cases of transitional cell carcinoma which show morphological features which mimic lobular carcinoma of the breast and diffuse carcinoma of the stomach.
Ten cases were identified from the files at Southampton University Hospitals NHS Trust and from the authors' consultation files. Immunostains were performed and clinical information was obtained. Eight of the patients were male and two female. Ages ranged from 52 to 77 years at presentation. All of the tumours showed areas where the tumour was composed of uniform cells with a discohesive single-cell, diffusely invasive growth pattern. In areas the tumour cells were arranged in linear single-cell files and in separate areas solid sheets of discohesive cells. In all of the cases some tumour cells showed prominent intracytoplasmic vacuoles. In addition to this pattern, four cases showed typical transitional cell carcinoma or carcinoma in situ. The majority of the tumours expressed cytokeratin 20 but not oestrogen receptors.
This study highlights a pattern of diffusely invasive transitional cell carcinoma not previously described and one which is important to recognize in order to avoid misdiagnosis of metastatic lobular carcinoma of the breast, especially in small biopsies.
A 28-year-old woman underwent renal transplantation in 1993. Eight years later, she experienced macroscopic hematuria, and Epstein-Barr virus-negative solitary extramedullary plasmacytoma (EMP) of the urinary bladder was diagnosed. After the reduction of immunosuppressive therapy, she received combined chemotherapy, resulting in complete tumor disappearance. However, 10 months later, she relapsed with aggressive multiple EMP and died of disease progression in 2003. This report is the first of a case of solitary EMP of the urinary bladder appearing as posttransplantation plasma cell dyscrasias after renal transplantation.
An aggressive urothelial carcinoma classified as lipid cell variant with plasmacytoid features was diagnosed in a 67-year-old man. His overall survival was 18 months after limited surgery followed by chemotherapy. The histopathologic features were the same in the recurrences.
A case of rare plasmacytoid transitional cell carcinoma of the urinary bladder in a 60-year old man is described. The presence of end-stage disease did not allow for any efficacious therapy. Immunohistochemistry showed the tumor cells to be reactive for epithelial markers and syndecan-1 (CD138).
Syndecan-1, a heparan sulfate-rich membrane glycoprotein, is expressed in plasma cells and is considered a reliable marker of plasmacytic differentiation. However, it has not been widely tested in non-hematolymphoid tissues, and thus its utility in the setting of an undifferentiated malignant neoplasm has not been evaluated. The authors conducted an extensive study of CD138 staining in over 1,700 normal, benign, and malignant non-hematolymphoid tissues, using five tissue microarrays. Immunohistochemical staining was performed with two commercially available CD138 monoclonal antibodies directed against syndecan-1 (Serotec, Oxford, UK, and DAKO, Carpenteria, CA). In addition to the specific membrane staining, many normal tissues and epithelial tumors showed strong cytoplasmic immunoreactivity. A small subset of mesenchymal neoplasms also showed membrane and cytoplasmic immunoreactivity. In squamous cell carcinoma of the head and neck, renal cell carcinoma, and prostate adenocarcinoma, the intensity of CD138 staining inversely correlated with the histologic grade of the carcinoma. However, statistically significant staining differences and their correlation with histologic grades differed depending on whether the Serotec or the DAKO antibody was used. These results indicate that CD138 immunoreactivity is widespread in normal and neoplastic epithelial tissues, as well as a variety of undifferentiated epithelial and mesenchymal processes. The authors conclude that the expression of syndecan-1, although relatively specific to plasma cells within the hematolymphoid system, should be interpreted with extreme caution in the setting of an undifferentiated neoplasm. Furthermore, the two commercially available monoclonal CD138 antibodies tested in this study showed significant differences in their immunoreactivity in different tumor types.
Extrarenal rhabdoid tumors have been described in a variety of primary sites with only rare case reports of urothelial carcinomas with rhabdoid features in the literature. In this report, we describe the clinicopathologic characteristics, including clinical follow-up on 6 cases of urothelial carcinoma with prominent rhabdoid features. Four cases were retrieved from the consultation files of one of the authors and 2 were retrieved from the surgical pathology files at our institution. The patients were all men, with ages ranging from 53 to 86 years (mean, 66.5 years). Patients initially presented with hematuria or obstructive symptoms. The sites included bladder (n = 4) and renal pelvis (n = 2). All cases had a prominent rhabdoid component (mean, 60%), ranging from 40% to 80%. In addition to the rhabdoid component, multiple coexistent histological components were seen, including in situ urothelial carcinoma (carcinoma in situ) and high-grade papillary urothelial carcinoma (n = 2), poorly differentiated carcinoma with small-cell features (n = 1), sarcomatoid (n = 2), and a myxoid component (n = 2). All cases in this series had focal or diffuse positive staining with one or more cytokeratin markers (epithelial membrane antigen, CAM 5.2, AE1/AE3). Of the 6 patients, 4 were treated initially with surgery (radical cystoprostatectomy, n = 2; radical nephrectomy, n = 2). Of 6 patients, 2 died within 1 month, whereas a third patient died within 4 months. The remaining 3 patients were alive at 3, 3, and 9 months after diagnosis. The histological and immunohistochemical findings in this study serve to broaden the morphological spectrum of urothelial carcinomas with prominent rhabdoid features and add further evidence as to their poor prognosis.
Plasmacytoid urothelial carcinoma (PUC) is a rare tumor of the urinary bladder. Its clinical and histopathological features have not been well characterized. In this study we report seven cases of PUC from our institution.
A pilot case of PUC was recently diagnosed at our institution. Cases of urothelial carcinoma (UC) were reviewed for a period of seven years to identify PUC. Representative sections from each case of PUC were submitted for immunohistochemical studies. Clinical charts were reviewed.
There were a total of seven cases of PUC out of 260 cases of invasive urothelial carcinoma. The common type of urothelial carcinoma (CUC) was present in focal areas in five cases. Cases with extensive PUC showed coarse and indurated mucosal folds and thickened bladder walls, with no grossly identifiable tumor. Urine cytology showed a scant number of atypical single cells, frequently without tumor diathesis, leading to a shortfall in the positive cytological diagnosis. Histologically, PUC appeared as dyscohesive, plasmacytoid cells with eccentric nuclei, extending widely into the bladder walls and extensively into adjacent pelvic organs.
PUC is a distinct clinical and pathological subtype of urothelial carcinoma. The clinical presentation is frequently late due to the frequent absence of hematuria and indurated mucosal surface at cystoscopy. The disease followed an ominous course with recurrence in all the patients, and with patient death.
We report the first case of a pathological complete response for plasmacytoid urothelial carcinoma of the bladder. A 76-year-old man was diagnosed with plasmacytoid urothelial carcinoma (T4, N0, M0) by the microscopically plasmacytoid appearance of the specimen from the transurethral resection. Immunohistochemical studies were positive for epithelial markers and negative for lymphoid markers. Two cycles of systemic chemotherapy were performed with methotrexate, etoposide, vinblastine, and cisplatin, followed by radical cystectomy. The pathological examination revealed no residual cancer cells in the resected specimen.
Plasmacytoma of the bladder is an extremely rare tumor, with all information concerning this neoplasm derived from case reports. It can be a major diagnostic pitfall on both histology and urine cytology.
A 95-year-old woman presented with gross hematuria and a large bladder mass detected by ultrasound. The case was initially misdiagnosed as a high grade urothelial carcinoma. Since the urine cytology did not show the classical cytologic features of urothelial carcinoma, the histologic sections were reviewed and immunohistochemical staining performed. The final diagnosis was plasmacytoma of the bladder. Subsequently the patient underwent a skeletal survey and bone scan, which did not reveal any lesion suspicious for multiple myeloma. The patient was scheduled for radiotherapy.
In this case of bladder plasmacytoma, urine cytology provided a clue to the diagnosis. Urine cytology can be a diagnostic tool to help make this diagnosis in the case of poorly differentiated bladder neoplasm, especially in a patient with a known history of multiple myeloma.
Plasmacytoid urothelial carcinoma is a rare malignant neoplasm in the urinary bladder. A 46-year-old man presented with gross hematuria and increased serum concentrations of both carbohydrate antigen (CA) 19-9 and beta-human chorionic gonadotropin (beta-hCG). The tumor was composed of conventional urothelial carcinoma and plasmacytoid variant, both positive for epithelial markers. In addition, plasmacytoid tumor cells were positive for an accepted marker of plasma cell origin, CD138. CA19-9 was mainly expressed in conventional urothelial carcinoma cells, and beta-hCG was mainly produced by plasmacytoid tumor cells. This is the first report, to our knowledge, indicating beta-hCG can be produced by plasmacytoid bladder cancer cells lacking trophoblastic features.
We present the characteristics and outcomes of a large, contemporary, consecutive series of patients treated with radical cystectomy and pelvic lymphadenectomy for transitional cell carcinoma of the bladder.
We developed a multi-institutional database and collected retrospective and prospective data on 888 consecutive patients with bladder transitional cell carcinoma who were treated with radical cystectomy and pelvic lymphadenectomy at 3 academic centers in the United States between 1984 and 2003.
Of the patients 25% had extravesical tumor extension with negative lymph nodes and 23% had lymph node metastasis. The rate of lymph node involvement increased with advancing pathological stage. Mean recurrence-free and bladder cancer specific survival +/- SE was 58% +/- 2% and 66% +/- 2% at 5 years, respectively. On preoperative multivariate analysis clinical tumor stage and neoadjuvant systemic chemotherapy were associated with cancer recurrence, while more advanced age, clinical tumor stage and preoperative carcinoma in situ were associated with bladder cancer specific mortality. On postoperative multivariate analysis pathological tumor stage, lymph node metastasis, lymphovascular invasion, adjuvant radiotherapy and adjuvant chemotherapy were associated with cancer recurrence, while higher pathological tumor stage, more advanced age, lymph node metastasis, lymphovascular invasion and adjuvant radiotherapy were associated with disease specific survival. Patients with metastasis to regional lymph nodes (pT any N1-3) were at significantly higher risk for bladder cancer recurrence and death than patients with extravesical tumor extension (pT3N0), who in turn were at significantly higher risk than patients with organ confined disease (pT2 N0 or less).
The results of this large, contemporary, multi-institutional series show that radical cystectomy and pelvic lymphadenectomy provide durable local control and disease specific survival in patients with localized invasive transitional cell carcinoma.
Invasive urothelial carcinoma may present with many deceptive morphologic variants. We report the clinicopathologic and immunohistochemical features of 5 cases of the so-called lipid-cell variant of urothelial carcinoma. The tumors occurred in 4 men and 1 women aged from 56 to 80 years. Four cases were developed in the bladder and 1 case in the renal pelvis. All cases were revealed by a macroscopic hematuria. The tumors were composed of sheets and nests of large epithelial cells with an abundant clear multivacuolated cytoplasm mimicking lipoblasts. Nuclei were irregular, hyperchromatic, eccentric, and frequently indented by cytoplasmic vacuoles. Mucin stains (PAS, Alcian Blue) were negative. Tumor cells were strongly stained with cytokeratin 7, cytokeratin 20, and EMA but were negative with S-100 protein. In all cases, a usual high-grade urothelial carcinoma component was admixed with lipoid tumor cells. Two tumors infiltrated the bladder muscle, 2 cases invaded the bladder submucosa, and 1 case invaded the renal parenchyma. In the follow-up, despite appropriate surgical treatment, 4 patients died of the disease and 1 patient is alive without recurrence. Because of its rarity and the tumor cells' appearance, the lipoid-cell variant may be misdiagnosed and must be distinguished from liposarcoma or signet-ring cell carcinoma. In the present series, the lipoid-cell variant of urothelial carcinoma was associated with an aggressive behavior and a poor prognosis.
Tissue-specific expression is of key importance in gene therapy and can be achieved by using tissue-specific promoters to drive therapeutic gene expression. The uroplakin (UP) promoter is a powerful tool for bladder cancer gene therapy, but the role of UP protein in the bladder remains unknown. This study aimed to detect UP III expression in transitional cell carcinoma (TCC) of the bladder and to determine whether the role of UP III heterogeneity is associated with predicting disease recurrence and patient survival.
Immunohistochemical staining for UP III was carried out in 92 archival radical cystectomy and 38 normal specimens and correlated with pathologic features and clinical outcomes.
UP III expression was significantly decreased in bladder cancer tissues compared with normal controls (P <0.0001). Loss of UP III expression was associated with high-grade, muscle-invasive cancer, lymphovascular invasion (P <0.01), and decreased cancer-specific survival at a median follow-up of 25.3 months (P = 0.04). When adjusted for the effects of standard pathologic features, only lymph node metastases were associated with bladder cancer progression (P = 0.01) and mortality (P = 0.04).
Loss of UP III expression is associated with established markers of biologically aggressive bladder cancer such as lymphovascular invasion, pathologic stage, and grade. UP III expression has limited prognostic value in patients with bladder TCC, but gene therapy viral vectors driven by the UP promoter would drive therapeutic gene expression in high-UP-expressing TCC cells, but not in aggressive low-UP-expressing TCC cells.
In this report, we summarized the clinicopathologic features of 9 cases of plasmacytoid transitional cell carcinoma (TCC) of the urinary bladder, a rare variant of TCC. All 9 patients were men with a mean of age 64.3 years (range, 46 to 81 y). All but 1 patient presented with gross hematuria; the remaining patient had urgency and microscopic hematuria. Cystoscopic findings revealed a dominant solid mass with surrounding multiple papillary lesions in 6 cases and multiple masslike lesions in 3 other cases. The initial diagnosis of plasmacytoid TCC was made on transurethral resection in 8 cases and cystoscopic biopsy in 1. One patient had TNM stage I disease, 2 had stage II disease, 3 had stage III disease, and 3 had stage IV disease. Four patients were treated by radical cystectomy with chemotherapy, 2 by radical cystectomy alone, 1 each by chemotherapy or intravesical bacillus Calmette-Guerin infusion alone, and 1 did not receive any further therapy. Microscopically, all tumors contained plasmacytoid cells, which composed 30% to 100% of the entire tumor. Eight of 9 cases were associated with high-grade TCC, and transitional cell carcinoma in situ was present in 4 cases. The plasmacytoid tumor cells were characterized by eccentrically located nuclei and abundant eosinophilic cytoplasm. Interestingly, plasmacytoid transitional cell carcinoma in situ was noted in 1 case. Immunohistochemical staining demonstrated that both plasmacytoid and conventional TCC components were positive for cytokeratins 7 and 20. The mean Ki-67 labeling index was 30% (range, 10% to 50%), and p53 expression in the majority of cases was low (5% to 10%), except for in 2 cases (70% and 80%). The mean follow-up in 8 patients was 24.5 months (range, 5 to 47 mo); the other patient was lost to follow-up. Five patients died of disease from 5 to 36 months, 2 patients were alive with disease at 30 and 47 months, and 1 patient was alive and well at 36 months with no evidence of disease. In summary, plasmacytoid TCC tends to present at an advanced stage and to have a poor prognosis. Morphologic recognition and distinction from other plasmacytoid malignant neoplasms is critical for its clinical management and immunohistochemical studies may be required for differential diagnosis.
We performed a critical analysis of the results of radical cystectomy for invasive bladder carcinoma treated at 1 center.
Between 1970 and 2000, 2,090 men and 630 women with invasive bladder cancer were treated with 1-stage radical cystectomy and urinary diversion. Followup ranged from 0 to 34.2 years with a mean of 5.5 +/- 5.7. Survival data were correlated to patient and tumor characteristics using univariate and multivariate analysis.
Postoperative mortality was 2.6%. Squamous tumors accounted for 49.4% of cases, transitional cell carcinoma for 36.4% and adenocarcinoma for 9.6%. Regional lymph nodes were involved in 20.4% of cases. The 5 and 10-year disease-free survival rates were 55.5% and 50.03%, respectively. Evidence was provided that tumor stage, histological grade and lymph node status are the only independent variables which affect survival probability.
Contemporary cystectomy can be performed with minimal mortality. Radical cystectomy for organ confined disease is followed by good therapeutic results and enhances the possibilities for functional restoration. With stage progression there is a stepwise reduction in survival probability. The radical operation can provide disease-free survival for an important subgroup of node positive cases (27.3%). Additional therapy is needed to improve the oncological outcome for advanced locoregional disease.
Urothelial carcinoma is well known for its divergent differentiation. Several "variant" morphologies have been described in the literature in recent years and have additionally been recognized in the recent World Health Organization classification of urothelial neoplasms. The importance of recognizing these variant histologies lies in the potential diagnostic, prognostic, or therapeutic implications that accompany these diagnoses. The range of variant morphology seen in the urinary bladder may also be seen in urothelial tumors of the renal pelvis. Herein we review select variants of urothelial carcinoma focusing on the relatively recently recognized variants, outlining the diagnostic features, common differential diagnostic dilemmas, and clinical relevance. This review also includes a discussion on variants on which there is recent information available.
The many faces of urothelial carcinoma—an update with an emphasis on recently described variants
- Nigwekar