Delphi: A Democratic and Cost-Effective Method of Consensus Generation in Transplantation.

The Thrombotic Microangiopathy Banff Working Group (TMA-BWG) was formed in 2015 to survey current practices and develop minimum diagnostic criteria (MDC) for renal transplant TMA (Tx-TMA). To generate consensus among pathologists and nephrologists, the TMA BWG designed a 3-Phase study. Phase I of the study is presented here. Using the Delphi methodology, 23 panelists with >3 years of diagnostic experience with Tx-TMA pathology listed their MDC suggesting light, immunofluorescence, and electron microscopy lesions, clinical and laboratory information, and differential diagnoses. Nine rounds (R) of consensus resulted in MDC validated during two Rs using online evaluation of whole slide digital images of 37 biopsies (28 TMA, 9 non-TMA). Starting with 338 criteria the process resulted in 24 criteria and 8 differential diagnoses including 18 pathologic, 2 clinical, and 4 laboratory criteria. Results show that 3/4 of the panelists agreed on the diagnosis of 3/4 of cases. The process also allowed definition refinement for 4 light and 4 electron microscopy lesions. For the first time in Banff classification, the Delphi methodology was used to generate consensus. The study shows that Delphi is a democratic and cost-effective method allowing rapid consensus generation among numerous physicians dealing with large number of criteria in transplantation.

Thrombotic Microangiopathy in the Renal Allograft: Results of the TMA Banff Working Group Consensus on Pathologic Diagnostic Criteria.

The Banff community summoned the TMA Banff Working Group to develop minimum diagnostic criteria (MDC) and recommendations for renal transplant TMA (Tx-TMA) diagnosis, which currently lacks standardized criteria. Using the Delphi method for consensus generation, 23 nephropathologists (panelists) with >3 years of diagnostic experience with Tx-TMA were asked to list light, immunofluorescence, and electron microscopic, clinical and laboratory criteria and differential diagnoses for Tx-TMA. Delphi was modified to include 2 validations rounds with histological evaluation of whole slide images of 37 transplant biopsies (28 TMA and 9 non-TMA). Starting with 338 criteria in R1, MDC were narrowed down to 24 in R8 generating 18 pathological, 2 clinical, 4 laboratory criteria, and 8 differential diagnoses. The panelists reached a good level of agreement (70%) on 76% of the validated cases. For the first time in Banff classification, Delphi was used to reach consensus on MDC for Tx-TMA. Phase I of the study (pathology phase) will be used as a model for Phase II (nephrology phase) for consensus regarding clinical and laboratory criteria. Eventually in Phase III (consensus of the consensus groups) and the final MDC for Tx-TMA will be reported to the transplantation community.

Non-choriocarcinomatous trophoblastic tumors of testis in postchemotherapy retroperitoneal lymph node dissections.

Non-choriocarcinomatous trophoblastic tumors (NCTTs) are seldomly diagnosed in male genital tract. As they have been recently described among the testicular germ cell tumor (TGCT) variants, pathologists' familiarity with their morphology is limited. We searched our electronic hospital records covering the years 2000-2017 for post-chemotherapy retroperitoneal TGCT metastectomies. Slides of all cases with viable tumor were retrieved from the archives and reviewed. Cases suspected of N-CTT morphologies were subjected to immunohistochemistry. Twelve NCTTs were identified, 9 of which were unseen or misdiagnosed by the original pathologists: Cystic trophoblastic tumor (CTT) (n = 5), placental site trophoblastic tumor (n = 2), epithelioid trophoblastic tumor (ETT) (n = 4), and coinciding PSTT + ETT (n = 1). Eight of these were associated with mature teratoma components, and one case (ETT) contained embryonal carcinoma and yolk sac tumor in addition to teratoma. Ten patients were clinically N1 at the time of primary tumor detection and orchiectomy. One patient had burned-out primary testicular tumor. Six patients were clinical M1a at presentation, while one male was cM1b. Six patients had mildly elevated ß-HCG (≤ 410 mIU/ml) just prior to retroperitoneal lymph node dissections (RPLND), while the others had normal ß-HCG levels. All patients had follow-ups ranging from 8 to 118 months (mean 42.3 months). Three patients died of disease-related and two of unrelated causes. In conclusion, because NCTTs are rare and newly described tumor types, their diagnosis is difficult and most of them are missed in post-chemotherapy RPLNDs. The majority of patients exhibit normal or slightly elevated ß-HCG levels. N-CTTs are usually accompanied by other components of TGCT, the most common being teratoma. Despite the high survival rate of the patients, our study points to the unpredictable evolution of NCTT cases, which may concur with a high-stage or progressive disease.

Cytoplasmic WT1 in IgA nephropathy, an indicator of poor prognosis associated with mesangial/peri-mesangial C4d.

BACKGROUND: We aimed to investigate the immuno-histochemical expression of C4d, ADAM10 and WT1 in kidney biopsies of immunoglobulin A nephropathy (IgAN) patients and correlate the findings with clinical, laboratory and histopathologic features in the hope of defining new parameters to better understand the pathogenesis of the disease, and predict prognosis. MATERIALS AND METHODS: Paraffin-embedded kidney biopsy samples of 128 IgAN patients were immuno-histochemically treated with C4d and ADAM10/WT1 dual stain. Results were evaluated according to Oxford classification parameters, epidemiologic features, laboratory findings at presentation and clinical follow-up. RESULTS: We observed C4d positivity in 40.6% of our patients, 25% of which was mesangial/peri-mesangial (m/pm) staining. Only m/pmC4d positivity statistically correlated with progression to end-stage renal disease (ESRD). M/pmC4d positive patients had statistically significantly higher baseline proteinuria levels, presence of crescents and > 25% segmental sclerosis of glomeruli. There was cytoplasmic staining of WT1 in 11.2% of cases. Presence of cWT1 correlated with m/pmC4d positivity and progression to ESRD. There was no glomerular ADAM10 detected and tubular expression of this protein did not relate to amount of tubular damage or other parameters. CONCLUSION: This study is the first to show that cWT1is involved in IgAN and appears as an independent variable for worse prognosis.

Pathological Accuracy in Prostate Cancer: Single-Center Outcomes of 3 Different Magnetic Resonance Imaging-Targeted Biopsy Techniques and Random Systematic Biopsy.

OBJECTIVE: The aim of this study is to compare systematic, cognitive fusion, in-bore, and software fusion prostate biopsies regarding rates of and risk factors for pathological upgrading. MATERIAL AND METHODS: Charts of 291 patients with systematic biopsy (n = 105), magnetic resonance imaging- targeted cognitive fusion (n = 58), in-bore (n = 68), and software fusion biopsy (n = 60), and who subsequently underwent radical prostatectomy were retrospectively evaluated. The degree of similarity between the grade groups reported in the biopsy and radical prostatectomy pathology results was recorded. Analyses of the associated factors for concordance and discordance were performed with univariate and multivariate methods. RESULTS: The concordance rates were as follows: systematic biopsy = 42.8%, cognitive fusion-targeted biopsy = 50%, in-bore fusion-targeted biopsy = 61.8, and software fusion biopsy = 58.4%. The upgrade rate of systematic biopsy (46.6%) was higher than cognitive fusion-targeted biopsy (27.6%), in-bore fusiontargeted biopsy (26.4%), and software fusion-targeted biopsy (18.3%). The number of positive cores was significantly associated with grade group concordance for the systematic biopsy group (P = .040). Within the cognitive fusion-targeted biopsy cohort, number of positive cores was the only parameter that exhibited a significant association with grade group concordance in multivariate analysis (P = .044). Considering the in-bore fusion-targeted biopsy group, maximum tumor length was statistically significant (P = .021). In the software fusion-targeted biopsy group, low prostate volume was found to be the only significant predictor for grade group accordance (P = .021). CONCLUSION: Magnetic resonance imaging-targeted biopsy techniques showed higher concordance and lower upgrade rates compared to systematic biopsy. For systematic biopsy and cognitive fusion-targeted biopsy, the number of positive cores was associated with grade group concordance, while maximum tumor length in in-bore fusion-targeted biopsy and low prostate volume for in-bore fusion-targeted biopsy were associated with grade group concordance. Among the MRI-targeted biopsy methods, in-bore fusion-targeted biopsy and software fusion-targeted biopsy were more accurate than cognitive fusion-targeted biopsy in terms of grade group.

Pathology associated with adherent perirenal fat and its clinical effect.

INTRODUCTION: The dissection of perirenal fat is of critical importance to kidney surgery and ease of dissection is more important when using minimally invasive approaches. This study aimed to determine the clinical, radiological, and pathological significance of adherent perirenal fat (APF). MATERIALS AND METHODS: This prospective study included 22 patients scheduled for partial nephrectomy and 40 patients for donor nephrectomy. Intraoperative fat dissection time was recorded, and the complexity of perirenal fat dissection was surgeon-classified as easy, moderate, and difficult. Perirenal fat and subcutaneous fat thickness were measured. Measurement of perirenal fat depth and the Hounsfield unit (HU) for both perirenal and subcutaneous fields were performed using computed tomography (CT) images. All specimens were submitted for histopatological analysis. Researchers in each arm were blinded to other researchers' data. RESULTS: Mean age of the patients was 51.3 ± 12.7 years. Mean perirenal fat dissection time was 15.0 ± 13.5 minutes. Patient demographics, BMI, nor occupational status differed between the 3 complexity of perirenal fat dissection groups. Radiological findings showed that there was a significant correlation between perirenal fat depth and complexity of perirenal fat dissection (P < .05), but not with HU measurements or subcutaneous fat thickness. Surgeon classification of the complexity of perirenal fat dissection was in accordance with the duration of dissection (P < .05). Perinephric fat contained more fibrous tissue in the patients with histologically proven APF than in those without (P < .05). CONCLUSIONS: APF is a challenge during kidney surgery. Difficult dissection prolongs the duration of perirenal fat dissection and surgery. Perirenal fat thickness measured via preoperative CT might be used to predict APF.

Diagnostic ability of Ga-68 PSMA PET to detect dominant and non-dominant tumors, upgrading and adverse pathology in patients with PIRADS 4-5 index lesions undergoing radical prostatectomy.

BACKGROUND: To evaluate the additive role of Ga-68 PSMA PET as a primary staging tool in patients bearing prostate cancer in single PIRADS 4 or 5 index lesions. METHODS: Eighty-one biopsy-naive patients with preoperative mpMRI and Ga-68 PSMA PET who underwent radical prostatectomy (RP) were evaluated retrospectively. Forty-nine patients had PIRADS 4 and 32 had PIRADS 5 index lesions. The localization, grade, and volumetric properties of dominant (DT) and non-dominant tumors (NDT) in RP were compared to the index lesions of mpMRI and Ga-68 PSMA PET. RESULTS: The median age and PSA level were 62 (IQR; 59-69) years and 7 (IQR; 2-8) ng/ml, respectively. Ga-68 PSMA PET detected DTs in 100% of the patients including 13 patients in whom mpMR failed. In 45 patients an NDT was reported in RP. Ga-68 PSMA PET accurately detected NDT in 24 of 45 (53.3%) patients. Six patients (12.2%) in PIRADS 4 and 8 (25%) in PIRADS 5 group showed upgrading. In PIRADS 4, Ga-68 PSMA PET localized DT in all patients with upgraded tumors whereas mpMRI missed exact location in 2 of 6 (33.3%). In PIRADS 5 both mpMRI and Ga-68 PSMA PET accurately located all DTs. Overall detection rates of extracapsular extension (ECE) and seminal vesicle invasion (SVI) by mpMRI were 51.1% and 53.8%, respectively. Ga-68 PSMA PET detected ECE and SVI in 27.9% and 30.7%, respectively. When mpMRI and Ga-68 PSMA PET were used in combination detection rates of ECE and SVI increased to 65.1 and 61.5%. Ga-68 PSMA PET-detected six of ten patients with positive lymph nodes whereas mpMRI could not identify any. CONCLUSIONS: Ga-68 PSMA PET has a better diagnostic accuracy in detecting DT, NDT, upgrading, adverse pathology in patients with PIRADS 4 index lesions. However, mpMRI better predicted ECE and SVI than Ga-68 PSMA PET.

Secukinumab may be remedy for systemic amyloidosis findings secondary to hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory disease of follicular epithelium; many comorbidities occur that disrupt the quality of life of patients. Amyloidosis is one of them. We present a case with systemic amyloidosis secondary to HS and responding positively to secukinumab therapy. Secukinumab may also be an important option for amyloidosis findings in HS patients.

Desmoplastic small round cell tumor of the kidney: a case report.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive neoplasm seen in children and young adults, usually manifested by involvement of abdominal serosa. Here, we present an unusual case of primary DSRCT of kidney. CASE PRESENTATION: The patient was an 8-year-old girl with a large renal mass which was confused with primitive neuroectodermal tumor (PNET) in the needle biopsy. The tumor had a variegated histology revealing frequent pseudo-rosette formations, pseudopapillary architecture, rhabdoid, clear or pleomorphic cells in addition to typical small round cell morphology and desmoplasia. It showed immunohistochemical features of DSRCT, and EWSR1 re-arrangement. CONCLUSIONS: Proffering this diagnosis is particularly difficult for tumors of viscera because of the incognizance of the entity in these locations. Moreover, DSRCT is a great mimicker and may get easily confused with more common kidney malignancies of childhood such as Wilms tumor, PNET/EWS, rhabdoid tumor, clear cell sarcoma, and other small round cell tumors as well as renal cell carcinomas. The distinction is critical as the accurate therapeutic approach will require correct diagnosis.

Squamous cell carcinoma of the penis: a clinicopathological study from a population with late circumcision.

Squamous cell carcinoma (SCC) of the penis has been subject to only a few studies in populations where late childhood circumcision is performed. To asses clinicopathological features and human papillomavirus (HPV) status of penile SCC in men with late circumcision, eight institutions in the country volunteered to collaborate and 15 cases of penile SCC were collected from their pathology archives. The presence and genotype of HPV were determined in addition to clinicopathological features of the tumors. Findings were correlated with disease outcome. The mean age of the patients evaluated was 66.5 years. Histological subtypes were usual SCC (6∕15), papillary (2∕15), mixed (2∕15), basaloid (2∕15), acantholytic (1∕15), pseudohyperplastic (1∕15), and warty-basaloid (1∕15) carcinomas. HPV was identified in 33.3% of samples; HPV16 was detected in 60% of positive cases and was associated with basaloid and/or warty morphology. Cause-specific 1-year and 2-year survivals were 76.9% and 54.5%, respectively. The usual subtype and nodal metastasis were associated with worse outcome (p=0.045 and p=0.047, respectively). As a conclusion, our results suggest an inclination for penile SCC to develop at a later age in a population with late circumcision than the patients from the regions of high penile cancer incidence. These men seem to have less frequent HPV association and their outcome appears poorer than other populations, although reaching substantial provision is not possible due to our limited case number.

Massive Localized Lymphedema in an Unreported Location (Retroperitoneum).

BACKGROUND: Massive localized lymphedema (MLL) is a non-neoplastic benign soft tissue lesion that may be confused with sarcomas or other neoplastic proliferations both clinically and morphologically. Most occur in morbidly obese adults on the lower extremities. The objective of this article is to document a case of MLL in the retroperitoneal cavity which is a previously unreported site for this lesion, and to highlight its unusual clinical features. CASE PRESENTATION: The patient was a non-obese male who had undergone major abdominal surgery due to bladder extrophy 17 years ago. Abdominal ultrasonography detected a large incidental mass in the right renal sinus during his investigation for nephrolithiasis. The lesion extending from renal pelvis down to pelvis was resected and its histopathological findings were compatible with massive localized lymphedema. CONCLUSIONS: Retroperitoneum has to be added to the list of locations that MLL can be found. Liposarcoma will be a challenging differential diagnosis when the lesion is encountered in an unusual site.

Reduced immunohistochemical PTEN staining is associated with higher progression rate and recurrence episodes in non-invasive low-grade papillary urothelial carcinoma of the bladder.

Non-invasive low-grade papillary urothelial carcinoma (NILGPUC) of the bladder is regarded as a relatively indolent disease. However, its propensity for frequent recurrences constitutes a major clinical problem. Additionally, there is a progression risk of 10-15% to either a higher grade and/or a higher stage disease in these tumors. The molecular factors that will predict recurrence and progression in low-grade pTa bladder carcinoma have not yet been elucidated. Herein, we investigated the association of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) alterations with recurrence and progression in NILGPUC using immunohistochemistry. Eighty-one cases of bladder cancer initially diagnosed as NILGPUC in a single institution with follow-up were encountered after searching medical records. Tissue microarrays (TMA) that contained both tumor and non-neoplastic mucosa from each case were constructed using paraffin blocks of transurethral resections. Sections from TMA blocks were stained immunohistochemically for PTEN protein and were evaluable in 76 cases. Any absence of staining was recorded and correlated with clinical findings. Ten patients (13.2%) showed progression and 41 (53.9%) showed recurrence. Reduced PTEN expression was observed in 29 cases (38.1%). Cases with reduced PTEN had higher progression rate compared to cases with intact PTEN (p = 0.026). Tumor relapse was more frequent in cases with reduced PTEN (65.5 vs 46.8%), but this difference was not statistically significant (p = 0.112). On the other hand, decreased PTEN expression was associated with higher number of recurrence episodes (p = 0.002). PTEN seems to have a link with the disease course in NILGPUC of the bladder.

Chronic levetiracetam decreases hippocampal and testicular aromatase expression in normal but not kainic acid-induced experimental model of acute seizures in rats.

Reproductive disorders are more common in men with epilepsy taking anticonvulsant medications. Antiseizure/anticonvulsant drugs and seizures in medial temporal lobe structures may cause gonadal dysfunction, including infertility, decreased libido, and potency. Levels of circulating bioavailable testosterone are affected by the aromatase enzyme, which converts testosterone into estrogen and may be affected by seizure medications. However, the relationship of anticonvulsant drugs with central aromatase levels is not clear. This study investigated the possible effects of the highly efficient, new-generation antiseizure/anticonvulsant drug levetiracetam on central and gonadal aromatase expression and gonadal tissue functionality at 27 and 54 mg/kg/day doses. Epileptogenesis was generated in male Wistar rats by an intraperitoneal injection of the excitotoxic agent kainic acid. Aromatase levels were 1.5 times higher in the brain cortex of the kainic acid groups after 4 weeks and the hippocampus after 4 and 8 weeks compared with the controls. Decreased basal aromatase levels were observed after 1 week of levetiracetam treatment (27 mg/kg/day). Administration of 27 mg/kg/day levetiracetam did not alter vas deferens contractions at 1, 4, or 8 weeks compared with the controls. No histological changes were observed in the vas deferens, epididymis, or testis after 8 weeks of levetiracetam administration at both doses. Administration of 27 and 54 mg/kg/day levetiracetam downregulated testis aromatase expression at 8 weeks compared with the controls. These results suggest that levetiracetam decreases aromatase levels in the testis and increases the seizure threshold by a possible decrease in systemic estradiol levels.

The Influence of Inverted Growth Pattern on Recurrence for Patients with Non-Invasive Low Grade Papillary Urothelial Carcinoma of Bladder.

AIMS: To evaluate the impact of a histologically inverted pattern on recurrence in patients with newly diagnosed non-invasive, low-grade papillary urothelial carcinoma of the urinary bladder. METHODS: A total of 81 patients with primary bladder non-invasive, low-grade papillary urothelial carcinoma diagnosed in a single tertiary-care centre who had at least 1-year follow-up after an initial resection were included. All slides from each case were reviewed to determine the growth pattern (exophytic versus endophytic, i.e. inverted) and other histological parameters. Clinical data were retrieved from hospital records. RESULTS: Disease recurrence occurred in 41 (50.6%) patients. Cases with an inverted pattern showed a lower recurrence rate than those with pure exophytic tumours (37.5% versus 52.1%), a longer time to first recurrence (mean 34 versus 21.5 months) and fewer recurrence episodes (p=0.482, 0.564 and 0.051, respectively). All recurring inverted cases recurred only once during follow-up. No tumour with >80% inverted architecture recurred. CONCLUSION: Our results suggest that non-invasive, low-grade papillary urothelial carcinoma of the bladder tends to have a better outcome in terms of disease recurrence if it shows an inverted growth pattern. To indicate the presence and percentage of the inverted pattern in low-grade urothelial carcinomas in the pathology report might be considered as an adjunct to help long-term patient management.

Primary malignant melanoma of the urinary bladder: clinical, morphological, and molecular analysis of five cases.

The aim of our study was to evaluate the clinical and morphological features of primary malignant melanomas of the urinary bladder. We obtained information on five such cases from three different institutions. These were three men and two women between 52 and 76 years of age. Three tumors presented with hematuria, one with dysuria, and one was discovered incidentally on imaging studies. All were invasive to muscularis propria on transuretral resections performed for diagnosis. Neoplastic cells showed variable patterns (large cell epithelioid, small cell diffuse, storiform, or mixed) in different tumors. Pigmentation was prominent in all except one case. Each case was labeled diffusely for S-100, HMB-45, and Melan-A. Pan-cytokeratin showed a perinuclear dot-like reaction in two tumors. Three cases showed the BRAF mutation in molecular studies. Two patients were already metastatic at the time of diagnosis. Two patients died, one is alive with disease after 15 months, and two patients are disease free at 1 and 5 years of surveillance.

Primary sclerosing epithelioid fibrosarcoma of kidney with variant histomorphologic features: report of 2 cases and review of the literature.

The authors present two cases of primary sclerosing epithelioid fibrosarcoma (SEF) of the kidney. Both patients had a mass in the upper part of the left kidney without any primary extrarenal neoplastic lesions. Grossly, the tumors were solid masses both measuring 7.5 cm in the greatest diameter. Histologically, one of the lesions exhibited a predominantly lobular growth of round or oval small uniform epithelioid cells in variable cellularity. Circular zones of crowded tumor cells alternating with hypocellular collagenous tissue in a concentric fashion around entrapped native renal tubules were distinctive. The second case was distinctive with significant cytological atypia in the neoplastic cells and prominent reactive proliferations in the trapped renal tubules. Immunohistochemically, vimentin, bcl-2 and MUC4 were diffusely positive in both. They were negative for S-100 protein, CD34, and desmin, whereas CD99 were positive in one lesion. Fluorescence in situ hybridization assay using dual staining probes detected EWSR1-CREB3L1 fusion in each lesion, which is characteristic molecular findings of SEF. One patient presented widespread distant metastases at the time of diagnosis. In the other, no tumor deposits were detected other than primary. Both patients have been alive with 30 and 10 month follow-ups, respectively. These tumors are 6th and 7th cases of primary renal SEF in the literature confirmed by FISH study, which exhibit unique and remarkable histomorphologic features.

An atypical case of anti-GBM antibody disease with renal function deterioration from normal to end stage renal disease

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Pauci-immune necrotizing crescentic glomerulonephritis with crescentic and full moon extracapillary proliferation: clinico-pathologic correlation and follow-up study.

The prognostic value of the type and extent of extracapillary proliferation (ECP) in pauci-immune necrotizing crescentic glomerulonephitis (PIGN) was evaluated in this study. In 141 PIGN cases, all glomeruli with ECP were grouped according to type (cellular, fibrocellular and fibrous) and extent of the lesions in Bowman's space; (segmental, semicircumferential and circumferential, which might be termed full moon-FM). Cases with cellular and fibrous lesions involving ≥ 50% of glomeruli with ECP were classified as cellular and fibrous groups, respectively, while the remaining cases were classified as fibrocellular. Cases with segmental and circumferential (FM glomerulus) lesions involving ≥ 50% of glomeruli with ECP were classified as ECPI and ECPIII (FM) groups, respectively, while the rest were classified as ECPII. All the cases were classified according to Berden et al. Significant results were only nearly obtained for the FM group, including the need for dialysis. The Cox regression model revealed a 2.6-fold risk for FM cases regarding dialysis requirement. We propose that the percentage of FM glomeruli should be noted in the pathology report, and cases with more than 50% of FM glomeruli (FM group) should be identified in the group with increased risk of dialysis requirement. Our series also suggests that classification according to Berden et al. is of clinical relevance.

A case of familial glomerulopathy with fibronectin deposits caused by the Y973C mutation in fibronectin.

Glomerulopathy with fibronectin deposits is a rare hereditary kidney disease characterized by the extensive deposition of fibronectin in glomeruli, particularly in mesangial regions and subendothelial zones. Prognostically, the disease is known as slowly progressive, leading to kidney failure in most cases. We recently diagnosed glomerulopathy with fibronectin deposits in a 24-year-old man in whom proteinuria was detected incidentally. Genetic analysis of the fibronectin 1 (FN1) gene showed heterozygosity for the Y973C mutation. The same mutation was found in his elder brother, who similarly experienced proteinuria. Both patients had normal kidney function but persistent proteinuria after 30 months and 11 years of follow-up, respectively.