[Prostate biopsy: characteristics of the histological sample].
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Biopsy↗
Biomedical subjects
Rodolfo Montironi
Publications and source records attributed to Rodolfo Montironi.
Handling and pathology reporting of specimens with carcinoma of the urinary bladder, ureter, and renal pelvis. A joint proposal of the European Society of Uropathology and the Uropathology Working Group.
Pathologists play a pivotal role in the diagnosis and in the report of the pathological features related to prognosis. To meet these endpoints, the following issues must be addressed: adequate information about the patient history, proper handling of the specimens, identification of the reliable histopathological techniques necessary to reach the more detailed diagnostic information and evaluation of the prognostic variables, and standardized pathological reporting. In this review we discuss a proposal for standardization of sampling and reporting of the urothelial tissues achieved within uropathology. The urologists have a great role in assisting pathologists in the proper examination by providing them with clinical information.
Carcinoma↗
Carcinoma of the prostate: inherited susceptibility, somatic gene defects and androgen receptors.
Multiple factors contribute to the development of prostate carcinoma (PCa) and to its progression to an androgen-independent state. In addition to the expected role of androgens and their receptors in facilitating the development of PCa, mutations in a growing number of candidate hereditary prostate cancer loci and genes, such as RNASEL and MSR1, have been detected, suggesting that defects in critical pathways involving DNA damage response, apoptosis and innate immunity may have a particularly important role in the initiation of PCa. Many somatic mutations, gene deletions, gene amplifications, chromosomal rearrangements, and changes in DNA methylation are detectable in PCa cells at the time of diagnosis. The identification of key molecular alteration cells implicates carcinogen defenses, including GSTP1, growth factor signaling pathways (such as PTEN and p27) and androgens as critical determinants of the phenotype of PCa.
Adenocarcinoma↗
Androgen ablation therapy for prostate carcinoma suppresses the immunoreactive telomerase subunit hTERT.
BACKGROUND: Telomerase is a ribonucleoprotein complex that protects the ends of chromosomes from degradation. Its catalytic subunit, hTERT, controls its activity. Prior data in prostate carcinoma cases indicated that immunohistochemical hTERT reactivity increases with tumor grade and may be absent in lower grade cases. The effect of complete androgen ablation (CAA) on tumor hTERT expression was uncertain. METHODS: hTERT immunostaining was performed on the cancerous pretreatment biopsy tissue of 30 men who consecutively underwent CAA with bicalutamide and goserelin acetate for 30 days prior to undergoing radical prostatectomy, and on their tumor tissue from radical prostatectomy. As controls, biopsy and prostatectomy samples from 30 untreated men were studied. Nuclear staining was evaluated by two observers, and the change in staining between biopsy and prostatectomy samples was evaluated using the Student t test in both groups. RESULTS: The percent of reactive tumor nuclei in treated men declined from 36.7% to 13.2% (P = 0.0001), and declined from 19.8% to 16.1% in untreated men (P = 0.4). The greater mean hTERT reactivity in the treated men's biopsy specimens was attributed to an increased proportion of higher (Gleason score > or = 7) grade tumors. The decline in hTERT immunostaining remained significant after normalizing it to that of the untreated group (P = 0.002). The original Gleason scores, corresponding declines in the percentage of reactive tumor nuclei, and significance were: Gleason score < or = 6: 11% (P = 0.03); Gleason score of 7: 23% (P < 0.006); and Gleason score > or = 8: 46% (P < 0.005) (from a mean 63% to 17%). CONCLUSIONS: CAA for prostate carcinoma can be considered an antitelomerase therapy. The steepest reduction in telomerase activity was noted in the highest grade tumors.
Aged↗
Handling and pathology reporting of specimens with carcinoma of the urinary bladder, ureter, and renal pelvis.
OBJECTIVE: Pathologists play a pivotal role in the diagnosis and in the report of the pathological features related to prognosis. METHODS: To meet these endpoints, the following issues must be accomplished: adequate information about the patient history, proper handling of the specimens, identification of the reliable histopathological techniques necessary to reach the more detailed diagnostic information and evaluate the prognostic variables, and a standardized pathological report. RESULTS: Recent efforts to standardize the histopathological evaluation have generated significant confusion among the urological and pathological communities as well. No consensus has been achieved about the optimal pathological grading of urothelial tumors, to date. CONCLUSION: A proposal for standardization of sampling and reporting of the urothelial tissues achieved within Uropathology follows. The urologists have a great role in assisting pathologists in the proper examination by providing them with clinical information.
Biopsy↗
Non-invasive urothelial neoplasms: according to the most recent WHO classification.
The key points of the latest World Health Organization (WHO) classification of non-invasive urothelial tumors are: the description of the categories has been expanded in the current version to improve their recognition; one group (papillary urothelial neoplasm of low malignant potential) with particularly good prognosis does not carry the label of 'cancer'; it avoids use of ambiguous grading such as grade 1/2 or 2/3 (according to the WHO classification published in 1973, i.e., 1973 WHO classification); the group of non-invasive high grade carcinoma is large enough to contain virtually all those tumors that have biological properties (and a high level of genetic instability) similar to those seen in invasive urothelial carcinoma. This scheme is meant to replace the 1973 WHO classification. Changes in classification have their own inherent problems, tending to lead to confusion, at least for a period of time. From the practical point of view, the use of both the 1973 and the latest WHO classifications is recommended until the latter is sufficiently validated.
Adult↗
Handling and pathology reporting of prostate biopsies.
Appropriate handling and processing of prostate needle biopsies is critical for an optimal examination by pathologists. Reporting by pathologists should be accurate, unequivocal and concise, giving the information needed for the urologist. Quality parameters need to be developed to survey the performance of pathology laboratories.
Humans↗
The use of morphological characteristics and texture analysis in the identification of tissue composition in prostatic neoplasia.
Quantitative examination of prostate histology offers clues in the diagnostic classification of lesions and in the prediction of response to treatment and prognosis. To facilitate the collection of quantitative data, the development of machine vision systems is necessary. This study explored the use of imaging for identifying tissue abnormalities in prostate histology. Medium-power histological scenes were recorded from whole-mount radical prostatectomy sections at x 40 objective magnification and assessed by a pathologist as exhibiting stroma, normal tissue (nonneoplastic epithelial component), or prostatic carcinoma (PCa). A machine vision system was developed that divided the scenes into subregions of 100 x 100 pixels and subjected each to image-processing techniques. Analysis of morphological characteristics allowed the identification of normal tissue. Analysis of image texture demonstrated that Haralick feature 4 was the most suitable for discriminating stroma from PCa. Using these morphological and texture measurements, it was possible to define a classification scheme for each subregion. The machine vision system is designed to integrate these classification rules and generate digital maps of tissue composition from the classification of subregions; 79.3% of subregions were correctly classified. Established classification rates have demonstrated the validity of the methodology on small scenes; a logical extension was to apply the methodology to whole slide images via scanning technology. The machine vision system is capable of classifying these images. The machine vision system developed in this project facilitates the exploration of morphological and texture characteristics in quantifying tissue composition. It also illustrates the potential of quantitative methods to provide highly discriminatory information in the automated identification of prostatic lesions using computer vision.
Humans↗
Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia.
This digital texture analysis-based study evaluates the chromatin organization state in flat and cribriform high-grade prostatic intraepithelial neoplasia (PIN), in the adjacent normal looking secretory epithelium and in the co-occurring adenocarcinoma. Digital texture analysis (karyometry) was carried out on hematoxylin and eosin-stained sections from 24 radical prostatectomy specimens with high-grade PIN (12 with flat and 12 with cribriform architectural pattern, respectively) and cancer. Quantification was also conducted on the normal looking secretory epithelium. Discriminant analysis and the nonsupervised learning algorithm P-index were used to identify suitable subsets of features useful for the discrimination and classification of pathological groups and to explore multivariate data structure in the pathological subgroups. The average nuclear abnormality increases monotonically from the histologically normal appearing secretory epithelium to high-grade PIN and to adenocarcinoma. The nuclei from the so-called perimeter compartment of the flat high-grade PIN lesions show a higher nuclear abnormality compared to the nuclei of the cribriform high-grade PINs. Discriminant analysis shows that flat and cribriform high-grade PINs fall into two populations. Processing by the nonsupervised learning algorithm P-index revealed the existence of three well-defined, distinct subpopulations of nuclei of different chromatin phenotype. In the flat high-grade PIN lesions the proportions of nuclei in the three subpopulations are 16.5% (low abnormality), 25.0% (mid abnormality) and 58.5% (high abnormality), respectively. In the cribriform high-grade PIN lesions, 100% of the nuclei are in the mid-abnormality subpopulation. These differences are also discernible in the co-occurring adenocarcinoma and the histologically normal appearing secretory epithelium. To conclude, karyometry and statistical analysis detect the existence of distinct cell subpopulations of different chromatin packaging and phenotype, with the nuclei from the flat high-grade PIN lesions, adjacent normal looking epithelium and co-occurring adenocarcinoma expressing a greater nuclear abnormality than in the specimens with cribriform high-grade PIN.
Cell Nucleus↗
Comparison of proliferating cell nuclear antigen immunostaining in lymph node metastases and primary prostate adenocarcinoma after neoadjuvant androgen deprivation therapy.
OBJECTIVE: To evaluate the effect of neoadjuvant androgen deprivation therapy (NADT) on the cellular proliferative activity in primary prostate cancer and lymph node metastases using proliferating cell nuclear antigen (PCNA) immunostaining. MATERIAL AND METHODS: Metastatic pelvic lymph nodes and tumoral prostatic tissue were obtained from 21 patients after radical prostatectomy and pelvic lymphadenectomy. Sixteen patients received NADT for 3 months prior to surgery; five patients did not and were evaluated as a control group. Histopathologic analysis was performed using PCNA immunostaining. and histopathologic findings of primary tumors and lymph node metastases after NADT were reported. Clinical follow-up was performed for a mean of 43.7 months. RESULTS: Evaluation of PCNA immunostaining of lymph node metastases in the 16 treated patients revealed a mean positivity for metastatic tumor of 4.5% (SD 3.1%); the corresponding value for the five patients who were not treated with NADT was 19.6% (SD 0.94%) (p < 0.05). In four of the treated cases the proliferative activity in the lymph node metastases was greater than that in the other 12 (9.3% and 3.0%, respectively) and no histopathologic regressive changes were observed in these four cases. The residual tumoral proliferative activity in lymph nodes was greater than that in primary tumors (4.5% and 1.3%, respectively). CONCLUSIONS: This study shows that the nodal metastases were responsive to hormonal therapy, as assessed by PCNA staining, although a greater residual proliferative activity was observed after NADT in lymph node metastases in comparison with the primary prostatic tumor. This can be attributed to a metastatic phenotype less responsive to hormonal therapy compared to the primary tumor.
Adenocarcinoma↗
Neoadjuvant hormone treatment with leuprolide acetate depot 3.75 mg and cyproterone acetate, before radical prostatectomy: a randomized study.
OBJECTIVES: To assess the effect of neoadjuvant hormone treatment before radical prostatectomy on: tumor/prostate volume, prostate-specific antigen (PSA) and testosterone levels, surgical margin status and tumor stage, and the ease of surgery following treatment. METHODS: Patients with clinically localized prostatic carcinoma were randomized to receive leuprolide acetate depot 3.75 mg once a month for 3 months and cyproterone acetate 300 mg once a week for 3 weeks prior to surgery (group A). A control group of patients had surgery without any pretreatment (group B). RESULTS: 167 patients were evaluated for the efficacy parameters. In group A, 31% of patients had a reduction in tumor/prostate volume following hormone therapy. PSA and testosterone levels were significantly reduced (p = 0.0001) in patients in group A compared to basal values. Centralized histopathological data evaluated in 145 patients (group A and 75 group B) showed that more patients in group B had tumors at stages T3A and T3B than in group A; this difference was close to significance (p = 0.057). Positive surgical margins were more common in group B (60% of patients) compared to group A (39% of patients). Similarly lymph node involvement was more common in group B compared to group A (11 versus 3%). There was little difference between the 2 study groups for the other surgical parameters assessed (ease of dissection, duration of surgery, blood loss). CONCLUSIONS: Neoadjuvant hormone therapy before radical prostatectomy has some effects in the treatment of prostate cancer. However, long-term follow-up of patients is needed to assess the impact of this therapy on morbidity and mortality.
Adenocarcinoma↗
Prognostic factors in survival of patients with stage Ta and T1 bladder urothelial tumors: the role of G1-S modulators (p53, p21Waf1, p27Kip1, cyclin D1, and cyclin D3), proliferation index, and clinicopathologic parameters.
We studied 159 cases of superficial (stage Ta or T1) bladder tumors to determine the significance on survival of a subset of regulators of transition from G1 to S phase of the cell cycle (p53, p21Waf1, p27Kip1, cyclin D1, cyclin D3) and tumor proliferation (Ki-67 [MIB-1]). Clinical findings (patient age, sex, tumor size, grade, stage [Ta or T1]) were included in the analysis. Univariate analysis revealed association of tumor size (P = .0353), grade in stage Ta tumors (P = .0074), cyclin D1 expression (P = .0182), and Ki-67 index (P = .0033) with disease-free survival and of tumor size (P = .0005), stage (P = .0494), cyclin D3 expression (P = .0105), and Ki-67 index (P = .0272) with overall survival. Cox multivariate analysis revealed cyclin D1 expression and high proliferation index (disease-free) and tumor size, cyclin D3 expression, and high proliferation index (overall survival) as independent predictors. Results suggest that alterations of the progression from the G1 to S phase of the cell cycle are common in papillary urothelial bladder tumors. High tumor proliferation, expression of cyclins D1 and D3, and tumor size at diagnosis might be relevant predictors of survival in patients with stage Ta and T1 bladder urothelial tumors.
Adult↗
Does finasteride alter the pathology of the prostate and cancer grading?
All forms of androgen-deprivation therapy, including finasteride, induce distinctive histologic changes in benign and neoplastic prostatic epithelial cells, including cytoplasmic clearing, nuclear and nucleolar shrinkage, and chromatin condensation. Treated cancer has a significantly higher architectural (Gleason) grade, lower nuclear grade, and smaller nucleolar diameter than untreated controls, creating the potential for grading bias. Recognition of these changes may be difficult in needle biopsies and lymph node metastases with treated cancer because of the subtle infiltrative pattern and inconspicuous nucleoli. The effects of finasteride may be less pronounced than other forms of therapy with variable distribution throughout the prostate; further, there may be greater sensitivity of low and intermediate-grade cancer than high-grade cancer. The Gleason grading system for cancer should not be used after finasteride treatment as it is not validated in this setting and is likely to overestimate the biologic potential of high-grade cancer observed after therapy. Chemoprevention trials with agents such as finasteride that alter morphology should not rely on cancer grading as a secondary endpoint owing to grading bias.
5-alpha Reductase Inhibitors↗
Immunohistochemical evaluation of urokinase plasminogen activator receptor in noninvasive and early invasive urothelial papillary neoplasia.
OBJECTIVE: To investigate urokinase plasminogen activator receptor (uPAR) expression in urothelial papilloma and in noninvasive and early invasive papillary carcinoma. STUDY DESIGN: The study included 40 cases of papillary neoplasia of the urinary bladder subdivided into 10 cases of urothelial papilloma (UP); 10 of papillary carcinoma, grade 1; 10, grade 2 (G2); and 10, grade 3 (G3). Invasion of the subepithelial connective tissue was present in 5 cases of G2 and 7 cases of G3. According to the 2002 revision of the TNM system, these cases were defined as T1 and the others as Ta. uPAR expression was evaluated with an immunohistochemical technique in 5-microns-thick tissue sections. RESULTS: Difference in the distribution of positive cases in the 4 groups were statistically significant and greatest in G3. Statistically significant differences were also observed between Ta and T1 cases in terms of uPAR intensity. CONCLUSION: Detection of immunoreactivity for uPAR was associated with high grade UP carcinomas. These data indicate that uPAR is potentially an important prognostic factor in bladder carcinoma.
Biomarkers, Tumor↗
Karyometric features of low and high grade glial tumors as compared with their MRI appearance.
OBJECTIVE: To compare the results of a magnetic resonance imaging (MRI) grading designed to identify low and high grade gliomas with karyometry used as a tool to grade primary brain tumors. STUDY DESIGN: A consecutive series of 23 primary brain tumors was selected for this study. The neuroradiologist, not knowing the histologic diagnoses, divided the cases into low and high grade categories on the basis of the following 7 features: border sharpness, heterogeneity without contrast, cavitation, contrast enhancement, hypervascularity, mass effect and perifocal T2 hyperintensity. To each feature was given a numerical value, ranging from 1 to 3. All the cases were reviewed and classified by the same pathologist, blinded to the MRI diagnosis. Two hundred nuclei per case were recorded, and 93 karyometric features related to nuclear area, total optical density and chromatin distribution were analyzed for each nucleus. Statistical analysis included discriminant analysis, Kruskal-Wallis test, nonsupervised learning algorithm P-index and Beale statistic. RESULTS: Ten cases were classified as low grade on the basis of their MRI features. The corresponding histopathologic diagnoses were: grade 2 astrocytoma in 2 cases and grade 2 oligodendroglioma in 8 cases. An MRI diagnosis of high grade tumor was made in 13 cases. In 10 cases it was confirmed by the histopathologic diagnosis (3 grade 3 astrocytomas, 1 grade 3 oligodendroglioma and 6 glioblastomas). In the remaining 3 cases the histologic examination revealed a low grade tumor, 1 grade 2 astrocytoma and 2 grade 2 oligodendrogliomas. For the purposes of the karyometric analysis the cases were allocated to the low or high grade category according to their histologic diagnosis (13 cases low grade and 10 cases high grade). Nuclei from low and high grade tumors showed clearly different karyometric characteristics. The oligodendroglioma nuclei had abnormality values close to the low grade standard, while the astrocytoma nuclei were a highly dispersed group with characteristics indicative of a higher degree of nuclear abnormality than the oligodendroglioma nuclei. The results of karyometric analysis showed that grade 2 tumors, corresponding to the low grade group, form a rather distinct category from grade 3 and 4 tumors belonging to the high grade group. CONCLUSION: The results of MRI grading based on a series of features that are routinely assessed by the neuroradiologist to reach a final diagnosis correlate highly with the histopathologic diagnosis. Karyometry can be a useful adjunct to histologic grading.
Astrocytoma↗
Morphological assessment of radical prostatectomy specimens. A protocol with clinical relevance.
The increase in prostate cancer detection has induced a sharp increase in the number of radical prostatectomies Proper examination of radical prostatectomy (RP) specimens by pathologists is critical in determining the need for adjuvant treatment and prediction of patient outcome. The pathology report should include relevant clinical information as well as provide prognostically useful information derived from the macroscopic examination and microscopic evaluation of the RP specimen
Histological Techniques↗
Subvisual changes in chromatin organization state are detected by karyometry in the histologically normal urothelium in patients with synchronous papillary carcinoma.
This study analyzed the chromatin organization state in histologically normal urothelium in patients with synchronous papillary carcinoma using digital texture analysis. The quantitative evaluation was carried out on hematoxylin and eosin-stained sections from 17 cases of urothelial papillary carcinoma in which a simultaneous biopsy specimen featuring histologically normal urothelium was available. Five bladder biopsy specimens of histologically normal urothelium from patients with prostate pathology in whom cystoscopy revealed a normal bladder mucosa were also analyzed. Karyometry showed that the 17 cases of papillary carcinoma, morphologically classified according to the 1973 World Health Organization scheme, belonged to a continuous spectrum or trend curve spanning grade 1 to grade 3. An abnormal pattern and distribution of the nuclear chromatin was seen in the normal-looking urothelium from the 17 bladders with papillary lesions. When this population was plotted along the trend curve, it occupied an intermediate position between the normal samples and samples from grade 1 carcinoma. When the nuclei were considered individually, the changes were detected only in a subpopulation of nuclei with chromatin alteration pointing toward that seen in grade 1 cases, even though distinct from them. In conclusion, karyometry can detect an abnormal chromatin pattern and distribution in the normal-looking urothelium adjacent to papillary carcinoma. Such alterations correspond to the so-called "malignancy-associated change."
Carcinoma, Papillary↗
Molecular techniques and prostate cancer diagnostic.
Recent advances in molecular techniques have given the opportunity to assess genomic and proteomic alterations comprehensively and rapidly in routinely acquired tissue samples. In particular, new markers derived from qualitative and quantitative DNA, RNA, and protein analysis have provided additional objective information to supplant and extend the morphologic interpretations and have been increasingly integrated into the final surgical pathology diagnosis. In this review several recently developed molecular techniques are described and illustrated. The focus is on prostate cancer diagnostics, as an example of their application.
Humans↗