Sarcoidosis-associated renal AA amyloidosis and crescentic necrotizing glomerulonephritis.

Sarcoidosis has a rare and independent association with renal AA amyloidosis and crescentic necrotizing glomerulonephritis. However, coexisting entities in sarcoidosis have not been previously described. Herein, we report a 66-year-old Caucasian woman who presented with generalized fatigue, weight loss, and acute kidney injury in the setting of likely sarcoidosis. Renal biopsy revealed AA amyloid fibrils with fibrocellular crescents. The patient's clinical symptoms and laboratory results improved with high-dose glucocorticoids and azathioprine.

Histologic acute graft pyelonephritis after kidney transplantation: Incidence, clinical characteristics, risk factors, and association with graft loss.

BACKGROUND: Histologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known. METHODS: We performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution. We compared the HAGPN cases to a randomly selected control group of KTs to identify risk factors using univariate and multivariate Cox regression models. The association between HAGPN and graft loss was also assessed, similarly. RESULTS: HAGPN was identified in 46 of 1391 patients (cumulative incidence, 5% [95% CI, 3%-7%]) undergoing KT at a single center from January 2008 through December 2017 (median time to diagnosis, 241 days after KT; interquartile range, 122-755 days). Indications for biopsy were follow-up of treated rejection (n = 20 [43%]), KT protocol biopsy (n = 19 [41%]), and acute kidney injury (n = 7 [15%]). Histologic rejection, UTI, and asymptomatic bacteriuria (ASB) were present in 23 (50%), 9 (20%), and 16 (35%). Multivariate Cox proportional hazards models comparing KT recipients with or without HAGPN (n = 46 and n = 138, respectively) showed that HAGPN was associated with urologic complication by day 30, delayed graft function, previous UTI or ASB, and a history of rejection. In the univariate and multivariate analyses, HAGPN was associated with an increased risk of graft loss. CONCLUSION: HAGPN is an infrequent, unanticipated, and clinically significant complication of KT.

Mucinous Tubular and Spindle Cell Carcinoma of the Kidney with Nodal Metastasis Managed with Surgical Resection.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal malignancy that usually follows an indolent course. The few existing reports of metastatic MTSCC show poor response to systemic therapy. Here we describe the unusual case of a 39-yr-old male with MTSCC presenting as a large renal mass with bulky retroperitoneal lymphadenopathy managed with complete resection of disease. He has remained free of recurrence for 1 yr postoperatively. On the basis of the experience reported here, aggressive surgical resection of MTSCC with isolated nodal metastases may be considered for similar patients in the future given the historically poor response rates to systemic therapy.

Fibrillary glomerulonephritis or complement 3 glomerulopathy: a rare case of diffuse necrotising crescentic glomerulonephritis with C3-dominant glomerular deposition and positive DNAJB9.

Fibrillary glomerulonephritis (FGN) and complement 3 glomerulopathy (C3G) are rare forms of glomerulonephritis with distinct aetiologies. Both FGN and C3G can present with nephritic syndrome. FGN is associated with autoimmune disease, dysproteinaemia, malignancy and hepatitis C infection. C3G is caused by the unregulated activation of the alternative complement pathway. We present a rare case of diffuse necrotising crescentic glomerulonephritis with dominant C3 glomerular staining on immunofluorescence-consistent with C3G-but electron microscopy (EM) findings of randomly oriented fibrils with a mean diameter of 14 nm and positive immunohistochemistry for DNAJB9-suggestive of FGN. To the best of our knowledge, this is the first reported case of FGN to show dominant C3 glomerular deposits. This case report reaffirms the utility of EM in the evaluation of nephritic syndrome and highlights the value of DNAJB9-a novel biomarker with a sensitivity and specificity near 100% for FGN.

Prosthetic valve endocarditis from Mycobacterium chimaera infection causing granulomatous interstitial nephritis.

Mycobacterium chimaera is a rare infection associated with cardiopulmonary bypass. We describe a case of granulomatous interstitial nephritis caused by M. chimaera in a patient with prosthetic aortic valve endocarditis. A 63-year-old female with a mechanical aortic valve replacement developed fatigue, 20 lbs. weight loss, anemia, and an elevated creatinine. Fat pad aspirate at an outside hospital was suspicious for amyloidosis which prompted hematology referral at our institution. Bone marrow biopsy revealed a single granuloma, negative for amyloid or acid fast bacillus (AFB). She was admitted to our hospital for worsening kidney function refractory to intravenous fluid challenge. Transesophageal echocardiogram showed aortic root abscess and valve vegetation with negative blood cultures at seven days. Renal biopsy showed granulomatous interstitial nephritis and negative AFB stain. Prednisone 40 mg was started and renal function partially improved. Blood cultures obtained before biopsy subsequently grew M. chimaera. Three-drug antimicrobial therapy was initiated and prednisone discontinued. One month later, creatinine improved and follow up echocardiogram showed no lesion. Our case highlights this rare infection inducing granulomatous interstitial nephritis despite lack of positive AFB or gram stains on renal biopsy.

Arterial Blood Pressure at Liver Transplant Evaluation Predicts Renal Histology in Candidates With Renal Dysfunction.

Renal dysfunction is common in liver transplantation (LT) candidates, but differentiating between reversible and irreversible renal injury can be difficult. Kidney biopsy might be helpful in differentiating reversible from irreversible renal injury, but it is associated with significant complications. We aimed to identify pre-LT predictors of potentially reversible renal injury using histological information obtained on pre-LT renal biopsy. Data on 128 LT candidates who underwent pre-LT kidney biopsy were retrospectively collected and correlated with renal histological findings. Indications for kidney biopsy were iothalamate glomerular filtration rate (iGFR) ≤40 mL/minute, proteinuria >500 mg/day, and/or hematuria. According to the biopsy diagnosis, patients were grouped into the following categories: normal (n = 13); acute tubular necrosis (ATN; n = 25); membranoproliferative glomerulonephritis (n = 19); minimal histological changes (n = 24); and advanced interstitial fibrosis (IF) and glomerulosclerosis (GS) (n = 47). Compared with patients having advanced IF/GS, patients with normal biopsies and those with ATN had lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) and higher international normalized ratio and total bilirubin levels (<0.05 for all). Both SBP and DBP directly correlated with the degree of IF and GS (R = 0.3, P ≤ 0.02 for all). SBP ≤90 mm Hg was 100% sensitive and 98% specific in correlating with normal biopsies or ATN, whereas SBP ≥140 mm Hg was 22% sensitive and 90% specific in correlating with advanced IF/GS. Model for End-Stage Liver Disease score, serum creatinine, iGFR, urinary sodium excretion, and renal size did not correlate with biopsy diagnosis or degree of IF or GS. In conclusion, SBP at the time of LT evaluation correlates with renal histology, and it should be included along with other clinical and laboratory markers in the decision-making process to list patients with renal dysfunction for LT alone versus simultaneous liver-kidney transplantation.

Cystic Fibrosis-Associated Liver Disease in Lung Transplant Recipients.

Cystic fibrosis (CF) is an autosomal recessive disease characterized by mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator protein (CFTR). CFTR gene mutations manifest as epithelial cell dysfunction in the airways, biliary tract, pancreas, gut, sweat glands, paranasal sinuses, and genitourinary tract. The clinical manifestations of this dysfunction include respiratory tract infections, bronchiectasis, pancreatic insufficiency, malabsorption, intestinal obstruction, liver disease, and male infertility. The liver disease manifestations of CF can include biliary disease, multilobular cirrhosis, and portal hypertension with and without cirrhosis. Pulmonary disease is the main cause for morbidity and mortality in individuals with CF, and according to the International Society for Heart and Lung Transplantation, CF is the third most common indication for lung transplantation in adults, accounting for 16% of procedures performed. The survival after lung transplantation in individuals with CF continues to improve and is now the highest among end-stage lung diseases requiring transplant. The survival rate at 10 years is close to 50%. Given the potential presence of liver disease in CF patients undergoing an evaluation for lung transplantation and in lung transplant recipients, it is important to understand the manifestations of liver disease in CF patients and the recommended workup and follow-up. This review aims to discuss the current literature and provide guidance in the management of these patients.

A novel variant in FN1 in a family with fibronectin glomerulopathy.

Glomerulopathy with fibronectin deposits (GFND) is a rare glomerular disorder. We report a 28-year-old male diagnosed with GFND by mass spectrometry on kidney biopsy tissue. Whole-exome sequencing (WES) identified that a previously undescribed FN1 gene mutation (c.3051G > T, p.W1017C) was likely responsible for this patient's fibronectin glomerulopathy. We discuss the implications of this novel variant of FN1 and the importance of WES to identify a mutation in a gene of interest.

Karyomegalic interstitial nephritis in a renal allograft.

Karyomegalic interstitial nephritis (KIN) is a rare renal interstitial disease entity characterized by large tubular nuclei, accompanied by interstitial inflammation, tubular atrophy, and interstitial fibrosis. Approximately 50 cases of KIN have been described in the native kidney. In this case study, we describe the first case of KIN in a kidney allograft. A 41-year-old man presented with declining kidney function and a serum creatinine of 2.7 mg/dL. The native kidney biopsy showed large pleomorphic nuclei in the proximal and distal tubular epithelial cells, which was associated with interstitial inflammation, and extensive interstitial fibrosis and tubular atrophy. Immunohistochemistry for cytomegalovirus, adenovirus, and simian virus 40 were negative. A diagnosis of KIN was rendered. The patient received a living-related kidney transplant from his sister. At 4-, 12-, and 24-months posttransplant, protocol allograft biopsies showed KIN with large pleomorphic nuclei in the proximal and distal tubules with mild interstitial inflammation, minimal tubular atrophy, and interstitial fibrosis. At 24.7 months of follow-up, the patient has stable renal function with a serum creatinine of 1.6 mg/dL. The KIN may represent recurrent KIN or donor-associated KIN. Recognition of this rare disease entity is important as it can be mistaken for a viral infection.

A method to reduce variability in scoring antibody-mediated rejection in renal allografts: implications for clinical trials - a retrospective study.

Poor reproducibility in scoring antibody-mediated rejection (ABMR) using the Banff criteria might limit the use of histology in clinical trials. We evaluated the reproducibility of Banff scoring of 67 biopsies by six renal pathologists at three institutions. Agreement by any two pathologists was poor: 44.8-65.7% for glomerulitis, 44.8-67.2% for peritubular capillaritis, and 53.7-80.6% for chronic glomerulopathy (cg). All pathologists agreed on cg0 (n = 20) and cg3 (n = 9) cases, however, many disagreed on scores of cg1 or cg2. The range for the incidence of composite diagnoses by individual pathologists was: 16.4-22.4% for no ABMR; 17.9-47.8% for active ABMR; and 35.8-59.7% for chronic, active antibody-mediated rejection (cABMR). A "majority rules" approach was then tested in which the scores of three pathologists were used to reach an agreement. This increased consensus both for individual scores (ex. 67.2-77.6% for cg) and for composite diagnoses (ex. 74.6-86.6% cABMR). Modeling using these results showed that differences in individual scoring could affect the outcome assessment in a mock study of cABMR. We conclude that the Banff schema has high variability and a majority rules approach could be used to adjudicate differences between pathologists and reduce variability in scoring in clinical trials.

Behçet's syndrome and focal segmental glomerulosclerosis with nephrotic syndrome - successful treatment with etanercept
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Behçet's syndrome (BS) often presents with aphthous and genital ulcers, uveitis, and erythema nodosum. Renal involvement has been reported with most cases presenting with renal amyloidosis, IgA nephropathy, or crescentic glomerulonephritis. We describe a case of a 49-year-old woman with relapsing BS symptoms coinciding with new-onset development of nephrotic syndrome. Renal biopsy showed focal segmental glomerulosclerosis (FSGS) that was treated with prednisone and etanercept for BS therapy. Both proteinuria and BS symptoms responded to treatment with complete remission. To our knowledge, our report is the first to show evidence of a possible connection between BS and FSGS and discusses the pathophysiologic mechanism that explains this link.
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Primary synovial sarcoma of the kidney-A case report and literature review.

Primary synovial sarcoma of the kidney is a very rare spindle cell neoplasm that occasionally displays epithelial differentiation. It occurs between 15-60 years of age with a mean of 35 years and a slight male predilection. Most of synovial sarcomas appear as relatively nonspecific soft tissue masses involving the kidney. This rare entity has some overlapping morphologic and immunohistochemical characteristics with other more common renal spindle cell neoplasms. Molecular tools add valuable diagnostic confirmation. We report a 56 year old male who presented to the emergency department with hematuria and abdominal pain. He had an abdominal CT-scan which showed a 6.6 cm enhancing right renal mass. Morphologic and immunohistochemical studies were directed towards synovial sarcoma with confirmation by SYT-SSX gene fusion using RT-PCR molecular technique. We reviewed the literature on the epidemiologic, histologic spectrum, immunophenotypic, clinical significance and prognosis and therapy.

Criteria for Risk Stratification of Vulvar and Vaginal Smooth Muscle Tumors: An Evaluation of 71 Cases Comparing Proposed Classification Systems.

Accurate risk stratification of smooth muscle tumors (SMTs) is essential for appropriate patient management. Yet, the rarity of SMTs of the vagina and vulva makes development of a prognostically meaningful classification system challenging. While 2 classification methods for vulvar SMTs and 1 for vaginal SMTs have been proposed, it is our experience that many pathologists tend to apply criteria for uterine SMTs when evaluating vulvovaginal tumors. We retrospectively reviewed a large cohort of vulvovaginal SMTs with clinical follow-up and evaluated which method most accurately classified tumors according to patient outcome. A total of 71 tumors, 53 vaginal (75%) and 18 vulvar (25%), from 71 patients were identified. All tumors were centrally examined for degree of cytologic atypia, morphology (spindled, epithelioid, myxoid), mitotic index per 10 high power fields, atypical mitotic figures, tumor cell necrosis, ischemic necrosis, tumor interface (circumscribed or infiltrative) and margin status. Clinical features were recorded for each patient. Follow-up was available for 63 patients (89%), and ranged from 1 to 234 months (median: 64 mo). While site-specific and uterine criteria showed equally excellent sensitivity in classifying smooth muscle neoplasms as leiomyosarcoma according to patient outcome, uterine criteria showed improved specificity relatively to site-specific methods in classifying tumors as nonsarcoma according to patient outcome. We recommend that uterine SMT criteria and nomenclature be adopted for evaluation and classification of vulvovaginal SMTs.

Recurrent myxoinflammatory fibroblastic sarcoma: a case report.

Myxoinflammatory fibroblastic sarcoma is a rare sarcoma which typically presents in the extremities and is treated by definitive surgery. In recurrent disease, the reported utilization of radiotherapy is increasing, and more modern techniques such as intensity-modulated radiotherapy may be improving long-term outcomes.

Langerhan's Cell Sarcoma: Two Case Reports.

Langerhan's cell sarcoma (LCS) is a rare neoplasm with a poor prognosis. To our knowledge, only sixty-six cases have been published. We discuss two patients who presented very differently with LCS, as well as a recently published review of all sixty-six cases. Our first case had a complicated history of metastatic, high-grade myxofibrosarcomas and presented with a single skin lesion of LCS which was treated with resection to a positive margin and adjuvant radiotherapy. The LCS recurred locoregionally and was again resected. The patient is alive two years after initial diagnosis. The second case presented with bone marrow and splenic involvement, leukocytosis, and thrombocytopenia. This patient had an excellent response to etoposide, prednisone, oncovorin, cyclophosphamide, and adriamycin, with normalization of the complete blood count, negative bone marrow biopsy at follow up, and splenectomy without viable neoplasm. This patient is alive without signs of disease at 16 months after initial diagnosis.

Tumor induced osteomalacia secondary to anaplastic thyroid carcinoma: A case report and review of the literature.

CONTEXT: Tumor induced osteomalacia related to anaplastic thyroid cancer has never been reported. OBJECTIVE: We describe a case of tumor induced osteomalacia (TIO) in a patient with a fibroblast growth factor 23 (FGF-23) secreting anaplastic thyroid carcinoma. The current imaging modalities are reviewed. DESIGN AND INTERVENTION: Clinical, biochemical, and radiological assessments were done, including computer tomography (CT) of the neck and skull to thigh positron emission tomography (PET)/CT. The patient underwent surgical tumor debulking three days after presentation due to airway compromise. Molecular studies of the resected tissue were performed using reverse transcriptase-polymerase chain reaction (RT-PCR) and gel electrophoresis for the phosphaturic mesenchymal tumor FGF-23. RESULTS: Resected tissue demonstrated features of anaplastic thyroid cancer with positive markers for FGF-23 protein, consistent with a FGF-23 secreting paraneoplastic tumor. The patient's metastatic burden rapidly progressed as demonstrated by a dramatic rise in serum FGF-23 levels and worsening hypophosphatemia in concert with progression of the metastatic lesions on PET/CT. CONCLUSION: We believe that our patient's rapidly progressive anaplastic thyroid cancer was responsible for persistent hypophosphatemia and osteomalacia, substantiated by the finding of FGF-23 protein within the thyroid tumor cells. Our case indicates that anaplastic thyroid cancer can cause TIO.

Clinical Activity of Pazopanib in Metastatic Extraosseous Ewing Sarcoma.

We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371). This national multi-institutional study is ongoing.

Trisacryl Gelatin Microembolism and Metastases in the Lung after Renal Artery Embolization and Nephrectomy for Renal Cell Carcinoma.

This is the first report, to our knowledge, of widespread, histologically confirmed trisacryl gelatin pulmonary microembolism after renal artery embolization (RAE). In addition, this is the first report of lung involvement by both metastatic renal cell carcinoma (RCC) and an embolic agent used for RAE. The patient was a 63-year-old woman who recently presented with both dyspnea on exertion and productive cough. Her past medical history included clear cell RCC, which was treated with preoperative trisacryl gelatin microsphere RAE and right nephrectomy 9 years earlier. Computed tomography of the chest showed multiple lung nodules, a mass-like density in the left lower lobe, and mediastinal and hilar lymphadenopathy. Wedge resections of the lung showed multiple foci of metastatic RCC and extensive involvement of the muscular pulmonary arteries by trisacryl gelatin microspheres.

Renal outcomes of liver transplant recipients who had pretransplant kidney biopsy.

BACKGROUND: Kidney biopsy has been recommended to guide kidney allocation in selected liver transplant (LT) candidates with renal dysfunction. However, post-LT-alone renal outcomes in recipients who showed evidence of reversible renal injury and limited chronicity on pre-LT kidney biopsy are unclear. METHODS: Renal outcomes of 41 LT recipients who had pre-LT kidney biopsy for unexplained renal dysfunction, proteinuria, and hematuria were retrospectively reviewed. All biopsies showed less than 30% interstitial fibrosis and less than 30% to 40% glomerulosclerosis. Study endpoints were renal replacement therapy (RRT) at 1 month and the need for kidney transplantation at 1 year from LT. RESULTS: Six patients were on RRT at time of biopsy. Median (range) iothalamate glomerular filtration rate and 24-hr urinary protein excretion for the remaining 35 patients were 29 (6-88) mL/min per 1.73 m(2) and 65 (0-4,338) mg/day, respectively. Glomerulonephritis and acute tubular necrosis were present in 28 (68%) and 16 (39%) of the cases. Six patients (15%) did not recover kidney function at 1 month and RRT at time of LT was the only factor associated with this endpoint (P=0.04). Seven of the 31 (22%) patients with 1-year data met criteria for kidney transplantation within the first post-LT year. Surgical re-exploration was the only factor associated with the need for kidney transplantation at 1 year (P=0.05). CONCLUSIONS: The most LT recipients with minimal chronic changes on pre-LT kidney biopsy recovered kidney function within 1 month from LT. A small but significant percentage met criteria for kidney transplantation at 1 year because of the development of unforeseen post-LT complications.