Primary signet ring cell carcinoma of bladder exemplifying vesical epithelial multipotentiality.

The eighth reported case of primary signet ring cell carcinoma of the urinary bladder is described clinically and pathologically. It is unusual because of complete replacement of the transitional epithelium by squamous and glandular metaplasia. The latter was particularly striking, demonstrating "normal" colonic mucosa, cystitis glandularis, well-differentiated adenocarcinoma, poorly differentiated adenocarcinoma, and the rare signet ring cell carcinoma variant. The possible origin of such changes is discussed.     

ABH cell surface isoantigens in invasive bladder carcinoma associated with schistosomiasis

The immunoperoxidase technique for demonstrating blood group ABH isoantigens was used to compare 33 patients with invasive stages T2 and T3 bladder carcinoma with (18) and without (15) schistosomiasis. Of the 18 patients with schistosomiasis 11 (61 per cent) had cell surface antigens present (9 with squamous cell carcinoma and 2 with transitional cell carcinoma and areas of squamous metaplasia), while isoantigens were absent in the remaining 7 (1 with well differentiated squamous cell, 2 with moderately to poorly differentiated squamous cell and 4 with transitional cell carcinoma). Cell surface isoantigens were present in only 3 of the 15 patients (20 per cent) without schistosomiasis (2 with squamous cell and 1 with transitional cell carcinoma) and absent in the remaining 12 with transitional cell carcinoma. This preliminary study shows that a significant percentage of patients with schistosomiasis-associated invasive bladder carcinoma maintain the blood group isoantigens, in contrast to those with bladder carcinoma not associated with schistosomiasis. The better prognosis of schistosomiasis-associated carcinoma could be linked conceivably to isoantigen maintenance. If this speculation is supported by further studies the determination of blood group isoantigens in these patients would be of prognostic value.     

The perineal implantation of a bladder tumor through urethro-vasal reflux]

Perineal implantation of urinary bladder cancer in a 57-year-old male is reported. The patient had been suffering from incomplete paraplegia and neurogenic bladder for these 29 years because of accidental injury of lumbar spinal cord with episodes of bladder stones two times and right epididymitis three times, and presented urinary leakage from a perineal fistula. The fistula orifice was surrounded by a hard mass lesion. Bilateral swelling of inguinal lymph nodes was present. Fistulogram and voiding cysto-urethrography revealed reflux from posterior urethra to the fistula through right vas and epididymis. Histological diagnosis of resected perineal mass and biopsied left inguinal lymph node was transitional cell carcinoma with predominant metaplasia of squamous cell carcinoma. Tissues obtained by TUR-biopsy of a mass lesion at bladder wall was also histologically diagnosed transitional cell carcinoma with metaplasia of squamous cell carcinoma. The present case indicates implantation of a bladder tumor to perineum by urethero-vasal reflux and metastases to inguinal lymphnodes from the perineal lesion.     

Squamous Metaplasia of the Bladder: Findings in 14 Patients and Review of the Literature

We have documented the data of squamous metaplasia of the bladder in 14 patients who had undergone cystoscopies for different reasons. In two biopsies, there were marked keratinization and cellular atypia. One of these two subjects was diagnosed as squamous carcinoma of the prostate and transitional cell carcinoma of the bladder. The lesions of 8 female patients were on the trigone and evaluated as normal anatomical variants due to hormonal changes. Three of them were remarkable because of recurrent urinary infections. Apart from the two male patients with squamous cell carcinoma of the prostate the two male patients with current squamous metaplasia have been following up. In this study, we have also reviewed the relationship between squamous metaplasia, infection and malignancy.     

Progression of leukoplakia of the bladder to squamous cell carcinoma 19 years after complete urinary diversion

We report a rare case of squamous cell carcinoma developing in a defunctionalized bladder with known leukoplakia 19 years after urinary diversion. We conclude from this case that once the initial metaplasia of the transitional epithelium of the urinary tract to leukoplakia has occurred chronic irritation by (infected) urine is not required to cause further progression to squamous cell carcinoma. Therefore, we recommend prophylactic cystectomy if palliative urinary diversion for relief of symptoms is considered in patients with leukoplakia of the bladder.     

Chronically infected and postdiversionary bladders: cytologic and histopathologic study.

Cytologic and histopathologic study of 36 patients demonstrated an 86 to 92 per cent incidence of squamous metaplasia of the bladder among patients with chronically infected bladders and a 64 per cent incidence in patients with postdiversionary bladders left behind. The relationships of infection, inflammation, squamous meetaplasia, and squamous cell carcinoma of the bladder are reviewed. It is postulated that the same carcinogenic factors which induce transitional cell carcinoma might cause squamous cell carcinoma if the epithelium had previously undergone squamous metaplasia.     

The impact of squamous metaplasia in transitional cell carcinoma of the bladder

The authors report a case of squamous cell carcinoma of the bladder induced by radiation therapy for transitional cell carcinoma, possibly from sites of squamous metaplasia, which were present at the time of initial diagnosis. Although data in the literature are not sufficient at the moment in terms of implication on prognosis, foci of squamous metaplasia during the initial diagnosis of transitional cell carcinoma must be carefully sought and their presence warrants caution in utilizing irradiation in the management of the disease.     

Squamous cell carcinogenesis and squamous cell carcinoma of the urinary bladder: A contemporary review with focus on nonbilharzial squamous cell carcinoma

Bladder squamous cell carcinoma, squamous metaplasia, and transitional cell carcinoma with squamous differentiation are infrequent findings in Western countries. A common risk factor for their development consists of chronic bladder irritation and inflammation. The prognostic and clinical relevance and natural history of squamous cell lesions has been under investigation, revealing individual premalignant characteristics. Recent developments in molecular characterization of squamous alterations of the urinary tract indicate pathogenetic similarities and interrelations and might lead to more precise tumor classification and risk stratification in the future. Nevertheless, current clinical management of patients with premalignant and malignant bladder squamous cell lesions remains challenging, as high evidence level studies are not available and prognosis of invasive squamous carcinoma is poor. Our review summarizes the available data on clinical presentation, treatment, and outcome of bladder squamous cell carcinoma, metaplastic lesions, and transitional cell carcinoma with squamous differentiation and discusses implementable current advances in the understanding of bladder cancer tumorigenesis.     

Noninvasive squamous lesions in the urinary bladder: a clinicopathologic analysis of 29 cases

Noninvasive squamous lesions are distinctively uncommon in biopsies of the urinary bladder with the exception of nonkeratinizing squamous metaplasia. The clinical significance of these squamous lesions in the bladder remains to be explored. A total of 29 cases of transurethral biopsies and resections of the bladder containing noninvasive squamous lesions (excluding nonkeratinizing metaplasia) were studied from the consult files of one of the authors. These cases included keratinizing squamous metaplasia (5), verrucous squamous hyperplasia (5), squamous papilloma (5), condyloma acuminatum (3), and squamous cell carcinoma in situ (CIS) (11). Immunohistochemistry for epithelial growth factor receptor (EGFR) and in situ hybridization for wide-range human papillomavirus was performed on 23 cases. The follow-up period ranged from 2 months to 3 years with an average of 1.5 years. After the initial diagnoses in biopsies of the bladder, 10 patients received cystectomies, and 7 patients received repeat tissue sampling of the bladder. Of the 5 patients with keratinizing squamous metaplasia, 2 patients had invasive urothelial carcinoma with squamous features in their cystectomy specimens at intervals of 3 and 14 months, respectively, 1 had persistent keratinizing squamous metaplasia on rebiopsy. Of the 5 patients with verrucous squamous hyperplasia, 1 patient had invasive squamous cell carcinoma at cystectomy at an interval of 14 months, 1 had squamous cell CIS on rebiopsy, 1 had persistent verrucous squamous hyperplasia on rebiopsy, and 2 had no evidence of disease at 6 and 24 months. Of the 5 patients with squamous papilloma, 1 patient had low-grade urothelial carcinoma at cystectomy at an interval of 21 months (h/o low-grade urothelial carcinoma preceding papilloma diagnosis), 2 were free of lesions at rebiopsy. Of the 3 patients with condyloma acuminatum, 1 had squamous CIS at cystectomy at an interval of 3 months, 1 had invasive squamous cell carcinoma at 20 months. Of the 11 patients with squamous cell carcinoma in situ (CIS), 3 patients had invasive squamous cell carcinoma at intervals of 2, 3, and 4 months, respectively, 1 had invasive urothelial carcinoma with squamous features in cystectomies at an interval of 12 months, 1 had squamous cell CIS at 10 months, 1 had high-grade urothelial carcinoma (not otherwise specified) at rebiopsy at an interval of 6 months, and 1 had no evidence of disease at 8 months. Among the 9 patients with invasive carcinoma, 4 patients died in the period of 0.5 to 3 years after the diagnoses. Immunohistochemical study with EGFR demonstrated strong signals in 20 cases and no signals in 2 cases. Wide-range human papillomavirus DNA signal was detected in 1 case of condyloma acuminatum and 1 case of squamous cell CIS. Keratinizing squamous metaplasia, verrucous squamous hyperplasia, and condyloma acuminatum in the urinary bladder can be associated with subsequent or concurrent in situ, or invasive squamous carcinoma and should be closely followed. Squamous cell CIS in the urinary bladder is often associated with subsequent or concurrent invasive carcinoma with squamous differentiation. Enhanced expression of EGFR in these bladder squamous lesions suggests that EGFR may represent a logic therapeutic target in those squamous lesions that are difficult to manage clinically.     

Histopathologic changes of transitional cell carcinoma of bladder after M-VAC chemotherapy

Over the past several years, we have utilized methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) as definitive, neoadjuvant, and adjuvant therapy for various stages of transitional cell carcinoma with reduced toxicities. Currently, there is little information concerning the histopathologic changes after M-VAC therapy. We report on the histopathologic changes of bladder transitional cell carcinoma following M-VAC chemotherapy in our protocol for treatment of bladder cancer. The main histopathologic findings after M-VAC therapy are squamous metaplasia, necrosis, fibrosis, and persistent transitional cell carcinoma. In 2 cases, there were persistent adenocarcinoma and squamous cell carcinoma. The importance of these observations in terms of diagnostic and therapeutic implications is reviewed.     

28K antigen in the urothelium.

We have been investigating the nature of the mucosal lining of human urinary bladder. Surface material was obtained from bladders at autopsy and used for biochemical analysis. Western immunoblotting and tissue immunochemistry identified a molecule of Mr 28,000 (28K) which is present within surface cells of the urothelium (umbrella cells). Antiserum to 28K stained sections of the bladder of two patients with squamous cell carcinoma of the bladder and other patients with squamous metaplasia. We consider 28K to be a component of the normal human bladder surface that is increased in patients with squamous metaplasia and may also be present in squamous cell carcinoma of the bladder.     

Primary carcinoma in situ of the ureter: a case report]

A 47-year-old man presented with gross hematuria and left lower abdominal dull pain of 6-weeks duration. Cystoscopic examination revealed bloody efflux from the left ureteral orifice but no tumor in the bladder. Retrograde pyelogram showed irregular stricture of middle portion of the left ureter. Cytologic studies of the voided urine and left ureteral urine were positive for cancer, and nephro-ureterectomy with excision of a bladder cuff was carried out. The surgical specimen showed no intraluminal mass but histologically, transitional cell carcinoma in situ with G3 anaplasia and squamous metaplasia was found in the narrowed portion of the ureter. Followup examinations, including exfoliative urinary cytology, cystoscopy and IVP revealed no abnormalities until intravesical recurrence was confirmed 34 months later. Transurethral resection of bladder tumor was performed and superficial papillary transitional cell carcinoma with G2 anaplasia was found in the trigone of the bladder. Followup examinations for the last one year have revealed no abnormalities.     

Squamous metaplasia and invasive epidermoid carcinoma of bladder

Invasive epidermoid carcinoma of the urinary bladder is described in a young woman with a long history of bladder infections and extensive squamous metaplasia without atypia. The literature on squamous metaplasia and leukoplakia progressing to epidermoid carcinoma of the bladder is reviewed, and the confusion between the two terms is explored. Young women with chronic dysuria, bladder infections, and long histories of squamous metaplasia of the bladder should be followed up very closely. If epidermoid carcinoma of the bladder develops, they should undergo radical surgery.     

Transitional cell carcinoma of the urinary bladder accompanied by signet-ring cell carcinoma: a case report

A 58-year-old man visited our clinic with complaints of gross hematuria and pollakisuria. Cystoscopic examination revealed multiple non-papillary broad based tumors and reddish unstable mucosa in the bladder. The pathological specimen of the transurethral biopsy of the tumors showed signet-ring cell carcinoma predominantly and adenocarcinoma transforming into signet-ring cell carcinoma partially. A total cystectomy with ileal conduit urinary diversion was performed. The histopathological finding of the radical cystectomy specimen was grade 3 transitional cell carcinoma accompanied by adenocarcinoma. These findings suggest that the adenomatous metaplasia of transitional cell carcinoma in the bladder could differentiate into signet-ring cell carcinoma.     

Detection of early squamous metaplasia in bladder biopsies of spinal cord injury patients by immunostaining for cytokeratin 14

STUDY DESIGN: A prospective, immunohistochemical study of bladder biopsies taken from spinal cord injury (SCI) patients. OBJECTIVES: To investigate whether cytokeratin 14 immunostaining may be useful to detect early squamous metaplasia in bladder biopsies from patients with SCI. SETTING: Southport, United Kingdom. METHODS: Biopsy of bladder mucosa was taken from adults with SCI, while they underwent an elective therapeutic procedure in the urinary tract. A total of, 54 biopsies, which showed transitional epithelium only with no evidence of squamous metaplasia on routine H&E staining, formed the study group. In all, 22 biopsies, which showed squamous metaplasia on routine H&E staining, acted as controls. All biopsies were benign with no evidence of dysplasia or malignancy. Immunohistochemical staining for cytokeratin 14 was performed on all biopsies in a single batch, using a standard avidin-biotin complex method. RESULTS: All control biopsies showed positive immunostaining for cytokeratin 14 in basal and parabasal cells in areas of squamous metaplasia. Of the 54 biopsies, which showed only transitional epithelium on H&E staining, immunohistochemistry for cytokeratin 14 showed no staining in 47 biopsies. The remaining seven biopsies showed positive immunostaining for cytokeratin 14 in the epithelium, in individual cells or clusters of basal cells, revealing unexpected early squamous metaplasia in these biopsies. CONCLUSION: Immunostaining for cytokeratin 14 identifies an early phenotypic switch from transitional to squamous epithelium in bladder mucosa. Cytokeratin 14 staining is sufficiently sensitive to identify early squamous metaplasia, which is not yet evident on examination of routine H&E stained sections. This early identification may be of use in alerting physicians to change bladder management regimens to prevent predisposition to recurrent urinary infection and progression of squamous metaplasia. A cost/benefit analysis should be performed to assess the feasibility of routine cytokeratin 14 immunostaining of bladder biopsies from SCI patients.     

Monoclonal antibody to desmosome associated 34 kD protein and immunohistochemical study in relation to the malignancy of transitional cell carcinomas of urinary bladder

A mouse monoclonal IgG1 antibody (B-11) that recognized desmosomes in some human tissues was isolated and characterized. By Western blotting, B-11 recognized 34 kD protein only in squamous and transitional epithelium. By avidin-biotin complex (ABC) and immunofluorescence method, B-11 was reactive to squamous and transitional epithelium, but was not reactive to simple columnar epithelium from stomach and colon, simple cuboidal epithelium from urinary tubule and thyroid, and pseudostratified ciliated epithelium from trachea and ductus epididymidis. ABC method of B-11 was performed in 47 patients with transitional cell carcinoma of bladder. The higher positive staining was observed in well differentiated (83% in Grade (G) 1, 73% in G2 and 20% in G3), superficial (76% in non-invasive and 20% in invasive) and expansive growth (68% in Infiltration (INF) alpha, 24% in IFN beta and 18% in IFN gamma) carcinomas. 34 kD protein recognized by a new monoclonal antibody (B-11) is a new cell-type-specific desmosomal component which relates to the histological grade, stage and invasive manner of the transitional cell carcinoma of bladder. The transitional cell carcinoma of bladder obtained by operation or surgical biopsy from 47 patients was stained by ABC method using B-11.     

膀胱癌术中放射治疗

４例膀胱腺癌以及２例广泛、多发的移行上皮癌患者采用术中放射治疗，近期效果较好，保留了膀胱功能，其中一例Ｔ４期腺癌患者无法切除，暴露病灶后术中放疗，术后外放疗，一年后死于肝转移，但膀胱病灶消退，无复发。对术中放疗的方法、优缺点，膀胱肿瘤行术中放疗的适应证进行了讨论。     

Prophylactic radical cystectomy for the management of keratinizing squamous metaplasia of the bladder in a man with tetraplegia

BACKGROUND/OBJECTIVE: To report a case of keratinizing squamous metaplasia of the bladder treated with radical cystectomy. DESIGN: Case report and discussion of management options. METHODS: Keratinizing squamous metaplasia of the bladder is a rare entity that can result from chronic irritative stimuli involving the bladder. It is considered a premalignant condition associated with invasive squamous cell carcinoma. A case report is presented describing the diagnosis and management of keratinizing squamous metaplasia of the bladder in a tetraplegic man with a chronic indwelling urinary catheter. RESULTS: Radical cystectomy with an Indiana continent reservoir was performed after cystoscopy with biopsy confirmed keratinizing squamous metaplasia. Final pathology revealed focal erosion and diffuse keratinizing squamous metaplasia of the bladder with prostatic adenocarcinoma as an incidental finding. CONCLUSIONS: Patients with spinal cord injury who use indwelling catheters for bladder management are at higher risk of developing keratinizing squamous metaplasia. Surveillance for early detection of this entity is recommended. Prophylactic cystectomy is sometimes warranted; however, observation and frequent cystoscopic surveillance to identify potential malignant transformation can be an alternative strategy. An interdisciplinary approach is recommended before consideration of bladder resection.     

Malignant mixed mesodermal tumor of bladder occurring after radiotherapy for cervical cancer: report of a case

A rare case of radiation-induced malignant mixed mesodermal tumor of the bladder is reported. A 78-year-old woman complained of hematuria, which originated from a polypoid tumor in the bladder 15 years after radiotherapy for squamous cell carcinoma of the uterine cervix. The bladder tumor recurred 9 months after resection and partial cystectomy then was performed. Histological findings revealed malignant mixed mesodermal tumor composed of carcinomatous and sarcomatous elements. The former element consisted mainly of transitional cell carcinoma with occasional foci of squamous metaplasia and glandular differentiation, while the latter consisted of spindle cell sarcoma showing partly cartilaginous and osseous differentiation. The histogenesis of malignant mixed mesodermal tumor of the bladder also is discussed.     

Partial replacement of urinary bladder by autologous gallbladder

In an effort to find a more suitable method of partial urinary bladder replacement for those patients with either a damaged or contracted bladder, the use of the autologous gallbladder was studied. The urinary bladders of 6 female dogs were partially resected, and the defective portions were replaced by autologous gallbladder transplants. After six weeks, the gallbladder mucosa showed evidence of squamous cell metaplasia progressing toward transitional cell epithelium with minimal necrosis. The muscular layer showed extensive granulation tissue and revascularization. No changes were detected in the upper urinary tracts. No mortality or detectable morbidity was associated with the procedure. It appears that the gallbladder may have a role to play in partial urinary bladder replacement.