New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.

The Genitourinary Pathology Society (GUPS) reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature. Key prognostic features for clear cell renal cell carcinoma (RCC) remain WHO/ISUP grade, AJCC/pTNM stage, coagulative necrosis, and rhabdoid and sarcomatoid differentiation. Accrual of subclonal genetic alterations in clear cell RCC including SETD2, PBRM1, BAP1, loss of chromosome 14q and 9p are associated with variable prognosis, patterns of metastasis, and vulnerability to therapies. Recent National Comprehensive Cancer Network (NCCN) guidelines increasingly adopt immunotherapeutic agents in advanced RCC, including RCC with rhabdoid and sarcomatoid changes. Papillary RCC subtyping is no longer recommended, as WHO/ISUP grade and tumor architecture better predict outcome. New papillary RCC variants/patterns include biphasic, solid, Warthin-like, and papillary renal neoplasm with reverse polarity. For tumors with 'borderline' features between oncocytoma and chromophobe RCC, a term "oncocytic renal neoplasm of low malignant potential, not further classified" is proposed. Clear cell papillary RCC may warrant reclassification as a tumor of low malignant potential. Tubulocystic RCC should only be diagnosed when morphologically pure. MiTF family translocation RCCs exhibit varied morphologic patterns and fusion partners. TFEB-amplified RCC occurs in older patients and is associated with more aggressive behavior. Acquired cystic disease (ACD) RCC-like cysts are likely precursors of ACD-RCC. The diagnosis of renal medullary carcinoma requires a negative SMARCB1 (INI-1) expression and sickle cell trait/disease. Mucinous tubular and spindle cell carcinoma (MTSCC) can be distinguished from papillary RCC with overlapping morphology by losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. MTSCC with adverse histologic features shows frequent CDKN2A/2B (9p) deletions. BRAF mutations unify the metanephric family of tumors. The term "fumarate hydratase deficient RCC" ("FH-deficient RCC") is preferred over "hereditary leiomyomatosis and RCC syndrome-associated RCC". A low threshold for FH, 2SC, and SDHB immunohistochemistry is recommended in difficult to classify RCCs, particularly those with eosinophilic morphology, occurring in younger patients. Current evidence does not support existence of a unique tumor subtype occurring after chemotherapy/radiation in early childhood.

Evaluation of Apparent Diffusion Coefficient as a Predictor of Grade Reclassification in Men on Active Surveillance for Prostate Cancer.

OBJECTIVE: To evaluate the association between apparent diffusion coefficient (ADC) on initial multiparametric MRI (mpMRI) and biopsy grade reclassification (GR) to grade group (GG) ≥2 prostate cancer (CaP) in men on active surveillance (AS) with GG 1 CaP. METHODS: We retrospectively identified 242 AS patients with reported ADC values on their initial mpMRI. ADC value from the index lesion was assessed as an independent predictor of GR using a Cox model. To ease clinical interpretation, we used a log-rank test to establish an ADC cutoff of 1128 × 10-6 mm2/s for Kaplan-Meier analysis. RESULTS: Of the 242 men, 70 underwent GR following initial mpMRI, of which 26 (37%) had GR at the index lesion. There was no significant difference in the median interval between biopsies for men with and without GR (P >.9). Men with GR had significantly lower median ADC than those without GR (P = .01). In multivariable analysis adjusting for age, prostate-specific antigen density, and National Comprehensive Cancer Network risk group, a 100-unit decrease in ADC was associated with a 12% increase in the risk of GR (HR = 1.12, 95% CI: 1.01-1.22, P = .03). Two- and 4-year rates of freedom from GR were significantly lower for men with ADC <1128 × 10-6 mm2/s vs ADC ≥1128 × 10-6 mm2/s (62% and 42% vs 78% and 68%, respectively; P <.001). CONCLUSION: For AS patients, lower ADC on initial mpMRI index lesion is associated with increased risk of GR to GG ≥2 CaP and would be a useful component of multivariable risk prediction tools.

Defining clinically significant prostate cancer on the basis of pathological findings.

The definition of clinically significant prostate cancer is a dynamic process that was initiated many decades ago, when there was already evidence that a great proportion of patients with prostate cancer diagnosed at autopsy never had any clinical symptoms. Autopsy studies led to examinations of radical prostatectomy (RP) specimens and the establishment of the definition of significant cancer at RP: tumour volume of 0.5 cm3 , Gleason grade 6 [Grade Group (GrG) 1], and organ-confined disease. RP studies were then used to develop prediction models for significant cancer by the use of needle biopsies. The first such model was used to delineate the first active surveillance (AS) criteria, known as the 'Epstein' criteria, in which patients with a cancer Gleason score of 3 + 3 = 6 (GrG1) involving fewer than two cores, and <50% of any given core, and a prostate-specific antigen density of <0.15 ng/ml per cm3 had a minimal risk of significant cancer at RP. These were adopted as components of the 'very-low-risk category' of the National Comprehensive Cancer Network guidelines, in which AS is supported as a management option. With the increase in the popularity of AS, much research has been carried out to better define significant/insignificant cancer, in order to be able to safely offer AS to a larger proportion of patients without the risk of undertreatment. Research has focused on allowing higher volume tumours, focal extraprostatic extension, and a limited amount of Gleason pattern 4, and the significance of different morphological patterns of Gleason 4. Other areas of research that will probably impact on the field but that are not covered in this review include the molecular classification of tumours and imaging techniques.

Older Age Predicts Biopsy and Radical Prostatectomy Grade Reclassification to Aggressive Prostate Cancer in Men on Active Surveillance.

PURPOSE: Age at prostate cancer diagnosis has been positively associated with prostate cancer specific mortality and in men on active surveillance with a higher risk of biopsy grade reclassification to Gleason score 3 + 4 or greater (Grade Group 2 or greater). However, to our knowledge the association between age and biopsy grade reclassification to an aggressive phenotype (Gleason score 4 + 3 or greater [Grade Group 3 or greater]) has not been explored. MATERIALS AND METHODS: From 1995 to 2016 we followed 1,625 men 41 to 81 years old with NCCN® (National Comprehensive Cancer Network®) very low (68%) or low (32%) risk prostate cancer on active surveillance. We determined the rate of biopsy grade reclassification to Grade Group 3 or greater. Competing risk analysis was applied to evaluate the association between age at enrollment and the risk of biopsy grade reclassification. Additionally, in men who underwent radical prostatectomy after biopsy grade reclassification we assessed the rate of radical prostatectomy grade reclassification (ie radical prostatectomy Grade Group greater than biopsy Grade Group). RESULTS: The 5-year incidence of biopsy grade reclassification to Grade Group 3 or greater was 4%, 7% and 14% in men younger than 60, 60 to 69 and 70 years old or older, respectively (p <0.001). On univariate analysis older age was associated with biopsy grade reclassification to Grade Group 3 or greater (per 10-year increase HR 2.43, p <0.001). On multivariable analysis adjusting for year of diagnosis, race, prostate specific antigen density and cancer volume at diagnosis older age remained associated with biopsy grade reclassification to Grade Group 3 or greater (per 10-year increase HR 2.19, p <0.001). In men who underwent radical prostatectomy after biopsy grade reclassification those who were older had a higher rate of radical prostatectomy grade reclassification (p <0.05). CONCLUSIONS: In men on active surveillance older age at diagnosis was positively associated with biopsy grade reclassification to Grade Group 3 or greater and radical prostatectomy grade reclassification. These observations imply that for many older men, active surveillance as opposed to watchful waiting remains a more appropriate management strategy.

Prostatic Adenocarcinoma With Focal Pleomorphic Giant Cell Features: A Series of 30 Cases.

Prostatic adenocarcinoma with focal pleomorphic giant cell features is rare with the only prior series consisting of 6 cases. From 2005 to 2018, we identified 29 cases from our consult service and 1 case from our own institution. Men ranged in age from 39 to 90 years (median=75.5). Diagnostic specimens consisted of needle biopsies (n=13); transurethral resections (n=7), urethral/bladder biopsies (n=8), radical prostatectomy (n=1), and orchiectomy (n=1). In all cases, there was usual acinar prostatic adenocarcinoma, where the highest grade in all cases was Gleason score 9 to 10 (Grade Group 5). On average, 68% of the involved cores had cancer with a maximum percent of cancer averaging 55%; on average, transurethral resections had 85% of the area involved by cancer. Areas of cancer showing pleomorphic giant cell features were focal (<5%). Two of the needle biopsies showed extraprostatic extension. The radical prostatectomy had seminal vesicle invasion and positive margins with lymphovascular invasion. Prostatic adenocarcinoma with focal pleomorphic giant cell features is always accompanied by extensive usual acinar prostate adenocarcinoma where the highest grade in all cases was Gleason score 9 to 10 (Grade Group 5). Although the pleomorphic component is focal, it can mimic urothelial carcinoma. IHC can be misleading as PSA staining is often negative or focal in both the pleomorphic and usual prostatic adenocarcinoma components. NKX3.1 is the most sensitive prostate marker, but was still focal in 1 usual prostatic adenocarcinoma and negative in 2 pleomorphic components. Prostatic adenocarcinoma with focal pleomorphic giant cell features has a dismal prognosis. In men with no prior diagnosis of prostate adenocarcinoma and >1-year follow-up, 7/19 (37%) were dead at a median of 8 months after diagnosis. Of the 7 men with a prior history of prostate adenocarcinoma, 4/7 (57%) were dead at a median of 7 months after diagnosis of recurrent prostate adenocarcinoma with pleomorphic giant cell features.

African-American Men with Gleason Score 3+3=6 Prostate Cancer Produce Less Prostate Specific Antigen than Caucasian Men: A Potential Impact on Active Surveillance.

PURPOSE: We assess the difference in prostate specific antigen production between African-American and Caucasian men with Gleason score 3+3=6 prostate cancer. MATERIALS AND METHODS: We measured tumor volume in 414 consecutive radical prostatectomies from men with National Comprehensive Cancer Network(®) low risk prostate cancer (348 Caucasian, 66 African-American) who had Gleason score 3+3=6 disease at radical prostatectomy. We then compared clinical presentation, pathological findings, prostate specific antigen, prostate specific antigen density and prostate specific antigen mass (an absolute amount of prostate specific antigen in patient's circulation) between African-American and Caucasian men. The t-test and Wilcoxon rank sum were used for comparison of means. RESULTS: African-American and Caucasian men had similar clinical findings based on age, body mass index and prostate specific antigen. There were no statistically significant differences between the dominant tumor nodule volume and total tumor volume (mean 0.712 vs 0.665 cm(3), p=0.695) between African-American and Caucasian men. Prostates were heavier in African-American men (mean 55.4 vs 46.3 gm, p <0.03). Despite the significantly greater weight of benign prostate tissue contributing to prostate specific antigen in African-American men, prostate specific antigen mass was not different from that of Caucasian men (mean 0.55 vs 0.558 µg, p=0.95). Prostate specific antigen density was significantly less in African-American men due to larger prostates (mean 0.09 vs 0.105, p <0.02). CONCLUSIONS: African-American men with Gleason score 3+3=6 prostate cancer produce less prostate specific antigen than Caucasian men. African-American and Caucasian men had equal serum prostate specific antigen and prostate specific antigen mass despite significantly larger prostates in African-American men with all other parameters, particularly total tumor volume, being the same. This finding has practical implications in T1c cases diagnosed with prostate cancer due to prostate specific antigen screening. Lowering the prostate specific antigen density threshold in African-American men may account for this disparity, particularly in selecting patients for active surveillance programs.

Development and clinical validation of an in situ biopsy-based multimarker assay for risk stratification in prostate cancer.

PURPOSE: Prostate cancer aggressiveness and appropriate therapy are routinely determined following biopsy sampling. Current clinical and pathologic parameters are insufficient for accurate risk prediction leading primarily to overtreatment and also missed opportunities for curative therapy. EXPERIMENTAL DESIGN: An 8-biomarker proteomic assay for intact tissue biopsies predictive of prostate pathology was defined in a study of 381 patient biopsies with matched prostatectomy specimens. A second blinded study of 276 cases validated this assay's ability to distinguish "favorable" versus "nonfavorable" pathology independently and relative to current risk classification systems National Comprehensive Cancer Network (NCCN and D'Amico). RESULTS: A favorable biomarker risk score of ≤0.33, and a nonfavorable risk score of >0.80 (possible range between 0 and 1) were defined on "false-negative" and "false-positive" rates of 10% and 5%, respectively. At a risk score ≤0.33, predictive values for favorable pathology in very low-risk and low-risk NCCN and low-risk D'Amico groups were 95%, 81.5%, and 87.2%, respectively, higher than for these current risk classification groups themselves (80.3%, 63.8%, and 70.6%, respectively). The predictive value for nonfavorable pathology was 76.9% at biomarker risk scores >0.8 across all risk groups. Increased biomarker risk scores correlated with decreased frequency of favorable cases across all risk groups. The validation study met its two coprimary endpoints, separating favorable from nonfavorable pathology (AUC, 0.68; P < 0.0001; OR, 20.9) and GS-6 versus non-GS-6 pathology (AUC, 0.65; P < 0.0001; OR, 12.95). CONCLUSIONS: The 8-biomarker assay provided individualized, independent prognostic information relative to current risk stratification systems, and may improve the precision of clinical decision making following prostate biopsy.

Pathological examination of radical prostatectomy specimens in men with very low risk disease at biopsy reveals distinct zonal distribution of cancer in black American men.

PURPOSE: Of men with very low risk prostate cancer at biopsy recent evidence shows that black American men are at greater risk for adverse oncologic outcomes after radical prostatectomy. We studied radical prostatectomy specimens from black and white men at very low risk to determine whether there are systematic pathological differences. MATERIALS AND METHODS: Radical prostatectomy specimens were evaluated in men with National Comprehensive Cancer Network® (NCCN) very low risk prostate cancer. At diagnosis all men underwent extended biopsy sampling (10 or more cores) and were treated in the modern Gleason grade era. We analyzed tumor volume, grade and location in 87 black and 89 white men. For each specimen the dominant nodule was defined as the largest tumor with the highest grade. RESULTS: Compared to white men, black men were more likely to have significant prostate cancer (61% vs 29%), Gleason 7 or greater (37% vs 11%, each p <0.001) and a volume of greater than 0.5 cm(3) (45% vs 21%, p = 0.001). Dominant nodules in black men were larger (median 0.28 vs 0.13 cm(3), p = 0.002) and more often anterior (51% vs 29%, p = 0.003). In men who underwent pathological upgrading the dominant nodule was also more frequently anterior in black than in white men (59% vs 0%, p = 0.001). CONCLUSIONS: Black men with very low risk prostate cancer at diagnosis have a significantly higher prevalence of anterior cancer foci that are of higher grade and larger volume. Enhanced imaging or anterior zone sampling may detect these significant anterior tumors, improving the outcome in black men considering active surveillance.

Prostatic ductal adenocarcinoma: a mini review.

Prostatic ductal adenocarcinomas may arise either in large primary periurethral prostatic ducts or in the peripheral prostatic ducts. Ductal adenocarcinomas are composed of tall columnar cells arranged in cribriform, papillary, solid, single glands, and PIN-like patterns. Other than the prostatic intraepithelial neoplasia (PIN)-like ductal pattern, which behaves like Gleason pattern 3, ductal adenocarcinoma is comparable to Gleason pattern 4 prostate cancer. Ductal adenocarcinoma can have a patchy basal cell layer and typically expresses prostate-specific antigen (PSA) immunohistochemically. Mimickers of ductal adenocarcinoma include prostatic urethral polyps, hyperplastic benign prostate glands, high-grade PIN, colorectal adenocarcinoma, and papillary urothelial carcinoma.

Cytomegalovirus prostatitis: a series of 4 cases.

Cytomegalovirus (CMV) prostatitis is very rare with only 1 report of biopsy-proven CMV prostatitis in the literature. The authors report 4 cases, 3 detected on needle biopsy and 1 detected on transurethral resection. Patients were 36, 41, 48, and 71 years old. All patients were immunosuppressed, including 1 with AIDS and 3 undergoing immunosuppressive therapy following organ transplantation. CMV inclusions were seen in secretory cells of the prostatic glands, endothelial cells of small vessels, and prostatic stromal cells associated with a dense lymphoid inflammation. Only very rarely is CMV prostatitis detected on clinical specimens, typically in immunosuppressed hosts undergoing immunosuppressive therapy following organ transplantation. Patients with CMV prostatitis may harbor multiple infections or have other serious medical conditions adversely affecting their prognosis.

High-grade foamy gland prostatic adenocarcinoma on biopsy or transurethral resection: a morphologic study of 55 cases.

Foamy gland carcinoma is a variant of adenocarcinoma of the prostate that typically is assigned a Gleason score 3+3=6. The morphologic features of high foamy gland carcinoma have not been previously studied. We analyzed 55 cases of high-grade (Gleason score 7 or greater) foamy gland carcinoma of the prostate in needle biopsy (n=49) or transurethral resection (n=6) specimens. The number of cores involved by high-grade foamy gland carcinoma ranged from 1 to 12, with more than 1 core involved in 61% of cases (mean 3.4 cores). On average, 84% of the total tumor volume was foamy gland carcinoma, with high-grade foamy gland cancer averaging 73% of the total foamy gland carcinoma. The following results pertain only to the high-grade foamy gland cancer component. The most common architectural pattern was cribriform (73%), followed by fused/poorly defined glands (55%), cords/single cells (11%), and solid sheets (5%). Nuclear enlargement was observed in 45 of the 55 studied cases (82%). Prominent nucleoli were either absent or infrequent in 38 cases (69%). Frequent to numerous prominent nucleoli were seen more frequently in foamy gland carcinoma with Gleason score 8 or above (52%) than those with Gleason score 7 (16%) (P<0.004). Mitotic figures were observed in 22 cases (40%), and present in 65% of the cases with Gleason score 8 or above, but only in 22% of the cases with Gleason score 7 (P<0.002). In 31 cases (56%), intraluminal dense pink secretions were identified. Perineural invasion and extraprostatic extension identified on the biopsy specimens were noted in 18 cases (33%) and in 5 cases (9%), respectively. In 18 cases (33%), there was at least a moderate stromal reaction. A moderate or greater stromal reaction was seen in 48% (11/23) of the cases with Gleason score 8 or above compared with 22% (7/32) of the cases with Gleason score 7 (P=0.04). In 6 cases, there was a peculiar extensive desmoplastic reaction almost obscuring the carcinoma component, 5 of which were Gleason scores 4+4=8. Concurrent ordinary acinar nonfoamy adenocarcinoma was encountered in 26 of 55 cases (47%) with the following Gleason scores: Gleason 6 (27%); Gleason 7 (27%); and Gleason 8 to 10 (46%). Associated ordinary high-grade prostatic intraepithelial neoplasia and foamy gland variant of high-grade prostatic intraepithelial neoplasia/intraductal adenocarcinoma were seen in 13 cases (24%) and 11 cases (20%), respectively. Of the 19 cases with available immunohistochemical stains for high molecular weight cytokeratin, 7 (37%) showed nonspecific labeling of cancer cells in a nonbasal cell pattern. A similar finding was seen in 1 of the 7 (14%) cases with available stains for p63. Alpha-methyl-CoA racemase positivity was noted in all 9 cases stained. In summary, uncommonly foamy gland carcinoma consists of cribriform, fused/poorly formed glands, cords/single cells, and solid sheets typical of Gleason patterns 4 and 5. High-grade foamy gland cancer shares certain morphologic features with more typical lower-grade foamy gland cancer including relatively bland nuclei with more difficult to identify nucleoli and frequent intraluminal dense pink secretions. However, consistent with their higher architectural grade, high-grade foamy gland cancers had more prominent nucleoli and increased mitotic figures compared with lower-grade foamy gland cancer. A unique subset of high-grade foamy gland carcinoma poses particularly difficult diagnostic challenges, with scattered, scant, relatively bland foamy glands imbedded in an extensive densely sclerotic desmoplastic stroma.

False positive labeling of prostate cancer with high molecular weight cytokeratin: p63 a more specific immunomarker for basal cells.

Occasional nonspecific staining of prostate cancer cells with high molecular weight cytokeratin (HMWCK) can lead to false-negative diagnoses. We compared p63 and HMWCK immunostaining to check their specificity for basal cell identification. Out of 6887 prostate cancer cases sent in consultation to one of the authors over 1.5 years, we identified 22 (0.3%) cases with HMWCK labeling of cancer cells, including 20 needle biopsies and 2 transurethral resections of prostate (TURP). Cases were sent in consultation because of the confusing immunostaining pattern, where prostate cancer cells labeled with HMWCK at the outside institutions. In 6 cases, p63 immunostains were also received from the outside institution, whereas in the remaining 16 cases p63 immunohistochemistry was performed at our institution. In 14 cases, we used either an extra destained hematoxylin and eosin slide or a negative control slide for immunohistochemistry with antibodies to p63, and in the 2 remaining cases submitted unstained slides were used. The Gleason scores were 3+3=6 in 20 cases and 4+4=8 in 2 cases. The size of the tumor on needle biopsy ranged from 0.5 to 6.0 mm (mean 1 mm) and on the 2 TURP cases consisted of 44 and 68 cancer glands, respectively. The number of tumor cells positive for HMWCK in each of the needle biopsy cases ranged from 3 to 48 (mean 13 cells), whereas on the 2 TURP cases 26 and 10 cells were labeled with HMWCK. Corresponding stains for p63 on the same cases were negative in 18 cases. In 3 of 4 cases, p63 labeled 1, 1, and 2 tumor cells, respectively. The fourth case had 5 positive cells on p63 staining with 4 positive for HMWCK. To assess whether overstaining was a factor, we evaluated the intensity of HMWCK staining in the basal cells of the benign glands, which was moderate in 6 and strong in 16 cases. The cytoplasm of benign secretory cells showed focal weak (n=3), diffuse weak (n=1), and focal moderate (n=2) staining for HMWCK. HMWCK labeling of prostate cancer cells is uncommon and does not seem to be solely attributable to overstaining. p63 is a more specific marker for basal cells than HMWCK, with less labeling of tumor cells. Recognition of this phenomenon and performing stains for p63 when it occurs can help prevent underdiagnosing prostatic carcinoma.

Subclassification of clinical stage T1 prostate cancer: impact on biochemical recurrence following radical prostatectomy.

PURPOSE: We investigated biochemical outcomes following radical prostatectomy across subclassifications of clinical stage T1 prostate cancer. MATERIAL AND METHODS: Of 8,658 men who underwent radical prostatectomy for clinical stage T1 prostate cancer 85, 156 and 8,417 had clinical stage T1a, T1b and T1c disease, respectively. Age, race, prostate specific antigen, year of surgery and preoperative Gleason scores were compared across clinical stage T1 subcategories. Time to prostate specific antigen recurrence was compared among groups using Kaplan-Meier and Cox hazards modeling. RESULTS: Patients with clinical stage T1a prostate cancer had more favorable postoperative pathological features, including lower prostatectomy Gleason scores (p <0.001), rates of extraprostatic extension (p <0.001), lymph node invasion (p <0.001) and positive surgical margins (p = 0.006). Patients with T1a cancer also showed significantly lower rates of biochemical recurrence on Kaplan-Meier analysis than men with T1b and T1c disease (log rank 0.006). Cox regression analysis adjusted for known predictors of biochemical recurrence demonstrated that clinical tumor stage in the subgroup of patients with T1 disease was not an independent predictor of biochemical recurrence (p = 0.321). CONCLUSIONS: Men with clinical stage T1a prostate cancer who undergo radical prostatectomy have significantly lower biochemical recurrence rates than men with stage T1b or T1c disease. However, subclassification of tumors in this group of patients was not an independent prognostic factor for biochemical recurrence after accounting for preoperative variables, including prostate specific antigen and Gleason score.

Solitary fibrous tumor on needle biopsy and transurethral resection of the prostate: a clinicopathologic study of 13 cases.

One of the least commonly encountered spindle cell tumors seen on prostatic needle biopsy or transurethral resection (TUR) of the prostate is solitary fibrous tumor (SFT). We studied 13 cases of SFTs identified on either prostate needle biopsy (n=9) or TUR of the prostate (n=4). Mean patient age at diagnosis was 63 years (range: 46 to 75 y; median: 65 y). Twelve men presented with urinary tract symptoms and 1 patient was biopsied during work-up of bone metastases. Ten cases were SFTs originating in the prostate, 2 cases arose between the prostate and rectum extending into the prostate (n=2), and 1 case was a pelvic mass without infiltration of the prostate. In 9 cases, a complete tumor resection was attempted by cystoprostatectomy (n=2), radical prostatectomy (n=4), pelvic exenteration (n=2), or pelvic tumor resection (n=1). Enucleation (n=1) and TUR (n=1) were performed in 2 other cases. Tumor sizes ranged from 8.5 to 15 cm in 7 radically resected cases. Mitotic rates were 3 to 5 per 10 high power fields in 5 cases, with the remaining cases having either rare (n=4) or no mitoses (n=4). Seven cases demonstrated areas of necrosis. Based on a combination of increased cellularity, mitotic activity, necrosis, nuclear pleomorphism, and infiltrativeness, 4 prostatic SFTs were malignant, 4 were benign, and 2 were borderline. Of the 3 non-prostatic SFTs, 1 was malignant and 2 were borderline. All tumors but 1 were immunoreactive for CD34 (n=12). Material for additional immunohistochemistry was available for the majority of cases with positive stains for Bcl-2 (11/11), CD99 (7/10), beta-catenin (5/10), and c-kit (0/11). Three SFTs demonstrated >or=10% p53 immunoreactivity including 1 tumor with 50% positivity; and 3 cases had Ki-67 rates of >or=20%. Although all SFTs were initially clinically considered to be of prostatic origin, some of the cases arose in the pelvis with secondary involvement of the prostate. Approximately 50% of prostatic SFTs were malignant. Even in the prostatic and nonprostatic SFTs with no overt malignant features, sometimes it was necessary to remove the prostate and in some instances the adjacent organs because of the large size of the tumors. SFTs must be differentiated from other spindle cell neoplasms of the prostate especially from gastrointestinal stromal tumors that may arise from the rectal wall with invasion of the prostate or from the region between the rectum and the prostate.

Basal cell carcinoma of the prostate: a clinicopathologic study of 29 cases.

We studied 29 cases of basal cell carcinoma of the prostate including what others call adenoid cystic carcinoma of the prostate. Patients' age ranged from 42 to 89 (mean 69) years. The most common methods of diagnosis was transurethral resection (TURP) (n=29) and needle biopsy (n=9). In 28/29 cases, slides were reviewed and 24 (86%) cases showed more than 1 pattern: adenoid cysticlike (AC-P) pattern and small solid nests with peripheral palisading were the most predominant patterns, each seen in 18 cases (64%). Other patterns included: basal cell hyperplasialike in 9 cases (32%); small tubules occasionally lined by a hyaline rim in 9 cases (32%), with 4 of these cases also demonstrating intermingling cords of cells; and large solid nests in 8 cases (28.5%), 5 of which had central necrosis. Fourteen cases of small nests and tubules were centrally lined by eosinophilic cells. Desmoplasia was noted in 20 (71%) cases. Infiltration around benign glands was seen in 10 (36%) cases, with predominantly small nests and AC-P. Invasion of thick muscle bundles of the bladder neck was seen in 10 of 21 TURP cases. Perineural invasion was noted in 3 cases with AC-P and 1 case of small basaloid nests. Perineural and vascular invasion was seen in 2 basal cell carcinomas with large basaloid nests. Mitoses ranged from 0 to 60/10 hpf (mean=4). bcl2 was diffusely positive in 22/24 (92%) cases. Ki67 ranged from 2% to 80% (mean=23%). Ki67 > or =20% was seen in 13 (56.5%) cases, including all patterns except small solid nests. Basal cell markers (HMWCK, p63) either: (1) highlighted multiple layers of cells in 15/25 (60%) cases with sparing of the inner most luminal layer; (2) labeled just the outermost layers in 6/25 (24%) cases; or (3) reacted with only a few scattered cells in 4/25 (16%) cases (3 with large solid nests with central necrosis, 1 with tubules and cords). Seven patients had RP with: 5/7 showing extraprostatic extension with 1/5 also showing seminal vesicle involvement and 2/5 also with a positive margin; 1/7 having organ confined disease; and 1/7 showing no residual disease. An additional 11 cases showed extraprostatic extension on TURP with bladder neck invasion (n=10) or periprostatic adipose tissue invasion (n=1). Of 29 (65.5%) cases, 19 had follow-up > 1 year with a mean of 4.3 years (1 to 19 y). Of 19 (77%) cases, 14 had no evidence of disease after 1 to 19 (mean 5.8) years. Of 19 patients, 4 locally recurred with 2 after TURP, 1 after enucleation, and 1 after RP. Metastases developed in 4/29 patients: 1 in lung, 1 in lung and liver, 1 in lung, bone and liver, 1 in penile urethra. Basal cell carcinomas are rare tumors with a broad morphologic spectrum. These tumors predominantly show an indolent course with local infiltrative behavior. A small subset behaves aggressively with local recurrences and distant metastases. The most common morphology among those with an aggressive behavior is large solid nests more often with central necrosis, high Ki67%, and less staining with basal cell markers.

Specialized stromal tumors of the prostate: a clinicopathologic study of 50 cases.

Specialized stromal tumors of the prostate encompass stromal sarcoma and stromal tumors of uncertain malignant potential (STUMP). As a result of their relative rarity and lack of long-term follow-up, the prognosis of STUMP is unclear. We studied 50 cases of STUMP and stromal sarcoma with regard to their clinical presentation and follow-up. Patients ranged in age from 27 to 83 years (mean 58 years). The major presenting signs and symptoms were urinary obstructive symptoms (n=25), abnormal digital rectal exam (n=15), hematuria (n=7), hematospermia (n=1), and rectal dysfunction/fullness (n=3). An elevated prostate-specific antigen was either the sole or a compounding rationale for initial urologic examination and prostate biopsy in a subgroup of patients (n=11). The histology in the 36 cases of STUMP not associated with sarcoma were as follows: 25 composed of stroma with scattered cytologically atypical cells associated with benign glands; 8 resembling glandular-stromal hyperplasia but with hypercellular stroma; 6 with extensive myxoid stroma; and 1 with phyllodes pattern. Four of these cases had mixed patterns. Seven cases of STUMP were associated with sarcoma, either concurrently or subsequently. In another 7 cases, pure sarcomas were encountered: 3 low grade (LG) and 4 high grade (HG). In 19 STUMPs, the location of the lesion was determinable: 10 cases arose in the peripheral zone, 7 cases were located in the transition zone, and 2 cases seemed to involve both zones. In 3 of these cases, tumors were adherent to the rectum at the time of resection. There was no evidence of progression of disease for 14 STUMPs after biopsy, TUR, or enucleation where follow-up ranged from 0.3 to 14 years (mean 4.9 years). Five cases of STUMP showed local tumor growth: 1 case increased in size from 6 to 7.5 cm in 3 years and 4 cases recurred frequently necessitating multiple TURs of the prostate (n=2, n=3, n=3, n=3) over 1.1, 2, 7, and 8 years, respectively. Fourteen patients with STUMP underwent radical prostatectomy (RP) soon after diagnosis; of these, 12 were organ confined where the tumor size ranged from 0.7 to 7.5 cm (mean 2.7 cm); 2 cases with a history of a 28 g TUR and a 275 g enucleation showed no residual tumor in the RP specimen. Three cases were lost to follow-up. The histologic subtypes of STUMP did not correlate with the clinical behavior or likelihood of being associated with sarcoma. Two of the LG sarcomas locally invaded around the seminal vesicle, yet all of the LG sarcomas with follow-up were free of disease at 3, 13, 24, 25, 30, and 36 months. Of the 6 HG sarcomas with follow-up, 3 were free of disease at 3, 17, and 72 months. One man was alive with metastasis to the lung 10 months after RP, 1 man was alive at 280 months with multiple metastases, and another died of disease at 115 months. STUMPs can recur frequently, occur at a young age, often involve the peripheral zone where they can be adherent to the rectum requiring its removal, and can be associated with stromal sarcoma. Although STUMPs can be histologically misdiagnosed as nodular hyperplasia, it is important to recognize that these are neoplasms with unique local morbidity and malignant potential. Whereas LG stromal sarcomas can locally invade, HG sarcomas can metastasize and lead to death.

Saw palmetto alters nuclear measurements reflecting DNA content in men with symptomatic BPH: evidence for a possible molecular mechanism.

OBJECTIVES: To examine the nuclear chromatin characteristics of epithelial cells, looking for an SPHB-mediated effect on nuclear DNA structure and organization. Saw palmetto herbal blend (SPHB) causes contraction of prostate epithelial cells and suppression of tissue dihydrotestosterone levels in men with symptomatic benign prostatic hyperplasia, but a fundamental mechanism remains unknown. METHODS: A 6-month randomized trial, comparing prostatic tissue of men treated with SPHB (n = 20) or placebo (n = 20), was performed. At baseline, the two groups were similar in age (65 versus 64 years), symptoms (International Prostate Symptom Score 18 versus 17), uroflow (maximal urinary flow rate 10 versus 11 mL/s), prostate volume (59 versus 58 cm(3)), prostate-specific antigen (4.2 versus 2.7 ng/mL), and percentage of epithelium (17% versus 16%). Prostatic tissue was obtained by sextant biopsy before and after treatment. Five-micron sections were Feulgen stained and quantitatively analyzed using the AutoCyte QUIC-DNA imaging system. Images were captured from 200 randomly selected epithelial cell nuclei, and 60 nuclear morphometric descriptors (NMDs) (eg, size, shape, DNA content, and textural features) were determined for each nucleus. Logistic regression analysis was used to assess the differences in the variances of the NMDs between the treated and untreated prostate epithelial cells. RESULTS: At baseline, the SPHB and placebo groups had similar NMD values. After 6 months of placebo, no significant change from baseline was found in the NMDs. However, after 6 months of SPHB, 25 of the 60 NMDs were significantly different compared with baseline, and a multivariate model for predicting treatment effect using 4 of the 25 was created (P <0.001). The multivariate model had an area under the receiver operating characteristic curve of 94% and an accuracy of 85%. CONCLUSIONS: Six months of SPHB treatment appears to alter the DNA chromatin structure and organization in prostate epithelial cells. Thus, a possible molecular basis for tissue changes and therapeutic effect of the compound is suggested.