Concurrent Anti-glomerular Basement Membrane Nephritis and IgA Nephropathy

Anti–glomerular basement membrane (GBM) nephritis is characterized by circulating anti-GBM antibodies and crescentic glomerulonephritis (GN) with deposition of IgG along the GBM. In a limited number of cases, glomerular immune complexes have been identified in anti-GBM nephritis. A 38-year-old female presented azotemia, hematuria, and proteinuria without any pulmonary symptoms. A renal biopsy showed crescentic GN with linear IgG deposition along the GBM and mesangial IgA deposition. The patient was diagnosed as concurrent anti-GBM nephritis and IgA nephropathy. Therapies with pulse methylprednisolone and cyclophosphamide administration were effective. Concurrent cases of both anti-GBM nephritis and IgA nephropathy are rare among cases of anti-GBM diseases with deposition of immune complexes. This rare case of concurrent anti-GBM nephritis and IgA nephropathy with literature review is noteworthy.

Peritoneal Fluid Cytology of Disseminated Large Cell Neuroendocrine Carcinoma Combined with Endometrioid Adenocarcinoma of the Endometrium

No abstract available.

Investigation and Standardization on Current Practice of Renal Transplant Pathology in Korea / 대한이식학회지

We need to establish an informative guideline to increase inter-institutional and inter-observer reproducibility of renal transplant diagnosis, and to improve the diagnostic ability of pathologists in Korea. A first nation-wide survey for renal transplant pathology was conducted by Renal Pathology Study Group of the Korean Society of Pathologists in 2016, to provide the continued excellence in the transplantation pathology laboratory, and to improve the diagnostic ability for the best treatment of transplant patients. This survey revealed the significant variations in scale, work load and biopsy indications for the renal transplant pathology in various institutions in Korea. The Banff classification were used by all institutions for the diagnosis of renal transplant pathology, but different formats were used: most institutions (70%) used the “2013 Banff classification” while the others were using “2007 Banff classification” (20%) or even older formats. In daily diagnostic practice of the renal allografts, difficulties that pathologists encounter were quite diverse due to different environments they work in. Most respondents agreed that standardized diagnostic practice guidelines, regular education on renal transplant pathology and convenient ways of consultation are further needed. We are currently working toward the enhancement of the expertise of renal pathologists and to increase inter-institutional and inter-observer reproducibility by 1) development of a set of virtual slides of renal allograft biopsies for the training, 2) validation and gathering expert's consensus on the core variables of rejection diagnosis by using virtual slides, and 3) continued education by the developed virtual slide atlas.

Nafamostat Mesilate Inhibits TNF-alpha-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production

Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-alpha (TNF-alpha). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-alpha for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogen-activated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM (0.01~100 microg/mL) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-alpha (3 ng/mL), and it dose dependently prevented the TNF-alpha-induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-alpha-induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-alpha-induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation.

Positive Expression of Insulin-Like Growth Factor-1 Receptor Is Associated with a Positive Hormone Receptor Status and a Favorable Prognosis in Breast Cancer / 한국유방암학회지

PURPOSE: Insulin-like growth factor 1 receptor (IGF-1R) is commonly expressed in primary breast cancers. Understanding the role of IGF-1R signaling in the different subtypes of breast cancer is important because each subtype has a different outcome and requires different treatment modalities. However, the precise biological significance of IGF-1R expression in cancer cells is still unclear. In this study, we examined the expression of IGF-1R in the different molecular subtypes of breast cancer. The effects of IGF-1R expression on the survival rates and outcomes of breast cancer were also examined. METHODS: IGF-1R expression was evaluated immunohistochemically in tissue microarray blocks constructed from 1,198 invasive breast cancer samples collected from six medical institutions. IGF-1R expression was interpreted according to the human epidermal growth factor receptor 2 (HER2)/neu immunohistochemistry scoring system. Scores of 2+ and 3+ were considered positive. RESULTS: Positive IGF-1R expression was observed in 65.4% of invasive breast cancer samples. IGF-1R expression was detected in all cancer subtypes (luminal A, 84.4%; luminal B, 75.9%; HER2, 21.2%; triple-negative, 46.6%) and was found to be associated with a positive hormone receptor status and the absence of HER2 amplification (p<0.001). Positive IGF-1R expression was significantly associated with high survival rates (p=0.014). However, a multivariate analysis revealed that the expression levels of IGF-1R did not achieve statistical significance. In the triple-negative cancer subtype, IGF-1R expression was found to be associated with a lower disease-free survival rate (p=0.031). CONCLUSION: Positive IGF-1R expression is associated with a favorable prognosis in breast cancer. IGF-1R is frequently expressed in the luminal A/B subtypes of breast cancer, and its expression is related to the hormone receptor status.

Nondiabetic kidney diseases in type 2 diabetic patients

BACKGROUND: The aim of this study was to evaluate the clinical characteristics of nondiabetic nephropathy in type 2 diabetes mellitus patients and to find a clinical significance of renal biopsy and immunosuppressive treatment in such a patient. METHODS: Renal biopsy results, clinical parameters, and renal outcomes were analyzed in 75 diabetic patients who underwent kidney biopsy at Chungnam National University Hospital from January 1994 to December 2010. RESULTS: The three most common reasons for renal biopsy were nephrotic range proteinuria (44%), proteinuria without diabetic retinopathy (20%), and unexplained decline inrena lfunction (20.0%). Ten patients (13.3%) had only diabetic nephropathy (Group I); 11 patients (14.7%) had diabetic nephropathy with superimposed nondiabetic nephropathy (Group II); and 54 patients (72%) had only nondiabetic nephropathy (Group III). Membranous nephropathy (23.1%), IgA nephropathy (21.5%), and acute tubulointerstitial nephritis (15.4%) were the three most common nondiabetic nephropathies. Group III had shorter duration of diabetes and lesser diabetic retinopathy than Groups I and II (P = 0.008).Group II had the lowest baseline estimated glomerular filtration rate (P = 0.002), with the greatest proportion of renal deterioration during follow-up (median 38.0 months, P < 0.0001). The patients who were treated with intensive method showed better renal outcomes (odds ratio 4.931; P = 0.01). Absence of diabetic retinopathy was associated with favorable renal outcome in intensive treatment group (odds ratio 0.114; P = 0.032). CONCLUSION: Renal biopsy should be recommended for type 2 diabetic patients with a typical nephropathy because a considerable number of these patients may have nondiabetic nephropathies. And intensive treatment including corticosteroid or immunosuppressants could be recommended for type 2 diabetic patients with nondiabetic nephropathy, especially if the patients do not have diabetic retinopathy.

Atypical form of Nodular Sclerosing Adenosis in the Breast: Mammography, US, and MR Imaging Findings: A Case Report

Sclerosing adenosis is a benign proliferating disease which arises from a terminal ductolobular unit in the breasts. When sclerosing adenosis combines to form a mass, it is called an adenosis tumor. There are few reports about mammography, ultrasonography, and MRI findings of adenosis tumors. Also, reports on adenosis tumors until now were based on a single mass. This report is about imaging findings of scleoring adenosis showing bilateral multiple masses in breasts which have never been reported.

Metaplastic Carcinoma with an Adenomyoepithelioma Component : A Case Report

Metaplastic carcinoma of the breast is rare. We report a case in a 53-year-old woman who presented with a rapidly-growing breast mass. The lesion had a complex echogenicity in ultrasonography and a high signal intensity in a T2-weighted image with rim enhancement in contrast-enhanced MR images. The PET/CT images showed high uptake for the lesion. The lesion was biopsied and found to be a metaplastic carcinoma with an adenomyoepithelioma component. Although metaplstic carcinoma was difficult to differentiate from other common breast cancers, it showed complex echogenicity on ultrasonography and high signal intensity on a T2 weighted image with rim enhancement on contrast-enhanced MR images.

Proposal for Creating a Guideline for Cancer Registration of Microinvasive Tumors of the Breast and Ovary (II)

BACKGROUND: Cancer registration in Korea has a longer than 30-years of history, during which time cancer registration has improved and become well-organized. Cancer registries are fundamental for cancer control and multi-center collaborative research. However, there have been discrepancies in assigning behavior codes. Thus, we intend to propose appropriate behavior codes for the International Classification of Disease Oncology, 3rd edition (ICD-O-3) for microinvasive tumors of the ovary and breast not only to improve the quality of the cancer registry but also to prevent conflicts. METHODS: As in series I, two pathology study groups and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated. To prepare a questionnaire on provisional behavior code, the relevant subjects were discussed in the workshop, and consensus was obtained by convergence of opinion from members of KSP. RESULTS: Microinvasive tumor of the breast should be designated as a microinvasive carcinoma which was proposed as malignant tumor (/3). Serous borderline tumor with microinvasion of the ovary was proposed as borderline tumor (/1), and mucinous borderline tumor with microinvasion of the ovary as either borderline (/1) or carcinoma (/3) according to the tumor cell nature. CONCLUSIONS: Some issues should be elucidated with the accumulation of more experience and knowledge. Here, however, we present our second proposal.

Proposal for Creating a Guideline for Cancer Registration of Microinvasive Tumors of the Breast and Ovary (II)

BACKGROUND: Cancer registration in Korea has a longer than 30-years of history, during which time cancer registration has improved and become well-organized. Cancer registries are fundamental for cancer control and multi-center collaborative research. However, there have been discrepancies in assigning behavior codes. Thus, we intend to propose appropriate behavior codes for the International Classification of Disease Oncology, 3rd edition (ICD-O-3) for microinvasive tumors of the ovary and breast not only to improve the quality of the cancer registry but also to prevent conflicts. METHODS: As in series I, two pathology study groups and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated. To prepare a questionnaire on provisional behavior code, the relevant subjects were discussed in the workshop, and consensus was obtained by convergence of opinion from members of KSP. RESULTS: Microinvasive tumor of the breast should be designated as a microinvasive carcinoma which was proposed as malignant tumor (/3). Serous borderline tumor with microinvasion of the ovary was proposed as borderline tumor (/1), and mucinous borderline tumor with microinvasion of the ovary as either borderline (/1) or carcinoma (/3) according to the tumor cell nature. CONCLUSIONS: Some issues should be elucidated with the accumulation of more experience and knowledge. Here, however, we present our second proposal.

HER2 Status by Standardized Immunohistochemistry and Silver-Enhanced In Situ Hybridization in Korean Breast Cancer / 한국유방암학회지

PURPOSE: Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in 18% to 20% of breast cancers, and it is recognized as a prognostic and predictive marker. We investigated the HER2 status in Korean breast cancer by immunohistochemistry (IHC) and silver-enhanced in situ hybridization (SISH), as the first step toward building a nationwide quality assurance program for HER2 testing. METHODS: A total of 1,198 breast carcinoma samples were collected from six institutions and IHC and SISH were performed using tissue microarrays in central laboratories. The results were compared to those of local laboratories. RESULTS: Available data were obtained from 959 samples. Central IHC results were negative, equivocal, and positive for 756 (78.8%; range among institutions, 76.8-81.8%), 37 (3.9%; 1.9-6.2%), and 166 (17.3%; 13.6-20%), respectively. SISH results were negative, equivocal, and positive for 756 (78.8%; 77.4-79.9%), 2 (0.2%; 0-0.7%), and 201 (21%; 20.1-22.2%), respectively. HER2 gene amplification was observed in 4.4%, 19%, and 73.9% of the negative, equivocal and positive groups stratified by local IHC results, respectively. When central SISH was considered to be the gold standard method for measuring HER2 status, the false-negative and false-positive rates of local IHC were 14.4% (29/201) and 7.1% (54/756). The concordance rate between central IHC and SISH was 98.4%. CONCLUSION: Central IHC and SISH markedly decreased the interlaboratory variability of HER2 status and the results of the two were highly concordant. The quality control program for HER2 testing must be focused on decreasing both the false negativity and positivity of IHC in local laboratories.

Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors

BACKGROUND/AIMS: The diagnosis of gastrointestinal stromal tumors (GIST) relies on the demonstration of KIT expression, but KIT expression is absent or reduced in approximately 15% of GIST. METHODS: Eighty-one GISTs were diagnosed between January 1998 and December 2007 at the Department of Pathology at both Chungnam National University Hospital and Eulji University Hospital, Daejeon. Medical history, patient follow-up, and radiographic data were collected if available in the medical records. To determine diagnostic and prognostic markers for GISTs focused on PDGFRA mutation and clinicopathologic features, we analyzed 81 GIST cases for KIT, PDGFRA, DOG1, and p16 expression and for mutation of PDGFRA genes. RESULTS: Among 81 GIST cases, 20 high risk cases (24.7%) were recurred or metastasized. Immunohistochemically, KIT was positive in 76 (93.8%), PDGFRA in 75 (92.7%), and DOG1 in 77 (95.1%). With a cutoff value of 50%, p16 expression was positive in 26 cases were positive (32.1%). A correlation between p16 expression or negative DOG1 expression and recurrence or metastasis was demonstrated (p<0.05). Four cases showed a missense mutation in exon 12 of PDGFRA gene, three of these were of epithelioid GISTs. Two cases showed a silent mutation in exon 18 of PDGFRA. CONCLUSIONS: These results indicate that the expression of DOG1 and PDGFRA is observed in a majority of GIST cases. Expression of p16 and negative DOG1 expression is predictive for development of recurrence and/or metastasis. Even though mutation of the PDGFRA gene is frequently seen in epithelioid GISTs, a clinicopathologic correlation was not demonstrated.

Concurrence of Fibrillary Glomerulonephritis and AL Amyloidosis Associated with Monoclonal Gammopathy / 대한신장학회지

Renal diseases with organized deposits include amyloid, fibrillary, immunotactoid, and cryoglobulinemic glomerulopathies. AL amyloidosis and fibrillary glomerulonephritis are different in the composition of their immunoglobulin deposits. Fibrils of fibrillary glomerulonephritis are usually composed of polyclonal, occasionally oligoclonal or monoclonal, immunoglobin G, but amyloidosis consists of monoclonal light chains. Simultaneous occurrence of fibrillary glomerulonephritis and AL amyloidosis is very rare. We report a case of fibrillary glomerulonephritis combined with AL amyloidosis in a 71-yr-old man.

Inflammatory Myofibroblastic Tumor of the Breast: A Case Report

An inflammatory myofibroblastic tumor is an uncommon type of tumor composed of spindle-shaped myofibroblast admixed with mature plasma and inflammatory cells. It is most common in the lungs and in various organs; however, a few cases of inflammatory myofibroblastic tumor of the breast have been reported in the literature. To date, there are no typical radiologic findings but an ill-defined marginated mass which was a suspicious malignancy has been reported in the literature. Here, we describe the mammographic and ultrasonographic findings of a case of an inflammatory myofibroblastic tumor of the breast with a spiculated margin which was strongly suspect as being a malignancy in a 36-year-old woman.

Mutation-Free Expression of c-Kit and PDGFRA in Phyllodes Tumors of the Breast / 한국유방암학회지

PURPOSE: Phyllodes tumors (PTs) of the breast have been classified as benign, borderline, or malignant based on their histopathologic features. However, predicting clinical behavior based on these features has proven to be difficult given that local recurrence occurs in both benign and malignant PTs. Recurrence has been shown to mirror the histologic pattern of the primary tumor or to show dedifferentiation. The aim of this study was to assess the value of the histopathologic parameters, expression or mutation of c-Kit and platelet derived growth factor receptor alpha (PDGFRA) in predicting tumor recurrence. METHODS: Representative areas from 39 benign, 16 borderline, and 12 malignant PTs were selected for construction of tissue microarrays. Immunohistochemical analyses for p53, Ki-67, c-Kit, and PDGFRA were performed and SSCP-PCR analysis was carried out to identify mutations in exons 9, 11, 13, and 17 of the c-Kit gene and exons 12 and 18 of the PDGFRA gene. Clinicopathologic features, including tumor recurrence and margin status, were also evaluated. RESULTS: Of the 67 PTs, 11 cases (16.4%) recurred from 3 to 92 months following initial diagnosis (4 benign, 2 borderline, and 5 malignant). One benign PT case recurred as a borderline tumor and two borderline PT cases recurred as malignancies. Three patients died of malignant PT. No mutations of the c-Kit or PDGFRA genes were found and there was no statistically significant association of either p53 or p16 immunostaining with recurrent disease (p>0.05). However, histologic grade (p=0.033), margin status (p<0.001), Ki-67 (p=0.012), c-Kit (p=0.002), and PDGFRA (p=0.007) stromal immunopositivity were significantly correlated with recurrence. CONCLUSION: Even though positive or close margins were significantly associated with tumor recurrence, stromal c-Kit, PDGFRA positivity, and the Ki-67 index were useful for predicting recurrent PTs. Despite this, no c-Kit or PDGFRA mutations were found.

Practical Standardization in Renal Biopsy Reporting

BACKGROUND: To standardize renal biopsy reporting and diagnosis, The Renal Pathology Study Group of the Korean Society of Pathologists (RPSKSP) has developed a renal pathology reporting format for the native and allograft kidney. METHODS: A consensus checklist of a provisional renal biopsy format was sent to all members of the RPSKSP. Feed back opinions regarding the practical application of the checklist to the diagnostic work were received. RESULTS: Kidney biopsies require three essential examinations: by light microscopy, immunofluorescence (IF), and electron microscopy (EM). A final report of a renal biopsy should include information on specimen adequacy and a description of the morphologic change using a systematic semiquantitative method for each of the compartments, with optional separate IF and EM reports. CONCLUSIONS: A standard renal biopsy report format is important in establishing clinicopathologic correlations, making reliable prognostic considerations, comparing the findings in sequential biopsies and evaluating the effects of therapy.

A Case of Lupus-like Glomerulonephritis in an HIV-infected Patient

Many types of glomerulonephritis are associated with human immunodeficiency virus (HIV) infection. We present a case of a 50-year-old Korean man with an HIV infection, who developed nephrotic syndrome and progressive renal failure. Renal biopsy showed lupus-like glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. After the administration of antiretroviral agents and steroids, there was reduction in the amount of proteinuria and improvement in renal function.

A Case of Lupus-like Glomerulonephritis in an HIV-infected Patient

Many types of glomerulonephritis are associated with human immunodeficiency virus (HIV) infection. We present a case of a 50-year-old Korean man with an HIV infection, who developed nephrotic syndrome and progressive renal failure. Renal biopsy showed lupus-like glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. After the administration of antiretroviral agents and steroids, there was reduction in the amount of proteinuria and improvement in renal function.

Expression of CXCR4 and SDF-1alpha in Primary Breast Cancers and Metastatic Lymph Nodes / 한국유방암학회지

PURPOSE: A CXCR4/stroma derived factor-1alpha (SDF-1alpha, CXCL12) interaction is involved in many metastatic cancer mechanisms, including breast cancer. The primary objectives of this study were to investigate the correlation between CXCR4 and axillary lymph node metastasis and to clarify the interaction between CXCR4 in primary tumor cells and SDF-1alpha in metastatic lymph nodes. An analysis of the correlation between CXCR4, SDF-1alpha and clinicopathologic features was also performed. METHODS: Representative areas from 44 invasive ductal carcinomas were selected for construction of tissue microarrays using a 5 mm punch. Breast cancers (n=44), metastatic axillary lymph nodes (n=18) and non-metastatic axillary lymph nodes (n=26) were immunohistochemically stained for CXCR4, SDF-1alpha, estrogen receptor (ER), progesterone receptor (PR) and HER2. The parameters of age, tumor size, nuclear grade, histologic grade, lymph node status and pathologic node (pN) stage pN0 to pN3 were evaluated. RESULTS: CXCR4 expression was negatively correlated with increased age (p=0.005) and positively correlated with a large tumor size (p=0.043) and PR expression (p=0.027). CXCR4 expression was not correlated with metastatic lymph nodes (p=0.079) and SDF-1alpha expression in metastatic lymph nodes (p=0.062). However, CXCR4 nuclear positivity is correlated with lymph node metastasis (p=0.044). SDF-1alpha was not correlated with any clinicopathologic feature in a statistically significant manner. CONCLUSION: An evaluation of young age, large tumor size and PR expression helps predict lymph node metastasis and poor prognosis. Expression of CXCR4 nuclear positivity is correlated with a poor prognosis.

The Preconditioning with AICAR Protects Against Subsequent Renal Ischemia Reperfusion Injury / 대한신장학회지

PURPOSE:Preconditioning due to activation of AMPK might reduce ischemia-reperfusion (I/R) injury in the kidney, based on the key role of AMPK in preserving ATP. To evaluate this possibility, the effect of preconditioning with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), AMPK activator, before sustained ischemia was investigated. METHODS:Adult male Sprague-Dawley rats weighing approximately 220-250 g were used. To induce renal ischemia, a laparotomy was performed under ketamine and xylazine hydrochloride, and the blood supply to both kidneys was interrupted by placement of vessel clamps at the level of the renal pedicles. Reflow was initiated by removing the clamps. The following experimental groups were defined 1. Acute renal ischemia 0 sec, 10 min, 15 min, 2. AICAR treatment, 3. Sham group (S), 4. Ischemia/ Reperfusion group (I/R), 5. AICAR+I/R group (A+I/R), 6. AraA (Adenine-9-b-D-arabinofuranoside, an AMPK) inhibitor+AICAR+I/R group (AraA+A+I/R) RESULTS:There was only faint AMPK phosphorylation in the sham group. After 10 minutes of ischemia, or AICAR preconditioning however, Thr172 phosphorylation of AMPK was increased (p<0.05). The serum levels of BUN and creatinine were significantly decreased in AICAR preconditioning group (A+I/R). (128.0+/-7.33 mg/dL, 4.18+/-0.27 mg/dL vs. 90.2+/-11.13 mg/dL, 2.58+/-0.7 mg/dL, p<0.05), but these effects were attenuated by AMPK inhibitor, AraA (AraA+A+I/R group). In quantitative analysis of tubular injury, tubular injury score in AICAR preconditioning group significantly decreased (p<0.05). CONCLUSION:The AMPK activator AICAR has a protective effect against renal I/R injury.