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We report a scrotal epidermal inclusion cyst located outside the median raphe which a rare entity in the absence of trauma and few cases have been reported. 47 year old male presents with a complaint of right sided testicular swelling and discomfort. On examination a 3 cm mass was palpated between the scrotum and the medial thigh on the subcutaneous tissue with a positive slip sign. Complete surgical excision of the cyst was performed. Histopathology confirmed epidermal inclusion cyst with no evidence of malignancy.

Primary adenocarcinoma of urinary bladder is an uncommon neoplasm and is a source of diagnostic confusion with adenocarcinomas arising in adjacent organs, especially colon. These tumors show varied histologic picture and degree of differentiation. Clinical association with bladder exstrophy and schistosomiasis has been well documented. Primary bladder adenocarcinomas have overlapping histologic and immunohistochemical features with adenocarcinomas arising from other primary sites and the suggested immunohistochemical panel includes cytokeratins 7 and 20, 34βE12, thrombomodulin, CDX2, and β-catenin. Clinical, imaging, histologic, and immunohistochemical correlation should be done while rendering this diagnosis, as prognosis and therapeutic options for primary versus metastatic adenocarcinoma vary widely.

Loss of chromosome 14 has been associated with poor outcomes in clear-cell renal cell carcinoma. Expression of HIFα isoforms has been linked to distinct molecular phenotypes of clear-cell renal cell carcinoma. We hypothesized that chromosome 14 loss could lead to a decrease in HIF1α levels, as its gene (HIF1A) resides in this chromosome. We analyzed 112 archival clear-cell renal cell carcinoma tumor specimens with 250K SNP microarrays. We also evaluated expression of HIFα isoforms by qPCR and immunohistochemistry in a subset of 30 patients. Loss of chromosome 14q was associated with high stage (III-IV, P=0.001), high risk for recurrence (P=0.002, RR 2.78 (1.506-5.153)) and with decreased overall survival (P=0.030) in non-metastatic clear-cell renal cell carcinoma. HIF1α mRNA and protein expression was reduced in specimens with loss of 14q (P=0.014) whereas HIF2α was not. Gain of 8q was associated with decreased overall survival (P<0.0001). Our studies confirm an association between 14q loss and clinical outcome in non-metastatic clear-cell renal cell carcinoma patients and that 8q gain is a candidate prognostic marker for decreased overall survival and appears to further decrease survival in patients with 14q loss. We have also identified that differential expression of HIF1α is associated with 14q loss. Further exploration of 8q gain, 14q loss, MYC, HIF1A and EPAS1 (HIF2α) as molecular markers of tumor behavior and prognosis could aid in personalizing medicine for patients with clear-cell renal cell carcinoma.

Background: Conflicting roles for Slit2, a protein involved in mediating the processes of cell migration and chemotactic response, have been previously described in prostate cancer. Here we use immunohistochemistry to evaluate the expression of Slit2 in normal donor prostate (NDP), benign prostatic hyperplasia (BPH), high-grade prostatic intraepithelial neoplasia (HGPIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets)., Methods: Tissue microarrays were immunostained for Slit2. The staining intensities were quantified using automated image analysis software. The data was statistically analyzed using one-way analysis of variance with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Eleven cases of NDP, 35 cases of NAC, 15 cases of BPH, 35 cases of HGPIN, 106 cases of PCa, and 37 cases of Mets were analyzed., Results: Specimens of PCa and HGPIN had the highest absolute staining for Slit2. Significant differences were seen between PCa and NDP (P < .05), PCa and NAC (P < .05), HGPIN and NDP (P < .05), and HGPIN and NAC (P < .05). Whereas the average Mets staining was not significantly different from NDP or NAC, several individual Mets cases featured intense staining., Conclusions: To our knowledge, this represents the first study comparing the immunohistochemical profiles of Slit2 in PCa and Mets to specimens of HGPIN, BPH, NDP, and NAC. These findings suggest that Slit2 expression can be increased in HGPIN, PCa, and Mets, making it a potentially important biomarker for prostate cancer.

Primary renal carcinoid tumors are rare neoplasms. Because of the rarity of these neoplasms, clinicopathologic and immunohistochemical characteristics have not been fully characterized. Immunohistochemistry for renal cell lineage transcription factors, such as paired box gene 2 and paired box gene 8, has not been studied in renal carcinoid tumors and may be useful in demonstrating nephrogenic differentiation. We studied the clinical, morphological, and immunohistochemical features in 9 primary renal carcinoid tumors from multiple institutions with particular emphasis on immunohistochemical findings, in particular, expression of paired box gene 2 and paired box gene 8. All 9 cases expressed at least 1 neuroendocrine marker (CD56, synaptophysin, chromogranin). The renal-associated (paired box gene 2/paired box gene 8), gastrointestinal (caudal-related homeobox-2), and pulmonary/thyroid (thyroid transcription factor-1) transcription factors were not expressed in renal carcinoids (0/9). Of interest, CD99 was expressed in 8 of 9 cases, with the one negative case representing an atypical carcinoid. Perinephric extension and nodal and distant metastases are common. The absence of expression of paired box gene 2 and paired box gene 8, although not conclusive, supports the theory that these are derived from nonnephrogenic elements. CD99 was expressed in almost all cases (8/9); recognition of this could prevent misdiagnosis of a renal primitive neuroectodermal tumor., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We present the case of a 69-year-old male with incidentally discovered capillary hemangiomas at radical prostatectomy. Hemangiomas of genitourinary origin are extremely rare, typically benign vascular tumors. This finding represents the first reported hemangioma within a radical prostatectomy specimen.

Testicular and paratesticular tumors resembling mullerian epithelium of the ovary are extremely uncommon. This study reports a case of paratesticular serous papillary adenocarcinoma (SPA) in an 87-year-old man that was misdiagnosed as malignant mesothelioma (MM) and is 37 years older than previous cases, highlighting that SPA does not occur exclusively in young patients as described. Immunohistochemistry revealed expression of pankeratin, CAM 5.2, CK7, CK903, Ber-EP4, vimentin, S100, and CEA and virtually no expression of CK5/6, CK20, calretinin, thrombomodulin, or glypican 3. Expression of adjacent nonneoplastic tunica vaginalis mesothelium was assessed in this patient and additional specimens. Profiles of paratesticular SPA and MM were summarized and compared with paratesticular mesothelium. Nontumoral stromal and entrapped mesothelial expression were 2 diagnostic pitfalls in this case that have not been previously described. Based on these data, a panel of markers and the use of sections containing nonneoplastic mesothelium to facilitate interpretation is recommended.

Over the past decade, 3 novel, typically cystic renal neoplasms have been described: angiomyolipoma with epithelial cysts (AMLEC), mixed epithelial stromal tumor (MEST), and primary renal synovial sarcoma (SS). In all 3 neoplasms, the nature of the cystic epithelium is not clear; some have postulated that the cysts represent cystically dilated, entrapped renal tubular epithelium, whereas an alternative interpretation is that the epithelium represents epithelial differentiation by the stromal component of the neoplasm. The latter is supported by the extrarenal location of the epithelium in some cases. PAX2 and PAX8 are tissue-specific transcription factors expressed primarily in the renal and Müllerian systems and also in Wolffian duct structures (such as seminal vesicle). Their expression has not been examined in these lesions. We performed PAX2 and PAX8 immunohistochemistry on representative sections of cases of AMLEC (8 cases), MEST (8 cases), and renal SS (3 cases). The relative percentage and intensity (none, weak, moderate, and strong) of nuclear labeling were evaluated in both the benign adjacent renal tubules and the lesion's epithelial cysts. In the benign kidney, distal convoluted tubules (DCTs) labeled strongly for PAX2 and PAX8, whereas proximal convoluted tubules labeled minimally. The cystic epithelium of all 8 cases of AMLEC, including 5 that protruded beyond the renal capsule into the perirenal fat, demonstrated strong diffuse labeling for both PAX2 and PAX8. We also identified a mimic of entirely extrarenal AMLEC, angiomyolipoma with endosalpingiosis. PAX2 and PAX8 diffusely and strongly labeled the epithelial component of all 8 cases of MEST, including all architectural (phyllodes-like, large cysts, small cysts, clustered microcysts) and virtually all cytologic (hobnail, flat, cuboidal, columnar, apocrine, and clear cell) epithelial variants present. The epithelial cysts of all 3 cases of primary renal SS labeled diffusely and strongly for PAX2 and PAX8. Cyst epithelial labeling intensity was similar to that of renal DCT in all cases. The diffuse labeling for PAX2/PAX8 in the epithelial cysts of AMLEC, taken together with their consistent negativity for estrogen receptor and HMB45, supports the hypothesis that this epithelium represents entrapped, cystically dilated renal tubules that commonly herniate beyond the renal capsule. The diffuse labeling of the cyst epithelium of renal SS supports the previously proposed hypothesis that this cyst epithelium represents entrapped dilated renal tubules in a monophasic spindle cell lesion and not neoplastic epithelial differentiation. The diffuse labeling for PAX2/PAX8 in MEST epithelium, coupled with its usual estrogen receptor negativity, is consistent with the hypothesis that the epithelium of MEST demonstrates renal tubular differentiation and undergoes architectural and cytologic changes as it grows along with the stromal component. Whether this complex epithelium represents entrapped or neoplastic renal tubular epithelium remains an open question.

Background: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (Figueiredo et al., J Natl Cancer Inst 2009; 101(6): 432-435). As tumor cells in culture proliferate directly in response to available folic acid, the goal of our study was to determine if there is a similar relationship between patient folate status, and the proliferative capacity of tumors in men with prostate cancer., Methods: Serum folate and/or prostate tissue folate was determined in 87 randomly selected patients undergoing surgery for prostate cancer, and compared to tumor proliferation in a subset., Results: Fasting serum folate levels were positively correlated with prostate tumor tissue folate content (n = 15; r  = 0.577, P < 0.03). Mean serum folate was 62.6 nM (7.5-145.2 nM), 39.5% of patients used supplements containing folic acid (n = 86). The top quartile of patients had serum folates above 82 nM, six times the level considered adequate. Of these, 48% reported no supplement use. Among 50 patients with Gleason 7 disease, the mean proliferation index as determined by Ki67 staining was 6.17 ± 3.2% and 0.86 ± 0.92% in the tumors from patients in the highest (117 ± 15 nM) and lowest (18 ± 9 nM) quintiles for serum folate, respectively (P < 0.0001)., Conclusions: Increased cancer cell proliferation in men with higher serum folate concentrations is consistent with an increase in prostate cancer incidence observed with folate supplementation. Unexpectedly, more than 25% of patients had serum folate levels greater than sixfold adequate. Nearly half of these men reported no supplement use, suggesting either altered folate metabolism and/or sustained consumption of folic acid from fortified foods., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Distinguishing urothelial carcinoma (UC) from prostate carcinoma (PC) is important due to potential therapeutic and prognostic implications. However, this can be a diagnostic challenge when there is limited tissue and in poorly differentiated tumors. We evaluated the diagnostic utility of a dual immunohistochemical stain comprising p63 and P501S (prostein), applied sequentially on a single slide and visualized by double chromogen reaction, in differentiating these two cancers. Thus far, there have been no previous studies assessing the diagnostic utility of p63 and P501S combined together as a dual immunostain in distinguishing between these two cancers., Methods: p63/P501S dual-color sequential immunohistochemical staining was performed on archival material from 132 patients with high-grade UC and 23 patients with PC, and evaluated for p63 (brown nuclear) and P501S (red cytoplasmic) expression. Both the staining intensity and percentage of positive tumor cells were assessed., Results: p63 was positive in 119/132 of UC and negative in PC. P501S was positive in 22/23 of PC and negative in UC. The p63+/P501S- immunoprofile had 90% sensitivity and 100% specificity for UC. The p63-/P501S+ immunoprofile had 96% sensitivity and 100% specificity for PC., Conclusion: Our results indicate that double sequential immunohistochemical staining with p63 and P501S is highly specific and can be a useful tool in distinguishing UC from PC especially when there is limited diagnostic tissue as it can be performed on a single slide.

Background: Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is an adapter protein which has been shown to play an active role in a wide variety of cellular processes, including interactions with proteins related to both tumor suppression and oncogenesis. Here we use immunohistochemistry to evaluate EBP50's expression in normal donor prostate (NDP), benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets)., Methods: Tissue microarrays were immunohistochemically stained for EBP50, with the staining intensities quantified using automated image analysis software. The data were statistically analyzed using one-way ANOVA with subsequent Tukey tests for multiple comparisons. Eleven cases of NDP, 37 cases of NAC, 15 cases of BPH, 35 cases of HGPIN, 103 cases of PCa, and 36 cases of Mets were analyzed in the microarrays., Results: Specimens of PCa and Mets had the lowest absolute staining for EBP50. Mets staining was significantly lower than NDP (p = 0.027), BPH (p = 0.012), NAC (p < 0.001), HGPIN (p < 0.001), and PCa (p = 0.006). Additionally, HGPIN staining was significantly higher than NAC (p < 0.009) and PCa (p < 0.001)., Conclusions: To our knowledge, this represents the first study comparing the immunohistochemical profiles of EBP50 in PCa and Mets to specimens of HGPIN, BPH, NDP, and NAC and suggests that EBP50 expression is decreased in Mets. Given that PCa also had significantly higher expression than Mets, future studies are warranted to assess EBP50's potential as a prognostic biomarker for prostate cancer.

Glomus tumor is a benign mesenchymal neoplasm of the subcutaneous tissue of the distal extremities and head and neck region. Glomus tumor rarely occurs in the visceral organs. This study reports the sixth case of a glomus tumor arising in the kidney in a 62-year-old man who presented with weight loss and an incidental kidney lesion detected by computed tomographic scan. Radiologically, the tumor was difficult to differentiate from a malignant lesion and was therefore excised by partial nephrectomy. The tumor was challenging to diagnose by routine hematoxylin and eosin microscopic examination, necessitating immunohistochemical analysis. Immunoreactivity was demonstrated for smooth muscle actin, vimentin, collagen IV, and CD57, with little to no expression of neuroendocrine, endothelial, or epithelial markers. To date, the tumor has followed a benign course without evidence of local recurrence or metastasis.

Idiopathic granulomatous orchitis is a rare inflammatory process of the testis of unknown etiology. It is characterized by presence of non-specific granulomatous inflammation and admixed multinucleated giant cells. It usually presents as a testicular mass which is highly suspicious of malignancy. Histologically, there is extensive destruction of seminiferous tubules with tubular or interstitial pattern of granulomatous inflammation and prominent collagen fibrosis. Trauma and possible auto-antibodies against sperms have been postulated to be the underlying mechanism. Differential diagnoses include intratubular germ-cell neoplasia, malignant lymphomas, and malakoplakia. Orchiectomy is currently the most appropriate therapy for this condition., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Xanthogranulomatous pyelonephritis is an uncommon chronic destructive granulomatous process of renal parenchyma in association with long-term urinary tract obstruction and infection. It affects females more often than males, with a wide range of age, from newborn to elderly. Almost all patients are symptomatic and the most common symptoms are flank or abdominal pain, lower urinary tract symptoms, fever, palpable mass, gross hematuria, and weight loss. The common laboratory findings are leukocytosis and anemia. Urine cultures most often reveal Escherichia coli and Proteus mirabilis . Computed tomography is the mainstay of diagnostic imaging for xanthogranulomatous pyelonephritis. Imaging studies may demonstrate diffuse or focal form. Histologically, xanthogranulomatous pyelonephritis presents a granulomatous inflammatory infiltrate composed of neutrophils, lymphocytes, plasma cells, xanthomatous histiocytes, and multinucleated giant cells. The differential diagnosis includes clear cell renal cell carcinoma, papillary renal cell carcinoma, sarcomatoid renal cell carcinoma, leiomyosarcoma, malakoplakia, and megalocytic interstitial nephritis. Both antibiotics and surgery can be treatment options depending on the patient's disease status.

Context: Novel anatomic pathology technologies allow pathologists to digitally view and diagnose cases. Although digital pathology advocates champion its strengths and move to integrate it into practice and workflow, the capabilities and limitations of digital slides have not been fully investigated., Objectives: To estimate intrapathologist diagnostic discrepancy between glass and digital slides and to determine pathologists' diagnostic certainty when diagnosing with the 2 formats., Design: Intrapathologist diagnostic consistency between glass and digital slides was measured. Three pathologists diagnosed 101 cases digitally and with corresponding glass slides. Discrepancies between formats were evaluated, and diagnostic precision and certainty were compared., Results: A total of 606 diagnoses were evaluated in pairs (202 per pathologist). Seven cases did not transfer to the database and were eliminated from further study. We report no discrepancies between media in 75%, 87%, and 83% of the cases diagnosed by the 3 pathologists, respectively; significant discrepancies were identified in 3%, 3%, and 7% of cases by each pathologist. In total, we identified significant clinical and therapeutic discrepancies in 13 of 296 cases (4.4%). The certainty values provided by each pathologist were similar between formats., Conclusions: This study did not detect significant differences between diagnoses based on digital and glass slides. We believe that this study further supports the integration of digital slides into pathology workflow, particularly considering the low rate of discrepancy documented here.

Background: Claudins are integral membrane proteins that are involved in forming cellular tight junctions. One member of the claudin family, claudin-3, has been shown to be overexpressed in breast, ovarian, and pancreatic cancer. Here we use immunohistochemistry to evaluate its expression in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets)., Methods: Tissue microarrays were immunohistochemically stained for claudin-3, with the staining intensities subsequently quantified and statistically analyzed using a one-way ANOVA with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Fifty-three cases of NAC, 17 cases of BPH, 35 cases of PIN, 107 cases of PCa, and 55 cases of Mets were analyzed in the microarrays., Results: PCa and Mets had the highest absolute staining for claudin-3. Both had significantly higher staining than BPH (p < 0.05 in both cases) and NAC (p < 0.05 in both cases). PIN had a lower, but non-significant, staining score than PCa and Mets, but a statistically higher score than both BPH and NAC (p < 0.05 for both cases). No significant differences were observed between PCa, Mets, and PIN., Conclusions: To our knowledge, this represents one of the first studies comparing the immunohistochemical profiles of claudin-3 in PCa and NAC to specimens of PIN, BPH, and Mets. These findings provide further evidence that claudin-3 may serve as an important biomarker for prostate cancer, both primary and metastatic, but does not provide evidence that claudin-3 can be used to predict risk of metastasis.

Background: Some members of the Protein 4.1 superfamily are believed to be involved in cell proliferation and growth, or in the regulation of these processes. While the expression levels of two members of this family, radixin and moesin, have been studied in many tumor types, to our knowledge they have not been investigated in prostate cancer., Methods: Tissue microarrays were immunohistochemically stained for either radixin or moesin, with the staining intensities subsequently quantified and statistically analyzed using One-Way ANOVA or nonparametric equivalent with subsequent Student-Newman-Keuls tests for multiple comparisons. There were 11 cases of normal donor prostates (NDP), 14 cases of benign prostatic hyperplasia (BPH), 23 cases of high-grade prostatic intraepithelial neoplasia (HGPIN), 88 cases of prostatic adenocarcinoma (PCa), and 25 cases of normal tissue adjacent to adenocarcinoma (NAC) analyzed in the microarrays., Results: NDP, BPH, and HGPIN had higher absolute staining scores for radixin than PCa and NAC, but with a significant difference observed between only HGPIN and PCa (p = < 0.001) and HGPIN and NAC (p = 0.001). In the moesin-stained specimens, PCa, NAC, HGPIN, and BPH all received absolute higher staining scores than NDP, but the differences were not significant. Stage 4 moesin-stained PCa had a significantly reduced staining intensity compared to Stage 2 (p = 0.003)., Conclusions: To our knowledge, these studies represent the first reports on the expression profiles of radixin and moesin in prostatic adenocarcinoma. The current study has shown that there were statistically significant differences observed between HGPIN and PCa and HGPIN and NAC in terms of radixin expression. The differences in the moesin profiles by tissue type were not statistically significant. Additional larger studies with these markers may further elucidate their potential roles in prostatic neoplasia progression.

The Transfusion Medicine Service (TMS) covers diverse clinical and laboratory-based services that must be delivered with accuracy, efficiency and reliability. TMS oversight is shared by multiple regulatory agencies that cover product manufacturing and validation standards geared toward patient safety. These demands present significant informatics challenges. Over the past few decades, TMS information systems have improved to better handle blood product manufacturing, inventory, delivery, tracking and documentation. Audit trails and access to electronic databases have greatly facilitated product traceability and biovigilance efforts. Modern blood bank computing has enabled novel applications such as the electronic crossmatch, kiosk-based blood product delivery systems, and self-administered computerized blood donor interview and eligibility determination. With increasing use of barcoding technology, there has been a marked improvement in patient and specimen identification. Moreover, the emergence of national and international labeling standards such as ISBT 128 have facilitated the availability, movement and tracking of blood products across national and international boundaries. TMS has only recently begun to leverage the electronic medical record to address quality issues in transfusion practice and promote standardized documentation within institutions. With improved technology, future growth is expected in blood bank automation and product labeling with applications such as radio frequency identification devices. This article reviews several of these key informatics issues relevant to the contemporary practice of TMS.

Background: Male infertility is traditionally evaluated by tissue core biopsies of the testes. Touch preparations (TP) of these biopsies have been infrequently used. The aim of this study is to report our experience with using testicular biopsy TP for the evaluation of male infertility., Materials and Methods: A retrospective search was performed for cases of testes biopsies with concurrent TP. These cases were evaluated for clinical information, specimen adequacy, and cytological-histological correlation., Results: A total of 39 cases were identified from men with a mean age of 34 years (range 23 to 50 years). TP slides were satisfactory for evaluation in 31 (89%) cases, and less than optimal in four due to low cellularity, obscuring blood or air drying artifact. Cytopathology showed concordance with the biopsy in almost all cases. In one discordant case where the biopsies showed no active spermatogenesis, a rare sperm were identified on the TP., Conclusions: TP of the testis is a helpful adjunct to biopsy because of its ability to clearly evaluate all stages of spermatogenesis. These data demonstrate that TP cytopathology of the testes in our experience has an excellent correlation with both normal testicular biopsies and those showing pathological spermatogenesis, and in rare cases may provide added benefit in evaluating the presence of spermatogenesis for male infertility. Albeit uncommon, cytopathologists may be required to identify and evaluate spermatogenic elements in cytology specimens being submitted from men with infertility.

Vitamin D has been shown to have anti-proliferative effects in a wide variety of cancers including lung cancer. The anticancer effects of vitamin D are mediated primarily by its active metabolite, 1,25-dihydroxyvitamin D (calcitriol), through vitamin D receptor (VDR) signaling. However, thus far there have been no studies evaluating the association between VDR expression and survival outcome in lung cancer. Using immunohistochemical analysis, we evaluated VDR expression, separately in the nucleus and cytoplasm, in lung cancer samples from 73 non-small cell lung carcinoma (NSCLC) patients with no prior therapy, and investigated the association between VDR expression and overall survival (OS). Cox proportional hazard models were used for our primary analyses. There were 44 deaths during a median follow-up of 51 months (range 13-93 months). High nuclear VDR expression was associated with improved OS after adjusting for age, gender, stage, smoking status, and histology (adjusted hazard ratio, 0.36; 95% confidence interval, 0.17-0.79). There was no association between cytoplasmic VDR expression and OS. Our results suggest that nuclear VDR status may be a prognostic marker in NSCLC. Future large studies to replicate our findings and to assess the impact of VDR gene polymorphisms on VDR expression are required as therapies targeting the vitamin D signaling pathway may be influenced by VDR status in the target lung cancer tissue., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Quality assurance (QA) programs in cytopathology laboratories in the USA currently primarily involve the review of Pap tests per clinical laboratory improvement amendments of 1988 federal regulations. A pre-signout quality assurance tool (PQAT) at our institution allows the laboratory information system (LIS) to also automatically and randomly select an adjustable percentage of non-gynecological cytopathology cases for review before release of the final report. The aim of this study was to review our experience and the effectiveness of this novel PQAT tool in cytology., Materials and Methods: Software modifications in the existing LIS application (CoPathPlus, Cerner) allow for the random QA of 8% of cases prior to signout. Selected cases are assigned to a second QA cytopathologist for review and all agreement and disagreements tracked. Detected errors are rectified before the case is signed out. Data from cases selected for PQAT over an 18-month period were collected and analyzed., Results: The total number of non-gynecological cases selected for QA review was 1339 (7.45%) out of 17,967 cases signed out during this time period. Most (1304) cases (97.4%) had an agreement in diagnosis. In 2.6% of cases, there were disagreements, including 34 minor and only 1 major disagreement. Average turnaround time of cases selected for review was not significantly altered., Conclusion: The PQAT provides a prospective QA mechanism in non-gynecological cytopathology to prevent diagnostic errors from occurring. This LIS-driven tool allows for peer review and corrective action to be taken prior to reporting without delaying turnaround time, thereby improving patient safety.

Rapid advances are occurring in the field of cytopathology, particularly in the field of digital imaging. Today, digital images are used in a variety of settings including education (E-education), as a substitute to multiheaded sessions, multisite conferences, publications, cytopathology web pages, cytology proficiency testing, telecytology, consultation through telecytology, and automated screening of Pap test slides. The accessibility provided by digital imaging in cytopathology can improve the quality and efficiency of cytopathology services, primarily by getting the expert cytopathologist to remotely look at the slide. This improved accessibility saves time and alleviates the need to ship slides, wait for glass slides, or transport pathologists. Whole slide imaging (WSI) is a digital imaging modality that uses computerized technology to scan and convert pathology and cytology glass slides into digital images (digital slides) that can be viewed remotely on a workstation using viewing software. In spite of the many advances, challenges remain such as the expensive initial set-up costs, workflow interruption, length of time to scan whole slides, large storage size for WSI, bandwidth restrictions, undefined legal implications, professional reluctance, and lack of standardization in the imaging process.

Nephrogenic adenoma is an uncommon benign lesion. Its pathogenesis is as yet unclear although various theories have been proposed, including the embryological and inflammatory theory. The proposal that nephrogenic adenoma originates from the implantation of exfoliated renal tubular cells is lately gaining wider acceptance. Careful histological examination is essential to accurately identify this lesion and to differentiate it from other locally arising malignant lesions. The role of immunohistochemistry cannot be undermined in the diagnosis of nephrogenic adenoma, although histological diagnosis is usually conclusive. The possibility of nephrogenic adenoma should always be in the differential diagnosis when evaluating patients with predisposed urinary tract symptoms., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

Background: The Early Detection Research Network (EDRN) colorectal and pancreatic neoplasm virtual biorepository is a bioinformatics-driven system that provides high-quality clinicopathology-rich information for clinical biospecimens. This NCI-sponsored EDRN resource supports translational cancer research. The information model of this biorepository is based on three components: (a) development of common data elements (CDE), (b) a robust data entry tool and (c) comprehensive data query tools., Methods: The aim of the EDRN initiative is to develop and sustain a virtual biorepository for support of translational research. High-quality biospecimens were accrued and annotated with pertinent clinical, epidemiologic, molecular and genomic information. A user-friendly annotation tool and query tool was developed for this purpose. The various components of this annotation tool include: CDEs are developed from the College of American Pathologists (CAP) Cancer Checklists and North American Association of Central Cancer Registries (NAACR) standards. The CDEs provides semantic and syntactic interoperability of the data sets by describing them in the form of metadata or data descriptor. The data entry tool is a portable and flexible Oracle-based data entry application, which is an easily mastered, web-based tool. The data query tool facilitates investigators to search deidentified information within the warehouse through a "point and click" interface thus enabling only the selected data elements to be essentially copied into a data mart using a dimensional-modeled structure from the warehouse's relational structure., Results: The EDRN Colorectal and Pancreatic Neoplasm Virtual Biorepository database contains multimodal datasets that are available to investigators via a web-based query tool. At present, the database holds 2,405 cases and 2,068 tumor accessions. The data disclosure is strictly regulated by user's authorization. The high-quality and well-characterized biospecimens have been used in different translational science research projects as well as to further various epidemiologic and genomics studies., Conclusions: The EDRN Colorectal and Pancreatic Neoplasm Virtual Biorepository with a tangible translational biomedical informatics infrastructure facilitates translational research. The data query tool acts as a central source and provides a mechanism for researchers to efficiently query clinically annotated datasets and biospecimens that are pertinent to their research areas. The tool ensures patient health information protection by disclosing only deidentified data with Institutional Review Board and Health Insurance Portability and Accountability Act protocols.

We report a case of heterotopic breast epithelial inclusion of the heart incidentally found on a native heart in a 73-year-old man who received orthotopic heart transplantation for ischemic cardiomyopathy. The lesion could not be recognized on gross inspection. Histologic sections from the left anterior atrium to interatrial septum showed focally microcystic ductal/tubular structures lined by a biphasic pattern of cuboidal to columnar apical epithelial cells with an outer layer of flattened basal cells. These glandular structures were arranged in vaguely lobular and focally infiltrative patterns in the epicardium and interstitium. No architectural or cytologic atypia or mitotic or apoptotic figures were seen. The apical epithelial cells were immunoreactive for pankeratin, cytokeratin (CK) 7, estrogen receptor, progesterone receptor, gross cystic disease fluid protein-15, and negative for CK20, calretinin, Wilms' tumor suppressor gene (WT1), CD31, suggestive of mammary epithelial differentiation. The basal cells were immunoreactive for pankeratin, CK7, CK5/6, D2-40, smooth-muscle actin and focally S100, suggestive of myoepithelial differentiation. Although the heterotopic breast tissue on the skin along the milk line is well recognized, it has not been described to involve internal organs including the heart.

We recently implemented a novel pre-sign-out quality assurance tool in our subspecialty-based surgical pathology practice at the University of Pittsburgh Medical Center. It randomly selects an adjustable percentage of cases for review by a second pathologist at the time the originating pathologist's electronic signature is entered and requires that the review be completed within 24 hours, before release of the final report. The tool replaced a retrospective audit system and it has been in successful use since January 2009. We report our initial experience for the first 14 months of its service. During this time, the disagreement numbers and levels were similar to those identified using the retrospective system, case turnaround time was not significantly affected, and the number of case amendments generated decreased. The tool is a useful quality assurance instrument and its prospective nature allows for the potential prevention of some serious errors.

Context: Tissue banking informatics deals with standardized annotation, collection and storage of biospecimens that can further be shared by researchers. Over the last decade, the Department of Biomedical Informatics (DBMI) at the University of Pittsburgh has developed various tissue banking informatics tools to expedite translational medicine research. In this review, we describe the technical approach and capabilities of these models., Design: Clinical annotation of biospecimens requires data retrieval from various clinical information systems and the de-identification of the data by an honest broker. Based upon these requirements, DBMI, with its collaborators, has developed both Oracle-based organ-specific data marts and a more generic, model-driven architecture for biorepositories. The organ-specific models are developed utilizing Oracle 9.2.0.1 server tools and software applications and the model-driven architecture is implemented in a J2EE framework., Result: The organ-specific biorepositories implemented by DBMI include the Cooperative Prostate Cancer Tissue Resource (http://www.cpctr.info/), Pennsylvania Cancer Alliance Bioinformatics Consortium (http://pcabc.upmc.edu/main.cfm), EDRN Colorectal and Pancreatic Neoplasm Database (http://edrn.nci.nih.gov/) and Specialized Programs of Research Excellence (SPORE) Head and Neck Neoplasm Database (http://spores.nci.nih.gov/current/hn/index.htm). The model-based architecture is represented by the National Mesothelioma Virtual Bank (http://mesotissue.org/). These biorepositories provide thousands of well annotated biospecimens for the researchers that are searchable through query interfaces available via the Internet., Conclusion: These systems, developed and supported by our institute, serve to form a common platform for cancer research to accelerate progress in clinical and translational research. In addition, they provide a tangible infrastructure and resource for exposing research resources and biospecimen services in collaboration with the clinical anatomic pathology laboratory information system (APLIS) and the cancer registry information systems.

We describe the development and testing of a novel pre-sign-out quality assurance tool for case diagnoses that allows for the random review of a percentage of cases by a second pathologist before case verification and release of the final report. The tool incorporates the ability to record and report levels of diagnostic disagreement, reviewers' comments, and steps taken to resolve any discrepancies identified. It is expandable to allow for the review of any percentage of cases in any number of subspecialty or general pathology "benches" and provides a prospective instrument for preventing some serious errors from occurring, thereby potentially affecting patient care in addition to identifying and documenting more general process issues. It can also be used to augment other more conventional methods of quality control such as frozen section/final diagnosis correlation, conference review, and case review before interdisciplinary clinicopathologic sessions. There has been no significant delay in case turnaround time since implementation. Further assessment of the tool's function after full departmental application is underway.

Background: Automated, high-speed, high-resolution whole slide imaging (WSI) robots are becoming increasingly robust and capable. This technology has started to have a significant impact on pathology practice in various aspects including resident education. To be sufficient and adequate, training in pathology requires gaining broad exposure to various diagnostic patterns through teaching sets, which are traditionally composed of glass slides., Methods: A teaching set of over 295 glass slides has been used for resident training at the Division of Genitourinary Pathology, Department of Pathology, University of Pittsburgh Medical Center. Whole slide images were prepared from these slides using an Aperio ScanScope CS scanner. These images and case-related information were uploaded on a web-based digital teaching model., Results: THE WEB SITE IS AVAILABLE AT: https://www.secure.opi.upmc.edu/genitourinary/index.cfm. Once logged in, users can view the list of cases, or search cases with or without diagnoses shown. Each case can be accessed through an option button, where the clinical history, gross findings are initially shown. Whole slide images can be accessed through the links on the page, which allows users to make diagnoses on their own. More information including final diagnosis will display when the diagnosis-button is clicked., Conclusion: The web-based digital study set provides additional educational benefits to using glass slides. Residents or other users can remotely access whole slide images and related information at their convenience. Searching and sorting functions and self-testing mode allow a more targeted study. It would also prepare residents with competence to work with whole slide images. Further, the model can be expanded to include pre-rotation and post-rotation exams, and/or a virtual rotation system, which may potentially make standardization of pathology resident training possible in the future.

Background: This study carried out was to assess the feasibility of using robotic microscopy (RM) for cytologic evaluation of direct smears from fine needle aspiration biopsy (FNAB)., Methods: Three board-certified cytopathologists reviewed representative direct smears from 40 image-guided FNABs using RM and subsequently re-reviewed the same smears using conventional microscopy. Adequacy of the smears and cytologic diagnosis, as determined using the two approaches, were compared for each individual cytopathologist (intraobserver) and between the three cytopathologists (interobserver). The intraobserver and interobserver discrepancies were analyzed and discussed in a follow-up consensus conference., Results: FOR ASSESSMENT OF ADEQUACY, THERE WERE HIGH CONCORDANCE RATES (INTRAOBSERVER: 92.5-97.5%; interobserver: 90-92.5%), with a few discrepancies involving distinctions between suboptimal and satisfactory smears. Analysis of diagnostic interpretations showed correct classification of 92.5-95% (intraobserver) or 90-92.5% (interobserver) of benign and malignant cases combined, with the discrepancies being between benign and atypical cells in the benign group, and between suspicious and malignant in the malignant group. Within the malignant group, 94% of cases were accurately subclassified via RM. The quality of images viewed by using RM was rated adequate (fair or good) for 95% of the slides., Conclusions: The results demonstrate that cytologic evaluation of direct smears from FNABs using RM is feasible. Problems encountered included the longer times needed to evaluate cases with thick, bloody smears and/or low numbers of diagnostic cells, and difficulties in recognizing neuroendocrine differentiation and mimics of hepatocellular carcinoma.

Clinical studies have confirmed that renal oncocytoma (RO) is a benign neoplasm with excellent prognosis. In diagnostically challenging cases of renal oncocytic epithelial neoplasms, fluorescent in-situ hybridization (FISH) is increasingly being used and its ability to distinguish RO from chromophobe renal cell carcinoma (ChRCC) has been documented. In this study, we evaluated the differential diagnostic contribution of FISH in cases of RO.Clinicopathologic data and glass slides from 73 patients with RO were reviewed; 20 cases of ChRCC were included for comparison. FISH analysis of formalin-fixed, paraffin-embedded sections was performed using centromeric probes for chromosomes 1, 2, 7 and 17. FISH analysis revealed ROs had frequent loss of signal for chromosome 1 (56%) and 17 (44%). Tumors with more than one loss were common (41%) and 10% cases showed loss of all chromosomes examined. A total of 18% cases did not show any abnormality.Our study shows that chromosomal abnormalities in both ROs and ChRCCs are common with frequent loss of chromosomes 1 and 17. No association was found between overall patient survival and the extent of chromosomal abnormalities. FISH results, even those showing significant chromosomal abnormalities, should not alter the primarily morphology-based diagnosis of RO.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal tumor. Here we report two cases of MTSCC which were initially evaluated by fine needle aspiration biopsy (FNAB) and followed by surgical resection of the tumors. The cytomorphologic features of MTSCC were characterized by aggregates of relatively uniform, predominantly oval to spindle cells intermixed with abundant metachromatic myxoid matrix. Only rare epithelioid tumor cells with vacuolated cytoplasm were present. Immunohistochemically, the tumor cells were positive for CK7, CK19, CD10, vimentin, E-cadherin, alpha-methyl CoA racemase, and negative for CK903 and CK20. EMA and carbonic anhydrase IX immunoreactivity was seen in one of the two cases. Multiple chromosomal losses involving chromosomes 1, 2, 17 and likely chromosome 7 were revealed by fluorescence in situ hybridization (FISH). These cytomorphologic, immunophenotypic, and cytogenetic features were helpful for including this entity in the differential diagnosis of renal cell carcinomas., ((c) 2009 Wiley-Liss, Inc.)

There are few reports of institutional use of voice recognition technology in clinical practice. We describe our experience with voice recognition-integrated synoptic-like dictation, associating templates with key spoken phrases, that we have used in gross examination of common specimens and as a major component of our workflow since 2001. The primary application is VoiceOver Enterprise (Voicebrook, Lake Success, NY), which uses Dragon NaturallySpeaking Medical Edition (Nuance Communications, Burlington, MA) as its speech engine. This integrates with the anatomic pathology laboratory information system (APLIS) and other applications, such as Microsoft Office (Microsoft, Redmond, WA). The largest user group, pathology assistants, mainly dictates biopsy reports, numbering approximately 210,000 specimens since 2001. The technology has been useful in our anatomic pathology workflow and provided a good return on investment, including marked improvements in turnaround time, results standardization, error reduction, and cost savings. The most helpful features of the software are templating, the seamless integration with APLIS, and the voice command creation tools.

CD10 has recently been described as a marker that can distinguish wolffian duct derivatives from müllerian remnants but has yet to be tested in vasectomy specimens. We sought to determine if CD10 and pankeratin could corroborate the presence of vas deferens (VD). For the study, 103 consecutive vasectomy specimens were immunohistochemically analyzed for CD10, pankeratin, and CD31 expression in luminal and basal layer cells. In all cases with optimal epithelial histologic features (92/103), CD10 demonstrated intense apical membranous expression in all VD and weak basal cytoplasmic staining in about 98% of cases. Pankeratin demonstrated cytoplasmic and membranous expression in apical and basal layers in 99% of VD. In cases with suboptimal epithelial histologic features (11/103), the detection of epithelia was 100% for CD10 and pankeratin. Our data show that CD10 and pankeratin can be used to confirm the presence of VD in vasectomy specimens in which the epithelial histologic features are suboptimal.

Background: The Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer neoplasm virtual biorepository is a bioinformatics-supported system to incorporate data from various clinical, pathological, and molecular systems into a single architecture based on a set of common data elements (CDEs) that provides semantic and syntactic interoperability of data sets., Results: The various components of this annotation tool include the Development of Common Data Elements (CDEs) that are derived from College of American Pathologists (CAP) Checklist and North American Association of Central Cancer Registries (NAACR) standards. The Data Entry Tool is a portable and flexible Oracle-based data entry device, which is an easily mastered web-based tool. The Data Query Tool helps investigators and researchers to search de-identified information within the warehouse/resource through a "point and click" interface, thus enabling only the selected data elements to be essentially copied into a data mart using a multi dimensional model from the warehouse's relational structure.The SPORE Head and Neck Neoplasm Database contains multimodal datasets that are accessible to investigators via an easy to use query tool. The database currently holds 6553 cases and 10607 tumor accessions. Among these, there are 965 metastatic, 4227 primary, 1369 recurrent, and 483 new primary cases. The data disclosure is strictly regulated by user's authorization., Conclusion: The SPORE Head and Neck Neoplasm Virtual Biorepository is a robust translational biomedical informatics tool that can facilitate basic science, clinical, and translational research. The Data Query Tool acts as a central source providing a mechanism for researchers to efficiently find clinically annotated datasets and biospecimens that are relevant to their research areas. The tool protects patient privacy by revealing only de-identified data in accordance with regulations and approvals of the IRB and scientific review committee.

Background: Distinction between non-neoplastic and neoplastic bladder lesions is therapeutically and prognostically important. Our objective is to describe the use of double immunohistochemistry (DIHC) for p53+CK20 as a tool for diagnosing neoplasia in bladder biopsies., Methods: p53+CK20 DIHC were examined in 38 reactive atypia, 10 dysplasia, 9 carcinoma in situ (CIS) and 7 invasive carcinoma (IC) cases. CK20 was evaluated according to distribution extent and degree of intensity whereas percentage of positive cells together with staining intensity was taken into account in the evaluation of p53., Results: 92% of reactive cases were either CK20(-) or (+) only in the upper 1/3 urothelium. In dysplastic cases CK20 staining distribution was as follows: 60% in 2/3 of the urothelium, 30% full thickness, 10% in the upper 1/3 urothelium. Among CIS cases, 89% had full thickness CK20 positivity, of which 62% were p53(+). 71% of IC cases exhibited strong and full thickness dual staining., Conclusion: This is the first study in the literature to use DIHC of p53+CK20 in distinction of non-neoplastic and neoplastic bladder lesions. Dual staining by p53+CK20 cocktail allows for histologic correlation and diminishes the risk of losing the area of interest in limited biopsy specimens.

The primary source of information that clinicians use when evaluating and managing patients with cancer is the surgical pathology report. Omission of critical information from the report is a recognized problem in pathology, especially considering the expanding amount of information, such as molecular diagnostics data, that is now routinely included in reports. To standardize surgical pathology reports, the College of American Pathologists (CAP) introduced the CAP checklists. In 2004, the American College of Surgeons Commission on Cancer mandated that 90% of pathology reports indicating a cancer diagnosis at participating centers contain all scientifically validated or regularly used data elements. The University of Pittsburgh Medical Center has implemented synoptic reporting based on the CAP checklists for all major tumor types. We report our experience with synoptic reporting on head and neck neoplasms, demonstrating, in particular, how this can be customized according to needs of each institution.

Purpose: The transmembrane molecule, translocator protein (TSPO), has been implicated in the progression of epithelial tumors. TSPO gene expression is high in tissues involved in steroid biosynthesis, neurodegenerative disease, and in cancer, and overexpression has been shown to contribute to pathologic conditions including cancer progression in several different models. The goal of our study was to examine the expression and biological relevance of TSPO in prostate cancer and show that the commonly prescribed benzodiazepine lorazepam, a ligand for TSPO, exhibits anticancer properties., Experimental Design: Immunohistochemical analysis using tissue microarrays was used to determine the expression profile of TSPO in human prostate cancer tissues. To show the effect of TSPO ligands (lorazepam and PK11195) in prostate cancer, we used cell proliferation assays, apoptosis ELISA, prostate cancer xenograft study, and immunohistochemistry., Results: TSPO expression is increased in prostatic intraepithelial neoplasia, primary prostate cancer, and metastases compared with normal prostate tissue and benign prostatic hyperplasia. Furthermore, TSPO expression correlates with disease progression, as TSPO levels increased with increasing Gleason sum and stage with prostate cancer metastases demonstrating the highest level of expression among all tissues examined. Functionally, we have shown that lorazepam has antiproliferative and proapoptotic properties in vitro and in vivo. Additionally, we have shown that TSPO overexpression in nontumorigenic cells conferred susceptibility to lorazepam-induced growth inhibition., Conclusion: These data suggest that blocking TSPO function in tumor cells induces cell death and denotes a survival role for TSPO in prostate cancer and provides the first evidence for the use of benzodiazepines in prostate cancer therapeutics.

Adenomatoid tumors are responsible for 30% of all paratesticular masses. These are usually asymptomatic, slow growing masses. They are benign tumors comprising of cords and tubules of cuboidal to columnar cells with vacuolated cytoplasm and fibrous stroma. They are considered to be of mesothelial origin supported by histochemical studies and genetic analysis of Wilms tumor 1 gene expression. Excision biopsy is both diagnostic and therapeutic procedure. The main clinical consideration is accurate diagnosis preventing unnecessary orchiectomy. Diagnostic studies include serum tumor markers (negative alpha fetoprotein, beta HCG, LDH) ultrasonography (hypoechoic and homogenous appearance) and frozen section.

Efforts are being made to provide informatics training in residency programs. However, various factors limit this process: (1) limited access to pathology informatics expertise and resources, (2) crowded rotation schedules, and (3) incompatible rotation structures at different institutions. We devised a novel e-learning solution (located at https://secure. opi.upmc.edu/VRPI/index.cfm) that circumvents these limitations. The course includes didactic lectures given by experts in the field and video-recorded hands-on laboratories. The lectures are supplemented by readings from a textbook. Because it is self-paced, it can accommodate various rotation structures. Module topics and depth of coverage are directed to the level of general practicing pathologists, with quizzes provided for each module. Course progress can be tracked on the Web site by an administrator. The experience so far with this resource has been positive, and it seems to be effective in improving resident competency in pathology informatics and basic computer skills.

Background: Malignant transformation of mature cystic teratoma is a rare complication. While any of the constituent tissues of a teratoma has the potential to undergo malignant transformation, squamous cell carcinoma is the most commonly associated malignancy. Renal carcinoid tumors are rare and frequently associated with horseshoe kidney and renal teratoma. Renal teratoma rarely presents together with carcinoid tumor or adenocarcinoma. To the best of our knowledge, there has never been a report of renal teratoma coexisting with both carcinoid tumor and adenocarcinoma., Methods: Here, we present a unique and first case of synchronous primary carcinoid tumor and moderately differentiated adenocarcinoma arising within mature cystic teratoma of horseshoe kidney in a 50-year-old female. Lumbar spine X-ray, done for her complaint of progressive chronic low back pain, accidentally found a large calcification overlying the lower pole of the right kidney. Further radiologic studies revealed horseshoe kidney and a large multi-septated cystic lesion immediately anterior to the right renal pelvis with central calcification and peripheral enhancement. She underwent right partial nephrectomy., Results: Macroscopically, the encapsulated complex solid and multiloculated cystic tumor with large calcification, focal thickened walls and filled with yellow-tan gelatinous material. Microscopically, the tumor showed coexistent mature cystic teratoma, moderately differentiated adenocarcinoma and carcinoid tumor. Immunohistochemically, alpha-methylacyl-coenzyme A-racemase, calretinin, CD10 and thyroid transcription factor-1 were negative in all the three components of the tumor. The teratomatous cysts lined by ciliated epithelium showed strong staining for cytokeratin 7 and pancytokeratin, and those lined by colonic-like epithelium showed strong staining for CDX2, cytokeratin 20 and pancytokeratin, but both were negative for calretinin. Additionally, the teratomatous cyst wall showed strong staining for smooth muscle actin, and weak staining for carbonic anhydrase IX, CD99, chromogranin and synaptophysin. The adenocarcinoma component was strongly positive for cytokeratin 7 and pancytokeratin, weakly positive for synaptophysin and CD56, and negative for carbonic anhydrase IX, CD99, CDX2, chromogranin, cytokeratin 20 and smooth muscle actin. The carcinoid tumor component was strongly positive for CD56, chromogranin and synaptophysin, weakly positive for pancytokeratin, and negative for carbonic anhydrase IX, CD99, CDX2, cytokeratin 7, cytokeratin 20 and smooth muscle actin. She received no adjuvant therapy and is alive without evidence of disease six months after diagnosis and surgery., Conclusion: This unique and first case herein presented with synchronous primary carcinoid tumor and primary adenocarcinoma arising within mature cystic teratoma of horseshoe kidney emphasizes the need for thorough sectioning and entire submission for histologic evaluation of mature cystic teratomas, in order to avoid missing multiple additional histogenetically distinct neoplasms.

The recently recognized renal cell carcinomas (RCCs) associated with Xp11.2 translocations (TFE3 transcription factor gene fusions) are rare tumors predominantly reported in children. They comprise at least one-third of pediatric RCCs and only few adult cases have been reported. Here, we present a case of Xp11.2 translocation RCC in 26-year-old pregnant female. Her routine antenatal ultrasonography accidentally found a complex cystic right renal mass. Further radiologic studies revealed unilocular cyst with multiple mural nodules at inferior pole of right kidney, which was suspicious for RCC. She underwent right radical nephrectomy at 15 weeks gestation. Macroscopically, the cystic tumor was well encapsulated with multiple friable mural nodules on its inner surface. Microscopically, the tumor consisted of clear and eosinophilic/oncocytic voluminous cells arranged in papillary, trabecular, and nested/alveolar patterns. Occasional hyaline nodules and numerous psammoma bodies were present.Immunohistochemically, the tumor showed strong nuclear positivity for TFE3. Epithelial membrane antigen, CD10, and E-cadherin were strongly positive. Cytokeratin AE1/AE3, cytokeratin CAM-5.2, calveolin, and parvalbumin were moderately positive. Cytokeratin 7, renal cell carcinoma antigen, and colloidal iron were focally weakly positive. BerEP4 and carbonic anhydrase IX were negative. Cytogenetically, the tumor harbored a novel variant translocation involving chromosomes X and 19, t(X;19)(p11.2;q13.1). Interphase FISH analysis performed on cultured and uncultured tumor cells using a dual-color break-apart DNA probe within the BCL3 gene on 19q13.3 was negative for the BCL3 gene rearrangement. She received no adjuvant therapy, delivered a normal term baby five months later, and is alive without evidence of disease 27 months after diagnosis and surgery. Unlike most recently reported Xp11.2 translocation RCCs in adult patients with aggressive clinical course, this adult case occurring during pregnancy with a novel translocation involving chromosome 19 followed an indolent clinical course.

With the advent of newer molecular technologies, our knowledge of cellular mechanisms with tumors of the kidney and testis has grown exponentially. Molecular technologies have led to better understanding of interplay between the von Hippel-Lindau gene and angiogenic cytokines in renal cancer and isochromosome 12p in testicular neoplasms. The result has been development of antiangiogenic-targeted therapy within recent years that has become the mainstay treatment for metastatic renal cell cancer. In the near future, classification and diagnosis of renal and testicular tumors through morphologic analysis will be supplemented by molecular information correlating to prognosis and targeted therapy. This article outlines tumor molecular pathology of the kidney and testis encompassing current genomic, epigenomic, and proteonomic findings., (Copyright © 2009 Elsevier Inc. All rights reserved.)

Benign and malignant tumors of the testes and paratesticular tissues present an interesting spectrum of diagnostic entities often encountered in routine surgical pathology practice. Germ cell tumors are the most common tumors of the testes and, despite a rising incidence, have excellent prognosis because of their radiosensitivity and/or effective chemotherapeutic agents. The proper classification of these tumors aids in the choice of appropriate treatment options. This article reviews benign and malignant neoplastic entities of the testes and paratesticular tissues and illustrates the classic pathologic characteristics. The differential diagnosis, along with ancillary studies, clinical significance, and presentation are discussed also., (Copyright © 2009 Elsevier Inc. All rights reserved.)

Recent studies have shown that estrogens promote the growth of lung cancer cells and may potentially be responsible for increased susceptibility to lung cancer in women. These observations raise the possibility of using antiestrogens in treating and preventing lung cancer. However, it is not clear how estrogen receptors (ERs) modulate the growth of non-small cell lung cancer (NSCLC) cells. Our Western blotting and real-time PCR analysis showed that NSCLC cells expressed ERbeta, but not ERalpha. In addition, ERbeta-specific ligands, but not ERalpha-specific ligands, promoted the growth of lung cancer cells. Furthermore, knockdown of ERbeta by short hairpin RNA constructs resulted in loss of estrogen-dependent growth of lung cancer cells. Interestingly, endogenous ERbeta failed to transcriptionally activate estrogen response element (ERE)-luciferase constructs in NSCLC cells, suggesting a lack of genomic function. Upon further investigation, ERbeta was found to be in the cytoplasm in all lung cancer cells and failed to translocate to the nucleus in the presence of estrogen, as observed by biochemical, ArrayScan, and confocal microscopy experiments. Nonetheless, estrogen caused rapid activation of cAMP, Akt, and MAPK signaling pathways in lung cancer cells. Immunohistochemical analysis of lung tumor biopsies showed strong ERbeta staining in the cytoplasm, whereas no staining was observed for ERalpha. In conclusion, our results suggest that that proliferative effects of estrogen in lung cancer cells is mediated primarily, if not exclusively, by the nongenomic action of ERbeta.

The authors in this study describe the case of a patient with a history of multiple malignancies who underwent total cystectomy with ileal loop urinary diversion and presented with a lower extremity angiosarcoma on the background of lymphedema a decade later. Shortly thereafter, she was diagnosed with metastatic ileal conduit angiosarcoma. The authors state that to their knowledge, this is the first case of ileal conduit angiosarcoma reported in the English literature.