Clear cell renal cell carcinoma with smooth muscle stroma.

A recent publication described 5 unusual clear cell renal tumors with prominent smooth muscle stroma that were characterized only by immunostaining. We report 3 additional tumors composed of clear cell renal cell carcinoma intimately admixed with abundant smooth muscle stroma. Epithelial differentiation of the malignant clear cell components and smooth muscle differentiation of the benign spindle cell stroma was confirmed by the immunostaining profiles and by electron microscopy. Fluorescence in situ hybridization analysis of chromosome 3 showed loss of the entire chromosome in 2 cases and loss of 3p in the third case. We therefore interpret these tumors as unique low-grade variants of clear cell renal cell carcinoma that have induced a prolific metaplastic stromal reaction. Extensive tissue sampling and immunostaining are recommended to distinguish cases with an extensive smooth muscle component from morphologically similar but benign lesions including angiomyolipoma, leiomyoma, or mixed epithelial and stromal tumor of the kidney.

The value of preoperative needle core biopsy for diagnosing benign lesions among small, incidentally detected renal masses.

PURPOSE: We determined the safety and accuracy of preoperative needle core biopsy for diagnosing benign lesions among small incidental asymptomatic renal masses. MATERIALS AND METHODS: Between February 2000 and December 2007 we received a total of 235 preoperative core biopsies from 222 less than 5 cm incidental renal masses. Biopsy results were correlated with surgical specimen final pathology findings or with patient followup if surgery was avoided. RESULTS: Of the 235 biopsies 184 (78%) were diagnostic, whereas 51 (22%) were nondiagnostic due to insufficient material or contents of only normal, inflammatory, fibrotic or necrotic tissue, or blood clot. Diagnostic biopsies revealed 138 malignant (75%) and 46 benign (25%) lesions. Of these patients 108 (59%) underwent renal surgery, which showed a 100% biopsy accuracy rate for distinguishing malignant from benign lesions and a 98% rate for determining histological tumor type. Followup with radiological imaging was performed for 59 lesions in patients with nondiagnostic biopsies or benign masses and for 16 low grade malignant tumors in elderly patients. Lesions remained stable in 61 cases, showed minor size changes in 9 and resolved in 5. No patient has shown symptoms or required renal surgery to date. Significant biopsy related complications were noted in only 2 patients (0.9%). CONCLUSIONS: We found that needle core biopsy was a safe and accurate technique for distinguishing between malignant and benign tumors in small asymptomatic incidentally detected renal masses. Biopsy of small tumors is associated with a relatively high rate of technical biopsy failure, although this may be addressed by adopting improved biopsy techniques, as discussed.

Influence of 16S rDNA primer sequence mismatches on the spectrum of bacterial genera detected in prostate tissue by universal eubacterial PCR.

BACKGROUND: Propionibacterium sp. and Staphylococcus spp. are the most frequent bacteria cultured from prostatectomy specimens but are seldom detected by universal eubacterial PCR. MATERIALS AND METHODS: We obtained from GenBank representative 16S rRNA gene sequences from Propionibacterium sp., Staphylococcus spp. and from 34 bacterial genera that were recently detected in prostate tissues using universal eubacterial PCR. We compared these 16S rDNA sequences with the universal eubacterial 16S PCR primer sets chosen for detection of bacterial DNA in prostate tissues. RESULTS: We show that failure to detect DNA from Propionibacterium sp. and Staphylococcus spp. in prostate tissues is strongly associated with the presence of mismatches near the 3' termini of the 16S rDNA primer sets used. CONCLUSIONS: The choice of 16S PCR primers may play an important role in determining the spectrum of bacterial genera detected in prostate tissue by universal eubacterial PCR.

Central zone carcinoma of the prostate gland: a distinct tumor type with poor prognostic features.

PURPOSE: The central zone of the prostate gland is a region rarely associated with carcinoma. To our knowledge central zone tumors have not previously been compared to carcinoma originating in the peripheral or transition zone of the prostate gland. MATERIALS AND METHODS: All 2,010 radical prostatectomy cases seen at our institution from October 1998 to December 2006 were reviewed to identify tumor zonal origin. Central zone carcinoma was characterized and compared with tumors of other zones. RESULTS: Zonal origin was determined in a total of 2,494 tumors in 1,703 cases. Of the tumors 63 (2.5%) were of central zone origin with 59 of the 63 representing the index or main tumor. Comparative analysis of a defined subset of 726 cases showed that central zone cancers were significantly more aggressive than peripheral or transition zone cancers with a far greater risk of extracapsular extension, seminal vesicle invasion and positive surgical margins. Escape from the gland was often via the ejaculatory ducts and seminal vesicles. Kaplan-Meier analysis confirmed that the probability of post-prostatectomy biochemical failure was double that of tumors of the other zones with a far more rapid rate of failure. Multivariate Cox regression analysis identified Gleason grade, positive margins, extracapsular extension, tumor volume and preoperative serum prostate specific antigen as the major contributors to this poor prognosis, rather than specific zonal origin. CONCLUSIONS: To our knowledge this study provides the first characterization and comparative analysis of central zone carcinoma, identifying these tumors as a rare but highly aggressive form of prostate carcinoma with a distinct route of spread from the gland that contrasts with tumors of other zones. Preoperative identification is currently hampered by the avoidance of biopsy targeting the central zone. However, if recognized preoperatively, aggressive intervention may possibly improve the currently bleak outlook.

The antibody response to Propionibacterium acnes is an independent predictor of serum prostate-specific antigen levels in biopsy-negative men.

OBJECTIVE: To investigate whether the serum titres of Propionibacterium acnes antibodies in patients undergoing prostate biopsy are associated with prostate cancer or markers of prostate disease, including serum prostate-specific antigen (PSA) levels. PATIENTS AND METHODS: The cell wall-associated proteins from P. acnes types IA, IB and II were extracted and characterized by Western blotting and immunoblotting. We developed an enzyme-linked immunosorbent assay (ELISA) based on extracted proteins to determine the anti-P. acnes antibody titres in the sera of 68 patients undergoing prostate biopsy. Correlations between these titres and multiple markers of prostate disease were investigated. RESULTS: In patients with biopsies negative for cancer, a high anti-P. acnes antibody titre was associated with high serum PSA levels (>or=10.0 ng/mL, P = 0.04), and multiple linear regression analysis identified antibody titre as the predominant independent predictor of serum PSA level (P = 0.03). The titre was positively correlated with patient age, prostate volume and aggressive inflammation, suggesting an involvement with benign prostatic hyperplasia (BPH). However in patients with histologically detected cancer, the volume of cancer in the biopsy cores was the predominant independent predictor of serum PSA (P = 0.01). CONCLUSIONS: These results support our hypothesis that P. acnes might be involved in the development of inflammation-related prostate diseases, in particular with BPH. Our ELISA might be valuable for identifying P. acnes infection of the prostate gland in patients with elevated serum PSA levels but a negative biopsy, and might identify men at risk of developing clinical BPH. However, an investigation with more patients is needed to confirm these preliminary findings.

Polymerase chain reaction-based identification of Propionibacterium acnes types isolated from the male urinary tract: evaluation of adolescents, normal adults and men with prostatic pathology.

OBJECTIVE: To assess whether colonization of the male urinary tract with Propionibacterium acnes, in particular types IB and II (which are associated with inflammation in radical prostatectomy specimens and might be involved in the development of prostate cancer), is associated with prostate disease, and thus to develop a urine test to detect men at risk of prostate disease. PATIENTS, SUBJECTS AND METHODS: We developed the first polymerase chain reaction (PCR)-based technique for identifying P. acnes types IA, IB and II, and used this in combination with selective culture medium to compare the prevalence of these subtypes in the urinary tract of adolescent males, healthy adult men and patients with confirmed prostate pathology. RESULTS: P. acnes types IB and II were no more prevalent in the urinary tract of patients with prostate pathology than in normal control men. However, the prevalence of types IB and II appeared to be higher in adult men (at 11 of 15 and six of 15, respectively) than in adolescents (two of six and one of six), suggesting an age-related increase. Comparison of urinary tract and facial skin P. acnes from three subjects showed that type IA was more often predominant on facial skin, whereas types IB or II were more often predominant in the urinary tract. CONCLUSIONS: A urine test might not be useful for detecting men with prostatic P. acnes infection and thus at greater risk of associated prostate disease. However, this work validated our technique for detecting and identifying the three P. acnes subtypes, and identified some interesting trends worth further investigation.

Incidental renal tumours: the frequency of benign lesions and the role of preoperative core biopsy.

OBJECTIVE: To determine the incidence of benign renal lesions in incidentally discovered small renal tumours, increasingly detected by the widespread use of abdominal imaging, and to evaluate whether preoperative renal core biopsy is effective in identifying benign lesions. MATERIALS AND METHODS: In a retrospective study, renal core biopsies for incidental tumours over a 5-year period were analysed. The biopsies were correlated with the final pathology of the nephrectomy specimens, or with patient follow-up if nephrectomy was avoided. RESULTS: Of 70 diagnostic core biopsies, a third of cases were considered benign. The sensitivity and specificity for both benign and malignant lesions when compared to definitive pathology was 100% in all cases subjected to nephrectomy. Of the 30 non-diagnostic biopsies, three were proved to be benign, and 18 likely to be benign. The only complication of renal biopsy was one case of bleeding after biopsy. CONCLUSION: A higher than previously anticipated proportion of incidentally detected small renal masses are benign. Given the high sensitivity and specificity, there is value in taking a core biopsy of small incidental renal lesions, a procedure with a low complication rate (1%). When analysed by a pathologist familiar with renal biopsy, this might avoid radical nephrectomy in many patients.

Links between Propionibacterium acnes and prostate cancer.

Incidental foci of prostate cancer are found at autopsy in 30% of men in their third decade, and by their eighth decade more than 75% have histological evidence of cancer. This unprecedented cancer prevalence points to a ubiquitous causative agent or perhaps an interaction between multiple common carcinogenic cofactors. We propose that one of these carcinogens is Propionibacterium acnes. Several characteristics of prostate cancer suggest the involvement of an infectious agent and we provide evidence that P. acnes is an excellent candidate. We have cultured P. acnes from a substantial proportion of prostate glands containing cancer and shown a significant positive association with prostatic inflammation. P. acnes is well suited to cause persistent, low-grade infection involving a marked inflammatory response and the P. acnes subtypes most frequently associated with prostate cancer become highly prevalent in the urinary tract of males following puberty.

Propionibacterium acnes associated with inflammation in radical prostatectomy specimens: a possible link to cancer evolution?

PURPOSE: Inflammation is commonly observed in the prostate gland and has been implicated in the development of prostate cancer. The etiology of prostatic inflammation is unknown. However, the involvement of a carcinogenic infectious agent has been suggested. MATERIALS AND METHODS: Prostatic tissue from 34 consecutive patients with prostate cancer was cultured to detect the presence of bacterial agents. Prostatic inflammation was assessed by histological examination of wholemount tissue sections. RESULTS: The predominant microorganism detected was Propionibacterium acnes, found in 35% of prostate samples. A significantly higher degree of prostatic inflammation was observed in cases culture positive for P. acnes (p =0.007). P. acnes was separated into 3 groups based on cell surface properties, phenotype and genetic grouping. All skin control isolates were classified as group 1 whereas most prostatic isolates were classified as groups 2 and 3. CONCLUSIONS: P. acnes has been isolated from prostatic tissues in men who underwent radical prostatectomy for localized cancer and has been shown to be positively associated with prostatic inflammation. This inflammation may then be linked to the evolution of carcinoma. Furthermore, organisms infecting these patients with prostate cancer differ genetically and phenotypically from the commonly identified cutaneous P. acnes isolates, suggesting that specific subtypes may be involved in development of prostatic inflammation.

Primary renal synovial sarcoma confirmed by cytogenetic analysis: a lesion distinct from sarcomatoid renal cell carcinoma.

Primary synovial sarcoma rarely originates in the renal parenchyma. When this occurs, origin of this unusual tumor type has been the subject of debate in the literature, with a suggestion that previously reported cases may be more correctly described as renal cell carcinoma with sarcomatoid dedifferentiation. Synovial sarcoma and sarcomatoid renal cell carcinoma may be indistinguishable on pure histologic and immunohistochemical grounds, but these tumors contain distinctly different sets of chromosomal abnormalities. Most previous cases of primary renal synovial sarcoma were confirmed by molecular biology techniques, which detected the SYT-SSX gene fusion transcript typical of this tumor, but no details of the other chromosomal anomalies have been published. We report a case of primary renal synovial sarcoma confirmed by standard cytogenetic analysis, showing the characteristic t(X; 18)(p11.2:q11.2) translocation and other chromosomal aberrations that are typical of synovial sarcoma as opposed to sarcomatoid renal cell carcinoma.

Transition zone carcinoma of the prostate gland: a common indolent tumour type that occasionally manifests aggressive behaviour.

AIMS: Tumours arising in the transition zone (TZ) of the prostate gland are often well differentiated and considered clinically unimportant. We have observed examples of high-grade TZ cancers that prompted this study. METHODS: Review of 654 radical prostatectomy specimens previously assessed by systematic whole organ histology identified 187 (29%) TZ cancers of which 76 (11.6%) represented the index (main) tumour. These were compared with a volume-matched group of 76 peripheral zone (PZ) carcinomas. RESULTS: Fifty-nine of 76 TZ index carcinomas had additional minor tumours mainly located in the PZ. Compared to PZ tumours of similar size, TZ tumours had significantly lower Gleason scores, less Gleason grade 4/5 and lower rates of capsular penetration and positive surgical margins. However, within this TZ tumour group, seven carcinomas had a major Gleason grade 4 or 5 component with high rates of capsular penetration (57%) and positive surgical margins (43%). Positive anterior and bladder neck margins were more common in TZ carcinoma than peripheral tumours and transperineal biopsy was the method of choice for TZ cancer diagnosis. CONCLUSIONS: A subset of TZ carcinoma characterised by high tumour grade has a significant risk of extraprostatic spread, margin positivity and possible biochemical failure. We recommend transperineal prostate biopsy for TZ tumour diagnosis and histological sampling of the anterior TZ at radical prostatectomy, even if macroscopically normal, to detect patients at risk from aggressive TZ carcinoma.

Rhabdoid differentiation of chromophobe renal cell carcinoma.

AIMS: Rhabdoid change represents an aggressive form of divergent differentiation previously reported in conventional (clear-cell) and papillary renal cell carcinoma. This study aims to characterise rhabdoid differentiation in a case of chromophobe renal cell carcinoma (ChRCC) and to investigate its origin by genetic analysis. METHODS: A large tumour mass arising in the right kidney of a 76-year-old male was investigated using routine stains (H&E, Hale's colloidal iron), immunostains (vimentin, cytokeratin) and genetic analysis for loss of heterozygosity (LOH) on chromosomes 1, 2, 3p, 6q, 10q, 13q, 17q, 17p and 21q. RESULTS: The tumour mass was comprised of the following histological subtypes: (i) typical ChRCC, (ii) eosinophilic variant ChRCC and (iii) rhabdoid variant RCC. Tumour cells of all three different histological subtypes had a positive reaction to Hale's colloidal iron stain, negative immunostaining for vimentin and LOH on chromosomes 2, 10q, 13q and 17p. These results are consistent with a diagnosis of ChRCC and indicate a common genetic origin for all three histological cell types. CONCLUSIONS: This study confirms that the aggressive rhabdoid variant can arise from ChRCC, as has been previously demonstrated for conventional (clear-cell) and papillary RCC.