Quantitative expression profile of PSGR in prostate cancer.

PSGR is a novel member of the G-protein-coupled olfactory receptor family. Our initial report showed predominant expression of the PSGR in human prostate gland and significant alterations of PSGR expression in primary prostate cancer (CaP) specimens. The aim of this study was to provide in-depth evaluations of the expression profile of PSGR in prostatic epithelial cells of CaP patients and to evaluate the association of PSGR expression characteristics with clinico-pathologic features. In total, 220 RNA specimens, from laser capture microdissected paired benign and malignant prostatic epithelial cells of 110 CaP patients, were analyzed for PSGR expression by quantitative real-time PCR. The differential expression of PSGR between the prostatic epithelial cells of malignant and benign glands was statistically significant (P<0.0001). Comparison of PSGR expression between paired benign and tumor cells revealed prostate tumor cell-specific overexpression in 67.2% of tumor specimens (74 of 110), decreased expression in 20.9% of tumor specimens (23 of 110) and no difference of PSGR expression between tumor and normal cells in 11.8% of specimens (13 of 110). In representative cases, PSGR expression patterns were independently confirmed by in situ RNA hybridization. The PSGR overexpression associated with higher percentage of pathologic stage, pT3, and a higher level of preoperative serum PSA. CaP cells of African-American CaP patients exhibited about two-fold increase of PSGR expression in comparison to the Caucasian American CaP patients. Strikingly high-percentage CaP cells overexpress PSGR warrants further studies of PSGR expression alterations to define subsets of CaPs.

Classification of canine urinary bladder urothelial tumours based on the World Health Organization/International Society of Urological Pathology consensus classification.

One hundred canine urinary bladder urothelial (transitional cell) tumours, including roughly equal numbers of benign and malignant forms, were retrospectively categorized in accordance with the newly described human consensus classification of the World Health Organization/International Society of Urological Pathology (WHO/ISUP). The tumours were reviewed and classified by three veterinary pathologists from Michigan State University and two human pathologists from the Armed Forces Institute of Pathology (AFIP). The current human WHO/ISUP classification system was considered to be readily applicable to the dog. Canine tumours, however, differed from human tumours in that the great majority showed extensive glandular differentiation (or metaplasia) and hyperplastic lesions tended to be more florid than those seen in human beings. The various diagnoses and grades assigned to the tumours were highly consistent between all reviewing pathologists. This paper presents the salient features of the new WHO and ISUP consensus classification and provides illustrations of the various tumour types that were directly applicable to the dog.

Percentage of embryonal carcinoma and of vascular invasion predicts pathological stage in clinical stage I nonseminomatous testicular cancer.

We analyzed 92 clinical stage I nonseminomatous testicular germ cell tumors for primary tumor histological factors that would distinguish true pathological stage I disease (N = 54) from those patients who harbored occult disease and actually were later found to have pathological stage II disease (N = 38). Primary tumor pathological material was analyzed for vascular invasion, lymphatic invasion, tunical invasion, and quantitative determination of percentage of the primary tumor composed of embryonal carcinoma, yolk sac carcinoma, teratoma, and seminoma. Univariate logistic regression analyses revealed that vascular invasion (P = 0.0001), percentage of embryonal carcinoma (P = 0.0001), lymphatic invasion (P = 0.0001), and tunical invasion (P = 0.0013) were higher in pathological stage II and that percentage of teratoma (P = 0.0001) and of yolk sac carcinoma (P = 0.0174) were higher in stage I. Percentage of seminoma was not significant. Individually, these parameters were able to correctly predict occult disease 66.3 to 80.4% of the time. In multivariate logistic regression analysis, only vascular invasion and percentage of embryonal carcinoma remained significant, and a model using these two variables was able to correctly predict stage 85.9% of the time. Vascular invasion and determination of percentage of embryonal carcinoma should be assessed for all clinical stage I nonseminomatous germ cell tumor patients and the model presented herein can be used clinically to predict the likelihood of occult disease and dictate therapy.

Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China.

The length of the polymorphic CAG trinucleotide repeat in the polyglutamine region of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Because increased androgenic activity has been linked to prostate cancer and because an ethnic variation exists in the CAG repeat length, this polymorphism has been suggested to explain part of the substantial racial difference in prostate cancer risk. We conducted a population-based case-control study in China to investigate whether CAG and other polymorphisms of the AR gene are associated with clinically significant prostate cancer in this low-risk population. Genomic DNA from 190 prostate cancer patients and 304 healthy controls was used for direct sequencing to evaluate the relationship of CAG and GGN (polyglycine) repeat length in the AR gene. Relative to western men, our study subjects had a longer CAG repeat length, with a median of 23 and only 10% of the subjects having a CAG repeat length shorter than 20. Men with a CAG repeat length shorter than 23 (median length) had a 65% increased risk of prostate cancer (odds ratio, 1.65; 95% confidence interval, 1.14-2.39), compared with men with a CAG repeat length of 23 or longer. For the GGN tract (GGT3GGG1GGT2GGCn), based on the sequencing results from 481 samples, we are the first to show that although GGC regions in the polyglycine tract are highly variable, there are no mutations or polymorphisms in the GGT and GGG regions. More than 72% of the subjects had a GGN repeat length of 23, and those with a GGN repeat length shorter than 23 had a 12% increased risk of prostate cancer (95% confidence interval, 0.71-1.78), compared with those with > or = 23 GGN repeats. Our study not only confirms that Chinese men do have a longer CAG repeat length than western men but also represents the first population-based study to show that even in a very low-risk population, a shorter CAG repeat length confers a higher risk of clinically significant prostate cancer. These results imply that CAG repeat length can potentially serve as a useful marker to identify a subset of individuals at higher risk of developing clinically significant prostate cancer. Larger studies are needed to evaluate the combined effect of CAG and GGN repeats. Because of the significance of AR in prostate cancer, investigation of factors that interact with the polyglutamine region of the AR gene to alter AR function and modulate prostate cancer risk is an important area for future research.

Vitamin D receptor gene polymorphisms, insulin-like growth factors, and prostate cancer risk: a population-based case-control study in China.

Operating through the vitamin D receptor (VDR), vitamin D inhibits prostate cancer growth and increases insulin-like growth factor binding protein (IGFBP) expression, suggesting that the vitamin D and insulin-like growth factor (IGF) regulatory systems may operate together to affect prostate cancer. Among 191 newly diagnosed prostate cancer cases and 304 randomly selected population controls in Shanghai, China, we found no significant association between the BsmI or FokI VDR gene polymorphisms and prostate cancer risk. However, we found that among men with the ff FokI genotype, those in the highest tertile of plasma IGFBP-3 had a decreased risk versus those in the lowest tertile (odds ratio, 0.14; 95% confidence interval, 0.04-0.56; P(trend) < 0.01), whereas among men with the FF and Ff genotypes, IGFBP-3 was not associated with risk. Similarly, IGFBP-1 was inversely associated with prostate cancer risk only among men with the ff FokI genotype (odds ratio, 0.25; 95% confidence interval, 0.07-0.85; P(trend) = 0.02). No such FokI genotype-specific effects were observed for IGF-I or IGF-II. Our findings in a low-risk population suggest that the IGF and vitamin D regulatory systems may interact to affect prostate cancer risk. Larger studies are needed to confirm these findings and clarify the underlying mechanisms.

Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers.

Prostatic tissue specimens derived from transurethral resections of patients with metastatic prostate cancer were analyzed for genetic alterations in the hormone-binding domain of the androgen receptor (AR) gene. Direct sequencing of the polymerase chain reaction-derived DNAs of 6 of 24 specimens revealed a codon 877 mutation (ACT-->GCT, Thr-->Ala) in the hormone-binding domain of the AR gene. This same AR mutation has been reported previously in a metastatic prostate cancer cell line, LNCaP, where this mutation confers upon the AR an altered ligand-binding specificity which is stimulated by estrogens, progestagens, and antiandrogens. It is possible that analogous to an activated/altered growth factor receptor oncogene, codon 877 mutant AR with altered ligand binding may provide a selective growth advantage in the genesis of a subset of advanced prostate cancer. Although estrogens are used infrequently, antiandrogens are used increasingly in hormonal therapy for patients with advanced prostate cancer. The stimulatory effect of these therapeutic agents on the codon 877 mutant AR further suggests that this frequently observed AR mutation may contribute to the treatment refractory disease.

PSGR, a novel prostate-specific gene with homology to a G protein-coupled receptor, is overexpressed in prostate cancer.

PSGR, a new prostate tissue-specific gene with homology to the G protein-coupled odorant receptor gene family, has been identified. Here we report the characteristics of the predicted protein sequence of PSGR and its prostate tissue specificity and expression profile in human prostate cancer and matched normal tissues. Using multiple tissue Northern blots from over 50 different tissues, PSGR expression was restricted to human prostate tissues. Paired normal and tumor specimens from 52 primary prostate cancers, obtained by laser capture microdissection or manual microdissection, were analyzed for PSGR expression by semiquantitative and real-time PCR assays. The differential expression of PSGR between normal and tumor tissues was highly significant (P < 0.001), and 32 of 52 (62%) matched prostate specimens exhibited tumor-associated overexpression of PSGR. Of note, there was very little or no expression of PSGR in many normal specimens in comparison with the generally high expression of PSGR seen in matched tumor specimens. In situ hybridization assays showed restricted PSGR expression in the epithelial cells of the normal and tumor tissue sections. Restricted expression of PSGR in prostatic epithelial cells, overexpression of the PSGR in a significant percentage of prostate cancers, and the predicted protein sequence of PSGR with seven transmembrane domains provide a foundation for future studies evaluating the potential of PSGR as a prostate cancer gene expression marker and the utility of PSGR protein as a novel target for developing immunotherapeutic strategies for prostate cancer.

A novel human cancer culture model for the study of prostate cancer.

Research into molecular and genetic mechanisms underlying prostate carcinogenesis would be greatly advanced by in vitro models of prostate tumors representing primary tumors. We have successfully established an immortalized human prostate epithelial (HPE) cell culture derived from a primary tumor with telomerase. The actively proliferating early passaged RC-58T cells were transduced through infection with a retrovirus vector expressing the human telomerase catalytic subunit (hTERT). A high level of telomerase was detected in RC-58T/hTERT cells but not RC-58T cells. RC-58T/hTERT cells are currently growing well at passage 50, whereas RC-58T cells senesced at passage 7. RC-58T/hTERT cells exhibit transformed morphology. More importantly, these immortalized cells showed anchorage-independent growth as they formed colonies in soft agar and grew above the agar layer. Expression of androgen-regulated prostate specific gene NKX3.1 and epithelial specific cytokeratin 8 (CK8) but not prostate specific antigen (PSA) and androgen receptor was detected in RC-58T/hTERT cells. Prostate stem cell antigen (PSCA) and p16 were also expressed in this cell line. RC-58T/hTERT cells showed growth inhibition when exposed to retinoic acid and transforming growth factor (TGF)-beta1 known potent inhibitors of prostate epithelial cell growth. A number of chromosome alterations were observed including the loss of chromosomes Y, 3p, 10p, 17p, 18q and the gain of chromosomes 16 and 20. These results demonstrate that this primary tumor-derived HPE cell line retained its transformed phenotypes and should allow studies to elucidate molecular and genetic alterations involved in prostate cancer. This is the first documented case of an established human prostate cancer cell line from a primary tumor of a prostate cancer patient with telomerase.

Prognosis and other clinical correlates of pathologic review in stage I and II testicular carcinoma: a report from the Testicular Cancer Intergroup Study.

PURPOSE: The Testicular Cancer Intergroup Study (TCIS) was undertaken to evaluate the pathologic findings in early-stage testicular cancer as determined by central pathology review, to compare these findings with the interpretation by the contributing pathologists, and to make correlations with various clinical parameters and outcomes. PATIENTS AND METHODS: The prospective study of non-seminomatous germ cell testicular cancer staged surgically involved 459 eligible patients with stage I (node-negative) or stage II (node-positive) disease. Pathologic materials from both the orchiectomy and lymphadenectomy specimens were submitted to a central laboratory for evaluation. RESULTS: Central and local pathologists differed significantly in their identification of certain cellular histologies (primarily yolk sac tumors [YST]) and recognition of invasion into vascular structures. In contrast to our prior findings with local pathologic assessment, venous/lymphatic invasion as determined by central review predicted relapse in both stages. In pathologic stage I disease, the relapse rate was 19.4% (12 of 62 cases) for those with invasion versus 6.0% (10 of 168 cases) for those without invasion. In pathologic stage II disease, the respective relapse rates were 63.5% (40 of 63 cases) and 24.0% (six of 25 cases). Vascular invasion was jointly predictive with nodal stage for risk of relapse. The percentage of embryonal carcinoma (EC) in the primary tumor was predictive of nodal stage and relapse in a univariate, but not a multivariate, analysis. In a large substudy, immunohistochemical staining identified a correlation between stain intensity in YST and serum alpha-fetoprotein (AFP) levels. In a similar fashion human chorionic gonadotropin (HCG) staining reactivity occurred exclusively in patients with syncytiotrophoblasts and correlated with serum levels of beta-HCG. CONCLUSIONS: A number of tumor histology correlates with clinical parameters have been identified or confirmed. Careful pathologic scrutiny of the primary testicular tumor, especially for vascular invasion, provides important prognostic information.

Risk of prostate cancer and family history of cancer: a population-based study in China.

We evaluated prostate cancer risk and family history of cancers using data from a case-control study in China. Cancer information among first-degree relatives was collected from 709 subjects (238 cases and 471 controls). None of the subjects reported a family history of prostate cancer. However, excess prostate cancer risk was associated with a family history of any cancer (OR = 1.79, 95% CI: 1.21-2.63) and esophageal cancer (OR = 2.39, 95% CI: 1.15-5.00). Nonsignificant risk was seen for family history of cancers of the stomach, lung, and female breast. Our results did not confirm the familial tendency toward prostate cancer but other cancers prevalent in China appeared to be aggregate, particularly esophageal cancer. Larger studies are needed to confirm these findings, and to clarify the genetic and lifestyle factors that may be involved.

p53 nuclear protein expression is an independent prognostic marker in clinically localized prostate cancer patients undergoing radical prostatectomy.

Immunohistochemical (IHC) staining for p53 protein nuclear expression was evaluated in archival paraffin-embedded radical prostatectomy specimens from 139 patients with clinically localized prostate cancer followed up from 1 to 8 (mean, 4) years. Elevated nuclear p53 protein expression was detected in 85 (61%) of 139 patients, being heterogeneous and focal in the majority of specimens. Only four specimens displayed homogeneous nuclear accumulation of p53 protein. Disease progression, most commonly prostate-specific antigen elevation, was noted in 46 (33%) patients, with 39 (85%) having positive p53 protein IHC stains. Conversely, 93 (67%) of 139 have not recurred, with 46 (49%) having positive p53. Of all 54 p53-negative patients, 47 (87%) have had no disease recurrence. An increased p53 protein IHC stain was associated with a higher pathological stage (T1 and T2, 51% versus >/=T3, 69%) and Gleason score 2-4, 17%; 5-7, 72%; and 8-10, 87.5%). Despite these associations, p53 IHC staining was an independent predictor of disease-free survival in a multivariate analysis of p53, age, race, stage, and grade. This study revealed that a majority of clinically localized prostate cancers heterogeneously express elevated nuclear levels of p53 protein in at least a subset of malignant cells, and that this expression is an independent predictor of disease progression in prostate cancer patients after radical prostatectomy.

Leydig cell hypoplasia causing male pseudohermaphroditism: diagnosis 13 years after prepubertal castration.

An 11-yr-old patient with male pseudohermaphroditism who was castrated at nine days of age and raised thereafter as a female was evaluated to determine the cause of abnormal sexual differentiation. Stimulation with ACTH for 8 h revealed no abnormality in the biosynthesis of cortisol or adrenal androgens. The administration of fluoxymesterone (10 mg, orally, daily) for 5 weeks at age 13 yr led to significant decrements in serum levels of sex steroid-binding globulin and T4-binding globulin to a degree similar to that found in 2 normal men, but no change in the basally elevated levels of FSH and LH. LH bioactivity was normal in the rat Leydig cell bioassay. Skin fibroblasts cultured from a labial skin biopsy revealed normal 5 alpha-reductase activity and normal androgen receptors. Reexamination of the original testis specimens by light microscopy failed to reveal Leydig cells. Furthermore, when immunoperoxidase staining for testosterone was performed on the tissue sections, only 30-35 positive cells/10 high power fields were seen. In contrast, examination of testis sections from 4 male infants who died of other causes revealed 94-836 cells/10 high power fields that stained positively for testosterone. Although hCG stimulation testing to confirm Leydig cell hypoplasia could not be done in this patient because of previous castration, this patient demonstrates that the diagnosis can be made without it by the use of immunohistochemical stains and in vivo and in vitro tests to exclude other disorders of androgen biosynthesis or androgen action.

Body size and prostate cancer: a population-based case-control study in China.

We conducted a population-based case-control study in China to investigate whether body size plays a role in prostate cancer etiology and whether it can explain the rapid increase in prostate cancer incidence rates in China. A total of 238 cases newly diagnosed with primary prostate cancer in Shanghai, China, during 1993-1995 were included in the study. Four hundred and seventy-one healthy control subjects were randomly selected from among residents of Shanghai and frequency-matched to cases on the basis of age. In-person interviews were conducted to elicit information on height, weight history, and other lifestyle factors. Waist and hip circumferences were measured at interview. Odds ratios (ORs) were used to measure the association between prostate cancer and anthropometric variables including height, weight, body mass index (BMI), waist, hip, and right upper arm circumferences, and waist-to-hip ratio (WHR; an indicator of abdominal adiposity). High levels of WHR were related to an excess risk, with men in the highest quartile (WHR > 0.92) having an almost 3-fold risk (OR, 2.71; 95% CI = 1.66-4.41; Ptrend = 0.0001) compared with men in the lowest quartile (WHR < 0.86). In contrast, men in the highest quartile of hip circumference (>97.4 cm) had a reduced risk (OR, 0.46; 95% CI = 0.29-0.74; Ptrend = 0.0002) relative to men in the lowest quartile (<86 cm). No association was found for height, usual adult weight, or preadult and usual adult BMI. Our results suggest that even in a very lean population (average BMI = 21.9), abdominal adiposity may be associated with an increased risk of clinical prostate cancer, pointing to a role of hormones in prostate cancer etiology. Additional research is needed to confirm these findings in prospective studies, especially in Western populations where abdominal obesity is much more common, and to clarify the underlying hormonal mechanisms involved.

Polymorphic markers in the SRD5A2 gene and prostate cancer risk: a population-based case-control study.

It has been suggested that the activity of the steroid 5alpha-reductase type II enzyme (encoded by the SRD5A2 gene) may be associated with prostate cancer risk and that population differences in this enzyme's activity may account for part of the substantial racial/ethnic disparity in prostate cancer risk. To provide etiological clues, we evaluated the relationships of four polymorphic markers in the SRD5A2 gene, specifically, A49T (a substitution of threonine for alanine at codon 49), V89L (a substitution of leucine for valine at codon 89), R227Q (a substitution of glutamine for arginine at codon 227), and a (TA)n dinucleotide repeat, with prostate cancer risk in a population-based case-control study in China, a population with the lowest reported prostate cancer incidence rate in the world. Genotypes of these four markers were determined from genomic DNA of 191 incident cases of prostate cancer and 304 healthy controls using PCR-based assays, and serum androgen levels were measured in relation to these genotypes. All study subjects had the wild-type AA genotype of the A49T marker, and 99% had the RR genotype of the R227Q marker. For the V89L marker, prevalences of the LL, VV, and VL genotypes among controls were 35%, 21%, and 45%, respectively. Compared with men with the VV genotype, those with the LL genotype had a statistically nonsignificant 12% reduced risk (odds ratio = 0.88, 95% confidence interval, 0.53-1.47). In addition, men with the LL genotype had significantly higher serum levels of testosterone and significantly lower serum levels of 5alpha-androstane-3alpha,17beta-diol glucuronide than men with other genotypes. Men heterozygous for the (TA)0 allele of the (TA)n marker had a modest, statistically nonsignificant risk reduction (odds ratio = 0.67; 95% confidence interval, 0.39-1.12) compared with men homozygous for the (TA)0 allele, along with significantly higher serum dihydrotestosterone levels. The observed V89L genotype prevalences and the association between V89L genotypes and serum androgen levels support the hypothesis that genotypes associated with lower levels of 5alpha-reductase activity are more common in low-risk populations. Although we found no statistically significant associations of these SRD5A2 polymorphisms with prostate cancer risk, a small effect of these markers cannot be ruled out because of the rarity of certain marker genotypes. Larger studies are needed to further clarify the role of these markers and to elucidate whether genetic diversity of the SRD5A2 gene, alone or in combination with other susceptibility genes, can help explain the large racial/ethnic differences in prostate cancer risk.

Insulin-like growth factors and prostate cancer: a population-based case-control study in China.

Insulin-like growth factors (IGFs) have potent mitogenic and antiapoptotic effects on prostate epithelial cells. Through modulation of IGF bioactivity and other mechanisms, IGF-binding proteins (IGFBPs) also have growth-regulatory effects on prostate cells. Recently, IGF-I and IGFBP-3 have been implicated in prostate cancer risk among Western populations. To assess whether IGF-I, IGF-II, IGFBP-1, or IGFBP-3 are also associated with prostate cancer in a low-risk population, we measured plasma levels of these factors among 128 newly diagnosed prostate cancer cases and 306 randomly selected population controls in Shanghai, China. Relative to the lowest quartile of IGF-I levels, men in the highest quartile had a 2.6-fold higher prostate cancer risk, with a significant trend [odds ratio (OR) = 2.63; 95% confidence interval (95% CI) = 1.19-5.79; P(trend) = 0.01]. In contrast, men in the highest quartile of IGFBP-3 levels had a 46% decreased risk relative to the lowest quartile (OR = 0.54; 95% CI = 0.26-1.15; P(trend) = 0.08). A similar but less distinct result was observed for IGFBP-1 (OR = 0.60; 95% CI = 0.31-1.17; P(trend) = 0.25). Men in the highest quartile for the IGF-I:IGFBP-3 molar ratio (an indirect measure of free IGF-I) had a 2.5-fold higher risk compared with the lowest quartile (OR = 2.51; 95% CI = 1.32-4.75, P(trend) < 0.001). These associations were more pronounced after adjustment for serum 5alpha-androstane-3alpha,17beta-diol glucuronide and sex hormone-binding globulin levels. There was no significant association with IGF-II levels. Our findings in a low-risk population provide evidence that IGF-I, IGFBP-3, and IGFBP-1 are determinants of prostate cancer and indicate that additional studies are needed to evaluate their effects on ethnic and geographic incidence differentials and to elucidate carcinogenic mechanisms.

Renal medullary carcinoma. The seventh sickle cell nephropathy.

Over the last 22 years, we have encountered 34 examples of a highly aggressive neoplasm with a microscopic morphology that is highly predictive of finding sickled erythrocytes in the tissue. With the exception of one patient, all are believed to have had sickle cell trait or, in one case, hemoglobin SC disease. These 33 patients are the subject of this report and, where their race was known, they were all blacks between the ages of 11 and 39 years. Between the ages of 11 and 24 years, males predominated by 3 to 1. Beyond age 24, however, the tumors occurred equally in men and women. The dominant tumor mass was in the medulla and ranged from 4 to 12 cm in diameter. Mean size was 7 cm; median, 6 cm. Peripheral satellites in the renal cortex and pelvic soft tissues, as well as venous and lymphatic invasion, were usually present. The lesions exhibited a reticular, yolk sac-like, or adenoid cystic appearance, often with poorly differentiated areas in a highly desmoplastic stroma admixed with neutrophils and usually marginated by lymphocytes. The tumors had usually metastasized when first discovered, and none was confined to the kidney at the time of nephrectomy. The mean duration of life after surgery was 15 weeks. These tumors probably arise in the calyceal epithelium in or near the renal papillae, the same site that produces the more familiar picture of unilateral hematuria in patients with sickle cell trait. We have concluded that renal medullary carcinoma represents another example of renal disease associated with sickle cell disorders. The other six are unilateral hematuria, papillary necrosis, nephrotic syndrome, renal infarction, inability to concentrate urine, and pyelonephritis.

Bile duct adenoma. A study of 152 cases.

In order to determine the morphologic spectrum of bile duct adenoma (BDA), we reviewed the clinical, gross, and histopathological features of 152 cases. All BDA were asymptomatic nodules discovered incidentally during intra-abdominal surgery (103 cases) or at autopsy (49 cases). They were usually subcapsular, ranged in size from 1 to 20 mm (mean, 5.8 mm), and were well circumscribed but nonencapsulated. Histologically, BDA was composed of benign, noncystic ductules and variable degrees of inflammation and fibrosis. The immunophenotype of these ductules was similar to that of interlobular bile ducts. Follow-up of 38 of the surgically treated patients confirmed the benign behavior of this lesion. BDA should be distinguished from an adenocarcinoma by the absence, in the former, of nuclear hyperchromasia, mitotic activity, and vascular invasion. The absence of bile and cystic changes and lack of association with polycystic disease of the liver and kidneys are the main features distinguishing BDA from von Meyenburg complex. We believe that BDA is a reactive process to a focal injury rather than a true neoplasm or a developmental anomaly.

Metanephric adenoma. Clinicopathological study of fifty patients.

We report 50 examples of an uncommon type of renal adenoma from the files of the Armed Forces Institute of Pathology. They appear to be benign tumors with no malignant potential, and their chief importance is related to the fact that they are most often misinterpreted as renal cell carcinoma or epithelial Wilms' tumor. They predominated in females by well over 2:1. The mean age of the patients was 41 years, with a range of 5 to 83 years, and the mean size was 5.5 cm, with a range of 0.3 to 15.0 cm. Presenting signs and symptoms included pain in 11, hematuria in five, and palpable mass in five. In 20 patients the tumors were found incidentally during evaluation for other problems, and in six the other problem was polycythemia. This finding establishes a higher incidence of polycythemia in renal adenoma than in other previously reported renal diseases. Also of preoperative importance is the fact that these tumors are more commonly calcified than other renal neoplasms. Microscopically, these tumors consist of very small epithelial cells that form very small acini in an acellular stroma. Less often, they form tubular, glomeruloid, or polypoid and papillary formations. Most also show evidence of regression in the form of scarring and calcification. These lesions seem histogenetically related to epithelial Wilms' tumor, and, in fact, the two may occur together. They are histologically very similar to the metanephric hamartomatous element of nephroblastomatosis.

A distinctive myointimal proliferation ('myointimoma') involving the corpus spongiosum of the glans penis: a clinicopathologic and immunohistochemical analysis of 10 cases.

This study details the clinicopathologic and immunohistochemical features associated with 10 cases of a distinctive myointimal proliferation involving the corpus spongiosum of the glans penis. Patients ranged in age from 2 to 61 years old (mean age, 29 yrs) and presented with a mass that varied in size from 0.5 to 1.9 cm in greatest dimension. The process was said to be present from 4 days to more than 6 months before surgical intervention. In each case, microscopic examination revealed almost identical histology. There was a prominent, often occlusive, fibrointimal proliferation with plexiform architecture involving the vasculature of the corpus spongiosum. The proliferation consisted of stellate-shaped and spindled cells embedded in abundant fibromyxoid matrix. Occasional lesional cells had well-developed myoid characteristics with moderately abundant eosinophilic cytoplasm, blunt-ended nuclei, and juxtanuclear vacuoles. Foci with degenerative changes, including "ghost cell" morphology, were also present. The myointimal process was extensively immunoreactive for alpha-smooth muscle actin, muscle-specific actin (HHF-35), and calponin, but it was minimally reactive for the D33 and D-ER-11 desmin clones. In contrast, native vascular smooth muscle encompassing the proliferation was strongly immunoreactive for all five markers. The myointimal cells were nonreactive for CD34, S-100 protein, and keratin. Factor VIIIrAg, CD31, and CD34 highlighted intact endothelial cells lining suboccluded vessels, scattered capillaries that penetrated the proliferation, and the normal uninvolved vasculature. The examined specimens were punch, incisional, or excisional biopsies, and in each instance, the process microscopically extended to the tissue margin. Follow-up data are available for 8 cases (median follow-up interval, 5 yrs 8 mos): one incompletely excised lesion with 6 months follow-up is stable but persistent, one lesion with 10 years follow-up regressed spontaneously after a punch biopsy, and the remaining six lesions have not recurred. A differential diagnosis of myofibroma, late-stage intravascular (nodular) fasciitis, vascular leiomyoma, and plexiform fibrohistiocytic tumor is discussed.

Smooth muscle hyperplasia of the testicular adnexa clinically mimicking neoplasia: clinicopathologic study of sixteen cases.

Sixteen cases of a largely unrecognized benign cause for an intrascrotal mass are reported herein. These cases represent a nonneoplastic excess of native smooth muscle in the paratestis or spermatic cord growing between or around vessels or efferent ducts. The patients ranged in age from 46 to 81 years, with a mean age of 63 years. The size, available in 10 of the cases, ranged from 6 mm to 7 cm, with a mean of 2.5 cm; there was no side predilection. Microscopically, the lesions consisted of fascicles of smooth muscle, growing in a periductal, perivascular, interstitial, or mixed pattern. The cohesive, interlacing growth pattern of a leiomyoma was missing in all cases. The cause of this lesion is not apparent, although microscopic epididymal or vas deferens duct ectasia in some cases suggests a possible obstructive etiology. In any case, these are benign and without clinical significance after excision and correct diagnosis. Follow-up was available in 13 patients with no recurrences observed from 1 month to 16 years postoperatively.