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D G Bostwick

Publications and source records attributed to D G Bostwick.

At least 181 records · Page 10Linked to original sources

Identification of a novel transcript up-regulated in a clinically aggressive prostate carcinoma.

OBJECTIVES: To identify differentially expressed genes in tumor cells of patients with prostate cancer by means of tissue microdissection and targeted differential display. METHODS: RNA was recovered from pure populations of microdissected normal epithelium and invasive tumor from frozen tissue sections of a radical prostatectomy specimen. Reverse transcription-polymerase chain reaction (PCR) using arbitrary and zinc finger PCR primers was performed. RESULTS: A 130-base pair product was identified that appeared selectively in the tumor sample. DNA sequence analysis revealed it to be a clone from the expressed sequence tag database (GenBank accession R00504). Microdissection of normal epithelium and the corresponding invasive tumor was subsequently performed on a test panel of 10 prostate carcinoma specimens. Comparison of R00504 levels in normal epithelium and invasive carcinoma, using beta-actin as an internal control, showed the transcript to be substantially overexpressed in 5 of 10 carcinomas. Northern blotting revealed R00504 to be a 2.6-kilobase gene. CONCLUSIONS: A novel transcript up-regulated in an aggressive prostate carcinoma was identified using degenerate zinc finger primers in microdissected tissue samples. The approach used in this study may be helpful in quantitative comparison of known genes and identification of novel genes in microdissected human tissue samples.

Humans↗

High-power (60-watt) potassium-titanyl-phosphate laser vaporization prostatectomy in living canines and in human and canine cadavers.

OBJECTIVES: We studied the safety and efficacy of 60-W potassium-titanyl-phosphate (KTP) laser prostatectomy in living dogs and compared the efficacy with that in fresh human and dog cadavers. METHODS: Ten dogs underwent 60-W KTP laser prostatectomy and were sacrificed 3 hours (n = 5) or 7 weeks (n = 5) after operation. Two thawed fresh-frozen human cadaver prostates and two thawed fresh-frozen canine prostates were also vaporized with the 60-W KTP laser. All prostates were weighed, measured, serially sectioned, and whole mounted for histologic analysis. RESULTS: In dogs, the in vivo procedure was hemostatic, and no irrigant absorption was detected. Prostatic defects with a mean diameter of 3.0 and 2.5 cm at 3 hours and 7 weeks postoperatively, respectively, were produced. With experience, resection time was reduced to 14 minutes. Of the 5 dogs that were studied for 7 weeks, 4 voided immediately after removal of the urethral catheter on the morning after operation, and 1 dog required recatheterization but voided with a strong stream when the urethral catheter was removed 4 days later. All 5 dogs were continent and had normal erectile function postoperatively. Defects of 2.0 and 2.5 cm were produced in the two human cadaver prostates (weight, 29.5 and 55 g) with resection times of 26 and 54 minutes, respectively. Human and canine cadaver prostates required similar energies for tissue vaporization (15.2 and 13.7 kJ/cm3 cavity created, respectively, P > 0.6), whereas living canine prostates required only 7.0 kJ/cm3 cavity created (P < 0.01 compared with cadaver tissue). CONCLUSIONS: The 60-W KTP laser allows technically easy, safe, rapid, and hemostatic removal of canine prostatic tissue in vivo. Furthermore, there is no difference in the efficacy of KTP laser vaporization between human and canine cadaver prostates. These findings suggest that KTP laser vaporization may be as effective in living human prostates as it is in living dogs, and thus it may be a useful technique in the surgical treatment of human benign prostatic hyperplasia.

Animals↗

Clinical significance of high-grade prostatic intraepithelial neoplasia in transurethral resection specimens.

OBJECTIVES: High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of invasive prostatic adenocarcinoma. The incidence and clinical significance of this lesion have not been previously defined in specimens from transurethral resections of the prostate (TURP). METHODS: To determine the frequency of PIN in TURP specimens and its relationship with adenocarcinoma, we reviewed 698 resections performed at Mayo Clinic between 1989 and 1990. A mean of 6 slides was analyzed for each case (range 1 to 36). The presence, extent, and architectural pattern of PIN were recorded. The results were correlated with many clinical and pathologic features, including patient age, Gleason score, stage, serum prostate-specific antigen (PSA) concentration, and patient follow-up. In a 1:2 nested matching case-control study, we compared the outcome of cases with PIN alone with that of the control group. Each patient with PIN alone (16 patients) was matched randomly with 2 patients with benign prostatic hyperplasia (BPH) alone (32 patients) according to age (+/- 5 years) and serum PSA concentration (+/- 1 ng/mL). RESULTS: Of 698 TURP specimens, 570 (81.7%) contained BPH and 128 (18.3%) contained adenocarcinoma and BPH. High-grade PIN was identified in 29 cases (4.2%), including 16 (2.8%) of those with BPH and 13 (10.2%) of those with cancer and BPH. Follow-up revealed adenocarcinoma in 3 of 14 patients (21.4%) with PIN and BPH only after 3, 5, and 7 years, respectively; mean follow-up for the 14 patients was 6 years (range 4 to 7 years), and none of the patients died of prostate cancer. Conversely, none of the patients (0%) without PIN in TURP specimens in the case-control study had subsequent adenocarcinoma. CONCLUSIONS: The overall incidence of PIN in TURP specimens was 4.2%, including 2.8% without cancer and 10.2% with coexistent cancer. Prostatic adenocarcinoma was diagnosed within 7 years in 21.4% of patients with PIN in TURP specimen. Conversely, none of those without PIN matched for age and serum PSA had adenocarcinoma at follow-up. These results indicate that high-grade PIN is uncommon in TURP specimens and, when found, indicates a significant risk of cancer. The presence of PIN in TURP specimens should be reported by the pathologist; in addition, the entire specimen should be submitted for histologic examination to exclude carcinoma.

Adenocarcinoma↗

Intestinal metaplasia is not a strong risk factor for bladder cancer: study of 53 cases with long-term follow-up.

OBJECTIVES: Intestinal metaplasia often coexists with adenocarcinoma of the urinary bladder, suggesting to some investigators that it is premalignant. However, the natural history and long-term outcome of intestinal metaplasia in isolation are unknown. We report 53 cases of intestinal metaplasia of the urinary bladder followed for more than 10 years. METHODS: We reviewed the Mayo Clinic surgical pathology files between 1926 and 1996 and all patients with exstrophic bladder recorded in the files of the Hospital for Sick Children (Toronto, Ontario, Canada) and Dallas Children's Hospital (Dallas, Texas) between 1953 and 1987, and identified all patients with intestinal metaplasia of the bladder. RESULTS: A total of 53 cases were identified from both series, and none of the patients developed adenocarcinoma of the bladder. The Mayo Clinic series consisted of 24 patients. Nineteen of the 24 (79.1%) were alive without evidence of cancer (median follow-up 14 years, range 0.9 to 53), and 5 patients died of intercurrent disease (at 0.9, 4, 8, 11, and 53 years after diagnosis) without evidence of bladder cancer. The Dallas Children's Hospital and the Hospital for Sick Children series consisted of 29 patients. Twenty-seven of the 29 (93.1%) were alive without evidence of cancer (median follow-up 13 years, range 3 to 23.9). Two patients died of trauma (at 10.9 and 12 years after diagnosis) and at autopsy had no evidence of bladder cancer. CONCLUSIONS: Intestinal metaplasia of the urinary bladder is not a strong risk factor for adenocarcinoma or urothelial cancer.

Adenocarcinoma↗

Low-grade collecting duct carcinoma of the kidney: report of 13 cases of low-grade mucinous tubulocystic renal carcinoma of possible collecting duct origin.

OBJECTIVES: To assess the nature of a series of unusual low-grade mucin-producing tubulocystic renal cancers diagnosed at the Mayo Clinic since 1985. METHODS: We reviewed the clinical, radiologic, and pathologic features of 13 unusual low-grade renal carcinomas with features most suggestive of collecting duct origin. RESULTS: In 8 cases, the tumor was discovered incidentally. Presenting symptoms in the other 5 patients were similar to those of typical renal carcinoma. Imaging studies and angiography disclosed solid, cystic, or complex masses that were relatively avascular. Pathologic assessment revealed good circumscription, minimal hemorrhage and/or necrosis, minimal tendency to extend beyond the kidney, tubulocystic architecture, a fibrotic interface with adjacent normal renal parenchyma, low nuclear grade, and minimal mitotic activity. Mucin production was noted in all evaluable cases. All tumors expressed keratins AE1/AE3 and/or Cam 5.2. The tumors showed immunoreactivity to antibodies directed against keratin 34 beta E12 (8 of 13 cases), and Ulex Europeus antigen 1 (6 of 10 cases). Follow-up ranged from 12 to 114 months (mean 62). No metastases occurred in 12 patients. One patient died of metastatic carcinoma morphologically identical to the primary renal neoplasm 46 months after his tumor had been misinterpreted as a benign condition. CONCLUSIONS: We believe the tumors described in this article may be of collecting duct origin, representing the low-grade end of a spectrum of cancers arising in collecting duct epithelium.

Adenocarcinoma, Mucinous↗

Anatomic site-specific positive margins in organ-confined prostate cancer and its impact on outcome after radical prostatectomy.

OBJECTIVES: The impact of a positive surgical margin in otherwise confined prostate cancer after radical prostatectomy remains unclear. We analyzed the outcome of a large number of patients with organ-confined prostate cancer according to the presence and anatomic site of margin positivity. METHODS: We evaluated 2712 prostatectomy patients with Stage pT2N0 cancer (ie, no evidence of extra-prostatic disease, seminal vesicle or regional node involvement) and no prior therapy who were treated by radical prostatectomy between 1987 and 1995 at Mayo Clinic. A total of 697 patients (26%) had positive margins. To assess the effect of margin status in the absence of treatment, 378 patients with postoperative adjuvant therapy were not considered for the study group: the final group consisted of 2334 patients. RESULTS: Overall, 253 (58%) tumors were positive at the apex and/or urethra, 85 (19%) at the prostate base, 11 (2.5%) at the anterior prostate, and 174 (40%) at the posterior prostate; 89 (20%) had at least two margins involved and 21 (8.3%) had more than two involved. The apex/urethra was the only positive anatomic site in 183 (42%). Five-year survival free of clinical recurrence or prostate-specific antigen (PSA) biochemical failure (postoperative serum PSA of 0.2 ng/mL or more) for patients with a single positive margin was 79% for apex or urethra, 78% for anterior/posterior, and 56% for prostate base. Five-year survival free of clinical recurrence or PSA (biochemical) failure was slightly higher for those with one versus two margin-positive regions (77% versus 68%, respectively). Multivariate analysis revealed that positive surgical margins were a significant predictor of clinical recurrence and PSA (biochemical) failure (relative risk [95% confidence interval]: 1.65 [1.24, 2.18]) after controlling for Gleason grade, preoperative PSA, and deoxyribonucleic acid (DNA) ploidy. The effect of margin positivity on recurrence at a specific anatomic site (versus negative margins or positive at a different anatomic site) revealed the prostate base to be the only significant anatomic site when adjusted for grade, PSA, and ploidy. Five-year survival free of the combined clinical or PSA failure end point for those with versus those without positive margins at the prostate base was 56% versus 85%, respectively (P < 0.0001). CONCLUSIONS: Positive surgical margins are a significant predictor of recurrence in Stage pT2N0 cancer, which is independent of grade, PSA, and DNA ploidy. The impact of positive margin status on recurrence-free survival appears to be anatomic and site-specific, with prostate base positivity significantly associated with poor outcome. The benefit of adjuvant therapy based on anatomic site-specific margin positivity remains to be tested in order to optimize recurrence-free survival.

Follow-Up Studies↗

Minimal criteria for the diagnosis of prostate cancer on needle biopsy.

Increased clinical screening of men at risk for prostate cancer, and the realization of the benefits of performing multiple biopsies per prostate, have facilitated early detection of malignancy, while presenting the pathologist with a growing array of diagnostic findings. Interpretation of these findings requires discussion of the minimal criteria required for the diagnosis of cancer on needle biopsy within a wide spectrum of related histologic findings. This spectrum includes small acinar proliferations suspicious for but not diagnostic of cancer, benign mimics of cancer, the preinvasive entity of high-grade prostatic intraepithelial neoplasia, and various treatment effects. Clinical implications of these findings and other prognostic factors are detailed.

Adenocarcinoma↗

The focus of "atypical glands, suspicious for malignancy" in prostatic needle biopsy specimens: incidence, histologic features, and clinical follow-up of cases diagnosed in a community practice.

This study was undertaken to determine retrospectively the prevalence and histologic features of the atypical foci that are suspicious for but are not diagnostic of a malignancy in contemporary prostate needle biopsy specimens reported in a community practice. Histologic features were examined in detail to identify features that prevented an unequivocal diagnosis of carcinoma. Of 1,009 prostate needle biopsy specimens obtained between January 1, 1993, and August 1, 1995, the diagnosis of an atypical focus suspicious for malignancy was made in 48 (4.8%). In review of the biopsy specimens diagnosed as benign, an additional 7 cases (0.7%) were identified. The following histologic features were identified in 54 cases: enlarged nucleoli, 54 (100%); enlarged nuclei, 45 (83%); intraluminal eosinophilic secretions, 40 (74%); infiltrative growth, 37 (68%); small acinar proliferation, 37 (68%); intraluminal basophilic mucin, 23 (42%); amphophilic cytoplasm, 18 (33%); high-grade prostatic intraepithelial neoplasia, 17 (31%); and crystalloids, 12 (22%). Corpora amylacea were not identified. The foci contained from 1 to 67 acini (mean, 20.7). Although each atypical focus showed most of the features of adenocarcinoma, an unequivocal diagnosis of malignancy was not given owing to four features: the small size of the focus, the small number of cells with enlarged nucleoli, the clustered growth pattern, and the presence of high-grade prostatic intraepithelial neoplasia within many of the foci. At initial examination, 36 of 41 patients (83%) had an elevated serum concentration of prostate-specific antigen (mean, 10 ng/mL), and 20 (49%) had abnormal findings on a digital rectal examination. Twenty-five patients (46%) underwent additional sampling of the prostate, and 15 of these (60%) were found to have adenocarcinoma; the remaining 30 patients did not undergo a subsequent biopsy. Patients with subsequent cancer had higher mean serum concentrations of prostate-specific antigen and change in concentrations of prostate-specific antigen than those whose repeat biopsy results were negative; no other clinical or histologic differences were observed between these two groups. To the community pathologists in this study, the lack of prominent nucleoli, the small size of the focus, clustered acini, and/or adjacent high-grade prostatic intraepithelial neoplasia prevented an unequivocal diagnosis of malignancy. If a prostate needle biopsy specimen is reported as containing an atypical focus suspicious for malignancy, a subsequent biopsy is warranted given the high predictive value for adenocarcinoma.

Aged↗

Stability of the glycoprotein A-80 in prostatic carcinoma subsequent to androgen deprivation therapy.

Androgen deprivation therapy (ADT) results in profound morphologic changes in the benign and malignant prostatic epithelium, including acinar shrinkage and distortion, cytoplasmic clearing, and nuclear hyperchromatism. Data on the immunophenotype of prostatic carcinoma following ADT are limited. A-80 is an oncodevelopmental, mucinous glycoprotein that is strongly and consistently upregulated in high-grade prostatic intraepithelial neoplasia and adenocarcinoma; its expression following ADT has not been investigated. We applied a monoclonal antibody to A-80 to paraffin sections of 54 prostatic carcinomas surgically removed after ADT (Leupron with or without flutamide) and found immunoreactions in 53 of 54 samples (98%). Intense staining was seen in cancer glands, solid aggregates, single cells, and mucinous pools as well as in poorly defined acini lined by shrunken and distorted cells that were difficult to identify as malignant. Hemangiopericytoma-like areas showed A-80 staining in the lumina. Normal, metaplastic, hyperplastic, and atrophic ducts were not similarly reactive. Our findings indicate that there is remarkable stability of the upregulated A-80 glycoprotein in prostatic adenocarcinoma after ADT, despite severe architectural and cytologic alterations. The A-80-reactive colloid pools may reflect ruptured neoplastic glands and spillage of secreted material into stromal spaces. Strong A-80 staining, combined with sporadic cytokeratin reactions in the lumina of hemagiopericytomatous areas, suggests that these are souvenirs of carcinomatous glands revealed by antigenic relics of their component cells. The persistence of A-80 immunoreactivity provides a useful marker for recognizing and monitoring prostatic carcinoma after ADT.

Androgen Antagonists↗

Prostatic adenocarcinoma with atrophic features: malignancy mimicking a benign process.

Acinar atrophy and postatrophic hyperplasia in the prostate are commonly confused with adenocarcinoma. The converse situation may also present a diagnostic dilemma. We recently encountered a number of cases of adenocarcinoma with features that mimicked atrophy, raising the serious concern for the underdiagnosis of malignancy. To investigate the frequency of prostatic adenocarcinoma with atrophic features and the histologic criteria that allow its distinction from benign processes, we reviewed the histopathologic findings in 202 consecutive totally embedded whole-mount radical prostatectomy specimens with adenocarcinoma, 100 consecutive routine needle biopsy specimens, and five additional selected needle biopsy specimens. None of the patients had received androgen deprivation therapy before specimen acquisition. Prostatic adenocarcinoma with atrophic features was defined as a proliferation of malignant acini that architecturally resembled atrophy or postatrophic hyperplasia but retained the diagnostic cytologic features of cancer. The acini were round, often dilated and distorted, and lined by flattened attenuated epithelium with scant cytoplasm. All cases had cytologic evidence of malignancy, including nuclear enlargement and prominent nucleoli; these findings could not be attributed to inflammation or treatment effect. Atrophic features were identified in cancer in six radical prostatectomy specimens (3%) and two routine needle biopsy specimens (2%). The proportion of cancer with atrophic features comprised a mean of 27% of each tumor in the prostatectomy specimens (range 10-60%) and 24% in the needle biopsies (range 10-90%). In the prostatectomy cases, the Gleason score of the cancers was 7 (in five cases) and 5 (in one case); in the biopsy specimens the Gleason score was 6 (in five cases) and 7 (in two cases). In addition, atrophic cancer in the prostatectomy cases had luminal eosinophilic proteinaceous secretions (six cases), blue mucin (five cases), crystalloids (two cases), apocrine blebs (three cases), collagenous micronodules (one case), and high-grade prostatic intraepithelial neoplasia within two high-power fields (three cases); the histologic features were similar in the needle biopsy specimens. We conclude that prostatic adenocarcinoma with atrophic features is an unusual finding that is easily confused with benign acinar atrophy. It is recognized by a combination of architectural and cytologic findings and usually coexists with typical Gleason score 5-7 acinar adenocarcinoma. This pattern is important to recognize to avoid the underdiagnosis of malignancy.

Adenocarcinoma↗

Malignant lymphoma of the bladder: evidence from 36 cases that low-grade lymphoma of the MALT-type is the most common primary bladder lymphoma.

Patients with malignant lymphoma of the bladder were studied, and three clinical groups were defined: those with primary lymphoma localized in the bladder, lymphoma presenting in the bladder as the first sign of disseminated disease (nonlocalized lymphoma), and recurrent bladder involvement by lymphoma in patients with a history of malignant lymphoma (secondary lymphoma). The differences in these groups regarding lymphoma type, clinical presentation, and clinical outcome were studied. Mayo Clinic Tissue Registry records from 1940 to 1996 were searched to identify patients with lymphomas involving the bladder. The lymphomas were classified based on review of the histology and immunophenotype performed by immunoperoxidase methods. Clinical records were reviewed. Presenting symptoms included urinary frequency, dysuria, hematuria, and lower abdominal and back pain. Primary lymphoma was present in six patients. All were B-cell lineage low-grade lymphomas of the mucosa-associated lymphoid tissue (MALT) type. No patient had recurrent lymphoma or died of lymphoma. Nonlocalized bladder lymphoma occurred in 17 patients; one with low-grade lymphoma of the MALT type, four with follicle center lymphomas, and 12 with large cell lymphomas. Excluding two patients who died postoperatively, median survival was 9 years. Six patients died of lymphoma in the follow-up period. Secondary bladder lymphoma occurred in 13 patients: two with low-grade lymphoma of the MALT type, one with follicle center lymphoma, one with mantle cell lymphoma, and nine with diffuse large cell lymphomas. Median survival in this group was 0.6 years. Low-grade lymphoma of the MALT type was the most frequent type of primary bladder lymphoma and was associated with an excellent prognosis. The bladder can be the presenting site of lymphomatous involvement in patients with more widespread disease. Survival in this group is quite favorable and is presumably dependent on lymphoma histologic type, stage of disease, and other prognostic factors. Bladder involvement by recurrent lymphoma is a sign of widely disseminated disease and is associated with a very poor prognosis.

Adult↗

Atypical small acinar proliferation suspicious for malignancy in prostate needle biopsies: clinical significance in 33 cases.

Prostate needle biopsies occasionally contain an atypical small acinar proliferation (ASAP) that is suspicious for, but not diagnostic of, adenocarcinoma. The histologic features and clinical significance of this finding are unexplored. We evaluated 33 cases of ASAP with at least one follow-up needle biopsy seen at Mayo Clinic from 1993 to 1996. Numerous histologic and clinical features were assessed to determine their predictive value for adenocarcinoma on subsequent biopsy. Mean patient age was 61.6 years (range 45-72). Adenocarcinoma was identified on follow-up biopsy in 15 of 33 patients (45%), with a median follow-up of 9 months (range 1-27). Gleason score varied from 4 to 7 (mean 5.9). Two patients (6%) had subsequent diagnoses of ASAP after one and three repeat biopsies. Digital rectal examination, serum prostate-specific antigen, and a variety of histologic findings were not predictive of cancer on follow-up biopsy. These histologic findings included number of biopsy cores (mean 5.5), number of acini per focus of ASAP (mean 7.9), number of foci (mean one), variation in acinar size, nuclear enlargement (none, 12% of cases; mild, 45%; moderate, 33%; severe, 10%), nucleolar enlargement (none, 27%; mild, 46%; moderate, 27%), luminal mucin (39%), crystalloids (6%), focal chronic inflammation (64%), adjacent atrophy (100%), and adjacent high-grade prostatic intraepithelial neoplasia (PIN) (42%). Stratification of suspicion in cases of ASAP without PIN into three categories ("favor benign, uncertain, and favor carcinoma") was somewhat predictive of subsequent cancer (20%, 25%, and 60% of cases with subsequent cancer, respectively), but the results were not significant. The high predictive value of ASAP for subsequent adenocarcinoma warrants repeat biopsy. No single clinical or pathologic feature appeared to increase the likelihood of subsequent cancer.

Adenocarcinoma↗

Prediction of extraprostatic extension of prostate cancer based on needle biopsy findings: perineural invasion lacks significance on multivariate analysis.

Extraprostatic extension (EPE) and seminal vesicle invasion (SVI) are adverse prognostic factors in prostate cancer, and their prediction before prostatectomy would be useful. Perineural invasion in needle biopsy has been advocated as a marker of extraprostatic extension, but its independent value as a predictor of stage has not been established. We studied 349 previously untreated men with prostatic adenocarcinoma who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy. All patients were clinically free of metastases and had cancer that was diagnosed on needle biopsy. Five preoperative variables were collected: clinical stage (TNM staging system), serum prostate-specific antigen (PSA), Gleason score on needle biopsy, presence or absence of perineural invasion, and proportion of the biopsy involved by cancer. The subsequent prostatectomy specimens were completely embedded, and whole mount sections were used to evaluate four outcome staging variables: EPE (absent/present), EPE (absent/unilateral/bilateral), seminal vesicle invasion, and pathologic stage (TNM). On univariate analysis, each preoperative variable was significantly associated with each outcome variable except for a lack of association between clinical stage and SVI. Perineural invasion in the biopsy predicted EPE with a sensitivity of 51%, specificity of 70%, positive predictive value of 49%, and negative predictive value of 71%. On multivariate analysis (stepwise logistic regression), only preoperative PSA, proportion of the biopsy involved by cancer, and Gleason score were significant (p < 0.05); perineural invasion and clinical stage had no independent predictive value for any of the outcome variables. We conclude that the finding of perineural invasion in needle biopsy of prostatic carcinoma has no independent predictive value for the presence of extraprostatic extension, seminal vesicle involvement, or pathologic stage in the radical prostatectomy. Accordingly, we no longer routinely evaluate this finding in biopsy specimens.

Adenocarcinoma↗

Prostate cancer masquerading as a zygomatic posttraumatic mass.

A zygomatic mass is a rare occurrence. We describe a 52-year-old man with a zygomatic arch mass and a recent history of facial trauma. Findings on a computed tomographic scan of the facial bones were interpreted as callus formation, consistent with fracture of the zygomatic arch. The level of the prostate-specific antigen was increased to 62.3 ng/mL, and a biopsy of a nodular prostate specimen revealed adenocarcinoma (Gleason sum, 3 + 4 = 7). Because the laboratory data, history, and findings on physical examination did not correlate, we suspected a tumor metastatic to the facial bones.

Adenocarcinoma↗

Prostatic intraepithelial neoplasia occurs spontaneously in the canine prostate.

PURPOSE: Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer. Although the dog is the only non-human species in which spontaneous prostate cancer occurs frequently, the prevalence of PIN in the canine prostate is unknown. A naturally occurring animal model of PIN has not been described. MATERIALS AND METHODS: To determine if high grade PIN occurs spontaneously in the canine prostate, we evaluated totally embedded prostates from 35 outbred dogs that had no clinical evidence of prostatic disease. Prostates from three groups of dogs were analyzed: (1) 11 sexually intact dogs 7-17 years old (elderly sexually intact); (2) 13 sexually intact dogs 1-4 years old (young sexually intact); and (3) 11 dogs 7-17 years old that had been castrated (elderly castrated). The prevalence of PIN was determined by systematic evaluation of hematoxylin/eosin and high molecular weight keratin 34 beta-E12 stained tissue sections from formalin-fixed, paraffin embedded prostates that had been serially sectioned at 4 mm intervals. RESULTS: Canine high grade PIN showed cytologic features identical to the human counterpart, including cell crowding, loss of polarity, and nuclear and nucleolar enlargement. Foci of high grade PIN were present in the prostates of 6 of 11 (55%) elderly, sexually intact dogs but only 1 of 13 (8%) dogs less than 4 years old. Foci of high grade PIN were detected in 1 of 11 (9%) elderly castrated dogs. In elderly, sexually intact dogs with PIN, foci of high grade PIN were present in 13 of 83 (16%) tissue sections evaluated; one of these dogs had focal adenocarcinoma in addition to PIN. CONCLUSIONS: These results indicate that high grade PIN is frequently present in the prostate of elderly, sexually intact dogs. The prevalence of canine PIN, like human PIN, is apparently influenced by age and testicular androgens. The canine prostate may serve as a useful model to determine the factors that regulate the apparent progression from benign epithelium to PIN and invasive carcinoma.

Age Factors↗

Simultaneous chromosome 7 and 17 gain and sex chromosome loss provide evidence that renal metanephric adenoma is related to papillary renal cell carcinoma.

PURPOSE: Metanephric adenoma has recently been recognized as a unique renal tumor characterized by an unusual degree of cellular differentiation and maturation. We recently studied metanephric adenoma using metaphase analysis and observed concomitant chromosome Y loss and chromosome 7 and 17 gain. To determine if these chromosomal anomalies are consistently present in renal metanephric adenoma, we studied all 11 tumors in the pathology tissue registry at our institution using fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: FISH, using deoxyribonucleic acid probes for chromosomes 1, 7, 8, 17, X and Y, was performed in isolated nuclei from 11 paraffin embedded renal metanephric adenoma specimens. RESULTS: Of the 11 tumors (73%) 8 demonstrated chromosome 7 and 17 gain by FISH, and the remaining 3 were found to have an apparently normal chromosomal content. Of the 8 tumors (75%) from men showed 6 chromosome 7 and 17 gain with Y chromosome loss. Of the 3 tumors (33%) from women 1 had chromosome 7 and 17 gain with X chromosome loss, while 1 had chromosome 7 and 17 gain without sex chromosome aneusomy. Metaphase analysis performed on 2 tumors revealed chromosome 7 and 17 gain and Y chromosome loss in 1, and no apparent, chromosome anomaly in the other, confirming the results of FISH analysis. CONCLUSIONS: FISH analysis of renal metanephric adenoma identified frequent chromosome 7 and 17 gain and sex chromosome loss. These results are consistent with a clonal neoplastic disorder in which chromosomes 7, 17, X and Y are likely to be involved in the pathogenesis of this tumor. These characteristic chromosomal alterations have also been observed in papillary renal cell adenoma and papillary renal cell carcinoma, providing evidence that these tumors may be related.

Adenoma↗

Staging prostate cancer--1997: current methods and limitations.

Clinical and pathologic staging of prostate cancer involves determination of the anatomic extent and burden of tumor based on the best available data. The TNM system [primary tumor (T), regional lymph node (N), and metastases (M)] is the most widely used system for prostate cancer staging. It stratifies patients according to the method of tumor detection, separating nonpalpable 'incidental' prostate cancers detected during transurethral resection for clinically benign prostatic hyperplasia and palpable cancers detected by digital rectal examination. This staging system also recognizes nonpalpable cancer detected by an elevated serum prostate-specific antigen level or an abnormal transrectal ultrasound image (stage T1c). Current staging is limited by a significant level of clinical understaging (up to 59% in our experience) and overstaging (up to 5%) based on comparison with pathologic examination of resected specimens. Proposed improvements in staging include preoperative systematic biopsies to assess tumor volume, the use of a volume-based prognostic index, and a multiple prognostic index. Currently, staging of prostate cancer falls short of meeting some of these goals, creating controversy and uncertainty about the comparative efficacy of various forms of therapy and expected outcomes for patients. In this report, we evaluate the current aspects of clinical and pathologic staging of prostate cancer with emphasis on the early stages in which there is the greatest chance of cure. Recent international agreement on the pathologic staging of prostate cancer should allow valid comparisons of surgical treatment from different institutions.

Adenocarcinoma↗