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Background: Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Many genetic and environmental risk factors including atherogenic dyslipidemia contribute towards the development of CAD. Functionally relevant mutations in the dyslipidemia-related genes and enzymes involved in the reverse cholesterol transport system are associated with CAD and contribute to increased susceptibility of myocardial infarction (MI)., Method: Blood samples from 990 angiographically confirmed Saudi CAD patients with at least one event of myocardial infarction were collected between 2012 and 2014. A total of 618 Saudi controls with no history or family history of CAD participated in the study. Four polymorphisms, rs2230806, rs2066715 (ABCA1), rs5882, and rs708272 (CETP), were genotyped using TaqMan Assay., Results: CETP rs5882 (OR = 1.45, P < 0.005) and ABCA1 rs2230806 (OR = 1.42, P = 0.017) polymorphisms were associated with increased risk of CAD. However, rs708272 polymorphism showed protective effect (B1 vs. B2: OR = 0.80, P = 0.003 and B2B2 vs. B1B1: OR = 0.68, P = 0.012) while the ABCA1 variant rs2066715 was not associated., Conclusion: This study is the first to report the association of these polymorphisms with CAD in the population of the Eastern Province of Saudi Arabia. The rs5882 polymorphism (CETP) showed a significant association and therefore could be a promising marker for CAD risk estimation while the rs708272 polymorphism had a protective effect from CAD.

KRAS(G12D) can cause lung cancer rapidly, but is not sufficient to induce thyroid cancer. It is not clear whether long-term serum thyroid stimulating hormone (TSH) stimulation can promote KRAS(G12D)-mediated thyroid follicular cell transformation. In the present study, we investigated the effect of long-term TSH stimulation in KRAS(G12D) knock-in mice and the role of Sprouty1 (SPRY1) in KRAS(G12D)-mediated signaling. We used TPO-KRAS(G12D) mice for thyroid-specific expression of KRAS(G12D) under the endogenous KRAS promoter. Twenty TPO-KRAS(G12D) mice were given anti-thyroid drug propylthiouracil (PTU, 0.1% w/v) in drinking water to induce serum TSH and 20 mice were without PTU treatment. Equal number of wild-type littermates (TPO-KRAS(WT)) was given the same treatment. The expression of SPRY1, a negative regulator of receptor tyrosine kinase (RTK) signaling, was analyzed in both KRAS(G12D)-and BRAF(V600E)-induced thyroid cancers. Without PTU treatment, only mild thyroid enlargement and hyperplasia were observed in TPO-KRAS(G12D) mice. With PTU treatment, significant thyroid enlargement and hyperplasia occurred in both TPO-KRAS(G12D) and TPO-KRAS(WT) littermates. Thyroids from TPO-KRAS(G12D) mice were six times larger than TPO-KRAS(WT) littermates. Distinct thyroid histology was found between TPO-KRAS(G12D) and TPO-KRAS(WT) mice: thyroid from TPO-KRAS(G12D) mice showed hyperplasia with well-maintained follicular architecture whereas in TPO-KRAS(WT) mice this structure was replaced by papillary hyperplasia. Among 10 TPO-KRAS(G12D) mice monitored for 14 months, two developed follicular thyroid cancer (FTC), one with pulmonary metastasis. Differential SPRY1 expression was demonstrated: increased in FTC and reduced in papillary thyroid cancer (PTC). The increased SPRY1 expression in FTC promoted TSH-RAS signaling through PI3K/AKT pathway whereas downregulation of SPRY1 by BRAF(V600E) in PTC resulted in both MAPK and PI3K/AKT activation. We conclude that chronic TSH stimulation can enhance KRAS(G12D)-mediated oncogenesis, leading to FTC. SPRY1 may function as a molecular switch to control MAPK signaling and its downregulation by BRAF(V600E) favors PTC development.

Germ cell tumors of the testis may be divided into 3 broad categories according to age at presentation. The tumors in the pediatric age group include teratoma and yolk sac tumor. These tumors are generally not associated with convincing intratubular neoplasia. The second group consists of tumors presenting in third and fourth decade of life and include seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma as well as mixed germ cell tumors. The precursor cell for these tumors is an abnormal gonocyte that fails to differentiate completely into spermatogonia. These abnormal cells stay dormant in the gonad during intrauterine life as well as infancy and childhood, but undergo proliferation during puberty and can be identified as intratubular germ cell neoplasia unclassified (IGCNU). These tumor cells continue to manifest protein expression pattern that resembles primitive germ cells (PLAP, c-KIT, OCT3/4). After a variable interval following puberty, IGCNU cells may acquire ability to penetrate the seminiferous tubules and present as an overt germ cell tumor. Acquisition of isochrome 12 and other genetic abnormalities are usually associated with this transition. The level of DNA methylation generally determines the phenotype of the germ cell tumor. The third type of germ cell tumors is spermatocytic seminoma, which is a rare tumor encountered later in life usually in fifth and sixth decade. The cell of origin of this tumor is probably postpubertal mature spermatogonia which acquire abnormal proliferative capability probably due to gain of chromosome 9 resulting in activation and amplification of genes such as DMRT1. The tumor cells manifest many of the proteins normally expressed by mature sperms such as VASA, SSX2, and occasionally OCT2. Although spermatocytic seminoma may also have an intratubular growth phase, it completely lacks features of IGCNU.

Monoclonal gammopathy is produced by neoplastic or non-neoplastic expansion of a clone of plasma cells or B lymphocytes. Monoclonal gammopathy of unknown significance is characterized by low levels of the monoclonal protein and a relatively small population of clonal lymphocytes or plasma cells in the bone marrow. In these cases, the patient is asymptomatic with no evidence of overt myeloma or lymphoma. The abnormal serum protein may be present as a complete immunoglobulin molecule or may consist of ≥1 of its components such as light chains or heavy chains. These proteins may cause a variety of diseases in various tissues and organs, of which the kidney appears to be the most vulnerable. Renal involvement in monoclonal gammopathy may occur as part of a generalized disease such as amyloidosis, immunoglobulin deposition disease, and cryoglobulinemia. In addition, there may be evidence of kidney damage by processes which are renal specific. These include light chain proximal tubulopathy, light chain cast nephropathy, and a variety of glomerulopathies encompassing a wide spectrum of disease patterns.

A 24-year-old Nepali man presented to hospital with a short history of feeling unwell with a flu-like illness. He subsequently went into acute renal failure requiring several sessions of renal replacement therapy by haemofiltration. The underlying aetiology of his renal failure was unclear. His renal function recovered following haemofiltration and he was discharged home with a plan for outpatient follow-up and investigations. He re-presented to hospital 6 days later with severe fluid overload. Echocardiogram was suggestive of impaired left ventricular systolic function; subsequent cardiac MRI confirmed this and was indicative of a dilated cardiomyopathy. A diagnosis of dilated cardiomyopathy with cardiorenal syndrome was made, most likely secondary to viral myocarditis in view of his initial presentation. He was diuresed and treated with prognostic medications for heart failure. His symptoms resolved and on subsequent outpatient review he was feeling well., (2015 BMJ Publishing Group Ltd.)

Viruses are known to be etiologically related to several types of human cancer. In several published studies, viruses such as human mammary tumor virus, human papillomaviruses, Epstein-Barr virus, human cytomegalovirus, herpes simplex virus, and measles virus have been implicated in the pathogenesis of a subset of breast cancers (BC). However, these studies have produced conflicting results, causing considerable controversy. In this context, recent demonstration of elevated levels of mutagenic antiviral enzyme APOBEC3B in a majority of BCs is a highly significant development, as it provides a possible mechanism for development of large numbers of mutations (kataegis) that characterize many of the BCs. It has also provided further impetus for revaluating the role of viruses in the pathogenesis of BC.

Wilms tumor (WT) is the most common neoplasm of the kidney in children. It is an embryologic tumor that histologically mimics renal embryogenesis and is composed of a variable mixture of stromal, blastemal, and epithelial elements. Nephrogenic rests, generally considered to be precursor lesions of the WT, are foci of the embryonic metanephric tissue that persist after the completion of renal embryogenesis. These are classified as perilobar and intralobar based on their location and maybe present as single or multiple foci. Intralobar and perilobar rests and the tumors arising from these rests differ morphologically and are characterized by 2 different sets of genetic abnormalities involving 2 adjacent foci, WT1 and WT2, on the short arm of chromosome 11. WTs arising in the intralobar rests tend to be stromal predominant and have a mutation or deletion of WT1. Germline mutation in WT1 may be associated with syndromic conditions such as WAGR and Denys-Drash syndromes. Perilobar rests and their corresponding tumors usually have loss of imprinting/loss of heterozygosity involving WT2, which contains several parentally imprinted genes. Loss of function of these genes, if present constitutionally, may be associated with Beckwith-Wiedemann syndrome or may result in isolated hypertrophy. Abnormalities in several other genes may also be seen in WT. These include WTX, (on chromosome X), CTNNB1 (chromosome 3), and TP53 (chromosome 17) among others. WT with loss of heterozygosity at 1p and 16q may have poor prognosis, requiring aggressive therapy. Treatment modalities for WT have evolved over many decades, primarily through the efforts of Dr J Bruce Beckwith at National WT study. This work is now being carried out by Children Oncology Group in North America and International Society of Pediatric Oncology in Europe. Although their therapeutic approaches are somewhat different, both have reported excellent results with equally high cure rates.

Human cancer has been one of the most difficult and tenacious problems that has defied many therapeutic regimens in the past. In recent years, there has been an explosive growth in our knowledge about molecular cell biology of cancer leading to the development of several molecularly targeted therapies. These therapeutic agents are used specifically for those tumors that are found to be susceptible to such a therapeutic approach. These therapies include a variety of monoclonal antibodies that target cell-surface receptors or, in some cases, their ligands. A second type of targeted therapies consists of small molecules that are designed to inhibit tyrosine kinase activity within the cancer cells. Despite initial optimism, this approach to cancer therapy is proven to be problematic because of inherent cancer heterogeneity and frequent development of drug resistance. The targeted therapies have improved survival time for many cancer patients but have not provided any definitive cures. The treating physicians constantly face the daunting challenge of balancing expected benefit with risk for complications, to achieve the most successful outcome. Still, the results often fall short of expectations. Personalized cancer treatment on the basis of targeted therapies is certainly an achievable goal, but more work is needed to make it a reality.

We report a case of extragonadal seminoma presenting as a polypoid mass in the urinary bladder. The patient presented with two months history of hematuria. Evaluation by CT scan and cystoscopic examination revealed a polypoid mass in the base of the bladder. Biopsy of the mass revealed a classical type of seminoma. The diagnosis of seminoma was supported by strong immunostaining of the tumor cells for C-Kit and placental alkaline phosphatase. Thorough physical examination and radiologic imaging of other organ systems failed to reveal any other tumor. Both testes were found to be normal on examination and on ultrasound imaging. Patient responded well to chemotherapy. This case is unique because to the best of our knowledge there are no previously reported cases in the literature with seminoma presenting as a bladder mass.

A case of renal cell carcinoma with sarcoid-like granulomatous reaction within the tumor was reported. The granulomas were confined to the carcinoma while renal parenchyma and regional lymph nodes were completely free of involvement. Clinical workup of the patient did not reveal any evidence of sarcoidosis, tuberculosis, or any other systemic disease except for diabetes mellitus. Sarcoid-like granulomatous reaction confined to renal carcinoma is a rare finding with only a few cases reported in the published reports.

Sarcomatoid renal cell carcinoma (SRCC) with rhabdoid features is a rare tumor with aggressive behavior and poor prognosis. We report a case of a 71-year-old man with a large left-sided renal mass. Nephrectomy specimen revealed clear cell carcinoma with sarcomatoid and rhabdoid tumor cells. The rhabdoid cells were immunoreactive for mesenchymal markers such as vimentin, epithelial markers such as cytokeratin, and epithelial membrane antigen. These cells were also positive for p53 and had a high proliferation index. The rhabdoid component also demonstrated the loss of immunostaining for integrase interactor 1 (INI1), which stained the other components of the tumor. Only a few cases are available in the published reports documenting rhabdoid cells in SRCC. None of these cases were studied by INI1 immunostain.

Bladder cancer is a relatively common and potentially life-threatening neoplasm. The diagnosis of urothelial carcinoma usually entails a lifelong surveillance to detect recurrent disease. In recent years, significant progress has been made in understanding the molecular mechanisms of carcinogenesis in urinary bladder. An early step in the process of carcinoma development is establishment of a premalignant abnormal urothelial patch that may give rise to various types of urothelial carcinoma and may provide a fertile ground for development of multifocal synchronous and metachronous tumors. Two distinct molecular pathways are involved. Low-grade papillary carcinoma is associated with mutation in the FGFR3 or in some cases mutations in RAS genes. High-grade in situ/muscle-invasive carcinoma on the other hand is characterized by alteration of p53 and pRB. Loss of function of these key genes, which play a crucial role in the control of cell cycle, leads to accumulation of additional mutations and deletions of genes resulting in an aggressive phenotype. It is hoped that a thorough understanding of the molecular basis of urothelial cancer will facilitate early diagnosis and will lead to development of new modalities for the management and treatment of these carcinomas.

Ganfort eye drops are indicated for adult patients with open-angle glaucoma who have poor response to topical β-blockers or prostaglandin analogues. They contain 0.3 mg of bimatoprost (a prostaglandin) and 5 mg of timolol (β-blocker). The authors present a case of a 45-year-old man with glaucoma presenting with shortness of breath. On admission, he had a normal heart rate, pulse oximetry and examination. Despite being of low risk stratification using the Wells score and the Modified Geneva Score for pulmonary emboli, CT pulmonary angiogram scan subsequently showed extensive bilateral multiple large pulmonary emboli. This case demonstrates that the systemic absorption of ocular β blockers is extremely high and it bypasses the first pass metabolism. Therefore, even one drop of Ganfort into each eye once a day was sufficient to disguise the tachycardia of a large pulmonary emboli.

The authors present the case of a 61-year-old woman who was troubled by regular episodes of throat discomfort, headache, dyspnoea and tingling sensation in the upper limbs. These were associated with occasional episodes of transient loss of consciousness accompanied by urinary incontinence over a period of 5 years. As these episodes became increasingly frequent, she was referred to a neurologist. Initial neurological assessment and investigations had a negative diagnostic yield and she was therefore referred for cardiac review. A repeat 24 h Holter revealed intermittent episodes of significant ST-segment elevation associated with a Mobitz type II atrio-ventricular block correlating with her symptoms. Her echocardiography and coronary angiography were normal; hence a diagnosis of Prinzmetal angina was made. She was treated appropriately with nitrates and a calcium channel blocker and followed up in cardiology clinic with no further recurrence of symptoms.

More than a century has passed since the first description of Hashimoto thyroiditis (HT) as a clinicopathologic entity. HT is an autoimmune disease in which a breakdown of immune tolerance is caused by interplay of a variety of immunologic, genetic, and environmental factors. Thyrocyte injury resulting from environmental factors results in expression of new or hidden epitopes that leads to proliferation of autoreactive T and B cells. Infiltration of thyroid by these cells results in HT. In addition to the usual type of HT, several variants such as the fibrous type and Riedal thyroiditis are also recognized. The most recently recognized variant is immunoglobulin G4(+) HT, which may occur as isolated thyroid limited disease or as part of a generalized Ig4-related sclerosing disease. The relationship between HT and Riedel thyroiditis remains unclear; however, recent evidence seems to suggest that it may also be part of the spectrum of Ig4-related sclerosing disease. HT is frequently associated with papillary thyroid carcinoma and may indeed be a risk factor for developing this type of cancer. The relationship between thyroid lymphoma and HT on the other hand appears well established.

Background: Simultaneous pancreas kidney transplantation (SPK) is accepted as a therapy for patients with type 1 diabetes and coexisting renal failure. Mycotic pseudoaneurysm formation is a life-threatening complication of transplantation, despite this however, little has been published with regards to its occurrence following SPK transplantation., Case Report: We describe the case of a 35 year old patient who 18 days after receiving a SPK transplant developed an iliac-enteric fistula, following mycotic pseudoaneurysm formation. An emergency laparotomy was required to manage a life threatening gastrointestinal hemorrhage, which necessitated graft pancreatectomy. Resection of the diseased segment of recipient iliac artery onto which the allograft was anastomosed was also required. The patient went on to develop a vascular leak, managed initially by endovascular stenting. With the development of subsequent sepsis and a further leak, operative management was required to remove the infected stent and achieve hemostasis. Immunosupression was withdrawn in an attempt to tackle the ensuing life-threatening sepsis. The patient showed signs of improvement over the following weeks, but unfortunately, developed signs of recurrent sepsis and increasing, unremitting discomfort over the kidney allograft. On re-exploration the allograft was found to be heavily infected, with the concurrent progressive renal failure, the decision was made to remove the allograft., Conclusions: This case highlights important considerations when managing mycotic pseudoaneurysms in transplant recipients. Stent placement to manage such complications may not be a long lasting solution and where stent deployment is used close follow-up of patients is mandatory.

Acute coronary syndrome (ACS), encompassing unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI), is often the result of an acute thrombotic occlusion of the coronary vessels, associated with atheromatous plaque rupture or erosion. ACS is associated with a severely impaired prognosis and requires prompt and efficient specialist treatment. The clinical presentation may be identical across all three components of ACS. Establishing an accurate diagnosis without delay is of paramount importance to start treatment promptly. Patients with suspected ACS need to be referred immediately to A&E. Prehospital treatment, which includes aspirin, nitrates, morphine and oxygen (if hypoxic), should be initiated rapidly. Important features pointing towards a diagnosis of ACS include: typical characteristics of chest pain, presence of risk factors, and ECG changes suggestive of myocardial ischaemia. Chest discomfort in patients with ACS typically occurs at rest, is anginal in character and can range from mild tightness to central crushing chest pain. It may be associated with nausea, dyspnoea or diaphoresis. The chest pain may radiate to the arms, back or jaw and is often >20 minutes in duration. An accurate clinical history and a detailed examination are vital. Initial investigations are the same for all ACS events, with the need for urgent serial ECGs and the measurement of cardiac troponin levels, to assess myocardial damage. In NSTEMI, ECG changes suggestive of ischaemia are often present and associated with elevated cardiac troponin. In UA, there is a considerable reduction in myocardial perfusion leading to symptoms; but there is no rise in cardiac troponin. Risk stratification is imperative in assessment of ACS to allow efficient delivery of specialist care. Treatment includes: antiplatelets; antithrombotic agents; angina drugs; analgesia, and PCI.

At the time of diagnosis, approximately 75% of bladder cancers are non-muscle invasive. Appropriate diagnosis and surgical resection at this stage improves prognosis dramatically. However, these lesions, being small and/or flat, are often missed by conventional white-light cystoscopes. Furthermore, it is difficult to assess the surgical margin for negativity using conventional cystoscopes. Resultantly, the recurrence rates in patients with early bladder cancer are very high. This is currently addressed by repeat cystoscopies and biopsies, which can last throughout the life of a patient, increasing cost and patient morbidity. Multiphoton endoscopes offer a potential solution, allowing real time, non-invasive biopsies of the human bladder, as well as an up-close assessment of the resection margin. While miniaturization of the Multiphoton microscope into an endoscopic format is currently in progress, we present results here indicating that Multiphoton imaging (using a bench-top Multiphoton microscope) can indeed identify cancers in fresh, unfixed human bladder biopsies. Multiphoton images are acquired in two channels: (1) broadband autofluorescence from cells, and (2) second harmonic generation (SHG), mostly by tissue collagen. These images are then compared with gold standard hematoxylin/eosin (H&E) stained histopathology slides from the same specimen. Based on a "training set" and a very small "blinded set" of samples, we have found excellent correlation between the Multiphoton and histopathological diagnoses. A larger blinded analysis by two independent uropathologists is currently in progress. We expect that the conclusion of this phase will provide us with diagnostic accuracy estimates, as well as the degree of inter-observer heterogeneity.

Autosomal recessive polycystic kidney disease (ARPKD) is a serious genetic disease characterized by cystic changes in the collecting ducts of the kidney and bile ducts within the liver. The gene for ARPKD (PKHD1) is located on chromosome 6p12 and encodes a protein called fibrocystin/polyductin (FPC), 1 of many proteins that are normally present at the primary cilia of the renal tubules and intrahepatic bile ducts. The severity of the clinical disease depends on the type of genetic mutations. Although exact function of FPC is not fully known, it is generally felt that like many of the other ciliary proteins, it plays a vital role in maintaining the structural integrity of organs such as kidney and liver, by modulating important cellular functions, including proliferation, secretion, apoptosis, and terminal differentiation. FPC probably works in conjunction with cellular proteins involved in autosomal dominant polycystic kidney disease that is, polycystin-1 and polycystin-2, which are also located in the primary cilia. Genetic abnormalities in PKHD1 may result in structural and functional abnormalities of FPC, leading to cystic phenotype.

Survivin belongs to a family of proteins, which serve as inhibitors of apoptosis. Survivin inhibits apoptosis by blocking activation of effector caspases in both extrinsic and intrinsic pathways of apoptosis. Expression of survivin has been demonstrated in several malignant neoplasms and is generally associated with adverse prognosis. In the case of bladder cancer, survivin is expressed in the neoplastic epithelium but not in the uninvolved mucosa. Several studies on bladder cancer have indicated that there may be a relationship between survivin expression and ultimate behavior of the carcinoma, although the exact nature of this relationship is still not fully understood, because the results of some of these studies seem to be contradictory. As survivin is differentially expressed in bladder cancer and not in the normal urothelium, several studies have demonstrated efficacy of urine testing of survivin as a diagnostic tool for an early detection of bladder cancer. Survivin has also been suggested as a suitable target for developing specific therapy for local treatment of bladder cancer with encouraging initial results. Thus, survivin is a potentially significant protein with a crucial role in the diagnosis, prognosis, and treatment of bladder cancer.

Autosomal dominant polycystic kidney disease (ADPKD) is a serious, life-threatening genetic disease in which extensive epithelial-lined cysts develop in the kidneys and, to a lesser extent, in other organs such as liver, pancreas, and ovaries. In a majority of cases (80-85%), the gene involved is PKD1, which is located on chromosome 16 (16q13.3) and encodes polycystin-1, a large receptor-like integral membrane protein that contains several extracellular motifs indicative of cell-cell and cell-matrix interaction. In the remaining (10-15%) cases, the disease is milder and is caused by mutational changes in another gene (PKD2), which is located at chromosome 4 (4q21-23) and encodes polcystin-2, a transmembrane protein, which acts as a nonspecific calcium-permeable channel. Both polycystins function together in a nonredundant fashion, through a common pathway, and produce cellular responses that regulate proliferation, migration, differentiation, and kidney morphogenesis. Through combined function of polycystins, normal tubular cells are maintained in a state of terminal differentiation, and their proliferation is strictly controlled. Loss of function of either protein due to gene mutations results in the tubular cells reverting to a less differentiated state, which is more prone to proliferation. Patients with ADPKD carry a germ-line mutation in PKD1 or PKD2. A second somatic mutation in some of the tubular cells results in loss of both normal alleles, leading to loss of polycystin function. The affected cells lose the normal terminally differentiated state, revert to less differentiated phenotype, and undergo proliferation, which leads to cyst formation. As the cysts enlarge over many decades, the normal renal parenchyma is progressively destroyed, leading to renal failure. Recently, the crucial role of primary cilia in modulating proliferation, migration, and differentiation of tubular epithelium has been recognized. Most of the tubular cells have one or two primary cilia projecting from the apical surface into the luminal space. The cilia act as mechanoreceptors as they bend with the urinary flow within the tubules. Both polycystins are strategically located within the cilia and act as important mediators of ciliary mechanosensation. Loss of this important function due to mutational changes in PKD1 or PKD2 leads to loss of normal control over cellular proliferation, resulting in cyst formation. Several other ciliary proteins have recently been found to contribute directly to a wide spectrum of human kidney diseases with cystic phenotype, thus underscoring the pivotal role the primary cilia play in maintaining the normal structure and function of the tubular cells and probably other cells in the body.

Intravascular papillary endothelial hyperplasia is a benign intravascular process thought to arise from an organizing thrombus. The lesion may present clinically as an abnormal mass and, depending on the location, may be confused with benign or malignant neoplasms. It has been described in a variety of locations. Involvement of the renal vein by papillary endothelial hyperplasia is extremely rare, with only 4 cases reported in the literature. We describe 2 additional cases. In both cases, the radiologic examination revealed a well-circumscribed mass in the hilar region of the kidney, which was considered to be a renal neoplasm. Nephrectomy specimen in each case revealed characteristic features of intravascular papillary endothelial hyperplasia. It is suggested that intravascular papillary endothelial hyperplasia should be included in the differential diagnosis of a hilar renal mass.

The glomerular filtration barrier is composed of endothelial cells, basement membrane, and podocytes. In recent years, remarkable progress has been made in our understanding of the molecular structure of the filtration barrier and its relation to the effectiveness of the barrier function. The glomerular basement membrane is composed of a multitude of proteins, including collagen IV, heparan sulfate proteoglycans, and laminin, among others. The slit diaphragm, which is seen as a membrane covering the space between adjacent foot processes close to the basement membrane, is an extremely important structure with a crucial role in permselectivity of the filtration barrier. Its composition is now understood to consist primarily of a unique protein called nephrin. Mutations in the gene-encoding nephrin are known to result in the Finnish type of nephrotic syndrome. The exact mechanism by which nephrin controls permselectivity is not yet clear, but it is known to interact with several podocyte proteins including CD2AP, podocin, and alpha-actinin-4. Abnormalities of any of these proteins may result in proteinuria. The role of nephrin and its associated proteins in the pathogenesis of common acquired glomerulopathies in humans is still under investigation. Normal function of podocyte also depends upon maintaining a fully mature and terminally differentiated phenotype. A host of transcription factors, especially WT1 and PAX2, play a significant role in modulating podocyte function.