Primary high grade malignant lymphoma of bladder

Primary malignant lymphoma of bladder is one of the rarest extranodal site for lymphomas. Less than 100 cases have been reported so far. A history of chronic cystitis has been shown to be a preceding feature in many cases (40%) of primary bladder lymphoma. Most of the cases reported in the literature have a low-grade lymphoma including the subtypes of mucosa-associated lymphoid tissue. The diffuse large cell lymphoma is the most frequent type among the subtypes of high-grade bladder lymphomas. In this report, a case with high-grade primary malignant lymphoma of bladder is reported and the clinical, pathological aspects of diseases are reviewed.     

Recurrence, progression and success in stage Ta grade 3 bladder tumors treated with low dose bacillus Calmette-Guerin instillations

PURPOSE: Bacillus Calmette-Guerin (BCG) therapy is considered to be an effective prophylactic and therapeutic agent for high risk superficial transitional cell carcinoma of the bladder. Nevertheless, in a select uncommon population of stage Ta grade 3 superficial lamina-free tumors the results of this treatment have not yet been well established. We evaluated recurrence and progression rates, and the success of BCG therapy in a population with stage Ta grade 3 transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Of the 605 patients treated at our institution from 1982 to 1996 for the histopathological diagnosis of primary bladder cancer 32 (5.3%) with stage Ta grade 3 noninvasive primary bladder tumor were treated with intravesical instillations of 75 mg. Pasteur strain BCG in 50 ml. saline weekly for 6 weeks. At a followup of 2 to 13 years (mean 58.4 months) patients were evaluated with urinary cytology, cystoscopy, transurethral resection and random mucosal biopsies. Recurrence, grade and stage progression, death and causality were analyzed. RESULTS: Of the 32 patients 9 (28%) responded positively to BCG without recurrence, while disease recurred as stage Ta in 8 (25%) and T1 in 7 (22%), and progressed to muscle layer infiltration in 8 (25%). Four patients (12%) died of bladder cancer. The number of tumors at primary resection, gross examination, the mitotic index or an association with carcinoma in situ did not appear to be predictive factors of progression to muscle invasion. Urine cytology (I to II versus III to IV) appeared to correlate highly with progression and BCG response (p<0.001) with excellent sensitivity (1) but low specificity (0.67). CONCLUSIONS: Our study demonstrates the high progression potential of stage Ta grade 3 tumors, since nearly 50% recurred and 25% progressed to invasive disease. These results may be closely compared with the results of previous trials of stage T1 grade 3 disease. We suggest that recurrence should be detected at an early stage using long-term followup with strict observance of the surveillance protocols during a minimum 5-year tumor-free period.     

CD44 standard form expression as a predictor of progression in high risk superficial bladder tumors

Objective: The purpose of this study was to assess the significance of the standard CD44 adhesion molecule expression in predicting progression of high risk superficial bladder carcinoma in the short term.Methods: Sixty-six patients (51 males and 15 females, aged 27 to 89 years (mean 64.75 years) with primary superficial transitional cell bladder cancer initially treated with transurethral resection (TURBT) were enrolled in the study. Only pTa/pT1 grade 2 multiple tumors as well as all grade 3 tumors were included in this study. All tumor samples obtained after the resection were immunohistochemically evaluated for the expression of the CD44 standard molecule. Fifty eight patients remained during the follow up period which ranged from 3 to 36 months (mean 11.8 months). Tumor progression in the short term was considered as the critical end point of interest in this study. The prognostic significance of tumor stage, grade, presence of carcinoma-in-situ (CIS) and expression of CD44 in determining the risk for progression, was studied with both univariate (log rank test) and multivariate (Cox proportional hazards) methods of analysis.Results: Kaplan-Meier survival curves indicated that a shorter median progression-free survival is expected for those patients with G3 bladder tumors (p = 0.0055), concomitant CIS (p = 0.0051), and loss of expression of CD44 (p = 0.0015), whereas a similar association with stage was not detected (p = 0.5793). The cox regression multivariate analysis did not yield a significant result for any of the studied parameters therefore no one of the factors taken into account can serve as an independent predictor of progression in superficial bladder cancer in the short term.Conclusion: The immunohistochemically detectable loss of the expression of CD44 standard form from superficial bladder tumor samples may be, complementary to the established prognostic factors, a useful predictor of tumor progression in the short term.     

Long-term followup of initial Ta grade 1 transitional cell carcinoma of the bladder

PURPOSE: We evaluate the long-term outcome of initial Ta grade 1 transitional cell carcinoma. MATERIALS AND METHODS: A total of 152 patients with initial Ta grade 1 bladder tumor were followed for a mean of 76 months (range 6 to 241). Recurrence was defined as positive findings on cystoscopy or biopsy. Progression was defined as an increase in tumor grade or stage. RESULTS: Tumor recurrence in 83 of 152 patients (55%) was noted within 12 months of followup in 38 patients (46%), between 12 and 24 in 11 (13%), and between 24 and 60 in 22 (27%). A significant number of recurrences (12, 14%) were diagnosed more than 60 months after the first tumor. Of 83 patients with recurrence 31 (37%) had progression, including 21 to grade 2 and 2 to grade 3 disease. Carcinoma in situ was diagnosed in 3 patients and 5 had muscle invasive disease. Progression occurred more than 24 months after initial diagnosis in 20 patients and more than 60 months after first tumor event (2 had carcinoma in situ and 2 had muscle invasive disease) in 12. CONCLUSIONS: Ta grade 1 bladder transitional cell carcinomas have a high recurrence rate and progression is not uncommon. These findings warrant close long-term followup, even when in some settings the trend is to discontinue followup after 5 years without any abnormal findings.     

Clinical analysis of high grade bladder cancer

The prognosis and other clinical manifestation of 128 patients with high grade bladder tumor were analyzed. Thirty two percent of the total cases of bladder cancer were high grade bladder cancer and 83% of their tumors were invasive tumor at stage T2 and worse. Urinary cytologies were positive in 88% of these patients. The 5-year survival rate in these patients was 32% and those in T1, T2 T3 and T4 cases were 64.2%, 55.6%, 22.7% and 8.0% respectively. The patients treated with radical (total) cystectomy showed a much better survival rate than the cases treated with TUR or partial cystectomy. These results suggest that high grade bladder cancers tend to be invasive and the patients with high grade bladder cancer would have a poorer prognosis than the patients with other histological grade tumors. Thus, these patients should be treated more aggressively including radical cystectomy than the other cases of bladder cancers.     

The treated histories of patients with Ta grade 1 transitional-cell carcinoma of the bladder

One hundred sixty patients with grade 1 transitional-cell carcinoma of the bladder were evaluated and treated at the Massachusetts General Hospital, Boston. The mean follow-up period was 57 months. There were 92 new patients and 68 patients who had a history of transitional-cell carcinoma. Fifty-three patients (33%) never had another transitional-cell carcinoma. Sixty-eight (43%) of the remaining 107 patients had recurrent Ta grade 1 transitional-cell carcinoma. In 32 patients (20%) disease progressed in grade, in seven patients (4%) invasive transitional-cell carcinoma developed, five patients underwent cystectomy, and one patient died of transitional-cell carcinoma. High-risk factors included positive results of cytologic studies after therapy and three or more recurrences. Multiple therapies were used, but it is impossible to determine if anything other than transurethral resection altered the course in these patients. The data suggest that patients with low-risk factors and Ta grade 1 tumors might be followed up with a quarterly cytologic examination and cystoscopy once or twice a year, unless a change in symptoms occurs.     

Stage progression in Ta papillary urothelial tumors: relationship to grade, immunohistochemical expression of tumor markers, mitotic frequency and DNA ploidy

PURPOSE: We studied 363 patients with stage Ta bladder tumors during long-term followup who were classified according to the 1998 WHO and International Society of Urological Pathology consensus classifications. We determine whether various immunohistochemical and molecular markers could predict tumor progression. MATERIALS AND METHODS: A total of 680 patients in western Sweden with a first diagnosis of bladder carcinoma in 1987 and 1988 were registered and followed for at least 5 years. There were 363 (53%) tumors that were papillary stage pTa. The tumors were classified as papillary urothelial neoplasm of low malignant potential in 95 patients, low grade papillary urothelial carcinoma in 160 and high grade carcinoma in 108. Of the patients in the latter group 95 were subdivided into WHO grade 2 and 13 into WHO grade 3. Tissue from the primary tumors that progressed in stage during followup was further analyzed with immunohistochemical methods (p21, p53, Ki67 and pRb), DNA ploidy and mitotic frequency. The results were compared with those in matched controls (nonprogressors). RESULTS: Recurrence developed in 35% of patients with papillary urothelial neoplasm of low malignant potential compared to 71% with low grade urothelial carcinoma and 73% with high grade carcinoma (p <0.0001). No papillary urothelial neoplasm of low malignant potential progressed in stage. Disease progressed in 4% of patients with low grade compared to 23% with high grade carcinoma (p <0.0001). Of the patients with WHO grade 3 disease progressed in 45% compared to grade 2 in 20% (p <0.0011). At first diagnosis p53 score was significantly higher (p <0.0022) among patients with WHO grade 2 carcinoma which later progressed compared to that in matched controls but there was no significant difference regarding the other markers. In contrast to grade 2 most grade 3 carcinoma was aneuploid, had high mitosis frequency, high p53 and Ki67 scores as well as loss of retinoblastoma gene expression. CONCLUSIONS: The 1988 WHO and International Society of Urological Pathology consensus classifications divide noninvasive papillary bladder tumors into 3 subgroups with different clinical behavior, which seems to be an advantage compared with the 1973 WHO classification. A disadvantage is that the high grade carcinoma group contains 2 subgroups with different progression rates and immunohistochemical marker profiles, corresponding to the 1999 WHO grades 2 and 3. Grade 2 tumors in patients that progressed in stage years later seem to have different immunohistochemical and molecular marker profiles compared to those in matched controls.     

Long-term follow-up of noninvasive bladder tumours (stage Ta): recurrence and progression

OBJECTIVE: To evaluate long-term recurrence-free and progression-free survival of noninvasive bladder tumours (stage Ta), and the significance of simple risk factors, including concomitant epithelial dysplasia. PATIENTS AND METHODS: The study included 217 patients with primary noninvasive bladder tumour (stage Ta) who were followed routinely for up to 20 years. Voided urine cytology (VUC) and preselected site biopsies (PSB) were obtained prospectively to evaluate the significance of concomitant epithelial dysplasia. RESULTS: The mean follow-up was 84 months (maximum 238). Of all tumours, 39% did not relapse, a further 20% recurred infrequently (less than once a year) and 41% recurred frequently, amongst which the most frequent were multiple and early recurrent tumours; 42 (19%) tumours progressed to stage T1+ and 23 (11%) progressed further (stage T2+ or metastases). No grade 1 tumours became invasive. Positive VUC or PSB, a short recurrence-free period or multiplicity, and size > 3 cm were significant predictive factors. The treatment and surveillance of epithelium-confined bladder tumours are discussed. CONCLUSION: Concomitant dysplasia and early recurrence are associated with considerable risk of progression in the long-term follow-up in a group of otherwise low-risk superficial bladder tumours (stage Ta).     

Prognosis of the patients with high grade bladder carcinoma

The pathological features and clinical outcome of grade 3 transitional cell carcinoma of the bladder, excluding CIS, encountered between 1972 and 1988 were studied to clarify the clinical characteristics of the disease. The subjects of this study were 108 patients consisting of 76 males and 32 females aged 33-87 years, with a mean age of 66 years. The survival rate according to each factor was calculated by Kaplan-Meier method, and the survival curves were compared by generalized Wilcoxon test. Grade 3 bladder cancer was often papillary, sessile and about 3 cm in diameter and showed a tendency of multiple occurrence. Histopathologically, it was often in high stages of pT2 or above and frequently with vascular invasion. Total cystectomy is not considered to be an absolute necessity for pT1, G3 bladder cancer patient, because, in our experience, it did not improve the prognosis. However, bladder-preserving operation requires strict postoperative follow-ups. After this operation, the 5-year survival rate was higher in the no-recurrence group than in the recurrence group, and the out come tended to be better in the group that had undergone intravesical instillation chemotherapy for prevention of recurrence than in the group without this therapy. Ample intravesical instillation chemotherapy after bladder-preserving operation seems to improve the postoperative course of bladder cancer patients. Total cystectomy may be unavoidable in patients with pT2 or above, and no effect of postoperative adjuvant chemotherapy was noted in our series. The establishment of multidisciplinary approaches is considered to be needed for improvement of the prognosis of high stage bladder cancer.     

Primary epithelial tumors of the bladder in children

Epithelial tumors of the bladder in children are extremely rare and recurrences are even more unusual. We report 3 cases of which 2 had recurrence. ABO(H) antigens were negative in 1 case and they were mildly positive in the other. Although the current opinion is that epithelial tumors in children are benign and single, with a low incidence of malignancy, 3 other pediatric cases of epithelial tumor recurrence have been reported in the literature. Therefore, we wish to emphasize the importance of long-term and careful followup of these patients, since further recurrences are possible.     

Watchful waiting policy in recurrent Ta G1 bladder tumors

OBJECTIVE: To determine the outcome of a watchful waiting policy in patients suffering from small, recurrent, papillary bladder tumors. METHODS: Watchful waiting has been considered an option when a small (<10 mm) papillary, asymptomatic tumor with negative urinary cytology was found on follow-up cystoscopy in patients who had previous resection(s) of superficial, low-grade (Ta) bladder tumor(s). The watchful waiting protocol included cystoscopy and urinary cytology every 3 months for 2 years (and then every 6 months). Surveillance was stopped if the patient had developed either symptoms related to the tumor or positive cytology, or if there had been a significant alteration in tumor morphology or size. RESULTS: Thirty-eight watchful waiting periods were documented in 28 patients (mean age 67.7 years). Mean period length was 13.5 months (SD 14.4 months; range 3-60 months). Thirty periods were terminated with tumor resection. The main reasons for termination of surveillance were the appearance of additional tumors (19 patients) and excessive tumor growth (9 patients). Hematuria indicated tumor removal in only one patient. All resected tumors were stage Ta (23 were grade 1, and 7, grade 2). The rate of tumor growth during the watchful waiting period depended highly on the tumor's largest diameter at the beginning of surveillance. If the initial tumor diameter was smaller than 5 mm (32 cases), the tumor growth rate was 4+/-5.1 mm3/mo (mean+/-SD); if the initial tumor diameter was > or =5 mm (6 cases), the tumor growth rate was 870+/-1116 mm3/mo (p < 0.05). CONCLUSIONS: Small, recurrent papillary bladder tumors after resection of low-grade Ta tumor(s) pose minimal risk for the patient. A watchful waiting policy- without resection of the tumor-may be considered in these patients.     

Patterns of recurrence and outcomes following induction bacillus Calmette-Guerin for high risk Ta, T1 bladder cancer

PURPOSE: The standard approach to treatment for patients with high risk Ta, Tis, or T1 bladder cancer that persists or recurs after bacillus Calmette-Guerin is radical cystectomy in medically fit patients. Maintenance bacillus Calmette-Guerin has been shown in both SWOG (Southwest Oncology Group) and EORTC (European Organization for Research and Treatment of Cancer) studies to reduce the probability of disease worsening events. As new drugs come on line and experience with maintenance and combination immunotherapy increases, there may be a tendency to delay definitive local therapy and thereby expose patients to a higher risk of progression to invasive and potentially metastatic disease. We explored a large prospective data set from the SWOG 8507 randomized trial of maintenance bacillus Calmette-Guerin to better understand this risk and specifically to assess the impact of timing of recurrence on survival. MATERIALS AND METHODS: The database includes 501 evaluable patients who were treated with induction bacillus Calmette-Guerin and then were randomized to maintenance bacillus Calmette-Guerin or observation. Recurrence patterns were defined as early (less than 12 months following randomization) or late (12 or more months after randomization). Patients were identified who underwent cystectomy at any time after induction bacillus Calmette-Guerin. All patients were followed for life for determination of vital status. Outcome measure of overall survival was assessed using Kaplan-Meier analysis and adjustment for covariates was done with proportional hazards models. Survival was defined from date of randomization to death from any cause. RESULTS: A total of 501 patients were randomized after induction bacillus Calmette-Guerin, of whom 251 had recurrence and 229 died. Of the patients who died 59% had recurrence following randomization. Early recurrence was not associated with a higher risk of death compared to late recurrence (p=0.68). There was no evidence that bacillus Calmette-Guerin affected the relationship of timing of relapse and survival. There was no difference in progression to T2 or greater between early and late recurrence (38 of 117, 32% vs 34 of 134, 25%; p=0.21). Cystectomy was performed infrequently as 56 of 251 patients who had recurrence underwent the operation. Patients who had early recurrence had a slightly higher cystectomy rate than those with late recurrence (32 of 117, 27% vs 24 of 134, 18%; p=0.07). Among 394 patients with no evidence of disease at randomization those who underwent cystectomy for T2 or greater disease had a higher risk of death compared to patients who underwent cystectomy for Tis or T1 disease (HR 1.76; 95% CI 0.77, 4.00; p=0.18). CONCLUSIONS: There was no association of the timing of recurrence after induction bacillus Calmette-Guerin on long-term survival probability. When patients had early recurrence there was a slightly higher probability of cystectomy but not progression to muscle invasive cancer. When cystectomy was performed the 5-year postoperative survival probability was lower than that reported in contemporary series.     

Prognostic significance of mucosal aneuploidy in stage Ta/T1 grade 3 carcinoma of the bladder.

In a prospective series of 71 patients with newly detected grade 3, stages Ta and T1 bladder carcinoma tumor characteristics, including the results of deoxyribonucleic acid (DNA) analysis as well as morphological and DNA characteristics of the grossly normal urothelium, were investigated and related to progression-free survival. The mean duration of followup was 57 months, with a minimum of 24 months. Of the 71 patients 24 underwent primary cystectomy, and 47 were conservatively treated with transurethral resection alone, or followed by instillation therapy or irradiation therapy. Of the cystectomy and conservatively treated patients 2 (8%) and 16 (34%), respectively, died of bladder carcinoma. Among the 47 conservatively treated patients tumor progression could not be predicted by the initial characteristics of tumor stage, papillary or nonpapillary growth, tumor multiplicity, tumor size, existence of 1 or multiple aneuploid cell populations, S phase value, carcinoma in situ and atypia or aneuploidy in the mucosal biopsies. Neither was progression predicted by the recurrence rate during year 1 of observation. However, a change to or persistent mucosal aneuploidy and a change to or persistent morphological abnormality of the mucosa during year 1 of observation were predictive for tumor progression (p = 0.001 and 0.045, respectively). When compared in stepwise regression analysis (Cox's proportional hazard model), DNA aneuploidy in the mucosa at 12 months after diagnosis was a highly significant predictor, whereas morphology added no further prognostic information. Therefore, progression is related to gross chromosomal abnormalities of the mucosa. High risk patients can be identified by evaluation of the grossly normal mucosa, which should be done as part of the initial diagnosis and during followup in conservatively treated patients with stages Ta and T1, grade 3 bladder carcinoma.     

Total enbloc spondylectomy for metastatic high grade spinal tumors: Early results

Background:High grade metastatic spinal tumors are most common and are invasive. These patients can succumb to disease progression if not treated timely. Although considered as invasive and morbid, total enbloc spondylectomy (TES) in selected cases has better survival rates. The authors describe the results of TES for high grade metastatic spinal tumors.Results:Average duration of followup was 18 months (range 16–20 months). The average preoperative visual analog scale score of 9.4 (range 9–10) improved to 2 (range 1–4) at last followup. Average blood loss was 1440 mL (range 1000–2000 mL). Average duration of surgery was 198 min (range 180–240 min). Significant pain relief was noticed in each patient in the immediate postoperative period and during followups. These patients attained complete functional activities of daily living with in a month. The imaging showed implants in situ, no recurrence of tumor, and no activity on PET scan at the final followup.Conclusion:The present series shows favorable short term results of TES for solitary, metastatic, high grade vertebral body tumors by a team approach.