Tracking of neurocognitive outcomes over time in children with perinatal stroke and associated complex medical conditions: a case series.

Neurocognitive outcomes in children with perinatal stroke are complicated by additional neurological/medical factors. The main objective of this study was to retrospectively examine long-term neurocognitive outcomes in five children with perinatal stroke with increasingly complex comorbidities; ages 5-7 at first evaluation. Results revealed that intelligence and academic skills were significantly decreased in cases with combined perinatal stroke and comorbidities. Early language development was particularly vulnerable to disruption over time in children with increasing medical complexity. The delayed emergence of neurocognitive deficits emphasizes the need for serial assessment of neurocognitive development to identify early services and interventions.

Noninvasive Papillary Urothelial Carcinoma of the Bladder: An Institutional Experience Focusing on Tumors With Borderline Features.

CONTEXT.­: Noninvasive papillary urothelial carcinomas (PUCs) comprise most urinary bladder tumors. Distinction between low-grade (LG-PUC) and high-grade (HG-PUC) PUCs is pivotal for determining prognosis and subsequent treatment. OBJECTIVE.­: To investigate the histologic characteristics of tumors with borderline features between LG-PUC and HG-PUC, focusing on the risk of recurrence and progression. DESIGN.­: We reviewed the clinicopathologic parameters of noninvasive PUC. Tumors with borderline features were subcategorized as follows: tumors that look like LG-PUC but have occasional pleomorphic nuclei (1-BORD-NUP) or elevated mitotic count (2-BORD-MIT), and tumors with side-by-side distinct LG-PUC and less than 50% HG-PUC (3-BORD-MIXED). Recurrence-free, total progression-free, and specific invasion-free survival curves were derived from the Kaplan-Meier method, and Cox regression analysis was performed. RESULTS.­: A total of 138 patients with noninvasive PUC were included, with the following distribution: LG-PUC (n = 52; 38%), HG-PUC (n = 34; 25%), BORD-NUP (n = 21; 15%), BORD-MIT (n = 14; 10%), and BORD-MIXED (n = 17; 12%). Median (interquartile range) follow-up was 44.2 months (29.9-73.1 months). Invasion-free survival was different between the 5 groups (P = .004), and pairwise comparison showed that HG-PUC had a worse prognosis compared with LG-PUC (P ≤ .001). On univariate Cox analysis, HG-PUC and BORD-NUP were 10.5 times (95% CI, 2.3-48.3; P = .003) and 5.9 times (95% CI, 1.1-31.9; P = .04) more likely to invade, respectively, when compared to LG-PUC. CONCLUSIONS.­: Our findings confirm a continuous spectrum of histologic changes in PUC. Approximately a third of noninvasive PUCs show borderline features between LG-PUC and HG-PUC. Compared with LG-PUC, BORD-NUP and HG-PUC were more likely to invade on follow-up. BORD-MIXED tumors did not statistically behave differently from LG-PUC.

Parental distress, parenting practices, and child adaptive outcomes following traumatic brain injury.

Moderate and severe pediatric traumatic brain injuries (TBI) are associated with significant familial distress and child adaptive sequelae. Our aim was to examine the relationship between parental psychological distress, parenting practices (authoritarian, permissive, authoritative), and child adaptive functioning 12-36 months following TBI or orthopedic injury (OI). Injury type was hypothesized to moderate the relationship between parental distress and child adaptive functioning, demonstrating a significantly stronger relationship in the TBI relative to OI group. Authoritarian parenting practices were hypothesized to mediate relationship between parental distress and child adaptive functioning across groups. Groups (TBI n = 21, OI n = 23) did not differ significantly on age at injury, time since injury, sex, race, or SES. Parents completed the Brief Symptom Inventory, Parenting Practices Questionnaire, and Vineland-II. Moderation and mediation hypotheses were tested using hierarchical multiple regression and a bootstrapping approach, respectively. Results supported moderation and revealed that higher parental psychological distress was associated with lower child adaptive functioning in the TBI group only. Mediation results indicated that higher parental distress was associated with authoritarian parenting practices and lower adaptive functioning across groups. Results suggest that parenting practices are an important area of focus for studies attempting to elucidate the relationship between parent and child functioning following TBI.

A pilot study evaluating an abbreviated version of the cognitive remediation programme for youth with neurocognitive deficits.

PRIMARY OBJECTIVE: To determine the effectiveness of an abbreviated version of an established cognitive remediation programme for children with neurological disorders and attention problems in an outpatient setting. METHODS AND PROCEDURES: Eighteen 6-15-year-old children diagnosed with neurological and attention difficulties completed a six-module training programme aimed at improving attention. This programme was a shorter version of the Cognitive Remediation Programme (CRP), which has been successfully implemented with children with neurocognitive deficits. Parents completed measures of their children's attention and children completed neuropsychological measures of attention. MAIN OUTCOMES AND RESULTS: The programme was associated with improvement in several aspects of parent-reported attention and children's performance on tasks measuring attention. CONCLUSIONS: The shortened version of the CRP shows promise as a brief treatment for attention problems in outpatient neurological populations. Future research should assess programme effectiveness using a control group, longer-term follow-up and teacher reports.

Comparison of two core biopsy techniques before and after laparoscopic cryoablation of small renal cortical neoplasms.

INTRODUCTION: Cryoablation is an acceptable treatment option for small renal cortical neoplasms (RCN). Unlike extirpative interventions, intraoperative needle biopsy is the only pathologic data for ablated tumors. It is imperative that sampled tissue accurately captures pathology. We studied the optimal intraoperative needle core biopsy protocol for small RCN during laparoscopic renal cryoablation (LCA). METHODS: Patients with RCN<4cm underwent intraoperative biopsy during LCA. Four biopsy cores were taken per tumor, 2 before and 2 after LCA by using both a standard and modified technique. Standard technique: needle biopsy device was deployed after insertion into the renal tissue at a depth of 5mm. Modified technique: needle biopsy device was deployed 1mm outside of the renal tissue. Biopsies were examined and compared with reference standard pathology. Percentage agreement was calculated across biopsy types (standard vs. modified) and time points (pre- vs. postcryoablation). Logistic regression was used to identify factors impacting biopsy accuracy. RESULTS: Thirty patients with 33 RCNs underwent LCA. The mean patient age was 69.1±8.0yrs, and mean tumor size was 2.3±0.7cm. No significant bleeding resulted from biopsies. A definitive diagnosis was made in 31/33 RCNs (94.0%). Ten tumors (30.3%) were benign, 21 (63.7%) were malignant, and 2 (6.0%) were nondiagnostic. Biopsy length was significantly longer using the standard vs. modified technique with mean lengths of 9.3mm vs. 7.0mm, respectively (P=.02). Highest agreement was seen in preablation biopsies (90.3%). A significant association with agreement was seen for younger age (P=.05) and larger tumor size (P=.02). CONCLUSIONS: Younger age and larger tumor size were associated with improved accuracy. Preoperative sampling resulted in superior accuracy and the standard technique resulted in significantly longer cores. Use of preablation standard biopsy technique may result in the most accurate pathologic diagnosis for patients undergoing cryoablation for small RCNs.

Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study.

Cell-lineage-specific transcription factors are a group of regulatory proteins expressed in embryonic, differentiated, or neoplastic cells of the same lineage and represent a valuable repertoire of tissue-specific markers for the diagnosis of human tumors. Together with PAX2, PAX8 is a nephric-lineage transcription factor and is required for the establishment of renal-lineage cells and the formation of the kidney. In contrast to PAX2, little is known about the expression of PAX8 in adult kidney and renal tumors. In this study, we used immunohistochemistry to investigate the expression of PAX8 in adult human kidney and renal epithelial tumors. We report here that PAX8 was detected in renal epithelial cells in all segments of renal tubules from the proximal tubules to the renal papillae and in the parietal cells of Bowman's capsule in the adult kidney. PAX8 was also present in 98% of clear cell renal cell carcinomas (RCCs), 90% of papillary RCCs, and 95% of oncocytomas, similar to PAX2. In addition, PAX8 was found in 82% of chromophobe RCCs, 71% of sarcomatoid components of RCCs, and 100% (2/2) of renal medullary carcinomas. Overall, PAX8 was detected in 85% of metastatic renal tumors. Interestingly, expression of PAX8 was noted in some urothelial cells in the renal pelvis and ureters and approximately 23% of urothelial carcinomas of the renal pelvis, but not in the urothelium or urothelial carcinomas of the urinary bladder; this probably underlines the different embryonic origins of urothelial cells in the upper and lower urinary tracts. As shown in this study, PAX8 is widely expressed in normal and neoplastic renal tissues. PAX8 may be a useful additional marker for renal epithelial tumors; however, its specificity and sensitivity await further investigation.

The efficacy of a pilot pediatric cognitive remediation summer program to prepare for transition of care.

This study assessed the efficacy of a time-sensitive cognitive remediation summer program (CRSP) that provided patients and their families with tools to help mitigate neurocognitive deficits and promote independence to foster precursor transition of medical care skills. A total of 38 participants (aged 9-15) were included in one of the CRSPs offered yearly from 2013 to 2016. A longitudinal design was employed and at each evaluation time point, one week before start of the CRSP (pre-testing) and within three weeks after the end of the program (post-testing)), participants were administered measures of executive functioning in addition to parent ratings of behavior, executive functioning, and adaptive skills (Year 1-Year 4). In Year 4, additional measures were collected, including parenting style and parent engagement and involvement in the program. Results from Year 1 to Year 4 (n = 35) demonstrated that participants in the CRSP showed significant improvement on neuropsychological testing in sustained and selective attention, planning, and cognitive flexibility. Robust changes in parent ratings of adaptive functioning from pre- to post-treatment were also found. Specific to Year 4 (n = 13), results revealed that participants showed improvement in levels of independence with at least one of the individualized goals focused on during the program. This study provided a systematic method to gauge the levels of instruction necessary to reach goals, a crucial tool in skill-teaching. Overall, our study provides evidence for the efficacy of the CRSP and validates a feasible intervention that can be integrated into standard of care for pediatric medical populations.

A two-stage, p16(INK4A)- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status.

With increasing frequency during serial passage in culture, primary human keratinocytes express p16(INK4A) (p16) and undergo senescence arrest. Keratinocytes engineered to express hTERT maintain long telomeres but typically are not immortalized unless, by mutation or other heritable event, they avoid or greatly reduce p16 expression. We have confirmed that keratinocytes undergo p16-related senescence during growth in culture, whether in the fibroblast feeder cell system or in the specialized K-sfm medium formulation, and that this mechanism can act as a barrier to immortalization following hTERT expression. We have characterized the p16-related arrest mechanism more precisely by interfering specifically with several regulators of cell cycle control. Epidermal, oral mucosal, corneal limbal, and conjunctival keratinocytes were transduced to express a p16-insensitive mutant cdk4 (cdk4(R24C)), to abolish p16 control, and/or a dominant negative mutant p53 (p53DD), to abolish p53 function. Expression of either cdk4(R24C) or p53DD alone had little effect on life span, but expression of both permitted cells to divide 25 to 43 population doublings (PD) beyond their normal limit. Keratinocytes from a p16(+/-) individual transduced to express p53DD alone displayed a 31-PD life span extension associated with selective growth of variants that had lost the wild-type p16 allele. Cells in which both p53 and p16 were nonfunctional divided rapidly during their extended life span but experienced telomere erosion and ultimately ceased growth with very short telomeres. Expression of hTERT in these cells immortalized them. Keratinocytes engineered to express cdk4(R24C) and hTERT but not p53DD did not exhibit an extended life span. Rare immortal variants exhibiting p53 pathway defects arose from them, however, indicating that the p53-dependent component of keratinocyte senescence is telomere independent. Mutational loss of p16 and p53 has been found to be a frequent early event in the development of squamous cell carcinoma. Our results suggest that such mutations endow keratinocytes with extended replicative potential which may serve to increase the probability of neoplastic progression.

Understanding the neuropsychologic outcome of pediatric AVM within a neurodevelopmental framework.

OBJECTIVE: This case series describes the long-term neuropsychologic functioning of 5 children with repaired arteriovenous malformations (AVMs). Results are presented within the context of a neurodevelopmental model to facilitate conceptualization and generate appropriate rehabilitation strategies for children with AVMs. BACKGROUND: The current case series expands upon previous research examining the long-term psychosocial functioning of these children with AVMs in which it was found that overall emotional functioning appeared adequate, although there were suggestions of defensiveness and areas of worry. In addition, global adaptive functioning was below average for most children with parental concerns about their child's socialization. METHOD: Five children with repaired AVMs in the cerebellum and frontal, temporal, and parietal lobes participated in a neuropsychologic evaluation assessing intellectual, language, memory, motor, visual-perceptual and visual-motor, and executive functions. RESULTS: These children demonstrated both localized and remote findings. More specifically, mild to moderate weaknesses in executive functions were suggested regardless of AVM location. CONCLUSIONS: The finding that children exhibited executive function difficulties regardless of AVM location is in keeping with the understanding of multiple cortical and subcortical pathways to and from the frontal lobes. In addition, it is possible that the processes of diaschisis and plasticity may play a role in the functional outcome of AVMs.

Fine-needle aspiration biopsy of monophasic variant of spindle epithelial tumor with thymus-like differentiation of the thyroid: report of one case and review of the literature.

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare biphasic tumor of the thyroid with approximately 20 well-documented cases reported in the English literature. Although a monophasic variant of SETTLE is conceivable, the majority of the reported cases were truly biphasic tumors. A minimal amount of epithelial component was present in the reported cases of so-called spindle-cell predominant SETTLE. Here, we report an apparently monophasic case of SETTLE in a 16-yr-old girl, in which no epithelial cells were identified in either fine-needle aspiration biopsy (FNAB) or the subsequent hemithyroidectomy specimen. The FNAB smears were moderately cellular and composed of single and loosely grouped spindle cells with homogenous metachromatic material, which could be mistaken as amyloid, erroneously suggesting medullary thyroid carcinoma. The compact nodules of uniform spindle cells in histology sections raised the possibility of monophasic synovial sarcoma. The spindle cells stained positive for both cytokeratin and vimentin, but were negative for thyroglobulin and calcitonin as well as neuroendocrine markers, confirming the diagnosis of SETTLE.

Management of benign middle ear tumors: A series of 7 cases.

Benign middle ear tumors represent a rare group of neoplasms that vary widely in their pathology, anatomy, and clinical findings. These factors have made it difficult to establish guidelines for the resection of such tumors. Here we present 7 unique cases of these rare and diverse tumors and draw from our experience to recommend optimal surgical management. Based on our experience, a postauricular incision is necessary in nearly all cases. Mastoidectomy is required for tumors that extend into the mastoid cavity. Whenever exposure or hemostasis is believed to be inadequate with simple mastoidectomy, canal-wall-down mastoidectomy should be performed. Finally, disarticulation of the ossicular chain greatly facilitates tumor excision and should be performed early in the procedure.

Vascular remodeling marks tumors that recur during chronic suppression of angiogenesis.

The potential for avoiding acquired resistance to therapy has been proposed as one compelling theoretical advantage of antiangiogenic therapy based on the normal genetic status of the target vasculature. However, previous work has demonstrated that tumors may resume growth after initial inhibition if antiangiogenic blockade is continued for an extended period. The mechanisms of this recurrent growth are unclear. In these studies, we characterized molecular changes in vasculature during apparent resumption of xenograft growth after initial inhibition by vascular endothelial growth factor blockade, "metronome" topotecan chemotherapy, and combined agents in a xenograft murine model of human Wilms' tumor. Tumors that grew during antiangiogenic blockade developed as viable clusters surrounding strikingly remodeled vessels. These vessels displayed significant increases in diameter and active proliferation of vascular mural cells and expressed platelet-derived growth factor-B, a factor that functions to enhance vascular integrity via stromal cell recruitment. In addition, remodeled vessels were marked by expression of ephrinB2, required for proper assembly of stromal cells into vasculature. Thus, enhanced vascular stability appears to characterize tumor vessel response to chronic antiangiogenesis, features that potentially support increased perfusion and recurrent tumor growth.

Effects of potent VEGF blockade on experimental Wilms tumor and its persisting vasculature.

We characterized the effect of potent vascular endothelial growth factor (VEGF) blockade on early-stage Wilms tumor xenograft growth, vasculature and metastasis. VEGF is a key mediator of both physiologic and tumor angiogenesis. We recently described that potent VEGF blockade induces regression of established Wilms tumor xenografts and vessels, also reducing the size but not the incidence of pre-existing metastases. In these studies, we examined the effects of potent VEGF blockade on earlier stages of experimental Wilms tumors, focusing on tumor growth, vasculature and metastasis. Athymic mice received intrarenal human Wilms tumor cell implants. Biweekly treatment with vehicle or the VEGF-Trap, a high-affinity soluble decoy receptor incorporating regions of VEGFR1 and VEGFR2, was begun 1 week later (100 or 500 micrograms/dose, n=20 in each group). Mice were euthanized at week 6 to examine tumor weight, incidence of lung metastases, vascularity and expression of angiogenic factors. A cohort of mice was examined 2 weeks after cessation of treatment. Compared to controls, VEGF-Trap treated tumors were significantly smaller (100 micrograms/dose: 92.7% smaller, p=0.0017; 500 micro g/dose: 99.0% smaller, p=0.0009). The incidence of lung metastasis also decreased significantly (p<0.0055). VEGF-Trap nearly eradicated tumor vasculature. Rare persisting vessels were characterized by large caliber, quiescence (lacking proliferation/apoptosis) and arterialization (both phenotypic and molecular). Potent VEGF blockade caused near-arrest of experimental Wilms tumor growth, resulted in nearly avascular tumors, and also decreased the incidence and size of metastases. Persistent vessels in tumors treated with VEGF-Trap displayed specific morphologic and molecular features, suggestive of arterialization. Future strategies that target these persisting vessels may enhance the efficacy of VEGF blockade therapy.

Blockade of her2/neu decreases VEGF expression but does not alter HIF-1 distribution in experimental Wilms tumor.

Her2/neu regulates angiogenesis in human breast cancer, in part by stabilizing hypoxia-inducible factor 1alpha (HIF-1alpha), causing accumulation of the HIF-1 heterodimer and thus increasing expression of the proangiogenic cytokine VEGF. Her2/neu has recently been shown to be overexpressed in a subset of Wilms tumors. Using her2/neu (+) and her2/neu (-) Wilms tumor cell lines, we tested the effect of blocking anti-her2/neu antibody in vitro and in vivo. Blocking antibody did not alter VEGF expression in vitro, but decreased expression of VEGF in her2/neu (+) Wilms tumor xenografts. Tumor suppression was less marked than in parallel experiments using agents directly blocking VEGF. HIF-1alpha immunostaining was not altered in her2/neu (+) xenografts exposed to blocking antibody. These results suggest that her2/neu contributes to Wilms tumor angiogenesis in vivo by regulating VEGF, but other processes may act to rescue HIF-1alpha and thus to support tumor growth in this system.

Nonneoplastic lesions of the prostate and bladder.

CONTEXT: Specimens from the prostate and bladder are commonly encountered by the general surgical pathologist. Emphasis is usually placed on neoplasms of the bladder and prostate, particularly if malignant, owing to their therapeutic consequences. A good command of benign lesions occurring in the bladder and prostate, and knowledge of their preneoplastic potential will help pathologists confidently diagnose malignancy versus its benign mimickers and guide the urologists in choosing the appropriate therapy and follow-up for the patient. OBJECTIVE: To present a mixture of benign entities, and discuss their histologic and clinical characteristics, hoping to provide a practical review for the general surgical pathologist. DATA SOURCES: An extensive review of the literature on the entities discussed was performed. CONCLUSIONS: A wide variety of benign entities are present in the prostate and bladder. Benign lesions in the prostate can be age related, such as prostatic atrophy and benign prostatic hyperplasia; transition zone associated, such as basal cell hyperplasia, adenosis, and sclerosing adenosis; or prostatic urethra associated. Benign lesions of the bladder encompass a wide variety of reactive changes that can occur in the urothelium, as well as hyperplastic lesions or reactive proliferations that could be misdiagnosed as malignant. The bladder responds to chronic irritation through several reactive/metaplastic lesions such as cystitis cystica/glandularis, keratinizing squamous metaplasia, or nephrogenic metaplasia. The urothelium can also give rise to hyperplastic/proliferative lesions, in particular von Brunn nest hyperplasia, papillary polypoid cystitis, and pseudocarcinomatous proliferation, which should be distinguished from malignant processes. Ectopic tissue, such as prostatic or mullerian, can also be seen.

Establishing a pediatric cognitive rehabilitation program: insurance issues and clinical rationale.

Technological and medical advances have greatly improved survival rates for many disorders; therefore, more attention is being given to functional outcomes in individuals who have been diagnosed with neurological diseases or disorders. One example of such an endeavor consists of a cognitive rehabilitation program to improve attentional abilities. The current study uses a modification of the original Cognitive Remediation Program to address attentional deficits in children with a variety of neurological disorders. The abbreviated program is designed as a focused, time-limited program that can be easily implemented in inpatient, partial day, or outpatient medical settings using third party payment to fund the program. This article seeks to inform psychologists about how to establish a cognitive rehabilitation program with emphasis placed on providing information about insurance reimbursement and billing procedures. Information is presented regarding billing codes, materials required for reimbursement, the denial/approval process, and percent of the Usual Customary Reasonable charge that was covered. Recommendations to improve the timeliness and efficiency of the reimbursement process, as well as to increase the amount of reimbursement, are highlighted. Directions for future research, including continued documentation of the effectiveness of cognitive rehabilitation programs to establish credibility for procurement of third party payment, are also offered.

Nonischemic laparoscopic partial nephrectomy using a novel wet monopolar device in a porcine model.

BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy (LPN) is the minimally invasive standard of care for the management of a cT(1a) renal mass. We evaluated a novel saline enhanced electrosurgical resection (SEER) device for performance of a nonischemic LPN. MATERIALS AND METHODS: Six pigs were used in a nonsurvival pilot study. Energy penetration was characterized by applying the SEER to the lower pole of each kidney for 30 seconds, 1 minute, and 3 minutes using pure cutting energy at 100W and a drip rate of 1 drip per second. Energy testing was performed with the hilum clamped in six kidneys and without clamping in six kidneys. Subsequently, a nonischemic upper pole LPN was performed with the SEER device, and the kidneys were harvested. The areas of necrosis were sectioned and stained with hematoxylin and eosin. Depth of necrosis was visualized grossly and microscopically for each time point. We also recorded time to perform LPN, estimated blood loss (EBL), and subjective severity of bleeding. RESULTS: The average operative time was 15.4 minutes. The mean EBL was 44.2 mL with nine (75%) cases classified as minimal, 2 (17%) moderate, and 1 (8%) severe bleeding. The mean depth of necrosis on the kidney remnants was 2.97 mm. The mean depth of necrosis for unclamped kidneys at 30 seconds, 1 minute, and 3 minutes was 0.38 mm, 0.88 mm, and 1.27 mm, respectively. The mean depths for the clamped kidneys were 2.73 mm, 3.23 mm, and 8.68 mm respectively. Depth of necrosis was significantly higher in the clamped kidneys at 3 minutes (P=0.0035). CONCLUSIONS: In the porcine model, the SEER transected parenchyma and collecting system with low resection times and minimal blood loss. Use of coagulation during resection is the main advantage of a monopolar resection compared with cold scissors. Testing performed for 3 minutes during hilar clamping demonstrated a significantly deeper level of necrosis.

PAX8 and PAX2 immunostaining facilitates the diagnosis of primary epithelial neoplasms of the male genital tract.

PAX8 and PAX2 are cell-lineage-specific transcription factors that are essential for the development of Wolffian and Müllerian ducts and have recently emerged as specific diagnostic markers for tumors of renal or Müllerian origin. Little is known about their expression in the Wolffian duct-derived human male genital tract. We report our findings of PAX8 and PAX2 expression in the epithelium of the normal male genital tract and in epithelial tumors derived therefrom using immunohistochemistry (IHC). We found that PAX8 and PAX2 were expressed in the epithelium of the male genital tract from the rete testis to the ejaculatory duct. Rare glands in the prostatic central zone, a tissue of purported Wolffian duct origin, were focally positive for PAX2, but no PAX8 was detected in this area, a finding that may warrant further study. We found diffuse expression of PAX8 and PAX2 in 1 case each of serous cystadenoma of the epididymis, carcinoma of the rete testis, Wolffian adnexal tumor of the seminal vesicle, and endometrioid carcinoma of the seminal vesicle. Neither PAX8 nor PAX2 was detected in the seminiferous tubules and interstitium of the normal testis, nor in Leydig cell tumors (n=6), Sertoli cell tumors (n=2), or 48 of 49 germ cell tumors. One pediatric yolk sac tumor showed focal and weak staining for PAX8. Tumors of mesothelial origin, that is, adenomatoid tumors (n=3) and peritoneal malignant mesotheliomas (n=37) in men, were negative for PAX2 and PAX8. Neither PAX2 nor PAX8 was present in other areas of the prostate. Expression of PAX8 and PAX2 in these primary epithelial neoplasms of the male genital tract is due to their histogenetic relationship with Wolffian or Müllerian ducts. PAX8 and PAX2 IHC may facilitate the diagnosis of these tumors and should be included in the differential diagnostic IHC panel.