Marina Scarpelli

2009 update on the classification of renal epithelial tumors in adults

The classification of kidney tumors in adults expands rapidly with new categories recently incorporated. This will result in the modification of the current 2004 World Health Organization (WHO) classification of the adult renal epithelial neoplasms. Emphasis should be placed in defining risk groups categorized as malignant or benign tumors, including a category of tumors with low malignant potential to accommodate recently recognized categories with extremely good prognosis after surgery. Unusual tumors such as familial renal cell carcinoma (RCC), translocation RCC, renal cell carcinoma after neuroblastoma, tubular mucinous and spindle cell carcinoma, and mixed epithelial and stromal tumors are also presented. A number of recently described entities and morphologic variants of classical categories deserve recognition since they can be important in differential diagnosis. This review emphasizes clinical, pathological and genetic features defining renal epithelial tumors in adults.

Gleason grading of prostate cancer in needle biopsies or radical prostatectomy specimens: contemporary approach, current clinical significance and sources of pathology discrepancies

The Gleason grading system is a powerful tool to prognosticate and aid in the treatment of men with prostate cancer. The needle biopsy Gleason score correlates with virtually all other pathological variables, including tumour volume and margin status in radical prostatectomy specimens, serum prostate‐specific antigen levels and many molecular markers. The Gleason score assigned to the tumour at radical prostatectomy is the most powerful predictor of progression after radical prostatectomy. However, there are significant deficiencies in the practice of this grading system. Not only are there problems among practising pathologists but also a relative lack of interobserver reproducibility among experts.

Mechanisms of Disease: high-grade prostatic intraepithelial neoplasia and other proposed preneoplastic lesions in the prostate

High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor of prostatic adenocarcinoma according to virtually all available evidence. This lesion is characterized by cellular proliferations within pre-existing ducts and acini, with nuclear and nucleolar enlargements similar to those seen in prostate cancer, although unlike cancer HGPIN retains a basal-cell layer. The recognition of HGPIN is clinically important because of the strong association between this disease and prostatic carcinoma. The predictive value for cancer of an initial diagnosis of HGPIN on needle biopsy has substantially declined, with values falling from 36% to 21%. A major factor contributing to this decline is related to increased use of needle biopsy core sampling, which has provided the means for many cancers associated with HGPIN to be detected on initial biopsy; repeat biopsy, even with good sampling, does not detect many additional cancers. Other possible findings in the prostate might indicate premalignant disease (low-grade prostatic intraepithelial neoplasia, atrophy, malignancy-associated changes, and atypical adenomatous hyperplasia or adenosis), but the data for these premalignant diseases are much less convincing than those for HGPIN.

Role of immunohistochemistry in diagnosing renal neoplasms when is it really useful

CONTEXT With the refinement of molecular and histologic classifications of renal neoplasms and the availability of more-effective molecular targeted therapy for specific renal neoplasms, immunohistochemical techniques will play an increasingly important role in the diagnosis of renal neoplasm. During the past few decades, many markers have been evaluated for their role in the diagnosis, prognosis, and prediction of treatment for renal neoplasms. The number of useful markers in our routine practice continues to increase. The challenge will be to choose among them and to decide in which situations immunohistochemistry will be truly useful. OBJECTIVES To review the diagnostic utility of molecular markers for renal neoplasms and common diagnostic scenarios that call for immunohistochemistry in routine practice. DATA SOURCES This review is based on published literature and personal experience. CONCLUSIONS Some of the most important and useful markers for the diagnosis of renal neoplasm include cytokeratins, vimentin, PAX2, PAX8, RCC marker, CD10, E-cadherin, kidney-specific cadherin, parvalbumin, claudin-7, claudin-8, α-methylacyl coenzyme A racemase, CD117, TFE3, thrombomodulin, uroplakin III, p63, CD57, and carbonic anhydrase IX. Each marker has its diagnostic role in a specific diagnostic setting. The common diagnostic situations that call for immunohistochemical staining are differential diagnoses of renal versus nonrenal neoplasms, histologic subtyping of renal cell carcinoma, diagnosis of rare primary renal neoplasms, diagnosis of renal neoplasms in small core-biopsy specimens, diagnosis of possible metastatic renal carcinomas, and less frequently, molecular prognostication.

Prostatic intra-epithelial neoplasia: Qualitative and quantitative analyses of the blood capillary architecture on thin tissue sections

The aim of our study was to qualitatively and quantitatively investigate the capillary architecture on lectin Ulex Europaeus agglutinin I-stained histological section in prostatic intra-epithelial neoplasia. The capillaries appeared as small, short or elongated vessels with either a smooth or undulated external contour and either virtual or visible lumen, sometimes with a clearly identifiable endothelial nucleus/i. In the benign prostatic hyperplasia and prostatic intra-epithelial neoplasia categories, the capillaries appeared located in close contact with (i.e. touching) or in proximity to the basement membrane of ducts and acini. In the invasive adenocarcinoma category, on the contrary, the capillaries in general appeared interspersed within the tumour stroma and septa. Our quantitative studies of the capillary architecture showed that, going from benign prostatic hyperplasia through prostatic intra-epithelial neoplasia up to invasive adenocarcinoma, an increasing proportion of capillaries becomes shorter, with open lumen and undulated external contour and with a greater number of endothelial cells. The highest proportion of touching capillaries was seen in benign prostatic hyperplasia, while the lowest was in invasive adenocarcinoma, being intermediate in prostatic intra-epithelial neoplasia. When the prostatic intra-epithelial neoplasia samples were divided into low-grade and high-grade, the feature values in the low-grade approached those in benign prostatic hyperplasia, whereas in the high-grade they were close to invasive adenocarcinoma. Half of the benign prostatic hyperplasia samples were taken from total prostatectomies because of the preoperative diagnosis of prostatic adenocarcinoma. The feature values in this subcategory were close to those of prostatic intra-epithelial neoplasia of low grade.

Morphological diagnosis of urothelial neoplasms

The morphological classification and diagnosis of bladder neoplasms is summarised, with specific focus on histological typing, grading and staging. Four diagnostic categories are described on the basis of the pattern of growth of the urothelial lesions and tumours (flat, exophytic or papillary, endophytic, and invasive). The WHO 2004 classification is currently used. However, the WHO 1973 classification is still considered by many urologists and oncologists as the international standard in patient management.

Changes produced in the urothelium by traditional and newer therapeutic procedures for bladder cancer

A handful of traditional and newer therapeutic procedures, such as chemotherapy, immunotherapy, radiotherapy, photodynamic and laser treatment, and gene therapy, are used to treat epithelial malignancies of bladder origin. These treatment modalities, used either intravesically or systemically, produce morphological changes in the urothelial mucosa that can be mistaken for carcinoma. The pathologist must be able to separate toxic and drug related alterations from tumour related changes. The clinical history is usually invaluable in this assessment.

Precancerous lesions and conditions of the prostate: from morphological and biological characterization to chemoprevention.

Abstract: Prostatic intraepithelial neoplasia (PIN) is composed of dysplastic cells with a luminal cell phenotype, expressing the androgen receptor as well as prostate‐specific antigen. PIN is characterized by progressive abnormalities of phenotype that are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of carcinogenesis. High‐grade PIN is considered the most likely precursor of prostatic carcinoma, according to virtually all available evidence. Androgen deprivation decreases the prevalence and extent of PIN and the degree of capillary vascularization (e.g., angiogenesis) in the surrounding stroma via suppression of vascular endothelial growth factor production. Prostatic carcinoma is also likely to arise from precursor lesions other than high‐grade PIN such as low‐grade PIN, atypical adenomatous hyperplasia, malignancy‐associated foci, and atrophy.

Is incidentally detected prostate cancer in patients undergoing radical cystoprostatectomy clinically significant

Cystoprostatectomy specimens obtained from patients with bladder cancer provide a unique opportunity to assess the features of silent prostate adenocarcinoma (PCa). The whole-mount prostate sections of 248 totally embedded and consecutively examined radical cystoprostatectomy (RCP) specimens were reviewed to determine the incidence and features of incidentally detected PCa. PCa was considered clinically significant if any of the following criteria were present: total tumor volume, 0.5 cc or more; Gleason grade, 4 or more; extraprostatic extension; seminal vesicle invasion; lymph node metastasis (of PCa); or positive surgical margins. PCa was present in 123 (49.6%) of 248 specimens. Features were as follows: acinar adenocarcinoma, 123 (100.0%); peripheral zone location, 98 (79.7%); pT2a, 96 (78.0%); pT2b, 11 (8.9%); pT2c, 9 (7.3%); pT3a, 5 (4.1%); pT3b, 2 (1.6%); pT4, 0 (0.0%); Gleason score 6 or less, 107 (87.0%); negative margins, 119 (96.7%); pN0 for PCa, 123 (100.0%); and tumor volume less than 0.5 cc, 116 (94.3%). Of the 123 incidentally detected cases of PCa, 100 (81.3%) were considered clinically insignificant. Incidentally detected PCa is frequently observed in RCP. The majority are clinically insignificant.

Nerve regeneration through a combined autologous conduit (vein plus acellular muscle grafts)

The authors describe nerve regeneration obtained by using a combined autologous conduit, consisting of a vein plus acellular muscle grafts. The right sciatic nerve of seven Sprague Dawley rats was transected for a length of 2 cm and the gap was filled with 2 cm long femoral vein conduit in which two autologous acellular muscle grafts had been previously inserted. Clinical and electrophysiologic tests were carried out twelve weeks after the surgical procedure. The nerve was then removed and a morphological study, including histologic examination, immunohistochemistry and quantitative analysis, was performed. The left sciatic nerve was also removed and used as a control. Regeneration was observed in the middle and distal parts of the conduit in 5 rats. Nerve conduction velocity ranged between 0 and 14.9 ms(-1). In the distal part the nerves were enclosed by a perineurium thicker than their normal counterpart and in which groups of small axons were surrounded by thin myelin sheaths. Quantitative analysis showed that the operated nerve presented a wide variation of the area of the fascicle and the density of the fibres per area, while the diameter of the axons and myelinated fibres showed only small variation, independent of the size of the fascicle. In conclusion, by using this technique, the authors succeeded in obtaining regeneration of a well formed nerve fascicle.