Biopsy Findings In Patients Research Articles

Liver histology during Mipomersen therapy for severe hypercholesterolemia.

Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein B synthesis and lowers plasma low-density lipoprotein cholesterol even in the absence of low-density lipoprotein receptor function, presumably from inhibition of hepatic production of triglyceride-rich very low-density lipoprotein particles. By virtue of this mechanism, mipomersen therapy commonly results in the development of hepatic steatosis. Because this is frequently accompanied by alanine aminotransferase elevations, concern has arisen that mipomersen could promote the development of steatohepatitis, which could in turn lead to fibrosis and cirrhosis over time. The objective of this study was to assess the liver biopsy findings in patients treated with mipomersen. We describe 7 patients who underwent liver biopsy during the mipomersen clinical development programs. Liver biopsies were reviewed by a single, blinded pathologist. The histopathological features were characterized by simple steatosis, without significant inflammation or fibrosis. These findings suggest that hepatic steatosis resulting from mipomersen is distinct from nonalcoholic steatohepatitis.

Renal Structure in Normoalbuminuric and Albuminuric Patients With Type 2 Diabetes and Impaired Renal Function

OBJECTIVEThe structural basis of normoalbuminuric renal insufficiency in patients with type 2 diabetes remains to be elucidated. We compared renal biopsy findings in patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) and measured GFR of <60 mL/min/1.73 m2, associated with either normo-, micro-, or macroalbuminuria.RESEARCH DESIGN AND METHODSIn patients with normo- (n = 8) or microalbuminuria (n = 6), renal biopsies were performed according to a research protocol. In patients with macroalbuminuria (n = 17), biopsies were performed according to clinical indication. Findings were categorized according to the Fioretto classification: category 1 (C1), normal/near normal; category 2 (C2), typical diabetic nephropathy (DN) with predominantly glomerular changes; and category 3 (C3), atypical with disproportionately severe interstitial/tubular/vascular damage and with no/mild diabetic glomerular changes.RESULTSIn our study population (mean eGFR 35 mL/min/1.73 m2), typical glomerular changes (C2) of DN were observed in 22 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 subjects with normoalbuminuria (P = 0.002). By contrast, predominantly interstitial or vascular changes (C3) were seen in only 1 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 normoalbuminuric subjects (P = 0.08). Mesangial area increased progressively from normal controls to patients with type 2 diabetes and normo-, micro-, and macroalbuminuria. Varying degrees of arteriosclerosis, although not necessarily the predominant pattern, were seen in seven of eight subjects with normoalbuminuria.CONCLUSIONSTypical renal structural changes of DN were observed in patients with type 2 diabetes and elevated albuminuria. By contrast, in normoalbuminuric renal insufficiency, these changes were seen less frequently, likely reflecting greater contributions from aging, hypertension, and arteriosclerosis.

The Modern Spectrum of Renal Biopsy Findings in Patients with Diabetes

Renal biopsies performed in diabetic patients are increasing in number and complexity. This study sought to determine the usefulness of renal biopsy in patients with diabetes and the predictability of diagnosing diabetic nephropathy (DN) versus nondiabetic renal disease (NDRD) from clinical and laboratory data. To assess modern trends, a retrospective study was performed of clinical-pathologic findings in all patients with diabetes who had a biopsy in 2011. Among 2642 native kidney biopsies, 620 (23.5%) were from patients with diabetes. The cohort included 371 men (60.7%) aged a median (interquartile range) 62 years (52-69) with 10-year (5-15) duration of diabetes mellitus (DM). Median serum creatinine was 2.5 mg/dl (1.6-4.4), and 52% of patients had stage 4-5 CKD. On biopsy, 37% of patients had DN alone, 36% had NDRD alone, and 27% had DN plus NDRD. In NDRD alone, FSGS (22%), hypertensive nephrosclerosis (18%), acute tubular necrosis (ATN) (17%), IgA nephropathy (11%), membranous GN (8%), and pauci-immune GN (7%) comprised 80% of diagnoses, compared with ATN (43%), hypertensive nephrosclerosis (19%), FSGS (13%), and IgA nephropathy (7%) for DN plus NDRD. In multivariate analyses, longer duration of DM was associated with a greater likelihood of DN and a lower likelihood of NDRD: each added year of DM reduced the odds of NDRD by 5% (odds ratio, 0.95; 95% confidence interval, 0.91 to 0.98; P=0.004). DM duration ≥ 12 years was the best predictor (58% sensitivity, 73% specificity) of DN alone. Approximately one-quarter of all renal biopsies are performed in patients with DM. Judicious use of renal biopsy has uncovered NDRD alone or superimposed on DN in the majority of such biopsies. ATN is emerging as an important category of NDRD, which has not been reported previously.

Prostate MRI: Who, when, and how? Report from a UK consensus meeting

The current pathway for men suspected of having prostate cancer [transrectal biopsy, followed in some cases by magnetic resonance imaging (MRI) for staging] results in over-diagnosis of insignificant tumours, and systematically misses disease in the anterior prostate. Multiparametric MRI has the potential to change this pathway, and if performed before biopsy, might enable the exclusion of significant disease in some men without biopsy, targeted biopsy in others, and improvements in the performance of active surveillance. For the potential benefits to be realized, the setting of standards is vital. This article summarizes the outcome of a meeting of UK radiologists, at which a consensus was achieved on (1) the indications for MRI, (2) the conduct of the scan, (3) a method and template for reporting, and (4) minimum standards for radiologists.

Bone Marrow Biopsy Findings in Patients with Hepatitis C Infection

AbstractAbstract 4840Patients with hepatitis C often present with cytopenias - thrombocytopenia, neutropenia and less commonly anemia. Hypersplenism may contribute to cytopenias but effects on the bone marrow due to the hepatitis C infection also likely play a role in its pathogenesis. Hepatitis C infection predisposes to development of lymphomas as well. The bone marrow findings in patients with hepatitis C infection are not well described and to our knowledge there has only been one peer reviewed study published till date.In order to elucidate this further, we conducted a retrospective review of bone marrow biopsies performed at our institution on patients with known hepatitis C infection.Between years 1999 and 2010, 56 adults (36 male and 20 female) patient with hepatitis C underwent bone marrow biopsies. The indications for bone marrow biopsy included evaluation or staging of lymphoma or myeloma (24 patients) OR investigation of cytopenias (32 patients). None of the patients were on treatment for Hepatitis C at the time of the bone marrow biopsy.Of the 24 patients with lymphoma/myeloma, 11 showed bone marrow involvement, while 10 patients had benign lymphocyte aggregates in the marrow. 9 out of 24 patients had a hypercellular marrow and 8 had a hypocellular marrow. Mild to moderate megaloblastic change in the erythrocyte series was seen in 5 patients and dyserythropoiesis in 2. Hyperplasia of megakaryocytes was seen in 11/24 and 6/24 showed atypical megakaryocytes with focal clustering in 7/24. Reticulin fibrosis was noted in 7 patients. Iron stores were increased in 13/24 with decreased sideroblasts in 15/24 patients.Review of the 32 patients who had the bone marrow biopsy done for cytopenias showed 16 were hypocellular and 9 were hypercellular while 4 patients had variable cellularity. Mild to moderate megaloblastic change in the erythrocyte series was seen in 12/32 and dyserythropoiesis in 11/32. Granulocytic hypoplasia was seen in 14/32. Benign lymphoid aggregates were noted in 20 patients. Hyperplasia in the megakaryocytes was seen in 8 while 11 had decreased megakaryocytes. Atypical megakaryocytes were noted in 10/32 with clustering seen in 4 patients. Reticulin fibrosis was noted in 13 patients. Iron stores were increased in 16/32 and sideroblasts were decreased in 13/32. Frank hemophagocytosis was observed in 5 patients. Of these 32 patients, 4 were HIV positive. Myelodysplastic syndrome was diagnosed in 2/32, AML and Hemophagocytic lymphohistiocytosis in one each. Conclusions:Bone marrow biopsies are usually performed in patients with Hepatitis C to investigate cytopenias and for diagnosis or staging lymphoma or myeloma. Even without lymphoma involving the marrow, a substantial number of patients have benign lymphocyte infiltrates seen in the marrow. Marrow hypocellularity is common. Megaloblastic change in the erythroid series, dyserythropoiesis, atypical megakaryocytes and reticulin fibrosis can be seen in a substantial minority of the patients which contribute to cytopenias. Disclosures:No relevant conflicts of interest to declare.

Magnetic Resonance Imaging for Predicting Prostate Biopsy Findings in Patients Considered for Active Surveillance of Clinically Low Risk Prostate Cancer

A barrier to the acceptance of active surveillance for men with prostate cancer is the risk of underestimating the cancer burden on initial biopsy. We assessed the value of endorectal magnetic resonance imaging in predicting upgrading on confirmatory biopsy in men with low risk prostate cancer. A total of 388 consecutive men (mean age 60.6 years, range 33 to 89) with clinically low risk prostate cancer (initial biopsy Gleason score 6 or less, prostate specific antigen less than 10 ng/ml, clinical stage T2a or less) underwent endorectal magnetic resonance imaging before confirmatory biopsy. Three radiologists independently and retrospectively scored tumor visibility on endorectal magnetic resonance imaging using a 5-point scale (1-definitely no tumor to 5-definitely tumor). Inter-reader agreement was assessed with weighted kappa statistics. Associations between magnetic resonance imaging scores and confirmatory biopsy findings were evaluated using measures of diagnostic performance and multivariate logistic regression. On confirmatory biopsy, Gleason score was upgraded in 79 of 388 (20%) patients. Magnetic resonance imaging scores of 2 or less had a high negative predictive value (0.96-1.0) and specificity (0.95-1.0) for upgrading on confirmatory biopsy. A magnetic resonance imaging score of 5 was highly sensitive for upgrading on confirmatory biopsy (0.87-0.98). At multivariate analysis patients with higher magnetic resonance imaging scores were more likely to have disease upgraded on confirmatory biopsy (odds ratio 2.16-3.97). Inter-reader agreement and diagnostic performance were higher for the more experienced readers (kappa 0.41-0.61, AUC 0.76-0.79) than for the least experienced reader (kappa 0.15-0.39, AUC 0.61-0.69). Magnetic resonance imaging performed similarly in predicting low risk and very low risk (Gleason score 6, less than 3 positive cores, less than 50% involvement in all cores) prostate cancer. Adding endorectal magnetic resonance imaging to the initial clinical evaluation of men with clinically low risk prostate cancer helps predict findings on confirmatory biopsy and assess eligibility for active surveillance.

Clinicopathologic Correlations in Multiple Myeloma: A Case Series of 190 Patients With Kidney Biopsies

Renal involvement is common in multiple myeloma. In this study, we examined kidney biopsy findings in patients with multiple myeloma and correlated them with their clinical renal and hematologic characteristics. Case series. 190 Mayo Clinic patients with multiple myeloma who underwent kidney biopsy between 1997-2011 were identified from our kidney biopsy database. Patients had an established diagnosis of multiple myeloma or multiple myeloma was diagnosed shortly after the results of kidney biopsy, which prompted bone marrow biopsy. Myeloma cast nephropathy (MCN), AL amyloidosis, and monoclonal immunoglobulin deposition disease (MIDD). Renal morphologic changes, clinical renal and hematologic characteristics at kidney biopsy, renal and patient outcomes. Paraprotein-associated lesions were seen in 73% of patients; non-paraprotein-associated lesions, in 25%; and no pathology, in 2%. The most common paraprotein-associated lesions were MCN (33%), MIDD (22%), and amyloidosis (21%). The most common non-paraprotein-associated lesions were acute tubular necrosis (9%), hypertensive arteriosclerosis (6%), and diabetic nephropathy (5%). Patients with MIDD were younger than those with MCN or amyloidosis. Urine paraprotein size and bone marrow plasma cell percentage were higher in MCN than amyloidosis or MIDD. Nephrotic syndrome was more common in amyloidosis than MIDD. Percentage of albuminuria was highest in amyloidosis and lowest in MCN. Median kidney survival from kidney biopsy was 20, 30, and 51 months for MCN, amyloidosis, and MIDD, respectively (P = 0.2). Median patient survival from multiple myeloma diagnosis was 44, 58, and 62 months for MCN, amyloidosis, and MIDD, respectively (P = 0.4). Retrospective nature. The spectrum of renal lesions in multiple myeloma is more heterogeneous than previously reported. Clinical features favoring amyloidosis over MIDD include older age, absence of kidney failure, presence of nephrotic syndrome, absence of hematuria, and >50% albuminuria.

Abstract C28: MRI/Ultrasound image fused guided TRUS prostate biopsy: Multiparametric MRI low suspicion lesions do not correlate with high-grade prostate cancer

Abstract Introduction and Objectives: 3Telsa endorectal coil multiparametric magnetic resonance imaging (mpMRI) has been investigated as a new tool for physicians to improve prostate cancer detection. Depending on the number of MR sequences that are suggestive of cancer, MR lesions can be reported as having a low, moderate or high level of suspicion. Biopsy techniques to sample the MR lesions suspicious for cancer include in gantry platforms. While performing a prostate biopsy inside the MR gantry is challenging (long procedure times, expensive, not well tolerated by patients), platforms to perform office based MR / Ultrasound image fused TRUS biopsies have developed. While high suspicion lesions on MRI correlate strongly with the presence of cancer, the importance of low suspicion lesions has not been well characterized. We report the biopsy findings of patients with low suspicion lesions. Methods: We reviewed all patients who underwent a 3 Tesla mpMRI of the prostate with endorectal coil from March 2007 to July 2011. Two radiologists independently reviewed and graded any suspicious lesions into low, moderate, or high risk groups. Lesions were stratified based on T2-weighted, spectroscopic, dynamic contrast enhanced (DCE) and diffusion weighted (DWI) MRI sequences. Low suspicion lesions are defined by a maximum of two positive parameters on mpMRI. Patients with only low suspicion lesions who subsequently underwent a random 12 core US biopsy + mpMRI/US fusion targeted biopsy were selected for and analyzed. Results: Of 800 patients who received a mpMRI of the prostate, 92 patients (12%) had only low suspicion lesions on mpMRI. Mean age and PSA in this cohort were 59.7 years (36-81) and 7.84 ng/ml (0.3-64.7), respectively. All 92 patients underwent a mpMRI/US fusion biopsy plus a 12-core TRUS random biopsy. Sixty-two of these patients (67%) had no cancer detected. Of the remaining thirty patients (33%) who were diagnosed with cancer on biopsy, twenty-two patients had Gleason 6 disease and eight patients had Gleason 7 (3+4) disease. Ten patients went on to radical prostatectomy and no one was pathologically upgraded to high grade cancer. Thus, for low suspicion lesions, 90% had either Gleason 6 or no cancer on biopsy while 100% had no primary Gleason 4 on their biopsy. Conclusions: Prostate MR imaging has improved considerably, as is true for many technology dependant medical devices. Currently 3T mpMRI of the prostate has become the most widely used imaging modality for lesion detection outside of ultrasound. As previously published, our image fusion biopsy platform allows for sampling of MRI suspicious areas. These results demonstrate that low suspicion lesions on mpMRI do not signify high grade cancer. This has implications not only for initial cancer detection and patient selection for treatment options, but may also obviate the need for annual biopsies in men on active surveillance. Larger cohort studies are required. Citation Format: Peter A. Pinto, Jochen Kruecker, Maria Merino, W. Marston Linehan, Ismail Baris Turbey, Peter Choyke, Brad Wood. MRI/Ultrasound image fused guided TRUS prostate biopsy: Multiparametric MRI low suspicion lesions do not correlate with high-grade prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C28.

Serum complement C4 in chronic hepatitis C: Correlation with histopathologic findings and disease activity

Hepatitis C virus leads to chronic liver disease, cirrhosis and hepatocellular cancer. Viral markers and other laboratory tests used in the diagnosis and follow-up of chronic hepatitis C do not correlate well with disease activity and liver histopathology. Therefore, alternative tests that indicate disease activity and relate with liver biopsy findings are needed. We aimed to investigate the relationship between serum complement levels and biopsy findings in patients with chronic hepatitis C. One hundred cases (70 patients, 30 healthy controls) were included in the study. Patients were divided into two groups: chronic hepatitis C patients with high transaminase levels were evaluated as the first group and patients with normal transaminase levels as the second group. Patients with a high transaminase level were biopsied and activity scores were evaluated against complement C3c and C4 levels. In addition, demographic data and laboratory tests were evaluated. Patients with chronic hepatitis C without proteinuria, acute phase response, cirrhosis, or coinfection with another hepatitis virus were included in the prospective study. Serum complement C3c (p<0.01) and C4 (p<0.01) levels were significantly lower in the first group than the second group. Serum complement C3c levels did not correlate with laboratory tests, hepatitis C virus-RNA levels, histological activity index, or fibrosis scores in patients with high transaminase levels, whereas complement C4 levels showed significant correlation with alanine aminotransferase (r: -0.368, p: 0.001) and histological activity index (r: -0.639, p: 0.001). We could not find any relation between serum complement C4 level and fibrosis. Serum complement C4 levels correlate with the histological activity index of the Knodell scoring system.

Comparison of enzyme immunoassays detecting Helicobacter pylori specific IgG in serum and saliva with endoscopic and biopsy findings in patients with dyspepsia

Purpose: To compare the performance of two indirect enzyme-linked immunosorbent assays (ELISA) detecting Helicobacter pylori (HP)-specific IgG antibodies in serum and saliva with endoscopic observations and histologic findings of biopsies from dyspeptic patients, in an area of high HP prevalence. Materials and Methods: Sera, saliva and antral biopsies were obtained from 55 dyspeptic patients. IgG antibodies against HP were assayed in sera and saliva utilizing two indirect ELISAs. Biopsies were processed according to standard procedures in order to detect histological changes and the presence or absence of Helicobacter pylori. Laboratory data thus obtained were compared and statistically analyzed. Results: Forty-two (76.36%) biopsies were positive for HP. The organisms were detected in 4 of 16 (25%) cases with normal endoscopic findings, in all 16 cases of gastritis and in 22 of the 23 (95.6%) cases of duodenal ulcers (DU). Serum and saliva HP-specific IgG antibodies were detected in 4 normal cases with positive biopsies, in 12 and 14 cases of gastritis, respectively, and in all 22 (100%) biopsy positive cases of DU. The sensitivities of the serum and saliva tests were 90.5% and 95%, respectively, while the specificities were 84.5% and 70%, respectively. Conclusion: Due to their high sensitivity and specificity in diagnosing HP-associated DU and gastritis, serum and saliva antibody testing seems to offer a valuable alternative to invasive procedures especially in areas of high HP prevalence such as ours; saliva antibody testing is simple and practical especially in children and in difficult patients who resent venipuncture.

Clinical Benefits of Biochemical Markers of Fibrosis in Egyptian Children With Chronic Liver Diseases.

BackgroundThe need for repetition of liver biopsy, especially in assessing the degree of fibrosis and follow-up of treatment protocols, justifies an intensive search for non-invasive alternatives. We attempted to investigate the clinical usefulness of serum fibrogenesis markers in pediatric chronic liver diseases.MethodsWe measured serum levels of TGF-β1, collagen IV, laminin, MMP-2 and EGF-R, in 50 children with chronic liver disease (HBV, HCV and Bilharziasis) and 30 healthy controls, and determined their relationship to frequently used liver function tests and liver biopsy findings in patients.ResultsTGF-β1, collagen IV, laminin and MMP-2, but not EGF-R, were significantly higher in patients than in controls (P < 0.01). None of these markers correlated with the histological fibrosis stage, whereas laminin correlated with necroinflammatory activity (P < 0.01). TGF-β1, collagen IV, laminin and MMP-2 had the ability to discriminate patients with significant fibrosis, while only collagen IV and laminin were able to discriminate those with cirrhosis. Among these markers, collagen IV had the best predictive accuracy for significant fibrosis (AUROC 0.94; PPV 91.5%) and cirrhosis (AUROC 0.85; PPV 80%).ConclusionsIn conclusion, these markers may be useful in reducing but not replacing the need for liver biopsy in the monitoring of disease progression and treatment effectiveness and might be an inseparable part of assessment of chronic hepatopathies.

Comparison between Doppler Ultrasound and Biopsy Findings in Patients with Suspected Kidney Transplant Rejection

Introduction: The role of Doppler ultrasound in diagnosing kidney allograft rejections is controversial. Our goal in this study was to investigate the utility of Doppler-measured resistive index (RI) as a screening tool for kidney transplant rejection. Methods: We retrospectively studied a random sample of 188 kidney transplanted patients who had Doppler-ultrasound examination followed within two weeks by transplant biopsy. We evaluated the specificity and sensitivity of Doppler ultrasound in diagnosing rejection at different RI thresholds, using the reported biopsy findings as the gold standard. Results: The RI values of the study population had a mean value of 0.7 ± 0.11 (mean ± SD) and a range of 0.4-1.0. There was no significant difference in the mean RI between patients with biopsy proven rejection and patients without rejection (0.68±0.09 versus 0.71±0.12, P = 0.16). The sensitivity and specificity of Doppler-measured RI in diagnosing rejection was highly variable depending on the chosen cut-off value, ranging between 4.1-98.6% and 2.6-92.2% respectively. Acceptable specificity was only achieved at the expense of very low sensitivity. Acute tubular necrosis (ATN) and interstitial edema (IE) were associated with higher RI values than other pathological entities, while very low RI values had high specificity and low sensitivity for transplanted renal artery stenosis (TRAS). Conclusion: Doppler-measured RI lacks accuracy in diagnosing transplanted kidney rejection, resulting in poor utility of this test as a screening tool for rejection. Keywords: Doppler Ultrasound; Rejection; Resistive Index (RI); Transplant kidney

Serial biopsy findings in patients with small bowel allotransplantation

我们对2007年至2008年间南京军区南京总医院开展的4例异体小肠移植患者的194个肠黏膜活检标本(截至2009年5月1日)进行动态观察、分析,以提高对小肠移植后急性排异反应形态变化的认识。

Pathological Upgrading and Up Staging With Immediate Repeat Biopsy in Patients Eligible for Active Surveillance

Active surveillance with selective delayed intervention is a treatment regimen used in patients with low risk prostate cancer. Decision making is based on pretreatment prostate specific antigen, clinical stage and prostate biopsy results. We reviewed our experience with immediate repeat biopsy in patients eligible for active surveillance with selective delayed intervention. A retrospective review was done of the records of consecutive patients who underwent repeat biopsy within 3 months of a first positive biopsy from March 2002 to June 2007. Patients were considered eligible if they had prostate specific antigen less than 10 ng/ml, clinical stage T2a or less, Gleason pattern 3 or less, 3 or fewer positive cores and no single core with 50% or greater cancer involvement. A total of 104 patients met eligibility criteria. Of the 104 repeat biopsies performed 27 (26%) were negative, 59 (57%) had a Gleason score of 6 or less and 17 (16%) had a Gleason score of 7. One patient had a Gleason score of 9, while 10 of 104 (10%) had greater than 3 cores involved on repeat biopsy and 12 (12%) had 50% or greater involvement of at least 1 core. Of 104 cases (27%) 28 were upgraded and/or up staged. Treated cases that were upgraded and/or up staged were more likely to show higher pathological stage and grade at radical prostatectomy than those that were not (p = 0.003 and p = 0.001, respectively). Immediate repeat biopsy in cases of active surveillance with selective delayed intervention resulted in 27% being upgraded or up staged and those were more likely to show higher grade and stage disease at radical prostatectomy. We recommend repeat biopsy because it improved our discrimination of who are the best candidates for active surveillance with selective delayed intervention.

Sex, psychosocial factors, and reported symptoms influence referral for esophagogastroduodenoscopy and biopsy results in children with chronic abdominal pain.

To identify symptoms and psychosocial factors that predicted referral for esophagogastroduodenoscopy (EGD) and discriminated between patients with positive versus negative biopsy findings. Children age 8 to 16 years old and parents completed validated questionnaires assessing gastrointestinal symptoms and psychosocial characteristics. Biopsy results of esophagus, stomach, and duodenum were reviewed. From the total sample of 461 patients (mean age 11.87 years, 62% girls), 127 (28%) underwent EGD with biopsy (mean age 12.1 years, 57% girls). Upper abdominal gastrointestinal symptoms predicted EGD referral, and psychosocial characteristics did not. From the total of 127 patients who underwent EGD, complete biopsy results were available for 124 patients and were negative at all sites for 34.7% of patients (n = 43), equivocal for 20.2% (n = 25), and positive at 1 or more sites for 45.2% (n = 56). Boys were more likely than girls to have positive biopsy results (56.6% vs 36.6%, P < 0.03) because of the higher rate of positive esophageal biopsy results (47.2% vs 26.8%, P < 0.04). Among boys, vomiting (P < 0.02) and family stress (P < 0.04) predicted positive esophageal biopsy findings. Among girls, depressive symptoms predicted positive biopsy findings (P = 0.015). Upper abdominal symptoms, sex, stress, and depressive symptoms predict positive EGD biopsy findings in patients with chronic abdominal pain. Research on mechanisms linking these factors to mucosal damage in the gut is warranted.

Lithium-Associated Kidney Microcysts

Long-term lithium therapy is associated with impairment in concentrating ability and, occasionally, progression to advanced chronic kidney disease from tubulointerstitial nephropathy. Biopsy findings in patients with lithium-induced chronic tubulointerstitial nephropathy include tubular atrophy and interstitial fibrosis interspersed with tubular cysts and dilatations. Recent studies have shown that cysts are seen in 33–62.5% of the patients undergoing lithium therapy. MR imaging is highly capable of defining renal morphological features and has been demonstrated to be superior to US and CT scan for the visualization of small renal cysts. The microcysts are found in both cortex and medulla, particularly in the regions with extensive atrophy and fibrosis, and can be multiple and bilateral. They tend to be sparse and do not normally exceed 12 mm in diameter. The renal microcysts in the image here reported are subtle, but consistent with lithium-induced chronic nephropathy. An MRI of the kidneys provides noninvasive evidence that strengthens the diagnosis of lithium-induced nephropathy.

Survival Analysis and Clinicopathological Factors Associated With False-Negative Sentinel Lymph Node Biopsy Findings in Patients with Cutaneous Melanoma

Survival Analysis and Clinicopathological Factors Associated With False-Negative Sentinel Lymph Node Biopsy Findings in Patients with Cutaneous Melanoma

Alport’s syndrome and benign familial haematuria: Light and electron microscopic studies of the kidney

Hereditary nephropathy is clinically characterized by the familial occurrence in successive generations of progressive haematuric nephritis and neural hearing loss. Hereditary nephropathy of Alport's syndrome (AS) and benign familial (recurrent) haematuria (BFH) are morphologically characterized by specific and diagnostically important thickening and splitting of lamina densa of the glomerular basement membranes. Those lesions can be recognized only by electron microscopy. Hereditary nephritis is usually present clinically with haematuria, and new mutations without a family history of haematuria. It is therefore important to differentiate hereditary nephritis from BFH and no familial haematuria. Thus, electron microscopy is essential in diagnosis of haematuria. The aim of this study was to describe, by light microscopy, constellation of renal alterations by which hereditary nephropathy can be recognized with high probability as well as to compare the diagnostic validity of the findings observed by light and electron microscopy in AS and BFH. We examined 48 renal biopsies of the patients with hereditary nephoropathies by light and electron microscopy. Tissue samples were fixed in buffered paraformaldehyde and embedded in paraffin for long-term preservation. For the electron microscopy analysis, the following fixation in 4% glutaraldehyde tissue was postfixed in 1% osmium tetroxide. Thereafter, the following dehydration procedure tissue slices were embedded in epon. Our results demonstrated that the interstitial foam cells, foetal-like glomeruli, minimal glomerular abnormalities with stain less intense in basement membranes, mild irregular mesangial widening, focal thickening of Bowman's capsule, foci of dilatation tubules, tubular ectasia and atrophy, erythrocyte tubules casts were present in hereditary nephritis. Additionally, light microscopic biopsy findings in patients with BFH were either normal or revealed minor changes (e.g. increased mesangial matrix). All biopsies were reevaluated by electron microscopy and ultrastructural findings confirmed the diagnosis of hereditary nephropathies. The findings observed by light microscopy represent an important step that leads to a definitive diagnosis of AS and BFH.The definitive diagnosis, however, depends on electron microscopy.

Fine-Needle Aspiration Biopsy Findings in Patients With Small Lymphocytic Lymphoma Transformed to Hodgkin Lymphoma

Although small lymphocytic lymphoma (SLL) is an indolent lymphoma, approximately 5% of cases can transform to a higher-grade lymphoma, rarely Hodgkin lymphoma (HL). We report the fine-needle aspiration (FNA) results of 6 cases of SLL/chronic lymphocytic leukemia (CLL) that transformed to HL. FNA findings were correlated with the histologic features and clinical follow-up. The patients included 5 men and 1 woman, ranging in age from 49 to 72 years at the time of SLL/CLL diagnosis with time for development of HL ranging from 0 to 95 months (mean, 49.3 months). The FNA diagnoses were SLL with HL transformation (2 cases), SLL with large atypical cells (1 case), and atypical lymphoid proliferation with large atypical cells (3 cases). Flow cytometry performed in 5 cases (2 FNA specimens) demonstrated a monoclonal B-cell population with CD19/CD5 coexpression. The presence of large atypical mononucleated and binucleated cells in lymph node FNA specimens from patients with SLL/CLL with progressive adenopathy should raise the possibility of transformation to HL. In these cases, histologic confirmation is always recommended, not only to differentiate HL transformation from other entities but also for subclassification of HL.

Survival Analysis and Clinicopathological Factors Associated With False-Negative Sentinel Lymph Node Biopsy Findings in Patients with Cutaneous Melanoma

We analyzed the outcomes and factors associated with false-negative (FN) results of sentinel lymph node (SLN) biopsy findings in patients with cutaneous melanoma. SLN biopsy failure rate was defined as nodal recurrence in the biopsied regional basin without previous local or in-transit recurrence. Between April 1997 and December 2004, a total of 1207 patients with cutaneous melanoma with a median Breslow thickness of 2.4 mm underwent SLN biopsy by preoperative and intraoperative lymphoscintigraphy combined with dye injection. In 228 cases, we found positive SLNs; of these, 220 underwent completion lymph node dissection (CLND). Median follow-up was 3 years. The SLN biopsy failure rate was 5.8% (57 of 979 SLN negative). Median time to occurrence of FN relapse after SLN biopsy was 16 months (range, 3-74 months). The FN SLN biopsy results correlated with primary tumor thickness >4 mm (P = .0012), primary tumor ulceration (P = .0002), primary tumor level of invasion Clark stage IV/V (P = .0005), and nodular melanoma histological type (P = .0375). Five-year overall survival, calculated from the date of primary tumor excision, in the FN group was 53.7%, which was not statistically significantly worse than the CLND group (56.8%; P = .9). The FN group was characterized by a higher ratio of two or more metastatic nodes and extracapsular involvement of lymph nodes after LND compared with the CLND group (P < .0001 and P < .0001, respectively). Additional detailed pathological review of FN SLN revealed metastatic disease in 14 patients, which decreased the SLN biopsy failure rate to 4.4% (43 of 979). Survival of patients with FN results of SLN biopsy does not differ statistically significantly from that of patients undergoing CLND, although it is slightly lower. The SLN biopsy failure rate is approximately 5.0% in long-term follow-up and is associated mainly with the same factors that indicate a poor prognosis in primary melanoma.