Renal sinus pseudolymphoma in a patient with multiple carcinomas: a case report and a brief review of the literature.

The term pseudolymphoma refers to a heterogeneous group of benign reactive T-cell or B-cell lymphoproliferative processes of diverse causes that simulate lymphoma clinically and histologically but usually undergo spontaneous remission. Its pathogenesis is still unclear. The prognosis is good although some evidence suggests that pseudolymphoma may progress to lymphoma. Pseudolymphoma of the urinary tract is extremely rare. We herein report a case of pseudolymphoma of the renal sinus in a 70-year-old man, associated with a high grade urothelial carcinoma of the bladder and to a prostatic adenocarcinoma (Gleason score 6). A brief review of the literature is included. The kidney showed a well-defined, whitish soft mass which involved the renal sinus. Microscopically, the lesion of the renal sinus consisted of a proliferation of small to medium size lymphocytes (CD20 positive and Bcl-2 negative) sometimes arranged in hyperplastic follicular structures. The diagnosis was confirmed by molecular studies which showed an oligopolyclonal IgH rearrangement. To the best of our knowledge, this is the second case of pseudolymphoma with a complete molecular characterization ever described in the renal sinus and the first one associated with multiple urogenital carcinomas.

Secretion patterns and effect of prostate-derived granules on the sperm acrosome reaction of rabbit buck.

There is increasing evidence that the particulate fraction of seminal plasma plays an important role in reproduction of several mammalian species. However, the origin and role of these granules in the physiology of rabbit spermatozoa is partially unknown. The aim of this study was to investigate the implication of prostate gland in the production and secretion of granules into the rabbit semen and the role of prostate-derived granules in the sperm acrosome reaction. Light and electron microscopy of the prostate gland showed that the anterior and middle tracts of the prostate (namely the proprostate and prostate, respectively) are chiefly implicated in the secretion of granules of different size: smaller granules (SG; 0.5 µm) and large granules (LG; 4 µm). Two major patterns of secretion were identified, based on electron microscope views: storage granules (large granules) seem to empty inner smaller granules directly into the duct by exocytosis, or the storage vesicle itself is released in toto into the ducts (diacytosis). In vitro experiments using granules from vasectomized rabbits, to exclude testicular origin of granules, showed that granules reduce the acrosome reaction of Percoll-selected spermatozoa, independently of the size. Interestingly, spermatozoa incubated with heat-treated granules showed a higher sperm acrosome reaction rate, suggesting a potential role of granule-derived proteins in this process. Inhibition of the acrosome reaction is a crucial event in rabbit reproduction; ejaculated spermatozoa have to wait for a long time (8-16 h) for egg availability in the female tract after mating. Taking together, our results demonstrate that prostate granules secreted either by exocytosis or diacytosis can preserve spermatozoa fertilizing ability, by preventing sperm acrosome reaction. The type of granule-derived proteins or other macromolecules implicated in this process should be further investigated.

Cetuximab ± chemotherapy enhances dendritic cell-mediated phagocytosis of colon cancer cells and ignites a highly efficient colon cancer antigen-specific cytotoxic T-cell response in vitro.

Cetuximab is a human/mouse chimeric IgG1 monoclonal antibody (mAb) to epidermal growth factor receptor, approved for colorectal carcinoma treatment in combination with chemotherapy. The immune-mediated effects elicited by its human fraction of crystallization moiety might critically contribute to the overall anti-tumor effectiveness of the antibody. We therefore investigated cetuximab ability to promote colon cancer cell opsonization and phagocytosis by human dendritic cells (DCs) that are subsequently engaged in antigen-cross presentation to cytotoxic T-lymphocyte (CTL) precursors. Human colon cancer cell lines were evaluated for susceptibility to DC-mediated phagocytosis before and after treatment with chemotherapy ± cetuximab in vitro. Human DCs loaded with control or drug-treated cetuximab-coated colon cancer cells were used to in vitro generate cytotoxic T cell clones from peripheral blood mononuclear cells of human leucocyte antigen-A(*)02.01(+) donors. T-cell cultures were characterized for immune-phenotype and tumor-antigen specific CTL activity. The results confirmed that treatment of tumor cells with irinotecan + L-folinate + 5-flurouracil (ILF) or with gemcitabine + ILF increased tumor antigen expression. Moreover, malignant cells exposed to chemotherapy and cetuximab were highly susceptible to phagocytosis by human DCs and were able to promote their activation. The consequent DC-mediated cross-priming of antigens derived from mAb-covered/drug-treated cancer cells elicited a robust CTL anti-tumor response. On the basis of our data, we suggest a possible involvement of CTL-dependent immunity in cetuximab anti-cancer effects.

Effect of a bacterial lipopolysaccharide treatment on rabbit testis and ejaculated sperm.

In a previous study, we reported the short- and long-term effects of bacterial lipopolysaccharide (LPS)-induced inflammation on rabbit sperm quality. This study was aimed at exploring the spermatogenesis of the rabbit model focussing on the possible damages occurring to the testis and ejaculated sperm. Twenty New Zealand White rabbit bucks were divided into two groups. One group was inoculated intra-peritoneally with LPS, the other group, considered as control, was treated under the same conditions with saline only. Semen samples were collected before LPS injection, the 7th, 14th, 21st, 30th, 45th, 60th and 90th day after LPS treatment. Semen parameters were evaluated following international guidelines. The kinetic characteristics of ejaculated sperm were analysed using a computer-assisted sperm analyzer and the ultrastructural characteristics were explored by transmission electron microscopy (TEM). On the 7th, 14th and 30th day, testis from treated rabbits and controls were obtained. Testis samples were analysed by light microscopy and TEM. The induced LPS lesions in the testis became evident the 7th day after treatment, with a decrease in germinal cells and with an increase in structurally altered Sertoli cells; normal spermatogenesis was restored on the 30th day. The testicular damages observed on day 7 were probably responsible for the reduction in sperm concentration and motility and the ultrastructural alterations that were detected in the ejaculated sperm on the 14th through the 30th days after treatment. In conclusion, rabbit buck treated with LPS could be a useful model for studying the effect of an induced systemic inflammation on spermatogenesis.

State of the art on autologous mesothelial transplant in animals and humans.

Sixteen years ago rabbit and human mesothelial cells were successfully cultured and autoimplanted. The aim of the study was merely to demonstrate that mesothelial implant was possible and interesting not only in peritoneal dialysis, but also in the vaster field of medicine and surgery concerning all the mesothelial districts of the body. The aim of this paper is to recollect the steps which have led to autologous mesothelial transplantation and verify if the technique has been validated and adopted by others. Review of the literature published in the last 15 years shows that intraperitoneal transplantation of mesothelial cells has been effective in reducing the formation of peritoneal adhesions, and in remodeling the area of mesothelial denudation. New studies on the mesothelial cell opened the way to construction of transplantable tissue-engineered artificial peritoneum, to the utilization of mesothelial progenitor cells and to find simple methods to collect autologous mesothelial cells. Finally mesothelial transplantation may represent a new neovascular therapy in the prevention and treatment of ischemic coronary heart disease.

Chemo-hormone therapy of non-well-differentiated endocrine tumours from different anatomic sites with cisplatinum, etoposide and slow release lanreotide formulation.

We report the results of a phase II trial in patients with metastatic endocrine tumours from different sites, which aimed to evaluate the anti-tumour activity and toxicity of a cisplatinum and etoposide regimen administered in combination with the somatostatin agonist lanreotide given in slow release formulation. Between January 1999 and November 2003, 27 patients with histological diagnoses of endocrine tumours with different degrees of differentiation, excluding well differentiated carcinoid neoplasms, received intravenous (i.v.) administration of cisplatinum (30 mg m(-2)) and etoposide (100 mg m(-2)) on days 1-3 and intramuscular administration of 60 mg lanreotide on day 1, in a 21-day cycle. All of the patients were evaluable for toxicity and response. The treatment was very well tolerated as no grade 4 toxicity was observed. Four patients achieved a complete response, six a partial response, 12 experienced disease stabilisation and five disease progression. The average time to progression and to survival were 9 and 24 months respectively. These results suggest that this chemo-hormone therapy regimen is well tolerated and active in patients with non-well differentiated endocrine tumours.

Altered glutathione anti-oxidant metabolism during tumor progression in human renal-cell carcinoma.

It has been proposed that oxidative stress develops in tumors, with important consequences for growth and progression. To investigate this hypothesis, we measured low m.w. thiols, disulfides, protein-mixed disulfides and a pool of major anti-oxidant enzymes in renal-cortex as well as renal-cell carcinoma (RCC) specimens at stages I-II and III. Our data showed (i) a significant increase in the levels of total intracellular glutathione at both tumor stages (levels were 2.6-2.8 fold higher than those in the normal renal cortex), (ii) a marked lowering of the GSH/GSSG ratio in stage I-II accompanied by a significant decrease of many GSH-dependent enzymes (i.e., GPX, GST, GGT, GR) and (iii) unchanged GSH/GSSG ratio and GSH-dependent enzyme activity in stage III with respect to normal renal cortex. These results indicate that relevant variations exist in the glutathione antioxidant system in the different stages of RCC and support the hypothesis that oxidative stress plays an important role in RCC growth and progression.

Macrophage migration inhibitory factor in prostatic adenocarcinoma: correlation with tumor grading and combination endocrine treatment-related changes.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a ubiquitary cytokine whose expression has been investigated in tumors, showing a correlation between tumor aggressiveness and production of this protein by neoplastic cells. The aim of our study was to correlate MIF expression with tumor grade (Gleason scoring system) and histopathological changes after combined endocrine treatment (CET) of prostate adenocarcinoma. METHODS: We analyzed MIF immunoreactivity in 124 paired needle biopsies and radical prostatectomy specimens from 62 prostate cancer patients, of which 20 had been treated with CET. RESULTS: In untreated prostates, MIF expression significantly correlated with tumor grading, being stronger in low-grade than in high-grade adenocarcinoma. In treated prostates, histopathological changes also correlated with MIF immunoreactivity, but not in a significant manner. CONCLUSIONS: The results of the current study demonstrated that with histological dedifferentiation, prostate adenocarcinoma cells show a reduced MIF expression. This finding may be the consequence of a reduced MIF synthesis or the result of an enhanced and altered secretion by tumor cells into the surrounding stroma. The consequent abnormal interaction between MIF and environmental factors might influence tumor growth and diffusion. On the other hand, the minor but not significantly reduced MIF expression by tumor cells after CET seems to exclude a hormonal regulation of MIF secretion.

Macrophage migration inhibitory factor in the human prostate: identification and immunocytochemical localization.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a lymphokine originally identified for its capacity to inhibit the random migration of macrophages. Recent data have further extended knowledge of the physiological role of this protein, showing that MIF is produced by several human organs and tissues. The present study was intended to evaluate the expression and tissutal localization of MIF in the human prostate. METHODS: Prostate tissues were obtained from patients undergoing surgical adenomectomy for benign prostatic hyperplasia and were analyzed by Western blot, reverse transcriptase-polymerase chain reaction, immunohistochemistry, and immunoelectron microscopy. RESULTS. The presence of both MIF protein and mRNA was demonstrated in the prostate. Immunocytochemical studies localized MIF protein in the secretory luminal epithelial and basal layer cells. CONCLUSIONS: The present study demonstrated that the human prostate is a site of MIF synthesis. Macrophages populate the human prostate and represent an important mechanism of defense of integrity and functionality of the gland. It is speculated that MIF might play a role in preserving prostate physiological activity by maintaining its macrophage population.

Cell growth and death in malignant lymphomas. A quantitative analysis.

OBJECTIVE: To review the value of biopathologic factors in single lymphomatous patients across the boundaries of histologic classification. STUDY DESIGN: In a series of previous studies, based on a large collection of biopsy samples, the value of the above biopathologic characteristics in individual lymphomatous patients was quantitatively evaluated. RESULTS: The relationships between apoptotic index and growth fraction, in light of the expression of oncogenes, which regulate cell birth and death, were of particular value in determining the growth pattern of different lymphoma cases across the boundaries of histologic classification. CONCLUSION: The study of mechanisms that regulate cell proliferation and death might have therapeutic implications as the proper therapeutic approach should be based on detailed knowledge of the kinetic and molecular characteristics of each tumor.

Congenital fibroepithelial polyp of prostatic urethra in an adult.

OBJECTIVE: To describe an unusual case of congenital fibroepithelial polyp of the prostatic urethra in an adult, presented with acute urinary retention. METHODS: Cystouretrographic, endoscopical and pathological investigations are discussed. RESULTS: The definitive diagnosis of the tenth case of this benign lesion was made only after endoscopic resection and pathological examination. The complete resolution of the symptoms has been quick. CONCLUSIONS: We stress this unusual pathology in order to focus its peculiarity in aetiopathogenesis, diagnosis and treatment.

[Granulomatous prostatitis as collateral effect of intravesical immunotherapy with BCG]. / Prostatite granulomatosa come effetto collaterale dell'immunoterapia endovescicale con BCG.

Twenty-five male patients with superficial bladder cancer underwent intravesical Bacillus Calmette Guerin immunotherapy. A high incidence of side effects has occurred using three different substrains of BCG. Our interest has been focused on BCG related granulomatous prostatitis: we have found four asymptomatic patients with histologically diagnosed disease. We suppose therefore that its incidence is underestimated.

DNA ploidy pattern in papillary renal cell carcinoma. Correlation with clinicopathological parameters and survival.

Papillary renal cell carcinoma (PRCC) is a less frequent histomorphologic variant of renal cortical carcinoma (RCC). Morphologically, PRCC differs from other forms of RCC in that it is associated with frequent tumor infiltration by macrophages and lymphocytes, and a tendency for central necrosis and cystic change. Follow-up data revealed that survival rates are higher among patients with PRCC than among patients with other forms of RCC. The authors explore the DNA content in a series of PRCC and correlate the findings with nuclear grade, pathological stage and survival. Using Flow Cytometry, we analysed the DNA ploidy pattern of 37 paraffin-embedded PRCC. At least 3 tumor fragments were analysed in each case. To obtain the reference diploid standard, the non-tumor renal tissue from the same case was added to the solution. Tumor ploidy was classified as diploid and aneuploid. The degree of DNA content abnormalities was given by the DNA Index (DI). An aneuploid DNA profile was found in 65% of the tumors. 25% of the aneuploid tumors presented near diploid peaks (1.10 < DI < 1.30; low degree aneuploidy), 25% were hyperdiploid, while 22% had a hypodiploid profile (DI < 0.90). A homogeneous DNA ploidy pattern was observed in 25 tumors (68%), while there was intratumoral heterogeneity in 12 tumors (32%). Patients with aneuploid DNA patterns had high grade/stage tumors and died at the end of the follow-up period, while patients with diploid/near diploid profiles had low grade/stage tumors and survived. However, the multi-way analysis of variance performed in order to investigate the prognostic significance of ploidy pattern against tumor stage and grade showed a highly significant main effect of ploidy pattern. Moreover, the patients with hypodiploid DNA profile presented the worst prognosis. These results suggest that the DNA profile of PRCC is a highly significant prognostic index.