Does subdivision of the "atypical" urine cytology increase predictive accuracy for urothelial carcinoma?

Urine cytology is routinely used for early diagnosis and monitoring of patients with hematuria or a history of urothelial carcinoma, but its clinical utility is greatly diminished by a high frequency of "atypical" specimens, reportedly around 20% in the literature. We compared our results with double-stained urine cytology specimens (papanicolaou and acid hematoxylin stains) with published results with only a single or double papanicolaou stain. The acid hematoxylin stain enhanced nuclear chromatin staining, eliminated significant background debris, and improved visibility of diagnostic cells in the presence of obscuring blood. Medical records of all urine cytologies received between 2005 and 2012 in our laboratories were reviewed. The study group consisted of all cases with bladder biopsy follow-up within one year of cytology. Of 43,131 urine cytologies diagnosed in our laboratories, biopsy follow-up results were available within one year in 10,473 cases, including 852 for symptoms and 1,461 for follow-up of bladder cancer. An additional 6,427 cases had cystoscopy results in which no biopsy was obtained. Cases were classified as negative (81.6%), atypical, favor reactive (2.9%), atypical, favor neoplastic (7.3%), suspicious (5.7%), and malignant (2.5%), with subsequent frequencies for urothelial cancer on biopsy of 13.3%, 31.1%, 37.6%, 53.6%, and 74.3%, respectively. No significant difference was found if atypical was subdivided into two categories: favor reactive and favor neoplastic. Subdivision of the atypical category did not improve diagnostic accuracy. Addition of the acid hematoxylin stain decreased the incidence of atypical urine cytologies from about 20% to 10.2%.

Participation of functionally active plasma cells in acute rejection and response to therapy in renal allografts.

Acute rejection (AR) includes T-cell-mediated and antibody-mediated rejection. The inflammatory infiltrate comprised not only T cells but also varying amounts of B cells (CD20(+)) and plasma cells (CD138(+)). The latter are associated with poor clinical outcomes, but their functional status is not clear. The phosphorylation of the S6 ribosomal protein (p-S6RP) is present in cells that are metabolically active, thus identifying functionally active antibody-secreting plasma cells. This study was designed to evaluate the clinical significance of functionally active p-S6RP plasma cells in AR in renal allografts. Renal allografts with biopsy evidence of AR during 2006-2009 were included. Immunohistochemistry staining for CD20, CD138, and p-S6RP was performed on paraffin-embedded slides and scaled as 0-6. The response to antirejection treatment was assessed by the serum creatinine ratio (CrR) at rejection episode (time 0) and following treatment (4 and 12 weeks). Patients with lower scores (0-2) were compared with a higher scored group (3-6). The T-test was conducted using statistical significance of p<0.05. A total of 28 patients (40.7 ± 14.3 year; M:F=15:13) were diagnosed with acute T-cell-mediated rejection (I and II). The p-S6RP staining in the high-score group had a significantly higher CrR (p<0.05) than the low-score group at the time of biopsy, 4 and 12 weeks following treatment. There was no significant difference in the CrR between groups for CD20 or CD138 staining. Functional antibody-secreting p-S6RP plasma cells are actively participating in AR and associated with poor response to treatment in renal allografts.

Urinary ß2-Microglobulin Is a Good Indicator of Proximal Tubule Injury: A Correlative Study with Renal Biopsies.

Objective. After filtration through glomeruli, ß2-microglobulin is reabsorbed in proximal tubules. Increased urinary ß2-microglobulin indicates proximal tubule injury and measurement of ß2-microglobulin in urine is useful to determine the source of renal injury. Kidney injury molecule-1 (KIM-1) has been characterized as a selective proximal tubule injury marker. This study was designed to evaluate the correlation of urinary ß2-microglobulin concentration and KIM-1 expression as evidence of proximal tubule injury. Methods. Between 2009 and 2012, 46 patients with urine ß2-microglobulin (RenalVysion) had follow-up kidney biopsy. Diagnoses included glomerular and tubule-interstitial disease. Immunohistochemical staining for KIM-1 was performed and the intensity was graded from 0 to 3+. Linear regression analysis was applied to correlate the values of urinary ß2-microglobulin and KIM-1 staining scores. P < 0.05 was considered statistically significant. Results. Thirty patients had elevated urinary ß2-microglobulin. KIM-1 staining was positive in 35 kidney biopsies. There was a significant correlation between urinary ß2-microglobulin and KIM-1 staining (P < 0.05). Sensitivity was 86.6%, specificity was 43.7%, positive predictive value was 74.2%, and negative predictive value was 63.6%. Conclusion. Increased urinary ß2-microglobulin is significantly correlated with KIM-1 staining in injured proximal tubules. Measurement of urine ß2-microglobulin is a sensitive assay for proximal tubule injury.

Does polyomavirus infection interfere with bladder cancer fluorescence in situ hybridization?

Urine cytology is a proven and widely used screening tool for the detection of urothelial carcinoma. However, morphologic features of polyomavirus infected cells, characterized by nuclear inclusions (decoy cells) are a known source of diagnostic confusion with malignancy. Fluorescence in situ hybridization (FISH) is now routinely used to support the cytological diagnosis of urothelial carcinoma and monitor for recurrence. We sought to determine whether polyomavirus infection could result in positive FISH results (aneuploidy). This study deals with retrospective study of 100 polyomavirus-infected urine samples from patients with no history of urothelial carcinoma or organ transplantation. All cases were stained with Papanicolaou and acid hematoxylin stain. One slide from each sample was de-stained and FISH was performed using chromosome enumeration probes 3, 7, 17, and locus-specific probe 9p21. Adequate cells for FISH analysis (25 cells) were present in 81 cases; 19 cases were insufficient due to loss of cells during de-staining and FISH preparation process. All polyomavirus-infected cells (decoy cells) exhibited a normal chromosome pattern. Four cases were FISH positive, but there were no positive decoy cells. Decoy cells did not exhibit aneuploidy by FISH. The presence of decoy cells does not exclude the possibility of concurrent urothelial carcinoma. Acid hematoxylin stain appeared to supplement the Papanicolou stain in identifying and confirming the presence of polyomavirus infection.

Differentiation of melanoma and benign nevi by fluorescence in-situ hybridization.

Malignant melanoma is sometimes difficult to distinguish from benign nevus, and ancillary confirmatory studies would be of value in selected cases. To accurately differentiate melanoma from benign nevus, we investigated the utility of chromosomal anomalies in skin biopsy specimens using multitargeted fluorescence in-situ hybridization (FISH). Skin biopsy specimens were retrospectively collected from 63 patients diagnosed with benign compound nevus (n=32) or malignant melanoma (n=31); each diagnosis was independently confirmed before study by a second dermatopathologist. Unstained tissue sections were hybridized for 30 min using fluorescence-labeled oligo-DNA probes for chromosomes 6, 7, 11, and 20. Fluorescent signals for each chromosome were enumerated in 30 cells per case. Numeric chromosomal anomalies were found in 0% (0 of 32) of normal epidermis, 6% (two of 32) of compound nevi, and 94% (29 of 31) of melanomas (nevus vs. melanoma, P<0.0001). The mean number of cells with chromosomal changes was 23 in melanoma specimens, significantly higher than that in compound nevi (P<0.0001). The most frequent chromosomal anomaly in melanoma was gain of chromosome 11, followed consecutively by gains of chromosomes 7, 20, and 6. Chromosomal anomalies detected by FISH had an overall sensitivity of 94% and specificity of 94% in the separation of nevus and melanoma. With the use of oligo-DNA probes, multitargeted FISH directed against chromosomes 6, 7, 11, and 20 is highly sensitive and specific for separation of nevus and melanoma. Unlike other traditional FISH probes, oligo-DNA probes required shorter hybridization time, allowing faster diagnostic evaluation.

Detection of chromosomal anomalies in endometrial atypical hyperplasia and carcinoma by using fluorescence in situ hybridization.

BACKGROUND: Endometrial cancer is the most common pelvic gynecological malignancy. The diagnosis of well-differentiated endometrial adenocarcinoma, atypical hyperplasia, and hyperplasia is often challenging. The authors sought to investigate the utility of chromosomal anomalies for the detection of endometrial hyperplasia and carcinoma using multitarget fluorescence in situ hybridization (FISH). METHODS: Samples were collected by endometrial Tao brush and processed by liquid-based cytological preparation protocol from consecutive cases to include 50 benign, 50 hyperplasia without atypia, 47 atypical hyperplasia, and 53 endometrial cancers. Each was hybridized using fluorescence-labeled DNA probes to chromosomes 1, 8, and 10. The FISH signals were enumerated in 100 cells per case, and the chromosomal anomalies were correlated with pathologic findings, including histologic diagnoses on matched endometrial tissue samples. RESULTS: Numeric chromosomal anomalies were found in 0% (0 of 50) of benign, 20% (10 of 50) of hyperplasia, 74% (35 of 47) of atypical hyperplasia, and 87% (46 of 53) of carcinoma specimens. The mean percentage of cells with chromosomal changes was 55% in cancer specimens, which was significantly higher than that in hyperplasia without atypia (13%, P < .0001) and atypical hyperplasia (32%, P = .003). The most frequent chromosomal anomaly was gain of chromosome 1. FISH anomalies had an overall sensitivity of 81% and specificity of 90% for the detection of atypical hyperplasia and/or endometrial carcinoma. There was no association with grade of endometrial carcinoma. CONCLUSIONS: Multitarget FISH appears to be useful for the differential diagnosis of hyperplasia, atypical hyperplasia, and endometrial adenocarcinoma, with a high level of sensitivity and specificity. It is also a potential tool for the early detection of neoplastic cells in endometrial cytology specimens. Endometrial hyperplasia with FISH-detected chromosomal anomalies may represent a clinically significant subset of cases that warrant close clinical follow-up.

Precursor of prostate-specific antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 90 cases.

OBJECTIVE: To assess the expression of the precursor of prostate-specific antigen (pro-PSA), a distinct molecular form of serum-free PSA that includes native and truncated forms, in benign epithelium, high-grade prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma. MATERIALS AND METHODS: We immunohistochemically evaluated 90 formalin-fixed, paraffin-embedded prostate needle biopsies using monoclonal antibodies against [-2] pro-PSA, native [-5/-7] pro-PSA, prostate-specific membrane antigen (PSMA), PSA and racemase. Staining intensity was recorded using a scale of 0-3 (0, no staining; 3, highest staining). The percentage of immunoreactive cells in benign epithelium, high-grade PIN and adenocarcinoma was estimated in increments of 10%. RESULTS: All cases had [-5/-7] pro-PSA immunoreactivity. There was weak focal perinuclear cytoplasmic immunoreactivity for [-5/-7] pro-PSA in 62% (range 0-90%) of benign epithelial cells, whereas there was strong diffuse cytoplasmic staining in 83% (range 10-90%) of high-grade PIN and 87% (range 40-90%) of cancer cells. Almost all (99%) cases were immunoreactive for [-2] pro-PSA. The median (range) proportion of cells expressing [-2] pro-PSA was lower in benign epithelium, at 17 (0-80)%, than in high-grade PIN, at 55 (0-90)% (P < 0.001) and adenocarcinoma, at 55 (0-100)% (P < 0.001). The intensity of immunoreactivity for both isoforms increased from benign to neoplastic (high-grade PIN and adenocarcinoma) epithelium. A total of 31% of high-grade PIN and 11% of cancer cases with negative racemase staining showed strong staining for [-5/-7] pro-PSA. CONCLUSION: The expression of [-5/-7] pro-PSA in benign and neoplastic cells might be used in combination with high molecular weight keratin, p63, and racemase to distinguish benign epithelium from high-grade PIN and adenocarcinoma, particularly when racemase staining is negative. Both isoforms are sensitive markers for prostatic epithelium, making them possible candidates for investigating carcinoma with an unknown primary, particularly in cases in which PSA staining is negative and the level of suspicion is high.

Prostatic stromal hyperplasia with atypia: follow-up study of 18 cases.

CONTEXT: Prostatic stromal hyperplasia with atypia is a rare lesion that can be mistaken for sarcoma because of the presence of atypical, bizarre, degenerative myocyte nuclei. OBJECTIVE: To determine the diagnostic criteria and clinical significance of prostatic stromal hyperplasia with atypia. DESIGN: Eighteen cases of prostatic stromal hyperplasia with atypia were reviewed from the consultation file of one of the authors (D.G.B.). RESULTS: Prostatic stromal hyperplasia with atypia consists of 1 or more ill-defined, uncircumscribed, hyperplastic stromal nodules, with variable numbers of atypical, bizarre giant cells, with vacuolated nuclei, smudged chromatin, and frequent multinucleation infiltrating around benign acini. There was a hypocellular, loose, myxoid stromal matrix, with ectatic hyalinized vessels and mild to moderate chronic inflammation. Stromal cells displayed intense immunoreactivity for androgen receptors and vimentin, but moderate reactivity for desmin and actin. There were 3 local recurrences, with a mean follow-up of 6.3 years (range, 0.5-14 years), but none developed evidence of sarcomatous transformation or malignancy. CONCLUSIONS: Prostatic stromal hyperplasia with atypia is a rare, benign lesion, composed of degenerative myocytes with atypia that is histologically and clinically reminiscent of benign counterparts in the myometrium, breast, vulva, vagina, and elsewhere. Recognition of this distinctive entity should allow separation from phyllodes tumor and sarcoma of the prostate. The phrase stromal tumor of uncertain malignant potential is inappropriate for this benign tumor, and its use is discouraged.

Prostatic leiomyoma with atypia: follow-up study of 10 cases.

We studied the clinical and histologic features of 10 cases of prostatic leiomyoma with atypical bizarre nuclei. Immunohistochemical studies were undertaken in 6 cases. Patient follow-up was obtained in all cases. Patients ranged in age from 50 to 82 years (mean, 65 years) and presented with urinary obstructive symptoms in 7 cases, abnormal digital rectal examination in 3 cases. The histologic findings consisted of a solid circumscribed expansile stromal nodule with abundant smooth muscle and variable numbers of atypical bizarre giant cells. The cells of the tumor displayed intense immunoreactivity for desmin, actin, and androgen receptor and weak to moderate reactivity for vimentin. Four local recurrences were seen, with a follow-up for 3 to 16 years (mean, 7.4 years), but no evidence of sarcomatous transformation occurred. Despite worrisome histologic appearance, a benign clinical behavior was seen in all cases.

Preoperative prediction of unifocal, unilateral, margin-negative, and small volume prostate cancer.

OBJECTIVES: Contemporary prostate carcinoma is frequently of small volume and early stage. Subtotal gland ablation by minimally invasive therapies such as cryotherapy demands preoperative prediction of unifocal, unilateral, margin-negative, and small volume (less than 0.5 mL) cancer. METHODS: We examined matched biopsy and prostatectomy and clinical data from 393 patients at two institutions who underwent surgery in 2000 through 2003. Radical prostatectomy specimens were uniformly sectioned at 5-mm intervals and completely embedded. Numerous clinical and biopsy variables were correlated by regression analysis with unifocal, unilateral, margin-negative, and 0.5 mL or less volume cancer in the prostatectomy specimen. Odds ratios (OR) were determined. RESULTS: At prostatectomy, 92 (23%) had unifocal cancer, 90 (23%) had unilateral cancer, 348 (89%) had organ-confined cancer, and 106 (31%) had small volume cancer. Unilateral cancer occurred in 71% to 76% of cases of unilateral cancer in the biopsy (OR, 4.30; if 9 or more cores were sampled, OR rose to 6.83), and was predicted by unifocality in the biopsy (OR, 2.63). Unifocal cancer was predicted by unilateral (OR, 2.66) but not unifocal, cancer present in the biopsy. Negative surgical margins were predicted by unilateral (OR, 2.53; positive predictive value, 82%) cancer in the biopsy and by serum prostate specific antigen (OR, 5.33). Small volume cancer was predicted by unilateral (OR, 5.50) and unifocal (OR, 7.98) cancer in the biopsy; Gleason score greater than 7 predicted a non-small volume cancer (OR, 7.52). CONCLUSIONS: Unilateral or unifocal cancer on biopsy are among the strongest predictors of unilateral, unifocal, and small volume prostate cancer in contemporary practice.

Trials of new germ cell immunohistochemical stains in 93 extragonadal and metastatic germ cell tumors.

Organic cation transporter 3/4 (OCT3/4) is a transcription factor of embryonic stem cells; c-kit (CD117) is a tyrosine kinase receptor implicated in seminoma carcinogenesis. Their reactivity is well characterized in testicular, but not extragonadal and metastatic, germ cell tumors. A total of 93 germ cell tumors (41 seminoma, 22 embryonal carcinoma, 18 teratoma, and 12 yolk sac tumor) were obtained from the central nervous system (30), mediastinum (23), retroperitoneum/abdomen (31), and other locations (9). Immunohistochemical staining for c-kit, placental-like alkaline phosphatase (PLAP), OCT3/4, and new markers D2-40 and AP-2gamma was performed on seminomas; CD30 and epithelial membrane antigen were added for nonseminomas. In embryonal carcinoma, c-kit reacted in 17 of 22 cases, OCT3/4 in 18 of 22, and PLAP in 13 of 22. OCT3/4 was superior to PLAP in intensity and percent cells staining. In seminoma, OCT3/4 and D2-40 were superior to PLAP in intensity and percent cells; c-kit and AP-2gamma were superior in percent cells. D2-40 stained 23 of 24 seminomas strongly but had only weak focal reactivity in 6 of 17 embryonal carcinomas. Sensitivity and specificity were high for OCT3/4 discriminating seminoma and embryonal carcinoma, and c-kit discriminating seminoma, from other germ cell tumors. For embryonal carcinoma, OCT3/4 had higher specificity (0.94) than CD30 (0.786) owing to CD30 reactivity in 3 of 10 teratomas. Epithelial membrane antigen discriminated teratoma from other nonseminomas with a sensitivity of 1 but reacted occasionally in embryonal carcinoma (3/15) and yolk sac tumor (2/7). In conclusion, for extragonadal seminoma, OCT3/4, AP-2gamma, D2-40, and c-kit were equivalently superior to PLAP. For embryonal carcinoma, OCT3/4 was superior to PLAP and more specific than CD30. D2-40 is recommended to discriminate between seminoma and embryonal carcinoma.

Improved filter method for urine sediment detection of urothelial carcinoma by fluorescence in situ hybridization.

CONTEXT: Fluorescence in situ hybridization (FISH) of voided urine sediment is a sensitive and specific test for the detection of urothelial carcinoma. The time required for slide preparation using the conventional cytospin method is lengthy. OBJECTIVE: To present an alternative to the conventional cytospin method. DESIGN: We compared the results of an improved filter monolayer method with published results of the conventional cytospin method. A total of 624 patients with cytology and FISH analyses were followed with cystoscopy and/or bladder biopsy. Fluorescence in situ hybridization analysis was performed on 624 cases using fluorescence-labeled probes to the pericentromeric regions of chromosomes 3, 7, and 17 and band 9p21; cytology was also performed in all cases. RESULTS: A total of 217 (34.7%) of 624 patients had follow-up bladder biopsies, and 170 of these (78.3%) had urothelial carcinoma. The sensitivity for cancer detection was higher for FISH than for urine cytology (92.9% [158/ 170] for FISH vs 72.9% [124/170] for urine cytology, P = <5%). The specificity was equivalent for FISH and urine cytology (97.5% [443/454] for FISH vs 92.2% [419/454] for cytology). The sensitivity for FISH was better (92.9% vs 81%), and there was no significant difference in specificity (97.5% vs 96%) between the filter method and the conventional cytospin method. Unlike the conventional cytospin method, the filter method did not require multiple centrifugation and decantation steps or investment in dedicated equipment. CONCLUSIONS: The improved filter method was faster, easier, and less expensive than published results with the conventional cytospin method with better sensitivity and equivalent specificity.

Appropriateness of testicular cancer management: a population-based cohort study.

OBJECTIVE: Testicular cancer is a highly curable malignancy of young men. Appropriate and timely management is critical to ensure optimal clinical outcomes. A 3-year population-based review of testicular cancer patients in Manitoba, Canada was undertaken to evaluate our management patterns. METHODS: Men diagnosed with testicular cancer from 1998 to 2000 were identified from the Provincial Cancer Registry. Chart review was utilized to collect information on demographic characteristics, timelines of diagnostic and staging investigations, completeness of pathology reports, management, and outcomes. RESULTS: Seventy-eight men were identified with 80 testicular cancers: 46 (59%) patients had 48 seminomas and 32 (41%) had non-seminomatous germ cell tumors (NSGCT). One or more pre-operative tumor markers were missing or unavailable in 41 (52%) cases. Median time from scrotal ultrasound to orchiectomy was 7 days, but was greater than 2 weeks in 13 (16%) patients. Pathology reports provided acceptable detail in only 21 (27%) cases. Eighteen subjects (23%) did not complete necessary staging investigations (chest and abdominal imaging, and post-orchiectomy markers) until at least 3 weeks after surgery. Post-orchiectomy management of both seminoma and NSGCT patients was largely within acceptable limits apart from some non-standard chemotherapy choices in advanced stage disease, and significant departures from standard recommendations regarding surveillance. The Kaplan-Meier estimate of overall survival at 5 years is 97% in seminoma and 84% in NSGCT. CONCLUSIONS: Although clinical outcomes do not appear to have been compromised, deficiencies are evident in testicular cancer management in Manitoba from 1998 to 2000, indicating the need for well-defined management guidelines and improved education of caregivers.

Small lung tumors: long-scan-time CT for planning of hypofractionated stereotactic radiation therapy--initial findings.

PURPOSE: To prospectively use long-scan-time computed tomography (CT) to visualize the trajectory of tumor movements or the internal target volume. MATERIALS AND METHODS: The study was approved by the institutional review board. Written informed consent was obtained from participants after the study and the role of procedures were explained fully. During the planning of stereotactic radiation therapy for 10 patients (nine men, one woman; mean age, 77 years; range, 69-89 years) with small lung tumors (mean volume, 9.0 cm3; range, 3.6-24.9 cm3), fluoroscopic imaging, long-scan-time CT, and thin-section CT were performed. The tumor and the partial-volume-averaging effects that resulted from tumor movement were delineated on each section at long-scan-time CT performed during the patient's steady breathing with scan time of 8 seconds per image. Visualized internal target volume was defined by integrating the sections. A simple model was examined for estimating internal target volume on the basis of respiratory motion and gross target volume delineated on thin-section CT images. Visualized internal target volume and estimated internal target volume were compared quantitatively and graphically. The Mann-Whitney test was used to analyze the relation between gross target volume delineated on thin-section CT images and the ratio of visualized internal target volume to the defined gross target volume. RESULTS: The correlation coefficient between visualized internal target volume and estimated internal target volume was r = 0.98 (P < .001). The mean relative error +/- standard deviation was 1.9% +/- 19.0 (range, -11.0% to 56.4%). Excluding one case with an irregularly shaped tumor (56.4%), the mean relative error was -4.1% +/- 4.1. In patients with small tumors (defined gross target volume, < or = 10 cm3), the ratio of the visualized internal target volume to the defined gross tumor volume was significantly larger than that in patients with larger tumors (1.2-2.0 vs 1.0-1.2; P < .05). In some cases in which marginal spiculation depicted on thin-section CT images was blurred on long-scan-time CT images, the blurred area was erroneously excluded from the target volume. CONCLUSION: In most cases, values for visualized internal target volume and estimated internal target volume were similar and long-scan-time CT depicted virtually the entire tumor trajectory.

Phyllodes tumor of the prostate: long-term followup study of 23 cases.

PURPOSE: Phyllodes tumor of the prostate is a rare neoplasm of uncertain malignant potential. We studied a large series of phyllodes tumors to define the combination of histological features that are most useful for predicting patient outcome. MATERIALS AND METHODS: A total of 23 cases were obtained from our collective files from 1973 to 2002, and numerous clinical and pathological features were evaluated. A review of the reported cases of phyllodes tumor of the prostate was done. RESULTS: Patient age was 25 to 86 years (mean 55) and they usually presented with urinary obstructive symptoms and hematuria. The diagnosis was made in 18 tumors by transurethral resection, in 2 by enucleation, in 1 by tumor resection and in 2 by prostatectomy. We analyzed 5 histological features, including cellularity (scale of 1 to 3), cytologic atypia (scale of 1 to 3), the number of mitotic figures per 10 high power fields, the stroma-to-epithelium ratio (low or high) and necrosis (present or absent). This combination of features revealed that 14 cases were low grade phyllodes tumor, 7 were intermediate grade and 2 were high grade with the high grade cases characterized by increased cellularity, severe cytological atypia, more than 5 mitotic figures per 10 high power fields and a high stroma-to-epithelium ratio, indicating stromal overgrowth. Immunohistochemical studies of 8 tumors revealed consistent, intense cytoplasmic immunoreactivity in stromal cells for vimentin and actin, in luminal epithelial cells for prostate specific antigen, prostatic acid phosphatase and broad-spectrum keratin AE1/AE3, and in basal cells for high molecular weight keratin 34beta-E12. Recurrence was seen in 7 of 14 low grade tumors (50%) and in 1 patient low grade sarcoma emerged with subsequent distant metastases 14 years after initial diagnosis following 5 recurrences. Recurrence was seen in 6 of 7 intermediate grade tumors and low grade sarcoma emerged with subsequent abdominal wall metastases in 1 patient 11 years after initial diagnosis following 3 recurrences. The phyllodes tumor recurred in each patient with high grade tumors with a time to first recurrence of 6 and 0.2 years, respectively. Distant metastases developed in these 2 patients. CONCLUSIONS: Histological grading of prostatic phyllodes tumors is predictive of short-term outcome based on the combination of stromal cellularity, cytological atypia, number of mitotic figures and the stroma-to-epithelium ratio. However, these tumors usually recur after transurethral prostatic resection and they are often locally aggressive with time. The emergence of overt sarcoma and metastatic disease is more frequent than previously recognized. Complete resection at initial diagnosis appears to be indicated.

Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases.

Adenoid cystic/basal cell carcinoma (ACBCC) of the prostate has been considered to have indolent biologic potential. However, outcome data are scant, with only one documented metastasis and death. We describe clinicopathologic features of ACBCC in 19 patients and document outcome in 15. Patients ranged in age from 43 to 83 years. All but one presented with urinary obstruction. ACBCC was diagnosed by transurethral resection in 15 cases, by needle biopsy in 3 cases, and unexpected in 1 case. Four patients had concurrent acinar adenocarcinoma. Histologically, cribriform or adenoid cystic patterns predominated in 12 cases and basal cell carcinoma pattern in 7. Five cases had prominent perineural invasion. ACBCC was immunoreactive for p63 and cytokeratins 7 and 34 beta E12 but not cytokeratin 20. After diagnosis, 5 patients underwent radical prostatectomy, 2 underwent pelvic exenteration, and the rest had no treatment. ACBCC showed extraprostatic extension in 5 cases and involved the bladder margin in 3. Metastases developed in 4 (21%) patients: liver (2), lung (2), bowel (1), and corpus cavernosum (1). In 15 cases with follow-up (0.3-11.8 years), two patients died of cancer (at 1.5 and 3 years after diagnosis), 3 remain alive with cancer, and 10 have no evidence of cancer. Thus, ACBCC of the prostate is a potentially aggressive neoplasm requiring ablative therapy.