Nephrogenic Adenoma Research Articles

Nephrogenic Adenoma: A Pitfall on Frozen Section of Urethral Strictures.

Urethral strictures are a common cause of urinary obstruction which can be treated with surgical resection. Frozen sections are rare and pose a diagnostic challenge to pathologists due to the presence of benign lesions such as nephrogenic adenoma. We retrospectively examined all specimens of urethral stricture resections submitted to pathology at our institution from 2012 to 2022 (n = 258). Final pathology reports were searched to identify patients with dysplasia, carcinoma, or nephrogenic adenoma. When available, frozen section reports were also examined and compared to the final report, and additional clinical history and microscopic images were collected for patients with nephrogenic adenoma. Nephrogenic adenoma was identified in 3.8% (10/258) of urethral stricture resections. Dysplasia was identified in one patient who underwent two separate resections, and squamous cell carcinoma was found in one resection. Intraoperative frozen section was requested in 3.4% of resections (9/258). In two resections, an initial diagnosis of squamous cell carcinoma was initially favoured, however when reviewed with a genitourinary pathologist the diagnosis was changed to "reactive process" with a final diagnosis of nephrogenic adenoma. Nephrogenic adenoma can be challenging on frozen section due to variable architectural patterns, inflammation, and reactive changes. While urethral strictures are relatively common, their assessment by frozen section is rare and pathologists may lack familiarity with the variable morphology of benign entities that can be seen on frozen section resulting in their misinterpretation. We highlight this potential diagnostic pitfall and demonstrate the value of a second opinion prior to definitive frozen section diagnosis of malignancy.

Nephrogenic adenoma of the urinary bladder. Clinical features, long-term follow-up and recurrence predictors

ABSTRACT Objectives To review the clinical features of nephrogenic adenoma (NA) of the urinary bladder and assess the long-term recurrence rates. Material and methods A retrospective analysis of all diagnosed NA of the urinary bladder between 2000 and 2023 was done. All patients’ demographics, symptoms, history of previous bladder surgeries, macroscopic and microscopic features of NA and coincidental pathology were reviewed. The long-term recurrence rate including malignant recurrence was assessed. Univariate and multivariate analysis of predictor of recurrence was performed. Results We identified 24 patients diagnosed with NA with a mean (SD, range) age of 56 (16, 15–73) years. Eighteen (75%) patients had previous history of bladder surgeries. Macroscopic appearance on cystoscopy looked polypoidal, flat velvety, papillary and nodular in eight, seven, five, and four patients, respectively. At a median (range) follow-up of 35 (18–145) months, 15 (63%) patients developed one recurrence including NA, non-specific cystitis and urothelial carcinoma (UC) in nine, three and three patients, respectively. Of them, five had a second recurrence, and one patient had a third recurrence. Patients with malignant recurrence had previous history of UC and two of them required radical cystectomy and urinary diversion. Previous TURBT was the only independent predictor for recurrence [OR (95% CI) = 28 (2–37), p = 0.01]. Conclusion Nephrogenic adenoma is a benign disease that mimics malignant lesion clinically. It is associated with high recurrence rate. Previous resection of bladder lesion is the independent predictor of the recurrence.

1184 Bladder Nephrogenic Adenoma Occurred After Repeated IntravesicalOnabotulinumtoxinA (Botox®) Injection for Refractory Overactive

1184 Bladder Nephrogenic Adenoma Occurred After Repeated IntravesicalOnabotulinumtoxinA (Botox®) Injection for Refractory Overactive

Expression of L1 Cell Adhesion Molecule, a Nephronal Principal Cell Marker, in Nephrogenic Adenoma

Nephrogenic adenoma (NA) is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with antecedent inflammation, instrumentation, or an operative history. Its histopathologic diversity can create diagnostic dilemmas and pathologists use morphologic evaluation along with available immunohistochemical (IHC) markers to navigate these challenges. IHC assays currently do not designate or specify NA’s potential putative cell of origin. Leveraging single-cell RNA-sequencing technology, we nominated a principal (P) cell–collecting duct marker, L1 cell adhesion molecule (L1CAM), as a potential biomarker for NA. IHC characterization revealed L1CAM to be positive in all 35 (100%) patient samples of NA; negative expression was seen in the benign urothelium, benign prostatic glands, urothelial carcinoma (UCA) in situ, prostatic adenocarcinoma, majority of high-grade UCA, and metastatic UCA. In the study, we also used single-cell RNA sequencing to nominate a novel compendium of biomarkers specific for the proximal tubule, loop of Henle, and distal tubule (DT) (including P and intercalated cells), which can be used to perform nephronal mapping using RNA in situ hybridization and IHC technology. Employing this technique on NA we found enrichment of both the P-cell marker L1CAM and, the proximal tubule type-A and -B cell markers, PDZKI1P1 and PIGR, respectively. The cell-type markers for the intercalated cell of DTs (LINC01187 and FOXI1), and the loop of Henle (UMOD and IRX5), were found to be uniformly absent in NA. Overall, our findings show that based on cell type–specific implications of L1CAM expression, the shared expression pattern of L1CAM between DT P cells and NA. L1CAM expression will be of potential value in assisting surgical pathologists toward a diagnosis of NA in challenging patient samples.

Identification of uromodulin deposition in the stroma of perinephric fibromyxoid nephrogenic adenoma by mass spectrometry.

Nephrogenic adenoma (NA) is an epithelial lesion that usually occurs in the mucosa of the urinary tract. Rare cases of deep infiltrative or perinephric lesions have also been reported. Recently, NA with characteristic fibromyxoid stroma (fibromyxoid NA) has been proposed as a distinct variant. Although shedding of distal renal tubular cells due to urinary tract rupture has been postulated as the cause of NA in general, the mechanism underlying extraurinary presentation of NA and fibromyxoid stromal change in fibromyxoid NA remains unknown. In this study, we performed mass spectrometry (MS) analysis in a case of perinephric fibromyxoid NA of an 82-year-old man who underwent right nephroureterectomy for distal ureteral cancer. The patient had no prior history of urinary tract injury or radiation. Periodic acid-Schiff staining-positive eosinophilic structureless deposits in the stroma of fibromyxoid NA were microdissected and subjected to liquid chromatography/MS. The analysis revealed the presence of a substantial amount of uromodulin (Tamm-Horsfall protein). The presence of urinary content in the stroma of perinephric fibromyxoid NA suggests that urinary tract rupture and engraftment of renal tubular epithelial cells directly cause the lesion.

Diagnostic Approach to and Differential Diagnosis of Clear Cell and Glandular Lesions of the Lower Urinary Tract.

A variety of glandular and clear cell lesions may be seen in the urinary bladder and/or urethra, ranging from benign to malignant primary and secondary tumors. Lesions with no malignant potential include reactive processes, such as nephrogenic metaplasia, and may show similar morphologic features as an infiltrative neoplasm, particularly in small biopsies. Similarly, ectopic tissues of Müllerian origin may be seen in the lower urinary tract, and their distinction from a true glandular neoplasm is essential to avoid overtreatment. A wide variety of primary and secondary malignant tumors exist with varying degrees of glandular and clear cell features. Therefore, surgical pathologists must be aware of the full scope of possible lesions to avoid misdiagnosis. To provide a practical framework for approaching the diagnosis of clear cell and glandular lesions of the urinary bladder/urethra and prostate, highlighting the strengths and limitations of various diagnostic features and ancillary tests. A review of the current literature was performed to obtain data regarding up-to-date diagnostic features and ancillary studies. In summary, distinct morphologic and immunohistochemical features and clinical and radiologic correlation are essential to establish an accurate diagnosis when such cases with glandular and clear features are encountered in the lower urinary tract.

Tumefactive Nonneoplastic Proliferative Pseudotumors of the Kidneys and Urinary Tract: CT and MRI Findings with Histopathologic Correlation.

A diverse spectrum of pathologically distinct, nonneoplastic, proliferative conditions of the kidneys and urinary tract demonstrate a expansile growth pattern similar to that of neoplasms. The renal pseudotumors include myriad causes of infections as well as rare noninfectious causes such as sarcoidosis, amyloidosis, and immunoglobulin G4-related disease (IgG4-RD). Rare entities such as cystitis cystica, endometriosis, nephrogenic adenoma, and pseudosarcomatous myofibroblastic proliferation and distinct types of prostatitis comprise tumefactive nontumorous disorders that affect specific segments of the urinary tract. The pseudotumors of the kidneys and urinary tract demonstrate characteristic histopathologic and epidemiologic features, as well as protean clinical manifestations, natural history, and imaging findings. Many patients present with genitourinary tract-specific symptoms or systemic disease. Some cases may be incidentally discovered at imaging. Some entities such as perinephric myxoid pseudotumors, IgG4-RD, fibroepithelial polyp, and nephrogenic adenoma display specific anatomic localization and disease distribution. Imaging features of multisystem disorders such as tuberculosis, sarcoidosis, and IgG4-RD provide supportive evidence that may allow precise diagnosis. Fungal pyelonephritis, xanthogranulomatous pyelonephritis, IgG4-RD, actinomycosis, and endometriosis show markedly low signal intensity on T2-weighted MR images. Although some pseudotumors exhibit characteristic imaging findings that permit correct diagnosis, laboratory correlation and histopathologic confirmation are required for definitive characterization in most cases. A high index of suspicion is a prerequisite for diagnosis. Accurate diagnosis is critical for instituting optimal management while preventing use of inappropriate therapies or interventions. Surveillance CT and MRI are frequently used for monitoring the response of pseudotumors to therapy. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

RARE PRIMARY CLEAR CELL CARCINOMA OF BLADDER OF MULLERIAN ORIGIN: MORPHO- IMMUNOHISTOCHEMICAL PROFILING

Abstract Introduction/Objective Primary clear cell carcinoma of urinary bladder (PCCCUB) is a rare and aggressive cancer variant with uncertain and debatable histogenesis. The hypotheses include origins from the urothelium, pre-existing Müllerian precursors, or mesonephric remnants. Definitive diagnosis is achieved through histology and immunohistochemistry (IHC). We present an unusual case of PCCCUB in a sexagenarian woman. Methods/Case Report Patient with history of diabetes, hypertension, and smoking presented with gross hematuria. Computed tomography urogram revealed a 2.3 x 1.2 cm enhancing mass at the base of the urinary bladder. Patient underwent transurethral resection of the bladder tumor (TURBT). Histopathology revealed features of tubulo-papillary, solid, glandular structures with hyalinized stroma. Cytologic features varied from flat, hobnail, to polygonal with abundant clear to eosinophilic cytoplasm and prominent nucleoli. Immunohistochemistry revealed strong reactivity for PAX8, CK7, ER, and racemase; focal reactivity for vimentin, napsin A, p53, CA125; and non-reactivity for PAX2, WT1, PR, GATA3, pCEA, CK20, p63, p40, CD10, RCC, BRST-2, and mammaglobin. P53 showed a wild type staining pattern and Ki-67 was 10%. Combined morphologic and IHC features confirmed PCCCUB, and in the absence of muscularis mucosal invasion, tumor was staged pT1N0. PAX8 positivity and urothelial marker negativity excluded clear cell pattern of urothelial carcinoma. IHC also excluded nephrogenic adenoma, and metastasis. The female gender, and CK 7 (+)/CK 20 (−) profile supported Müllerian origin. Restaging TURBT showed consistent results. Subsequently, anterior pelvic exenteration and bilateral pelvic lymph nodes dissection was performed revealing muscularis propria invasion upstaging to mpT2 N0. Results (if a Case Study enter NA) NA Conclusion Poor prognosis, aggressive behavior, and advanced stage at the time of diagnosis warrants accurate diagnose of PCCCUB. Ambiguous origin, limited literature, and lack of clear management guidelines merit reporting in order to enhance knowledge of this rare and intriguing entity.

10-year Observation of A Rare Presentation of Pure Fibromyxoid Nephrogenic Adenoma in the Renal Pelvis

Abstract Introduction/Objective Pure fibromyxoid NA is an unusual rare variant that typically presents with a well circumscribed bulbous, or tumefacient architecture composed of mitotically inactive bland spindled cells and rare tubular structures within a myxoid or collagenized stroma. Here we report a rare case of pure fibromyxoid NA involving the renal pelvis with over 10-year clinical observation and comparison and correlation of biopsy and resection findings. To the best of our knowledge, this is the first reported case of pure fibromyxoid NA in renal pelvis with close comparison and correlation of biopsy and resection findings with over 10-year clinical manifestation, hoping that knowledge of this long-term rare spindle cell lesion will enhance awareness of pathologists to carefully consider this unusual entity, especially in the biopsy specimen in which typical histologic features of fibromyxoid NA are usually absent, as well as prevent misdiagnosis and overtreatment of a typically benign process. Methods/Case Report A retrospective case study of a 37-year-old female with multiple previous biopsy of the nodule in the renal pelvis, and final resection specimen. Biopsies of the mass showed predominantly bland spindle cell lesion with smooth muscle differentiation and scant urothelial epithelial cells, but no tubular structure identified at the biopsy specimen. On the final resection specimen, a urothelium-lining polypoid nodule composing of abundant bland spindle- shaped cells and scattered conventional tubules lined by a single layer of cuboidal epithelial cells in hobnail arrangement that are positive for PAX8 and GATA3 was identified. These morphological and immunohistochemical findings were consistent with the diagnosis of pure fibromyxoid NA. Results (if a Case Study enter NA) NA Conclusion To the best of our knowledge, this is the first description of a pure fibromyxoid NA of the renal pelvis with more than 10-year clinical observation, as well as comparison and correlation of biopsy and resection findings.Close observation and comparison of the findinigs between biopsy and resection specimen will enhance awareness of pathologists to carefully consider this unusual entity, especially in the biopsy specimen in which typical histologic features of fibromyxoid NA are usually absent, as well as prevent misdiagnosis and overtreatment of a typically benign process.

Rare presentation of nephrogenic adenoma at the meatus of penoscrotal hypospadias: A case report

Introduction: Nephrogenic adenoma is a rare benign condition that arises in the urothelium however can occur anywhere along the urinary tract. Mostly it occurs in Caucasian males with a ratio of 2:1 (male/female) . The condition mostly occurs in adults however 10% children are also affected. The lesion may occur as a metaplastic response to urothelium, or it may occur congenitally due to proliferation of meta nephrogenic rest. In this report , we emphasize on its congenital origin without any pre-existing cause in a patient of penoscrotal hypospadias.

A Case Report of Fibromyxoid Variant of Nephrogenic Adenoma of Prostatic Urethra: Morphology Mimicking Carcinoma

Background: Nephrogenic adenoma is an uncommon, benign, tumour-like lesion within the urothelial mucosa of the urinary tract caused by reimplantation and proliferation of the renal tubular cells that have been shed by chronic irritation of the mucosa of the urinary tract. Case Study: We report a case of the rare fibromyxoid variant of nephrogenic adenoma in the prostate urethra. To the best of our knowledge, only a few cases have been described in the literature. Conclusion: This tumour can have variable morphological patterns with occasional worrisome features that can mimic carcinoma of the lower urinary tract.

Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid

Cadherin-16 (CDH16) plays a role in the embryonal development in kidney and thyroid. Downregulation of CDH16 RNA was found in papillary carcinomas of the thyroid. To determine the expression of CDH16 in tumors and to assess the diagnostic utility a tissue microarray containing 15,584 samples from 152 different tumor types as well as 608 samples of 76 different normal tissue types was analyzed. A membranous CDH16 immunostaining was predominantly seen in thyroid, kidney, cauda epididymis, and mesonephric remnants. In the thyroid, CDH16 staining was seen in 100% of normal samples, 86% of follicular adenomas, 60% of follicular carcinomas, but only 7% of papillary carcinomas (p < 0.0001). CDH16 positivity was frequent in nephrogenic adenomas (100%), oncocytomas (98%), chromophobe (97%), clear cell (85%), and papillary (76%) renal cell carcinomas (RCCs), various subtypes of carcinoma of the ovary (16–56%), various subtyped of carcinomas of the uterus (18–40%), as well as in various subtypes of neuroendocrine neoplasms (4–26%). Nineteen further tumor entities showed a weak to moderate CDH16 staining in up to 8% of cases. Our data suggest CDH16 as a potential diagnostic marker—as a part of a panel—for the identification of papillary carcinomas of the thyroid, nephrogenic adenomas, and the distinction of renal cell tumors from other neoplasms.

P16 Immunohistochemical Expression in Nephrogenic Adenoma.

Nephrogenic adenoma (NA) is a rare metaplastic entitycommonly associated with a prior urothelial injury. Most are seen in the urinary bladder and a minority involve the urethra. In this study, we evaluated the expression of p16 as a surrogate marker of this entity and correlated it with clinical pathological parameters. A total of 17 cases ofNA were retrospectively studied to assess the immunohistochemical expression of p16 and its value for the diagnosis of this entity.

The natural course of bacillus Calmette-Guérin induced bladder lesions: A long-term follow-up study and systematic review

ObjectiveBacillus Calmette-Guérin (BCG) instillation is the standard adjuvant treatment for intermediate- and high-risk non-muscle-invasive bladder cancer after transurethral resection. Nevertheless, its toxicity often causes bladder complications. On follow-up cystoscopy, post-BCG bladder lesions can be pathologically benign, urothelial carcinoma recurrence, or other types of bladder malignancy. Only a small number of case reports have been published on post-BCG bladder lesions. Their clinical features, natural course, and management remain unknown. MethodsWe retrospectively studied cystoscopic videos and medical records of BCG-treated bladder cancer patients at our center. During a long-term follow-up, we took biopsies on tumor-like lesions and described their changes. In addition, we summarized previous studies on post-BCG bladder lesions by systematic literature searching and review. ResultsWe described a series of three cases with post-BCG bladder lesions mimicking tumor recurrence from a total of 38 cases with follow-up data for more than 5 years. Those lesions could last, grow, or disappear spontaneously, and remain pathological benign for years. In systematic review, we identified and analyzed a total of 15 cases with post-BCG bladder lesions with detailed clinical information. Eleven of the 15 were benign and have a good prognosis with nephrogenic adenoma being the most common pathological type. ConclusionBased on previous studies and our experience, benign lesions after BCG instillation cannot distinguish with cancer recurrence by cystoscopy alone, even under narrow band imaging mode. Nonetheless, given most of them have a good prognosis, random biopsy or transurethral resection might be spared in the patients with long-term negative biopsy and urine cytology.

SATB2 as a Marker of the Proximal Nephron: Expression in Nephrogenic Adenoma and Correlation With Other Renal Tubular Markers.

Nephrogenic adenoma (NA) is an infrequent reactive urothelial lesion. The expression of immunohistochemical renal tubular markers has been reported in NA, although a proximal or distal nephron phenotype has not been established. Special AT-rich sequence-binding protein 2 (SATB2) is a marker of a colorectal origin of adenocarcinomas, occasionally reported in renal samples. We have analyzed SATB2 expression in NA, with correlation with other tubular markers, as well as in the normal kidney. Fifty cases of NA were immunostained with PAX8, SATB2, proximal nephron markers [CD10, renal cell carcinoma (RCC) marker, alpha-methylacyl-CoA racemase (AMACR), and CD15], and distal markers (Ksp cadherin, cytokeratin 7, E-cadherin (E-cad), and cytokeratin 19). Ten normal kidney sections were stained with a double method combining SATB2 plus CD10, RCC marker, AMACR, Ksp cadherin, cytokeratin 7, or E-cad. All NA were immunoreactive for PAX8 and 57% for SATB2. Every case was positive for proximal and distal nephron markers: 100% for cytokeratins 7 and 19, 84.1% E-cad +, 81.6% AMACR +, 68.9% Ksp cadherin +, 63% CD15 +, 53.3% CD10 +, and 28.6 % RCC +. In the normal kidney, SATB2 was detected in the straight part of the proximal tubules and the thin descending loops of Henle. NA shows a multiphenotypic pattern with coexpression of both proximal and distal nephron markers, and constant expression of PAX8, cytokeratins 7 and 19. SATB2 is often positive in NA, which should be kept in mind to avoid a possible misdiagnosis of intestinal adenocarcinoma. SATB2 is a marker of the normal proximal nephron.

Primary clear cell adenocarcinoma within a urethral diverticula

Background: Primary clear cell adenocarcinoma of the urinary tract (PCCA) is rare.1 It is strongly associated with urethral diverticula.1,2 The pathological differential diagnosis includes nephrogenic adenoma, clear cell urothelial carcinoma, and metastasis from the female genital tract.2,3

Bladder nephrogenic adenoma as a complication of surgical correction of megaureter

BackgroundBladder nephrogenic adenoma (BNA) is a rare benign proliferative pathology of its mucosa. The etiopathogenesis of the disease remains uncertain, and the treatment is still challenging.Case presentationIn this article, we present a clinical case of bladder nephrogenic adenoma in a 6-year-old boy. Clinical symptoms of the disease appeared 3 years after surgical treatment of obstructive megaureter. Histopathological and immunohistochemical examination of glandular polyp biopsies allowed excluding the tumor process and making a diagnosis.ConclusionNephrogenic adenomas demonstrate a variety of morphologic patterns that may occasionally be confused with malignant processes. We described the endoscopic characteristics of BNA and characterized its histological and immunohistochemical features in a boy after ureteroneocystostomy.

Cadherin-16 (CDH16) Immunohistochemistry: A Novel Diagnostic Tool for Renal Cell Carcinoma and Papillary Carcinomas of the Thyroid

Abstract Introduction/Objective Introduction: Cadherin-16 (CDH16), also termed kidney specific cadherin (ksp-cadherin), is a membrane-associated glycoprotein with a role in the embryonal development of tubules in kidney and thyroid. Downregulation of CDH16 RNA was found in papillary carcinomas of the thyroid. Methods/Case Report Methods: A set of tissue microarrays containing 14,978 samples from 149 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry to determine the expression of CDH16 in cancer and to assess the diagnostic utility of immunohistochemical CDH16 analysis. Results (if a Case Study enter NA) Results: Among normal tissues, a membranous CDH16 immunostaining predominated in thyroid, kidney, cauda epididymis, and in mesonephric remnants. In the thyroid, CDH16 staining was seen in 100% of normal samples, 83% of follicular adenomas, 58% of follicular carcinomas, but in only 9% of papillary carcinomas (p&amp;lt;0.0001). Among non-thyroidal tumors, CDH16 positivity was particularly frequent in nephrogenic adenomas (100%), oncocytomas (98%), chromophobe (97%), clear cell (85%), and papillary (76%) renal cell carcinomas (RCCs), clear cell (56%), mucinous (36%), and endometroid (16%) carcinomas as well as carcinosarcomas (18%) of the ovary, adenocarcinomas of the cervix uteri (40%), serous (33%), clear cell (33%), and endometroid carcinomas (18%) of the endometrium and in various subtypes of neuroendocrine neoplasms (4-26%). Conclusion Given the massive loss of CDH16 expression in &amp;gt;90% of papillary carcinomas of the thyroid, CDH16 is a highly useful diagnostic marker for these tumors. CDH16 immunohistochemistry is also useful for the identification of nephrogenic adenomas and the distinction of renal cell carcinomas from other neoplasms.

Fibromyxoid Nephrogenic Adenoma: A Series of 43 Cases Reassessing Predisposing Conditions, Clinical Presentation, and Morphology.

Nephrogenic adenoma is a benign epithelial lesion of the genitourinary tract that arises from the reimplantation and proliferation of shed renal tubular cells in areas of urothelial injury and denudation. Fibromyxoid nephrogenic adenoma is a rare variant that consists of compressed spindle-shaped renal epithelial cells in a fibromyxoid background. Only 14 observations of this variant are reported in the literature. We performed a retrospective analysis of fibromyxoid nephrogenic adenomas from 3 large reference centers. We identified 43 lesions in 6 women and 36 men (2 in 1 man) with a median age of 72 years (range, 31 to 94y). Median lesion size was 0.7cm (range, 0.2 to 5cm). Nephrogenic adenomas were in the bladder (n=15), prostate/prostatic urethra (n=14), kidney (n=7), ureter (n=3), penile urethra (n=3), and urethral diverticulum (n=1). One of the kidney lesions developed in an end-stage kidney and radiologically mimicked cancer. Of 37 patients with information, 36 had predisposing conditions including prior biopsy, transurethral resection of bladder tumor, resection, Foley catheter, BCG treatment, urinary stones, (chemo)radiation, or diverticulum. Only 4/37 (10.8%) had a history of prior irradiation. Fifteen lesions had pure fibromyxoid morphology and 28 were admixed classic and fibromyxoid patterns. Three nephrogenic adenomas involved prostatic stroma, 3 renal sinus fat, 2 muscularis propria (1 bladder, 1 renal pelvis), 1 perinephric fat, and 1 corpus spongiosum. Ten fibromyxoid nephrogenic adenomas were intermixed with urothelial carcinoma, 1 with prostate adenocarcinoma, and 1 with malignant melanoma. By immunohistochemistry, PAX8 was positive in all the examined lesions (n=31). Napsin A was negative in all examined fibromyxoid nephrogenic adenomas (n=30). Twenty of them had classic nephrogenic adenoma component which was positive for napsin A. Similar to classic nephrogenic adenoma, fibromyxoid nephrogenic adenoma can occur anywhere along the urinary tract and is associated with a prior history that causes urothelial injury. In nearly a quarter of the cases, fibromyxoid nephrogenic adenoma extended beyond the lamina propria. Unlike previously suggested, fibromyxoid nephrogenic adenoma is not specifically related to prior radiation therapy. Awareness of this variant is important to avoid misdiagnosis and overtreatment.

GATA3 expression in clear cell adenocarcinoma of the lower urinary tract: a potential diagnostic pitfall

BackgroundClear cell adenocarcinoma of the lower urinary tract (CCACLUT) is a rare primary malignant neoplasm with heterogenous morphology. There is a paucity of data in the literature regarding its immunohistochemical profile.MethodsThe immunohistochemical features (extent and intensity) of a multinational cohort of CCACLUT were evaluated with comparison between clear cell adenocarcinoma of the female genital tract (CCACFGT, tissue microarray) and nephrogenic adenoma (NA).Results33 CCACLUT (24 female, 9 male; mean age 59 years) were collected. CCACLUT most commonly arose from the urinary bladder (26/33, 78%), particularly from the trigone (10/33, 30.3%) followed by the urethra (8/33, 22%). All 12 NA cases were located at the urinary bladder, whereas the most common CCACFGT location was the ovary (29/56, 52%). None of the CCACLUT patients had, intestinal metaplasia, NA, or urothelial carcinoma. One patient had concurrent endometriosis of the sigmoid colon. Most frequently observed morphology in CCACLUT was papillary/tubulocystic (9/3; 27.3%), followed by papillary/tubular (6/33; 18.2%) and papillary/solid (5/33; 15.2%). GATA3 expression was significantly higher in CCACLUT (18/33, 54.5%) and NA (6/12, 50%), when compared to CCACFGT cases 6/56, 11.7%)(p = 0.001 and p = 0.022, respectively). The extent of GATA3 was significantly higher in CCACLUT group (19.2 ± 16.6%) than the other groups (9.6 ± 22.5% in NA and 2.6 ± 9% in CCACFGT group) (p = 0.001). 4/33 patients (12.1) had weak, 10/33 patients (30.3%) had moderate, and 4/33 patients (12.1%) had strong GATA3 intensity in CCACLUT group. In NA group, one patient (8.3%, 1/12) had weak, one patient (8.3%, 1/12) had moderate and 4 patients (33.3%, 4/12) had strong GATA3 intensity. Most cases (CCACLUT 29/33, 88%; NA 11/12, 92%; CCACFGT 46/56, 82.1%) had positive Napsin A expression, by which CCACLUT had significantly more cases with Napsin A expression (p = 0.034). p63 was consistently negative in all cases (30/33 (91.9%) CCACLUT; 12/12 (100%) NA; 42/56 (75%) CCACFGT. Ki67 (MIB) proliferation index was significantly higher in CCACLUT group (54.6 ± 21%) when compared to NA group (4.5 ± 2.7%) and CCACFGT group (35.5 ± 25.8%) (p = 0.001).ConclusionCCACLUT has consistent GATA3 expression, which may cause challenge in the diagnosis of urothelial carcinoma but can be used to distinguish CCACLUT from CCACFGT.