Genitourinary Malignancies in Transplant or Dialysis Patients: The Frequency of Two Newly Described 2016 World Health Organization Histopathologic Types.

BACKGROUND: The aim of this study was to revise the histopathologic types of neoplasias in the genitourinary tract and determine the frequency of 2 new entities included in the 2016 book of World Health Organization classification of renal tumors. It is not established so far whether these 2 recently described tumors are the most frequent in association with end-stage kidney disease. METHODS: In a retrospective analysis, we revised the histopathologic type of 37 genitourinary tumors from 21 patients in dialysis and/or submitted to renal transplantation from 2003 to 2016 aiming to find the frequency of acquired cystic disease-associated renal cell carcinoma and clear cell papillary (tubulopapillary) renal cell carcinoma. RESULTS: From the total of 37 tumors, 34 were from native end-stage kidneys, 1 from the pelvis of the transplant kidney, and 2 from the urinary bladder. The frequencies from native kidneys were: papillary carcinoma, 13/34 (38.2%); papillary adenoma, 9/34 (26.5%); acquired cystic disease-associated renal cell carcinoma, 4/34 (11.8%); oncocytoma, 3/34 (8.8%); conventional clear cell renal cell carcinoma, 3/34 (8.8%); and clear cell papillary (tubulopapillary) renal cell carcinoma, 2/34 (5.34%). The pelvis and urinary bladder tumors were high-grade urothelial carcinomas. The patients with urinary bladder tumors had been treated for polyomavirus infection. CONCLUSIONS: The frequencies of acquired cystic disease-associated renal cell carcinoma and clear cell papillary renal cell carcinoma were 11.8% and 5.9%, respectively. However, the spectrum of adenoma/carcinoma papillary tumors composed the majority, 64.7%, of tumors.

Steroid hormone receptors, matrix metalloproteinases, insulin-like growth factor, and dystroglycans interactions in prostatic diseases in the elderly men.

OBJECTIVES: The aim of this study was to evaluate the reactivity of steroid hormone receptors (SHRs), dystroglycans (DGs), matrix metalloproteinases (MMPs), insulin-like growth factor receptor (IGFR-1), and laminin (Lam) in both prostatic stromal and epithelial compartments showing different diseases in elderly men. METHODS: Sixty prostatic samples were obtained from 60- to 90-year-old patients (mean 63 years) with and without prostatic lesions from Hospital of the School of Medicine, State University of Campinas (UNICAMP). The Samples were divided into standard (no lesions); high grade prostatic intraepithelial neoplasia (HGPIN); prostatic cancer (PC); and benign prostatic hyperplasia (BPH) groups. The samples were submitted to immunohistochemistry and Western blotting analyses. Research Ethics Committee of the School of Medicine, University of Campinas/UNICAMP (number 0094.0.146.000-08). RESULTS: The results showed increased IGFR-1 and MMPs protein levels in the PC and HGPIN groups. Decreased αDG and ßDG protein levels were verified in the PC and HGPIN groups. Androgen receptor (AR) reactivity was similar among all groups. Estrogen receptor α (Erα) immunoreactivity was more intense in the epithelium in the PC and HGPIN groups. Estrogen receptor ß (ERß) immunoreactivity was weak in the epithelium of the HGPIN and PC groups. CONCLUSIONS: To conclude, there was an association among IGFR-1, MMPs, and SHRs, indicating IGFR-1 as a target molecule in prostate therapy, considering the IGF proliferative properties. Also, the distinct SHRs reactivities in the lesions in both prostatic compartments indicated different paracrine signals and pointed out the importance of estrogenic pathways in the activation of these disorders.

Tumor grade heterogeneity in urothelial bladder carcinoma--proposal of a system using combined numbers.

OBJECTIVE: There is no consensus for grading when more than one grade is present in bladder carcinoma. We propose a grading system that considers the primary (most common) and secondary (second most common) grade of bladder cancer. Grade was correlated with stage of the tumors. MATERIAL AND METHODS: We studied 293 bladder transurethral resections or radical cystectomies. Grade was considered as 1, 2 or 3 according to the 1999 World Health Organization system. The number was repeated when only one grade was seen. A final score was obtained which ranged from 2 to 6. All cases were also graded according to the highest grade area even if it was focal. RESULTS: According to the highest grade area, the distribution was 80 (74.07%), 27 (25.00%) and 1 (0.92%) for grade 1; 31 (24.03%), 69 (53.48%) and 29 (22.48%) for grade 2; and 0 (0%), 17 (30.35%) and 39 (69.64%) for grade 3, corresponding to the stages Ta, T1 and T2-T3, respectively. Using the system of combined numbers, grade 2 was stratified into subgroups 1 + 2 and 2 + 2 which are statistically different (p < 0.05) when considering stage. In grade 3, there was also a trend for statistical difference (p = 0.066) between grades 2 + 3 and 3 + 3. CONCLUSIONS: The grading system of combined numbers, stratifies grade 2 into subgroups 1 + 2 and 2 + 2, and grade 3 into subgroups 2 + 3 and 3 + 3 which are statistically different when considering stage. This grading system of combined numbers takes into consideration tumor heterogeneity and may be of value in prospective studies for analysis of prognosis and therapeutic response.

Renal involvement in Adamantiades-Behçet's disease. Case report and review of the literature.

A patient with Adamantiades-Behçet's disease with renal involvement is reported. This patient fulfilled the International Study Group criteria for the disease. Kidney biopsy was performed and proliferative glomerulonephritis with deposition of IgA and IgM immunoglobulins were demonstrated. Review of the literature demonstrates that renal involvement in this disease is not so rare as it was believed. Crescent formation and IgA nephropathy are infrequently observed. Treatment of renal involvement may require immunosuppressive drugs.

Squamous and/or glandular differentiation in urothelial carcinoma: prevalence and significance in transurethral resections of the bladder.

BACKGROUND: It is controversial if urothelial carcinoma of the bladder with squamous and/or glandular differentiation is a more aggressive neoplasm than conventional urothelial carcinoma. DESIGN: A total of 165 transurethral resections of the bladder were reviewed. A group with squamous and/or glandular differentiation was compared to a group without this finding. The chi-square test was used to assess the association of the groups with stage (TNM, 1997). RESULTS: Of the total of 165 transurethral resections of the bladder, 153 (92.72%) were conventional urothelial carcinomas and 12 (7.27%) showed squamous and/or glandular differentiation. The distribution according to stage was 84 (54.9%), 35 (22.9%) and 34 (22.2%) for the group without differentiation and 0 (0%), 3 (25%) and 9 (75%) for the group with squamous and/or glandular differentiation, respectively for stages pTa, pT1 and pT2. Tumors with squamous and/or glandular differentiation showed a significant statistical correlation to higher stage at clinical presentation (p < 0.0001). There was no significant statistical relation according to age (p = 0.8433), sex (p = 0.5672) or race (p = 0.3137). CONCLUSIONS: The results suggest that urothelial bladder carcinomas with squamous and/or glandular differentiation are more aggressive neoplasms. There was a significant statistical correlation between tumors with this differentiation and higher stage at clinical presentation.

Prostate elastosis: a microscopic feature useful for the diagnosis of postatrophic hyperplasia.

BACKGROUND: Elastosis of the prostate may be seen on needle biopsy and radical prostatectomy specimens, but its significance is unknown. Prostatic atrophy (or postatrophic hyperplasia) is one of the most frequent mimics of prostatic adenocarcinoma. OBJECTIVE: To observe the frequent occurrence of elastosis of the prostate stroma in areas of postatrophic hyperplasia. DESIGN: A step-section method was used to cut the posterior lobe (or peripheral zone) in coronal planes at intervals of 0.3 to 0.5 cm in 100 consecutive autopsy specimens of men older than 40 years. Elastosis was detected because of a basophilic tinge of the stroma on hematoxylin-eosin stain and confirmed using elastic fiber stains. Presence of elastosis correlated with the following variables: age, prostatic atrophy (simple, hyperplastic, or sclerotic), local arteriosclerosis, histologic carcinoma, high-grade prostatic intraepithelial neoplasia, benign or malignant nephrosclerosis, generalized atherosclerosis, nodular prostatic hyperplasia, and acute inflammation. For statistics, a stepwise linear regression method adjusted for age was used. RESULTS AND CONCLUSIONS: Elastosis was found in 65 of the prostates examined and was significantly more frequent with increasing age (P <.001), prostatic atrophy (P <.001), and local arteriosclerosis (P <.02). There was no significant relation to histologic carcinoma, high-grade prostatic intraepithelial neoplasia, benign or malignant nephrosclerosis, generalized atherosclerosis, nodular prostatic hyperplasia, and acute inflammation. The correlation with local arteriosclerosis favors a possible role of ischemia to its etiopathogenesis. The absence of correlation to neoplastic and preneoplastic lesions and the striking spatial relationship of elastosis to prostatic atrophy (or postatrophic hyperplasia) add a new microscopic feature for the diagnosis of this latter lesion, helping in the differential diagnosis with prostate adenocarcinoma.

Epidemiology of high-grade prostatic intraepithelial neoplasia.

This review summarizes published data dealing with the prevalence of high-grade prostatic intraepithelial neoplasia (HGPIN) in a variety of prostate tissue samples. Additionally, we have attempted to document the relationship between HGPIN and the pathological parameters of prostate cancer in autopsy and radical prostatectomy specimens. Studies reporting the prevalence of HGPIN in needle biopsies, transurethral resection specimens and radical prostatectomy specimens, and those documenting the lesion in postmortem settings are compared. We also summarize studies in which the distribution and/or extent of HGPIN was correlated with prostate cancer stage, grade and volume. There is significant variation in the reported frequency of HGPIN, particularly in needle biopsy specimens, with a range of 0.8-23.9%. The factors responsible for these discrepancies include the population studied, the limited sample size that needle biopsies represent, diagnostic inconsistencies and, possibly, tissue preparation/staining variables. Because of the important implications a diagnosis of HGPIN carries, there is a pressing need to achieve greater consistency in diagnosing and reporting the lesion. Better targeted educational efforts, including teaching courses, websites with illustrations and the possibility of teleconsultations, are among possible means to attain this goal. Better documentation of the evolution of HGPIN to cancer through clinical follow-up is also recommended.

Correlation of bone mineral density with the histological findings of renal osteodystrophy in patients on hemodialysis.

AIMS: To examine the distribution of bone mineral density (BMD) in different histological groups of renal osteodystrophy. PATIENTS: We prospectively studied 62 patients, 41 men and 21 women, aged 57+/-11.5 years, who had been on hemodialysis for 60+/-55 months. The women had been amenorrheic for 13+/-4 years and 7 patients (11%) had a positive fracture history. METHODS: A bone biopsy was taken after tetracycline labelling and BMD of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry (DEXA); serum intact parathyroid hormone (iPTH), bone Gla protein (BGP), phosphorus, calcium and alkaline phosphatase (ALP) were also determined. RESULTS: Histologically, 40 patients showed secondary hyperparathyroidism (sHPT), 6 mixed bone disease, 14 adynamic bone disease (A) and 2 osteomalacia. BMD of the lumbar spine was decreased in 43 patients (69%) and in 9 (14.5%) it was lower than -2 Z score units. BMD of the femoral neck was low in 55 patients (89%) and in 22 (35.5%) it was lower than -2 Z scores. BMD was lower in patients with sHPT than in those with adynamic bone disease (p<0.05) in which it was close to normal. BMD in both these sites correlated inversely with the biochemical markers (serum iPTH, BGP and ALP) and the histomorphometric indices of bone turnover. CONCLUSIONS: Osteopenia is frequent in patients on hemodialysis, especially those with biochemical and histological findings of sHPT.

Regression of massive tumoral calcinosis of the ischium in a dialysis patient after treatment with reduced calcium dialysate and i.v. administration.

BACKGROUND: Tumoral calcinosis, an inherited metabolic disorder, has been described with increasing frequency over the last 20 years [Drueke 1966]. It is characterized by massive calcium phosphate deposits in periarticular tissues, usually around large joints, especially the hips, knees and elbows (editorial in Lancet 1987). PATIENT AND METHOD: We describe a 58-year-old male patient with tumoral calcinosis of the ischium and severe hyperparathyroid bone disease, successfully treated with reduced calcium dialysate and vitamin D. CONCLUSION: We believe that in cases of tumoral calcification with histologically proven hyperparathyroid bone disease, lowering the calcium dialysate concentration together with careful administration of vitamin analogs and monitoring of serum calcium, phosphate and parathyroid hormone levels, may be the ideal therapeutic approach. Control of hyperphosphatemia would be best achieved with measures other than administration of aluminium phosphate binders if one wishes to avoid the induction of adynamic bone.

Prostatic atrophy: an autopsy study of a histologic mimic of adenocarcinoma.

Prostatic atrophy (PA) is one of the most frequent mimics of prostatic adenocarcinoma. It occurs almost exclusively in the peripheral zone of the gland and gained importance with the increasing use of needle biopsies for the detection of prostatic carcinoma The etiopathogenesis is unknown, and there is controversy related to the potential of PA as a precancerous lesion. The frequency increases with age. Compressions caused by hyperplastic nodules, inflammation, hormones, nutritional deficiency, or systemic or local ischemia, are all possible factors in the pathogenesis of PA. The peripheral zone of the prostate was step-sectioned and totally embedded from the bodies of 100 consecutively autopsied men more than 40 years of age. The fragments were microscopically studied for presence of PA, latent (histologic) carcinoma, high-grade prostatic intraepithelial neoplasia, local arteriosclerosis, and prostatitis. The prostates were macroscopically examined for the presence of nodular prostatic hyperplasia. The autopsy reports provided information concerning the presence of generalized atherosclerosis and benign or malignant nephrosclerosis. PA was seen in 85 of the 100 prostates examined and histologically was subtyped into simple, hyperplastic, and sclerotic atrophy. In 65 (76.47%) of 85 cases, the histologic subtypes were combined. In 33 (50.76%) of these 65 cases, the three subtypes were seen concomitantly, favoring the hypothesis that they represent a morphologic continuum of only one lesion. Fibrosis of the stroma may or may not be present in simple and hyperplastic atrophy. Hyperplastic atrophy associated with fibrosis of the stroma is the histologic subtype that most frequently mimics adenocarcinoma Sclerotic atrophy always presents fibrosis of the stroma. PA increases with age, and, in our study, ischemia caused by local intense arteriosclerosis seems to be a potential factor for its etiopathogenesis. Because there was no relation to latent (histologic) carcinoma or high-grade prostatic intraepithelial neoplasia, PA is probably not a premalignant lesion.

Chromophobe renal cell carcinoma: clinicopathological study of 7 cases.

Chromophobe renal cell carcinoma (CRCC) may be grossly and microscopically confused with oncocytoma. It is now believed that many, if not all, of the so-called malignant oncocytomas or oncocytomas with metastases reported in the literature were indeed chromophobe renal cell carcinomas. CRCC is characteristically positive for colloidal iron and shows cytoplasmic microvesicles in electron microscopy. This study of CRCC is thought to be the first one done in Latin America. Of a total of 106 renal epithelial neoplasms, 7 (6.6%) fulfilled the criteria for chromophobe renal cell carcinoma. This frequency in Brazil is similar to that in other parts of the world. There was no difference in age, sex, and race distribution of CRCC compared to usual renal epithelial tumors. Grossly, the CRCC ranged in size from 3.5 to 20 cm (average: 10.2 cm) in greatest dimension. Most frequently, the tumor was brown on the cut surface. The growth pattern showed compact areas in all tumors and, in most of the cases, both clear and eosinophilic cellular subtypes were seen. The electron microscopic findings favor an origin of the microvesicles from outpouchings of the outer membrane of mitochondria. The strong positivity for colloidal iron in spite of the destruction of the cytoplasmic vesicles in paraffin-embedded specimens seems to indicate that the acid mucopolysaccharides are not located inside the microvesicles. By the time of diagnosis, only one case had regional lymph node metastases and this particular case was the only one mixed (associated with the usual renal cell carcinoma). The follow-up examination after nephrectomy showed that prognosis seems to be favorable in CRCC, except when the tumor coexists with the usual renal cell carcinoma.

HLA antigens in microscopic polyarteritis (MP) with renal involvement.

Serological HLA-A, B, C, DR and DQ typing was performed in 23 patients with microscopic polyarteritis and renal involvement and in 405 healthy individuals, all of Greek origin. An increased frequency of HLA-A26 (26% vs. 11.3%, x2 = 4.423, p < 0.05) and HLA-A11 (26% vs. 9.6%, x2 = 6.825, P < 0.02), and a decreased frequency of HLA-DR3 (4.3% vs. 24.1%, x2 = 5.935, p < 0.025) were found. Five out of six patients, who did not respond to treatment possessed HLA-DR5. These observations suggest that HLA gene products may influence the clinical expression, as well as the outcome of this disease.

Biochemical markers for non-invasive diagnosis of hyperparathyroid bone disease and adynamic bone in patients on haemodialysis.

UNLABELLED: The diagnostic and predictive value of serum intact parathyroid hormone (iPTH) and osteocalcin (bone Gla protein, BGP), alone or in combination, have been examined in only a small number of haemodialysis patients. METHODS: We studied prospectively 114 patients (46 women, 68 men; mean age 52 +/- 12 years) on regular haemodialysis for a mean of 55 (6-185) months. All patients underwent labelled transiliac bone biopsy, and serum levels of iPTH, BGP and alkaline phosphatase were determined. RESULTS: Seventy-one patients (62%) showed histological findings of hyperparathyroid bone disease, 24 (21%) mixed bone disease, six (5.5%) osteomalacia and 13 (11.5%) adynamic bone. Bone aluminium deposition over more than 25% of the trabecular bone interface was found in 66 patients (58%). Serum iPTH and BGP correlated with the majority of histomorphometric indices of bone formation, mineralization and resorption (r > 0.5, P < 0.01). iPTH levels > or = 200 pg/ml and BGP > or = 50 ng/ml were found to be indicative of hyperparathyroid bone disease, whilst iPTH levels < 65 pg/ml and BGP < 20 ng/ml were indicative of adynamic bone. However, the positive predictive value of these indices was limited (less than 80%), although their negative predictive value, especially when used in combination, was good (more than 90%) and the exclusion of hyperparathyroid bone disease and adynamic bone was possible. The diagnostic and predictive value of these bone markers were improved when patients with bone aluminium deposition were excluded. CONCLUSIONS: Diagnosis of hyperparathyroid bone disease and adynamic bone is difficult on the basis of iPTH and BGP, especially when bone aluminium deposition is prevalent. However, using these bone markers, preferably in combination, the exclusion of these lesions is feasible.