Athanase Billis

The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma.

Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging-targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed.

Xp11 Translocation renal cell carcinoma in adults: Expanded clinical, pathologic, and genetic spectrum

The recently recognized Xp11 translocation renal cell carcinomas (RCCs), all of which bear gene fusions involving the TFE3 transcription factor gene, comprise at least one-third of pediatric RCC. Only rare adult cases have been reported, without detailed pathologic analysis. We identified and analyzed 28 Xp11 translocation RCC in patients over the age of 20 years. All cases were confirmed by TFE3 immunohistochemistry, a sensitive and specific marker of neoplasms with TFE3 gene fusions, which can be applied to archival material. Three cases were also confirmed genetically. Patients ranged from ages 22 to 78 years, with a strong female predominance (F:M=22:6). These cancers tended to present at advanced stage; 14 of 28 presented at stage 4, whereas lymph nodes were involved by metastatic carcinoma in 11 of 13 cases in which they were resected. Previously not described and distinctive clinical presentations included dense tumor calcifications such that the tumor mimicked renal lithiasis, and obstruction of the renal pelvis promoting extensive obscuring xanthogranulomatous pyelonephritis. Previously unreported morphologic variants included tumor giant cells, fascicles of spindle cells, and a biphasic appearance that simulated the RCC characterized by a t(6;11)(p21;q12) chromosome translocation. One case harbored a novel variant translocation, t(X;3)(p11;q23). Five of 6 patients with 1 or more years of follow-up developed hematogenous metastases, with 2 dying within 1 year of diagnosis. Xp11 translocation RCC can occur in adults, and may be aggressive cancers that require morphologic distinction from clear cell and papillary RCC. Although they may be uncommon on a percentage basis, given the vast predominance of RCC in adults compared with children, adult Xp11 translocation RCC may well outnumber their pediatric counterparts.

International society of urological pathology (ISUP) consensus conference on handling and staging of radical prostatectomy specimens. working group 2: T2 substaging and prostate cancer volume

The 2009 International Society of Urological Pathology consensus conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the substaging of pT2 prostate cancers according to the TNM 2002/2010 system, reporting of tumor size/volume and zonal location of prostate cancers were coordinated by working group 2. A survey circulated before the consensus conference demonstrated that 74% of the 157 participants considered pT2 substaging of prostate cancer to be of clinical and/or academic relevance. The survey also revealed a considerable variation in the frequency of reporting of pT2b substage prostate cancer, which was likely a consequence of the variable methodologies used to distinguish pT2a from pT2b tumors. Overview of the literature indicates that current pT2 substaging criteria lack clinical relevance and the majority (65.5%) of conference attendees wished to discontinue pT2 substaging. Therefore, the consensus was that reporting of pT2 substages should, at present, be optional. Several studies have shown that prostate cancer volume is significantly correlated with other clinicopathological features, including Gleason score and extraprostatic extension of tumor; however, most studies fail to demonstrate this to have prognostic significance on multivariate analysis. Consensus was reached with regard to the reporting of some quantitative measure of the volume of tumor in a prostatectomy specimen, without prescribing a specific methodology. Incorporation of the zonal and/or anterior location of the dominant/index tumor in the pathology report was accepted by most participants, but a formal definition of the identifying features of the dominant/index tumor remained undecided.

The impact of the 2005 international society of urological pathology consensus conference on standard Gleason grading of prostatic carcinoma in needle biopsies.

PURPOSE At an International Society of Urological Pathology consensus conference in 2005 the Gleason grading system for prostatic carcinoma underwent its first major revision. We compared the concordance of pattern and change of prognostic groups for the conventional and the modified Gleason grading, and checked the discriminative power of the modified Gleason grading. MATERIALS AND METHODS The grading was based on 172 prostatic needle biopsies of patients subsequently undergoing radical prostatectomy. Four prognostic Gleason grading groups were considered, divided into scores of 2-4, 5-6, 7 and 8-10. To check the discriminative power of the modified Gleason grading we compared the time of biochemical (prostate specific antigen) progression-free outcome according to prognostic groups between standard and revised grading. RESULTS The greatest impact of the International Society of Urological Pathology consensus recommendations for Gleason grading was seen on the secondary pattern which had the lowest percentage of concordance and was reflected in a change toward higher Gleason prognostic groups. Of 172 patients in whom the Gleason prognostic group was changed (to higher grades) based solely on the consensus criteria, 46 (26.7%) had higher preoperative prostate specific antigen, more extensive tumors and positive surgical margins, and higher pathological stage. The revised Gleason grading identified in this series a higher number of patients in the aggressive prognostic group Gleason score 8-10 who had a significantly shorter time to biochemical progression-free outcome after radical prostatectomy (log rank p = 0.011). CONCLUSIONS The findings of this study indicate that the recommendations of the International Society of Urological Pathology are a valuable refinement of the standard Gleason grading system.

Multilocular cystic renal cell carcinoma : A report of 45 cases of a kidney tumor of low malignant potential

The 2004 World Health Organization (WHO) classification of kidney tumors recognizes multilocular cystic renal cell carcinoma (MCRCC) as a rare variant of clear cell renal cell carcinoma with a good prognosis. Available information on its clinical significance is limited. The study cohort included 45 MCRCC cases classified according to 2004 WHO criteria obtained through a multi-institutional international search. Most patients had unilateral MCRCC with no side predominance that was found incidentally; 62% were men, but women had tumors at an earlier age (P = .385). MCRCC occurred slightly more often in men than in women (1.7:1). At diagnosis, 82% of patients had stage T1 and 16%, stage T2; 1 patient had stage T3. The Fuhrman grade was 1 (62%) or 2 (38%), with smaller tumors (<or=4 cm) most likely Fuhrman grade 1 (P = .911). All 45 patients were alive with no evidence of disease at mean follow-up of 66.1 months, confirming an extremely good prognosis after surgery and a 5-year disease-specific survival rate of 100%. To rename this tumor as multilocular cystic renal cell neoplasm of low malignant potential might help urologists approach the patients conservatively.

Grading of invasive cribriform carcinoma on prostate needle biopsy: an interobserver study among experts in genitourinary pathology

The distinction between cribriform Gleason pattern 3 and 4 prostate cancer is controversial. Out of 3590 prostate cancers sent to one of the authors over 7 months, 30 needle biopsy cases were selected that possibly represented cribriform Gleason pattern 3 cancer. Thirty-six digital images were taken and sent to 10 experts in prostate pathology. Consensus was defined when at least 7/10 experts agreed on the grade. Sixty-seven percent (n=24) of images reached consensus (23 pattern 4; 1 pattern 3). Of the 12 nonconsensus images, 7 were favor pattern 4 (6/10 experts agreed), 1 was favor pattern 3 (6/10 experts agreed), and 4 were equivocal (<6 experts agreed). The most common criteria used to call pattern 4 in the 23 consensus pattern 4 images were in frequency: irregular contour, irregular distribution of lumens, slit-like lumens, large glands, number of glands, and small lumens. In the only consensus pattern 3 image, criteria used were regular contour, small glands, regular distribution of lumens, and uniform round lumens. Discrepancy between experts was qualified as primarily objective (different criteria present) in 38%, subjective (different interpretation of the same criteria) in 12%, and mixed (both objective and subjective) in 50%. The most frequent situation with different interpretations of the same criteria were regular versus irregular contour and small versus large glands, with the former more common. Even in this highly selected set of images thought to be the best candidates for cribriform pattern 3 from a busy consult service, most experts interpreted the cribriform patterns as pattern 4. Moreover, most of the cribriform foci investigated (73%) were associated with more definitive pattern 4 elsewhere on the needle biopsy specimen. In conclusion, most of the small cribriform cancer foci seen on needle biopsy should be interpreted as Gleason pattern 4 and not pattern 3.

Renal medullary carcinoma: report of seven cases from Brazil

We report seven cases of renal medullary carcinoma collected from several institutions in Brazil. In spite of a relatively high incidence of sickle cell trait in Brazil, this is a rare tumor. All patients were males between the ages of 8 and 69 years (mean 22 years). From the collected information, the most frequent presenting symptoms were gross hematuria and flank or abdominal pain. The duration of symptoms ranged from 1 week to 5 months. Most of the tumors were poorly circumscribed arising centrally in the renal medulla. Size ranged from 4 to 12 cm (mean 7 cm) and hemorrhage and necrosis were common findings. All seven cases described showed sickled red blood cells in the tissue and six patients were confirmed to have sickle cell trait. All cases disclosed the characteristic reticular pattern consisting of tumor cell aggregates forming spaces of varied size, reminiscent of yolk sac testicular tumors of reticular type. Other findings included microcystic, tubular, trabecular, solid and adenoid-cystic patterns, rhabdoid-like cells and stromal desmoplasia. A peculiar feature was suppurative necrosis typically resembling microabscesses within epithelial aggregates. The medullary carcinoma of the 69-year-old patient was associated with a conventional clear cell carcinoma. To our knowledge, this association has not been previously reported and the patient is the oldest in the literature. The survival after diagnosis or admission ranged from 4 days to 9 months. The 8-year-old African–Brazilian patient with a circumscribed mass is alive and free of recurrence 8 years after diagnosis. This case raises the question whether a periodic search for renal medullary carcinoma in young patients who have known abnormalities of the hemoglobin gene and hematuria could result in an early diagnosis and a better survival.

Inflammatory Atrophy of the Prostate Prevalence and Significance

CONTEXT Recently, prostatic atrophy associated with chronic inflammation has been linked to carcinoma either directly or indirectly by first developing into high-grade prostatic intraepithelial neoplasia. OBJECTIVE The purpose of our study was to test this hypothesis in autopsies. DESIGN A step section method was used to cut the posterior lobe in coronal planes at intervals of 0.3 to 0.5 cm in 100 consecutive autopsies of men older than 40 years. Prostatic atrophy was classified as simple, hyperplastic (or postatrophic hyperplasia), and sclerotic and was analyzed for the presence of chronic inflammation. Prostatic atrophy without (group A) and with inflammation (group B) was correlated with the following variables: age, race, histologic (incidental) carcinoma, high-grade prostatic intraepithelial neoplasia, and extent of both these lesions. RESULTS Of the 100 prostates examined, 12%, 22% and 66%, respectively, had no atrophy, atrophy without inflammation (group A), and atrophy with inflammation (group B). There was no statistically significant difference between groups A and B for age (P =.55), race (P =.89), presence of histologic (incidental) carcinoma (P =.89), extensive carcinoma (P =.43), presence of high-grade prostatic intraepithelial neoplasia (P =.65), extensive high-grade intraepithelial neoplasia (P =.30), or subtypes of prostatic atrophy. Neither a topographical relation nor a morphologic transition was seen between prostatic atrophy and histologic carcinoma or high-grade intraepithelial neoplasia. Sclerotic atrophy either alone or combined with other subtypes was more frequent in the group with inflammation. A striking morphologic finding was a topographical relation of focal inflammation with sclerotic atrophy in areas with erosion of the epithelium. CONCLUSIONS Inflammatory prostatic atrophy does not appear to be associated with histologic (incidental) carcinoma or high-grade intraepithelial neoplasia. One possible cause of inflammatory infiltrate associated with prostatic atrophy may be the extravasated prostatic secretions, which were noted in areas of eroded epithelium, a common finding in the sclerotic type of prostatic atrophy.

Histologic grading of prostatic adenocarcinoma: Intraobserver reproducibility of the Mostofi, Gleason and Böcking grading systems

Intraobserver variation of three grading systems—Mostofi, Gleason and Böcking—is examined. No significant difference was noted between the histological grades found in the two examinations by any of the three methods used. Neither the type of surgical procedure nor the number of slices with tumour influenced the reproducibility of histological grading within each system studied. In the Gleason system the intraobserver highest disagreement would not have resulted in change of therapy choice, but in 2% of tumours graded according to the Mostofi system this would have occurred if the choice of therapy would depend on the grading results.

Carcinoma of the collecting ducts of Bellini and renal medullary carcinoma: clinicopathologic analysis of 52 cases of rare aggressive subtypes of renal cell carcinoma with a focus on their interrelationship.

Carcinoma of the collecting ducts of Bellini and renal medullary carcinoma are rare aggressive neoplasms of putative distal nephron origin. First described in 1949, case reports and review articles constitute a major source of information on collecting duct carcinoma, whereas Davis and colleagues and the pediatric tumor registry have contributed the seminal works on renal medullary carcinoma. Here we present a detailed study of collecting duct carcinoma (n=39) and renal medullary carcinoma (n=13), characterizing these rare neoplasms and analyzing their interrelationship. Both collecting duct carcinoma and renal medullary carcinoma exhibited significant similarities, such as predilection for the right kidney, tumor mass with an epicenter in the renal medulla, and a mean size of 7 cm. Overall, both tumors exhibited a poorly differentiated adenocarcinoma histology with desmoplastic stromal response (100%), inflammatory infiltrate (100%), frequent perinephric extension (collecting duct carcinoma: 97%; renal medullary carcinoma: 83%), lymphovascular invasion (100%), intraluminal mucin (collecting duct carcinoma: 42%; renal medullary carcinoma: 73%), high nuclear grade (97%), overlapping immunoreactivity for Ulex europaeus agglutinin 1 (collecting duct carcinoma: 75%; renal medullary carcinoma:55%), CK7 (collecting duct carcinoma: 44%; renal medullary carcinoma: 71%), and high–molecular weight cytokeratin (collecting duct carcinoma: 26%; renal medullary carcinoma: 29%), and nonimmunoreactivity for Ksp-cadherin. Histologically, collecting duct carcinoma frequently had tubular, tubulopapillary, or irregular glandular architecture, whereas renal medullary carcinoma commonly demonstrated islands of anastomosing tubules and cords forming irregular microcystic spaces. Multiple metastases to the lymph nodes, lung, bone, and liver were observed in both categories at presentation (collecting duct carcinoma: 17%; renal medullary carcinoma: 36%). Only patients with organ-confined small tumors were disease free beyond the median survival time. Differential clinical features between collecting duct carcinoma and renal medullary carcinoma included proclivity for younger male individuals of African ancestry with hemoglobin abnormalities and a shorter median survival of 17 weeks (vs. 44 wk for collecting duct carcinoma) for renal medullary carcinoma. The markedly overlapping clinical features, histology, immunophenotype, metastasis patterns, and uniformly aggressive outcome in collecting duct and renal medullary carcinomas suggest that renal medullary carcinoma is a distinctive clinicopathologic subtype within the entity of collecting duct carcinoma. The extremely poor prognosis and ongoing clinical trials with specific therapeutic protocols argue for their accurate distinction from other renal cell carcinoma subtypes.