[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.

Brain tumor-polyposis syndrome: two genetic diseases?

PURPOSE AND DESIGN: This report presents a comprehensive and statistical analysis of the brain tumor-polyposis (BTP) cases referred to as Turcot's syndrome in the literature. RESULTS: BTP patients encompass a heterogeneous group that can be classified into two statistically distinct clinical entities based on phenotype of the polyps (P = .0001), presence of colorectal cancer (P = .0001), type of brain neoplasm, ie, glioma or medulloblastoma (P = .0001), presence of skin lesions (P = .0004) and cafe-au-lait spots (P = .0008), as well as consanguinity (P = .0135). CONCLUSION: The first entity (BTP syndrome type 1) consists of patients who have glioma and colorectal adenomas without polyposis (non-FAP cases), and their siblings with glioma and/or colorectal adenomas. For these patients, we show that the patient's age at malignant glioma occurrence is less than 20 years (50 to 80 years in the general population), which strongly supports the existence of an underlying genetic cause. The neoplasms of these patients show DNA replication errors, which suggests a relationship with hereditary nonpolyposis colorectal cancer (HNPCC), a disease characterized by germline alterations in DNA mismatch repair genes. The second entity (BTP syndrome type 2) consists of patients with a CNS tumor that occurs in a familial adenomatous polyposis kindred (FAP cases). These patients carry germline mutations in the APC gene, which suggests that mutations in this gene might predispose to brain tumors. Risk analysis shows increased incidence of medulloblastoma in FAP patients, but APC mutations are not found in sporadic glioma or medulloblastoma. Therefore, further investigations should establish whether the occurrence of medulloblastoma in an FAP family represents a variant of FAP.

Surgical pathology of adenocarcinoma arising in Barrett's esophagus. Analysis of 67 cases.

Numerous reviews of adenocarcinoma arising in Barrett's esophagus have been reported, but detailed pathologic findings or survival analysis have rarely been provided. This retrospective study analyzed 67 patients (mean age, 64 years; male-to-female ratio, 10:1) with an adenocarcinoma arising in Barrett's esophagus treated by surgical resection. Prevalence of smokers was 63%, alcohol users, 45%, and patients with hiatal hernia, 73%. Five patients had another synchronous cancer, and seven patients, previous esophageal surgery. Forty percent of the tumors were well differentiated, 31% moderately differentiated, 15% poorly differentiated, 7% mucinous, and 6% composed of signet-ring cells. Depth of invasion in the esophageal wall was limited to mucosa in 13% of cases and submucosa in 18%. Invasive adenocarcinomas extended to the muscular layer in 12% of cases, to adventitia in 33%, and to periesophageal tissue in 24%. Vascular and perineural neoplastic invasion was present in 67 and 38% of cases. Regional lymph node involvement and distant metastases were found in 51 and 9% of cases. Overall, 1-, 2-, and 5-year survival rates were 63, 41, and 32%, respectively. Five-year survival rate was significantly better for patients with superficial cancer limited to mucosa or submucosa (82 vs. 12%) or without regional lymph node involvement (59 vs. 10%). Tumor differentiation, vascular and perineural invasion, extranodal spread, distant metastases, and resection margins status also had a significant prognostic value on univariate analysis. In a multivariate Cox regression analysis for overall survival, depth of invasion in the esophageal wall and regional lymph node involvement were independent prognostic factors. Careful pathologic staging is of value in determining the prognosis of patients with adenocarcinoma arising in Barrett's esophagus.

Light chain deposition disease with liver dysfunction.

Light and transmission electron microscopic study as well as immunohistochemical investigation were performed on three cases of light chain deposition disease (LCDD) with severe liver dysfunction. In two cases, the amount of light chain deposits in the liver was moderate and did not correlate with the severity of clinical and biological symptoms. Ultrastructural study demonstrated a collagenization of the Disse's space, with basement membrane-like material in association with light chain deposits. Immunohistochemical investigation showed a marked increase of collagen types I, III, and IV, as well as fibronectin and laminin in perisinusoidal space. This study suggests that collagenization of the Disse's space has a minor role in liver dysfunction. The analogy between kidney and liver lesions in diabetes and in LCDD is stressed, but the mechanism of this abnormal accumulation of matrix proteins remains unknown.

Clinicopathological relevance of the association between gastrointestinal and sebaceous neoplasms: the Muir-Torre syndrome.

The association between sebaceous neoplasms of the skin and visceral cancers, known as Muir-Torre syndrome, is described in three patients, including one with an extensive history of cancer in his family. The first patient, a 54-year-old man, developed multiple sebaceous adenomas, epitheliomas, and carcinomas in association with a colonic carcinoma 6 years after cardiac transplantation. Family history in this patient disclosed colon cancer in 17 relatives. The second patient was a 51-year-old man who had recurrent adenocarcinoma of the sigmoid colon, adenocarcinoma arising in Barrett's esophagus, and sebaceous epithelioma during a period of 15 years. The third patient was a 90-year-old man with a sebaceous adenoma followed 5 months later by adenocarcinoma of the sigmoid colon with liver metastases. Muir-Torre syndrome in 129 other patients published in the literature is reviewed. Although it is a rare disease, Muir-Torre syndrome requires recognition because skin lesions may be the first sign of the syndrome and this may lead to early diagnosis of associated visceral cancers. Moreover, because this syndrome appears to be inherited, family members should be screened for visceral cancer, especially colorectal adenocarcinoma.

Expression of c-erbB-2 oncogene product in Barrett's adenocarcinoma: pathological and prognostic correlations.

AIMS: To establish the prevalence of c-erbB-2 protein expression in a surgical series of Barrett's adenocarcinomas; and to correlate this expression with clinicopathological data and prognosis. METHODS: Sixty six surgical specimens of Barrett's adenocarcinomas were included in this retrospective study. Blocks of the tumour and of non-dysplastic Barrett's mucosa were stained with a polyclonal antibody specific for the intracytoplasmic domain of the c-erbB-2 protein. RESULTS: Seven of 66 tumours showed membrane staining for the c-erbB-2 protein. The non-dysplastic Barrett's mucosa was negative in all cases. There was no difference between c-erbB-2 positive and negative tumours with regard to mean age, sex ratio, percentage of alcohol misusers, percentage of smokers, tumour differentiation, depth of invasion, lymph node response, and proliferative activity, assessed by the percentage of tumour cells positive with the MIB-1 antibody directed against the Ki-67 antigen. All c-erb B2 positive tumours were of Lauren's intestinal type compared with negative c-erbB-2 tumours. Patients with c-erbB-2 positive tumours had a significantly poorer prognosis than patients with negative tumours. CONCLUSIONS: The prevalence of Barrett's adenocarcinomas expressing c-erbB-2 found in this study (11%) was similar to that observed in published series of gastric adenocarcinomas. c-erbB-2 protein expression could be an important prognostic indicator in Barrett's adenocarcinoma.

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.

Intraoperative localization of neuroblastoma in children with 123I- or 125I-radiolabeled metaiodobenzylguanidine.

BACKGROUND: This study describes a novel method of intraoperative localization of neuroblastoma with a gamma-detecting probe, to detect in situ tumor binding of radiolabeled 123I- or 125I-metaiodobenzylguanidine (MIBG) and improve the quality of tumor resection. METHODS: Fifty-eight children underwent 66 surgical procedures with intraoperative detection of radiolabeled MIBG. All patients with positive MIBG scintiscans at diagnosis were included in the study. A tumor/background ratio exceeding 2:1 at the time of operation was considered positive, indicating a significant uptake of MIBG, compatible with the presence of malignant cells. The surgeons were requested to evaluate the contribution of the method to the surgical procedure. Sensitivity and specificity of the method with either 123I-labeled MIBG or 125I-labeled MIBG, on the basis of correlations between probe findings and pathologic analysis of 288 resected specimens, were determined. RESULTS: Intraoperative detection was helpful in 65% of surgical procedures, allowing a better definition of tumor limits and extension to locoregional nodes or detection of small and nonpalpable tumors in sites with difficult surgical access, especially during operation for relapse. The detection was not contributory in 35% of the procedures (well-localized tumors, thoracic neuroblastoma for technical reasons, highly differentiated tumors as ganglioneuroma, and tumors with mainly necrosis or fibrosis). The sensitivity of 123I and 125I was the same (91% and 92%), but the specificity of 125I (85%) was significantly higher than that of 123I (55%) (p < 0.005). CONCLUSIONS: First, this study demonstrates the feasibility of intraoperative detection, with radiolabeled MIBG, of neuroblastoma in children. We advocate the use of 125I rather than 123I. Second, the method is useful to improve the quality of macroscopic resection in widespread neuroblastoma with nodal involvement, in sites with difficult access, and in operations for relapse.

Superficial gastric carcinoma developed on localized hypertrophic lymphocytic gastritis: a variant of localized Ménétrier's disease?

Ménétrier's disease is a rare premalignant condition that usually involves the entire stomach. Only few cases of localized disease have been reported, rarely with cancer. Lymphocytic gastritis is a newly described entity that may share a common pathogenesis with Ménétrier's disease. The authors report the case of a 62 year old woman with known liver cirrhosis in whom endoscopic examination of the stomach showed an antral tumor. Examination of the surgical specimen showed a superficial gastric adenocarcinoma developed on an hypertrophic gastropathy with both Ménétrier's disease and lymphocytic gastritis features. This observation strengthens the hypothesis of a common mechanism between Ménétrier's disease and lymphocytic gastritis, which may be part of the same disease spectrum. This disease could also correspond to the "hypertrophic lymphocytic gastritis" recently described.

Adenomas arising in Barrett's esophagus with adenocarcinoma. Report of three cases.

Adenocarcinoma of the esophagus is a well known complication of Barrett's esophagus, and results from a dysplasia-carcinoma sequence. This report describes 3 patients with adenomatous polyps arising in Barrett's esophagus. One patient presented with multiple sessile or pedunculated polyps giving a polyposis appearance; the other two patients had single polyps associated with distinct adenocarcinoma arising in Barrett's esophagus. Polyps consisted of adenomatous proliferation with adenocarcinoma in the 3 patients. Review of the literature identified twelve previously reported cases. These cases show that although rare, adenomas may arise in Barrett's esophagus, and are most likely premalignant lesions such as other adenomas of the gastrointestinal tract.

Cytokeratins expression in paragangliomas of the cauda equina.

BACKGROUND: Paragangliomas rarely involve the cauda equina region. In this location, these tumors can show misleading morphological features such as trabecular or papillary growth patterns and variable expression of cytokeratins. METHODS: We comparatively studied the immunohistochemical and ultrastructural patterns of 3 paragangliomas of the cauda equina (PCE) and of 8 paragangliomas from other sites. RESULTS: All the paragangliomas expressed neuroendocrine markers (neuron-specific enolase, chromogranin A, synaptophysin and neurofilament protein). In PCE, chief cells exhibited a strong positivity with a broad spectrum anti-cytokeratin antibody. The staining was diffuse in the cytoplasm or had a paranuclear dot-like disposition. In other sites, only one paraganglioma showed a focal expression of cytokeratins. At ultrastructural level, chief cells of PCE contained characteristic dense core granules and intermediate-sized filaments sometimes grouped in paranuclear whorls. CONCLUSION: The dual immunophenotype of PCE, paraganglionic and epithelial, must be recognized in order to distinguish these tumors from, for example, a metastasis of a neuroendocrine carcinoma. PCE are slow-growing tumors and have mostly a favorable prognosis after complete surgical excision.

Localization of apolipoprotein A-I and apolipoprotein A-II in human atherosclerotic arteries.

Apolipoprotein A-I and apolipoprotein A-II, the two major protein components of the high-density lipoproteins, were visualized in human arteries using an immunofluorescence technique. Apolipoprotein A-I and apolipoprotein A-II were codeposited into the intima and upper media of normal arteries of atherosclerotic patients. The amount of deposits increased in fatty streaks. In atherosclerotic plaques, apolipoproteins accumulated around the necrotic material. These two apoproteins were present in the extracellular matrix as well as in the foam cells surrounding the atherosclerotic lesions. The concomitant intracellular localization of apolipoprotein A-I and of apolipoprotein A-II in the cytoplasm of foam cells supports the hypothesis that extracellular high-density lipoprotein particles are internalized in the macrophages during the atheromatous process.

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.

Adenocarcinoma of the lower esophagus and the esophagogastric junction.

This report describes adenocarcinoma in patients with Barrett's esophagus (BE) and adenocarcinoma of the esophagogastric junction (EGJ) and the gastric cardia. Definitions, frequency, and general features of both conditions are described. The macroscopic features and microscopic findings are detailed for invasive adenocarcinoma and superficial (early) adenocarcinoma. Prognosis and follow-up are evaluated using flow cytometry as a factor of prognosis. Precancerous conditions and etiological factors are discussed. In addition, primary adenocarcinoma of the lower esophagus not associated with BE is considered. The precancerous lesions and precancerous markers in BE and in the cardia are examined, including type of dysplasia, histochemical study, and other lines of research.

[Demonstration of muscular activity in the human aorta. Effects of trinitrin]. / Mise en évidence d'une activité musculaire au niveau de l'aorte humaine. Effet de la trinitrine.

The human thoracic aorta is usually considered to be a purely elastic vessel. Transoesophageal echo-cardiography (TEE) provides a new approach to study the mechanical properties of the descending aorta. The aim of the study was to evaluate the reproducibility and accuracy of M mode recordings of the human descending thoracic aorta and to appreciate the changes produced by an infusion of glyceryl trinitrate (GTN). The reproducibility of M mode recordings was studied in vitro on plexiglass tubes of different calibre, and also in vivo, the inter and intra-observer error was estimated to 0.6% in vitro and 1% in vivo. The accuracy of the method was evaluated in vitro by comparing the measured values (MV) with the actual diameters of the plexiglass tubes (T): MV = 1.012T + 0.9; r = 0.99; SE = 0.8 mm. The systolic and diastolic diameters of the descending thoracic aorta were measured in 8 healthy volunteers by TEE, before and during continuous intravenous infusion of GTN at a rate of 0.9 mg/hr and then 1.35 mg/hr after a 10 minutes interval. Systolic and diastolic blood pressures were recorded automatically every minute. The results showed a very significant increase in the systolic (from 20.3 +/- 0.7 to 20.9 +/- 1.3 and 22.1 +/- 2.2 mm) and diastolic diameters of the aorta (from 18.3 +/- 0.7 to 19.1 +/- 1.4 and 20.1 +/- 2.4 mm) despite a fall in systolic blood pressure (from 121.3 +/- 7.7 to 114.5 +/- 6.6 and 108.4 +/- 5.4 mmHg). This study shows that TEE is a reliable and reproducible method of measuring the diameter of the human descending thoracic aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

[Intramural diverticulosis and cancer of the gallbladder]. / Diverticulose intramurale et cancer de la vésicule biliaire.

Two cases of gallbladder carcinoma occurring in intramural diverticulosis (adenomyomatosis) are reported. The first was adenocarcinoma associated with cholesterolosis without gallstone formation. The second was squamous cell carcinoma. Four other carcinomas developing on diverticulosis were reported in the literature, none of them being squamous cell carcinoma. Our cases and those of the literature show that diverticulosis, a benign condition, can be associated with carcinoma which can make the pathological diagnosis difficult.

[Are industrial toxic substances a risk factor in gallbladder cancer?]. / Les toxiques industriels sont-ils un facteur de risque du cancer de la vésicule biliare?

Increased prevalence of gallbladder cancer has been related to specific occupations and suggests a possible professional exposure to carcinogens. The authors report the case of a 64-year-old woman who had a squamous cell carcinoma of the gallbladder with hepatic metastases, and professional exposure to trichloroethylene in a degreasing metal laboratory. Although trichlorothylene could not be assumed to be a true carcinogen for gallbladder cancer, this case underscores that epidemiologic studies taking into account professional exposure, in addition to the usual risk factors of gallbladder cancer, are requested, in order to detect a new patient group at risk for gallbladder cancer.

[Budd-Chiari syndrome secondary to post-traumatic stenosis of the inferior vena cava]. / Syndrome de Budd-Chiari secondaire à une sténose post-traumatique de la veine cave inférieure.

Budd-Chiari syndrome with inferior vena cava involvement is usually due to membranous obstruction; traumatic origin of inferior vena cava lesions is very rare. We report a case of Budd-Chiari syndrome in a 29 year-old man, 3 years after an abdominal trauma. Cavography showed 50% stenosis in the sushepatic portion of the inferior vena cava. After two unsuccessful percutaneous transluminal angioplasty procedures, a surgical resection of the stenotic vein was performed. The histological study of the stenotic segments showed that the three layers of the venous wall had been replaced by a dense fibrous tissue. No inflammation or thrombosis were found. This case of stenosis of the vena cava shows that histological examination can be used to assess the traumatic nature of the lesion, showing a different histological pattern from that of the membranous obstruction in which the basic structure of the venous wall is preserved.

[Ischemic cholecystitis from cholesterol crystal embolism]. / Cholécystites ischémiques par embolies de cristaux de cholestérol.

Cholesterol crystal embolism is a serious complication of atherosclerosis resulting in renal, cutaneous and rarely digestive manifestations. We report two cases of systemic cholesterol crystal embolization with gallbladder involvement in two patients with gallstones, severe atherosclerosis with an abdominal aortic aneurysm as well as predisposing factors for cholesterol crystal migration. These two cases show that, like vasculitis, cholesterol crystal embolization may result in ischemic cholecystitis, and that diagnosis of cholesterol crystal embolization on routine cholecystectomy suggests severe systemic involvement and a poor prognosis.