Original Article
Derivation of Nephrogenic Adenomas from Renal Tubular Cells in Kidney-Transplant Recipients
N Engl J Med 2002; 347:653-659August 29, 2002
- Abstract
Background
Nephrogenic adenomas are benign, tumor-like lesions within the urothelial mucosa of the urinary tract that are not uncommon in renal-transplant recipients. We investigated the origin of nephrogenic adenomas in renal-transplant recipients.
Methods
Tissue sections were analyzed by fluorescence in situ hybridization with the use of probes for the X and Y chromosomes, by immunohistochemical methods with the use of antibodies to renal tubular antigens, and by lectin histochemical methods. Forty-six nephrogenic adenomas from 29 patients were analyzed.
Results
All nephrogenic adenomas in 14 female recipients of transplants from male donors and 10 male recipients of transplants from female donors showed the same sex-chromosome status as the donor kidney, but not the same sex-chromosome status as the recipient's surrounding bladder tissue. The nephrogenic adenomas from all 6 female recipients of transplants from female donors showed female chromosomes, and those from the 16 male recipients of transplants from male donors showed male chromosomes. The presence of aquaporin 1, PAX2, and lectin-binding capacity for peanut agglutinin, Lotus tetragonolobus agglutinin, and Sophora japonica agglutinin in nephrogenic adenomas indicated an origin from renal tubular cells.
Conclusions
Nephrogenic adenomas in renal-transplant recipients are derived from tubular cells of the renal transplants and are not metaplastic proliferations of the recipient's bladder urothelium.
Media in This Article
Figure 1
Nephrogenic Adenoma of a Female Patient with a Renal Transplant from a Male Donor (×600).Figure 2
Nephrogenic Adenoma of a Male Patient with a Renal Transplant from a Female Donor (×500).Article Activity
- Article
Nephrogenic adenomas are rare, benign, tumor-like lesions within the urothelial mucosa of the urinary tract. Most nephrogenic adenomas are found in the bladder, but other locations (pelvic urothelium, ureter, and urethra) have been reported.1-6 They occur in patients with chronic bladder inflammation or previous genitourinary surgery, and they are particularly frequent in renal-transplant recipients.7-16 The pathogenesis of these lesions is enigmatic. The favored hypothesis is that nephrogenic adenomas are metaplastic alterations of resident urothelial tissue, and therefore the term “nephrogenic metaplasia” is used synonymously. Another hypothesis postulates development from hamartomatous cells.17 In this study, we investigated the origin of nephrogenic adenomas in renal-transplant recipients by analysis of sex chromosomes using fluorescence in situ hybridization and by immunohistochemical detection of aquaporins and other antigens of the nephrons, collecting ducts, and urothelium.
Methods
Patients
From March 1994 through February 2001, 29 renal-transplant recipients underwent cystoscopy because of hematuria or dysuria, followed by transurethral resection of a nephrogenic adenoma. The patients' ages ranged from 16 to 78 years (median, 49.6). Forty-six nephrogenic adenomas were resected, including 17 recurrent lesions. The interval between renal transplantation and the diagnosis of nephrogenic adenoma was 6 to 120 months (median, 44.6). Table 1Table 1
Characteristics of Patients with Nephrogenic Adenomas after Renal Transplantation. shows the sexes of the donors and recipients of the renal transplants. Post-transplantation renal-biopsy specimens were available from all patients and were obtained before any manifestation of a nephrogenic adenoma. Quantification of the grade of renal rejection in post-transplantation biopsies was performed with the Banff 97 classification.18 Histologic Examination
Specimens from transurethral resections were completely embedded in paraffin and cut into serial sections 4 to 6 μm in thickness. One section was stained with hematoxylin and eosin, and adjacent sections were used for fluorescence in situ hybridization, immunohistochemical analysis, and lectin staining. In selected cases, sections that were analyzed by fluorescence in situ hybridization were restained with hematoxylin and eosin to compare sex-chromosome analysis and histologic details in the same tissue section. Nephrogenic adenoma was diagnosed when typical histologic characteristics (tubular or cystic proliferations, or both, with or without papillary formations)5 were seen.
Fluorescence in Situ Hybridization
Food and Drug Administration–approved X and Y centromeric probes, directly labeled with Spectrum Orange and Spectrum Green (Vysis), were used according to the protocols of the manufacturer. Because tissue sections and not cytologic preparations were analyzed, some nuclei were cut through, and single cells did not show all sex chromosomes on the sections. We therefore assigned male chromosomal status to nephrogenic-adenoma tissue in a female patient if at least 75 percent of all nuclei of the nephrogenic-adenoma tissue showed one clear-cut Y chromosome, identified as a green, dotlike intranuclear hybridization signal, and no nuclei of the adjacent bladder tissue showed Y chromosomes. Similarly, we assigned female chromosomal status to nephrogenic adenoma tissue in a male patient if the nuclei of the nephrogenic-adenoma tissue did not show Y chromosomes and at least 75 percent of the nuclei of the adjacent bladder tissue showed Y chromosomes. Evaluation of fluorescence signals was performed on transparencies. Three female and three male patients who had nephrogenic adenomas without preceding renal transplantation (five patients with bladder endometriosis and one with prostatic hyperplasia) served as controls for fluorescence in situ hybridization experiments.
Immunohistochemical Analysis and Lectin Staining
Antibodies against aquaporins (water-channel membrane proteins) of the proximal tubules (aquaporin-1, dilution 1:400, Chemicon) and of the collecting ducts (aquaporin-2, 1:50, Chemicon) were used. In addition, Leu-M1 (1:10, Becton Dickinson); epithelial membrane antigen (1:50, Dako); vimentin (1:20, Immunotech); cytokeratins Cam 5.2 (undiluted, Becton Dickinson), CK7 (1:200, Dako), CK8 (1:25, Dako), and CK20 (1:20, Neomarkers); and PAX2, a transcription factor in renal development (1:100, Zymed), were used. Signal detection was performed with the peroxidase–antiperoxidase reaction. Antigen retrieval for aquaporin-1, aquaporin-2, and PAX2 was performed by microwave pretreatment in citrate buffer (pH 6.0) for 20 minutes at 120 W and three times for 5 minutes each at 450 W. Tumor-free renal tissue from five nephrectomy specimens (removed for renal tumor) and tumor-free bladder tissue from five cystoprostatectomy specimens served as controls. Evaluation was performed with use of a semiquantitative scale, with – indicating negative, + moderate, ++ strong, and +++ very strong staining. The avidin–biotin method was used to analyze the lectin-binding properties for Lotus tetragonolobus agglutinin, which is specific for proximal tubules and the thin limb of Henle's loop19 (200 μg per milliliter, Sigma); Sophora japonica agglutinin, which is specific for the proximal tubules and collecting ducts19 (50 μg per milliliter, Vector Laboratories); and Arachis hypogaea agglutinin (peanut agglutinin), which is specific for the distal tubules and collecting ducts20 (50 μg per milliliter, Vector Laboratories). Negative controls were achieved by blocking the lectins with their corresponding sugars (α-L-fucose for L. tetragonolobus agglutinin, N-acetyl-β-D-galactosamine for S. japonica agglutinin, and β-D-galactose for peanut agglutinin) before the staining procedure.21
Both pretransplantation and post-transplantation graft-biopsy specimens were available for 13 patients. Immunohistochemical analysis for Cam 5.2 was performed in these 13 patients to demonstrate casts of detached tubular cells within the tubular lumina. The interval between transplantation and graft biopsy ranged from 5 to 721 days. The proliferation index was evaluated by the MIB1 antibody (1:50, Dako) to detect Ki-67 antigen in the nuclei of the tubular cells. In addition, the expression of PAX2 was investigated. The results of pretransplantation and post-transplantation graft biopsies were compared.
Statistical Analysis
Medians and standard deviations are reported. The Wilcoxon–Mann–Whitney U test and Fisher's exact test were used.
Results
Fluorescence in Situ Hybridization
In 14 of 14 nephrogenic adenomas from female recipients of renal transplants from male donors, a male chromosomal status was demonstrated within the epithelial component (Figure 1Figure 1
Nephrogenic Adenoma of a Female Patient with a Renal Transplant from a Male Donor (×600).). In 10 of 10 nephrogenic adenomas from male recipients of renal transplants from female donors, a female chromosomal status was demonstrated (Figure 2Figure 2Nephrogenic Adenoma of a Male Patient with a Renal Transplant from a Female Donor (×500).). By contrast, the stromal component of all nephrogenic adenomas had the sex-chromosome status of the recipient. In 6 of 6 nephrogenic adenomas from women with renal transplants from female donors, a female chromosomal status was demonstrated, and in 16 of 16 nephrogenic adenomas from men with renal transplants from male donors, a male chromosomal status was demonstrated. In each nephrogenic adenoma from the renal-transplant recipients, the epithelial component had the same sex-chromosome status as the donor (Table 2Table 2
Results of Fluorescence in Situ Hybridization and Immunohistochemical Studies.). The control group of nephrogenic adenomas not associated with a kidney graft had the expected sex-chromosome status.Immunohistochemical Analysis and Lectin Staining
The results of analysis of the nephrogenic adenomas are summarized in Table 2. Epithelial components of the nephrogenic adenomas showed immunophenotypic characteristics of renal tubular cells: prominent staining for aquaporin-1 (Figure 3DFigure 3
Immunohistochemical Findings.), epithelial membrane antigen, and cytokeratins Cam 5.2 and CK7 and moderate reactivity for CK8, Leu-M1, and vimentin. CK20, which is expressed in urothelial cells, and aquaporin-2, which is confined to collecting ducts, were not detected. In addition, PAX2, which is usually found only during nephrogenesis, was found in epithelial components of nephrogenic adenomas, but not in the bladder urothelium (Figure 3E). Peanut agglutinin staining was found in all 46 nephrogenic adenomas, but not in the adjacent urothelium (Figure 3F). L. tetragonolobus agglutinin was found focally in 17 of the 46 nephrogenic adenomas (37 percent), but not in the adjacent urothelium. Focal staining was also found with S. japonica agglutinin in 26 of 46 (57 percent); however, the adjacent urothelium was positive.In renal-graft biopsies, we demonstrated casts of detached cells within tubular lumina (Figure 3C) in 7 of 13 patients (54 percent). However, the number of casts was highly variable. The proliferation index was low, at 0.11 to 1.43 percent of all nuclei of tubular cells in post-transplantation biopsy specimens (Figure 3B). It was slightly higher than in pretransplantation biopsy specimens from these patients, at 0.08 to 1.17 percent, but this difference was not statistically significant. In 3 of the 13 patients (23 percent), we demonstrated PAX2 expression in tubular epithelial cells in post-transplantation biopsy specimens (Figure 3A). Expression of this antigen was associated with interstitial renal-transplant rejection.
Comparison between Patient Groups
No significant differences were found between female and male recipients in age, frequency of graft rejection, interval from transplantation to the diagnosis of nephrogenic adenoma, or frequency of recurrence. We also found no significant difference in these variables between patients who had received basic antirejection therapy and those also treated with antithymocyte globulin.
Discussion
Nephrogenic adenoma was initially described as a benign hamartomatous bladder lesion by Davis in 1949.17 The term “nephrogenic adenoma” was introduced in 1950 by Friedman and Kuhlenbeck22 because of the lesion's histologic similarities to renal tubules. Although nephrogenic adenomas are rare, a high incidence has been noted in recipients of renal transplants.7-16 Other possible predisposing factors are genitourinary trauma,23,24 mechanical irritation or genitourinary surgery,4,10,14,25-31 local chemical irritation,14,26,32-34 irradiation, and chronic inflammation. The idea that nephrogenic adenomas are metaplastic proliferations of resident urothelial mucosa is widely accepted3,11,25,35,36 but has never been proved. Redondo Martinez and Rey Lopez37 and Strand and Alfert38 reported nephrogenic adenomas after cystectomy that were located in a sigmoid neobladder and an ileal conduit, findings that argue against metaplasia of resident urothelial mucosa.
In our fluorescence in situ hybridization experiments, we found that nephrogenic adenomas from women who received renal transplants from male donors had a male sex-chromosome status (XY), whereas the surrounding bladder tissue had a female sex-chromosome status (XX). The reverse was found in nephrogenic adenomas from men with transplants from female donors. These results demonstrate that nephrogenic adenomas in patients with renal transplants originate from the graft.
Immunohistochemical and lectin staining was performed to characterize the cell type in the nephrogenic adenomas. Aquaporin-1, a membrane protein of water channels, is expressed in the proximal renal tubule and the descending thin limb of Henle's loop, but not in the other nephron segments, the collecting ducts, and the urothelial cells.39,40 Extrarenal aquaporin-1 has been reported in capillary endothelium and red cells.39,40 Aquaporin-2 is selectively expressed in renal collecting ducts.39,40 We found prominent staining for aquaporin-1 but not for aquaporin-2 in nephrogenic adenomas. We also investigated the epithelial cells of nephrogenic adenomas for antigens that are not specific to the kidney. Leu-M1 is expressed in the proximal tubular cells but not in the distal tubules, collecting ducts, and urothelial cells; cytokeratins CK7 and CK8 and epithelial membrane antigen occur in the renal tubules, collecting ducts, and urothelial cells.40-42 A moderate-to-strong immunoreactivity with antibodies against these antigens was shown. CK20, which is found in urothelial cells43 but not in nephrons and collecting ducts, was not detected in the nephrogenic adenomas of our patients.
Binding of L. tetragonolobus agglutinin and S. japonica agglutinin, which are typically found in mature proximal tubular cells, was demonstrated in many of the nephrogenic adenomas we studied. Binding of peanut agglutinin, which is usually found in mature distal tubules, has been reported in nephrogenic adenomas,44 and was found in all the adenomas we studied. This finding suggests that the adenomas arise from an early developmental stage of the renal tubules, since free peanut-agglutinin receptors occur in embryonal renal mesonephric and metanephric tubules.44 All our immunohistochemical and lectin-binding analyses suggest that the adenomas originate from renal tubular cells.
The PAX genes encode a family of transcription factors that act as key regulators during organogenesis.45 PAX2 and PAX8 seem to be required for the development and proliferation of the renal tubules. After renal differentiation, PAX2 expression is down-regulated in mature tissue, and usually no expression is seen in the adult kidney.45 Expression of PAX2 in some biopsy specimens from the transplanted kidneys of our patients with nephrogenic adenoma might indicate an activation of tubular precursor-cell antigens. The presence of aquaporin-1 in nephrogenic adenomas, together with PAX2, peanut agglutinin, and L. tetragonolobus agglutinin, argues against an origin in urothelial cells. Aquaporin-1 is strictly confined to renal tubules and has never been reported to be expressed in urothelium; furthermore, urothelium does not bind peanut agglutinin and L. tetragonolobus agglutinin.
Detachment of viable renal tubular cells probably occurs throughout life. A high incidence of detachment is possible in renal diseases and hypoxic conditions.46-49 Seeding and implantation of neoplastic or non-neoplastic cells in distant tissues are known in the literature, as in the case of endometriosis.50
It seems that in certain circumstances, urothelial mucosa is able to incorporate renal cells, but how implantation of tubular cells after seeding is mediated remains to be clarified in further investigations. Allogeneic renal tubular cells, already implanted, have to survive in the environment of the recipient's connective tissue. We looked at some nephrogenic adenomas for evidence of rejection but found none (data not shown).
Our results show that nephrogenic adenomas in renal-transplant recipients originate not from the recipient's bladder urothelial mucosa, but from renal tubular cells of the transplanted kidney. In our opinion, the terms “nephrogenic adenoma” and “nephrogenic metaplasia” are imprecise; we think these lesions are a kind of renal tubular satellite. Seeding, implantation, and growth of renal cells in urothelial mucosa may be enhanced by increased loss of tubular cells, trauma, infection, and immunosuppression.
Supported by the Fonds zur Förderung der Wissenschaft und Forschung (SFB 05, project 007).
Drs. Mazal and Schaufler contributed equally to the article.
Source Information
From the Department of Clinical Pathology and Center of Excellence in Clinical and Experimental Oncology (P.R.M., A.H., G.K., H.R., D.K., M.S.), the Department of Internal Medicine III (B.W.), and the Department of Urology (C.K.), University of Vienna General Hospital; and the Departments of Nephrology (R.S., F.T.M.) and Urology (R.A.-M., O.Z.), Wilhelminen Hospital — all in Vienna, Austria.
Address reprint requests to Dr. Susani at the Department of Clinical Pathology, University of Vienna General Hospital, Währinger Gürtel 18-20, A-1090 Vienna, Austria, or at martin.susani@akh-wien.ac.at.
- References
References
1
Jakse G ,Mikuz G . Nephrogenic adenoma of the ureter. Eur Urol 1983;9:60-62
Web of Science | Medline2
Marek J ,Hradec E . Chronic sclerosing ureteritis and nephrogenic adenoma of the ureter in analgesic abuse. Pathol Res Pract 1985;180:569-575
CrossRef | Web of Science | Medline3
Kunze F ,Fischer G ,Dembowski J . Tubulo-papillary adenoma (so-called nephrogenic adenoma) arising in the renal pelvis: report of a case with a critical consideration of histogenesis and terminology. Pathol Res Pract 1993;189:217-225
CrossRef | Web of Science | Medline4
Malpica A ,Ro JY ,Troncoso P ,Ordonez NG ,Amin MB ,Ayala AG . Nephrogenic adenoma of the prostatic urethra involving the prostate gland: a clinicopathologic and immunohistochemical study of eight cases. Hum Pathol 1994;25:390-395
CrossRef | Web of Science | Medline5
Oliva E ,Young RH . Nephrogenic adenoma of the urinary tract: a review of the microscopic appearance of 80 cases with emphasis on unusual features. Mod Pathol 1995;8:722-730
Web of Science | Medline6
Gilcrease MZ ,Delgado R ,Vuitch F ,Albores-Saavedra J . Clear cell adenocarcinoma and nephrogenic adenoma of the urethra and urinary bladder: a histopathologic and immunohistochemical comparison. Hum Pathol 1998;29:1451-1456
CrossRef | Web of Science | Medline7
Gordon HL ,Kerr SG . Nephrogenic adenoma of bladder in immunosuppressed renal transplantation. Urology 1975;5:275-277
CrossRef | Medline8
Behesti M ,Morales A . Nephrogenic adenoma of bladder developing after renal transplantation. Urology 1982;20:298-299
CrossRef | Web of Science | Medline9
Beaudry C ,Bertrand PE ,Laplante L , et al. Nephrogenic adenoma of the bladder after kidney transplantation: spontaneous improvement with azathioprine removal: surgical trauma and cytomegalovirus infection as possible etiologic factors. J Urol 1983;130:1183-1185
Web of Science | Medline10
Young RH ,Scully RE . Nephrogenic adenoma: a report of 15 cases, review of the literature, and comparison with clear cell adenocarcinoma of the urinary tract. Am J Surg Pathol 1986;10:268-275
CrossRef | Web of Science | Medline11
Gonzalez JA ,Watts JC ,Alderson TP . Nephrogenic adenoma of the bladder: report of 10 cases. J Urol 1988;139:45-47
Web of Science | Medline12
Zeidan BS ,Shabtai M ,Waltzer WC ,Miller F ,Rapaport FT . Nephrogenic adenoma in renal transplant recipients. Transplant Proc 1992;24:752-754
Web of Science | Medline13
Fournier G ,Menut P ,Moal MC ,Hardy E ,Volant A ,Mangin P . Nephrogenic adenoma of the bladder in renal transplant recipients: a report of 9 cases with assessment of deoxyribonucleic acid ploidy and long-term follow-up. J Urol 1996;156:41-44
CrossRef | Web of Science | Medline14
Tse V ,Khadra M ,Eisinger D ,Mitterdorfer A ,Boulas A ,Rogers J . Nephrogenic adenoma of the bladder in renal transplant and non-renal transplant patients: a review of 22 cases. Urology 1997;50:690-696
CrossRef | Web of Science | Medline15
Banyai-Falger S ,Maier U ,Susani M , et al. High incidence of nephrogenic adenoma of the bladder after renal transplantation. Transplantation 1998;65:511-514
CrossRef | Web of Science | Medline16
Pycha A ,Mian C ,Reiter WJ , et al. Nephrogenic adenoma in renal transplant recipients: a truly benign lesion? Urology 1998;52:756-761
CrossRef | Web of Science | Medline17
Davis TA . Hamartoma of the urinary bladder. Northwest Med 1949;48:182-185
Medline18
Racusen LC ,Solez K ,Colvin RB , et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999;55:713-723
CrossRef | Web of Science | Medline19
Grupp C ,John H ,Hemprich U ,Singer A ,Munzel U ,Muller GA . Identification of nucleated cells in urine using lectin staining. Am J Kidney Dis 2001;37:84-93
CrossRef | Web of Science | Medline20
Holthofer H ,Miettinen A ,Paasivuo R , et al. Cellular origin and differentiation of renal carcinomas: a fluorescence microscopic study with kidney-specific antibodies, antiintermediate filament antibodies, and lectins. Lab Invest 1983;49:317-326
Web of Science | Medline21
Ulrich W ,Horvat R ,Krisch K . Lectin histochemistry of kidney tumours and its pathomorphological relevance. Histopathology 1985;9:1037-1050
CrossRef | Web of Science | Medline22
Friedman NB ,Kuhlenbeck H . Adenomatoid tumors of the bladder reproducing renal structures (nephrogenic adenomas). J Urol 1950;64:657-670
Web of Science | Medline23
Imahori SC ,Magoss IV . Nephrogenic adenoma of bladder: clinical and ultrastructural study. Urology 1980;16:310-312
CrossRef | Web of Science | Medline24
Johannes A ,Prantl F ,Peschke P ,Wenzl H . Sogenanntes nephrogenes Adenom (adenomatöse Metaplasie): Seltene tumorartige adenopapilläre Läsion des Urothels in der Harnblase bei einem 6-jährigen Knaben nach Trauma. Urologe A 1988;27:204-206
Medline25
McIntire TL ,Soloway MS ,Murphy WM . Nephrogenic adenoma. Urology 1987;29:237-241
CrossRef | Web of Science | Medline26
Wood DP Jr ,Streem SB ,Levin HS . Nephrogenic adenomas in patients with transitional cell carcinoma of the bladder receiving intravesical thiotepa. J Urol 1988;139:130-131
Web of Science | Medline27
Ford TF ,Watson GM . Cameron KM. Adenomatous metaplasia (nephrogenic adenoma) of urothelium: an analysis of 70 cases. Br J Urol 1985;57:427-433
CrossRef | Medline28
Kaver I ,Merimsky E ,Greenstein A ,Behar AJ ,Braf ZF . Nephrogenic adenoma: benign proliferative lesion of urothelium. Urology 1985;26:506-508
CrossRef | Web of Science | Medline29
Vorreuther R ,Nayal W ,Hake R ,Engelmann U . Nephrogenic adenoma of the bladder. Urol Int 1994;53:227-229
CrossRef | Web of Science | Medline30
Weingartner K ,Kozakewich HP ,Hendren WH . Nephrogenic adenoma after urethral reconstruction using bladder mucosa: report of 6 cases and review of the literature. J Urol 1997;158:1175-1177
CrossRef | Web of Science | Medline31
Piper NY ,Thompson IM . Large nephrogenic adenoma following transurethral resection of the prostate. J Urol 1999;161:605-605
CrossRef | Web of Science | Medline32
Stilmant MM ,Siroky MB . Nephrogenic adenoma associated with intravesical bacillus Calmette-Guerin treatment: a report of 2 cases. J Urol 1986;135:359-361
Web of Science | Medline33
Oyama N ,Tanase K ,Akino H ,Mori H ,Kanamaru H ,Okada K . Nephrogenic adenoma in a patient with transitional cell carcinoma of the bladder receiving intravesical bacillus Calmette-Guerin. Int J Urol 1998;5:185-187
CrossRef | Medline34
Kilciler M ,Tan O ,Ozgok Y ,Tahmaz L ,Deveci S ,Erduran D . Nephrogenic adenoma of the bladder after intravesical bacillus Calmette-Guerin treatment. Urol Int 2000;64:229-232
CrossRef | Web of Science | Medline35
O'Shea PA ,Callaghan JF ,Lawlor JB ,Reddy VC . “Nephrogenic adenoma“: an unusual metaplastic change of urothelium. J Urol 1981;125:249-252
Web of Science | Medline36
Peeker R ,Alenborg F ,Fall M . Nephrogenic adenoma -- a study with special reference to clinical presentation. Br J Urol 1997;80:539-542
CrossRef | Medline37
Redondo Martinez E ,Rey Lopez A . Adenoma nefrogénica en mucosa intestinal: un caso en una anastomosis uretro-sigmoidea. Arch Esp Urol 1998;51:284-286
Medline38
Strand WR ,Alfert HJ . Nephrogenic adenoma occurring in an ileal conduit. J Urol 1987;137:491-492
Web of Science | Medline39
Nielsen S ,Agre P . The aquaporin family of water channels in kidney. Kidney Int 1995;48:1057-1068
CrossRef | Web of Science | Medline40
Agre P ,Nielsen S . The aquaporin family of water channels in kidney. Nephrologie 1996;17:409-415
Medline41
Silva F ,Nadasdy T ,Laszik Z . Immunohistochemical and lectin dissection of the human nephron in health and disease. Arch Pathol Lab Med 1993;117:1233-1239
Web of Science | Medline42
Satoh F ,Tsutsumi Y ,Yokoyama S ,Osamura RY . Comparative immunohistochemical analysis of developing kidneys, nephroblastomas and related tumors: considerations on their histogenesis. Pathol Int 2000;50:458-471
CrossRef | Web of Science | Medline43
Schaafsma HE ,Ramaekers FCS ,van Muijen GNP , et al. Distribution of cytokeratin polypeptides in human transitional cell carcinomas, with special emphasis on changing expression patterns during tumor progression. Am J Pathol 1990;136:329-343
Web of Science | Medline44
Devine P ,Ucci A ,Krain H , et al. Nephrogenic adenoma and embryonic kidney tubules share PNA receptor sites. Am J Clin Pathol 1984;81:728-732
Web of Science | Medline45
Dahl E ,Koseki H ,Balling R . Pax genes and organogenesis. Bioessays 1997;19:755-765
CrossRef | Web of Science | Medline46
Racusen LC ,Fivush BA ,Li YL ,Slatnik I ,Solez K . Dissociation of tubular cell detachment and tubular cell death in clinical and experimental “acute tubular necrosis.“ Lab Invest 1991;64:546-556
Web of Science | Medline47
Racusen LC . Epithelial cell shedding in acute renal injury. Clin Exp Pharmacol Physiol 1998;25:273-275
CrossRef | Web of Science | Medline48
Racusen LC ,Wilson PD ,Hartz PA ,Fivush BA ,Burrow CR . Renal proximal tubular epithelium from patients with nephropathic cystinosis: immortalized cell lines as in vitro model systems. Kidney Int 1995;48:536-543
CrossRef | Web of Science | Medline49
Dorrenhaus A ,Muller JI ,Golka K ,Jedrusik P ,Schulze H ,Follmann W . Cultures of exfoliated epithelial cells from different locations of the human urinary tract and the renal tubular system. Arch Toxicol 2000;74:618-626
CrossRef | Web of Science | Medline50
van der Linden PJQ . Theories on the pathogenesis of endometriosis. Hum Reprod 1996;11:Suppl 3:53-65
Web of Science | Medline
- Citing Articles (41)
Citing Articles
1
Daniel Ansari, Jacob Elebro, Bobby Tingstedt, Emil Ygland, Madeleine Fabricius, Bodil Andersson, Roland Andersson. (2011) Single-institution experience with solid pseudopapillary neoplasm of the pancreas. Scandinavian Journal of Gastroenterology 46:12, 1492-1497
CrossRef2
Andreas H. Brunner, Paul Riss, Georg Heinze, Elisabeth Meltzow, Hermann Brustmann. (2011) Immunoexpression of PAX 8 in Endometrial Cancer. International Journal of Gynecological Pathology 30:6, 569-575
CrossRef3
Justine S. Broecker, Charlotte K. Steelman, Bruce H. Broecker, Bahig M. Shehata. (2011) Nephrogenic Adenoma of the Bladder in a Prune Belly Syndrome Patient: Case Report and Review of the Literature. Fetal & Pediatric Pathology 30:5, 296-300
CrossRef4
Sean R Williamson, Antonio Lopez-Beltran, Rodolfo Montironi, Liang Cheng. (2011) Glandular lesions of the urinary bladder:clinical significance and differential diagnosis. Histopathology 58:6, 811-834
CrossRef5
Martin Johansson. (2011) Lord of the Rings: A Promising Novel Treatment for Renal Cell Carcinoma?. European Urology 59:5, 745-746
CrossRef6
Enrica Rossi, Piero Pavanello, Andrea Marzola, Andrea Franchella. (2011) Eosinophilic cystitis and nephrogenic adenoma of the bladder: a rare association of 2 unusual findings in childhood. Journal of Pediatric Surgery 46:4, e31-e34
CrossRef7
S. A. Thiryayi, D. N. Rana, Zubair Baloch. (2011) Urine cytopathology: Challenges, pitfalls, and mimics. Diagnostic Cytopathologyn/a-n/a
CrossRef8
Peter G. Pavlidakey, Gregory T. MacLennan, Howard B. Goldman. (2010) Nephrogenic Adenoma of the Bladder. The Journal of Urology 184:6, 2535-2536
CrossRef9
Ankur R. Sangoi, Jason Karamchandani, Jinah Kim, Reetesh K. Pai, Jesse K. McKenney. (2010) The Use of Immunohistochemistry in the Diagnosis of Metastatic Clear Cell Renal Cell Carcinoma. Advances in Anatomic Pathology 17:6, 377-393
CrossRef10
Sean R. Williamson, Antonio Lopez-Beltran, Gregory T. MacLennan, Rodolfo Montironi, Liang Cheng. (2010) Unique clinicopathologic and molecular characteristics of urinary bladder tumors in children and young adults. Urologic Oncology: Seminars and Original Investigations
CrossRef11
Qihui Jim Zhai, Ayhan Ozcan, Candice Hamilton, Steven S. Shen, Donna Coffey, Bhuvaneswari Krishnan, Luan D. Truong. (2010) PAX-2 Expression in Non-neoplastic, Primary Neoplastic, and Metastatic Neoplastic Tissue. Applied Immunohistochemistry & Molecular Morphology 18:4, 323-332
CrossRef12
Mehsati Herawi, Peter A. Drew, Chin-Chen Pan, Jonathan I. Epstein. (2010) Clear cell adenocarcinoma of the bladder and urethra: cases diffusely mimicking nephrogenic adenoma. Human Pathology 41:4, 594-601
CrossRef13
Cristina Magi-Galluzzi, Ming Zhou. 2010. Ureter, Urinary Bladder, and Kidney. , 487-538.
CrossRef14
Gaelle Fromont, Lucile Barcat, Jean Gaudin, Jacques Irani. (2009) Revisiting the Immunophenotype of Nephrogenic Adenoma. The American Journal of Surgical Pathology 33:11, 1654-1658
CrossRef15
Guo-Xia Tong, Woojin M Yu, Nike T Beaubier, Erin M Weeden, Diane Hamele-Bena, Mahesh M Mansukhani, Kathleen M O'Toole. (2009) Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study. Modern Pathology 22:9, 1218-1227
CrossRef16
Paolo Cossu-Rocca, Marcella Contini, Matteo Brunelli, Antonella Festa, Francesca Pili, Stefano Gobbo, Albino Eccher, Antonica Mura, Giovannino Massarelli, Guido Martignoni. (2009) S-100A1 Is a Reliable Marker in Distinguishing Nephrogenic Adenoma From Prostatic Adenocarcinoma. The American Journal of Surgical Pathology 33:7, 1031-1036
CrossRef17
Robert H Young. (2009) Tumor-like lesions of the urinary bladder. Modern Pathology 22, S37-S52
CrossRef18
J H Shanks, K A Iczkowski. (2009) Divergent differentiation in urothelial carcinoma and other bladder cancer subtypes with selected mimics. Histopathology 54:7, 885-900
CrossRef19
Joshua F. Coleman, Donna E. Hansel. (2009) Utility of Diagnostic and Prognostic Markers in Urothelial Carcinoma of the Bladder. Advances in Anatomic Pathology 16:2, 67-78
CrossRef20
DAVID G. BOSTWICK, ISABELLE MEIERS. 2009. Prostate. , 1121-1180.
CrossRef21
RICHARD J. COTE, ANIRBAN P. MITRA, MAHUL B. AMIN. 2009. Bladder and Urethra. , 1079-1120.
CrossRef22
Joshua F. Coleman, Donna E. Hansel. (2008) Benign Diseases of the Bladder. Surgical Pathology Clinics 1:1, 129-158
CrossRef23
Guo-Xia Tong, Erin M. Weeden, Diane Hamele-Bena, Youming Huan, Pamela Unger, Lorenzo Memeo, Kathleen OʼToole. (2008) Expression of PAX8 in Nephrogenic Adenoma and Clear Cell Adenocarcinoma of the Lower Urinary Tract. The American Journal of Surgical Pathology 32:9, 1380-1387
CrossRef24
Vijaya M. Vemulakonda, Ryan P. Kopp, Mathew D. Sorensen, Richard W. Grady. (2008) Recurrent nephrogenic adenoma in a 10-year-old boy with prune belly syndrome : a case presentation. Pediatric Surgery International 24:5, 605-607
CrossRef25
Myoung S Kim, Sang K Kim, Soon I Kim, Yu S Kim, Hyeon J Jeong. (2008) Ureteral nephrogenic adenoma in a renal allograft patient. International Journal of Urology 15:2, 178-179
CrossRef26
Leal C. Herlitz, Guo-Xia Tong, Diane Hamele-Bena, Ellen Greenebaum. (2008) Nephrogenic adenoma identified on urine cytology using PAX-2 immunostaining. Diagnostic Cytopathology 36:1, 47-49
CrossRef27
Donna Elizabeth Hansel, Tibor Nadasdy, Jonathan I. Epstein. (2007) Fibromyxoid Nephrogenic Adenoma: A Newly Recognized Variant Mimicking Mucinous Adenocarcinoma. The American Journal of Surgical Pathology 31:8, 1231-1237
CrossRef28
Guo-Xia Tong, Luis Chiriboga, Diane Hamele-Bena, Alain C Borczuk. (2007) Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?. Modern Pathology 20:8, 856-863
CrossRef29
Aliyah Rahemtullah, Esther Oliva. (2006) Nephrogenic Adenoma: An Update on an Innocuous but Troublesome Entity. Advances in Anatomic Pathology 13:5, 247-255
CrossRef30
Mehsati Herawi, John T. Leppert, George V. Thomas, Jean B. De Kernion, Jonathan I. Epstein. (2006) Implants of noninvasive papillary urothelial carcinoma in peritoneum and ileocolonic neobladder: Support for “seed and soil” hypothesis of bladder recurrence. Urology 67:4, 746-750
CrossRef31
Dontscho Kerjaschki, Nicole Huttary, Ingrid Raab, Heinz Regele, Katalin Bojarski-Nagy, Gregor Bartel, Stefan M Kröber, Hildegard Greinix, Agathe Rosenmaier, Franz Karlhofer, Nikolaus Wick, Peter R Mazal. (2006) Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants. Nature Medicine 12:2, 230-234
CrossRef32
Guo-Xia Tong, Jonathan Melamed, Mahesh Mansukhani, Lorenzo Memeo, Osvaldo Hernandez, Fang-Ming Deng, Luis Chiriboga, Jerry Waisman. (2006) PAX2: a reliable marker for nephrogenic adenoma. Modern Pathology 19:3, 356-363
CrossRef33
Arndt Hartmann, Kerstin Junker, Wolfgang Dietmaier, Sören Schröder, Diego Lopez, Ferdinand Hofstädter, Hagen Blaszyk. (2006) Molecular evidence for progression of nephrogenic metaplasia of the urinary bladder to clear cell adenocarcinoma. Human Pathology 37:1, 117-120
CrossRef34
Peter R. Mazal, Martin Susani, Fritz Wrba, Andrea Haitel. (2005) Diagnostic significance of aquaporin-1 in liver tumors. Human Pathology 36:11, 1226-1231
CrossRef35
Peter R Mazal, Martin Stichenwirth, Anke Koller, Sabine Blach, Andrea Haitel, Martin Susani. (2005) Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study. Modern Pathology 18:4, 535-540
CrossRef36
Michael Mengel, Danny Jonigk, Ludwig Wilkens, Jörg Radermacher, Reinhard von Wasielewski, Ulrich Lehmann, Hermann Haller, Michael Mihatsch, Hans Kreipe. (2004) Chimerism of Metanephric Adenoma but Not of Carcinoma in Kidney Transplants. The American Journal of Pathology 165:6, 2079-2085
CrossRef37
Anita Gupta, Hanlin L Wang, Maria Luisa Policarpio-Nicolas, Maria S Tretiakova, Veronica Papavero, Michael R Pins, Zhong Jiang, Peter A Humphrey, Liang Cheng, Ximing J Yang. (2004) Expression of Alpha-Methylacyl-Coenzyme A Racemase in Nephrogenic Adenoma. The American Journal of Surgical Pathology 28:9, 1224-1229
CrossRef38
Zhong Jiang, Bruce A. Woda, Chin-Lee Wu, Ximing J. Yang. (2004) Discovery and Clinical Application of a Novel Prostate Cancer Marker a-Methylacyl CoA Racemase (P504S). American Journal of Clinical Pathology 122:2, 275-289
CrossRef39
Brian F Skinnider, Esther Oliva, Robert H Young, Mahul B Amin. (2004) Expression of ??-Methylacyl-CoA Racemase (P504S) in Nephrogenic Adenoma: A Significant Immunohistochemical Pitfall Compounding the Differential Diagnosis With Prostatic Adenocarcinoma. The American Journal of Surgical Pathology 28:6, 701-705
CrossRef40
Heinz Regele, Georg A. Böhmig. (2003) Tissue injury and repair in allografts: novel perspectives. Current Opinion in Nephrology and Hypertension 12:3, 259-266
CrossRef41
Ingelfinger, Julie R., . (2002) Nephrogenic Adenomas as Renal Tubular Outposts. New England Journal of Medicine 347:9, 684-686
Full Text
