High-altitude pulmonary edema: the intercellular network hypothesis.

The pathophysiology of high-altitude pulmonary edema is currently attributed to exacerbated heterogeneous hypoxic pulmonary vasoconstriction. However, although other cellular mechanisms have been hypothesized, they are still poorly understood. In this review, we focused on cells of the pulmonary acinus, the distal unit for gas exchange, known to be responders to acute hypoxia, notably through many humoral or tissue factors that connect this intercellular network constituting the alveolo-capillary barrier. Hypoxia could drive alveolar edema by: 1) damaging the fluid reabsorption capacity of alveolar epithelial cells, 2) increasing the endothelial and epithelial permeability, especially by alteration of occluding junctions, 3) triggering the inflammation mainly led by alveolar macrophages, 4) increasing interstitial water accumulation by disruption of extracellular matrix architecture and tight junctions, 5) inducing pulmonary vasoconstriction through an orchestrated response of pulmonary arterial endothelial and smooth muscle cells. Hypoxia may also alter the function of fibroblasts and pericytes that contribute to the interconnection of the cells of the alveolar-capillary barrier. Due to its complex intercellular network and delicate pressure gradient equilibrium, the alveolar-capillary barrier is simultaneously affected by acute hypoxia in all its components, leading to rapid accumulation of water in the alveoli.

Macroscopic hematuria with normal renal biopsy-following the chain to the diagnosis: Questions.

BACKGROUND: Alport syndrome (AS) is an inherited glomerular disease associated with hearing and eye defects; its morbidity is a public health issue in developed countries. AS results from mutations in COL4A3, COL4A4, or COL4A5 genes, respectively encoding the alpha-3, alpha-4, and alpha-5 chains of type IV collagen, a major component of the renal glomerular basement membrane (GBM). The diagnosis is usually confirmed by a renal biopsy showing a thinning/thickening of the GBM, with a longitudinal splitting of the lamina densa. CASE DIAGNOSIS: We report the case of a 10-year-old patient who presented multiple episodes of macroscopic hematuria. On renal biopsy, the electron microscopy analysis of the GBM was normal, as was the COL4A5 immunofluorescence assay. Genetic analyses showed a homozygous duplication of exons 44 to 47 of the COL4A3 gene, confirming the diagnosis of autosomal recessive AS. CONCLUSIONS: Our report suggests that, in patients with clinical evidence of AS, genetic testing should be performed whenever pathological analysis is not in favor of AS diagnosis. This will ensure that AS patients benefit from an early diagnosis, adequate treatment, and that end-stage renal disease (ESRD) onset is delayed.

Macroscopic hematuria with normal renal biopsy-following the chain to the diagnosis: Answers.

BACKGROUND: Alport syndrome (AS) is an inherited glomerular disease associated with hearing and eye defects; its morbidity is a public health issue in developed countries. AS results from mutations in COL4A3, COL4A4, or COL4A5 genes, respectively encoding the alpha-3, alpha-4, and alpha-5 chains of type IV collagen, a major component of the renal glomerular basement membrane (GBM). The diagnosis is usually confirmed by a renal biopsy showing a thinning/thickening of the GBM, with a longitudinal splitting of the lamina densa. CASE DIAGNOSIS: We report the case of a 10-year-old patient who presented multiple episodes of macroscopic hematuria. On the renal biopsy, the electron microscopy analysis of the GBM was normal, as was the COL4A5 immunofluorescence assay. Genetic analyses showed a homozygous duplication of exons 44 to 47 of the COL4A3 gene, confirming the diagnosis of autosomal recessive AS. CONCLUSIONS: Our report suggests that in patients with clinical evidence of AS, genetic testing should be performed whenever pathological analysis is not in favor of AS diagnosis. This will ensure that AS patients benefit from an early diagnosis, adequate treatment, and that end-stage renal disease (ESRD) onset is delayed.

Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN.

Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m(2) Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m(2)with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death.

Genetic background-dependent thrombotic microangiopathy is related to vascular endothelial growth factor receptor 2 signaling during anti-glomerular basement membrane glomerulonephritis in mice.

Because genetic background plays a pivotal role in humans and in various experimental models, we carefully monitored its impact on glomerular pathological characteristics during experimental anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN), using two leading mouse strains, 129S2/SvPas (129Sv) and C57bl/6J (B6J). These mice exhibited different severities of renal failure, hypertension, and glomerular lesions, according to their genetic background. In addition to the classic glomerular proliferative lesions, glomerular thrombotic microangiopathy (TMA) was found as a common genetic background-dependent histopathological hallmark of anti-GBM-GN, combined with hemolytic anemia and thrombocytopenia. Glomerular expression profiling, using microarrays and Western blot analysis in B6J TMA-resistant and 129Sv TMA-prone mice, demonstrated major differences in vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) 2 pathways, despite similar Vegfa expression levels. Further analysis revealed a lower basal glomerular endothelial Vegfr2 expression level in 129Sv TMA-prone mice compared with B6J TMA-resistant mice. This difference was even more pronounced during anti-GBM-GN, explaining why an exogenous VEGFA supply failed to rescue any 129Sv TMA lesions. Conversely, the systemic blocking of Vegfr2 amplified TMA lesions only in B6J mice. Herein, we specified the role that genetic background plays in determining, in particular, the level of Vegfr2 expression. We also demonstrated that glomerular Vegfr2-dependent TMA lesions are an underevaluated common hallmark of anti-GBM-GN in mice.

Allo-immune membranous nephropathy and recombinant aryl sulfatase replacement therapy: a need for tolerance induction therapy.

Nephrotic syndrome was reported in a highly-sensitized patient receiving enzyme replacement therapy (ERT) for Pompe disease, but the prevalence of ERT-induced renal complications and mechanisms to facilitate readministration of ERT in these patients remain unexplored. This work identifies a new antigen responsible for secondary membranous nephropathy (MN) in a patient with mucopolysaccharidosis type VI caused by aryl sulfatase B (ASB) deficiency. ERT (recombinant human ASB [rhASB]; 1 mg/kg per week) started at the age of 4 years led to a high anti-rhASB titer and dramatically improved clinical manifestations. However, 16 months later, the patient suddenly developed nephrotic syndrome resistant to steroid therapy 1 week after orthopedic surgery. Examination of the kidney biopsy specimen revealed glomerular deposition of IgG (mostly IgG4, C3, and C5b-9) in a granular pattern typical of MN. Double immunofluorescence staining showed that subepithelial granular deposits contained rhASB colocalized with IgG. Ig eluted from the patient's biopsy specimen reacted specifically with rhASB. On discontinuation of ERT, proteinuria progressively decreased, but the patient's clinical condition markedly deteriorated. Induction of tolerance to rhASB was initiated by coadministration of low-dose corticosteroids, rituximab, intravenous Igs, and oral methotrexate. ERT was resumed 8 weeks after starting immunosuppressive therapy without inducing a rebound of antibody titer or an increase in proteinuria. We conclude that the allo-immune response to the recombinant rhASB caused the nephropathy. Considering the critical requirement for ERT in patients with such enzyme deficiencies, immune tolerance induction should be advocated in the patients with allo-immune MN.

Light chain deposition disease without glomerular proteinuria: a diagnostic challenge for the nephrologist.

BACKGROUND: Renal involvement in light chain (LC) deposition disease (LCDD) is typically characterized by nodular glomerulosclerosis and nephrotic range proteinuria. Rare cases of LCDD without glomerular symptoms have been reported, but clinical and pathological characteristics of this entity remain poorly described. METHODS: This multi-centre retrospective study included 14 patients with biopsy-proven renal LCDD and proteinuria <0.5 g/day at diagnosis. RESULTS: Baseline median serum creatinine was 281 (136-594) µmol/L, with a glomerular filtration rate of 20 (6-48) mL/min/1.73 m(2). A serum monoclonal immunoglobulin was detected in 12 cases and LC proteinuria only in 7, always of kappa isotype. Monoclonal gammopathy of undetermined significance/indolent multiple myeloma (MM) was diagnosed in nine cases, symptomatic MM in three cases. Hypertension was almost constant (10 of 14). Immunofluorescence studies of kidney biopsies showed linear kappa LC deposition along tubular basement membranes in all cases, with linear glomerular and vascular LC deposits in 11 and 10 patients, respectively. By light microscopy, tubulo-interstitial lesions were prominent in all patients and focal nodular glomerulosclerosis was only observed in two cases. Identification of LCDD led to initiation of chemotherapy in 12 cases. After a median follow-up of 25.5 months, five patients died and four progressed to end-stage renal disease. Renal response occurred in five of the eight patients who achieved sustained haematological response. CONCLUSIONS: LCDD can cause severe renal dysfunction, despite the absence of glomerular symptoms. Early identification of the disease and introduction of a chemotherapy targeting the underlying plasma cell disorder may preserve long-term renal prognosis.

Bilirubin-associated acute tubular necrosis in a kidney transplant recipient.

Unlike hemoglobin or myoglobin, bilirubin, a breakdown product of the catabolism of heme molecules, usually is not seen as a nephrotoxic protein. We report the case of an adult kidney recipient who developed jaundice 4 years after transplantation because of a malignant cholangiocarcinoma. He progressively lost transplant function, accompanied by a continuous increase in bilirubinemia. Kidney biopsy showed bile granules in the cytoplasm of tubular epithelial cells and bile thrombi in dilated tubules, but no interstitial inflammation. The tumor was unresectable and the patient died 2 months later. Because the patient had no jaundice-associated confounding factor that could explain his kidney failure, such as sepsis, heart failure, or liver failure with hepatorenal syndrome, this exceptional case suggests that bilirubin per se should be seen as a potential cause of acute tubular necrosis.

Protocol biopsies in pediatric renal transplant recipients on cyclosporine versus tacrolimus-based immunosuppression.

BACKGROUND: Protocol biopsies can detect subclinical rejection and early signs of calcineurin inhibitor-induced nephrotoxicity. METHODS: In a prospective study, protocol biopsies 3 and 12 months after transplant in transplanted children from two centers were studied. One center used cyclosporine (CsA)-based immunosuppression and the other center used tacrolimus. Patients were on CsA (n = 26, group 1) or on tacrolimus (n = 10, group 2). Patients received basiliximab induction, mycophenolate mofetil, and prednisone. RESULTS: In patients on CsA, 26 kidney biopsies were performed during the 6 months after transplantation. Eighteen protocol biopsies were performed at 3 months post transplant; 13 were normal and five showed rejection (two borderline and three Banff II rejections). Eight biopsies were motivated by an increase of serum creatinine; four were normal and four revealed signs of acute rejection (two borderline and two Banff II). Twelve protocol biopsies were performed after 12 months; all were normal. For patients on tacrolimus (n = 10), ten protocol transplant biopsies were performed at 3 months post-transplant; none showed signs of rejection. No biopsy was performed for an increase of serum creatinine. There were no differences in patient age, number of human leukocyteantigen (HLA) incompatibilities, or other patient characteristics. CONCLUSIONS: Patients on tacrolimus had less acute rejection episodes detected on protocol biopsies 3 months after transplant. Protocol biopsies seem to play an important role in the detection of subclinical rejection in patients on CsA.

High incidence of triple-negative tumors in sub-saharan Africa: a prospective study of breast cancer characteristics and risk factors in Malian women seen in a Bamako university hospital.

OBJECTIVE: Few studies have been conducted on breast cancer in Sub-Saharan Africa and their results have been suspected to be impaired by artefacts. This prospective study was designed to determine tumor and patient characteristics in Mali with control of each methodological step. These data are necessary to define breast cancer treatment guidelines in this country. METHODS: Clinical and tumor characteristics and known risk factors were obtained in a consecutive series of 114 patients. Each technical step for the determination of tumor characteristics [histology, TNM, grade, estrogen (ER) and progesterone receptors (PR), HER2, and Ki67] was controlled. RESULTS: Patients had a mean age of 46 years. Most tumors were invasive ductal carcinomas (94%), T3-T4 (90%) with positive nodes (91%), grade III (78%), and ER (61%) and PR (72%) negative. HER2 was overexpressed in 18% of cases. The triple-negative subgroup represented 46%, displaying a particularly aggressive pattern (90% grade III; 88% Ki67 >20%). CONCLUSION: This study demonstrates the high incidence of aggressive triple-negative tumors in Mali. Apart from a higher prevalence of premenopausal women, no significant difference in risk factors was observed between triple-negative tumors and other tumors. The hormonal therapy systematically prescribed therefore needs to be revised in light of this study.

Renal arterial resistive index is associated with severe histological changes and poor renal outcome during chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a growing public health problem and end stage renal disease (ESRD) represents a large human and economic burden. It is important to identify patients at high risk of ESRD. In order to determine whether renal Doppler resistive index (RI) may discriminate those patients, we analyzed whether RI was associated with identified prognosis factors of CKD, in particular histological findings, and with renal outcome. METHODS: RI was measured in the 48 hours before renal biopsy in 58 CKD patients. Clinical and biological data were collected prospectively at inclusion. Arteriosclerosis, interstitial fibrosis and glomerulosclerosis were quantitatively assessed on renal biopsy in a blinded fashion. MDRD eGFR at 18 months was collected for 35 (60%) patients. Renal function decline was defined as a decrease in eGFR from baseline of at least 5 mL/min/ 1.73 m2/year or need for chronic renal replacement therapy. Pearson's correlation, Mann-Whitney and Chi-square tests were used for analysis of quantitative and qualitative variables respectively. Kaplan Meier analysis was realized to determine renal survival according to RI value using the log-rank test. Multiple logistic regression was performed including variables with p < 0.20 in univariate analysis. RESULTS: Most patients had glomerulonephritis (82%). Median age was 46 years [21-87], eGFR 59 mL/min/ 1.73m2 [5-130], percentage of interstitial fibrosis 10% [0-90], glomerulosclerosis 13% [0-96] and RI 0.63 [0.31-1.00]. RI increased with age (r = 0.435, p = 0.0063), pulse pressure (r = 0.303, p = 0.022), renal atrophy (r = -0.275, p = 0.038) and renal dysfunction (r = -0.402, p = 0.0018). Patients with arterial intima/media ratio ≥ 1 (p = 0.032), interstitial fibrosis > 20% (p = 0.014) and renal function decline (p = 0.0023) had higher RI. Patients with baseline RI ≥ 0.65 had a poorer renal outcome than those with baseline RI < 0.65 (p = 0.0005). In multiple logistic regression, RI≥0.65 was associated with accelerated renal function decline independently of baseline eGFR and proteinuria/creatininuria ratio (OR=13.04 [1.984-85.727], p = 0.0075). Sensitivity, specificity, predictive positive and predictive negative values of RI ≥ 0.65 for renal function decline at 18 months were respectively 77%, 86%, 71% and 82%. CONCLUSIONS: Our results suggest that RI ≥ 0.65 is associated with severe interstitial fibrosis and arteriosclerosis and renal function decline. Thus, RI may contribute to identify patients at high risk of ESRD who may benefit from nephroprotective treatments.

A case of phospholipase A2 receptor-positive membranous nephropathy preceding sarcoid-associated granulomatous tubulointerstitial nephritis.

We report the case of a 29-year-old man with membranous nephropathy that was associated with a sarcoidosic granulomatous tubulointerstitial nephritis, but was without an apparent calcium metabolism disorder. Corticosteroid treatment was associated with remission of nephrotic syndrome. We discuss the relationship between membranous nephropathy and sarcoidosis based on the close appearance of the 2 diseases and the detection of phospholipase A2 receptor in glomerular immune deposits.

Acute renal failure with lambda light chain-derived crystals in a patient with IgD myeloma.

Kidney involvement with immunoglobulin crystals usually relates to a light chain of the kappa type, in MGUS or smoldering myeloma, frequently causing Fanconi's syndrome with progressive renal insufficiency. We report on a case with severe myeloma featuring lambda light chain-derived crystals and acute kidney injury. Histology showed acute tubular necrosis and tubule obstruction with crystals, which were also abundant inside tubule epithelial cells, macrophages and bone marrow plasma cells. The light chain variable domain had a normal overall primary structure but included 11 somatic mutations, 3 of which likely increased the surface hydrophobicity, as observed in previously reported kappa-type crystals.

Evidence of follicular T-cell implication in a case of IgG4-related systemic disease with interstitial nephritis.

IgG4-related systemic disease is a protean disorder that covers a wide variety of lesions. We report on a patient with tubulointerstitial nephritis, lymphadenopathies, sialadenitis and retroperitoneal fibrosis. The salivary gland and kidney interstitium were infiltrated with B lymphocytes and T lymphocytes and IgG3(+) and IgG4(+) plasma cells. The overexpression of IgG1 and IgG3, in addition to IgG4, the unusual abundance of interfollicular plasma cells and CD4(+) T cells in germinal centres of lymph nodes, and the dramatic response to rituximab point to possible roles of follicular helper T cells in enhancing a skewed B-cell terminal maturation and of CD20(+) B cells in disease progression.

Immunoglobulin deposition disease with a membranous pattern and a circulating monoclonal immunoglobulin G with charge-dependent aggregation properties.

A 62-year-old woman presented with nephrotic syndrome, monoclonal gammopathy, and membranous-like nephropathy with nonorganized deposits composed of monoisotypic immunoglobulin G1 lambda protein. Nephrotic syndrome remitted after a brief course of treatment with melphalan despite ongoing production of the monoclonal protein. The circulating monoclonal immunoglobulin G1 lambda showed unusual in vitro aggregation properties, including dependence on low ionic strength and neutral pH, suggesting that electrostatic interactions had a role in the precipitation process. This case illustrates the importance of looking for monoclonal immunoglobulin deposits when kidney biopsy findings are suggestive of membranous nephropathy. In addition, our in vitro demonstrations of the role of physicochemical factors in immunoglobulin precipitation help elucidate the pathogenesis of immunoglobulin deposition disorders. Although binding to podocyte antigens is a well-recognized determinant of subepithelial immunoglobulin deposition, proneness to aggregation as described in this case also might be nephritogenic.

Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor.

We have recently described a new form of light chain deposition disease (LCDD) presenting as a severe cystic lung disorder requiring lung transplantation. There was no bone marrow plasma cell proliferation. Because of the absence of disease recurrence after bilateral lung transplantation and of serum-free light chain ratio normalization after the procedure, we hypothesized that monoclonal light chain synthesis occurred within the lung. The aim of this study was to look for the monoclonal B-cell component in 3 patients with cystic lung LCDD. Histologic examination of the explanted lungs showed diffuse nonamyloid kappa light chain deposits associated with a mild lymphoid infiltrate composed of aggregates of small CD20(+), CD5(-), CD10(-) B lymphocytes reminiscent of bronchus-associated lymphoid tissue. Using polymerase chain reaction (PCR), we identified a dominant B-cell clone in the lung in the 3 studied patients. The clonal expansion of each patient shared an unmutated antigen receptor variable region sequence characterized by the use of IGHV4-34 and IGKV1 subgroups with heavy and light chain CDR3 sequences of more than 80% amino acid identity, a feature evocative of an antigen-driven process. Combined with clinical and biologic data, our results strongly argue for a new antigen-driven primary pulmonary lymphoproliferative disorder.

Bullous pemphigoid after boiling water burn.

Bullous pemphigoid is the most frequent autoimmune blistering disease, usually affecting elderly patients. Most cases are idiopathic. We report a case of bullous pemphigoid developing four weeks after a boiling water burn, initially at the site of the burn, then elsewhere.

Corneal stromal stem cells restore transparency after N2 injury in mice.

Corneal scarring associated with various corneal conditions is a leading cause of blindness worldwide. The present study aimed to test the hypothesis that corneal stromal stem cells have a therapeutic effect and are able to restore the extracellular matrix organization and corneal transparency in vivo. We first developed a mouse model of corneal stromal scar induced by liquid nitrogen (N2 ) application. We then reversed stromal scarring by injecting mouse or human corneal stromal stem cells in injured cornea. To characterize the mouse model developed in this study and the therapeutic effect of corneal stromal stem cells, we used a combination of in vivo (slit lamp, optical coherence tomography, in vivo confocal microscopy, optical coherence tomography shear wave elastography, and optokinetic tracking response) and ex vivo (full field optical coherence microscopy, flow cytometry, transmission electron microscopy, and histology) techniques. The mouse model obtained features early inflammation, keratocyte apoptosis, keratocyte transformation into myofibroblasts, collagen type III synthesis, impaired stromal ultrastructure, corneal stromal haze formation, increased corneal rigidity, and impaired visual acuity. Injection of stromal stem cells in N2 -injured cornea resulted in improved corneal transparency associated with corneal stromal stem cell migration and growth in the recipient stroma, absence of inflammatory response, recipient corneal epithelial cell growth, decreased collagen type III stromal content, restored stromal ultrastructure, decreased stromal haze, decreased corneal rigidity, and improved vision. Our study demonstrates the ability of corneal stromal stem cells to promote regeneration of transparent stromal tissue after corneal scarring induced by liquid nitrogen.

Epithelial ovarian tumors: value of dynamic contrast-enhanced MR imaging and correlation with tumor angiogenesis.

PURPOSE: To retrospectively evaluate the diagnostic performance of dynamic contrast material-enhanced magnetic resonance (MR) imaging for the characterization of ovarian epithelial tumors, by using histologic findings as the reference standard, and to correlate dynamic contrast-enhanced MR imaging findings with angiogenesis biomarkers. MATERIALS AND METHODS: Ethics committee approval was obtained, with waiver of informed consent. Patients consented to having their data used for future retrospective research. Forty-one women (age range, 22-73 years) with 48 epithelial ovarian tumors underwent dynamic contrast-enhanced MR imaging before surgical excision. In case of bilateral tumors (n = 7), only the most complex tumor was analyzed. Thus, 41 tumors (12 benign, 13 borderline, and 16 invasive) were examined with dynamic contrast-enhanced MR imaging and immunohistochemical methods. Dynamic contrast-enhanced MR imaging parameters (enhancement amplitude [EA], time of half rising [T(max)], and maximal slope [MS]) were analyzed according to histopathologic findings, microvessel density, pericyte coverage index (PCI), and vascular endothelial growth factor receptor 2 (VEGFR-2) expression. Statistical analyses were performed by using Kruskal-Wallis, Fisher exact, and Spearman tests and receiver operating curve analysis. RESULTS: EA was higher for invasive tumors than for benign (P < .001) and borderline (P < .05) tumors. T(max) was longer for benign tumors than for borderline (P < .05) and invasive (P < .01) tumors. MS was steeper for invasive tumors than for benign (P < .001) and borderline (P < .001) tumors. PCI was lower in invasive tumors than in borderline (P < .05) and benign (P < .05) tumors. Microvessels showed stronger immunohistochemical VEGFR-2 expression in invasive tumors than in benign or borderline tumors (P < .05). MS correlated with a lower PCI (r = -0.34, P = .04) and stronger VEGFR-2 expression by using both epithelial (r = 0.41, P < .01) and endothelial (r = 0.66, P < .001) cells. CONCLUSION: The early enhancement patterns of ovarian epithelial tumors on dynamic contrast-enhanced MR images can help distinguish among benign, borderline, and invasive tumors and were found to correlate with tumoral angiogenic status.

Factors influencing the use and accuracy of frozen section diagnosis of epithelial ovarian tumors.

OBJECTIVE: The objective of the study was to study factors influencing the use and accuracy of frozen section diagnosis (FSD) of ovarian tumors. STUDY DESIGN: Surgery was performed in 414 patients with epithelial ovarian tumors between 2001 and 2006. Factors were identified by univariate and multivariate analysis. RESULTS: FSD was requested in 274 patients: 152 benign, 55 borderline, and 67 malignant tumors. Age 50 years or older, tumor size 10 cm or greater, and preoperative evidence of malignancy were associated with FSD request. The sensitivity and specificity of FSD for benign, borderline, and malignant tumors were 97% and 81%, 62% and 96%, and 88% and 99%, respectively. The histologic type (mucinous), tumor size (less than 10 cm), the borderline component (less than 10%), and the pathologist's experience predicted misdiagnosis of borderline tumors. Spread outside the ovary was the only significant predictor of accurate FSD of malignant tumors. CONCLUSION: FSD is less accurate for borderline than benign and malignant ovarian tumors. The pathologist's experience is a major determinant of diagnostic accuracy.