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We reviewed the indications for and the results of bone marrow examination (BME) from HIV-infected patients as an attempt to improve its diagnostic yield. One-hundred-and-eight bone marrow specimens from 90 patients during a 3-year period were examined. A cytological, histological and microbiological study was carried out on the specimens. Forty-three evaluable examinations (40% of total) performed for cytopenia showed normo- or hypercellularity in 33 (77%). Fifty bone marrow specimens were cultured for mycobacteria with a yield of 42% when the indication was persistent fever. Positive cultures yielded Mycobacterium avium complex in 8 out of 12 patients. Twenty-seven patients had both culture and biopsy; granulomas were associated with all the positive (10/10) and with 1 out of 17 negative cultures (chi-square test: p < 0.001). A bone marrow involvement with lymphoma was found in 2 out of 6 patients with previously diagnosed lymphoma, and biopsy revealed a lymphoma in 2 patients. Morphological bone marrow examination should be associated with other techniques in order to appreciate bone marrow production. Bone marrow biopsy is useful for the investigation of persistent fever since granulomas suggestive of disseminated mycobacteria are frequent and allow a treatment to be initiated before microbiological confirmation and antibiotic susceptibility test.

Background We explored the addition of rituximab to high-dose cytarabine (ara-C), oxaliplatin (L-OHP), and dexamethasone [R-DHAOx], in resistant and relapsed patients with CD20-positive follicular non-Hodgkin's lymphoma. Methods Twenty-two patients were included; they were treated previously with one to five chemotherapy regimens, including 13 patients who had also received rituximab. R-DHAOx consisted of rituximab, 375 mg/m 2 , day 1; dexamethasone, 40 mg/d, days one to four; L-OHP, 130 mg/m 2 , day 1; and ara-C, 2000 mg/m 2 every 12 h, day 2. Courses were repeated every 21 days for eight courses. Results Twenty-one patients (95%) achieved a complete response and one had a partial response. Responses were obtained in patients with and without resistance to prior treatment, either alone or combined with rituximab. The median follow-up time was 58.3 months (range, 8.7–92.6 months). Progression-free survival reached a plateau at 84% at 38.2 months. Only two of the 21 complete responders have relapsed. Tumor molecular markers disappeared in all 10 complete responders whose markers were found before treatment. Peripheral neuropathy related to the cumulative dose of L-OHP, and myelosuppression were the most prominent toxic effects. Conclusions R-DHAOx is highly active for salvage treatment of patients with follicular non-Hodgkin's lymphoma, and it produces long-term antitumor efficacy.

Hydroxyethyl starch (HES) is a macromolecular preparation that has been used as a volume expander since 1991. Renal toxicity of high-dose HES is now well recognized but potential renal toxicity of low-dose HES is poorly documented. Acute renal toxicity of cyclosporin A (CyA) may be responsible for osmotic nephrosis-like lesions. We report here the case of a 30-year-old male who developed cirrhosis due to hepatitis B and delta viruses and polymyositis. Polymyositis was treated with CyA, prednisone and plasma exchanges using low-dose HES as the replacement fluid. Renal insufficiency occurred with biopsy-proven osmotic nephrosis-like lesions, considered to be secondary to HES infusions and/or CyA.

The presence of Epstein-Barr virus (EBV) was studied in 56 gastric carcinomas from Western patients by in-situ hybridization for EBV-encoded RNAs (EBER). EBV-positive and negative carcinomas were compared for various pathological parameters including p53 overexpression.EBERs transcripts were detected in seven cases overall: four cases of 52 conventional carcinomas (7. 7%) and three cases of four gastric carcinomas with lymphoid stroma (75%). EBER positivity was diffuse in five cases and restricted to a localized area of the tumour in two cases of conventional carcinoma. A monoclonal EBV genomic pattern was demonstrated in the case tested by Southern blot analysis. By immunohistochemical analysis, neither EBV latent or lytic cycle proteins nor C3d/EBV receptor were expressed by neoplastic cells. EBER positivity was significantly correlated with prominent lymphoid reaction (P = 0.0002) which was associated with numerous PS100-positive dendritic cells and with HLA-DR expression by tumour cells (P = 0.03). p53 immunoreactivity in more than 30% of tumour cells was detected in 25 out 49 EBV-negative cases and was absent in EBV-positive cases except in one case with focal EBER-positivity.Focal staining for EBER is an unusual finding in the setting of gastric carcinoma and these results suggest that there might be two types of EBV-associated gastric carcinoma in which the viral infection will play a different role. The presence of a stromal lymphoid reaction which is strongly correlated with EBV positivity, is associated with antigen-presenting ability by HLA-DR-positive tumour cells or abundant dendritic cells. The function of p53 appears preserved in all EBV-associated carcinomas except in one case with focal EBER expression whereas the immunohistochemical pattern of p53 is suggestive of a mutational phenomenon in 51% of EBV-negative cases.

A case of laparoscopic autopsy for unexplained inpatient death is reported. The procedure is minimally invasive, easy to perform, accurate, and not disfiguring, rendering it easy to accept among mourning families.

In the West, hepatocellular carcinoma rarely occurs in patients without cirrhosis. In these patients, epidemiological factors and the histopathology of the non-neoplastic liver are not well known. The aim of this study was to clarify these points.We studied 30 patients (26 men, 28-87 years) with hepatocellular carcinoma and histologically-proven non-cirrhotic livers. Serological markers of HBV and HCV infection, as well as alcohol and tobacco consumption were evaluated. Pathological changes in the non-tumorous liver (fibrosis, inflammation, steatosis, alcoholic hepatitis lesions, iron overload, and large cell dysplasia) were systematically assessed using semi-quantitative scores.Twenty patients had alcohol intakeor =30 g/d and 16 were smokers. Serological HBV or HCV markers were positive in 10 patients. Only four patients had no exposure to alcohol or tobacco and no serological markers of HBV or HCV Histological examination showed that all livers had pathological changes. Seventeen patients (57%) had clearly-identified chronic liver disease: chronic hepatitis (n = 10) or alcoholic liver disease (n = 7). Non-specific and moderate pathological changes were observed in the 13 other patients (43%), with different degrees of fibrosis, activity, steatosis, and iron overload. Large cell dysplasia was present in 12 patients (40%).In our study, all patients with hepatocellular carcinoma and non-cirrhotic livers had non-tumorous pathological liver changes, especially iron overload and large cell dysplasia. These results suggest that hepatocellular carcinoma originates from an abnormal histological background, even in non-cirrhotic liver.

When renal insufficiency occurs in classical antineutrophil cytoplasm antibody- (ANCA) associated vasculitides, histological examination usually finds pauci-immune focal segmental glomerulonephritis. We report on 2 cases of histologically proven necrotizing vasculitis associated with IgA nephropathy. Concomitant vasculitis and IgA nephropathy has only rarely been reported but this joint occurrence may not be coincidental as its pathophysiology is not known. Among vasculitides, IgA nephropathy has more frequently been associated with Henoch-Schoenlein purpura: one microscopic polyangiitis unusual because the patient simultaneously presented ANCA and microaneurysms, and the other Churg-Strauss syndrome associated with mild renal insufficiency. This uncommon association might represent a possible overlap syndrome between these ANCA-associated vasculitides and IgA nephropathy or simply a new type of glomerulonephritis that must be taken into account in these vasculitides.

The authors report a case of laparoscopy post mortem for unexplained inpatient death. It is minimally invasive, easy to perform, accurate, and not disfiguring. As well, it is easy to accept among mourning families. It should be considered when consent for conventional autopsy is lacking.

The aim of this retrospective study is to evaluate the impact of laparoscopic appendicectomy on the incidence of histologically normal appendices. Between 1987 and 1997, 1220 consecutives patients--with an average age of 23.5 years (17-73) and including 841 women (69%)--underwent appendicectomy due to the presence of at least one of the following 3 criteria: right iliac fossa guarding, fever greater than 38 degrees C and hyperleucocytosis greater than 10,000. Patients were divided into two group.: First group with 930 patients were operated by laparotomy and the other group of 355 patients underwent laparoscopic exploration with appendicectomy when macroscopic abnormalities were observed (290 cases). In all cases, the appendices were examined under blind conditions and classified as normal or pathological, and were subsequently classified according to the nature and the severity of the lesions. In group I (laparotomy), the incidence of histologically normal appendices was 25.1%. In group II (laparoscopic), this incidence was only 8.2%. The difference was significant (p = 0.015). In 65 cases (18.3%), a macroscopically normal appendix was left in place: in 55 cases the symptoms were due to another identified cause, however, in 10 cases no cause was found. This study suggests that laparoscopy significantly reduces the number of histologically normal appendices because an other cause is identified more easily provided macroscopically normal appendices are not removed with a small proportion (5-10%) cases of early appendicitis with only mucosal involvement. In the absence of other causes for the symptoms, a three-day course of antibiotics can be tried in order to treat possible mucosal lesions. This approach reduces costs without having any adverse consequences on outcome.

Giant-cell hepatitis is rare in adults and its significance has not been clarified. We report the clinical and histological characteristics and outcome in a group of adult patients with giant-cell hepatitis.Seventeen patients with giant-cell hepatitis, hospitalized in our unit between 1976 and 1992, were studied retrospectively. Giant-cell hepatitis was defined as at least two hepatocytes with four or more nuclei per cell on liver biopsy. Clinical and biochemical parameters, liver histology, and the serological profile of HAV, HBV, HCV, HIV, HSV, EBV, CMV, and paramyxovirus were evaluated. Paramyxovirus immunochemistry was performed in 6 liver biopsies.There were 11 females and 6 males, an average of 48 years old (range: 29-80). Four patients had a well-defined etiology: acute hepatitis B infection with a favorable outcome in 2 cases, clometacine induced-hepatitis resulting in death from liver failure in one case, and chronic hepatitis B and C in one patient with AIDS. Among the 13 patients in which the etiology could not be determined, histologically defined acute hepatitis was observed in 8 and chronic hepatitis in 5. Nine patients were treated with immunosuppressive drugs. One patient was lost to follow-up. Eight patients responded to treatment, but 5 patients progressed to cirrhosis between 5 months and 7 years. Two of the 4 patients with unexplained liver disease who did not receive any treatment died of liver failure.In patient with acute or chronic hepatitis without an identified cause (with or without autoimmune abnormalities), the presence of giant-cell hepatitis seems to have a similar evolution as active autoimmune hepatitis. The poor prognosis of these patients suggests that early immunosuppressive treatment is justified.

Long term treatment by fibrates could induce chronic hepatitis associated with auto-antibodies. The aim of this study was to assess the features of this hepatitis.Baseline clinical and biological features, and liver biopsy in 5 patients with fibrate-induced chronic hepatitis were studied, as well as their outcome.At enrollment, patients (4 men, mean age 65 years) had highly (n = 3) or mildly (n = 2) increased serum aminotransferase activity, hypergammaglobulinemia and high titers of anti-nuclear antibodies (with homogenous fluorescence in 3 cases). Liver biopsies demonstrated a lympho-plasmocytic infiltrate in all cases. Hepatocellular necrosis was multilobular in 2 cases, and mild to moderate, located in lobular and periportal areas in 3 cases. Cirrhosis was found at presentation in 3 cases and developed within a few months in the 2 other patients. After discontinuation of fibrates, aminotransferase activity normalized within 6 weeks either spontaneously (n = 3) or under immunosuppressive treatment (n = 2). Immunosuppression was rapidly withdrawn in 2 patients (18 months) without relapse, while one patient was treated for 4 years because of relapse after early withdrawal. A second liver biopsy performed 6 months after discontinuation of fibrates in an untreated-patient showed no inflammation or necrosis.These observations suggest that fibrates could trigger chronic liver disease resembling type I auto-immune chronic hepatitis, which resolves after drug withdrawal.

Patients with acquired immunodeficiency syndrome are often susceptible to atypical dissemination of visceral leishmaniasis. Digestive localizations seem to be relatively frequent. Colonic localizations reported in the literature are endoscopically normal or show superficial mucosal lesions. We describe an original case of leishmaniasis associated with a colonic pseudotumoral stenosis with perforated ulcer penetrating in the mesocolon. Striking inflammation of mesenteric blood vessels, even far from the ulcer, suggested an ischemic mechanism for the colonic stenosis. These findings raise the hypothesis that vasculitis is secondary to mucosal parasitic infection.

Although many studies concerning the prognostic factors of resected hepatocellular carcinoma have been performed, the prognostic information provided by needle biopsy of these tumors has not yet been extensively studied.One hundred twenty-four white patients with histologically-confirmed hepatocellular carcinoma were entered into a prospective study from 1990 to 1992 with followed-up through October 1994. Most of the patients had cirrhosis (79%). Patients were classified according to Okuda's staging: Stage I (50%), Stage II (47%), and Stage III (3%). The one-year survival rate was estimated at 58% in Okuda's Stage I, and 15% in Stages II and III. Edmondson's grading, mitotic index, and proliferating cell nuclear antigen labeling index were studied on each biopsy. Univariate and multivariate analyses were performed to determine the prognostic significance of the different parameters.According to Edmondson's critera, 13 of the hepatocellular carcinomas were Grade I, 63 Grade II, 42 Grade III, and 6 Grade IV. There was a significant correlation between Edmondson's grade, mitotic index, and proliferating cell nuclear antigen labeling index (P0.01). Univariate analysis showed both the histologic grade (P0.001) and mitotic index (P0.05) correlated with survival. Cox's model indicated that Edmondson's grading yields additional prognostic information for Okuda's staging (P0.001). The one-year survival rate for Okuda's Stage I was 76% for Edmondson's Grades I + II versus 23% for Grades III + IV.Edmondson's grading appears to be an important prognostic parameter for patients with hepatocellular carcinoma, and could help stratify patients for clinical trials.

We report an Hepatitis B Virus reactivation, in a patient with an end-stage Human Immunodeficiency Virus infection who developed a rapidly progressive liver failure in four months. The main histological features include ballooning of hepatocytes and ground glass transformation, without significant inflammation. Immunohistochemical staining showed a high expression of viral antigens. This case can be related to "Fibrosing Cholestatic Hepatitis", first described after liver transplantation for cirrhosis B. The mechanism of hepatocellular damage is likely to be a direct cytotoxicity of hepatitis B virus.

We report a 25-year-old patient with a progressive asymmetric peripheral neuropathy of the distal lower limbs. Imaging studies showed enlargement of lumbosacral roots, plexus, and proximal sciatic nerve. Sacral plexus biopsy revealed amyloidosis associated with endoneurial edema. Immunohistochemistry with anti-prealbumin, serum amyloid A, and immunoglobulin light chain antisera failed to label the amyloid.

Whipple's disease and pulmonary and lymph node tuberculosis have been diagnosed in a 70 year-old man hospitalized for weight loss and fever. The tuberculous or Whipple's disease-related nature of associated non-necrotizing epithelioid hepatic granulomas could not be determined. The existence of cellular immune defects in Whipple's disease could explain the association with tuberculosis, which has not been previously reported in the literature.

The mechanism involved in glomerular fibrin deposition was investigated during mercuric chloride (HgCl2)-induced autoimmune glomerulonephritis in the Brown Norway rat. To ascertain whether the local hemostatic system was activated secondarily to the immunological conflict, the ability of glomerular lysates to induce coagulation in vitro was assessed in treated and control rats. Glomerular procoagulant activity (PCA) of HgCl2-injected rats was measured on day 12 (latent phase of the disease), day 20 (acme), and days 32 and 42 (recovery phase) after the first mercury injection. PCA rose 3-fold (p less than 0.02) at day 20 and then almost returned to control values. Proteinuria, PCA, and the incidence of glomerular fibrin deposits peaked concomitantly at day 20. Glomerular PCA was characterized as thromboplastin. The number of Ia positive cells detected by monoclonal OX-6 antibody was not different from the control number at any phase of the disease; the number of macrophages per glomerular section detected by electron microscopy at day 20 in HgCl2-injected rats was 1.80 +/- 0.60, versus 0.30 +/- 0.11 in the controls. No correlation was found between glomerular PCA and either the number of monocytes/macrophages or of Ia-positive cells present in the glomeruli. Since glomerular PCA was maximal at the onset of fibrin formation in the glomeruli and then decreased toward its basal level, and since the fibrin disappeared, it is concluded that increased production of thromboplastin by glomeruli, with activation of the extrinsic coagulation pathway, may contribute to intraglomerular fibrin deposition in HgCl2-induced glomerulonephritis.

A case of primary cardiac lymphoma (PCL) is reported in a patient presenting with chest pains. This PCL was treated with surgery. The histology showed a large cell lymphoma. The immunohistochemical study demonstrated the B cell origin of this PCL.

A case of massive amyloidosis without detectable monoclonal Ig component either in serum or in urines on classical electrophoresis and without obvious plasma cell proliferation is reported. Immunohistochemical study of renal and bone marrow biopsies showed that amyloid deposits were specifically stained with the anti-lambda antiserum and that 92% of the plasma cells were also lambda positive. Immunofixation following electrophoretic analysis of serum and urinary proteins exhibited a monoclonal lambda light chain at an advanced stage of the disease. Simple but not routinely used techniques are therefore of great interest to characterize apparently idiopathic amyloidosis which could have therapeutic implications.

The three cases reported here illustrate the diagnostic, therapeutic and prognostic problems raised by these tumours. These are rare lesions with little suggestive symptoms, which explains why they are exceptionally diagnosed before surgery. Mucosal hyperplasias and cystadenomas are benign formations with a 90-100% survival rate 5 years after appendicectomy, even when non-cellular mucoid effusion is present. Cystadenocarcinomas are malignant tumours with mucoid secretion containing epithelial cells; they have a tendency to recur despite repeated evacuations, and their 5-year survival rate is approximately 25%; death results from intestinal obstruction or compression of intra-abdominal viscera by the mucoid substance.

This case report describes a patient with IgG lambda myeloma and vascular amyloidosis. Remarkable is the presence of mesangial granular deposits revealed by electron microscopy and positive with anti-IgG and anti-kappa anti-serum in an immunofluorescence study. Granular dense deposits were also found at the inner side of the basement membrane of the skin and were positive with anti-kappa anti-serum in immunofluorescence study. Because no L kappa q light chain proliferation could be demonstrated, the nature and significance of these kappa deposits are not clear.

Gastrointestinal involvement has been reported in 12-21% of post-transplant lymphoproliferative disorders but is unusual in the setting of heart transplantation. We report four post-transplant lymphoproliferative disorders observed among the 174 heart transplant recipients of our series, all of which were primary malignant lymphomas of and confined to the digestive tract. The mean onset time from transplantation was 22 months. Small intestine lesions were present in all four patients, with gastric involvement in one. Histologically, the tumour was monomorphic of immunoblastic type in one case and polymorphic in the three other cases. Analysis of cytoplasmic immunoglobulins demonstrated the presence of a major monoclonal subset in all patients. Epstein-Barr virus genome was found in numerous tumour cells by in situ hybridization. The exclusive localization to the digestive tract and the lymphoepithelial lesions observed in two cases suggest that these lymphoproliferations might originate from mucosa-associated lymphoid tissue.