Rare case of aspergillosis with solitary renal involvement: micro-fungus ball in graft kidney.

Kidney transplant recipients are at an increased risk of various infections due to immunosuppressive medications. Among them, fungal infections are associated with high mortality and morbidity. This report presents the case of a 54-year-old kidney-transplant recipient who was diagnosed with aspergillosis with solitary renal involvement. He was diagnosed by kidney biopsy with the micro-fungus ball. In the biopsy sample, consisting mostly of the medulla, a small focus consisting of an aggregate of fungal microorganisms was identified. The micro-fungus ball, which was also present in serial sections, was characterized by slight pigmentation and septate hyphae with acute angle branching, highlighted by the silver stains. The patient was examined for invasive fungal infection. In CT scans, there were no signs of invasive fungal infection. Due to the unexpected kidney biopsy finding, the patient underwent a repeat allograft biopsy from which a culture was sent. Aspergillus fumigatus complex was detected in tissue fungal culture of this repeat biopsy. The patient was started on voriconazole treatment and was successfully treated. It should be kept in mind that fungal infections with isolated subtle renal involvement may be possible in KTR under immunosuppressive treatment without an obvious fungal focus being demonstrated by imaging methods.

Indolent B-cell non-Hodgkin lymphomas in children: high association with inborn errors of immunity.

Indolent lymphomas are rare in children and mostly consist of pediatric type follicular (PTFL) and pediatric marginal zone lymphomas (PMZL) and extranodal marginal zone lymphoma (ENMZL). Twenty children with indolent lymphoma (10 PTFL, 6 PMZL, 3 ENMZL, 1 mixed type) among 307 Non-Hodgkin Lymphoma (NHL) were retrospectively evaluated. The mean age of the entire group was 10.4 ± 4.4 and was significantly lower in PTFL than in PMZL. Seven patients (35%) had an associated inborn error of immunity (IEI) which was higher than that seen in aggressive lymphomas (5.9%) (p < 0.0001). Seventeen patients (85%) had stage I/II disease. Two patients received no treatment after surgery. Eleven patients were treated only with 3-6 courses of rituximab. Four patients received 3-6 courses of R-CHOP protocol. The prognosis was excellent Five years overall and event-free survivals were 100% and 85%, respectively.

Is it Possible to Obtain Immunofluorescence Data in Formalin-Fixed Paraffin-Embedded Skin Samples for the Diagnosis of Pemphigus Vulgaris and Bullous Pemphigoid.

OBJECTIVE: The gold-standard method for assessment of autoimmune bullous disease is direct/indirect immunofluorescence (IF) examination applied to fresh frozen tissue. Since the sensitivity of IF is greatly reduced in formalin-fixed paraffin-embedded (FFPE) tissues, IF cannot be relied upon in these samples. However, immunohistochemistry with the C4d antibody is a promising marker used as a surrogate for immune complex deposition, in nephropathology practice, and the paraffin IF method is also used as a `salvage` technique when fresh frozen tissue is not available or lacks glomeruli. We aimed to investigate whether it is possible to obtain immunofluorescence data from FFPE tissues diagnosed with bullous pemphigoid (BP) and pemphigus vulgaris (PV) and its relationship with inflammatory parameters in the skin. MATERIAL AND METHODS: Eighty-nine in-house cases with both IgG and C3 positivity by routine immunofluorescence examination were included in the study. Inflammation parameters were evaluated in hematoxylin-eosin sections. Immunofluorescence study with IgG protease digestion and C4d immunohistochemistry were performed. RESULTS: Results of 83 biopsies were obtained by paraffin immunofluorescence with IgG. There were positive reactions in 28 (34%) of these 83 biopsies. Five of the 28 positive results belonged to BP (18%), and 23 were PV (82%). Ten positive results were on lesional skin (36%), and 18 (64%) were on non-lesional skin. In the immunohistochemical study with C4d, 84 biopsy results were obtained. There were positive reactions in 34 (40.4%) of 84 biopsies. Of the 34 positive results, 12 belonged to BP (35.3%) and 22 to PV (64.7%). Again, 22 (64.7%) of 34 positive results belonged to lesional skin, and 12 (35.3%) belonged to non-lesional skin. When both techniques were used together, 44 (54%) of 81 biopsies yielded positive results for at least one of the two studies, while in 37 (46%), both tests showed negative results. CONCLUSION: The sensitivity of both IgG and C4d was less than in the literature, especially in BP-diagnosed biopsies. Positive samples were mostly PV. In conclusion, obtaining immunofluorescence data in FFPE samples is possible and is independent of the related skin being lesional or not, however, negative results should not be relied upon.

IgG4-related pachymeningitis-Long term follow up and outcome of six patients.

OBJECTIVE: Our understanding of IgG4-RD and pachymeningitis has grown substantially, but the optimal approach for diagnosis, management, and long-term outcomes is still an area of uncertainty. METHODS: HUVAC is a database for IgG4-RD patients, this database was retrospectively evaluated for pachymeningeal disease. Demographic, clinical, serological, imaging, histopathological data, and treatment details were re-interpreted in patients with pachymeningitis. RESULTS: Among 97 patients with IgG4-RD, 6 (6.2%) had pachymeningitis. None of these patients had extracranial features, and also, in most of the patients, serum IgG4 levels were normal. Tentorium cerebelli and transverse sinus dura were the most commonly involved in the posterior fossa. During 18 months of median follow-up on steroid+-rituximab, none of them relapsed as pachymeningitis. CONCLUSION: Our patients were mainly older males with sole neurological involvement. Non-specific headache was the most common manifestation, and serum IgG4 levels were not useful for diagnosis. Typical radiology and tentorial thickening should suggest IgG4-RD and prompt an early biopsy. Moreover, accompanying hypophysitis could also be a clue. With steroids+ rituximab treatment, no relapse related to meningeal involvement was seen in long-term follow-up.

[Q Fever Endocarditis-Associated Immune Complex-Mediated Proliferative Glomerulonephritis: Fourth Case from Türkiye]. / Q Atesi Endokarditi Iliskili Immün Kompleks Aracili Proliferatif Glomerülonefrit: Türkiye'den Dördüncü Olgu.

Q fever is a zoonosis caused by the intracellular gram-negative bacterium Coxiella burnetii. Infection can be asymptomatic, acute or can cause chronic disease. Chronic disease often presents with infective endocarditis (IE). Diagnosis of IE is difficult because the agent does not grow easily in standard blood cultures and valve vegetations are difficult to detect. Glomerular involvement in patients with Q fever endocarditis is limited to the case reports. In addition, a total of three cases of Q fever endocarditis from Türkiye have been published so far. In this case report, a fourth case of Q fever endocarditis from Türkiye accompanied by immune complex-mediated glomerulonephritis was presented. A 35-year-old male patient with a history of mitral and aortic heart valve replacement was admitted with complaints of fever, night sweats and involuntary weight loss. Cervical lymphadenopathy and hepatosplenomegaly were found during the examination. Laboratory investigations revealed anemia inflammation, acute kidney injury (AKI), hematuria and proteinuria. While no causative agent was detected in blood and urine cultures, no diagnosis could be made as a result of bone marrow and cervical lymph node biopsies.Transesophageal echocardiography was performed for the etiology of fever and revealed 7 mm vegetation on the prosthetic mitral valve. C.burnetii phase 1 IgG tested with indirect immunofluorescent antibody method was reported positive at 1/16384 titer and doxycycline and hydroxychloroquine treatments were initiated. Kidney biopsy for the etiology of AKI revealed focal segmental endocapillary proliferative glomerulonephritis with C3, C1q and IgM immunocomplex deposition. After the addition of methylprednisolone to the treatment, the patient's symptoms improved and creatinine and proteinuria levels decreased dramatically. Although Q fever is endemic in our country, it is detected in fewer numbers than expected. In addition to the difficulties in microbiological and clinical diagnosis, the low awareness of physicians about the disease is one of the important reasons for this situation. When the disease comes to mind, the diagnosis can be easily reached by serological methods. Therefore, Q fever should be investigated in the presence of lymphoproliferative disease-like findings fever of unknown origin and culture-negative endocarditis.

Splenic Gaucheroma Leading to Incidental Diagnosis of Gaucher Disease in a 46-Year-Old Man with a Rare GBA Mutation: A Case Report.

BACKGROUND: Gaucher disease is a common lysosomal storage disease caused by the deficiency of the ß-glucosidase enzyme, leading to sphingolipid accumulation in the reticuloendothelial system in Gaucher cells. Clinical findings are quite variable and some patients may remain asymptomatic lifelong. However, even when patients have mild symptoms, there is a significant increase in their quality of life with enzyme replacement therapy. We aimed to reveal the relationship between a rare mutation in the Glucosylceramidase Beta (GBA) gene and clinical signs and symptoms. Another aim of the study was to show the effect of enzyme replacement therapy on the quality of life, even in patients with mild symptoms. CASE PRESENTATION: Here, we report a 46-year-old male diagnosed with Gaucher disease based on splenic Gaucheromas incidentally discovered in a cardiac computerized tomography scan. In GBA gene analysis, the extremely rare R87W mutation was detected in a homozygous state. In retrospect, the patient had nonspecific symptoms such as fatigue and bone pain for a long time, which were substantially ameliorated by enzyme replacement therapy. CONCLUSION: In patients with adult-onset Gaucher disease, the symptoms may be mild, causing significant diagnostic delay. Gaucher disease may be included in the differential diagnosis of abdominal malignancies. Early diagnosis and treatment can improve quality of life and prevent unnecessary procedures.

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.

Copy Number Loss at Chromosome 14q11.2 Correlates With the Proportion of T Cells in Biopsies and Helps Identify T-Cell Neoplasms.

CONTEXT.­: Evidence of T-cell clonality is often critical in supporting the diagnosis of a T-cell lymphoma. OBJECTIVES.­: To retrospectively explore the significance of copy number losses at the 14q11.2 T-cell receptor α locus in relation to the presence of a T-cell neoplasm and proportion of T cells by targeted next-generation sequencing. DESIGN.­: Targeted next-generation sequencing data from 139 tissue biopsies, including T-cell lymphomas, B-cell lymphomas, classic Hodgkin lymphomas, nonhematopoietic malignancies, and normal samples, were reviewed for copy number losses involving the T-cell receptor α gene segments at chr14q11.2. RESULTS.­: We found that biallelic or homozygous deletion of 14q11.2 was found in most (28 of 33, 84.8%) T-cell lymphomas. The magnitude of 14q11.2 loss showed a statistically significant correlation with the proportion of T cells in lymphoma tissue samples. Copy number losses could also be detected in other lymphomas with high numbers of T cells (8 of 32, 25% of B-cell lymphomas, 4 of 4 classical Hodgkin lymphomas), though biallelic/homozygous deletion of 14q11.2 was not significantly observed outside of T-cell lymphomas. Most nonhematopoietic neoplasms and normal tissues (59 of 64, 92.2%) showed no significant copy number losses involving the T-cell receptor α locus at chr14q11.2. CONCLUSIONS.­: Analysis of copy number losses at the T-cell receptor α locus chr14q11.2 with targeted next-generation sequencing can potentially be used to estimate the proportion of T cells and detect T-cell neoplasms.

Clonal B-cell proliferations developing in the background of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder: A case series.

Clonal B-cell proliferations and B-cell lymphomas may co-occur in the background of follicular helper T-cell (TFH)-derived lymphomas, most associated with EBV, which has been a well-known fact for many years in the prototypical entity "TFH lymphoma, angioimmunoblastic-type." Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+ PCSM-LPD) is also a TFH-derived clonal proliferation. We searched the archives and identified four cases of CD4+ PCSM-LPD with accompanying clonal B-cell proliferation (one of which showed EBER positivity), and one longstanding case of CD4+ PCSM-LPD, in the background of which a B-cell lymphoma had developed. These five cases broaden experience on CD4+ PCSM-LPD with accompanying B-cell proliferations and also support routine evaluation of these cases with EBV in situ hybridization, to better determine whether or not there is an association with EBV.

Indolent T-lymphoblastic proliferation: A systematic review of the literature analyzing the epidemiologic, clinical, and pathologic features of 45 cases.

An indolent T-lymphoblastic proliferation (iT-LBP) is a rare benign disorder characterized by an abnormal expansion of immature T-cells, which morphologically can mimic malignancy. Since the first case was described in 1999, dozens more have been reported in the literature. However, the epidemiologic, clinical, pathologic, and biologic features of this disease have not been well described. Here, we retrospectively reviewed all known cases reported in the literature to better understand this entity. A PubMed search up to January 2022 highlighted 25 papers describing cases/case series of iT-LBP, one of which was a case presentation in a slide workshop. Except for 9 of the cases in one of the papers, where it was evident that the number of CD3+/TdT+ cells were too few to conform with a diagnosis of iT-LBP, all papers and all the cases reported were included in the study amounting to a total of 45 cases. Clinicopathologic characteristics were analyzed using descriptive statistics and frequencies. Our analysis highlighted the previously known association with Castleman disease and Castleman-like features and underlined its association with dendritic cell proliferations in general, as well as uncovering high frequency of concurrence with hepatocellular carcinoma and autoimmune diseases, most notably myasthenia gravis, paraneoplastic pemphigus and paraneoplastic autoimmune multiorgan syndrome. Furthermore, the co-expression of CD4 and CD8 and high prevalence of extranodal disease and recurrences were other less well described features that were revealed.

Comprehensive assessment and outcomes of patients with chronic periaortitis.

OBJECTIVES: Chronic periaortitis (CP) is a less known but more frequently diagnosed fibro-inflammatory disorder, but we know little about it and data regarding follow-up and outcome are still very limited. This study aims to identify the clinicopathologic, laboratory, and radiologic features, as well as outcomes of CP patients. METHODS: Patients with CP from HUVAC database were included in the study. CP was diagnosed based on compatible imaging findings and histopathological evaluation (if available), in addition to clinical findings. Demographics, laboratory, clinical, and imaging data were retrospectively reviewed from medical records. RESULTS: A total of 51 (male/female:37/14) patients were included in the study. Median (IQR) age was 63 (53-69) years and follow-up duration was 40 (4-60) months. 32 of the patients were IgG4-related CP. The most common form of CP in our cohort was idiopathic retroperitoneal fibrosis (82%), followed by inflammatory abdominal aortic aneurysms (12%) and peri-aneurysmal retroperitoneal fibrosis (8%). 8 (15.6%) patients had thoracic periaortitis and 16 (31.6%) venous involvement. Cyclophosphamide (CYC) combined with steroids was the most preferred treatment modality (43%), followed by rituximab (RTX) (31.3%). Follow-up imaging was done after a median (IQR) of 7(3-11) months, 30% of the patients were stable and 64.1% showed regression. A total of 18 (35.2%) had been taken off therapy at the last visit. CONCLUSIONS: Idiopathic retroperitoneal fibrosis was the most frequent presentation, whereas 15.6% of patients had thoracic involvement. Venous involvement was also not uncommon. Optimal time for follow-up imaging was determined as 6-9 months. Steroids along with CYC/RTX had a favourable outcome in the treatment of these patients.

Diffuse Large B-Cell Lymphoma, Epstein-Barr Virus -Positive Kappa Monotypic Plasma Cell Proliferation and Invasive Carcinoma, Developing in a Child With Defective Mismatch Repair.

Constitutional mismatch repair deficiency (CMMRD) syndrome is characterized by biallelic mutations in a mismatch repair gene and is associated with development of childhood cancers and symptoms resembling neurofibromatosis type 1, like café-au-lait spots. We describe the extremely rare case of a 12-year-old male presenting with several light brown macular lesions on the skin, gastrointestinal diffuse large B-cell lymphoma, adenomatous polyposis throughout the gastrointestinal tract and an intra-abdominal invasive carcinoma derived from upper gastrointestinal system. All neoplasia, as well as normal tissues, showed loss of Msh6 expression with immunohistochemistry. Molecular studies showed pathogenic homozygous p.F1088Sfs*2 mutation in MSH6. Furthermore, signs consistent with immunodeficiency, namely decreased levels of IgG and IgA in the serum, nodular lymphoid hyperplasia and EBV-associated plasma cell proliferation with monotypic kappa light chain expression in the ileum, were also noted. Our case depicts the phenotypic diversity of CMMRD syndrome and emphasizes its association with immunodeficiency, raising awareness to a feature not widely recognized.

Evaluation of renal fibrosis in various causes of glomerulonephritis by MR elastography: a clinicopathologic comparative analysis.

BACKGROUND: Renal parenchymal fibrosis is the most important determinant of kidney disease progression and it is determined via biopsy. The aim of this study is to evaluate the renal stiffness noninvasively by magnetic resonance elastography (MRE) and to compare it with clinicopathologic parameters in glomerulonephritis and AA amyloidosis patients. METHODS: Thirty-four patients with glomerular filtration rate (GFR) over 20 ml/min/1.73m2 had non-contrast MRE prospectively. Kidney stiffness values were obtained from whole kidney, cortex, and medulla. Values were correlated with GFR, albuminuria, proteinuria, and degree of fibrosis that are assessed via renal biopsy. Patients were grouped clinicopathologically to assess the relation between stiffness and chronicity. RESULTS: Mean whole kidney, cortex, and medulla stiffnesses were 3.78 (± 1.26), 3.63 (± 1.25), and 4.77 (± 2.03) kPa, respectively. Mean global glomerulosclerosis was 22% (± 18%) and median segmental glomerulosclerosis was 4% (min-max: 0%-100%). Extent of tubulointerstitial fibrosis was less than 25% in 26 of the patients (76.5%), 25%-50% in 6 of the patients (17.6%), and higher than 50% in 2 of the patients (5.9%). Fourteen patients were defined to have chronic renal parenchymal injury. MRE-derived stiffness values correlated negatively with parameters of fibrosis. Lower stiffness values were observed in patients with chronic renal injury compared to those without (P < 0.05 for whole kidney and medulla MRE-derived stiffness). CONCLUSION: MRE-derived stiffness values were lower in patients with chronic injury. Stiffness decreases as glomerulosclerosis and tubulointerstitial fibrosis progresses in patients with primary glomerulonephritis and AA amyloidosis. With future studies, there may be a role for MRE to assess renal function in concert with conventional markers.

STK4 deficiency and EBV-associated lymphoproliferative disorders, emphasis on histomorphology, and review of literature.

Aberrations of the STK4 gene in humans result in an autosomal recessively inherited primary immunodeficiency. We identified three patients with STK4 deficiency who had presented to our hospital and reviewed their biopsy samples with the goal of detailing the characteristics of STK4 deficiency from a pathology perspective. Case 1 was a 20-year-old male who presented with cervical and supraclavicular lymphadenopathy which showed plasmacytic hyperplasia and a concurrent bronchial mass, with AA amyloidosis and EBV-associated "polymorphic lymphoproliferative disorder (LPD) resembling polymorphic post-transplant LPD." The second case was an 8-year-old girl with abdominal lymphadenopathy; biopsy revealed a complex lymphoproliferation which consisted of EBV-associated "polymorphic LPD resembling polymorphic post-transplant LPD," plasmacytic hyperplasia, granulomatous reaction, and a CD4- and PD-1-positive clonal T cell proliferation. The third was a 15-year-old girl with a laryngeal mass, representing a high-grade B cell lymphoma with prominent plasmacytic differentiation. Our cases emphasize the complex and challenging histopathology of lymphoid proliferations in patients with STK4 deficiency.

Baseline renal functions predict the effect of canakinumab on regression of proteinuria in patients with familial Mediterranean fever / Las funciones renales iniciales predicen el efecto del canakinumab en la regresión de la proteinuria en pacientes con fiebre mediterránea familiar

Introduction and objectives: Canakinumab, an IL-1 blocking drug, decreases the frequency and severity of the attacks and decreases the proteinuria level in colchicine resistant/intolerant familial Mediterranean fever (FMF) patients. However, it is not known whether patients with impaired or preserved renal functions respond differently to IL-1 blocking therapies in terms of proteinuria reduction and progression of kidney dysfunction which was the aim of this study. Materials and methods: Adult FMF subjects with biopsy proven amyloidosis who had 24-h urine protein excretion>150mg/day before initiation of canakinumab were divided into two groups as patients with preserved renal function (GFR≥60mL/min) and patients with impaired renal function (GFR<60mL/min). The response in proteinuria and renal functions are compared between two groups in this cross-sectional study. Results: A total of 18 patients (11 with preserved and 7 with impaired renal function) were included in this study. Although proteinuria levels of both groups were similar at the baseline and at six months after initiation of canakinumab, proteinuria at 12 months was significantly lower for patients with preserved renal function compared to patients with impaired renal function (2462±1760mg/day vs. 7065±3035mg/day respectively, p=0.02). All of the patients with preserved renal function had more than 50% decrease in proteinuria at 12 months compared to baseline values, while none of the patients with impaired renal function had more than 50% decrease in proteinuria. (AU)

Introducción y objetivos: El canakinumab, un fármaco bloqueante de la IL-1, disminuye la frecuencia y la gravedad de los ataques y reduce el nivel de proteinuria en pacientes con fiebre mediterránea familiar (FMF) resistentes o intolerantes a la colchicina. Sin embargo, se desconoce si los pacientes con función renal deteriorada o preservada responden de forma diferente a los tratamientos de bloqueo de la IL-1 en cuanto a la reducción de la proteinuria y la progresión de la disfunción renal, que era el objetivo de este estudio. Materiales y métodos: Los sujetos adultos con FMF y amiloidosis demostrada por biopsia que tenían una excreción de proteínas en orina de 24 h > 150 mg/día antes de iniciar el tratamiento con canakinumab, se dividieron en dos grupos: pacientes con función renal preservada (TFG ≥ 60 mL/min) y pacientes con función renal deteriorada (TFG < 60 mL/min). En este estudio transversal se comparan la respuesta en la proteinuria y las funciones renales entre dos grupos. Resultados: En este estudio se incluyeron 18 pacientes (11 con función renal preservada y siete con función renal deteriorada). Aunque los niveles de proteinuria de ambos grupos fueron similares al inicio y a los seis meses de iniciar el tratamiento con canakinumab, la proteinuria a los 12 meses fue significativamente menor en los pacientes con función renal preservada, en comparación con los pacientes con función renal deteriorada (2.462 ± 1.760 mg/día vs. 7.065 ± 3.035 mg/día, respectivamente, p = 0,02). Todos los pacientes con función renal preservada presentaron una disminución de la proteinuria superior al 50% a los 12 meses, en comparación con los valores iniciales, mientras que ninguno de los pacientes con función renal deteriorada presentó una disminución de la proteinuria de más del 50%. (AU)

Significance of caveolin-1 immunohistochemical staining differences in biopsy samples from kidney recipients with BK virus viremia.

BK virus infections which usually remains asymptomatic in healthy adults may have different clinical manifestations in immunocompromised patient population. BK virus reactivation can cause BK virus nephropathy in 8% of kidney transplant patients and graft loss may be seen if not treated. Clathrin or Caveolar system is known to be required for the transport of many viruses from Polyomaviruses family including BK viruses. In this study, kidney transplant patients with BK virus viremia were divided into two groups according to the BK virus nephropathy found in kidney biopsy (Group I: Viremia+, Nephropathy+ / Group II: Viremia+, Nephropathy-). Kidney biopsies were examined with immunohistochemical staining to determine the distribution and density of the Caveolin-1 and Clathrin molecules. Immunohistochemical staining of the 31 pathologic specimens with anti-caveolin-1 immunoglobulin revealed statistically significant difference between group-I and group-II. The number of the specimens stained with anti-caveolin-1 was less in group I. On the other hand, we did not find any difference between the groups regarding the anti-clathrin immunochemical analysis. According to these findings, caveolin-1 expression differences in kidney transplant patients may be important in disease progression.

Loss of CTNNB1 exon 3 in sclerosing angiomatoid nodular transformation of the spleen.

Sclerosing angiomatoid nodular transformation (SANT) is a rare vascular lesion of the spleen. Although several hypotheses have been suggested, the etiopathogenesis of SANT remains unknown. It is also unclear whether SANT is a reactive or a neoplastic lesion. Since CTNNB1 (ß-catenin gene) exon 3 mutations were frequently detected in some rare fibrovascular lesions, we aimed to investigate the presence of oncogenic CTNNB1 mutations in SANT cases. For this purpose, 7 cases of SANT with typical histopathological features were retrieved. First, the presence of CTNNB1 exon 3 alterations was examined with a recently described immunohistochemistry-based method. Then, the findings were confirmed with polymerase chain reaction (PCR), reverse transcription PCR (RT-PCR), and Sanger sequencing. In all cases, immunochemistry of ß-catenin gave a staining pattern that was suggestive of exon 3 alteration; however, no missense mutations were found in any case at the CTNNB1 exon 3 hotspot region. Subsequently, we screened for large interstitial deletions of CTNNB1 exon 3 which revealed short PCR products in three cases. Sequencing confirmed that these cases had large interstitial deletions, resulting in loss of the entire exon 3 of CTNNB1. In the remaining four cases, loss of exon 3 was documented at the cDNA level, although genomic deletion was not identified. These results demonstrate that loss of CTNNB1 exon 3 and stabilization of ß-catenin with activation of Wnt signaling pathway might have a significant role in the pathogenesis of SANT. Through this study, we provided important evidence for the neoplastic nature and pathogenesis of this disorder.

Baseline renal functions predict the effect of canakinumab on regression of proteinuria in patients with familial Mediterranean fever.

INTRODUCTION AND OBJECTIVES: Canakinumab, an IL-1 blocking drug, decreases the frequency and severity of the attacks and decreases the proteinuria level in colchicine resistant/intolerant familial Mediterranean fever (FMF) patients. However, it is not known whether patients with impaired or preserved renal functions respond differently to IL-1 blocking therapies in terms of proteinuria reduction and progression of kidney dysfunction which was the aim of this study. MATERIALS AND METHODS: Adult FMF subjects with biopsy proven amyloidosis who had 24-h urine protein excretion>150mg/day before initiation of canakinumab were divided into two groups as patients with preserved renal function (GFR≥60mL/min) and patients with impaired renal function (GFR<60mL/min). The response in proteinuria and renal functions are compared between two groups in this cross-sectional study. RESULTS: A total of 18 patients (11 with preserved and 7 with impaired renal function) were included in this study. Although proteinuria levels of both groups were similar at the baseline and at six months after initiation of canakinumab, proteinuria at 12 months was significantly lower for patients with preserved renal function compared to patients with impaired renal function (2462±1760mg/day vs. 7065±3035mg/day respectively, p=0.02). All of the patients with preserved renal function had more than 50% decrease in proteinuria at 12 months compared to baseline values, while none of the patients with impaired renal function had more than 50% decrease in proteinuria. CONCLUSIONS: Canakinumab, an IL-1 blocking agent, is not effective in decreasing proteinuria in FMF patients with already impaired renal functions and should be started early in the course of disease to prevent renal impairment.