Squamous Cell Carcinoma Of Urinary Bladder Research Articles

Urinary Bladder Squamous Cell Carcinoma In-Situ in a Background of Condyloma Acuminatum – A Diagnostic Challenge

Abstract Introduction/Objective Condyloma acuminatum is a rare lesion of the urinary bladder and urethra, usually associated with extensive anogenital condyloma acuminatum and immunosuppression. It is considered a risk factor for developing urinary bladder squamous cell carcinoma. Methods/Case Report We report a case of an 80-year-old male with a history of invasive squamous cell carcinoma of the anus, status-post chemoradiation ten years prior, and renal transplantation for end-stage renal disease 15 years prior. He presented with a lesion adjacent to the neoureteral orifice at the bladder dome. Biopsy revealed nonkeratinizing, hyperplastic papillary fronds of squamous epithelium with koilocytic change and viral atypia. The tumor was positive for p16, GATA3, and p40 and negative for high-risk and low-risk Human Papilloma Virus by in-situ hybridization. However, the morphology was consistent with squamous cell carcinoma in-situ arising in a background of condyloma acuminatum, which was concurred by an outside expert. Bladder condyloma acuminata are often challenging to recognize, given their extreme rarity and the possibility of negative low-risk and high-risk Human Papilloma Virus tests. Lack of prior history of anogenital condylomas can further obscure this diagnosis. Results (if a Case Study enter NA) NA. Conclusion This case raises awareness of condyloma acuminatum as a rare entity that needs to be considered in the differential diagnosis of bladder tumors, especially in immunosuppressed patients. Given that the treatment strategies for squamous cell carcinoma arising from condyloma acuminatum differ from that for urothelial carcinoma with squamous differentiation, distinguishing these lesions from one another is imperative.

Squamous Cell Carcinoma of the Urinary Bladder: Clinicopathological and Molecular Update

Urinary bladder cancer is one of the most prevalent cancers worldwide.Squamous Cell Carcinoma (SCC) is an uncommon subtype of urinary bladder carcinoma.It is a malignant epithelial neoplasm arising in the urinary bladder demonstrating a pure squamous cell phenotype. On histopathology it is considered when tumor is showing pure squamous morphology without any component of conventional urothelial carcinoma. The SCC is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of cells showing particular cytological or tissue architectural characteristics of squamous cell differentiation, such as the presence of keratin, tonofilament bundles or desmosomes. Majority of bladder SCC are high grade, high stage tumors with most cancers having muscle invasion at the time of diagnosis while overall about 80% of bladder cancers are non-muscle invasive bladder cancer at diagnosis.COX-2 is markedly expressed in all SCCs. An increased COX-2 level induces the development of SCC of the bladder affecting many biological features of this tissue including apoptosis, cell adhesion, angiogenesis and invasiveness.TERT promoter mutations, commonly found in conventional urothelial carcinoma, are also highly prevalent in urinary bladder squamous cell carcinoma suggesting a common tumorgenesis and potential utility as a molecular urine-based-screening assay.This review summarizes the current features related to clinical , pathological, and molecular features of SCC of urinary bladder.

IMMUNOHISTOCHEMICAL EXPRESSION OF P16 IN CERVICAL AND URINARY BLADDER SQUAMOUS CELL CARCINOMA

Background: p16 is a tumor suppressor protein important in regulating cell cycle. In bladder cancer, p16 mutations are widespread and tend to be more prevalent in low-grade superficial tumors than in higher-grade invasive tumors. Objective: To evaluate expression of p16 in 25 cases of cervical squamous cell carcinoma and 25 cases of urinary bladder squamous cell carcinoma. Patients and methods: This study was carried out in the Histopathology Department of Al-Azhar University Hospitals and from some private laboratories during the period from August 2019 up to January 2020. H & E stained sections were prepared from paraffin blocks for revision of diagnosis. Immunohistochemical analysis was done on 4 micron sections of formalin-fixed paraffin-embedded tissue using the labeled streptavidin-biotin method after antigen retrieval. Antibodies against P16 were utilized on sections from paraffin blocks. CINtec Histology kit includes a two-step antibody method for detection of human p16 antibody. Results: Expression of P16 was positive in 92% of cases of squamous cell carcinoma of the uterine cervix and 60% of cases squamous cell carcinoma of the urinary bladder. In patients with cervical squamous cell carcinoma, there was statistically significant relation between intensity of P16 staining and tumor grading. In patients with squamous cell carcinoma of the urinary bladder, there was a statistically significant relation between intensity of P16 staining and tumor grading and staging. Moderate/strong staining intensity can predict staging 2B among patients with squamous cell carcinoma of the uterine cervix, and negative/weak staining intensity can predict staging 1A, 1B, 2A with sensitivity 52.9% and specificity 37.5% among patients with squamous cell carcinoma of the urinary bladder. Conclusion: p16 immunohistochemical expression alone should not be used as a marker for differentiation between cervical and urinary squamous cell carcinoma.

Portal Vein Thrombosis Associated with Trousseau Syndrome due to Urinary Bladder Squamous Cell Carcinoma in a Liver Cirrhosis Patient

A 75-year-old woman with liver cirrhosis was admitted for treatment of portal vein thrombosis (PVT). Computed tomography (CT) showed PVT, massive ascites, and multiple abdominal organ embolism. Blood tests revealed a decreased liver function (Child-Pugh grade C). Language impairment followed by progressive left hemi-paralysis was subsequently detected. Magnetic resonance imaging revealed multiple small acute cerebral infarctions and, on CT, a 30-mm bladder tumour; a biopsy specimen examination showed squamous cell carcinoma. Her general condition worsened rapidly, and the best supportive care was chosen. Our findings suggest that, in patients with PVT, Trousseau syndrome should be considered, even in cases of liver cirrhosis.

Expression and prognostic value of PD-L1 in non-schistosoma-associated urinary bladder squamous cell carcinoma.

BackgroundNon-schistosoma-associated urinary bladder squamous cell carcinoma (SqCC) has low incidence and is associated with chronic inflammation. Due to its unique etiology and pathology, expression of programmed cell death ligand 1 (PD-L1) in SqCC could be different from that of urothelial carcinoma, which may contribute to different responses to immunotherapy. In this study, we intended to explore the expression profile and prognostic value of PD-L1 in non-schistosoma-associated urinary bladder SqCC under the consideration of tumor-infiltrating lymphocytes’ (TILs) density.MethodsWe conducted a retrospective study to review 604 bladder cancer patients who received radical cystectomy (RC) from 2009 to 2013 in Peking University First Hospital. We enrolled 67 bladder SqCC patients in total, including pure SqCC (n=19) and mixed SqCC (n=48, with urothelial carcinoma). PD-L1 protein expression and TILs density were evaluated by immunohistochemistry.ResultsNine female and 58 male patients (median age 67.4 years) were enrolled in the present study. There were 15 stage T1–2 patients and 52 stage T3–4 patients. 27 patients had N1–2 lymph node metastasis. Overall, 61.2% cases were PD-L1-positive. Dense TILs coincided with higher PD-L1 expression rate. Median survival time of PD-L1 positive cases was significantly higher than negative cases (P=0.026). During multivariate analysis, positive PD-L1 expression and dense TILs were independent protective factors affecting overall survival (OS, PD-L1: P=0.022; TILs: P=0.010) and progression free survival (PFS, PD-L1: P=0.018; TILs: P=0.009).ConclusionsPD-L1 expression and dense TILs were frequently detected in urinary bladder SqCC tumors. Positive PD-L1 expression and dense TILs were correlated with better survival outcomes in non-schistosoma-associated urinary bladder SqCC. The immunotherapy targeting PD-L1 might be helpful to bladder SqCC patients.

A Case of Urinary Bladder Squamous Cell Carcinoma Post Renal Transplant with a Previous History of Bilharziasis.

A Case of Urinary Bladder Squamous Cell Carcinoma Post Renal Transplant with a Previous History of Bilharziasis.

Post renal transplant urinary bladder squamous cell carcinoma

Post renal transplant urinary bladder squamous cell carcinoma

High prevalence of TERT promoter mutations in primary squamous cell carcinoma of the urinary bladder

TERT promoter mutations (TERT-mut) are detectable in the majority of urothelial carcinomas. The detection of TERT-mut in urine is under investigation as a potential urine-based molecular-screening assay for bladder cancer. A small but significant number of bladder carcinomas are pure squamous cell carcinoma. We sought to assess the incidence of TERT-mut in squamous cell carcinoma of the urinary bladder. A retrospective search of the institutional pathology archives yielded 15 cystectomy specimens performed for squamous cell carcinoma (2000–2014). Histologic slides were reviewed by a senior urologic pathologist to confirm the diagnosis and select a representative formalin-fixed paraffin-embedded tissue block for mutational analysis. All cases yielded adequate material for DNA analysis. Sequencing for TERT-mut was performed using previously described SafeSeq technique. We detected TERT-mut in 12/15 (80%) of bladder squamous cell carcinomas. TERT promoter mutations, commonly found in conventional urothelial carcinoma, are also highly prevalent in urinary bladder squamous cell carcinoma suggesting a common tumorigenesis and potential utility as a molecular urine-based-screening assay.

Concomitant Occurrence of Psoas Muscle and Splenic Metastasis from Squamous Cell Carcinoma of the Urinary Bladder: A Case Report

Introduction: Skeletal muscle is a rare localization of bladder cancer metastasis. Very few cases of urothelial carcinoma metastasis in psoas muscle were reported in the literature. We report concomitant psoas muscle tumor metastasis and splenic metastasis originated from urinary bladder squamous cell carcinoma. This association was never, described in earlier medical literature. Case report: The patient was 45 years old Moroccan male. He underwent trans-urethral bladder tumor resection (TURB). The diagnosis was done a month earlier in the emergency department while consulting for side pain and right leg swelling. The patient was feverish and showed an advanced general state deterioration. The CT-scan revealed a typical aspect of right psoas abscess associating a metastatic splenic localization. The ultrasound of the right leg showed an extended thrombophlebitis. The patient underwent a surgical drainage of psoas abscess and biopsies. The histopathological and immunohistochemistry studies demonstrated squamous carcinoma of the psoas muscle with very low differentiation. These tumors were originated from metastasis of this abscess. Despite the anticoagulant treatment, the patient died of pulmonary embolism after 3 weeks of surgical treatment. Conclusion: The reported psoas squamous carcinoma was originated in the bladder with splenic metastasis. It is the first report in the literature. Considering the possible metastatic origin of the psoas abscess, it is recommended to avoid a useless surgical drainage.

Role of GATA3, CK7, CK20 and CK14 in distinguishing urinary bladder squamous cell carcinoma and urothelial carcinoma with squamous differentiation

Role of GATA3, CK7, CK20 and CK14 in distinguishing urinary bladder squamous cell carcinoma and urothelial carcinoma with squamous differentiation

Novel markers of squamous differentiation in the urinary bladder

Urinary bladder squamous cell carcinoma and urothelial carcinoma with squamous differentiation are often high-grade and high-stage tumors that are thought to be associated with a poorer prognosis and response to therapy compared with urothelial carcinoma without divergent differentiation. Therefore, recognition of a squamous component is increasingly important in guiding prognosis and therapy. We investigated the expression of MAC387, desmoglein-3, and TRIM29 in pure squamous cell carcinoma and urothelial carcinoma with squamous differentiation to determine whether they have utility as diagnostic biomarkers for squamous differentiation. Eighty-four cases were retrieved from participating institutions including 51 pure urinary bladder squamous cell carcinomas and 33 urothelial carcinomas with squamous differentiation. MAC387, desmoglein-3, and TRIM29 antibodies demonstrated positive staining in pure squamous cell carcinoma in 51 (100%), 46 (90%), and 48 (93%) cases, respectively. Urothelial carcinoma with squamous differentiation showed reactivity for MAC387, desmoglein-3, and TRIM29 in the squamous component for 32 (97%), 26 (79%), and 32 (97%) cases, respectively. MAC387 demonstrated a sensitivity of 99% and a specificity of 70% for squamous differentiation, whereas desmoglein-3 yielded a sensitivity of 86% and a specificity of 91%. No urothelial component showed greater than 10% labeling for desmoglein-3. TRIM29 labeling showed a sensitivity of 95%, but a poorer specificity of 33%. In summary, MAC387 and desmoglein-3 are reliable diagnostic markers for supporting the morphologic impression of squamous differentiation in urinary bladder carcinoma. Desmoglein-3 shows high specificity, whereas TRIM29 was most likely to demonstrate labeling in areas without light microscopically recognizable squamous differentiation.

C-KIT Positive Schistosomal Urinary Bladder Carcinomas are Frequent but Lack KIT Gene Mutations

Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.

P16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma

Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

Gene expression profile in squamous cell carcinoma of the urinary bladder using complementary deoxyribonucleic acid microarray

To date, molecular evidence studies for bladder cancer, using the microarray technology, are focusing on the transitional cell carcinoma, however, similar fingerprinting studies have rarely been performed on the other molecular phenotypes of bladder cancer, squamous cell carcinoma (SCC). This study was conducted to monitor the gene expression profiles for bilharzial-related SCC of the bladder to be able to compare its data with transitional cell carcinoma microarray data. A total of 17 paired bilharzial urinary bladder SCC specimens and their corresponding normal urothelium were analyzed using the complementary deoxyribonucleic acid microarray hybridization approach to study the molecular basis of the development of SCC of the urinary bladder. Validation of the microarray results was performed using the Northern blotting technique. After supervised analysis of the microarray data, there was at least a 3-fold difference in the expression between SCC of the bladder and normal urothelium in 82 genes. A total of 38 genes were up-regulated in SCC of the bladder, including matrix degradation-related genes, growth factors, different oncogenes, and immunology related genes. Conversely, 44 genes were down-regulated in SCC of the bladder, including integrins, laminins, cadherins, nonmetastatic cell 1 (NM23) and apoptosis-related genes. Our findings can explain the aggressive behavior of SCC of the bladder. Such gene profiling studies will add to our understanding of the mechanisms of carcinogenesis, and may also improve our ability to diagnose and treat bladder cancer.

UNME/K1: an IgG2a monoclonal antibody specific to cytokeratin of human urinary bladder squamous cell carcinoma

The main distinctive feature of carcinoma in schistosomal bladder is keratinized squamous cell carcinoma. Keratins/cytokeratins constitute a multigeneic family of structurally related polypeptide markers for the malignant state of epithelial cells. A monoclonal antibody (UNME/K1) regognizing keratins associated with squamous cell carcinoma of the human urinary bladder was generated at the Urology and Nephrology Center, Mansoura, Egypt (UNME), by fusion of spleenocytes from a BALB/c mouse immunized with a keratin extract (K1) of human squamous cell carcinoma and P3X63Ag8/U1 syngeneic myeloma cells. UNME/K1 was purified by a protein-A affinity column and was of the IgG2a type, as determined by immunoelectrophoresis and gel diffusion techniques. When tested against keratins of different types of urinary bladder tumors using enzym linked immunosorbent assay (ELISA), UNME/K1 reacted only with the high molecular weight keratin of squamous cell carcinoma and showed selectivity towards specific histopathological grades of tumors.