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Background Wilms Tumor (WT) can occur in association with tumor predisposition syndromes and/or with clinical malformations. These associations have not been fully characterized at a clinical and molecular genetic level. This study aims to describe clinical malformations, genetic abnormalities, and tumor predisposition syndromes in patients with WT and to propose guidelines regarding indications for clinical and molecular genetic explorations. Procedure This retrospective study analyzed clinical abnormalities and predisposition syndromes among 295 patients treated for WT between 1986 and 2009 in a single pediatric oncological center. Results Clinically identified malformations and predisposition syndromes were observed in 52/295 patients (17.6%). Genetically proven tumor predisposition syndromes (n = 14) frequently observed were syndromes associated with alterations of the chromosome WT1 region such as WAGR (n = 6) and Denys–Drash syndromes (n = 3), syndromes associated with alterations of the WT2 region (Beckwith–Wiedeman syndrome, n = 3), and Fanconi anemia (n = 2). Hemihypertrophy and genito-urinary malformations (n = 12 and n = 16, respectively) were the most frequently identified malformations. Other different syndromes or malformations (n = 10) were less frequent. Median age of WT diagnosis was significantly earlier for children with malformations than those without (27 months vs. 37 months, P = 0.0009). There was no significant difference in terms of 5-year EFS and OS between WT patients without or with malformations. Conclusions The frequency of malformations observed in patients with WT underline the need of genetic counseling and molecular genetic explorations for a better follow-up of these patients, with a frequently good outcome. A decisional tree, based on clinical observations of patients with WT, is proposed to guide clinicians for further molecular genetic explorations. Pediatr Blood Cancer 2014;61:140–144. © 2013 Wiley Periodicals, Inc.

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.

Whole slide imaging (WSI) has been used in conjunction with virtual microscopy (VM) for training or proficiency testing purposes, multicentre research, remote frozen section diagnosis and to seek specialist second opinion in a number of organ systems. The feasibility of using WSI/VM for routine surgical pathology reporting has also been explored. In this review, we discuss the utility and limitations of WSI/VM technology in the histological assessment of specimens from the prostate. Features of WSI/VM that are particularly well suited to assessment of prostate pathology include the ability to examine images at different magnifications as well as to view histology and immunohistochemistry side-by-side on the screen. Use of WSI/VM would also solve the difficulty in obtaining multiple identical copies of small lesions in prostate biopsies for teaching and proficiency testing. It would also permit annotation of the virtual slides, and has been used in a study of inter-observer variation of Gleason grading to facilitate precise identification of the foci on which grading decisions had been based. However, the large number of sections examined from each set of prostate biopsies would greatly increase time required for scanning as well as the size of the digital file, and would also be an issue if digital archiving of prostate biopsies is contemplated. Z-scanning of glass slides, a process that increases scanning time and file size would be required to permit focusing a virtual slide up and down to assess subtle nuclear features such as nucleolar prominence. The common use of large blocks to process prostatectomy specimens would also be an issue, as few currently available scanners can scan such blocks. A major component of proficiency testing of prostate biopsy assessment involves screening of the cores to detect small atypical foci. However, screening virtual slides of wavy fragmented prostate cores using a computer mouse aided by an overview image is very different from screening glass slides using a microscope stage. Hence, it may be more appropriate in this setting to mark the lesional area and focus only on the interpretation component of competency testing. Other issues limiting the use of digital pathology in prostate pathology include the cost of high quality slide scanners for WSI and high resolution monitors for VM as well as the requirement for fast Internet connection as even a subtle delay in presentation of images on the screen may be very disturbing for a pathologist used to the rapid viewing of glass slides under a microscope. However, these problems are likely to be overcome by technological advances in the future.

Our aims were to analyze reporting of Gleason pattern (GP) 3 and 4 prostate cancer with the ISUP 2005 Gleason grading and to collect consensus cases for standardization. We scanned 25 prostate biopsy cores diagnosed as Gleason score (GS) 6-7. Fifteen genitourinary pathologists graded the digital slides and circled GP 4 and 5 in a slide viewer. Grading difficulty was scored as 1-3. GP 4 components were classified as type 1 (cribriform), 2 (fused), or 3 (poorly formed glands). A GS of 5-6, 7 (3 + 4), 7 (4 + 3), and 8-9 was given in 29%, 41%, 19%, and 10% (mean GS 6.84, range 6.44-7.36). In 15 cases, at least 67% of observers agreed on GS groups (consensus cases). Mean interobserver weighted kappa for GS groups was 0.43. Mean difficulty scores in consensus and non-consensus cases were 1.44 and 1.66 (p = 0.003). Pattern 4 types 1, 2, and 3 were seen in 28%, 86%, and 67% of GP 4. All three coexisted in 16% (11% and 23% in consensus and non-consensus cases, p = 0.03). Average estimated and calculated %GP 4/5 were 29% and 16%. After individual review, the experts met to analyze diagnostic difficulties. Areas of GP 4 and 5 were displayed as heat maps, which were helpful for identifying contentious areas. A key problem was to agree on minimal criteria for small foci of GP 4. In summary, the detection threshold for GP 4 in NBX needs to be better defined. This set of consensus cases may be useful for standardization.

Lopez-Beltran A, Algaba F, Berney D M, Boccon-Gibod L, Camparo P, Griffiths D, Mikuz G, Montironi R, Varma M & Egevad L (2011) Histopathology 58, 579–585 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.

Translocation renal cell carcinomas represent a distinct clinicopathological entity. Studying the natural history, biological behavior and potential prognostic factors are crucially warranted.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.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.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.

Resume Le traitement du cancer de la prostate est appele a connaitre des innovations importantes : nouvelle classe therapeutique en hormonotherapie avec les antagonistes de la luteinizing hormone–releasing hormone qui permettent d’obtenir une reduction immediate, profonde et durable de la testosterone ; definition de criteres stricts d’eligibilite et de suivi dans des protocoles de surveillance active qui evitent au patient un traitement agressif sans diminuer ses chances de survie ; progres techniques de l’imagerie et des dosages biologiques permettent de diagnostiquer plus tot des tumeurs de petite taille ; revolution dans les traitements focalises, ciblant les cancers sans alterer les structures environnantes. Ces avancees concomitantes offrent au clinicien et au patient des options seduisantes de prise en charge. Mais il faut en connaitre les limites et les contraintes. Il faut egalement definir les profils de patients les plus adaptes a chaque type de traitement, prenant en compte les caracteristiques objectives de la tumeur et les caracteristiques psychologiques du patient.

Resume La place de l’hormonotherapie dans la strategie therapeutique du cancer de la prostate a evolue au cours du temps. Indiquee de facon indiscutable dans les cancers metastatiques et en cas d’envahissement ganglionnaire, elle est aussi utilisee dans les tumeurs localement avancees et a haut risque, combinee a la radiotherapie, mais les modalites d’association (neoadjuvante, concomitante et/ou adjuvante) restent a discuter au cas par cas en fonction du stade de la tumeur et du niveau de risque represente essentiellement par le score de Gleason, la valeur et la cinetique du PSA. L’hormonotherapie est aussi indiquee en cas de recidive biologique de type systemique, notamment quand le temps de doublement du PSA est inferieur a 12 mois. Elle repose le plus souvent sur l’utilisation des analogues de la GnRH auxquels sont associes en debut de traitement des anti-androgenes de facon a obtenir un blocage androgenique complet. Enfin, l’orientation se fait progressivement vers des traitements intermittents qui ont recemment montre la preuve de leur efficacite a condition de respecter des conditions de prescription et de suivi rigoureuses.

BACKGROUND. According to current International Society of Pediatric Oncology (SIOP) Wilms recommendations, all preoperative tumor ruptures should be classified as stage IIIc. However, to the authors' knowledge, the definition and diagnostic criteria of preoperative rupture have not been defined clearly. METHODS. The authors performed a retrospective analysis of 57 children with clinical and/or radiologic (computed tomography [CT]) signs of preoperative tumor rupture of a series of 250 patients enrolled in Wilms SIOP protocols at their institution. RESULTS. Clinical and radiologic signs of preoperative rupture were observed in 39 patients and 55 patients, respectively. The site of rupture on imaging was retroperitoneal only in 48 patients and both retroperitoneal and intraperitoneal in 7 patients. Surgery was performed after chemotherapy in 55 of 57 patients. Peritoneal disease recurrence occurred in 3 of 57 patients, including 2 patients with stage III tumors who had initial intraperitoneal rupture and 1 patient with a stage I tumor. Among the 48 patients who had radiologic signs of retroperitoneal-only rupture, the final pathologic stage was stage III in 22 patients, stage II in 9 patients, and stage I in 17 patients, and no abdominal disease recurrence was observed, although only 23 of 48 patients received flank radiotherapy. The 5-year local control rate was significantly higher in patients who had retroperitoneal-only rupture compared with patients who had intraperitoneal rupture (100% vs 83.3%; standard error, ±15.2%; P = .0015). CONCLUSIONS. The use of CT scans significantly increased the number of patients who could be classified with “tumor rupture.” Intraperitoneal rupture was diagnosed accurately with CT and was associated with a significant risk of peritoneal disease recurrence. In contrast, patients who have radiologic signs of localized retroperitoneal-only rupture at diagnosis most likely should not be upstaged, and their treatment may be determined according to pathologic stage only. Cancer 2008. © 2008 American Cancer Society.

We report clinicopathologic features of a large series of renal translocation carcinomas from a multicentric study. Diagnosis was performed by cytogenetic examination of fresh material and/or by immunochemistry with antibodies directed against the C-terminal part of transcription factor E3 (TFE3) and native transcription factor EB (TFEB) proteins. Clinical data, follow-up, and histologic features were assessed. Antibodies against CK7, CD10, vimentin, epithelial membrane antigen, AE1-AE3, E-cadherin, alpha-methylacyl-coenzyme A racemase, melan A, and HMB45 were tested on tissue microarrays. Whole-genome microarray expression profiling was performed on 4 tumors. Twenty-nine cases were diagnosed as TFE3 and 2 as TFEB renal translocation carcinomas, including 13 males and 18 females, mean age 24.6 years. Two patients had a previous history of chemotherapy and 1 had a history of renal failure. Mean size of the tumor was 6.9 cm. Thirteen cases were > or = pT3 stage. Twelve cases were N+ or M+. Mean follow-up was 29.5 months. Three patients presented metastases and 5 have died. Mixed papillary and nested patterns with clear and/or eosinophilic cells represented the most consistent histologic appearance, with common foci of calcifications regardless of the type of translocation. Using a 30 mn incubation at room temperature, TFE3 immunostainings were positive in only 82% of our TFE3 translocation carcinomas. Both TFE3 and TFEB renal translocation carcinomas expressed CD10 and alpha-methylacyl-coenzyme A racemase in all cases. An expression of E-cadherin was observed in two-third of cases. Cytokeratins were expressed in less than one-third of cases. Melanocytic markers were expressed at least weakly in all cases except two. Unsupervised clustering on the basis of the gene expression profiling indicated a distinct subgroup of tumors. TRIM 63 glutathione S-transferase A1 and alanyl aminopeptidase are the main differentially expressed genes for this group of tumors. Our results suggest that these differentially expressed genes may serve as novel diagnostic or prognostic markers.

We investigated the ability of a 20-core prostate biopsy protocol to enhance the prostate cancer diagnosis rate.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.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).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.

Kikuchi-Fujimoto's disease or histiocytic necrotizing lymphadenitis is a benign disease predominantly occurring in young women which etiology remains unknown and revealed by cervical lymphadenitis and/or prolonged fever. It has rarely been reported in children. Among the 5 cases reported, 1 child had a systemic localization. The diagnosis is based on the histological examination of a lymph node biopsy. The disease course was spontaneously favourable in 2 cases; a corticotherapy was needed in 3 children. A pathogen agent was found in 2 patients. Kikuchi's disease can reveal or evolve into autoimmune disease particularly lupus, thus a long clinical and biological follow-up is necessary.

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. (J Histochem Cytochem 54:575-584, 2006)

The aim of the study was to determine the characteristic features and outcome of carcinoid or mucoepidermoid tumours in children. A retrospective analysis of all patients treated for a carcinoid or mucoepidermoid tumour in France between 1984 and 2001 was performed. There were 11 cases of carcinoid tumour and 6 cases of mucoepidermoid tumour. The mean age of the patients was 10.5±3.0 years, with a range of 5 to 15 years. Twelve and 6 patients presented with evidence of bronchial obstruction and haemoptysis, respectively. Fibre optic bronchoscopy confirmed the presence of a bronchial tumour in all cases and endobronchial biopsies were diagnostic in 11 of 12 cases. A chest CT scan revealed the presence of a hypervascular tumour in 8 of 12 patients. The distribution of the location of the tumours was equal between the right and the left lung, and, in 9 cases, the airways were totally occluded by the tumour. Complete surgical resection (lobectomy in 15 patients and pneumonectomy in 2 patients) was performed in all cases without pre-operative chemotherapy or radiotherapy. The mean duration of follow-up was 4.0±3.0 years. In 2 patients, auscultation assymetry and an episode of haemoptysis revealed the recurrence of a mucoepidermoid tumour, successfully cured by removal of the tumour and chemotherapy and radiotherapy in one child. No death was observed. Conclusion:Pulmonary carcinoid and mucoepidermoid tumours are rare in children. Bronchoscopic removal should not be performed. With aggressive surgical therapy, the prognosis is excellent. Fibre optic bronchoscopy confirms the presence of an endobronchial mass. A biopsy is needed for diagnosis and complete surgical removal is the treatment of choice. Long-term results are excellent but a clinical follow-up is recommended.

Resume La fusariose disseminee de l'enfant est une infection fongique rare et grave, touchant particulierement les patients immunodeprimes neutropeniques, traites pour une hemopathie maligne, ou greffes de moelle osseuse. Les possibilites therapeutiques sont limitees et la mortalite varie de 50 a 70 % chez l'adulte. Observation 1. – Un garcon de dix ans, traite pour une leucemie aigue lymphoblastique T en deuxieme rechute, a presente une infection disseminee a fusarium spp, lors d'un episode de neutropenie. Il est decede de cette fusariose malgre un traitement par amphotericine B. Observation 2. – Une fille de dix ans, neutropenique sous chimiotherapie, pour une leucemie aigue myeloblastique, a presente une fusariose disseminee, non controlee par l'amphotericine B. L'infection a evolue favorablement, apres l'introduction du voriconazole et la sortie d'aplasie. Dix mois plus tard, cette enfant a presente une recidive de la leucemie, et a ete traitee par une nouvelle chimiotherapie intensive, sans reactivation de la fusariose, sous couvert d'une prophylaxie secondaire par voriconazole. Conclusion. – Le voriconazole, nouvel azole, semble representer une alternative au traitement classique de la fusariose disseminee par amphotericine B, soit a la phase aigue, soit en prophylaxie secondaire.

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.

Resume Grâce aux progres de l'echographie fœtale le diagnostic de certaines tumeurs est possible avant la naissance. Nous rapportons cinq cas de neuroblastomes surrenaliens de diagnostic antenatal. Le diagnostic a toujours ete effectue au troisieme trimestre de grossesse. A la naissance aucun retentissement fonctionnel n'a ete observe et les dosages des catecholamines urinaires etaient normaux. L'echographie montrait une tumeur kystique dans un cas, solide dans deux cas et d'echostructure mixte dans les deux derniers. Les cinq enfants ont ete operes sans chimiotherapie pre- ou postoperatoire. Dans chaque cas il s'agissait d'un neuroblastome de stade I selon la classification d'Evans. Tous sont vivants sans recidive avec un recul de 32 mois a 14 ans.

Resume Quand un nephroblastome s’accompagne de metastases ganglionnaires lymphatiques a l’examen de la piece operatoire, la tumeur est de stade III selon la classification de la Societe Internationale d’Oncologie Pediatrique (SIOP 2001), ce qui implique un traitement post-operatoire lourd comportant radiotherapie et chimiotherapie. Des cellules epitheliales benignes dans les ganglions lymphatiques de drainage d’une tumeur du rein chez l’enfant peuvent etre confondues avec des metastases. Elles sont le plus souvent associees a une accumulation de proteine de Tamm-Horsfall dans les sinus ganglionnaires lymphatiques. Nous rapportons une observation de cellules epitheliales benignes associees a des depots de proteine de Tamm-Horsfall au niveau d’un ganglion lymphatique latero-aortique chez une fille âgee de 16 mois operee pour nephroblastome apres chimiotherapie pre-operatoire. Le nephroblastome etait a predominance epitheliale et de stade SIOP I. Il existait une accumulation de proteine de Tamm-Horsfall dans les sinus ganglionnaires lymphatiques, dans les vaisseaux lymphatiques, dans le rein en dehors de la tumeur et dans le sinus renal. L’association des cellules epitheliales a des depots de proteine de Tamm-Horsfall et leur ressemblance avec les cellules des tubules contournes distaux sont des arguments en faveur de leur benignite. Celle-ci est reconnue par la petite taille des cellules, par l’aspect regulier de leur noyau et par leurs caracteristiques morphologiques differentes de celles des cellules tumorales, mais des depots de proteine de Tamm-Horsfall peuvent s’associer a d’authentiques metastases ganglionnaires lymphatiques.

Appropriate handling and processing of prostate needle biopsies is critical for an optimal examination by pathologists. Reporting by pathologists should be accurate, unequivocal and concise, giving the information needed for the urologist. Quality parameters need to be developed to survey the performance of pathology laboratories.

The nonfamilial Carney triad includes paraganglioma, gastrointestinal stromal tumor (GIST), and pulmonary chondroma. Some paraganglioma-GIST diads are familial and inherited in an apparent autosomal dominant manner. The familial paraganglioma-GIST syndrome differs from the Carney triad by the absence of female predilection and predominance of paragangliomas. We report the cases of a 12-year-old boy with a paraganglioma of the organ of Zuckerkandl, and his 13-year-old monozygotic twin with a gastric GIST. These two patients, to our knowledge, are the first to be reported as likely having the familial paraganglioma-GIST syndrome following its description by Carney and Stratakis (Am J Med Genet 2002;108:132–139) in 12 patients from five families. A lifetime follow-up and a periodic search for both tumors are indicated in these patients and their families.

The gold standard in the treatment of renal tumors is radical or partial nephrectomy. The surgical specimen handling is important since the pathologic features result in clinico-pathologic knowledge that determines prognosis, additional treatment and scientific studies. The correct handling of the specimen by urologists and pathologists becomes very basic in order to enable retrieval of a maximum of information. This protocol aims at standardization of the minimal criteria for handling, cellular subtyping, grading, staging and margin evaluation that must allow the comparison among the different scientific groups. (C) 2003 Elsevier B.V. All rights reserved.

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).

Fe ´deration de Genetique et INSERM U458, Hoˆpital Robert-Debre (AP-HP), Paris, FranceWehaveanalyzedsurfactantproteinB(SP-B)and its encoding gene (SFTPB, MIM 178640)in 40 unrelated pediatric patients with un-explained respiratory distress (URD). Therewas high consanguinity (eight kindreds)and an underlying autosomal recessive traitcould be inferred in most cases, with overallhigh sex ratio (32/17) suggesting proband’sgendertoimpactonpenetrance.Theclinical/biological presentations fitted into threemajor nosologic frameworks. I: SP-B de-ficiency (nine probands), complete or in-complete, with homozygous/compoundlyheterozygous mutations identified (six pro-bands), including one from the populationisolate of Re´union Island (496delG). In ad-dition, there was a consanguineous kindredin which incomplete deficiency was unam-biguously unlinked to SFTPB. II: pulmonaryalveolar proteinosis (PAP, 19 probands),withtypicalstorageofPAS-positivematerialwithin the alveoli with foamy macrophagesandvariableinterstitialreaction,whichwasdiagnosed in most patients from Re´unionIsland. In contrast to previously publishedfindings, mutation and/or segregation ana-lyses excluded SFTPB as a disease locus,although slight metabolic derangementrelated to SP-B and/or mild SFTPB changescould somehow contribute to disease. III:URD without evidence for SP-B deficiencyor PAP (12 probands), equally unlinked toSFTPB, although a single patient had apossibly causal, maternally-derived, hetero-zygous genetic change (G4521A). The popu-lation frequency of five known and fournovel SNPs was studied, providing as manypotential markers for pulmonary diseaserelated to SFTPB. Overall, URD was foundto be heterogeneous, both phenotypicallyand genetically, even in population isolateswhere a founder effect might have beenexpected. When disease loci are identified,patient genotyping will be crucial as a diag-nostic aid, for devising proper treatment,and as a basis for genetic counseling.

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.

Background Pulmonary alveolar proteinosis (PAP) is very rare in children. Only a few small series have been published, with little information about long-term progression. The objective of our study was to describe the clinical, radiological and pathological features, and the long-term course of PAP in a cohort of 34 children from La Réunion Island. Methods Data were retrospectively collected from medical files. Radiological and pathological elements were reviewed by two pediatric radiologists and three pathologists, respectively. Results Thirteen cases were familial and 32/34 (94%) cases were family connected. Disease onset occurred in the first six months of life in 82% of the patients. Thoracic computed tomography scans showed the typical “crazy-paving” pattern in 94% of cases. Respiratory disease was associated with a liver disorder, with the detection of liver enlargement at diagnosis in 56% of cases. The course of the disease was characterized by frequent progression to chronic respiratory insufficiency, accompanied by the appearance of cholesterol granulomas and pulmonary fibrosis. Overall prognosis was poor, with a mortality of 59% and an overall five-year survival rate from birth of 64%. Whole-lung lavages were performed in 21 patients, with no significant effect on survival. Liver disease progressed to cirrhosis in 18% of children, with no severe complication. Conclusions PAP in children from la Réunion Island is characterized by an early onset, associated liver involvement, poor prognosis and frequent progression to lung fibrosis, despite whole-lung lavages treatment. The geographic clustering of patients and the detection of many familial links between most of the cases strongly suggest a genetic etiology, with an autosomal recessive mode of inheritance.

This article describes the clinical and pathologic features of four unusual bone tumors. Three were congenital or most likely so; the fourth, detected at age 1 year, was probably of considerable duration. The patients, three boys and one girl, each presented with a painless mass. Two had the Carney complex, a familial lentiginous and multiorgan tumorous syndrome; another probably had this disorder; the fourth did not show it, but his mother did. The tumors occurred in the nasal region (n = 2) and the diaphysis of the tibia and radius (n = 1 each). Roentgenographically, three had benign characteristics; the fourth, malignant features. Grossly, the tumors were gelatinous, cartilaginous. and bony. Microscopically, they featured benign-appearing polymorphic cells with few division figures arranged in sheets and lobules set in a myxomatous, cartilaginous, osseous, and hyaline fibrous matrix. Cellularity was low to moderate. The tumors eroded bone, one infiltrated between bony trabeculae, and three had soft tissue extension. Complete resection of one tumor was curative; incomplete excision of two tumors resulted in local recurrence (intracranial and fatal) in one and persistence in the other; the fourth tumor remains under observation after biopsy. No tumor metastasized.

Adrenocortical carcinomas are rare malignant tumors. They have a poor prognosis, as they are often diagnosed late and are usually resistant to chemotherapy. The lack of a suitable animal model for these tumors has been a major obstacle to the evaluation of new therapeutic agents. The aim of this study was to establish and characterize xenografts of the human adrenocortical carcinoma NCI H295R cell line as a model of adrenocortical carcinoma for future therapeutic trials. This cell line was sc injected (6 × 106 cells) into nude mice (n = 20). Solid tumors were locally measurable after 45 days at 90% of the inoculation sites. The xenografts were similar histologically to the original adrenocortical carcinoma from which the cell line was derived. The xenografts precisely reproduced the dysregulation of the insulin-like growth factor (IGF) system[ overexpression of the IGF-II and IGF-binding protein-2 (IGFBP-2) genes] typical of adrenocortical carcinoma. Similarly to adrenocortical carcinomas, human IGFBP-2 (but not IGF-II) was secreted in mouse plasma. We analyzed steroid production (cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone,Δ 4-androstenedione, 11-deoxycortisol, corticosterone, and testosterone). Xenografts produced all three class of steroids, with the preferential production of androgens of the Δ4 pathway. The H295R xenograft model is a good model of human adrenocortical carcinoma, as it mimics dysregulation of the IGF system usually found in these tumors. It also produces IGFBP-2 and steroids that can be used as tumor markers. This model may therefore be useful for evaluating therapeutic agents.

Background The SIOP Nephroblastoma therapeutic protocols include a period of preoperative chemotherapy followed by nephrectomy and a period of postoperative chemotherapy. From the outset, identification of low-risk groups has been an aim of the SIOP Nephroblastoma Trials and Studies. Now that 90% of children with Wilms tumor can be cured, attention is even more focused on the identification of patients who could benefit from less aggressive postoperative therapy, thus minimizing the morbidity and late effects associated with treatment. The prognostic implications of total necrosis in nephroblastoma after chemotherapy have not been investigated hitherto. Procedure Between November 1, 1987 and June 30, 1993, 599 patients referred to the SIOP-9 Nephroblastoma Trial and Study were preoperatively treated and classified as stages I–IV nonanaplastic Wilms tumor. Results Of these 599 patients, pathologic examination of the nephrectomy specimen revealed a completely necrotic Wilms tumor (CNWT) with no viable tumor remaining in 59 (10%): these comprised 37 stages I–III and 22 stage IV. Of these patients, 58 (98%) had no evidence of disease at 5 years vs. 90% for the rest of the cohort (P < 0.05). Stages I–III patients represented 63% of CNWT and had a 97% overall survival rate. The only death was related to veno-occlusive disease and occurred in a stage I patient in the month following nephrectomy. Stage IV patients represented 37% of CNWT (vs. only 10% of all other cases of unilateral nonanaplastic Wilms tumor) and had a 100% rate of survival. Children with CNWT were older (mean 59 months vs. 43 months); their tumor at diagnosis was larger and had regressed more significantly at subsequent ultrasound examination. The data also uphold the hypothesis that Wilms tumors of blastemic pattern are most aggressive, but also are extremely responsive to chemotherapy. Conclusions Patients with unilateral nonanaplastic WT that showed total necrosis following preoperative chemotherapy had excellent outcome and should benefit from less aggressive postoperative treatment in further trials. Other very responsive tumors, such as Wilms with

To perform a multivariate analysis to investigate the usefulness of eight preoperative variables as predictors of final pathological stage (pT), positive surgical margins (PSM) and biological progression after radical prostatectomy (RP).In 143 patients undergoing RP for T1-T2 prostate cancer, the respective values of age, clinical stage, preoperative prostate-specific antigen (PSA), prostate-specific antigen density (PSAD), number of positive biopsies (NPB), Gleason score, length of tissue core invaded by cancer (LTI) and topography (uni/bilaterality) of positive biopsies for predicting extracapsular extension, PSM and biochemical failure (PSAor =0.05 ng/ml) were evaluated retrospectively. Univariate and multivariate analyses were applied to define the statistical significance of each variable. Actuarial survival without biological progression was calculated using the Kaplan-Meier method (log-rank test).In this series, 44.8% of patients had extracapsular extension with 41.3% PSM. The mean PSA was 12.4 ng/ml. In univariate analysis, LTI (p0.0001), NPB (p = 0.0023), PSA (p = 0.0039) and Gleason score (p = 0.0136) were the most powerful variables to predict pT stage; however, in logistic regression analysis, LTI was the most predictive feature. For prediction of PSM, some variables (LTI, NPB and PSA) were found to be of statistical value in univariate analysis, and LTI in combination with NPB and PSA in multivariate analysis. For biological progression, statistical analysis (log rank test) showed PSAD and LTI to be significant predictors.The pathological report regarding the biopsy contains crucial information influencing the prediction of pT stage, PSM and biological progression after RP. LTI, NPB and PSA are the most useful parameters for this purpose.

Resume L'objectif de l'etude est d'evaluer les niveaux d'expression tissulaire et les quantites circulantes de chromogranine A chez les patients ayant un cancer prostatique ou une hypertrophie benigne de la prostate (HBP). Parmi 100 patients ayant eu des biopsies prostatiques, 46 ont un adenocarcinome (groupe I) et 54 une HBP (groupe II). Les quantites de chromogranine A dans le sang circulant sont determinees avec un seuil de positivite de 100 ng mL−1. Une procedure immunohistochimique est appliquee chez tous les patients. L'expression tissulaire de la chromogranine A est cotee de 0 a 3+, selon le nombre de cellules marquees. Lorsque le patient a subi une prostatectomie radicale, le niveau d'expression tissulaire de la piece operatoire est rapporte a celui des biopsies. 17,4 % des patients du groupe I ont un taux serique de chromogranine A superieur a 100 ng mL−1 contre 3,7 % dans le groupe II. La moyenne des taux seriques dans le groupe I est de 66,8 ± 98,8 ng mL−1 et de 38,1 ± 27,8 ng mL−1 dans le groupe II. Dans le tissu sain, seuls 10 % des patients n'ont aucune expression tissulaire de chromogranine A, contre pres de la moitie des patients dans le tissu tumoral. La plus forte immuno-expression tissulaire de chromogranine A est retrouvee dans les prelevements tumoraux (10 % versus 1 %). La presente etude confirme que la chromogranine A est statistiquement plus abondante dans le serum des patients ayant un cancer prostatique que dans le serum des patients ayant une HBP.

The prognosis for children with chronic interstitial lung disease is poor and the mortality rate is high, especially in infants. This explains the many therapeutical protocols which have been proposed and investigated by several authors. In the present work, we evaluated the response of three infants with idiopathic pulmonary fibrosis to high-dose intravenous prednisolone pulses. The patients were referred to the department at the age of 4, 17, and 3 months, respectively. The diagnosis was confirmed by open lung biopsy and intravenous pulse methyl prednisolone therapy was started with the following protocol: 300 mg/m2 methylprednisolone daily for 3 days, repeated every 4 to 6 weeks. Because of the extreme severity of the respiratory distress at the time of diagnosis, the intravenous pulse treatments were initially complemented by oral prednisone. Clinical improvement was noticed within 6 months with progressive correction of hypoxemia. After follow-up for 3.5 to 4 years, with a total number of pulses of 37, 26, and 32, respectively, the children are symptom-free and do not require oxygen supplementation. During this period, no side effects and no adrenal insufficiency could be documented. Based on current knowledge of steroid action, it can be speculated that the response to intermittent high-dose intravenous methylprednisolone may explain the ability of this mode of hormone administration to maintain an adequate level of glucocorticoid receptor expression. More information and trials through multicenter collaborations are needed to assess therapeutical protocols of repeated high-dose intravenous steroid treatment.

We report a case of progressive osseous heteroplasia in a female infant who had progressive ossification of the skin and deep connective tissues. Isolated dermal ossification is present in her father and younger sister suggesting an autosomal dominant mode of inheritance with variable expressivity or possible somatic mosaicism. This report of a family with progressive osseous heteroplasia contributes to the understanding of this uncommon genetic disorder, which must be distinguished from fibrodysplasia ossificans progressiva and Albright’s hereditary osteodystrophy. The paucity of familial cases of progressive osseous heteroplasia currently limits the use of a genome-wide linkage analysis, but linkage exclusion analysis with promising candidate genes is a possibility.

Idiopathic pulmonary fibrosis is a poorly characterized disease in infants. In the present report, we reviewed our experience with 10 infants during a 10-year period. In 9 patients, onset of symptoms occurred before the age of 2 months and included tachypnea, cough, and inadequate weight gain. However, despite the presence of these symptoms, diagnosis was delayed for 3 months at which time the infants were referred to the pediatric pulmonary department, when the diagnosis was confirmed by open lung biopsy. At the time of admission, bronchoscopy with alveolar lavage was performed in 9 children and showed severe alveolitis with an increase in the neutrophil count. Nine infants were treated with prednisone alone or in combination with chloroquine, colchicine, or cyclophosphamide; all these patients died despite treatment. One infant was treated with pulses of methylprednisolone because of a failure in response to oral prednisone. This girl who displayed similar clinical, radiological, and histological abnormalities as the other children at the time of diagnosis is the only child still alive after 3 years of follow-up. She is now free of respiratory symptoms and has a normal growth curve. The present report raised two important points: (1) a thorough evaluation of characteristic symptoms should lead to an early diagnosis of pulmonary fibrosis in infants; and (2) administration of pulse therapy using corticosteroids has been helpful and needs to be evaluated further. Pediatr Pulmonol. 1997; 23:49–54. © 1997 Wiley-Liss, Inc.

The histologic and immunohistochemical features of three congenital pedunculated nasopharyngeal midline masses are reported. The follow-up in all cases was uneventful. The tumors were characterized by solid and cystic squamous nests and ductlike structures focally continuous with the surface squamous mucosa of the tumor. Most of epithelial structures coalesced with densely cellular stroma-like nodules. Immunoperoxidase staining showed the presence of epithelial markers in both spindle cells and epithelial structures. Spindle cells were also reactive to vimentin and smooth muscle actin, revealing their myoepithelial phenotype. Based on these observations, a diagnosis of salivary gland anlage tumor, also called congenital pleomorphic adenoma of the nasopharynx, was made. The similarity of these tumors' architecture and cellular composition to the normally developing salivary gland has led to the hypothesis of a tumorlike, hamartomatous lesion developing in a site in which minor salivary gland tissue occurs. This report reviews 12 identified cases of this tumor, of which all but one (in which the patient died of sepsis) had a favorable outcome. In an infant with respiratory distress and/or feeding difficulties, these tumors must be differentiated from other midline masses such as encephaloceles and teratomas. They appear curable by surgical exeresis only.

A clear cell rhabdomyosarcoma was studied by light microscopy, histochemistry, immunohistochemistry, and electron microscopy. It was a large, painful left parapharyngeal mass in a 10-year-old boy with intracranial extension and cervical metastatic enlarged lymph nodes. Tumor tissue was macroscopically grayish. At microscopic examination, the architecture was diffuse and focally alveolar. Tumor cells were of three types. Most cells were large, round or polygonal, with abundant clear vacuolated cytoplasm. Fibrils were sometimes found to be present around the nucleus. Nuclei often had irregular outlines and multiple nucleoli. Mitotic activity was high. Some round or elongated cells had eosinophilic fibrillar cytoplasm and were found to have a few double striations. A few cells were round and medium sized with a high nucleocytoplasmic ratio. Periodic acid-Schiff stain demonstrated huge amounts of intracytoplasmic glycogen in clear cells. Tumor cells showed positive immunostaining for muscle markers (desmin, muscle actins, dystrophin). Electron microscopy showed large lakes of glycogen, lipid droplets, and striated muscle features.

Resume Les carcinomes muco-epidermoides (CME) sont des tumeurs bronchiques exceptionnelles chez l'enfant: elles sont potentiellement malignes. Observations. — Deux garcons (7 et 11 ans) et une fille (5 ans) ont ete examines pour toux chronique, pneumopathies recidivantes et/ou hemoptysies, evoluant depuis 2 a 12 mois. L endoscopie bronchique montrait une tumeur siegeant sur la bronche souche gauche (deux cas) ou droite (un cas). La tomodensitometrie thoracique precisait les lesions parenchymateuses et l'extension locale. Le diagnostic de CME a ete fait par l'examen anatomopathologique. Le traitement a ete chirurgical : resection-anastomose bronchique, associee a une lobectomie superieure gauche (deux cas), bronchotomie-exerese tumorale (un cas). Il n'y avait pas de metastases. L'evolution a ete favorable avec un recul de 8 a 24 mois. Conclusion. — Les tumeurs des glandes bronchiques de l'enfant doivent etre recherchees devant des manifestations chroniques ou recidivantes, qui doivent conduire a la realisation d'une endoscopie bronchique.

Objective To evaluate whether a single positive prostate biopsy in six systematic transrectal ultrasonography (TRUS)-guided biopsies is predictive of a small tumour volume in a subsequent radical prostatectomy (RP) specimen. Patients and methods Of 158 patients submitted to RP for T1–T2 prostate cancer, 15.2% had one positive biopsy. The rate of positive margins (M+) and extracapsular involvement (C+) were assessed on the RP specimen in those with one positive biopsy (group I) and in those diagnosed by more than one positive biopsy (group II). The percentage of those with post-operative biological progression (P+), having a prostate-specific antigen (PSA) level>0.1 ng/mL, was evaluated in both groups. The Gleason scores in biopsies and specimens were also compared. Fifteen patients diagnosed by a single positive biopsy were management conservatively. Results The percentage of patients who were categorized C+, M+ and P+ was 29.2, 16.7 and 26% in group I and 70, 46.5 and 49.5%, respectively, in group II. All patients with

We present 22 (0.9%) cases of rhabdoid tumour of the kidney diagnosed amongst 2392 renal tumours in children. The patients ages ranged from 3 weeks to 94 months (median 7 months) and the female:male ration was 1.2:1. Clinically, they presented with an abdominal mass but four (18%) children also had hypercalcaemia and one (4.5%) developed a brain tumour (primitive neuroectodermal tumour). None of the children presented with stage I disease, five (23%) had stage II, ten (46%) stage III, and five (23%) stage IV disease. Two (9%) patients had bilateral tumours. Histologically, the vast majority (20/22) of the tumours exhibited a classical pattern but other histological patterns were also noted. Immunohistochemical studies performed in 12 cases showed vimentin positivity in all cases, CAM 5.2 in eight, epithelial membrane antigen in six, neuron specific enolase in four, S-100 protein in eight, and desmin in one case. In only 12 of the 22 tumours was there agreement between the reporting pathologist and the panel on a diagnosis of rhabdoid tumour of the kidney. Eight tumours originally diagnosed as rhabdoid tumour of the kidney were found to be other renal tumours and in another ten cases the initial diagnosis was changed by the panel to rhabdoid tumour. Metastases developed in 18 (82%) of the children--in eight they were present at the time of diagnosis and in 10 they developed from 2 weeks to 9 months after initial diagnosis. Metastases were found in the lung, abdomen, lymph nodes, liver, bone and brain. Of the 19 children with adequate follow-up, only two (10.5%) with stage II disease are alive, while 17 (89.5%) died 2 weeks to 20 months after the diagnosis.

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. 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 GS6 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). 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.

The increased survival rate of malignant diseases due to more aggressive treatments contributes to the occurrence of drug-induced pulmonary diseases (DIPD). We reviewed, retrospectively over a 10-year period, 15 children (8 girls) who presented a DIPD. Their mean age was 9 years (range, 1 to 17 years), with an underlying malignant disease in 14 (9 leukemias). Three typical patterns have emerged from this analysis: (1) acute hypersensitivity lung disease caused by methotrexate (in 6 patients) or azathioprine (in 1 patient). This acute syndrome consisted of alveolar-interstitial infiltrate with a hypercellularity on bronchoalveolar lavage (BAL) (mean, 714,286 cells/mL; range, 180,000-2,940,000 cells/mL) and an increase of lymphocyte counts (mean, 39%; range 11-64%) with predominantly CD8-suppressor/cytotoxic lymphocytes. Inhibition of leukocyte migration or leukocyte aggregation in the presence of low drug concentrations was positive in the 5 cases tested. Lung function tests showed a restrictive pattern and the outcome of DIPD was always favorable. (2) Chronic pneumonitis/fibrosis was seen in 6 patients who received a variable association of cyclophosphamide (3 patients), bleomycin (2 patients), BCNU (2 patients), and melphalan (1 patient). Symptoms of an alveolar-interstitial pneumonitis developed progressively. BAL showed a moderate increase of total cell numbers (mean, 495,000 cells/mL; range, 150,000-900,000 cells/mL). Lung function tests showed a restrictive pattern. Despite corticosteroid treatment in 4 children, one died after bleomycin lung injury and 2 had functional lung impairment. (3) Noncardiogenic pulmonary edema occurred in 2 patients with leukemia treated with recombinant interleukin II. BAL showed hypercellularity and outcome was rapidly favorable.(ABSTRACT TRUNCATED AT 250 WORDS)

To collect of information about European practices on handling and reporting of transurethral resection specimens of the bladder.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%).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.

A unilateral cystic renal process discovered prenatally was removed in a neonate. Dysplastic cysts were associated with diffuse (both intra- and perilobar) nephroblastomatosis. We describe a comprehensive immunohistological study confirming the transition observed on simple histology between the different structures: nephrogenic rests (CD9+, CD24+/-, CD56+/-), glomeruloid bodies (CD10++, CD35++), ducts lined by columnar epithelium (CD9+, CD24+, CD56++), cysts lined by cuboidal or thin epithelium (some cells CD10+, CD26+, others EMA+, CD24+). Although no typical S-shaped bodies are seen, small cysts and ducts with a columnar epithelium are considered similar. The dysplastic primitive ducts are KL1++, vimentin+/-, CD9+, CD24+. With a view to assessing dysplastic preneoplastic potential, the value of CD56 and Ki67 as activation antigens with possible prognostic significance is discussed.

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.

Metanephric stromal tumor is a rare benign entity belonging to the group of metanephric renal tumors in children. Although metanephric stromal tumors can be cured by simple nephrectomy, differential diagnosis based on histopathologic criteria with other pediatric renal tumors requiring aggressive chemotherapy can be difficult. To our knowledge, cytogenetic characterization of metanephric stromal tumor has never been reported. We describe conventional ("R-bands" karyotyping) and molecular [fluorescence in situ hybridization (FISH), multicolor FISH, oligo array-comparative genomic hybridization] cytogenetic examinations of a metanephric stromal tumor in a 3-year-old boy. Cytogenetic analysis revealed a complex homogeneous gain between bands 17q22 and 17q25.3, resulting in partial triplication of the segment between bands 17q22 and 17q24.3, and duplication of the segment between bands 17q24.3 and 17q25.3. Cytogenetic confirmatory studies in metanephric stromal tumors are currently needed to assess 17q22q25.3 gain as a recurring cytogenetic abnormality of metanephric stromal tumors.

Congenital chondroid lesions of the lung are rare pathological findings. They are a constant feature of lung malformations such as giant cystic pulmonary chondroid hamartoma, chondroid cystic malformation, and in the "cartilaginous variant" of congenital adenomatoid malformation. All of these present as a large single thoracic mass.We present the cases of three males and two females with hitherto undescribed diffuse chondroid lung disease, all but one of whom had neonatal respiratory distress syndrome with interstitial syndrome on chest radiograph. The pathological findings were similar in all patients, showing large areas of disorganized lung parenchyma containing diffusely distributed mature cartilage islands. With a mean follow-up of 6 years, all patients had a favorable outcome. This diffuse chondroid lung disease appears to be a new entity whose initial presentation mimicked interstitial lung disease without the usual clinical, radiological, and histological features. We speculate that it could be part of a clinical spectrum between malformative chondroid lung cyst and congenital pulmonary airway malformation.