Seife Hailemariam

Sarcomatoid differentiation in renal cell carcinoma : a study of 101 cases

Sarcomatoid renal cell carcinoma is not a distinct histologic entity and represents high-grade transformation in different subtypes of renal cell carcinoma. It is not known whether any particular histologic type has a predilection for sarcomatoid change or whether the primary histologic type of renal carcinoma undergoing sarcomatoid change affects prognosis. Of 952 consecutively histologically subtyped renal cell carcinomas, the incidence of sarcomatoid differentiation was 8% in conventional (clear cell) renal carcinoma, 3% in papillary renal carcinoma, 9% in chromophobe renal carcinoma, 29% in collecting duct carcinoma, and 11% in unclassified renal cell carcinoma. One hundred one renal cell carcinomas with sarcomatoid change were studied, and clinicopathologic parameters were correlated with outcome. The mean age of patients was 60 years (range, 33–80 years), and the male-to-female ratio was 1.6:1. The median tumor size was 9.2 cm (range, 3–25 cm). The primary histologic subtype of the carcinoma component was conventional (clear cell) renal carcinoma in 80 cases, papillary renal carcinoma in eight, chromophobe renal carcinoma in seven, collecting duct carcinoma in two, and unclassified renal cell carcinoma in four. The sarcomatoid component resembled fibrosarcoma in 54 cases, malignant fibrous histiocytoma in 44, undifferentiated sarcoma (not otherwise specified) in three with focal rhabdomyosarcomatous component in two of them. The spindled elements accounted for 1% to 99% of the sampled tumor (median, 40%; mean 45%). The histologic grade of the spindled elements was intermediate to high in 92 cases and low in nine cases. Most cases were TNM stages III and IV (seven stage I, six stage II, 63 stage III, and 25 stage IV). Follow-up was available in 88 patients; 61 (69%) patients died of disease and had a median survival time of 19 months. Distant metastases, most frequently to the lungs, were documented in 51 (66%) of 77 patients who had available clinical information regarding distant metastasis. The disease-specific survival rate was 22% and 13% after 5 and 10 years, respectively, compared with a cohort of renal cell carcinomas without sarcomatoid change with a 5-and 10-year disease-specific survival of 79% and 76%, respectively. Kaplan–Meier survival analysis showed that tumors with high TNM stage (p = 0.0027), at least 50% sarcomatoid component (p = 0.0453), and angiolymphatic invasion (p = 0.0282) were associated with decreased survival rates. The primary histologic subtype of the carcinoma component and the type and grade of the sarcomatoid component did not affect survival. In a Cox proportional hazard regression model, TNM stage appeared to be the only significant variable in predicting outcome among renal cell carcinomas with sarcomatoid change (p = 0.018; risk ratio, 6.984 and 8.439). Compared with a cohort of renal cell carcinomas without sarcomatoid change, sarcomatoid tumors tended to present at a more advanced stage (p = 0.0001). Also, when adjusted for stage, necrosis, and tumor size, patients with tumors with sarcomatoid differentiation had a worse prognosis than did patients with tumors without sarcomatoid change (p = 0.0001). In conclusion, sarcomatoid change in renal cell carcinoma portends a worse prognosis. Because tumors with even a small component of sarcomatoid change may have an adverse outcome, this finding, when present, should be noted in the surgical pathology report.

Early orchiopexy: prepubertal intratubular germ cell neoplasia and fertility outcome.

OBJECTIVES To investigate the prepubertal prevalence of intratubular germ cell neoplasia of the unclassified type (ITGCNU) and its significance as a predictor of testicular cancer and to evaluate the effect of early orchiopexy (at younger than 2 years of age) on subsequent fertility of patients with bilateral cryptorchidism. METHODS Testicular biopsies (n = 660) from 440 prepubertal patients with cryptorchidism who underwent orchiopexy between January 1, 1970 and December 31, 1979 were evaluated for ITGCNU using placental-like alkaline phosphatase (PLAP) antibody. The clinical outcome in 15 patients with PLAP-positive germ cells was evaluated in 1997. In addition, the effect of age at surgery on the fertility of patients with bilateral cryptorchidism was assessed by clinical follow-up until 1997 and was correlated with the histologic data at orchiopexy. RESULTS PLAP-positive germ cells morphologically identical with adult ITGCNU were found in the biopsies of 22 patients (5%). After more than two decades, none of the 15 patients with successful follow-up developed testicular cancer. The fertility outcome in the patients with bilateral cryptorchidism correlated with the number of spermatogonia at orchiopexy (P = 0.018), but correlated inversely with age at orchiopexy (P = 0.021). CONCLUSIONS PLAP-positive germ cells in prepubertal testicular biopsy specimens are not necessarily precursors of testicular cancer after orchiopexy. In addition, our data support the idea that early orchiopexy may be beneficial in preventing infertility.

Noninflammatory Chronic Pelvic Pain Syndrome: Immunological Study in Blood, Ejaculate and Prostate Tissue1

Objectives: The aim of this prospective study was to observe immunophenotypic patterns in patients with noninflammatory chronic pelvic pain syndrome (Cat IIIB CPPS) for further description and as possible surrogate markers for diagnosis and treatment. Methods: Eighty–eight patients with a referral diagnosis of chronic prostatitis underwent fractionated urinary cultures including expressed prostate secretion (EPS) and ejaculate analysis twice on two occasions. Monthly serum analyses included C3c, C4, IL–1α, sIL–2R, and IL–6. One hundred samples from healthy individuals were used as the control group for serum analysis. Monthly ejaculate testing was done for IgG, IgA, IgM, IL–1α, sIL–2R, and IL–6. The control group for ejaculate analysis was composed of 96 normal ejaculates (according to the WHO criteria). Immunohistochemical detection of CD3 cells (T lymphocytes) and CD20 cells (B lymphocytes) was performed in 71 biopsy cylinders of Cat IIIB CPPS patients and in 25 prostate biopsy cylinders of men without symptoms or obstruction. Results: Complete sampling of urinary, serum and ejaculate specimens was achieved in 50/88 (57%) patients. Cat IIIB CPPS was observed in 44/50 (88%) patients. Intra–acinar T–lymphocytic infiltrates were dominated by T cytotoxic cells (p = 0.05). Immunohistochemical studies showed inflammatory expression in serum complement, serum interleukin, and ejaculate interleukin concentrations in relation to the presence of large numbers of T cells (all p values ≤0.01). No difference was found in the proportion of B lymphocytes in patients with Cat IIIB CPPS compared to the control group. Serum and ejaculate IL–6 and ejaculate IgA increased significantly and dropped again, correlating with a release of clinical symptoms. Conclusions: Interleukin, complement and immunoglobulin determinations in serum and ejaculate reveal an inflammatory process even in Cat IIIB CPPS. The findings of intra–acinar T–cell–rich infiltrates and the associated inflammatory reaction may be a significant advance in defining Cat IIIB CPPS caused by a possible autoimmune component. Serum and ejaculate IL–6 and ejaculate IgA are possible surrogate markers for the diagnosis and treatment of Cat IIIB CPPS.

Colonic adenocarcinoma metastatic to the urinary tract versus primary tumors of the urinary tract with glandular differentiation: A report of 7 cases and investigation using a limited immunohistochemical panel

OBJECTIVE To determine whether a limited immunohistochemical panel can help differentiate metastatic colonic adenocarcinoma from primary enteric-type adenocarcinoma of the urinary tract and urothelial (transitional cell) carcinoma with glandular differentiation, which appear morphologically similar but most often necessitate different treatment protocols. DESIGN We examined lower urinary tract tumors (5 urinary bladder, 2 urethral) from 7 patients with a history of colonic adenocarcinoma. The differential diagnoses in these cases included metastatic colonic adenocarcinoma, primary enteric-type adenocarcinoma of the urinary tract, and urothelial carcinoma with glandular differentiation. An immunohistochemical panel consisting of cytokeratin 7 (CK-7), cytokeratin 20 (CK-20), and villin was evaluated in all cases. Four primary enteric-type adenocarcinomas of the urinary tract and 5 conventional urothelial carcinomas were also studied to compare morphologic features and immunohistochemical staining patterns. RESULTS Of the 7 cases, 6 were determined to be metastatic colonic adenocarcinoma and 1 was diagnosed as a primary urothelial carcinoma with glandular differentiation. All 6 metastatic colonic adenocarcinomas, 6 of the 7 primary colonic adenocarcinomas, and all 4 primary enteric-type adenocarcinomas of the urinary tract were CK-20 positive (1 was CK-20 negative), villin positive, and CK-7 negative. The single urothelial carcinoma with glandular differentiation and all 5 control cases of urothelial carcinoma were CK-7 and CK-20 positive, and villin negative. CONCLUSIONS We conclude that (1) villin is expressed in primary enteric-type adenocarcinoma of the urinary tract; (2) in difficult cases, urothelial carcinoma with glandular differentiation can be distinguished from colonic adenocarcinoma because the former is CK-7 positive, CK-20 positive, and villin negative, whereas the latter is CK-20 positive, villin positive, and CK-7 negative; (3) clinical information is essential when evaluating lower urinary tract tumors that are clinically and morphologically similar to enteric-type adenocarcinoma of the urinary tract; and (4) the similar immunohistochemical profiles of metastatic colonic adenocarcinoma and primary enteric-type adenocarcinoma of the urinary tract may be in keeping with the hypothesis that the latter arise from intestinal metaplasia.

Clear cell papillary renal cell carcinoma and renal angiomyoadenomatous tumor: two variants of a morphologic, immunohistochemical, and genetic distinct entity of renal cell carcinoma.

Clear cell papillary renal cell carcinoma (ccpRCC) and renal angiomyoadenomatous tumor (RAT) share morphologic similarities with clear cell (ccRCC) and papillary RCC (pRCC). It is a matter of controversy whether their morphologic, immunophenotypic, and molecular features allow the definition of a separate renal carcinoma entity. The aim of our project was to investigate specific renal immunohistochemical biomarkers involved in the hypoxia-inducible factor pathway and mutations in the VHL gene to clarify the relationship between ccpRCC and RAT. We investigated 28 ccpRCC and 9 RAT samples by immunohistochemistry using 25 markers. VHL gene mutations and allele losses were investigated by Sanger sequencing and fluorescence in situ hybridization. Clinical follow-up data were obtained for a subset of the patients. No tumor recurrence or tumor-related death was observed in any of the patients. Immunohistochemistry and molecular analyses led to the reclassification of 3 tumors as ccRCC and TFE3 translocation carcinomas. The immunohistochemical profile of ccpRCC and RAT samples was very similar but not identical, differing from both ccRCC and pRCC. Especially, the parafibromin and hKIM-1 expression exhibited differences in ccpRCC/RAT compared with ccRCC and pRCC. Genetic analysis revealed VHL mutations in 2/27 (7%) and 1/7 (14%) ccpRCC and RAT samples, respectively. Fluorescence in situ hybridization analysis disclosed a 3p loss in 2/20 (10%) ccpRCC samples. ccpRCC and RAT have a specific morphologic and immunohistochemical profile, but they share similarities with the more aggressive renal tumors. On the basis of our results, we regard ccpRCC/RAT as a distinct entity of RCCs.

Increased rate of Helicobacter pylori infection detected by PCR in biopsies with chronic gastritis.

Histology is considered a sensitive method for detection of Helicobacter pylori, in gastric biopsies. We investigated the diagnostic potential of qualitative nested (nPCR) and quantitative PCR (qPCR) for detection of H. pylori using different primers on 126 archived gastric biopsies with inflammation and correlated the inflammatory changes with the presence and density of bacteria. H. pylori was detected in 42.8% biopsies by histology and PCR, an additional 15 samples were positive exclusively by PCR: nPCR was positive in all histologically positive samples, but qPCR failed to detect H. pylori in 10 biopsies. The inflammatory score was significantly higher in biopsies positive for H. pylori only by PCR showed a significant higher inflammatory score compared with negative biopsies (mean of neutrophils score, 1.60 vs. 0.90, P < 0.01; mean of mononuclear cells score, 2.27 vs. 1.67, P < 0.01), whereas the inflammatory score was similar compared with biopsies positive for H. pylori by histology (mean of neutrophils score, 1.60 vs. 1.56, not significant; mean of mononuclear cells score, 2.27 vs. 2.20, not significant). A weak correlation between inflammatory score and the density of H. pylori detected by histology was observed. The mean values of H. pylori DNA were significantly higher in histologic-positive than in histologic negative biopsies. We have shown that PCR can detect H. pylori in about 20% of histologic-negative gastric biopsies, indicating the clinical relevance of H. pylori detection by PCR in biopsies with characteristic inflammatory changes.

Infrainguinal aneurysm formation in arterialized autologous saphenous vein grafts

True aneurysm formation in arterialized autologous veins is an unusual complication. We studied a patient with 2 aneurysms occurring in the mid and distal portion of an in situ femoropopliteal bypass. The first aneurysm led to graft occlusion 4 years after the primary intervention, requiring replacement of the ectatic graft segment. The graft was still patent when the patient was examined 7 years after the primary intervention and 3 years after the first aneurysm. In the mid portion of the graft, a true aneurysm measuring 5 by 8 cm had developed. The aneurysm was replaced by a reversed segment of the contralateral greater saphenous vein. Recovery was uneventful. Advanced atherosclerotic changes with extensive intimal fibroplasia, subendothelial cholesterol deposits, and ulcerations were revealed by means of histopathology of the aneurysm wall. Atherosclerosis is considered to be the main cause of aneurysm formation in vein grafts, but a review of the literature suggests the additional etiopathogenic factors should be further investigated.

Angiotensin converting enzyme gene polymorphisms do not predict the course of idiopathic nephrotic syndrome in Swiss children.

Aim:  Contradictory reports exist about a correlation of angiotensin I converting enzyme (ACE) gene polymorphisms to the outcome of idiopathic nephrotic syndrome (INS) in children. We investigated the frequency of ACE polymorphisms and their impact on the clinical course of INS in children in a Swiss hospital.

Intraductal carcinoma of the prostate: Interobserver reproducibility survey of 39 urologic pathologists

The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, χ(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.

PRIMARY LEIOMYOSARCOMA OF THE SEMINAL VESICLE

Sarcomas account for only 1% to 2% of all malignant tumors arising from the genitourinary tract, and primary sarcomas of the seminal vesicles are extremely rare.1 To our knowledge only 13 cases have been reported in the literature and most are poorly documented with little information on the followup. Therefore, data on optimum treatment of these tumors are limited. However, radical surgical excision offers the best chance for cure. Many of these tumors on detection have already widely invaded surrounding structures.2 The benefit of adjuvant or neoadjuvant treatment is uncertain. We report a case of primary leiomyosarcoma of the seminal vesicle.