PubMed Health⌕ Search

Biomedical subjects

J I Epstein

Publications and source records attributed to J I Epstein.

At least 55 records · Page 3Linked to original sources

Clinical significance of denuded urothelium in bladder biopsy.

PURPOSE: Although to our knowledge the significance of denuded urothelium in bladder biopsies has not been studied previously, it is thought to be a problem because benign urothelial cells are cohesive and not expected to shed into the urine. We correlated the pertinent clinical features of patients with denuded bladder biopsies and/or specific pathological features of denuded bladder biopsy specimens with patient outcome in regard to bladder lesions to help predict the subsequent likelihood of diagnosing bladder carcinoma in a patient with a nondiagnostic denuded biopsy. MATERIALS AND METHODS: We studied 51 denuded bladder biopsies from 44 patients in which the average extent of epithelial denudation was 90%. RESULTS: Of the 27 male (69%) and 17 female (31%) patients 22 to 86 years old (mean age 62) 34% had no history of bladder neoplasms. In remainder there were flat carcinoma in situ with or without other tumors (26%), high (20%) and low (14%) grade papillary tumors without carcinoma in situ and miscellaneous conditions (6%). Overall 31% of patients were diagnosed with carcinoma in situ within 24 months (median 5.5) after the denuded specimen was obtained. Parameters that did not correlate with the subsequent diagnosis of carcinoma in situ included cystoscopic impression, history of intravesical chemotherapy, sex, age, tissue inflammation, percent of tissue fragments with any denudation, number of denuded tissue fragments and percent of overall denuded epithelium. A history of carcinoma in situ before denuded biopsy predicted a diagnosis of carcinoma in situ within 24 months after denuded biopsy in 54% of patients in contrast to 19% of those without a history of carcinoma in situ (p = 0.03). Factoring in a history of other bladder tumor types in various combinations did not predict carcinoma in situ after denuded biopsy. The other predictive factor was cold cup biopsy. Carcinoma in situ developed within 24 months in 45% of patients in whom the denuded specimen was obtained by cold cup biopsy in contrast to none who underwent hot wire loop biopsy (p = 0.007). Cold cup biopsy and a history of carcinoma in situ were independently predictive. Carcinoma in situ developed within 24 months in 75% of patients with a history of that condition and a subsequent cold cup biopsy showing denuded epithelium. However, only 29% of those who underwent cold cup biopsy and had no history of carcinoma in situ were diagnosed with carcinoma in situ. CONCLUSIONS: In bladder biopsies obtained by a hot wire loop denudation most likely results from thermal injury when there is a low risk of subsequent carcinoma in situ. When the denuded biopsy sample was obtained by cold cup biopsy, particularly when associated with a history of carcinoma in situ, most cases represent neoplastic cell denudation and a high risk for subsequent carcinoma in situ.

Adult↗

Dedifferentiation of prostate cancer grade with time in men followed expectantly for stage T1c disease.

PURPOSE: We assess whether the Gleason grade changes in men followed expectantly with clinical stage T1c prostate cancer. MATERIAL AND METHODS: We studied 70 men with stage T1c prostate cancer who underwent watchful waiting with repeat needle biopsy sampling to assess for progression. After the initial cancer diagnosis all men had at least 1 other biopsy demonstrating cancer. RESULTS: Of 70 cases 9 (12.9%) showed a significant change in grade from Gleason scores 6 or less to 7 or greater. The average followup of those patients without a change in grade was 22 months and greater than those with a change in grade. There was no difference between the groups with and without changes in grade in regard to initial prostate specific antigen (PSA), percent-free PSA, or PSA density or velocity. Of 9 cases there were 5 (56%) and 8 (89%) with grade change that occurred at 12 and 15 months or less after initial biopsy, respectively. In contrast, only 1 of 24 (4%) patients in whom last re-biopsy was performed 24 months or greater after the initial cancer diagnosis had a change in grade. Of the 21 men who underwent radical prostatectomy 5 (24%) had worsening of grade on the radical prostatectomy specimen compared to biopsy, with a mean interval of 18 months between the initial cancer diagnosis and prostatectomy. This prevalence of grade change is less than in our population that underwent prostatectomy within 1 to 3 months after biopsy. CONCLUSIONS: Because most grade changes occurred relatively soon after biopsy, it implies that tumor grade did not evolve but rather the higher grade component was not initially sampled. During a 1 1/2 to 2-year period after biopsy there is no evidence that prostate cancer grade worsens significantly. Men with prostate cancer need not feel concerned about waiting several months before undergoing surgery after biopsy. Furthermore, men undergoing watchful waiting can be reassured that there is little evidence that prostate cancer grade worsens during the short term.

Adenocarcinoma↗

Does increased needle biopsy sampling of the prostate detect a higher number of potentially insignificant tumors?

PURPOSE: Several studies have documented that increased biopsy sampling, that is 6 versus 12 biopsy cores, can detect more prostate cancer. It is unknown whether increased sampling of the prostate will detect a higher number of potentially insignificant tumors. MATERIALS AND METHODS: We searched the surgical pathology files at The Johns Hopkins Hospital for patients in whom prostate needle biopsy was performed by a single urologist between April 1993 and April 2000, and subsequently underwent radical prostatectomy. Patients who underwent radical prostatectomy and had 8 core biopsies or less between March 1994 and August 1999 were also studied. Clinically significant tumors were defined as those with volume greater than 0.5 cc, Gleason score 7 or greater or nonorgan confined disease. RESULTS: A total of 297 patients with a mean age of 60 years (range 36 to 75) were evaluated. Group 1 consisted of 107 men with 8 core biopsies or less, including 51 with 6, and group 2 comprised 190 men with 9 cores or greater, including 145 with 12. The 2 groups were equal in regard to prostate specific antigen, age, digital rectal examination and transrectal ultrasound gland volume at biopsy. The only difference between the groups was a higher number of cores with cancer in group 2 (mean 2.8 versus 2.1, p = 0.0006). Of the patients who underwent radical prostatectomy 59.6% had Gleason score 6 or less, 26.3% 3+4, 6.7% 4+3 and 7.4% 8 to 9. There were 12.4% of patients with positive margins, 36.4% extraprostatic extension, and 5.4% seminal vesicle invasion and/or lymph node metastasis. Tumor volumes averaged 1.1 cc (range 0.01 to 10.7) and 60.9% of tumors were greater than 0.5 cc. Clinically significant tumors were seen in 77.4% of patients in group 1 and 74.6% in group 2. There was no significant difference in Gleason score, margin status, tumor volume, seminal vesicle invasion, or lymph node metastasis between groups 1 and 2, or in a subset analysis of men with 6 versus 12 core biopsies. However, patients in whom cancer was diagnosed with 9 core biopsies or greater were more likely to have organ confined disease (p = 0.02). CONCLUSIONS: Although increased sampling of the prostate does not increase the detection of potentially insignificant tumors, it does appear to detect earlier stage cancer.

Adult↗

A neural network predicts progression for men with gleason score 3+4 versus 4+3 tumors after radical prostatectomy.

OBJECTIVES: To determine the significance of Gleason scores 3+4 (GS3+4) versus 4+3 (GS4+3) with respect to biochemical recurrence in a retrospective review of a series of men with clinically localized prostate cancer who underwent radical retropubic prostatectomy (RRP) and to develop and test an artificial neural network (ANN) to predict the biochemical recurrence after surgery for this group of men using the pathologic and clinical data. METHODS: From 1982 to 1998, 600 men had pathologic Gleason score 7 disease without lymph node or seminal vesicle involvement. We analyzed the freedom from biochemical (prostate-specific antigen) progression after RRP on 564 of these men on the basis of their GS3+4 versus GS4+3 (Gleason 7) status. The Cox proportional hazards model was used to determine the importance of Gleason 7 status as an independent predictor of progression. In addition, an ANN was developed using randomly selected training and validation sets for predicting biochemical recurrence at 3 or 5 years. Different input variable subsets, with or without Gleason 7 status, were compared for the ability of the ANN to maximize the prediction of progression. Standard logistic regression was used concurrently on the same random patient population sets to calculate progression risk. RESULTS: A significant recurrence-free survival advantage was found in men who underwent RRP for GS3+4 compared with those with GS4+3 disease (P <0.0001). The ANN, logistic regression, and proportion hazard models demonstrated the importance of Gleason 7 status in predicting patient outcome. The ANN was better than logistic regression in predicting patient outcome, in terms of prostate-specific antigen progression, at 3 and 5 years. CONCLUSIONS: A simple modification of the Gleason scoring system for men with Gleason 7 disease revealed a difference in the patient outcome after RRP. ANN models can be developed and used to better predict patient outcome when pathologic and clinical features are known.

Disease Progression↗

Molecular and immunohistochemical staging of men with seminal vesicle invasion and negative pelvic lymph nodes at radical prostatectomy.

BACKGROUND: Patients with seminal vesicle invasion (SVI) at radical retropubic prostatectomy (RRP) have a poor prognosis. Routine microscopic examination of pelvic lymph nodes (LNs) can miss small metastases and, thereby, confuse tumor staging and clinical decision-making. The authors used immunohistochemical and molecular methods to examine archival paraffin-embedded LNs of men who had undergone RRP for clinically localized prostate carcinoma and who had tumors demonstrating SVI and negative LNs at surgery. METHODS: Between June 1982 and June 1997, 2151 consecutive men underwent RRP for clinically localized prostate carcinoma. Of these, 109 (5.1%) tumors had SVI with negative LNs. The actuarial likelihood of having a tumor that was undetectable by testing prostate-specific antigen (PSA) 5 and 10 years after surgery was 45% and 29%, respectively, for men with isolated SVI. Archival LN specimens were available for 102 men who had isolated SVI. Reverse transcription polymerase chain reaction (RT-PCR) was performed for PSA and prostate-specific membrane antigen (PSMA). All specimens were examined concurrently by immunohistochemistry (IHC). RESULTS: Careful reevaluation of pelvic LNs demonstrated metastases in 9 (8.8%) men originally classified as metastasis-free. Reevaluation by hematoxylin and eosin (H&E) staining identified three previously unrecognized cases of LN metastases. IHC identified six cases, three of which were missed by H&E. RT-PCR identified four cases, three of which were not revealed by other methods. CONCLUSIONS: The poor prognosis of patients with SVI does not seem due to occult LN metastases. The low yield of unsuspected foci of prostate carcinoma in the LNs of men with SVI and negative LNs by routine staging does not justify IHC or molecular examination to find occult carcinoma.

Adult↗

Papillary urothelial hyperplasia is a clonal precursor to papillary transitional cell bladder cancer.

Papilloma and papillary hyperplasia (PH) have been proposed to be the putative precursor lesions of papillary transitional-cell carcinoma of the urinary bladder. We examined 15 PH lesions and 4 papillomas for loss of heterozygosity (LOH) at 17 microsatellite markers on 9 chromosomal arms. Eight of 15 (53%) PHs were clonal, demonstrating LOH of at least 1 microsatellite marker. In contrast, none of the papillomas showed any genetic changes among the markers tested. In PH, chromosomal arm 9q was the most frequently lost (4/15), followed by 9p and 18q (n = 2) and, less frequently, 8p, 10q, 11p and 17p (n = 1). Furthermore, 2 hyperplastic lesions demonstrated LOH at 9q only, confirming the notion that allelic loss on chromosomal arm 9q is among the earliest events in bladder-cancer progression. In 1 patient, identical LOH patterns were observed between PH and a recurrent transitional-cell carcinoma. Our molecular data demonstrate that at least a proportion of PHs represent pre-cancerous lesions of the bladder that subsequently progress to papillary bladder cancer. Moreover, chromosomal arm 9q may harbor a tumor-suppressor gene(s) inactivated in the earliest stages of human bladder tumorigenesis.

Carcinoma, Transitional Cell↗

Prognostic significance of Gleason score 3+4 versus Gleason score 4+3 tumor at radical prostatectomy.

OBJECTIVES: To determine the clinical significance of Gleason score 3+4 versus 4+3 on radical prostatectomy. METHODS: Of 2390 men who underwent radical prostatectomy by a single surgeon, 570 had Gleason score 7 tumors without lymph node metastasis, seminal vesicle invasion, or tertiary Gleason pattern 5. Patients were evaluated for biochemical recurrence (prostate-specific antigen progression) and distant metastases. RESULTS: Eighty percent of patients had Gleason score 3+4, 20% had 4+3. The rate of established extraprostatic extension at radical prostatectomy for Gleason score 3+4 and 4+3 tumors was 38.2% and 52.7%, respectively (P = 0.008). With a mean follow-up of 4.6 years for men without progression, Gleason score 4+3 tumors had an increased risk of progression independent of stage and margin status (P <0.0001). The 5-year actuarial risk of progression was 15% and 40% for Gleason score 3+4 and 4+3 tumors, respectively. The mean time to progression was 4.4 years for Gleason score 3+4 tumors and 3.2 years for Gleason score 4+3 tumors. We stratified the patients into four prognostic groups on the basis of organ-confined status, margin status, and Gleason score (3+4 versus 4+3). The 5-year actuarial risk of progression was 10%, 35%, 45%, and 61%, with 10-year progression rates of 29%, 42%, 69%, and 84%, for the four groups. 3.9% of patients with Gleason score 3+4 and 10. 5% with Gleason score 4+3 tumors developed metastatic disease within a mean of 5.7 and 5.6 years, respectively. A Gleason score of 4+3 versus 3+4 was predictive of metastatic disease (P = 0.002) but not local recurrence. CONCLUSIONS: Gleason score 7 tumors are heterogeneous in their biologic behavior. The differences in prognosis for patients with Gleason scores 3+4 and 4+3 tumors at radical prostatectomy are significant. Although the assessment of the percentage of pattern 4 at radical prostatectomy is not likely to be reproducible, the distinction between Gleason score 3+4 and 4+3 should be easier for pathologists to perform.

Actuarial Analysis↗

A web-based tutorial improves practicing pathologists' Gleason grading of images of prostate carcinoma specimens obtained by needle biopsy: validation of a new medical education paradigm.

BACKGROUND: The Internet, although it is in widespread use in medicine, to the authors' knowledge has not been tested rigorously as an educational tool. The authors investigated, as a model to validate web-based education for physicians, the Gleason grading of images of prostate carcinoma tissue specimens that were obtained by needle biopsy, which provides critical information for patient management. METHODS: A free, web-based program (available at www. pathology.jhu.edu/prostate) was developed. It consisted of 20 pretutorial quiz images of prostate carcinoma specimens that were obtained by needle biopsy for grading, followed by 24 tutorial images with text describing the Gleason grading system. Subsequently, pathologists took a posttutorial quiz, which consisted of the same 20 images that were used in the pretutorial quiz. RESULTS: In 16 months, there were 2021 visits with 916 participants completing the entire web site; 643 participants (70.2%) were practicing pathologists and formed the basis of the current study. Only the location of practice within the United States compared with outside the United States (P < 0.0001) and < 5 years in practice (P = 0.003) were correlated independently with a higher pretutorial quiz score. Overall, the web-based tutorial significantly improved grading in 15 of 20 images. Of these, on average, there was an 11.9% increase (range, 6-25.3%) in assigning the correct Gleason score. Improvements were noted in images of tumors with the following grades: Gleason score, 2-4 (0 of 1 images); Gleason score, 5-6 (5 of 7 images); Gleason score, 7 (4 of 6 images); and Gleason score, 8-10 (6 of 6 images). Greater improvement after taking the tutorial was correlated with lower pretutorial scores (P < 0.0001). CONCLUSIONS: A web-based tutorial improves the accuracy of Gleason grading of practicing pathologists. To the authors' knowledge the current study is the first large scale, international study that has evaluated and validated the use of a web-based program to educate a population of widely dispersed physicians.

Biopsy, Needle↗

Adenocarcinoma of the prostate invading the seminal vesicle: prognostic stratification based on pathologic parameters.

OBJECTIVES: To stratify the prognosis of lymph node-negative, seminal vesicle-positive tumors in men with prostate cancer after radical retropubic prostatectomy. METHODS: Sixty cases were analyzed for multiple parameters and correlated with postoperative biochemical (prostate-specific antigen) progression. Variables included Gleason score, primary Gleason pattern, percentage of Gleason pattern 4, any presence of Gleason pattern 5, method of seminal vesicle invasion (SVI), margin positivity, SVI extent, SVI bilaterality, vascular invasion, extent of extraprostatic extension, length of tumor extending along the seminal vesicles, presence of intraductal carcinoma within the prostate, bladder neck margin positivity, and tumor volume. RESULTS: We were able to stratify the prognosis based on the combination of a variation of the Gleason score and margin status and vascular invasion status. Using this stratification, a few patients had an excellent long-term prognosis, with most patients split into two groups, one experiencing rapid and the other slower progression. CONCLUSIONS: SVI is not associated with a uniformly poor prognosis. Rather, tumors can be substratified by pathologic parameters into groups with differing prognoses based on routine histologic examination.

Adenocarcinoma↗

Molecularly confirmed primary prostatic synovial sarcoma.

We report the second molecularly-confirmed primary prostatic synovial sarcoma. The diagnosis was particularly elusive at the light microscopic level in that the tumor failed to show epithelial differentiation, but it did show combined spindle-cell and poorly differentiated (round-cell) morphologies. The immunohistochemical staining profile was nonspecific and potentially misleading. Only by demonstration of the characteristic SYT-SSX gene fusion of synovial sarcoma by reverse transcriptase polymerase chain reaction (RT-PCR) analysis of RNA extracted from archival material could the diagnosis be confirmed. This case further illustrates the use of this technique in diagnostic pathology.

Adult↗

Needle biopsy of recurrent adenocarcinoma of the prostate after radical prostatectomy.

The objective of this study was to evaluate needle biopsy of recurrent prostate cancer after radical prostatectomy. We evaluated 37 cases of recurrent prostate cancer after radical prostatectomy that were diagnosed by needle biopsy between March 1984 and July 1998. Fifteen were from consultations in which contributors were uncertain of the diagnosis, and 22 were from men who had come to The Johns Hopkins Hospital for treatment. The median interval from radical prostatectomy to biopsy showing recurrent tumor was 40 months. There was no correlation between the interval to recurrence and either pathologic features of the biopsy and radical prostatectomy or various clinical features. The mean extent of adenocarcinoma in the biopsies was 3.2 mm (range, 0.1 to 18 mm; median, 2 mm). The length of recurrent cancer on biopsy correlated with an abnormal rectal examination (P = .001). The mean Gleason score for the recurrent tumors was 6.5, which correlated with the grade of the radical prostatectomy cancer (P = .005). The cancers often lacked overt histologic features of malignancy. Benign prostatic acini were seen in five cases (14%), usually separate from the cancer. In 5 (33%) of the consultation cases, we would not have been able to diagnose cancer if not for the fact that atypical prostate glands should not be present after radical prostatectomy. In well-sampled radical prostatectomies, margins were almost always positive, as was extraprostatic extension. In cases with less sampling, there was a higher incidence of organ-confined disease and margin-negative disease implying suboptimal processing of the radical prostatectomy. After radical prostatectomy, recurrent cancer on needle biopsies may be focal and difficult to diagnose and must be assessed differently than in patients who have not had surgery.

Adenocarcinoma↗

Pathology residents' use of a Web-based tutorial to improve Gleason grading of prostate carcinoma on needle biopsies.

Little is known about pathology residents' ability to Gleason grade or their ability to learn surgical pathology using Internet-based technology. A free Web-based program (available at www.pathology. jhu.edu/prostate) was developed that consisted of 20 pretutorial images for grading, 24 tutorial images, and the same 20 posttutorial images for Gleason grading. The grading images were selected from cases that had a consensus Gleason grade from 10 uropathology experts. In 2.5 months, 255 residents visited the website, and 151 (59%) completed it. Of those who completed the website, their year in training was known in 85 (56%): 1st year, 25.8%; 2nd year, 20%; 3rd year, 22.3%; 4th year, 14.1%; 5th year, 15.3%; and 6th year, 2.4%. Eighty percent learned Gleason grading in residency versus being self-taught, and 66% were male. In a multivariate analysis, higher pretutorial scores were associated with both their year in training (P = .001) and their hospital size (P = .003). Improvements in grading posttutorial were not related to the residents' year in training. Overall, the website significantly improved grading in 11 of 20 images and had no effect in 9 of 20 images. Improvements were noted in 1 of 1 Gleason score 4; 2 of 7 Gleason score 5 to 6; 2 of 6 Gleason score 7; and 6 of 6 Gleason score above 7 tumors. In summary, a Web-based tutorial improved Gleason grading accuracy by pathology residents to an equal extent regardless of their year in training. It is more difficult to teach residents to grade Gleason scores 5 to 7 tumors, and additional training should be concentrated in this area.

Biopsy, Needle↗

Efficacy of restaining prostate needle biopsies with high-molecular weight cytokeratin.

Prostate tissue and lesions obtained by needle biopsy may be scant and not survive cutting into the block; this study examined the efficacy of destaining hematoxylin and eosin-stained sections and restaining the slides using immunohistochemistry with high-molecular weight cytokeratin (high-molecular weight cytokeratin). We identified 105 prostate needle biopsies referred to Johns Hopkins Hospital in an 18-month period (January 1997-June 1998) that had been destained and restained for high molecular weight cytokeratin. The slides were reviewed for the Johns Hopkins Hospital diagnosis (benign, malignant, or equivocal), which had factored in the immunohistochemistry results, and for immunohistochemistry staining quality (optimal, suboptimal, stain failed, or lesion fell off). We obtained data on 96 cases from the referring institutions about the fixative and glass slides used for processing the needle biopsy. In 58% of cases, destaining and restaining with high-molecular weight cytokeratin allowed a definitive benign or malignant diagnosis to be made; in 79% of these cases, the staining was optimal. In only 13% of cases the diagnosis remained equivocal; of these, the stain worked optimally in only 36%. In 19% of cases, the stain failed. In 9% of cases, the lesion fell off; in all 7 cases with available data the tissue had been cut on non-charged slides. All but 3 cases were received in 10% neutral buffered formalin. There was no correlation between the use of charged (plus or lysine coated) or non-charged slides and the staining quality. Furthermore, in 12 instances, we received more than 1 specimen from the same referring institution, and in 6 of these instances there was variable staining in the different cases from the same institution. Destaining hematoxylin and eosin-stained slides and restaining for high-molecular weight cytokeratin is a useful technique that in the majority of cases enables a definitive diagnosis to be made. Tissue may survive the procedure better if originally cut on charged slides, but staining quality is no different for charged or non-charged slides.

Adenocarcinoma↗

Foamy gland high-grade prostatic intraepithelial neoplasia.

A 60-year-old man underwent radical prostatectomy for biopsy-proved adenocarcinoma of the prostate. Histologic examination of the entirely embedded prostatectomy specimen revealed extensive ordinary adenocarcinoma, Gleason's grade 3 + 3 = 6, involving both sides of the gland, and extending into extraprostatic soft tissue at the left base. Adjacent to the carcinoma, and separately, extensive high-grade prostatic intraepithelial neoplasia (PIN) was identified, much of which showed bland nuclei and abundant xanthomatous cytoplasm, identical morphologically to that seen in foamy gland prostate carcinoma. However, unlike foamy gland carcinoma, the foamy glands in the current patient were large, showed papillary infolding, and were associated with a discontinuous layer of basal cells, demonstrated by immunostaining for high-molecular weight cytokeratin. No invasive foamy gland carcinoma was identified in the prostatectomy specimen. Immunostains for Ki-67 showed an increased proliferation rate in foamy high-grade PIN glands when compared with adjacent benign glands. Review of additional outside biopsy material revealed foamy gland high-grade PIN on four of seven needle cores, two of which showed no carcinoma. This patient demonstrates a new subtype of high-grade PIN that is difficult to recognize on needle biopsy. It is important to distinguish foamy gland high-grade PIN from its infiltrating counterpart, and it is critical to recognize because of the association of high-grade PIN with prostate carcinoma.

Adenocarcinoma↗

The prognostic significance of tertiary Gleason patterns of higher grade in radical prostatectomy specimens: a proposal to modify the Gleason grading system.

The Gleason grading system of prostatic adenocarcinoma does not account for the existence of a tertiary (third most prevalent) pattern, and there are no studies concerning the latter's prognostic influence. The authors analyzed 114 radical prostatectomies with small tertiary components, which mostly occupied less than 5% of whole tumors. These specimens were compared with a prostatectomy database comprised of 2,276 cases without a tertiary component. The pathologic stages of "typical" Gleason score 5 to 6 tumors (Gleason scores 2 + 3 = 5, 3 + 2 = 5, 3 + 3 = 6), which contained tertiary patterns 4 or 5, were significantly higher than those of "typical" Gleason score 5 to 6 tumors without pattern 4 (p = 0.018) but lower than those of "typical" Gleason score 7 tumors (p = 0.021; Gleason scores, 3 + 4 = 7, 4 + 3 = 7). Typical Gleason score 7 tumors with a tertiary pattern 5 showed significantly worse pathologic stages than typical Gleason score 7 tumors (p = 0.008) without pattern 5 and were not different statistically from typical Gleason score 8 (Gleason score, 4 + 4 = 8) tumors. Both typical Gleason score 5 to 6 and 7 tumors with tertiary components revealed significantly higher progression rates than typical Gleason score 5 to 6 tumors (p <0.0001) and Gleason score 7 tumors (p = 0.003) without tertiary components, and progressed like typical Gleason score 7 and 8 tumors respectively. Tertiary high-grade components have an adverse impact on biologic behavior. The authors propose that the Gleason system for radical prostatectomy specimens be modified to take into account small volumes of patterns 4 and 5, which are important prognostically.

Adenocarcinoma↗

Primary malignant melanoma of the urethra: a clinicopathologic analysis of 15 cases.

The clinical and pathologic features of 15 primary urethral melanomas occurring in patients (nine women and six men) age 44 to 96 years (mean age, 73 yrs) are described. In the men the tumor involved the distal urethra. In eight women it involved the distal urethra, usually the meatus; both the distal and proximal urethra were involved in one woman. The tumors were typically polypoid and ranged from 0.8 to 6 cm (mean, 2.6 cm) in maximum dimension. A vertical growth phase was present in all tumors, with a prominent nodular component in seven of them. A radial growth phase was seen in nine tumors. The depth of invasion ranged from 2 to 17 mm. The tumors had diffuse, nested, storiform, or mixed growth patterns. The neoplastic cells typically had abundant eosinophilic cytoplasm, large nuclei with prominent nucleoli, and brisk mitotic activity. Melanin pigment was seen in 12 tumors but was conspicuous in only six. At the time of diagnosis, 13 tumors were confined to the urethra and two patients had lymph node metastasis. Nine patients died of disease 13 to 56 months after initial diagnosis and treatment, and one patient had a local recurrence at 4 years and subsequently died of sepsis 1 year later. Three patients were alive and well at 11 months, 23 months, and 7 years. One patient died at the time of the initial operation, and one died of a ruptured aortic aneurysm at 3 years without evidence of melanoma at autopsy. Primary malignant melanomas of the urethra, one fifth of which are amelanotic, must be included in the differential diagnosis of a number of primary neoplasms that involve the urethra, including transitional cell carcinoma, sarcomatoid carcinoma, and sarcomas. Conventional prognostic factors, such as depth of invasion or tumor stage, do not seem to play as important a role in predicting survival as the mucosal location and the nodular growth present frequently in these tumors.

Adult↗