Practical utility of specific red cell adherence test in bladder cancer

There is a highly significant correlation between specific red cell adherence (SRCA) tests for ABO(H) blood group antigens and the biologic potential of a bladder cancer in terms of both superficial tumor recurrences and the subsequent development of invasive cancer. The correlation with superficial recurrences is of limited practical value because almost one half of patients with antigen-positive tumors have superficial recurrences. Similarly, because in approximately one third of patients with SRCA-negative tumors invasive cancer does not develop, SRCA tests cannot be used to select patients for early cystectomy. Because invasive cancer proceeds to develop in less than 10 per cent of patients with high-grade, antigen-positive tumors, SRCA tests may be of use to identify patients with high-grade tumors who deserve a trial of conservative therapy. SRCA tests must be interpreted with caution in patients who have been treated previously with radiation therapy or thiotepa, in whom false positive tests may occur, and in patients with type O blood in whom false negative tests may occur.     

Concomitant pathology in the prostate in cystoprostatectomy specimens: a prospective study and review

OBJECTIVES

To investigate possible associated pathology in the prostate removed from patients with invasive bladder cancer and determine if there is a justification for prostate‐sparing cystectomy.

PATIENTS AND METHODS

Between March 2005 and July 2007, 425 men (mean age 59 years, sd 8.23) had a cystoprostatectomy at our institute. The prostate was step sectioned at 2–3 mm intervals and any associated pathology determined; patient and tumour characteristics were correlated with prostatic pathology. The results were compared with those published previously, and the potential functional advantages of prostate sparing are reviewed and discussed.

RESULTS

Prostatic adenocarcinoma was detected in 90 of the 425 (21.2%) patients. There was no significant correlation between preoperative prostate‐specific antigen level and the presence of adenocarcinoma, Gleason score or prostatic tumour stage. There was prostatic involvement as a result of direct invasion by the primary bladder tumour (contiguous) in 39 cases (9.2%). Concomitant (non‐contiguous) transitional cell carcinoma of the prostatic urethra and/or ducts was detected in 27 specimens (6.4%). Additional findings were high‐grade prostatic intraepithelial neoplasia in 43 patients (10.1%) and benign prostatic hyperplasia in 175 (41.2%).

CONCLUSION

We think that the potential oncological risks of prostate‐sparing cystectomy outweigh any small and possible functional benefits; accordingly, the prostate should not be retained.     

Antigenic detection and prognosis of patients with transitional cell carcinoma of the urinary bladder

We used the specific red cell adherence (SRCA) technique to detect the A, B, O cell surface antigen on 61 transitional cell carcinomas of the urinary bladder seen from 1979 to 1982 at the Urology Department of Kaohsiung Medical College Hospital. It was suggested in this study that the loss of surface antigen had good correlation with both the pathological grade and clinical stage of tumors. On the other hand, the patients deprived of the surface antigen were poorer in prognosis than those with positive surface antigens. Among the four groups of A, B, O and AB patients, patients with blood group O had higher mortality rates, and more susceptibility to loss of the surface antigen. This study also demonstrated that the activation of surface antigen will reduce as the age increased. Of 11 patients with recurrent stage A tumors in this study, 8 had positive surface antigen and 3 had negative surface antigen. In 8 cases of positive surface antigen, 1 (13%) subsequently developed an invasive tumor. In contrast, 2 (67%) among the 3 negative surface antigens developed invasive tumors and the statistics showed significant differences (p less than 0.05). Consequently, the SRCA technique may be valuable for predicting malignant potential in early stage cancer of the bladder.     

Prostatic adenocarcinoma with endometrioid features. Clinical, pathologic, and ultrastructural findings

Thirteen cases of prostatic adenocarcinoma with endometrioid features were reviewed. The patients were older men (49-81 years) presenting with symptoms of hematuria and urinary obstruction. Each of the tumors displayed exophytic growth into the prostatic urethra, with involvement of the verumontanum. The urethral orifices of the large (primary) prostatic ducts were uniformly involved, and coexistent invasive (acinar) adenocarcinoma was identified in 10 cases (77%). The tumors exhibited a complex glandular pattern strikingly similar to uterine endometrial carcinoma, with prominent papillary formation in six cases. All cases demonstrated intense cytoplasmic immunoreactivity for prostatic acid phosphatase and prostate-specific antigen in at least part of the tumor. Focal staining for carcinoembryonic antigen was seen in three cases. Five tumors examined ultrastructurally demonstrated typical features of prostatic adenocarcinoma. Follow-up information was available on all 13 patients (6-83 months). Seven patients died of metastatic tumor (9-70 months after diagnosis), and the other six patients exhibited recurrent local or metastatic tumor. The sites of metastases were identical to those seen with invasive "acinar" prostatic adenocarcinoma, including pelvic lymph nodes, bones, and lungs. Crude 5-year survival was 15%, with a mean survival of 37 months. Adjuvant therapy provided palliative relief for many patients, but did not appear to influence survival. These findings indicate that endometrioid carcinoma is a histologically distinct variant of prostatic adenocarcinoma, with a more aggressive clinical behavior than previously thought.     

Pathological classification and follow-up of prostatic lesions initially diagnosed as "suspicious of malignancy"

Sections from a series of prostatic specimens (n = 44) in which the initial diagnosis implied a suspicion of malignancy were reviewed and the patients followed up (group 1). The aim was to categorise the morphological appearances according to current criteria and to determine the natural history of any pre-malignant lesions within this group. A "control" series of patients (n = 40) in whom the primary diagnosis was benign were also reviewed and their course followed (group 2). The heterogeneity of the abnormalities in group 1 was striking. Of the 44 cases, pre-malignant lesions were seen in 8, microinvasive adenocarcinoma in 11 and lesions not now considered pre-malignant in the remaining 25. None of the 8 patients with pre-malignant lesions developed clinical evidence of carcinoma over a follow-up period of 8 to 12 years. In contrast, 3 of the 11 diagnosed on review as having microscopic invasive adenocarcinoma developed clinically evident tumour within 5 years of surgery. Of the 25 patients whose prostatic lesions were considered benign, 2 developed carcinoma 12 and 13 years after surgery. Only 1 of the 40 patients in group 2 had a pre-malignant lesion and he did not develop tumour within 10 years. However, adenocarcinoma was diagnosed incidentally in 1 patient 3 years after surgery. It was concluded that there is a need to standardise interpretation and reporting of pre-malignant lesions and microscopic foci of adenocarcinoma in the prostate. The limited results on the course of pre-malignant lesions diagnosed incidentally in patients over 60 years of age do not indicate that follow-up would have prompted the early diagnosis of invasive disease.     

Immunohistological detection of T antigen and ABH blood group antigens in upper urinary tract tumours

The status of T antigen was assessed by means of peanut agglutinin (PNA) used in an immunoperoxidase technique, and the status of ABH blood group antigens was determined by the specific red cell adherence (SRCA) test. Thirty-eight patients with upper urinary tract tumours were examined. Our data indicated that T antigen status did not correlate with conventional prognostic indicators such as grade and stage of tumour and survival of patients, while the expression or deletion of ABH blood group antigens did correlate well. It was concluded that ABH blood group antigen determination might provide a useful prognostic probe in upper urinary tract tumours should it find clinical application.     

Significance of isoantigen in the management of the urinary bladder tumor--a basic study of ABO isoantigen in step sections of the entire bladder

Twenty cases of bladder cancer which had been treated by radical cystectomy were investigated, five out of these twenty were rendered to a specific red cell adherence test (SRCA test) using step section of entire bladder and for the other 15 cases malignant lesions and surrounding non-malignant lesions, which had been determined by histological mapping, were compared using the SRCA test. The SRCA test positive and negative lesions could coexist within the same tumor. Thus in the case of a large tumor, multiple biopsies were required to evaluate the results of the SRCA test. Since multiple bladder cancer lesions of the same patient revealed different results of the SRCA test, each lesion should be evaluated individually. Some dysplasia, down growth and squamous metaplasia were SRCA test negative and this phenomenon was frequently observed in the surrounding tissue of the bladder cancer. Histologically normal bladder epithelium and hyperplasia showed SRCA test positive by 100%. All the CIS showed SRCA test negative. Positive percentage of SRCA test in grade II and grade III tumors were 40% and 23.1% respectively. There was no relationship between the pathological stage and the results of SRCA test. There was no relationship between the existence of the intramural lymphatic invasion and/or the intramural venous invasion and the result of the SRCA test. From these results, we conclude that the SRCA test is a useful tool to predict the malignant potential of the bladder cancer, but when we utilize this test for the bladder biopsy specimens we found its reliability limited.     

Linitis plastica-like carcinoma of the urinary bladder

Two cases of signet-ring cell adenocarcinoma of the urinary bladder with a linitis plastica pattern of infiltration were studied. Mucin histochemistry indicated the presence of neutral and acid mucopolysaccharides and absence of sulphomucin. Immunocytochemistry of the tumour cells was positive for keratin and carcinoembryonic antigen, but negative for prostatic specific antigen and vimentin. The relevance of these observations to the differentiation and histogenesis of these tumours is discussed.     

Expression of alpha-methylacyl-CoA racemase (P504S) in nephrogenic adenoma: a significant immunohistochemical pitfall compounding the differential diagnosis with prostatic adenocarcinoma

Alpha-Methylacyl-CoA racemase (AMACR, P504S) has recently been shown to be a useful marker for the diagnosis of prostatic adenocarcinoma and a potential aid in its distinction from its many mimics, one of which is the benign lesion, nephrogenic adenoma (NA). The goal of this study was to assess the expression of AMACR in NA by immunohistochemistry, as well as other potentially useful markers, high-molecular-weight cytokeratin clone 34betaE12, p63, and prostate-specific antigen (PSA). AMACR was expressed in 4/4 NAs involving the prostatic urethra and underlying stroma, and in 3/16 NAs involving the bladder. The prostatic cases showed circumferential granular cytoplasmic AMACR expression of at least moderate intensity, in >75% of tubules in 3 cases and in <10% of tubules in the remaining case. The AMACR-positive cases in the bladder typically showed focal weak noncircumferential staining of the tubules and stronger staining of the cells lining the papillae. 34betaE12 staining was observed in 1/4 prostatic NAs and 4/16 bladder NAs, typically in a cytoplasmic pattern in a minority of cells. p63 and PSA were negative in all cases. Our data indicate that NA of the prostatic urethra commonly expresses AMACR and lacks basal cell-specific markers, making it not only a potential morphologic mimic of prostatic adenocarcinoma but also a significant immunohistochemical mimic as well. Awareness of NA as a significant pitfall in the diagnosis of prostatic adenocarcinoma and careful examination of hematoxylin and eosin-stained sections remains the key to the correct diagnosis, which can be supported by a negative PSA stain.     

Prognostic value of cell surface antigens using immunoperoxidase methods in bladder carcinoma

The presence of blood group cell surface antigens in carcinoma of the bladder has been shown to be associated with a relatively benign clinical course, whereas the absence of these antigens is often indicative of tumor recurrences and invasion. In practice, however, detection of these antigens using the SRCA test in tissue sections and urine specimens has been associated with some difficulties especially for O blood group individuals. We have used immunoperoxidase methods for detection of these tumor markers in tissue sections andlor urine specimens of normal individuals and patients with carcinoma of the bladder. The results were then compared with those obtained by SRCA test. Our present study indicates that the lectin antilectin immunoperoxidase method is a more sensitive and superior test for detecting antigen H in tissue sections as well as urine andlor bladderwashing specimens. It has clearly reduced the false negative test results and predicted subsequent recurrences and invasion more accurately in patients with bladder tumors. For best results in group A and B patients, both tests probably should be performed and compared.     

Intestinal-type mucinous adenocarcinoma arising from the prostatic duct

We present a case of mucinous adenocarcinoma of intestinal type arising from the prostatic duct in a 72-year-old Japanese man. The patient presented with macroscopic hematuria. Cystourethroscopy exhibited a mucus deposit at the 5 o'clock position of the verumontanum portion. A transurethral biopsy specimen revealed mucinous adenocarcinoma. A radical retropubic prostatectomy was performed. In the prostatectomy specimen, the cancer lesion mainly showed intraductal growth in the prostatic ducts with scattered mucin lakes in the prostatic stroma. There were no abnormalities in the urethral epithelium. The cancer cells resembled the intestinal epithelium rather than either the prostatic duct or the acinar epithelium, which showed diffusely positive immunohistochemical staining for carcinoembryonic antigen, but showed negative staining for prostate-specific antigen. Therefore, these findings suggest mucinous adenocarcinoma of intestinal type arising from the prostatic duct. A number of cases with mucinous adenocarcinoma arising from the prostatic urethra resembling the present case have been reported, but this is the first known case of carcinoma arising from the prostatic duct.     

T antigen expression in benign hyperplasia and adenocarcinoma of the prostate

The status of Thomsen-Friedenreich antigen (T antigen), in histological sections of human hyperplasia (30 cases) and adenocarcinoma (45 cases) of the prostate, was investigated by the immunohistochemical method. All benign prostatic hyperplasias were negative for T antigen but positive for cryptic T antigen after neuraminidase digestion. Of the 45 cases of adenocarcinoma of the prostate, 27 (60%) were positive for T antigen, 13 (29%) were negative for T antigen but positive for cryptic T antigen, and 5 (11%) were negative T and cryptic T antigens. The status of T antigen was found to be correlated with the histological grade and bone metastasis. However, there was statistically no definitive correlation between the status of T antigen and survival of patients with adenocarcinoma of the prostate.     

Study of growth fraction on fine needle aspirated prostatic tissue smear using monoclonal antibody Ki-67

Immunohistochemical staining using monoclonal antibody Ki-67 was performed in 30 patients with benign prostatic hypertrophy (BPH), one with prostatic tuberculosis (TB), 22 with prostatic adenocarcinoma, one with prostatic transitional cell carcinoma and one with prostatic invasion from a bladder cancer. Specimens were aspirated from the prostate transrectally and a cytological smear were made. This antibody is specific for a proliferation-associated nuclear antigen. Alkaline phosphatase anti-alkaline phosphatase stained immunopositive nuclei red making positive or negative specimens easy to recognize. In BPH and TB smears, no immunopositive cell was reactive with Ki-67. In prostatic malignancy were found many immunopositive cells ranging from 2.5 to 10.2% (mean 5.9%) in prostatic adenocarcinoma (n = 22), and from 11.9 to 24.3% (mean 18.1%) in prostatic transitional cell carcinoma. Transitional cell carcinoma may have a much greater growth fraction than adenocarcinoma in prostatic tissue. Poorly differentiated adenocarcinoma showed a higher growth fraction (from 4.2 to 10.2%, mean 6.9%) than well differentiated (from 3.1 to 8.9%, mean 5.8%) and moderately differentiated adenocarcinoma (from 2.5 to 10.1%, mean 5.6%), but this difference was not significant. There was no correlation with age, clinical stage, bone metastasis or B?cking's cytological grade. In conclusion, immunohistochemical staining using Ki-67 on aspirated prostatic smear is visualizes the growth fraction of prostatic disease well and is useful to diagnose prostate cancer.     

Prostatic ductal adenocarcinoma showing Bcl-2 expression

Prostatic ductal adenocarcinoma represents a rare histological variant of prostatic carcinoma with features of a papillary lesion at cystoscopy. There are conflicts regarding the existence, origin, staging, grading, treatment and clinical behavior of this tumor. The aim of the present study is to examine the expression of Bcl-2 and p53 in prostatic ductal adenocarcinoma and to evaluate its origin by analyzing prostate specific antigen, prostate specific acid phosphatase, cytokeratins, epithelial membrane antigen and carcinoembryonic antigen expressions. The results confirmed the expression of prostate specific antigen and prostate specific acid phosphatase in prostatic ductal adenocarcinoma. The demonstrated expression of Bcl-2 was predominant in the better-differentiated tumor. Bcl-2 expression appears not to be associated with neuroendocrine differentiation as assessed by chromogranin A reactivity. Thus, the first case of a prostatic ductal adenocarcinoma showing Bcl-2 expression is presented. The tumor was negative for p53.     

Pre-treatment and post-treatment evaluation of prostatic adenocarcinoma for prostatic specific acid phosphatase and prostatic specific antigen by immunohistochemistry

Prostatic specific acid phosphatase and prostatic specific antigen have been used as specific markers of prostatic adenocarcinoma in immunohistochemical studies, particularly when seeking the primary site of a poorly differentiated metastasis. We herein evaluate the effect of therapy on the persistence of these markers in surgically obtained tissues. Prostatic biopsies from 30 patients with adenocarcinoma of the prostate gland before and after treatment with orchiectomy alone, diethylstilbestrol, external beam radiation or combined radiation and diethylstilbestrol were studied for prostatic specific acid phosphatase and prostatic specific antigen using the indirect immunoperoxidase technique. The interval between biopsies ranged from 3 to 72 months, with an average of 28 months. All pre-treatment biopsies stained positively for prostatic specific acid phosphatase and prostatic specific antigen. Staining for prostatic specific antigen and prostatic specific acid phosphatase was seen easily in 29 of 30 post-treatment biopsies, while in 1 case infiltrating anaplastic cells surrounded by stroma showed staining for these antigens in an extremely small percentage of cells, which were overlooked easily unless examined carefully. In view of this small number of positively staining cells this case was designated as equivocal. While some cases demonstrated less intense staining in post-treatment biopsies compared to pre-treatment, this finding was by no means constant. With these primary antisera a higher percentage of cytologically malignant cells stained positively for prostatic specific acid phosphatase than for prostatic specific antigen in adjacent tissue sections in some cases. Prostatic specific acid phosphatase and prostatic specific antigen appear to be sensitive and persistent markers of prostatic adenocarcinoma despite morphologic changes accompanying various therapies.     

Immunoperoxidase versus specific red cell adherence in detection of ABO(H) antigens on normal urothelium: Double-blind study

In this study we compared the sensitivity of SRCA for detecting A, B, O(H) blood group antigens on the urothelial surface of normal renal pelvis, ureter, and bladder to that of immunoperoxidase staining via the avidin-biotin complex (ABC) method. In all, forty-three mucosal specimens from 23 patients were compared. There was little difference between SRCA and immunoperoxidase for the detection of A and of B antigens. H(O) antigen was detected in 94 per cent of the blood group O patients using immunoperoxidase while only 46 per cent were detected using the SRCA method. We therefore concluded that immunoperoxidase was superior to SRCA in detecting the H(O) antigen not only in normal ureter but also in normal renal pelvis and normal bladder.     

A choroid plexus metastasis of a prostatic adenocarcinoma mimicking a choroid plexus carcinoma: A case report

A multicystic intraventricular tumour of the right ventricular atrium was incidentally diagnosed on follow-up imaging of a 61-year-old man with a history of prostatic adenocarcinoma. Surgical resection of the lesion was performed after a one-year radio-clinical follow-up due to progressive expansion of the lesion size and a rising prostate specific antigen blood-level. Morphological features with papillary pattern on pathological examination were compatible with malignant adenocarcinoma or choroid plexus carcinoma. The immunoprofile was conclusive for an exceptional choroid plexus metastasis (CPM) of a prostatic adenocarcinoma. To our knowledge, this is the first report of a proven prostatic origin of a CPM.     

ABO(H) cell surface antigens in parathyroid adenoma and hyperplasia

Forty-three cases of primary hyperparathyroidism were studied with the specific red cell adherence test (SRCA) to determine the presence or absence of ABO(H) cell surface antigens on abnormal parathyroid tissue. Of the 27 patients with the clinicopathologic diagnosis (CPD) of adenoma, 24 (89%) had lost the ABO(H) cell surface antigen of the abnormal gland. Among the 15 patients with the CPD of hyperplasia, the parathyroid tissue from three (20%) had lost its red cell antigen. In one patient, a metastasis from a parathyroid carcinoma had lost the ABO surface antigen. Several patients in whom conflicting SRCA and CPD were obtained had factors that raised doubts as to the validity of their CPD. The SRCA is a simple test that may aid in the difficult differentiation between parathyroid adenoma and hyperplasia.     

Primary mucin-producing urothelial-type adenocarcinoma of prostate: report of 15 cases

Prostatic urothelial-type adenocarcinoma arises through a process of glandular metaplasia of the prostatic urethral urothelium and subsequent in situ adenocarcinoma sometimes associated with villous adenoma. These prostatic adenocarcinomas are analogous to nonurachal adenocarcinomas arising in the bladder from cystitis glandularis. Only 2 cases of urothelial-type adenocarcinoma from an institution other than our own have been previously described. The distinction between adenocarcinoma from another organ secondarily involving the prostate, usual adenocarcinoma of the prostate, and prostatic urothelial-type adenocarcinoma can present a significant diagnostic challenge and has significant therapeutic implications. Fifteen cases of prostatic urothelial-type adenocarcinoma were retrieved from the consult files of one of the authors. Mean patient age at diagnosis was 72 years (range 58 to 93 y). All men had negative colonoscopies, clinically excluding a colonic primary. Bladder primaries were ruled out clinically or pathologically in radical resection specimens. Follow-up was available on all men with a mean of 50.3 months (range 2 to 161 mo). All men presented with urinary obstruction symptoms with 3 (20%) also having mucusuria and 2 (13.3%) also having hematuria. Four men (26.7%) developed metastatic disease and 8 (53.3%) died of disease. In 8/15 (53%) cases, glandular metaplasia of the prostatic urethra and contiguous transition to adenocarcinoma were identified. Multiple histologic patterns were observed including dissection of the stroma by mucin pools 15/15 (100%), villous features 7/15 (47%), necrosis 2/15 (13.3%), signet ring cells 3/15 (20%), perineural invasion 1/15 (6.7%), focal squamous differentiation 1/15 (6.7%), and a granulomatous inflammatory response 1/15 (6.7%). Immunohistochemical stains were negative for prostate specific antigen, prostate specific acid phosphatase, CDX2, and beta-catenin in all cases. Stains were positive for high molecular weight cytokeratin in 12/12 cases (100%), and CK7 and CK20 in 10/12 cases (83.3%). Prostatic urothelial-type adenocarcinoma is a rare aggressive cancer arising in the prostate. The differential diagnosis includes conventional prostatic mucinous adenocarcinoma and secondary infiltration from a colonic or bladder adenocarcinoma. Immunohistochemistry for prostate specific antigen, prostate specific acid phosphatase, and high molecular weight cytokeratin along with morphology can help rule out conventional prostate carcinoma. beta-catenin, CDX2, and clinical studies are needed to rule out colonic adenocarcinoma. As prostatic urothelial-type adenocarcinoma is entirely analogous to bladder adenocarcinoma in both, its morphology and immunophenotype, only clinical studies or in some cases pathologic examination of the cystoprostatectomy specimen can exclude infiltration from a primary bladder adenocarcinoma.     

Origin of carcinomas causing bladder neck obstruction demonstrated by immunoperoxidase localisation of specific antigens

The immunohistological demonstration of prostate specific acid phosphatase, prostate specific antigen, epithelial membrane antigen and keratin was used to ascertain the origin of five advanced carcinomas involving the bladder neck and causing obstruction. Five prostatic carcinomas, 10 transitional cell and 10 squamous cell carcinomas with schistosomiasis of the bladder were studied for comparison. The concomitant localisation of prostate specific antigen and keratin was most useful in ascertaining the origin of tumour invading the bladder in contrast to the multiple use of other epithelial markers. It showed that 2/5 were of prostatic origin and 3/5 were urothelial. The markers did not discriminate with certainty between invasive poorly differentiated transitional or squamous cell carcinomas.