Findings in 1,123 Men with Preoperative 68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography/Computerized Tomography and Multiparametric Magnetic Resonance Imaging Compared to Totally Embedded Radical Prostatectomy Histopathology: Implications for the Diagnosis and Management of Prostate Cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) fails to identify some men with significant prostate cancer. Prostate-specific membrane antigen positron emission tomography/computerized tomography (PSMA PET/CT) is recommended for staging of prostate cancer, but its additional benefit above mpMRI alone in local evaluation for prostate cancer is unclear. The study aim was to evaluate the ability of mpMRI and PSMA PET/CT individually and in combination, to predict tumor location and Gleason score ≥3+4 on robot-assisted laparoscopic radical prostatectomy (RALP) histology. MATERIALS AND METHODS: We retrospectively reviewed 1,123 men with a preoperative mpMRI and 68Ga-PSMA PET/CT prior to a RALP. Tumor locations were collected from both imaging modalities and compared to totally embedded prostate histology. Lowest apparent diffusion coefficient value on mpMRI and the highest maximum standardized uptake value (SUVmax) on 68Ga-PSMA PET/CT were collected on the index lesions to perform analysis on detection rates. RESULTS: Median prostate specific antigen was 6. Median Gleason score on biopsy and RALP histology was 4+3. The index lesion and multifocal tumor detection were similar between mpMRI and 68Ga-PSMA PET/CT (p=0.10; p=0.11). When combining mpMRI and 68Ga-PSMA PET/CT, index Gleason score ≥3+4 cancer at RALP was identified in 92%. Only 10% of patients with Gleason score ≤3+4 on biopsy with an SUVmax <5 were upgraded to ≥4+3 on RALP histology, compared to 90% if the SUVmax was >11. CONCLUSIONS: The addition of a diagnostic 68Ga-PSMA PET/CT to mpMRI can improve the detection of significant prostate cancer and improve the ability to identify men suitable for active surveillance.

Dataset for the reporting of urinary tract carcinoma-biopsy and transurethral resection specimen: recommendations from the International Collaboration on Cancer Reporting (ICCR).

The International Collaboration on Cancer Reporting (ICCR) is an alliance of major pathology organisations in Australasia, Canada, Europe, United Kingdom, and United States of America that develops internationally standardised, evidence-based datasets for the pathology reporting of cancer specimens. This dataset was developed by a multidisciplinary panel of international experts based on previously published ICCR guidelines for the production of cancer datasets. It is composed of Required (core) and Recommended (noncore) elements identified on the basis of literature review and expert consensus. The document also includes an explanatory commentary explaining the rationale behind the categorization of individual data items and provides guidance on how these should be collected and reported. The dataset includes nine required and six recommended elements for the reporting of cancers of the urinary tract in biopsy and transurethral resection (TUR) specimens. The required elements include specimen site, operative procedure, histological tumor type, subtype/variant of urothelial carcinoma, tumor grade, extent of invasion, status of muscularis propria, noninvasive carcinoma, and lymphovascular invasion (LVI). The recommended elements include clinical information, block identification key, extent of T1 disease, associated epithelial lesions, coexistent pathology, and ancillary studies. The dataset provides a structured template for globally harmonized collection of pathology data required for management of patients diagnosed with cancer of the urinary tract in biopsy and TUR specimens. It is expected that this will facilitate international collaboration, reduce duplication of effort in updating current national/institutional datasets, and be particularly useful for countries that have not developed their own datasets.

Reconsidering the role of pelvic lymph node dissection with radical prostatectomy for prostate cancer in an era of improving radiological staging techniques.

BACKGROUND: Performing an extended pelvic lymph node dissection (PLND) on all men with intermediate- and high-risk prostate cancer at the time of a radical prostatectomy (RP) remains controversial. The majority of patients PLND histology is benign, and the long-term cancer-free progression in men with positive lymph node metastasis is low. The objective is to investigate the probability of long-term biochemical freedom from recurrent disease (bNED) in men with lymph node metastasis identified at the time of radical prostatectomy (RP). SUBJECTS AND METHODS: A retrospective review of the pathology of 1184 pelvic lymph node dissections performed at the time of a radical prostatectomy by multiple surgeons referred to a single uro-pathology laboratory between 2008 and 2014 identified 61 men with node-positive prostate cancer. Of the men with positive nodes, 24 had a standard PLND and 37 an extended PLND (ePLND). bNED was defined as a post-operative serum PSA < 0.2 ng/ml. RESULTS: The median follow-up is 4 years (2-8). The median lymph node count was 7 (range 2-16) for PLND and 22 (range 6-46) for the ePLND. A single lymph node metastasis was identified in 56% of the 61 men. Only 10% of men with a positive lymph node metastasis remained free of biochemical recurrence of disease, and only 5% had undetectable serum PSA. There was no difference in bNED outcome between a PLND and ePLND. The number of men needed to be treated with a PLND at the time of RP (NNT) to result in an undetectable post-operative PSA at a median follow-up of 4 years is 395. CONCLUSIONS: In men with lymph node metastasis, the probability of long-term bNED is low and the NNT for cure is high. With emerging improved radiological imaging techniques increasing the detection of lymph node metastasis outside the extended lymph node dissection templates, more scientific investigation is required to evaluate which men will benefit from a PLND and which men can avoid an unnecessary PLND procedure.

[The 2014 consensus conference of the ISUP on Gleason grading of prostatic carcinoma]. / Konsenskonferenz 2014 der ISUP zur Gleason-Graduierung des Prostatakarzinoms.

In 2005 the International Society of Urological Pathology (ISUP) held a concensus conference on Gleason grading in order to bring this grading system up to the current state of contemporary practice; however, it became clear that further modifications on the grading of prostatic carcinoma were necessary. The International Society of Urological Pathology therefore held a further consensus conference in 2014 to clarify these points. This article presents the essential results of the Chicago grading meeting.

[Vancouver classification of renal tumors: Recommendations of the 2012 consensus conference of the International Society of Urological Pathology (ISUP)]. / Vancouver-Klassifikation von Nierentumoren : Empfehlungen der Konsenskonferenz der Internationalen Gesellschaft für Uropathologie (ISUP) 2012.

The 2012 consensus conference of the International Society of Urological Pathology (ISUP) has formulated recommendations on classification, prognostic factors and staging as well as immunohistochemistry and molecular pathology of renal tumors. Agreement was reached on the recognition of five new tumor entities: tubulocystic renal cell carcinoma (RCC), acquired cystic kidney disease-associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription factor family RCC, in particular t(6;11) RCC and hereditary leiomyomatosis-associated RCC. In addition three rare forms of carcinoma were considered as emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC and anaplastic lymphoma kinase (ALK) translocation RCC. In the new ISUP Vancouver classification, modifications to the existing 2004 World Health Organization (WHO) specifications are also suggested. Tumor morphology, a differentiation between sarcomatoid and rhabdoid and tumor necrosis were emphasized as being significant prognostic parameters for RCC. The consensus ISUP grading system assigns clear cell and papillary RCCs to grades 1-3 due to nucleolar prominence and grade 4 is reserved for cases with extreme nuclear pleomorphism, sarcomatoid and/or rhabdoid differentiation. Furthermore, consensus guidelines were established for the preparation of samples. For example, agreement was also reached that renal sinus invasion is diagnosed when the tumor is in direct contact with the fatty tissue or loose connective tissue of the sinus (intrarenal peripelvic fat) or when endothelialized cavities within the renal sinus are invaded by the tumor, independent of the size. The importance of biomarkers for the diagnostics or prognosis of renal tumors was also emphasized and marker profiles were formulated for use in specific differential diagnostics.

[Diagnostics of radical prostatectomy specimens. Results of the 2009 consensus conference of the International Society of Urological Pathology]. / Diagnostik radikaler Prostatektomiepräparate. Ergebnisse der Konsensuskonferenz der Internationalen Gesellschaft für Urologische Pathologie 2009.

The 2009 consensus conference of the International Society of Urological Pathology (ISUP) made recommendations for standardization of handling and staging of radical prostatectomy specimens. The conference topics were preparation of specimens, the T2 subclassification, prostate cancer volume, extraprostatic tumor extent, lymphovascular invasion, seminal vesicle infiltration, lymph node metastases and surgical margins. This review article presents the essential results and recommendations of this conference.

Percentage grade 4 tumour predicts outcome for prostate adenocarcinoma in needle biopsies from patients with advanced disease: 10-year data from the TROG 03.04 RADAR trial.

Previous reports have shown that quantification of high tumour grade is of prognostic significance for patients with prostate cancer. In particular, percent Gleason pattern 4 (GP4) has been shown to predict outcome in several studies, although conflicting results have also been reported. A major issue with these studies is that they rely on surrogate markers of outcome rather than patient survival. We have investigated the prognostic predictive value of quantifying GP4 in a series of prostatic biopsies containing Gleason score 3+4=7 and 4+3=7 tumours. It was found that the length of GP4 tumour determined from the measurement of all biopsy cores from a single patient, percent GP4 present and absolute GP4 were all significantly associated with distant progression of tumour, all-cause mortality and cancer-specific mortality over a 10-year follow-up period. Assessment of the relative prognostic significance showed that these parameters outperformed division of cases according to Gleason score (3+4=7 versus 4+3=7). International Society of Urological Pathology (ISUP) Grade Groups currently divide these tumours, according to Gleason grading guidelines, into grade 2 (3+4=7) and grade 3 (4+3=7). Our results indicate that this simple classification results in the loss of important prognostic information. In view of this we would recommend that ISUP Grade Groups 2 and 3 be amalgamated as grade 2 tumour with the percentage of GP4 carcinoma being appended to the final grade, e.g., 3+4=7 carcinoma with 40% pattern 4 tumour would be classified as ISUP Grade Group 2 (40%).

Dataset for the reporting of carcinoma of the bladder-cystectomy, cystoprostatectomy and diverticulectomy specimens: recommendations from the International Collaboration on Cancer Reporting (ICCR).

The International Collaboration on Cancer Reporting (ICCR) is a not for profit organisation whose goal is to produce standardised internationally agreed and evidence-based datasets for pathology reporting. With input from pathologists worldwide, the datasets are intended to be uniform and structured. They include all items necessary for an objective and accurate pathology report which enables clinicians to apply the best treatment for the patient. This dataset has had input from a multidisciplinary ICCR expert panel. The rationale for some items being required and others recommended is explained, based on the latest literature. The dataset incorporates data from the World Health Organization (WHO) 2016, and also from the latest (8th edition) TNM staging system of the American Joint Committee on Cancer (AJCC). Fifteen required elements and eight recommended items are described. This dataset provides all the details for a precise and valuable pathology report required for patient management and prognostication. This dataset is intended for worldwide use, and should facilitate the collection of standardised comparable data on bladder carcinoma at an international level.

Loss of heterozygosity at 3p14.2 in clear cell renal cell carcinoma is an early event and is highly localized to the FHIT gene locus.

The VHL tumor suppressor gene (TSG) at 3p25-26 is strongly implicated in the pathogenesis of clear cell renal cell carcinoma (cRCC). In addition, 3p14.2 and 3p21 are suspected of harboring additional TSGs in cRCC, with FHIT being a candidate TSG at 3p14.2. We examined 87 microdissected, histologically well-defined cRCCs classified according to tumor-node-metastasis (TNM) stage (stage 1, 23 cases; stage 2, 14 cases; stage 3, 24 cases; stage 4, 26 cases) and Fuhrman grade (grade 1, 24 cases; grade 2, 19 cases; grade 3, 19 cases; grade 4, 8 cases; sarcomatoid cRCC, 17 cases) for loss of heterozygosity (LOH) at 3p14.2 and 3p25-26 using a series of precisely mapped microsatellite probes. We found that LOH at 3p14.2 exceeded LOH at 3p25-26 in frequency (69% versus 48.3%; P < 0.03) and was highly localized to markers within the FHIT gene locus (D3S1300 and D3S4260), with the majority of chromosomal breakpoints also mapping to this region. In addition, 3p14.2 LOH (P < 0.03), but not 3p25-26 LOH (P = nonsignificant), was associated with lower tumor grades (grades 1-3). These findings suggest that 3p14.2 genomic deletions may be among the earliest events in cRCC pathogenesis, preceding genomic deletions at the VHL locus. FHIT, or an as yet undiscovered TSG mapping to the D3S4103-D3S4260 interval, could be the molecular target of the 3p14.2 deletions.

VHL and FHIT locus loss of heterozygosity is common in all renal cancer morphotypes but differs in pattern and prognostic significance.

Deletions involving 3p are believed to be typical for conventional (clear cell) renal cell carcinoma (cRCC), with confirmed and suspected targets being the VHL and FHIT tumor suppressor genes, respectively. By contrast, 3p deletions are felt to be rare in papillary RCC (pRCC) and chromophobe RCC (chRCC); however, this belief is based on relatively scant data. In particular, 3p14.2 deletions, possibly resulting in FHIT inactivation, have been rarely studied in pRCC or chRCC even though they may be relevant in early renal tumorigenesis. We therefore examined 3p deletion rates and patterns in pRCC and chRCC with particular attention to 3p14.2. We examined 16 chRCCs and 27 pRCCs for loss of heterozygosity (LOH) at 3p25-26 and 3p14.2 using 13 well-mapped microsatellite markers. Those pRCC with LOH at 3p25-26 were also screened for VHL gene mutations. The results were correlated with tumor histology and patient outcome and compared with data we had obtained previously on cRCC. We found similar overall 3p LOH rates in pRCC (59%), chRCC (86.6%), and cRCC (75.8%). In pRCC and chRCC, LOH at 3p25-26 was more common than at 3p14.2, whereas the converse was true for cRCC. In the pRCC with 3p25-26 LOH, we confirmed that this was not associated with mutations of the VHL gene. At 3p14.2, LOH rates of pRCC were lower than those of cRCC and chRCC (p<0.02). All morphotypes showed a predominately interstitial LOH pattern, which was most pronounced in the 3p14.2 region in cRCC. 3p LOH in chRCC was associated with improved patient outcome, mirroring our previous cRCC data. We conclude that 3p LOH is a universal phenomenon in RCC, but has different underlying mechanisms, molecular targets, and implications in the different morphotypes, although FHIT inactivation may play a role in both cRCC and chRCC tumorigenesis.

Validation of International Society of Urological Pathology (ISUP) grading for prostatic adenocarcinoma in thin core biopsies using TROG 03.04 'RADAR' trial clinical data.

In 2014 a consensus conference convened by the International Society of Urological Pathology (ISUP) adopted amendments to the criteria for Gleason grading and scoring (GS) for prostatic adenocarcinoma. The meeting defined a modified grading system based on 5 grading categories (grade 1, GS 3+3; grade 2, GS 3+4; grade 3, GS 4+3; grade 4, GS 8; grade 5, GS 9-10). In this study we have evaluated the prognostic significance of ISUP grading in 496 patients enrolled in the TROG 03.04 RADAR Trial. There were 19 grade 1, 118 grade 2, 193 grade 3, 88 grade 4 and 79 grade 5 tumours in the series, with follow-up for a minimum of 6.5 years. On follow-up 76 patients experienced distant progression of disease, 171 prostate specific antigen (PSA) progression and 39 prostate cancer deaths. In contrast to the 2005 modified Gleason system (MGS), the hazards of the distant and PSA progression endpoints, relative to grade 2, were significantly greater for grades 3, 4 and 5 of the 2014 ISUP grading scheme. Comparison of predictive ability utilising Harrell's concordance index, showed 2014 ISUP grading to significantly out-perform 2005 MGS grading for each of the three clinical endpoints.

Phlyctainophora lamnae (Nematoda; Philometridae) from dogfish Squalus acanthias off southern New Zealand.

Coiled globose female nematodes and larvae, identified as Phlyctainophora lamnae Steiner, 1921, were found in tumour-like lesions on the tail fin of spiny dogfish Squalus acanthias L. (Squalidae) caught off southern New Zealand. Nematodes provoke a chronic inflammatory response by the host. No male nematodes were recovered. This is the first record of the genus from New Zealand and the first record of adult Phlyctainophora from the Southern Hemisphere. Phlyctainophora squali Mudrey & Dailey, 1969 is considered a synonym of P. lamnae.

Tumors of pineal parenchymal cells: a correlation of histological features, including nucleolar organizer regions, with survival in 35 cases.

We studied 35 parenchymal neoplasms arising in the pineal gland, including 11 pineoblastomas, 21 pineocytomas, and three mixed pineocytoma-pineoblastomas. Pineoblastomas were most commonly found in children (mean age, 12.6 years). The median postsurgical length of survival for seven patients, including five with remote metastases, with fatal outcome was 24 months. The 21 pineocytomas were found in older individuals (mean age, 26.8 years). Four patients with pineocytoma died; two before surgery and two in the immediate postoperative period. The remaining 17 patients survived for intervals between 6 and 118 months after surgery. Two mixed pineocytoma-pineoblastomas were found in infants who died a few months after biopsy, whereas a third patient, an adult, was alive at 46 months after excision and irradiation. Both pineoblastoma and pineocytoma exhibited variable immunoreactivity to neurofilament proteins, synaptophysin, glial fibrillary acidic protein, S-100 protein, retinal-S antigen, and rhodopsin; the highest percentages of positive cells stained with synaptophysin. Three pineocytomas exhibited ganglionic differentiation and two of them also showed a glial component. Prognosis could not be correlated with the degree of divergent differentiation. Comparison of silver-stained nucleolar organizer region (AgNOR) counts between pineoblastomas and pineocytomas suggests that the former are more actively proliferative than the latter, with mixed pineocytoma-pineoblastoma showing intermediate activity. There was no correlation between AgNOR score and prognosis within the three tumor groups.

Morphologic typing of papillary renal cell carcinoma: comparison of growth kinetics and patient survival in 66 cases.

Whereas papillary renal cell carcinoma is now established as a subtype of renal cell neoplasia, division of these tumors into 2 distinctive morphotypes has been proposed. Type 1 tumors have cells with scanty pale cytoplasm arranged in a single layer on the basement membrane of papillary cores. In these tumors, psammoma bodies and foamy macrophages are frequently seen, and the tumors frequently express cytokeratin 7. Type 2 tumor cells have pseudostratified nuclei and usually have voluminous eosinophilic cytoplasm. Recent studies have supported this subclassification of papillary renal cell carcinoma by demonstrating differing genotypes for type 1 and 2 tumors. To further study the subclassification of papillary renal carcinoma, we compared clinical features, nuclear grade, stage, tumor growth kinetics, and survival in a series of 50 type 1 and 16 type 2 papillary renal cell carcinomas. Comparison of patient age at presentation, sex, and primary tumor size shows no significant difference between the 2 tumor types. Type 1 tumors were of significantly lower Fuhrman grade (P =.0001) and higher Robson stage (P =.009) than type 2 tumors. There was no significant difference when tumors were staged according to the TNM classification. Assessment of tumor growth kinetics showed significantly different mean silver-staining nucleolar organizer region (AgNOR) scores and Ki-67 indices (AgNOR type 1, 3.83, type 2, 7.24, P =.0001; Ki-67 type 1, 3.17%, type 2, 6.01%, P =.0002). Multivariate analysis showed tumor type (P =.03), presence of metastases (P =.04), AgNOR score (P =.001), and Ki-67 index (P =.03) to be independently associated with survival. These results provide evidence of the clinical utility of dividing papillary renal cell carcinomas into 2 types according to histologic characteristics.

Serum creatine kinase levels parallel the clinical course for rhabdomyomatous Wilms tumor.

A right-sided renal mass in an 11-month-old girl was diagnosed by percutaneous needle biopsy as Wilms tumor, which on histologic examination was found to be predominantly rhabdomyomatous. As part of the examination, serum creatine kinase (CK) and CK-MB levels were measured and were significantly elevated at 994 U/L (reference range, 42-180 U/L) and 40 U/L (reference range, 0-3 U/L), respectively. Subsequently, an 8-month-old girl was admitted to the hospital with septicemia and was found to have an abdominal mass. A diagnosis of bilateral Wilms tumor was made following percutaneous biopsy of both kidneys; histologic examination confirmed that the tumor was predominantly rhabdomyomatous. Serum CK and CK-MB levels also were measured and were significantly elevated at 685 U/L and 84.4 U/L, respectively. In both cases, the serum CK and CK-MB levels reflected the clinical course; elevation in serum levels was associated with tumor recurrence, infarction, or chemotherapy-related necrosis. We conclude that these enzymes have clinical usefulness as markers for Wilms tumor showing rhabdomyomatous morphologic features.

The histopathology of endocardial sclerosis.

This histological study of endocardial thickening in human hearts revealed that as in adult hearts, the proliferation in fetal, neonatal, and infant hearts consisted of collagen, elastin, and smooth muscle cells. Variation in severity from chamber to chamber and site to site indicated that severity is not an aging phenomenon and that predominantly local blood flow conditions determine localization and progression of proliferation. The similarity to endocardial thickening of cardiac valves and to intimal proliferation in blood vessels was remarkable. In old age and in chronic rheumatic heart disease the proliferation exhibited hyalinization, cell depletion, loss and fragmentation of elastin, lipid accumulation, and thrombosis, indicative of a similar pathogenesis to atherosclerotic changes in valvular endocardium and blood vessels. It was concluded that these chronic hemodynamically induced degenerative changes in the endocardium, including cardiac valves, should be classified as endocardial atherosclerosis analogous to that in arteries and veins and that severity is aggravated by high blood pressure, cardiac malformations, and dysfunction or damage caused by other disease processes.

Smooth muscle cell depletion and collagen types in progeric arteries.

Review of two autopsy cases of progeria confirms severe smooth muscle cell (SMC) depletion in the atherosclerotic aortic media and the presence of collagen types I, III, IV, V, and VI in the aorta and renal vessels as is consistent with atherosclerotic disease.

Ultrastructure of streptozotocin-induced renal tumours in mice.

Streptozotocin-induced tumours in the kidneys of experimental animals have been shown to be histologically similar to human renal cell carcinoma. We report the ultrastructural features of renal tumours induced in 15 mice by a single intravenous bolus of 2.5% streptozotocin administered in a dose of 250 mg streptozotocin/kg mouse body weight. Animals were sacrificed 232-361 days after the administration of streptozotocin. On examination both kidneys from each animal contained 1-4 dysplastic tubules and 1-3 discrete tumours per kidney. Twelve dysplastic proximal convoluted tubules showing varying degrees of epithelial atypia and nine tumours exhibiting either a papillary or solid architecture were examined. Dysplastic epithelial cells and tumours of papillary and solid type exhibited complex cell borders with well-developed junctional complexes. The majority of cells contained surface microvilli, and in some cells microvilli-lined intracytoplasmic lumina were observed. Occasional dysplastic epithelial cells and tumour cells contained double-membrane vesicles 120-200 nm in diameter. These were similar to the intracytoplasmic vesicles characteristic of human chromophobe renal cell carcinoma. Intracytoplasmic collections of glycogen granules and flocculant protein were identified in both dysplastic and neoplastic cells, and where prominent they resulted in compression of cytoplasmic organelles. Coated vesicles were commonly observed. These were free within the cytoplasm and were also seen budding from strands of rough endoplasmic reticulum. The distribution of these vesicles suggested a role in protein transport from the rough endoplasmic reticulum. It is concluded that while streptozotocin-induced renal tumours have some ultrastructural features in common with human chromophobe renal cell carcinoma, the overall ultrastructural morphology differs significantly from that described for the various histological types of human renal cell carcinoma.

Reproducibility of new classification schemes for the pathology of ductal carcinoma in situ of the breast.

AIM: To compare the interobserver variation in the pathological classification of ductal carcinoma in situ of the breast using two recently proposed classification schemes. METHODS: 11 pathologists classified a set of 25 cases of ductal carcinoma in situ chosen to reflect a range of lesions, using the traditional architectural classification together with the modified cytonuclear grading scheme of Holland et al and the Van Nuys classification scheme. Participating pathologists received a standard tutorial, written information, and illustrative photomicrographs before their assessment of the cases. RESULTS: Interobserver agreement was poorest when using the architectural scheme (kappa = 0.44), largely owing to variations in classifying lesions with a mixed component of patterns (kappa = 0.13). Agreement was better using the modified cytonuclear grading scheme (kappa = 0.57), with most consistency achieved using the Van Nuys scheme (kappa = 0.66). Most discordant results using the later scheme were due to inconsistency in assessing the presence or absence of luminal necrosis. CONCLUSIONS: Both the new classification schemes assessed in this study were an improvement over the traditional architectural classification system for ductal carcinoma in situ, and resulted in more reproducible pathological assignment of cases. The Van Nuys classification scheme is easy to apply, even to small areas of carcinoma, resulting in acceptable interobserver agreement between reporting pathologists. Additional work will be required to arrive at a consensus definition of necrosis for cases in the non-high-grade group.

Proliferation kinetics of streptozotocin-induced renal tumours in mice.

Renal tumours were induced in female mice 132 days after intravenous administration of streptozotocin. The tumours exhibited papillary and/or solid architecture with papillary tumours showing no histological evidence of malignancy. Malignant behaviour, manifest as infiltration of adjacent renal tissue and lymphatic infiltration, was noted for tumours with solid architecture. Intermediate architectural forms exhibiting dual papillary and solid architecture were identified. Proliferation kinetics were evaluated by enumeration of silver-staining nucleolar organizer regions and proliferating cell nuclear antigen expression. The results showed a stepwise progress in cell proliferation between histologically normal renal tubule epithelium [untreated animals, mean AgNOR score (MAS) 2.32, mean PCNA index (MPI) 0.53%; treated animals, MAS, 2.44; MPI 0.99%], dysplastic tubule epithelium (MAS, 4.15; MPI 1.65%), papillary tumours (MAS, 5.90; MPI 3.89%) and solid tumours (MAS, 6.94; MPI, 6.80%). Solid tumours as a group were significantly larger than papillary tumours and were associated with a significantly longer mean post-injection survival interval. The findings suggest that at least some solid tumours evolve from tumours exhibiting papillary architecture.