Evaluation of a bladder and bowel training program for therapy-resistant children with incontinence.

INTRODUCTION: Daytime urinary incontinence (DUI) and fecal incontinence (FI) are common disorders in children. Although standard treatment is highly effective, subgroups of incontinence (combinations of nocturnal enuresis (NE), DUI and/or FI, or with psychological comorbidity) can relapse or take a chronic course. For these complex, therapy-resistant cases, a manualized outpatient bladder and bowel training program was developed. The aim of the study was to evaluate prospectively treatment effects of this training program, including a follow-up assessment. MATERIAL & METHODS: The training program was developed for small groups of 2-6 children (of same age and sex) aged 5-12 years with adaptations for 13-16 year-old adolescents. It consists of 7-9 weekly sessions for group training and 3 weekly sessions for individual training. The training comprises information about anatomy/physiology of the urogenital tract, pathophysiology, hygiene and balanced nutrition. Voiding and drinking diaries, stress management, relaxation and emotion regulation techniques are also included. Data of 32 children (mean age 8.6 years, range 5-13 years; 21 boys), who had received standard treatment (and did not reach complete response) are presented. 14 children received group therapy, 18 (younger children) were treated individually. Children were assessed before and after the treatment, as well as at a follow-up of 6 months later. Treatment effects were measured by incontinence frequency and treatment success according to the ICCS (complete response: 100% reduction of symptoms; partial response: 50-99% reduction of symptoms). Psychological symptoms were measured by the Child Behavior Checklist questionnaire (CBCL). RESULTS: Frequencies of DUI were significantly reduced from 5.7 wetting episodes/week (before training) to 4.9 (after training) to 2.0 (6 months after training). Frequencies of FI were reduced from 2.9 soiling episodes/week (before training) to 1.9 (after training), but increased to 2.6 (6 months after training). According to the ICCS classification, 11.1% of children with DUI had a complete response after training and 47.6% at follow-up after 6 months. In children with FI, 33.3% reached a complete response at the end of the training and 25% at follow-up. Additionally, psychological symptoms, especially internalizing, decreased significantly during training. Further, in 14 children with comorbid NE, nighttime wetting reduced from 5.9 before training to 1.5 episodes/week at follow-up. CONCLUSIONS: This bladder and bowel training program is an effective and successful treatment option for children with therapy-resistant subtypes of incontinence. Symptoms still improved 6 months after training in DUI. Additionally, the training program is helpful to decrease psychological symptoms.

Definitions, indications and practice of urotherapy in children and adolescents: - A standardization document of the International Children's Continence Society (ICCS).

BACKGROUND: Urotherapy is an umbrella term for all non-surgical, non-pharmacological interventions for lower urinary tract disorders (LUTD) in children and adolescents. Urotherapy is a specialized practice, which has become mainstay therapy not only for daytime urinary incontinence, but also for nocturnal enuresis, functional constipation and fecal incontinence. The aim of urotherapy is to achieve the normalization of the micturition and bowel pattern and to prevent further functional disturbances by repeated training. It is well known that in the treatment of adult and childhood incontinence a team approach is best, where there are shared areas of expertise and also discipline-specific expertise available. AIM: We present a consensus view from a cross-professional team of experts affiliated with the International Children's Continence Society on definitions, indications and practice of urotherapy. This is a selective, non-systematic review with practical recommendations for the implementation and research on urotherapy. METHODS: The document uses the globally accepted ICCS terminology. Evidence-based literature serves as the basis, but in areas lacking in primary evidence, expert consensus is used. Before submission, a full draft was made available to all ICCS members for additional comments. RESULTS: Urotherapy uses non-pharmacological, non-surgical methods and focuses on behavioral interventions, largely based on cognitive-behavioral psychotherapy (CBT). Standard urotherapy comprises components such as provision of information, instructions, life-style advice, counselling and registration of symptoms. Specific urotherapy is tailored towards specific disorders and includes alarm treatment, biofeedback training, pelvic floor training, neurostimulation and other interventions. Fig. 1. Urotherapy is a treatment that addresses all aspects of incontinence, leading to the best clinical outcome. This includes somatic, psychosocial, and behavioral problems and quality of life. Therefore urotherapy is recommended by the ICCS as the first-line treatment for most types of LUTD. The document is intended to be clinically useful in primary, secondary and tertiary care.

The ASCP Resident Physician Section: results of surveys pertaining to "graduated responsibility for residents in anatomic pathology". American Society of Cytopathology.

Graduated responsibility for residents in anatomic pathology has been the subject of discussion among supervising staff and residents during the past few years. Presently a wide variation exists within pathology residency programs in the United States both in the degree of autonomy given to residents and in the areas of anatomic pathology (ie, surgical pathology, cytopathology, and autopsy pathology) within which the autonomy is granted. Recent surveys of supervising staff and residents have indicated a willingness to increase the level of independence for residents, especially at senior levels. Impediments include reimbursement, credentialing, and medicolegal issues. The results of the ASCP-Resident Physician Section (RPS) surveys pertaining to graduated responsibility for residents in anatomic pathology are discussed.

Detecting disseminated Mycobacterium avium complex infections in HIV-positive patients. The usefulness of bone marrow trephine biopsy specimens, aspirate cultures, and blood cultures.

Disseminated Mycobacterium avium complex (MAC) infections are common in patients with acquired immunodeficiency syndrome (AIDS). These patients frequently seek care with fever accompanied by generalized systemic symptoms and undergo bone marrow biopsy. It is our practice to stain all bone marrow trephine biopsy specimens from patients infected with HIV for acid-fast bacilli (AFB). We evaluated this practice by comparing the sensitivity and turnaround time for detection of MAC by biopsy specimen staining, bone marrow aspirate culture, and blood culture. Bone marrow trephine biopsy specimens with corresponding bone marrow aspirate and blood cultures from 86 HIV-positive patients were reviewed. Of the 86 patients, 30 had positive results for disseminated MAC infection, and all 30 of those patients had positive blood cultures. Bone marrow aspirate cultures identified 17 MAC-positive cases, and AFB staining of the biopsy specimen identified 9. The mean times to detection of MAC positivity were 1.1 days for AFB staining of the biopsy specimen, 19 days for bone marrow aspirate culture, and 16 days for blood culture. While AFB staining of biopsy specimens was the least sensitive of the detection methods, it was useful for the rapid diagnosis of disseminated MAC infection, allowing for prompt initiation of antimycobacterial therapy in one third of patients.

Extramedullary plasmacytoma. A form of marginal zone cell lymphoma?

Extramedullary plasmacytoma (EMP), solitary plasmacytoma of bone, and multiple myeloma are related neoplasms, but EMP is clearly a distinct entity. Moreover, there are histologic and clinical similarities between EMP and marginal zone B-cell lymphomas (MZLs) displaying extensive plasma cell differentiation, suggesting a possible histogenetic relationship. The histologic and clinical features of 5 EMPs with extensive plasma cell differentiation were histologically reviewed for features of MZL. The previously diagnosed MZLs, mucosa-associated lymphoid tissue (MALT) type, of 2 patients also were reviewed. All patients were women aged 48 to 79 years. The EMPs originated in the parotid gland, lymph nodes, dura, or small bowel. The initial tumors diagnosed as MALT-type MZL were located in the lung and small bowel. All patients were treated with resection, with or without irradiation therapy. One patient also received systemic chemotherapy. All patients are alive with no evidence of disease. All tumors contained large numbers of plasma cells, constituting between 55% and 90% of the lymphoid cells. Centrocyte-like cells and monocytoid B cells each represented 0% to 25% of the infiltrate. Lymphoepithelial lesions were observed in all of the tumors in sites where epithelium was present. Reactive follicles were found in all of the tumors. EMPs may represent MZLs that have undergone an extensive degree of plasmacytic differentiation.

Evolving clinical problems with Streptococcus pneumoniae: increasing resistance to antimicrobial agents, and failure of traditional optochin identification in Chicago, Illinois, between 1993 and 1996.

Infections due to multidrug-resistant pneumococci are a growing concern. Through December 1995, over 85% of isolates recovered from our patients in Chicago, Illinois, were fully susceptible to penicillin, and only a rare resistant strain was recovered from blood or cerebrospinal fluid (CSF). In December 1995, we began to observe bloodstream infections due to Streptococcus pneumoniae with penicillin MICs that represented either intermediate or full resistance to penicillin. S. pneumoniae isolated between January 1, 1993, and December 31, 1996, were tested against 11 different antimicrobial agents. There were 158 from blood or CSF, and 303 from other (primarily respiratory) sources. During 1996, 46% of our total S. pneumoniae isolates were no longer fully susceptible to penicillin, representing a threefold increase from the previous year's experience. In isolates from blood and CSF, more than 90% of strains had been fully susceptible to penicillin through 1995, but since the start of 1996, 29% of our invasive isolates were no longer fully susceptible to penicillin. During 1996, vancomycin was the only currently approved agent that was active against all recovered isolates. We also noted two isolates during 1996 where optochin testing did not accurately identify strains as S. pneumoniae. A major problem with multidrug-resistant S. pneumoniae causing both respiratory and invasive diseases appears to have now reached the Chicago area. Laboratories need to be aware of a continued increase in antimicrobial agent resistance exhibited by this pathogen, as well as potential difficulties that can be encountered using traditional laboratory identification methods.

p53 protein overexpression in infiltrating ductal carcinoma of female breast and its association with lymph node metastasis.

Traditionally, prognosis in carcinoma of the breast is evaluated based on size and differentiation of the tumor and status of lymph node metastasis. In addition to these established markers, in this molecular age other parameters such as overexpression of p53, c-erbB-2 and c-myc proteins are increasingly used to assess the prognosis. At present, the prognostic value of the molecular markers, at best, is controversial and conflicting. In this study, we examined 67 infiltrating ductal. carcinomas of female breast with and without lymph node metastasis for p53 protein overexpression by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections to ascertain if p53 positive tumors have greater metastatic potential than p53 negative tumors. In addition, p53 overexpression was also correlated with tumor size, grade, expression of estrogen and progesterone receptors, and age of the patient to clarify the issue of relevance of p53 overexpression in prognostication, p53 overexpression was observed in 39% of tumors and showed strong correlation only with the histological grade of the tumor. The incidence of p53 overexpression in grade 1, grade 2 and grade 3 tumors was 0%, 33% and 58% respectively. Lymph node metastasis was less frequent in tumors that overexpressed p53 protein. Twenty-seven percent of primary tumors with lymph node metastasis showed p53 protein overexpression, in contrast to 44% of tumors without metastasis. No correlation was observed between p53 overexpression and all the other parameters evaluated except progesterone receptor negative status. These results suggest that p53 overexpression is not an independent prognostic indicator and should not be used to predict lymph node metastasis or aggressive behavior of the tumor.

Diagnosis and classification of lymphoma based on cytospin preparations: a comparison of hematopathologists and cytopathologists.

The diagnosis of malignant lymphoma based on cytologic preparations is a source of much debate. The purpose of this study was to assess the ability of a number of pathologists to diagnose and classify lymphoma using cytospin preparations, and to compare the rate of agreement between cytopathologists and hematopathologists. One hundred twenty-five cytospins prepared from histologically confirmed hematologic lesions were examined retrospectively and independently by four hematopathologists/fellows and two cytopathologists without knowledge of the final diagnosis; the results were compared with the final diagnoses derived from histology and immunophenotyping. Eighty-one cases were histologically diagnosed as lymphoma (including 67 cases of B-cell non-Hodgkin's lymphoma), and 44 cases represented a reactive process histologically. The distinction of a malignant from a benign process was made in 75% of the cases by cytospin examination, with cytopathologists correctly diagnosing 75% and hematopathologists 76% of the cases. The accuracy rate for subclassification of the lymphoma cases was 49% (46% for cytopathologists, 52% for hematopathologists). The cytopathologists correctly recognized large-cell lymphoma at an increased frequency compared with the hematopathologists (70% vs. 56%, P = 0.11), while the hematopathologists showed a greater ability to recognize and classify nonfollicle center low-grade B-cell lymphomas (57% vs. 28%, P = 0.01). We conclude that cytopathologists and hematopathologists generally achieve similar accuracy rates in the morphologic evaluation of cytologic preparations of lymphoid lesions, though some differences in their performance do exist.

Cilia-driven particle and fluid transport over mucus-free mice tracheae.

To date, there is only a fragmentary understanding of the fundamental mechanisms of airway mucociliary transport. Application of the latest measurement techniques can aid in deciphering the complex interplay between ciliary beat and airway surface liquid (ASL) transport. In the present study, direct, quasi-simultaneous measurements of the cilia-induced fluid and bead transport were performed to gain a better insight into both transport mechanisms. In this study cilia-induced periciliary liquid (PCL) transport is measured by means of micro Particle Image Velocimetry (µPIV) with neutrally buoyant tracers. Particle Tracking Velocimetry (PTV) with heavier polystyrene-ferrite beads is performed to simulate particle transport. Contrary to recent literature, in which the presence of mucus was deemed necessary to maintain periciliary liquid (PCL) transport, effective particle and fluid transport was measured in our experiments in the absence of mucus. In response to muscarine or ATP stimulation, maximum fluid transport rates of 250 µm/s at 15 µm distance to the tracheal epithelia were measured while bead transport rates over the epithelia surfaces reached 200 µm/s. We estimated that the mean bead transport is dominated by viscous drag compared to inertial fluid forces. Furthermore, mean bead transport velocities appear to be two orders of magnitude larger compared to bead sedimentation velocities. Therefore, beads are expected to closely follow the mean PCL flow in non-ciliated epithelium regions. Based on our results, we have shown that PCL transport can be directly driven by the cilia beat and that the PCL motion may be capable of driving bead transport by fluid drag.

Experimental investigation of the flow induced by artificial cilia.

The fluid transport produced by rectangular shaped, magnetically actuated artificial cilia of 70 µm length and 20 µm width was determined by means of phase-locked Micro Particle Image Velocimetry (µPIV) measurements in a closed microfluidic chamber. The phase-averaged flow produced by the artificial cilia reached up to 130 µm s(-1) with an actuation cycle frequency of 10 Hz. Analysis of the measured flow data indicate that the present system is capable of achieving volume flow rates of V[combining dot above](cilia) = 14 ± 4 µl min(-1) in a micro channel of 0.5 × 5 mm(2) cross-sectional area when no back pressure is built up. This corresponds to an effective pressure gradient of 6 ± 1 Pa m(-1), which equals a pressure difference of 0.6 ± 0.1 mPa over a distance of 100 µm between two rows of cilia. These results were derived analytically from the measured velocity profile by treating the cilia as a thin boundary layer. While the cilia produce phase-averaged velocities of the order of O(10(2)µm s(-1)), time-resolved measurements showed that the flow field reverses two times during one actuation cycle inducing instantaneous velocities of up to approximately 2 mm s(-1). This shows that the flow field is dominated by fluid oscillations and flow rates are expected to increase if the beating motion of the cilia is further improved.

Magnetically-actuated artificial cilia for microfluidic propulsion.

In this paper we quantitatively analyse the performance of magnetically-driven artificial cilia for lab-on-a-chip applications. The artificial cilia are fabricated using thin polymer films with embedded magnetic nano-particles and their deformation is studied under different external magnetic fields and flows. A coupled magneto-mechanical solid-fluid model that accurately captures the interaction between the magnetic field, cilia and fluid is used to simulate the cilia motion. The elastic and magnetic properties of the cilia are obtained by fitting the results of the computational model to the experimental data. The performance of the artificial cilia with a non-uniform cross-section is characterised using the numerical model for two channel configurations that are of practical importance: an open-loop and a closed-loop channel. We predict that the flow and pressure head generated by the artificial cilia can be as high as 18 microlitres per minute and 3 mm of water, respectively. We also study the effect of metachronal waves on the flow generated and show that the fluid propelled increases drastically compared to synchronously beating cilia, and is unidirectional. This increase is significant even when the phase difference between adjacent cilia is small. The obtained results provide guidelines for the optimal design of magnetically-driven artificial cilia for microfluidic propulsion.

Resistant keratinocytes in 7,12-dimethylbenz[a]anthracene-initiated hamster buccal pouch epithelium.

In order to test the hypothesis that the property of resistance to cytotoxicity is an acquired trait of premalignant oral mucosal epithelium, cell dissociates were prepared from in vivo initiated hamster buccal pouch epithelium (HBPE), non-initiated HBPE and malignant HBPE cell lines. These cell types were evaluated for resistance to the cytotoxic effects of the inducing carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA). A mitoinhibition assay and a clonogenicity assay were used to assess the ability of these cells to replicate or form colonies in the presence of 40 microM DMBA. Replication of primary plated HBPE cells was inhibited by 100% in both assays. PO II, a cell line derived from non-initiated, paraffin-oil-exposed HBPE, was inhibited by 97 and 100% in the mitoinhibition and colony-forming assays respectively. This same cell line, like primary plated HBPE, lacked the transformation-linked traits of angiogenesis and anchorage-independent growth. By contrast, three malignant HBPE cell lines, two derived during long-term culture of DMBA-initiated HBPE, and one from a DMBA-induced HBPE carcinoma, were inhibited by only 34% or less in the assays for resistance to cytotoxicity. Primary cell cultures derived from HBPE initiated in vivo with twice-weekly topical applications of a 0.5% solution of DMBA in paraffin oil, for 3 or 5 weeks, were inhibited to an intermediate degree, indicating the presence of DMBA-resistant cells. In addition, DMBA-resistant cell colonies were observed in cell cultures prepared at 2, 6 and 10 weeks after completing the 5 week initiation regimen. Progenitors of the resistant cells, persisting in vivo for several weeks after initiation, may represent early preneoplastic cell populations in this experimental model.

Evidence of increased angiogenesis in patients with acute myeloid leukemia.

Angiogenesis plays a key role in solid tumor growth. The purpose of this work was to study angiogenesis in acute myeloid leukemia (AML). We stained bone marrow samples from 20 adult patients with untreated AML and 20 normal controls using endothelial cell markers (ULEX-E and von Willebrand factor [vWF]). The number of vessels per millimeter length of bone marrow core biopsy specimen was scored by light microscopy. Using ULEX-E staining, AML marrows had (average +/- SEM) 8.3 +/- 3.6 vessels/mm (range, 3.7-19.3), whereas normal marrows had 4.3 +/- 1.8 vessels/mm (range, 1.6-7.9). A similar difference was noted using vWF staining (8.6 +/- 3.0 vessels/mm vs 4. 9 +/- 2.2 vessels/mm in AML vs normal bone marrows, respectively). The differences between the numbers of vessels/mm in AML and normal marrows were highly significant (P <.0001 for both ULEX-E and vWF staining). When analyzed by FAB category, there was no difference in the average number of vessels/mm among the different subgroups of AML. Using reverse transcriptase polymerase chain reaction, we observed that the HL-60 and U937 human AML cell lines and 4 of 4 freshly isolated AML cells from untreated patients expressed mRNA for vascular endothelial growth factor (VEGF). Both cell lines as well as all fresh AML isolates tested expressed VEGF protein. Basic fibroblast growth factor was expressed only in HL-60 cells and in only 3 of 4 fresh AML samples. These observations suggest that angiogenesis may play a role in the pathogenesis of AML. Inhibition of angiogenesis could constitute a novel strategy for the treatment of AML. (Blood. 2000;95:309-313).

Gonadoblastoma: immunohistochemical localization of Müllerian-inhibiting substance, inhibin, WT-1, and p53.

Gonadoblastomas are rare tumors composed of both germ cells and sex-cord cells. In this study, we investigated two such tumors for the expression of the Wilms' tumor gene (WT1), which has a key role in urogenital development, and the expression of markers associated with sex-cord differentiation, i.e., Müllerian-inhibiting substance (MIS) and inhibin (I). We also studied p53 expression. Archival, paraffin-embedded tissue from two patients with gonadoblastoma, one bilateral and both with concurrent germinomatous areas, were evaluated immunohistochemically with antibodies directed against I, MIS, WT1, and p53. I was noted in the sex-cord component of the gonadoblastoma and not in germinoma cells. MIS was noted in both, although it was more strongly expressed in the sex-cord component. p53 expression was noted in the germ cells of the gonadoblastoma, as well as in the frankly germinomatous areas, whereas WT1 was found only in the sex-cord region and not at all in the germ cells of either of our two cases. These findings lead us to propose that WT1 and I are present in the initiation of gonadoblastomas, but are lost with the progression of these tumors. Similarly, MIS may be involved in its tumorigenesis. The expression of p53 seems to support the concept that gonadoblastoma represents in situ germ cell neoplasia with malignant potential. Additional studies, however, are needed to validate this concept.

Risk factors in necrotizing fasciitis: a case involving Cryptococcus neoformans.

Necrotizing fasciitis is a destructive soft tissue infection that is most typically caused by group A streptococci or a combination of facultative and anaerobic bacteria. Patients at risk for the development of necrotizing fasciitis often have compromised immune function or poor tissue perfusion. This report describes a case of necrotizing fasciitis caused by Cryptococcus neoformans, a pathogen not previously associated with this primary destructive soft tissue infection. The process occurred in a patient at risk for the development of opportunistic infection. We briefly review the risk factors for the development of necrotizing fasciitis and the typical bacteriologic findings. Cryptococcal infections and their treatment are described. Despite the uncommon pathogen, the treatment of this patient followed established principles-prompt surgical intervention and systemic antimicrobial therapy tailored to the offending organisms.

Atypical acinar cell foci in human pancreas. Morphological and morphometric analysis.

CONCLUSION: The morphological and quantitative findings of the present study suggest that atypical acinar cell foci are not neoplastic in nature. BACKGROUND: Atypical acinar cell foci (AACF) are rare and unusual lesions in the human pancreas. The biological nature of AACF is poorly understood, and is not clear whether they represent neoplastic or degenerative changes in the acinar cells. METHODS: To further characterize and understand the significance of AACF in relation to acinar cell tumor development, we have examined these lesions by light and electron microscopy and evaluated the growth pattern by measuring cell proliferation and the size of the foci in the pancreas of a 16-yr-old male. RESULTS: The pancreas was grossly unremarkable. AACF were randomly distributed throughout the pancreas, well delineated, and showed minimal variation in sizes. The constituent cells contained uniform nuclei, pale vacuolated cytoplasm, and exhibited low nuclear-cytoplasmic ratio. Electron microscopic examination showed a few zymogen granules and markedly dilated rough endoplasmic reticulum. Proliferative index in AACF (13%) was less than in adjacent uninvolved acinar tissue (19%). Quantitative stereological analysis showed the pancreas to contain approximately 1800 AACF/cm3 with a mean focal diameter of 360 microns.

Comparison of DNA ploidy, histologic, and immunohistochemical findings with clinical outcome in inflammatory myofibroblastic tumors.

Inflammatory myofibroblastic tumors (IMTs) are uncommon spindle cell proliferations that occur in the viscera and soft tissue of children and young adults. Their biologic potential is indeterminate: 25% of IMTs recur, and rare examples undergo malignant transformation (MT). This study investigates histologic features, DNA ploidy, and expression of apoptotic regulatory and oncogenic proteins in IMTs in an attempt to identify those deviances that might correlate with aggressive behavior or MT. Twenty-four formalin-fixed, paraffin-embedded IMTs for which clinical outcome was known were evaluated for cellularity, cytologic atypia, mitoses, ganglion-like cells, inflammatory infiltrate, DNA ploidy by flow cytometric examination, and bax, bcl-2, p53, and c-myc expression by immunohistochemical analysis. Sixteen (67%) of the IMTs did not recur, 6 (25%) recurred, and 2 (8%) underwent MT. Cellular atypia was observed in 69% of the cases without recurrence, 100% with recurrence, and 100% with MT. Ganglion-like cells were present in 56, 100, and 100% of the IMTs without recurrence, with recurrence, and with MT, respectively. There was no difference in the degree of cellularity, mitoses, or inflammatory infiltrate among the outcome groups. All of the tumors expressed bax, and none expressed c-myc. Two (8%) were immunoreactive for p53, one of which recurred and one of which underwent MT. bcl-2 expression was observed in 9 (37%) of the IMTs, with no difference among the three groups. Two IMTs were aneuploid, one of which underwent MT. Neither morphologic evaluation for cellularity, mitosis, or inflammatory infiltrate nor expression of bax or c-myc were useful for prediction of clinical outcome. The combination of atypia, ganglion-like cells, p53 expression and DNA ploidy analysis, however, might be useful to identify IMTs that might undergo MT or pursue a more aggressive clinical course with recurrences.

CD10 antigen expression correlates with the t(14;18)(q32;q21) major breakpoint region in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a common morphologic term for a biologically diverse group of lymphomas. The chromosome translocation, t(14;18)(q32;q21), and its associated bcl-2 gene rearrangement are generally associated with follicular lymphomas. Some investigators, however, proposed that the presence of the t(14;18) in DLBCL suggests a possible follicle center cell origin and might correlate with a higher relapse rate after therapy. The CD10 antigen is expressed in a majority of follicular lymphomas but is also seen occasionally in DLBCLs. In this study, we examined 26 DLBCLs for CD10 expression by flow cytometric analysis and tested them for the t(14;18)(q32;q21) major breakpoint region by a polymerase chain reaction-based method. bcl-2 protein expression was analyzed by an immunoperoxidase method. Of the 26 DLBCLs, 9 (35%) were CD10 positive. bcl-2 protein was expressed in 7 (78%) of 9 CD10-positive cases and in 9 (53%) of 17 CD10-negative cases (P = .4). The t(14; 18) translocation was present in 6 (67%) of 9 CD10-positive cases but in only 2 (17%) of 12 CD10-negative cases (P = .03). Five cases did not yield amplifiable DNA for analysis. In summary, no difference in bcl-2 protein expression was seen in CD10-positive versus CD10-negative DLBCLs, but CD10-positive DLBCLs were significantly more likely than CD10-negative DLBCLs to harbor the t(14;18) translocation. This suggests that CD10 might be a marker of follicle center cell origin in DLBCL.

Familial Wilms' tumor with neural elements: characterization by histology, immunohistochemistry, and genetic analysis.

Wilms' tumor (WT) is the most common renal malignancy of children. While most occur sporadically, a small percentage are familial or occur as part of a developmental syndrome. Classic WTs exhibit a triphasic histologic pattern composed of blastema, epithelium, and stroma. Occasionally, heterologous elements may also be observed. In this study we investigated a series of four WTs that occurred within a single familial aggregate and contained focal areas of neural differentiation. The tumors were evaluated histologically for the presence of neural elements and immunohistochemically for expression of neural-related markers. Genetic linkage analysis was performed on 3 of the 4 WTs. In addition to the classic triphasic histology, the WTs contained tumor rosettes (4/4), ganglion cells (2/4), foci of ganglioneuromatous differentiation (2/4), and anaplasia (1/4). Staining for chromogranin, S-100, synaptophysin, vimentin, and neuron-specific enolase was positive in all 4 tumors within the areas of neural differentiation whereas staining for CD99 (013) and glial fibrillary acidic protein was negative. Linkage analysis studies suggest that the familial predisposition gene segregating in this family is at 19q13.4. To our knowledge, this is the first reported series of WTs with neural differentiation that occurred within a single family aggregate. Genetic linkage analysis of this family is consistent with linkage to the FWT2 WT predisposition gene at 19q13.4. We propose that these tumors may represent a unique manifestation of tumor susceptibility in this family.