Lyme endocarditis.

Lyme borreliosis is a common tick-borne disease with a wide variety of clinical manifestations. Cardiac involvement has been reported during both the acute phase (atrioventricular block, pericarditis) and the chronic stage (dilated cardiomyopathy), but is rare (<5%). Here we describe the first case of Borrelia afzelii Lyme endocarditis, in a 61-year-old man living in an endemic area of France. The diagnosis was confirmed by detection of B. afzelii DNA in the mitral valve by specific real-time PCR. He was treated empirically with amoxicillin for 6 weeks and remains well 12 months later.

[Preoperative factors of misdiagnosis of renal angiomyolipoma]. / Facteurs associés à l'échec du diagnostic préopératoire des angiomyolipomes rénaux.

OBJECTIVES: To explain the high incidence of misdiagnosis of angiomyolipoma (AML) prior to surgery. MATERIALS AND METHODS: Between 1989 and 2007, 2,657 patients were operated for a renal tumor at Dupuytren hospital in Limoges and at Cochin hospital in Paris. In 85 cases (3.2%), tumors were AMLs on pathology. The group of patients in which the diagnosis was done preoperatively was compared to the one in which the diagnosis was missed. RESULTS: Mean age of patients was 57-years-old and the sex-ratio was five women for one man. The mean size of AMLs was 5.4 cm. The patients were symptomatic in 46% of cases (39/85). The diagnosis of AML was ignored preoperatively in 62 patients (73%). In multivariate analysis, the small size of the AML, low proportion of fat and male sex were significantly associated with misdiagnosis of AML (p<0.001, p<0.018 and p<0.008, respectively). CONCLUSIONS: The incidence of misdiagnosis of AML preoperatively is high. The diagnosis seems particularly difficult when the tumor is small or contains a small proportion of fat. In addition, this study highlights that the diagnosis of AML is frequently ignored in men. The increased resolution of CTscan and the use of preoperative biopsies for tumors less than 4 cm could be helpful to decrease the incidence of useless surgery of AMLs.

Non-invasive imaging correlates with histological and molecular characteristics of an osteosarcoma model: application for early detection and follow-up of MDR phenotype.

BACKGROUND: In an orthotopic rat osteosarcoma model, histological and molecular findings were compared with the results of non-invasive imaging methods to assess disease progression at the primary site, the pattern of metastatic dissemination and the chemoresistance phenotype. MATERIALS AND METHODS: Primary tumor engraftment, vascularization, growth and metastatic spread were evaluated using 18FDG tomoscintigraphy. Bone neoformation in the primary tumor and metastasis was determined using 18FNa confirmed by classical histological studies. Chemoresistance phenotype was assessed by analysis of MDR1 and MRP1 genes expression compared to 99mTc MIBI imaging. RESULTS: 99mTc MIBI imaging correlated with the overexpression of the MDR1 and MRP1 genes. 18FDG, 18FNa and 99mTc tomoscintigraphies revealed that the pattern of vascularization, bone neoformation and hematogeneous metastatic dissemination in our animal model mimics its human counterpart. CONCLUSION: Multimodality, non-invasive imaging is a valid surrogate marker of histological and molecular characteristics in an orthotopic osteosarcoma model in immunocompetent rats; it allows extensive in vivo follow-up of osteosarcoma, including longitudinal analysis of chemoresistance.

Cyclooxygenase-2 is expressed frequently and early in Barrett's oesophagus and associated adenocarcinoma.

AIMS: To establish the prevalence of cyclooxygenase-2 (COX-2) expression in a large series of resected Barrett's adenocarcinoma and associated preneoplastic lesions and to correlate this expression with clinicopathological data and prognosis. METHODS: COX-2 expression was assessed by immunohistochemistry in resected surgical specimens of 66 Barrett's adenocarcinomas and 32 cases of Barrett's mucosa (with dysplasia in 17 cases). RESULTS: Epithelial expression of COX-2 protein was increased in Barrett's mucosa compared with normal oesophagus. Epithelial expression of COX-2 was found in 91% of Barrett's specialized mucosa negative for dysplasia, 94% of Barrett's mucosa with dysplasia, and 97% of Barrett's adenocarcinoma. COX-2 expression was significantly higher in the well-differentiated adenocarcinomas when compared with the poorly differentiated tumours. There was no significant correlation between COX-2 expression and the other pathological features of the tumours. Survival analysis showed no significant prognostic value for COX-2. CONCLUSION: Our results confirm up-regulation of COX-2 in Barrett's oesophagus-metaplastic and dysplastic-and in Barrett's adenocarcinoma. Increased COX-2 expression did not differ during the progression from Barrett's oesophagus negative for dysplasia to Barrett's adenocarcinoma and is related to adenocarcinoma whose histology is well differentiated. This suggests that enhanced expression of COX-2 may occur early during Barrett's-associated neoplastic transformation.

Molecular study of an IgG1kappa cryoglobulin yielding organized microtubular deposits and glomerulonephritis in the course of chronic lymphocytic leukaemia.

Glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits (GOMMID) and glomerulonephritis related to type I cryoglobulin are well-known but rare complications of B cell derived chronic lymphocytic leukaemia. In these disorders, monoclonal Ig have never been studied at the molecular level. We conducted a pathological and molecular analysis in a patient with chronic lymphocytic leukaemia, glomerulonephritis and a single circulating monoclonal Ig. Unusual IgG1kappa kidney deposits were observed. The heavy and light chain variable region sequences of that cryoprecipitating monoclonal Ig were characterized. Light microscopy revealed glomerulonephritis typical of cryoglobulinaemia, with neutrophil and macrophage infiltration, endocapillary hyperplasia and few protein thrombi. Electron microscopic study clearly evidenced numerous subepithelial mixed granular and organized deposits with a unique microtubular organization, reminiscent of the GOMMID. The Ig molecule sequence revealed alterations of charge and hydrophobicity potentially promoting a crystal-like aggregation and the aggregation of microtubules. This description suggests that common mechanisms are involved in various forms of precipitation and/or deposition of complete Ig molecules, with a variable extent of organization and with a possible overlap between pathological patterns of either glomerulonephritis with microtubular deposits or type I cryoglobulinic glomerulonephritis.

MLH1 and MSH2 protein immunohistochemistry is useful for detection of hereditary non-polyposis colorectal cancer in young patients.

AIMS: Hereditary non-polyposis colorectal cancer is related to germline mutations of DNA mismatch repair genes MLH1 and MSH2, which result in microsatellite instability and loss of protein expression of the corresponding mutated gene in the tumour tissue. METHODS AND RESULTS: MLH1 and MSH2 protein expression was studied by immunohistochemistry in paraffin-embedded surgical samples of 100 colorectal adenocarcinomas occurring before 50 years of age. Absence of tumour cell nuclear staining with positive internal control (normal mucosa, lymphoid follicles) was considered negative. Loss of MLH1 or MSH2 expression was found in 20 cases with microsatellite instability in 15 cases. Twelve of these patients had a family history of colorectal cancer. Compared with MLH1- and MSH2-positive cases, MLH1- or MSH2-deficient colorectal adenocarcinomas were significantly associated on multivariate analysis with a younger age (38 vs. 43 years, P;0.0224), a larger tumour size (60 +/- 6 vs. 46 +/- 2 mm, P=0.0291), an expanding margin (85% vs. 51%, P=0.0159), a higher number of tumour-infiltrating lymphocytes assessed by CD3 immunostaining (202 +/- 48 vs. 33 +/- 4 CD3+ lymphocytes/10 high-power fields, P=0.0039), and a grade 2 Crohn's like lymphoid reaction (70% vs. 9%, P=0.0037). The two groups were not different for tumour site, differentiation, pTNM stage, vascular and perineural invasion, peripheral adenomatous residue, and 5-year survival rates. CONCLUSIONS: MLH1- or MSH2-deficient colorectal carcinomas of young patients exhibit pathological and molecular features similar to hereditary non-polyposis colorectal cancer. This suggests that MLH1 and MSH2 immunohistochemistry is valuable for detecting hereditary non-polyposis colorectal cancer in young patients.

[Pseudoneoplastic forms of bronchiolitis obliterans with organizing pneumopathy (BOOP)]. / Formes pseudo-néoplasiques des BOOP.

Chronic obstructive bronchiolitis with organizing lung disease is an anatomoradioclinical entity characterized by nonspecific inflammation associated with recurrent migratory minimally dense alveolar opacities on the chest x-ray poorly responsive to corticosteroid therapy. Excepting this typical presentation, other clinical forms may occur. We report the cases of two patients with an exceptional localized presentation raising the differential diagnosis of lung cancer.

Renal angiomyolipoma: further immunophenotypic characterization of an expanding morphologic spectrum.

BACKGROUND: Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor. OBJECTIVE: To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell). DESIGN: Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases. RESULTS: All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin. CONCLUSION: In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.

[Epidural non-Hodgkin's lymphoma presenting as a spinal cord compression]. / Lymphomes non hodgkiniens épiduraux révélés par une compression médullaire.

OBJECTIVE AND METHODS: epidural localization is a rare presenting sign of non Hodgkin's lymphoma. In this study, we describe the clinical, histological and immunohistochemical data in 13 cases (9 men and 4 women) of non-Hodgkin's lymphoma with epidural involvement. RESULTS: the median age was 63 years (range 36-76 years). Clinically, most patients complained of back pain (median duration, 3.4 months) followed by acute neurological deterioration. In 10 out of 13 tumors, a thoracic localization was observed and a decompressive laminectomy was performed in all cases. Histology and immunohistochemistry showed all tumors to be B-cell lymphomas which were classified as: lymphocytic lymphoma (3 cases), prolymphocytic lymphoma (1 case), follicular lymphoma (2 cases), diffuse large cell lymphoma (6 cases) and AIDS associated Burkitt lymphoma (1 case). Post-operative staging revealed bone and/or paravertebral involvement in 11 cases and disseminated disease in 5 cases. Median survival following complementary therapy, radiotherapy and chemotherapy in most cases, was 20 months. CONCLUSION: histological features of epidural lymphomas are similar to other extranodal lymphomas and their prognosis is better than other epidural neoplasms, especially when the tumor is localized.

Detection of fastidious bacteria in cardiac valves in cases of blood culture negative endocarditis.

The diagnosis of blood culture negative endocarditis is still a problem. Fastidious bacteria such as bartonella and coxiella are responsible for cases of blood culture negative endocarditis, the identification of which is mainly based on serological and DNA studies only available in specialised centres. Therefore, a routine technique is needed in surgical pathology laboratories to detect these bacteria in cardiac valve tissue sections. This report describes a staining technique, the Gimenez stain, feasible and sensitive in detecting bartonella and coxiella in two cases of blood culture negative endocarditis.

Cholesterol crystal embolization demonstrated on GI biopsy.

OBJECTIVES: Cholesterol crystal embolism is a severe complication of atherosclerosis responsible for nonspecific cutaneous, renal, and, less often, digestive manifestations that may mimic other systemic diseases. METHODS: We reviewed retrospectively 10 patients with histologically proven cholesterol crystal emboli diagnosed by endoscopic GI biopsy. RESULTS: All patients had prior clinical manifestations of severe atherosclerosis and predisposing factors for cholesterol migration. They all had cutaneous manifestations of cholesterol crystal embolism, acute renal failure, and biological inflammatory syndrome. Digestive symptoms were found in the 10 patients: abdominal pain in eight, diarrhea in four, and GI bleeding in three. GI endoscopy ruled out specific digestive diseases, showing only a congestive or erosive mucosa. Histological diagnosis of cholesterol crystal emboli was based on gastric biopsy in nine patients, duodenal biopsy in four, colonic biopsy in three, and rectal biopsy in one, with six having positive biopsies on multiple sites. Outcome after the diagnosis of cholesterol crystal embolism was poor, with all patients requiring permanent hemodialysis. Death by atherosclerosis complications occurred in five patients. CONCLUSIONS: This cohort suggests that upper GI endoscopy may be helpful in demonstrating the presence of cholesterol crystal embolism, and that diagnosis of cholesterol crystal emboli on digestive tract biopsy indicates advanced systemic atherosclerosis disease of poor prognosis.

Colorectal cancer before the age of 40: a case-control study.

PURPOSE: Colorectal adenocarcinoma before the age of 40 is uncommon, and its prognosis is controversial, with many studies reporting a worse prognosis than in older patients and others showing no difference. The current study compared two groups of patients who had surgical resection for colorectal adenocarcinoma. METHODS: The case group was composed of 34 patients younger than 40 (34 +/- 4) years. Detailed pathologic prognosis factors, tumor cell proliferation measured by proliferating cell nuclear antigen, survival, family history, and predisposing conditions were analyzed. Results were compared with a control group constituted of 34 patients older than 65 (75 +/- 6) years matched by gender, cancer site, and Dukes stage. RESULTS: Tumor differentiation, presence of vascular and perineural neoplastic invasion, tumor growth pattern, tumor cell proliferation measured by proliferating cell nuclear antigen count, and survival according to the Kaplan-Meier method were not significantly different between younger and older patients. The only difference between the two groups was a higher prevalence of family history and predisposing conditions for colorectal cancer in younger patients (23 vs. 3 percent; P = 0.03). CONCLUSION: This case-control study documents that pathologic features and prognosis of colorectal adenocarcinoma are comparable in patients younger than 40 years compared with older patients for identical stages. The higher prevalence of positive family history in younger patients suggests a different genetic background compared with older patients.

Angiogenesis in the neoplastic sequence of Barrett's oesophagus. Correlation with VEGF expression.

The purpose of this study was to determine the angiogenic profile of human oesophageal adenocarcinoma. This study was carried out on a large series of surgically resected Barrett's adenocarcinomas and associated preneoplastic lesions. Vascularization was quantified by microvessel counting and measurement of the percentage microvessel surface area after immunohistochemistry using the CD34 antibody. The expression of vascular endothelial cell growth factor (VEGF) was also examined by immunohistochemistry. Results were correlated with clinico-pathological data and prognosis. Vascularization, assessed by both microvessel counting and measurement of the microvessel surface, was statistically higher in superficial cancers than in others. Higher vascularization was correlated with a lower rate of lymph node and distant metastasis, as well as with better survival. However, when superficial carcinomas were excluded from the study, microvessel count failed to provide any significant prognostic information. Irrespective of the inclusion or exclusion of superficial tumours, the expression of VEGF was correlated with a higher vascularisation but did not provide prognostic significance. It is concluded that high angiogenic properties are acquired in precancerous lesions and early cancers in Barrett's oesophagus. Vascularization as assessed by both microvessel counting and measurement of the microvessel surface is not informative for prognosis in infiltrative Barrett's adenocarcinomas. The expression of VEGF is correlated with vascularization, but has no independent prognostic relevance.

[External iliac artery endofibrosis of the cyclist]. / Endofibrose iliaque externe du cycliste.

Arterial endofibrosis is a rare disease usually affecting the external iliac artery in highly trained athletes. We report a case of bilateral external iliac endofibrosis in a 44-year-old cyclist. Microscopic examination of the resection specimen showed an isolated thickening of the arterial intima, and confirmed the diagnosis of this entity of unknown etiology.

Renal lesions in von Hippel-Lindau disease: immunohistochemical expression of nephron differentiation molecules, adhesion molecules and apoptosis proteins.

AIMS: Renal lesions in von Hippel-Lindau disease comprise clear cell simple cysts, atypical cysts and carcinomas. Although histological and molecular studies suggest that cystic lesions may represent precursors of carcinomas, there is no detailed phenotypic evidence of their relationship. METHODS AND RESULTS: To investigate such a possible relationship between cystic lesions and solid carcinomas, we studied the pathological and immunohistochemical features of 328 lesions of 33 kidneys originating from 23 patients with von Hippel-Lindau disease, using a panel of antibodies directed against cytoskeleton proteins, cell surface proteins, integrin subunits, adhesion molecules, lectins, and apoptosis and proliferation markers. Solid carcinomas (n = 175) were all of clear cell type and mostly nuclear grade 1. Cystic lesions (n = 138) consisted of cystic clear cell carcinomas (n = 15), atypical cysts (n = 20) and simple cysts (n = 103). Clear cells of the simple cysts, atypical cysts and solid carcinomas coexpressed cytokeratins (CK8, CK19) and vimentin, and expressed a similar pattern of tubular markers (CD24, tetraglonolobus), integrin subunits (alpha3, alpha5, alpha6, alphav, beta1) and cell adhesion molecules (ICAM 1, VCAM 1). In all lesions studied, proliferation rate (MIB1 index) was low, and apoptosis marker expression (fragmented DNA, p53, bcl-2) inconspicuous. CONCLUSIONS: Phenotypic alterations found in solid renal cell carcinomas are already present in simple and atypical renal cysts of von Hippel-Lindau disease.

[Pancreatic neuroendocrine tumors and von Hippel-Lindau disease]. / Tumeurs neuro-endocrines du pancréas et maladie de von Hippel-Lindau.

Pancreatic neuroendocrine tumors are rare in von Hippel-Lindau disease, most often asymptomatic, nonfunctioning, non secreting, and benign. We report a case of low grade malignant pancreatic, secreting and asymptomatic neuroendocrine tumors, occurring in a 27 year old woman in the setting von Hippel-Lindau disease with recurrent pheochromocytoma, retinal and medullary hemangioblastomas, paraganglioma of the carotid body and ovarian cystadenoma. Neuroendocrine pancreatic tumors of von Hippel-Lindau disease are often constituted by clear cells, in the contrary of other neuroendocrine tumors of the pancreas. Occurrence of a pancreatic neuroendocrine tumor, especially in association with pheochromocytoma, may be misdiagnosed with a type 2 multiple endocrine neoplasia syndrom instead of von Hippel-Lindau disease.