Pitfalls in the Use of Smoothelin to Identify Muscularis Propria Invasion by Urothelial Carcinoma

Introduction: Non-muscle-invasive bladder cancer is the most expensive malignancy to treat. Current Canadian guidelines recommend repeat transurethral resection of bladder tumour (TURBT) within six weeks after initial resection of T1 high-grade (T1HG) urothelial carcinoma, prior to initiation of intravesical bacillus Calmette- Guerin treatment. This is a burden on operating room usage and adds further cost and risk of complications. Internationally, major cancer centres report significant rates of recurrence and upstaging on repeat resection, however, minimal Canadian data is available. We aimed to determine the rate of recurrence and upstaging in a resource-limited, Canadian healthcare system.Methods: A retrospective review of patients receiving TURBT between November 2009 and November 2014 was performed. Patients were included if they had all three of the following: a pathological diagnosis of T1HG, adequate muscularis propria present in the specimen, and a repeat resection.Results: We reviewed 3166 patients who underwent TURBT and found 173 to meet our inclusion criteria. The overall recurrence and upstaging rates were 57.2% and 9.2%, respectively. Tumour recurrence and upstaging occurred more often in patients who had repeat resection after 12‒24 weeks compared to those patients whose repeat resection occurred within 12 weeks.Conclusions: Although recurrence rates are similar, we have found upstaging rates to be three- to four-fold lower than those previously reported. Despite this, one in 10 patients will be upstaged, justifying use of this resource within our healthcare system. Finally, timely repeat resection, within 12 weeks appears to be associated with preventing disease progression.

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Primary clear-cell urothelial carcinoma of urinary bladder: a not-so-clear entity with review of literature

BMJ Case Reports ◽

10.1136/bcr-2019-231192 ◽

2019 ◽

Vol 12 (10) ◽

pp. e231192 ◽

Cited By ~ 1

Author(s):

Lalit Kumar ◽

Anubhav Narwal ◽

Manoj Kumar ◽

Seema Kaushal

Keyword(s):

Urinary Bladder ◽

Urothelial Carcinoma ◽

Urothelial Cancer ◽

Clear Cell ◽

Muscularis Propria ◽

Urinary Bladder Cancer ◽

Review Of Literature ◽

Unusual Variant ◽

Urothelial Tumours

Primary clear-cell urothelial carcinoma (CCUC) is an uncommon type of urothelial cancer with only 16 cases reported in published literature. Due to the rarity of the tumour, its clinical and prognostic values have not been clearly understood. We present one such rare clinical diagnosis in a 60-year- old man who underwent radical cystectomy (RC) with ileal conduit for urinary bladder cancer. Histopathology showed features of high-grade CCUC infiltrating the muscularis propria. Immunohistochemistry revealed diffuse immunopositivity of pan cytokeratin (CK), GATA3, P40, CK7 but was immunonegative for CD10 and vimentin. Our patient expired 4 months after diagnosis. CCUC has recently been included in the WHO 2016 classification of urothelial tumours. Most of the patients present with poor prognosis. Accurate diagnosis and recognition of this unusual variant are essential for better patient management and prognosis. Early RC seems to be the preferred way of management.

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Diagnostic Utility of Antibody to Smoothelin in the Distinction of Muscularis Propria From Muscularis Mucosae of the Urinary Bladder: A Potential Ancillary Tool in the Pathologic Staging of Invasive Urothelial Carcinoma

Yearbook of Pathology and Laboratory Medicine ◽

10.1016/s1077-9108(09)79332-6 ◽

2010 ◽

Vol 2010 ◽

pp. 126-128

Author(s):

R. Dhir

Keyword(s):

Urinary Bladder ◽

Urothelial Carcinoma ◽

Muscularis Propria ◽

Diagnostic Utility ◽

Muscularis Mucosae ◽

Pathologic Staging

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Clinicopathologic analysis of patients undergoing repeat transurethral resection of bladder tumour following an initial diagnosis of urothelial carcinoma with lamina propria invasion and variant/divergent histology

Journal of Clinical Pathology ◽

10.1136/jclinpath-2021-207756 ◽

2021 ◽

pp. jclinpath-2021-207756

Author(s):

Patrick Mullane ◽

Shreyas Joshi ◽

Mehmet Bilen ◽

Adeboye O Osunkoya

Keyword(s):

Urothelial Carcinoma ◽

Lamina Propria ◽

Critical Role ◽

Bladder Tumour ◽

Significant Risk ◽

Muscularis Propria ◽

Giant Cells ◽

Senior Author ◽

Repeat Biopsy ◽

Male Predominance

AimsA subset of patients with urothelial carcinoma (UCa) and lamina propria (LP) invasion in bladder biopsies/transurethral resections (TURs) are at significant risk for recurrence and have increased rates of progression to UCa with muscularis propria (MP) invasion. The clinicopathologic features of this patient population has not been well characterised in the Pathology literature.MethodsWe performed a search through our urologic pathology files and expert consult cases of the senior author for bladder biopsies/TURs of UCa with LP invasion and variant/divergent histology from 2014 to 2020. Patients with a prior diagnosis of UCa with MP invasion or upper tract UCa were excluded. Clinicopathologic data were obtained.ResultsNinety-five patients with at least one biopsy/TUR of UCa with LP invasion and variant/divergent histology were identified. Mean patient age was 72 years (range: 46–92 years) with a male predominance 2.3:1. Initial variant/divergent histologies identified were: glandular (35.8%), squamous (23.2%), micropapillary (20%), clear cell/lipid rich (12.6%), diffuse/signet ring/plasmacytoid (10.5%), nested (9.5%), sarcomatoid (6.3%), poorly differentiated/anaplastic (4.2%), small cell (2.1%), lymphoepithelioma-like (2.1%), osteoclast-like giant cells (1.1%) and tumour giant cells (1.1%). Two or more variant histologies were identified in 18.9% of these cases. The rate of micropapillary UCa was significantly higher in multifocal tumours compared with unifocal tumours (37% vs 7.1%).ConclusionsIn our cohort of patients undergoing early repeat biopsy/TUR, 75% of patients had persistent UCa. Additionally, almost 25% of patients had a prior diagnosis of UCa without a variant/divergent histology identified. Our findings highlight the critical role of repeat biopsy/TUR especially in a subset of patients who have variant/divergent histology, even in the absence of MP invasion.

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Microcystic Variant of Urothelial Carcinoma

Advances in Urology ◽

10.1155/2013/654751 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Anthony Kodzo-Grey Venyo

Keyword(s):

Urothelial Carcinoma ◽

Neuroendocrine Differentiation ◽

Muscularis Propria ◽

Biological Behaviour ◽

Squamous Cells ◽

High Stage ◽

Microscopic Features ◽

Microcystic Variant ◽

The Moment ◽

Cystitis Cystica

Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004.Aims.To review the literature on microcystic variant of urothelial carcinoma.Methods.Various internet search engines were used to identify reported cases of the tumour.Results. Microscopic features of the tumour include: (i) Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii) The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii) The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv) Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour.Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

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Case Report: Large nested variant urothelial carcinoma –invasive malignancy masquerading as low grade disease

F1000Research ◽

10.12688/f1000research.5966.1 ◽

2014 ◽

Vol 3 ◽

pp. 314

Author(s):

Andrew Keller ◽

Ai Jye Lim ◽

Ahmad Ali

Keyword(s):

Case Report ◽

Urothelial Carcinoma ◽

Urothelial Cancer ◽

Muscularis Propria ◽

Low Grade ◽

Clinical Recurrence ◽

Non Invasive ◽

Operative Specimen ◽

Cytological Features ◽

Nested Variant

IntroductionThe large nested variant of urothelial carcinoma (LNVUC) is a newly described and rare subtype of urothelial carcinoma. It is characterised by bland cytological features and a large nested architecture similar in appearance to low grade urothelial carcinoma with an inverted growth pattern. To date only 23 cases in a single series have been described.Case ReportWe describe the case of a 59 year old male with LNVUC whose tumour was initially misdiagnosed as a non-invasive low grade urothelial carcinoma. At a subsequent re-resection, his tumour was correctly re-classified as LNVUC with extensive invasion of the muscularis propria. Radical cystectomy and formation of an ileal conduit was performed. His operative specimen revealed invasion of prostatic stroma and perivesical fat, with all surgical margins clear. He is currently free from clinical recurrence 12 months after his cystectomy.ConclusionLNVUC is a newly described and rare urothelial carcinoma subtype. It characteristically possesses bland cytological features and may mimic low grade urothelial cancer. Despite its bland appearance it behaves aggressively with invasion, metastasis and death being common.

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Nested Variant of Urothelial Carcinoma

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-1725-nvouc ◽

2007 ◽

Vol 131 (11) ◽

pp. 1725-1727 ◽

Cited By ~ 4

Author(s):

Deepti Dhall ◽

Hikmat Al-Ahmadie ◽

Semra Olgac

Keyword(s):

Urothelial Carcinoma ◽

Correct Diagnosis ◽

Muscularis Propria ◽

Urothelial Cells ◽

Significant Delay ◽

Benign Lesions ◽

Nephrogenic Adenoma ◽

Large Numbers ◽

Nested Variant ◽

Cystitis Cystica

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

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Overexpression of IGF1R to predict outcome in invasive urothelial carcinoma of urinary bladder.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.280 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 280-280

Author(s):

Jenny J. Kim ◽

Nilda Gonzalez-Roibon ◽

Alcides Chaux ◽

Enrico Munari ◽

Shiela F. Faraj ◽

...

Keyword(s):

Overall Survival ◽

Urothelial Carcinoma ◽

Proportional Hazards ◽

Muscularis Propria ◽

Cox Proportional Hazards ◽

Tyrosine Kinase Receptor ◽

Scoring Method ◽

Significant Independent Predictor ◽

Cancer Specific Survival ◽

Clinicopathologic Parameters

280 Background: Insulin-like growth factor-1 receptor (IGF1R) is a transmembrane tyrosine kinase receptor involved in cell proliferation and differentiation. IGF1R is overexpressed (OE) in several tumors including bladder cancer and is currently under investigation as a target of Rx. Here we explore IGF1R expression in urothelial carcinoma (UC), its association with clinicopathologic parameters and prognostic role. Methods: Fivetissue microarrays (TMA) were constructed from 100 cystectomy specimens performed for invasive UC at our institution (1994 to 2007). Formalin-fixed paraffin-embedded paired tumor and benign samples were spotted 3-4 times each. Membranous IGF1R staining was evaluated using immunohistochemistry (G11, Ventana Medical Systems). A scoring method analogous to that of Her2 expression in breast cancer was used and the highest score was assigned to each tumor. IGF1R was considered OE in cases with score 1. Endpoints of the study included overall survival and cancer-specific survival. Patients were followed-up for a median of 33.5 months (range 1, 141 months). Results: IGF1R was OE in 62% of UC. No differences were noted between normal urothelium and malignant counterparts (74% vs. 60%; P=0.14). IGFR1 was more frequently OE in tumors from African-American patients compared to Caucasians (100% vs. 59%, P=0.04). pT4 tumors OE IGF1R more frequently than pT1-pT3 tumors (71% vs. 29%, P=0.005). No association was found with other analyzed clinicopathologic parameters such as patient's age or gender, muscularis propria invasion, or lymph node metastasis). Overall survival (OS) and disease-specific survival (DSS) rates were 58% and 69%, respectively. Patients whose tumors OE IGF1R had a lower OS and DSS compared to those whose tumors did not OE IGF1R (Mantel-Cox P=0.0007 and P=0.006, respectively). Using Cox proportional hazards regression, IGF1R overexpression remained a significant predictor of OS (HR=3.49, P=0.001) and DSS (HR=3.54, P=0.007) after adjusting for pathologic stage. Conclusions: Overexpression of IGF1R was found in 62% of UC. High stage tumors OE IGF1R more frequently than low stage tumors. More importantly, IGF1R overexpression was a significant independent predictor of OS and DSS.

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