Omission of doxorubicin from the treatment of stage II-III, intermediate-risk Wilms' tumour (SIOP WT 2001): an open-label, non-inferiority, randomised controlled trial.

BACKGROUND: Before this study started, the standard postoperative chemotherapy regimen for stage II-III Wilms' tumour pretreated with chemotherapy was to include doxorubicin. However, avoidance of doxorubicin-related cardiotoxicity effects is important to improve long-term outcomes for childhood cancers that have excellent prognosis. We aimed to assess whether doxorubicin can be omitted safely from chemotherapy for stage II-III, histological intermediate-risk Wilms' tumour when a newly defined high-risk blastemal subtype was excluded from randomisation. METHODS: For this international, multicentre, open-label, non-inferiority, phase 3, randomised SIOP WT 2001 trial, we recruited children aged 6 months to 18 years at the time of diagnosis of a primary renal tumour from 251 hospitals in 26 countries who had received 4 weeks of preoperative chemotherapy with vincristine and actinomycin D. Children with stage II-III intermediate-risk Wilms' tumours assessed after delayed nephrectomy were randomly assigned (1:1) by a minimisation technique to receive vincristine 1·5 mg/m(2) at weeks 1-8, 11, 12, 14, 15, 17, 18, 20, 21, 23, 24, 26, and 27, plus actinomycin D 45 µg/kg every 3 weeks from week 2, either with five doses of doxorubicin 50 mg/m(2) given every 6 weeks from week 2 (standard treatment) or without doxorubicin (experimental treatment). The primary endpoint was non-inferiority of event-free survival at 2 years, analysed by intention to treat and a margin of 10%. Assessment of safety and adverse events included systematic monitoring of hepatic toxicity and cardiotoxicity. This trial is registered with EudraCT, number 2007-004591-39, and is closed to new participants. FINDINGS: Between Nov 1, 2001, and Dec 16, 2009, we recruited 583 patients, 341 with stage II and 242 with stage III tumours, and randomly assigned 291 children to treatment including doxorubicin, and 292 children to treatment excluding doxorubicin. Median follow-up was 60·8 months (IQR 40·8-79·8). 2 year event-free survival was 92·6% (95% CI 89·6-95·7) for treatment including doxorubicin and 88·2% (84·5-92·1) for treatment excluding doxorubicin, a difference of 4·4% (95% CI 0·4-9·3) that did not exceed the predefined 10% margin. 5 year overall survival was 96·5% (94·3-98·8) for treatment including doxorubicin and 95·8% (93·3-98·4) for treatment excluding doxorubicin. Four children died from a treatment-related toxic effect; one (<1%) of 291 receiving treatment including doxorubicin died of sepsis, three (1%) of 292 receiving treatment excluding doxorubicin died of varicella, metabolic seizure, and sepsis during treatment for relapse. 17 patients (3%) had hepatic veno-occlusive disease. Cardiotoxic effects were reported in 15 (5%) of 291 children receiving treatment including doxorubicin. 12 children receiving treatment including doxorubicin, and ten children receiving treatment excluding doxorubicin, died, with the remaining deaths from tumour recurrence. INTERPRETATION: Doxorubicin does not need to be included in treatment of stage II-III intermediate risk Wilms' tumour when the histological response to preoperative chemotherapy is incorporated into the risk stratification. FUNDING: See Acknowledgments for funders.

Standardization of Gleason grading among 337 European pathologists.

AIMS: The 2005 International Society of Urological Pathology (ISUP) modification of Gleason grading recommended that the highest grade should always be included in the Gleason score (GS) in prostate biopsies. We analysed the impact of this recommendation on reporting of GS 6 versus 7. METHODS AND RESULTS: Fifteen expert uropathologists reached two-thirds consensus on 15 prostate biopsies with GS 6-7 cancer. Eighty-five microphotographs were graded by 337 of 617 members of the European Network of Uropathology (ENUP), representing 19 countries. There was agreement between expert and majority member GS in 12 of 15 cases, while members upgraded in three cases. Among members and the expert consensus, a GS >6 was assigned by 64.5% and 60%, respectively. Mean member GS was higher than consensus GS in nine of 15 cases. A Gleason pattern (GP) 5 was reported by 0.3-5.6% in 10 cases. Agreement between consensus and member GS was 58.2-89.3% (mean 71.4%) in GS 6 cases and 46.3-63.8% (mean 56.4%) in GS 7 cases (P = 0.009). CONCLUSIONS: While undergrading of prostate cancer used to be prevalent, some now tend to overgrade. Minimum diagnostic criteria for GP 4 and 5 in biopsies need to be better defined. Image libraries reviewed by experts may be useful for standardization.

Transcription factor E3 and transcription factor EB renal cell carcinomas: clinical features, biological behavior and prognostic factors.

PURPOSE: Translocation renal cell carcinomas represent a distinct clinicopathological entity. Studying the natural history, biological behavior and potential prognostic factors are crucially warranted. MATERIALS AND METHODS: We selected 54 patients with renal cell carcinoma with positive nuclear transcription factor E3 and transcription factor EB expression from the Juvenile RCC Network. Recurrence-free survival and overall survival were assessed. RESULTS: Median patient age was 24 years (range 1 to 64) and the male-to-female ratio was 1:1.4. At diagnosis 35 patients (65%) had local disease while 19 (35%) presented with distant metastases. The latter patients were older (median age 36 years) and predominantly male (male-to-female ratio 2) whereas the former group had a median age of 16 years and a male-to-female ratio of 1:2.5. Overall 36 patients underwent complete tumor resection and of these 8 had recurring cancer. On univariate analysis only lymph node involvement and American Joint Committee on Cancer stage were associated with poor recurrence-free survival. When stratified according to lymph node status age 25 years or older was found to predict relapse (p = 0.03). With a median followup of 19.2 months (range 1 to 58) 3-year overall survival was 14.3% in patients with distant metastasis and 70.6% in those without distant metastasis. Distant metastasis developed in the 2 patients with ASPSCR1-TFE3 fusion vs 1 of 11 with other fusion genes. CONCLUSIONS: Transcription factor E3 and transcription factor EB renal cell carcinoma display different clinical behavior according to gender and age. Lymph node involvement represents the only factor that predicts recurrence. ASPSCR1-TFE3 might be the most aggressive among the transcription factor E3 fusion genes.

Handling and reporting of transurethral resection specimens of the bladder in Europe: a web-based survey by the European Network of Uropathology (ENUP).

AIMS: To collect of information about European practices on handling and reporting of transurethral resection specimens of the bladder. METHODS AND RESULTS: The European Network of Uropathology is a communication network that includes 335 pathology laboratories in 15 western European countries. A web-based questionnaire was answered by 52.2% of members. Some routines were adopted by a majority: formalin fixation (92.5%), separate containers for tumour and resection base (72%) and embedding of the entire specimen (60%). Cancer along/in adipose tissue would be reported as pT3a by 19.5% and non-invasive urothelial carcinoma in prostatic ducts/glands as pT4a by 16.1%. Papillary urothelial neoplasia of low malignant potential is recognized by 72.6% but rarely reported. Immunohistochemistry is rarely or sometimes used for diagnosing bladder cancer by 91.7%, and the most frequently used markers are CK20 (76.9%), CK7 (66.7%) and Ki67 (38.8%). Only 24.8% report prognostic markers, with Ki67 (84.4%) and p53 (64.4%) being most common. Only 50.9% use the International Society of Urological Pathology 1998/World Health Organization (WHO) 2004 grading system, followed by WHO 1973 (43.4%) and WHO 1999 (31.4%). CONCLUSIONS: There is still variability in routine practice and a need for standardization of methodologies. These results may be helpful when judging what recommendations are reasonable to issue.

WNT/beta-catenin pathway activation in Wilms tumors: a unifying mechanism with multiple entries?

Based on characterization of both genomic and expression status of WT1 and CTNNB1 (beta-catenin) in a series of 60 Wilms tumor samples, combined with genome-wide expression profiling of these tumors, normal mature and fetal kidney controls, we show that WT1/beta-catenin expression was a better classifier than WT1/CTNNB1 mutations. We present molecular data supporting that the WNT pathway is involved in both tumor classes, with and without WT1/beta-catenin alterations. In the tumor class with WT1/beta-catenin alterations, we identified overexpression of 14 previously unreported WNT target genes, including TWIST1. We show that the TWIST1 protein was specifically expressed in these tumors, where staining was restricted to the stromal, nuclear beta-catenin positive, component. By comparing the state of the WNT pathway in tumors without WT1/beta-catenin alterations and fetal kidneys we provide evidence that suggests that these tumors have a heightened level of pathway activation. We characterized mutations of the WNT pathway regulator gene WTX in 16% of this tumor class. Moreover, genome-transcriptome correlation analysis allowed us to identify three other WNT pathway regulator genes that could participate in the activation of the WNT pathway: BCL9 (1p36.2), CTNNBIP1 (1p36.2), and CBY1 (22q13.1). These genes thus represent new potential important actors in WT tumorigenesis.

The 20-core prostate biopsy protocol--a new gold standard?

PURPOSE: We investigated the ability of a 20-core prostate biopsy protocol to enhance the prostate cancer diagnosis rate. MATERIALS AND METHODS: We compared the diagnosis rate of prostate biopsies in 2 groups of consecutive patients, including group 1-10 cores and group 2-20 cores. The prostate specific antigen range in the 2 groups was 3 to 30 ng/ml and biopsies were performed because of increased prostate specific antigen (more than 3 ng/ml) and/or abnormal digital rectal examination. To analyze the results we divided each group into 3 subgroups according to prostate specific antigen, including group 1-3 to less than 6 ng/ml, group 2-6 or greater to less than 10 ng/ml and group 3-10 or greater to up to 30 ng/ml. Multivariate analysis was performed to assess the difference in the diagnosis rate among the subgroups according to the number of cores taken. RESULTS: The percent of positive biopsies was 39.7% in group 1 and 51.7% in group 2. Multivariate analysis confirmed that the number of biopsies taken was a factor that independently and significantly correlated with the prostate cancer diagnosis. The 20-core biopsy protocol was more efficient than the 10-core protocol in the 3 subgroups with 47.2% vs 28.1% of patients diagnosed in group 1 (OR 3.26, p = 0.001), 40.5% vs 36.1% in group 2 (OR 2.37, p = 0.009) and 69.8% vs 39.7% in group 3 (OR 2.01, p = 0.015). CONCLUSIONS: The 20-core biopsy protocol was more efficient than the 10-core biopsy protocol, especially in patients with prostate specific antigen between 3 and 6 ng/ml. Nevertheless, it is mandatory to confirm whether detected tumors are clinically significant on pathological examination of the radical prostatectomy specimens.

Expansion of regulatory T cells in patients with Langerhans cell histiocytosis.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare clonal granulomatous disease that affects mainly children. LCH can involve various tissues such as bone, skin, lung, bone marrow, lymph nodes, and the central nervous system, and is frequently responsible for functional sequelae. The pathophysiology of LCH is unclear, but the uncontrolled proliferation of Langerhans cells (LCs) is believed to be the primary event in the formation of granulomas. The present study was designed to further investigate the nature of proliferating cells and the immune mechanisms involved in the LCH granulomas. METHODS AND FINDINGS: Biopsies (n = 24) and/or blood samples (n = 25) from 40 patients aged 0.25 to 13 y (mean 7.8 y), were studied to identify cells that proliferate in blood and granulomas. We found that the proliferating index of LCs was low ( approximately 1.9%), and we did not observe expansion of a monocyte or dendritic cell compartment in patients. We found that LCH lesions were a site of active inflammation, tissue remodeling, and neo-angiogenesis, and the majority of proliferating cells were endothelial cells, fibroblasts, and polyclonal T lymphocytes. Within granulomas, interleukin 10 was abundant, LCs expressed the TNF receptor family member RANK, and CD4(+) CD25(high) FoxP3(high) regulatory T cells (T-regs) represented 20% of T cells, and were found in close contact with LCs. FoxP3(+) T-regs were also expanded compared to controls, in the blood of LCH patients with active disease, among whom seven out of seven tested exhibited an impaired skin delayed-type hypersensitivity response. In contrast, the number of blood T-regs were normal after remission of LCH. CONCLUSIONS: These findings indicate that LC accumulation in LCH results from survival rather than uncontrolled proliferation, and is associated with the expansion of T-regs. These data suggest that LCs may be involved in the expansion of T-regs in vivo, resulting in the failure of the host immune system to eliminate LCH cells. Thus T-regs could be a therapeutic target in LCH.

Sulfated HNK-1 epitope in developing and mature kidney: a new marker for thin ascending loop of Henle and tubular injury in acute tubular necrosis.

The HNK-1 carbohydrate epitope is a 3-sulfo-glucuronyl residue attached to lactosamine structures on glycoproteins, proteoglycans, or glycolipids mostly expressed in the nervous system. Here, using monoclonal antibodies against the sulfated HNK-1 carbohydrate epitope, we first examined its distribution in developing and adult kidneys, then its expression in kidneys with tubular necrosis and renal neoplasms. This HNK-1 epitope was expressed in the human, rabbit, and rat, but not mouse kidney. It was detected within a subset of epithelial cells in the renal vesicle and in comma- and S-shaped bodies during early stages of nephrogenesis. In ureteral bud derivatives, the epitope was present transiently in the area where the collecting duct fused with the nephron. In the adult kidney, expression of the HNK-1 epitope became mainly restricted to the thin ascending loop of Henle where this epitope was carried by heparan- and chondro-proteoglycan. In pathological conditions, HNK-1 epitope expression increased dramatically in proximal epithelial tubule cells in kidneys with acute tubular necrosis. In tumors, the HNK-1 epitope was expressed in the epithelial component of nephroblastomas and in a subgroup of papillary renal cell carcinomas. These data suggest that molecules carrying the sulfated HNK-1 carbohydrate epitope may play an important role in critical stages of renal development and in the physiology of thin ascending loop of Henle.

Changes in WT1 splicing are associated with a specific gene expression profile in Wilms' tumour.

Wilms' tumour (WT) or nephroblastoma is the most frequent kidney cancer in children. In a previous study, we reported alterations to WT1 transcription in 90% of WT tested, with decreased exon 5 +/- isoform ratio being the most frequent alteration (56% of WT). We now report an approach based on cDNA profiling of tumour pools to identify genes likely to be dysregulated in association with a decreased WT1 exon 5 +/- ratio. We compared the expression profiles of pools of tumours classified according to whether this isoform imbalance was present (five tumours) or not (four tumours), using Atlas Cancer cDNA expression arrays. Fourteen of 588 genes tested displayed specific up-regulation (CCND2, PCNA, N-MYC, E2F3, TOP2A, PAK1, DCC and PCDH2) or down-regulation (VEGF, IGFBP5, TIMP3, ARHB, C-FOS and CD9) in the pool of tumours with decreased exon 5 +/- ratio. These results were validated by RT-PCR analysis of four genes (CCND2, PCNA, VEGF and IGFBP5). We extended the analysis of VEGF expression to 51 tumours by real-time RT-PCR and ascertained differential expression of this gene associated with WT1 expression pattern. Moreover, our results suggest that the VEGF expression level may be of prognosis relevance for relapsed patients.

Outcome of infants with celiac disease.

AIMS: Determine the proportion of infants whose celiac disease (CD) was confirmed in childhood and evaluate their prognosis in adulthood. PATIENTS AND METHODS: The diagnosis of CD was established between 1971 and 1982 in 84 infants based on intestinal biopsy data; a gluten-free diet was prescribed and the cohort followed prospectively. RESULTS: Thirty-six infants were followed less than 5 years. A second biopsy was performed in 25. Mucosa had healed in 13 and remained atrophic in 12. Three children developed partial villous atrophy between 6 and 12 years of age in spite of the gluten-free diet. Forty-five patients underwent a gluten challenge between 5 and 10 years of age: in 41 histological lesions relapsed, in two mucosa remained normal and clinical and immunological relapse developed in two. Among those 45 patients, 18 were examined after 18 years follow-up: the exclusion diet was resumed in four, overt clinical relapse developed in four and four experienced intermittent gastrointestinal disorders. All biopsies performed during a period of normal diet showed villous atrophy (except in one patient) without correlation with clinical symptoms. CONCLUSION: The diagnosis of celiac disease in infants was confirmed in nearly all cases in childhood. When they reached adulthood, these patients had few symptoms but their histological lesions persisted. These data are in favor of a lifelong exclusion diet.

Prognostic and predictive factors in prostate cancer: historical perspectives and recent international consensus initiatives.

An understanding of prognosis in cancer medicine is important for patient care, research and cancer control programs. In prostate cancer, prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic and biomolecular levels. Clinical stage and histologic grade have historically played major roles in defining heterogeneity in prostate cancer. More recently, serum prostate-specific antigen measurement has assumed a significant prognostic role. Over the last two decades there has been an explosion of research into biomarkers, many of which have been purported to have prognostic significance. In this paper we present an overview of the various consensus initiatives that have transpired over the last dozen years. Criteria for evaluating prognostic factors and classifications of predictive factors have emerged that have proven useful and advanced our understanding of the biology of prostate cancer. The results of these consensus initiatives form a foundation on which the current international consultation on prognosis (prediction) in prostate cancer is built. Advances in our understanding of the new and promising prognostic factors will require a more rigorous evidence-based approach to the analysis of published studies. Furthermore, appropriate mathematical models for the analysis of the multiple factors that influence a prognostic system will have to be employed.

Prognostic and predictive factors and reporting of prostate carcinoma in prostate needle biopsy specimens.

The information provided in the surgical pathology report of a prostate needle biopsy of carcinoma has become critical in the subsequent management and prognostication of the cancer. The surgical pathology report should thus be comprehensive and yet succinct in providing relevant information consistently to urologists, radiation oncologists and oncologists and, thereby, to the patient. This paper reflects the current recommendations of the 2004 World Health Organization-sponsored International Consultation, which was co-sponsored by the College of American Pathologists. It builds on the existing work of several organizations, including the College of American Pathologists, the Association of Directors of Anatomic and Surgical Pathologists, the Royal Society of Pathologists, the European Society of Urologic Pathology and the European Randomized Study of Screening for Prostate Cancer.

Prognostic factors and reporting of prostate carcinoma in radical prostatectomy and pelvic lymphadenectomy specimens.

This paper, based on the activity of the Morphology-Based Prognostic Factors Committee of the 2004 World Health Organization-sponsored International Consultation, describes various methods of handling radical prostatectomy specimens for both routine clinical use and research purposes. The correlation between radical prostatectomy findings and postoperative failure is discussed in detail. This includes issues relating to pelvic lymph node involvement, detected both at the time of frozen section and in permanent sections. Issues of seminal vesicle invasion, including its definition, routes of invasion and relationship to prognosis, are covered in detail. The definition, terminology and incidence of extra-prostatic extension are elucidated, along with its prognostic significance relating to location and extent. Margins of resection are covered in terms of their definition, the etiology, incidence and sites of positive margins, the use of frozen sections to assess the margins and the relationship between margin positivity and prognosis. Issues relating to grade within the radical prostatectomy specimen are covered in depth, including novel ways of reporting Gleason grade and the concept of tertiary Gleason patterns. Tumor volume, tumor location, vascular invasion and perineural invasion are the final variables discussed relating to the prognosis of radical prostatectomy specimens. The use of multivariate analysis to predict progression is discussed, together with proposed modifications to the TNM system. Finally, biomarkers to predict progression following radical prostatectomy are described, including DNA ploidy, microvessel density, Ki-67, neuroendocrine differentiation, p53, p21, p27, Bcl-2, Her-2/neu, E-cadherin, CD44, retinoblastoma proteins, apoptotic index, androgen receptor status, expression of prostate-specific antigen and prostatic-specific acid phosphatase and nuclear morphometry.

[Effect of dutasteride on reduction of intraoperative bleeding related to transurethral resection of the prostate]. / Effet du dutastéride sur la réduction des saignements per-opératoires liés a la résection transuréthrale de prostate.

OBJECTIVE: The pharmacological action of 5-alpha-reductase inhibitors (5-ARI) would reduce angiogenesis associated with benign prostatic hyperplasia (BPH), thereby decreasing peroperative bleeding during transurethral resection of the prostate (TURP). Dutasteride, a double inhibitor of 5-alpha-reductase iso-enzymes types 1 and 2, was not been previously studied in the context of reduction of peroperative bleeding related to TURP. MATERIAL AND METHODS: We conducted a multicentre, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy of dutasteride 0.5 mg per day, in peroperative bleeding related to TURP for BPH in patients over the age of 50 years with a prostatic volume greater than 30 cm3. Treatment was administered for 4 weeks before the operation. The primary endpoint was haemoglobin, expressed in grams, and expressed in relation to the weight of prostate resected, also expressed in grams. RESULTS: 59 patients were evaluated (32 treated with dutasteride and 27 treated with placebo). A significant difference in peroperative bleeding was observed between the dutasteride group (1.944 +/- 1.816 g of Hb/g of prostate resected) and the placebo group (1.401 +/- 1.021 g of Hb/g of prostate resected). Preoperative treatment was well tolerated. CONCLUSION: The working hypothesis of the study was not confirmed due to the low bleeding rate in the placebo group and the results suggest that a longer duration of treatment with dutasteride would reduce intraoperative and postoperative bleeding in TURP.

Atypical goblet cell hyperplasia in congenital cystic adenomatoid malformation as a possible preneoplasia for pulmonary adenocarcinoma in childhood: A genetic analysis.

Congenital cystic adenomatoid malformation (CCAM) of the lung is a congenital lesion that is sometimes complicated by bronchioloalveolar adenocarcinoma (BAC). In some cases foci of atypical goblet cell hyperplasia (AGCH) can be found within the cysts. It has been proposed that CCAM and AGCH predispose to the development of BAC. The present study used comparative genomic hybridization (CGH) to screen 22 cases of CCAM (epithelium, surrounding normal lung tissue, and both preneoplastic and neoplastic lesions) for chromosomal imbalances. Of these 22 cases, 10 were CCAM type 1, 10 were type 2, and 2 were type 3. Of the 10 cases of CCAM type 1, 2 were associated with AGCH, 1 was associated with atypical adenomatous hyperplasia (AAH) and associated tubular adenocarcinoma (AC), and 2 were associated with BAC (1 mucinous and 1 predominantly nonmucinous). The present study also involved immunohistochemistry for interleukin (IL)-13, IL-4 receptor-alpha (IL-4r alpha), cytokines involved in the differentiation of goblet cells, and mucin 2 protein (Muc2). Chromosomal aberrations were not detected in the epithelium or the surrounding normal lung tissue, whereas varying aberrations were found in the neoplastic lesions. The most frequent genomic imbalances observed in both AGCH and the carcinomas were gains in chromosomes 2 and 4. Interestingly, a predominance of gains was also reported in AC of nonsmokers. Chromosomal aberrations in AGCHs arising in CCAMs support their preneoplastic status. Nuclear expression of IL-13, IL-4r alpha, and Muc2 was detected in AGCH, whereas a cytoplasmic and nuclear reaction was seen in normal epithelium. This likely reflects an association with goblet cell differentiation, but it also drives proliferation in AGCH.

An unusual renal angiomyolipoma with morphological lymphangioleiomyomatosis features and coexpression of oestrogen and progesterone receptors.

Angiomyolipoma is the most common mesenchymal renal tumour, the clonal origin of which has recently been demonstrated. It is composed of varying amounts of blood vessels, smooth muscle and fat. In this report, we describe a renal angiomyolipoma, which is unusual owing to the presence of a lymphangioleiomyomatosis-like component, occurring in a 41-year-old woman suffering from sporadic lymphangioleiomyomatosis. The diagnosis was based on histopathological and immunohistochemical findings. The tumour consisted of an intimate admixture of two components: one was typical of a classical angiomyolipoma and the other was reminiscent of lymphangioleiomyomatosis. HMB45 positivity was found on 5% of the cells of the angiomyolipoma component. Ten percent of the nuclei of the lymphangioleiomyomatosis and angiomyolipoma components expressed oestrogen receptors and 5% progesterone receptors. This case illustrates a very unusual pattern of a renal angiomyolipoma containing a lymphangioleiomyomatosis-like component. The oestrogen and progesterone immunoreactivity suggests that angiomyolipoma could be hormonally dependent. Therefore, we have emphasised the morphological and immunohistochemical similarities between angiomyolipoma and lymphangioleiomyomatosis.

Brain involvement in multicentric Epstein-Barr virus-associated smooth muscle tumours in a child after kidney transplantation.

Epstein-Barr virus (EBV)-associated smooth muscle tumours (SMT) have been reported in young patients with induced immunosuppression associated with organ transplantation, acquired immunodeficiency syndrome or congenital immunodeficiencies. EBV-associated SMT are frequently multicentric or multifocal and often occur in unusual locations. We are reporting a case of EBV-associated multicentric SMT that occurred after kidney transplantation in a 2-year-old boy with a history of oligomeganephrony. Headaches and left VIth cranial nerve paralysis led to the discovery of a brain tumour 3 years after transplantation. There were multiple pulmonary, hepatic and splenic nodules and enlarged mesenteric lymph nodes. Histological examination revealed multicentric SMT of uncertain malignant potential. Further investigations using in situ hybridisation demonstrated EBV early RNAs in the nucleus of most tumour cells. The immunosuppressive therapy was reduced, and the child was treated with chemotherapy, but died 2 months later, due to neurological complications.

Five new cases of juvenile renal cell carcinoma with translocations involving Xp11.2: a cytogenetic and morphologic study.

Two cases of renal cell carcinoma (RCC) carrying a t(X;1)(p11.2;q21) in a 12-year-old boy and a 14 year-old girl, two cases with a t(X;1)(p11.2;p34) in a 9-year-old boy and a 31-year-old woman, and one case with a t(X;17)(p11.2;q25) in a 15-year-old boy are reported. Two are likely papillary RCC, with clear or slightly eosinophilic cells, and two to a clear cell RCC; one shows a mixture of papillary and clear cell RCC architecture. Renal cell carcinomas with translocations involving Xp11.2 form a specific entity characterized by subtle pathologic features and younger age of occurrence, especially for those with the t(X;17).

[Fibroblastic-myofibroblastic proliferations of childhood and adolescents]. / Proliférations fibroblastiques et myofibroblastiques de l'enfance et de l'adolescence.

Fibroblastic-myofibroblastic proliferations of childhood and adolescents form a clinical and morphologic spectrum from benign reactive processes and pseudosarcomas, to fibromatoses, to various types of sarcoma. The diagnosis is challenging because of clinical and morphologic similarities, lack of specific immunohistochemical markers for different types of fibroblastic-myofibroblastic tumors, and limited molecular genetic information. Careful attention to clinical, macroscopic, and histopathologic features permits classification in most cases. This review focuses on the pathologic features of fibroblastic-myofibroblastic tumors with a predilection for children and adolescents.

[Benign epithelial cells and Tamm-Horsfall protein in lymph nodes from nephrectomy specimens with nephroblastoma: a diagnostic pitfall]. / Cellules épithéliales bénignes et protéine de Tamm-Horsfall dans les ganglions lymphatiques des pièces de néphrectomie pour néphroblastome: un piège diagnostique.

When a lymph node metastasis is discovered during the pathology examination of surgical specimens with nephroblastoma, the tumour is classified as stage III, according to the classification of the International Society of Paediatric Oncology (SIOP 2001), and post-operative intensive treatment of the patient includes irradiation and chemotherapy. Benign epithelial cells in perinephric lymph nodes in cases of renal tumours in childhood may be confused with metastases. They are often associated with an accumulation of Tamm-Horsfall protein in lymph node sinuses. This case illustrates latero-aortic lymph node complexes of benign epithelial cells and Tamm-Horsfall protein in a 16-month-old girl with surgical resection of a nephroblastoma after pre-operative chemotherapy. The nephroblastoma was predominantly epithelial and was classified as SIOP stage I. There were accumulations of Tamm-Horsfall protein in lymph node sinuses, in lymphatic vessels, in the kidney outside the tumour, and in the renal sinus. This association of epithelial cells with deposits of Tamm-Horsfall protein and their resemblance to cells of the distal convoluted tubules favour a diagnosis of benignity. A definitive diagnosis is supported by the small size of the cells, their bland nuclei, and morphological features differing from those of tumour cells, but deposits of Tamm-Horsfall protein may be associated with true lymph node metastases.