Small hepatic vein involvement in IgG multiple myeloma: a very unusual pattern of liver infiltration.
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Biomedical subjects
Publications and source records attributed to Thierry Lazure.
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B cell-activating factor (BAFF) has a key role in promoting B-lymphocyte activation and survival in primary Sjögren's syndrome (pSS). The cellular origin of BAFF overexpression in salivary glands of patients with pSS is not fully known. We investigated whether salivary gland epithelial cells (SGECs), the main targets of autoimmunity in pSS, could produce and express BAFF. We used quantitative RT-PCR, ELISA and immunocytochemistry in cultured SGECs from eight patients with pSS and eight controls on treatment with IL-10, tumor necrosis factor alpha (TNF-alpha), IFN-alpha and IFN-gamma. At baseline, BAFF expression in SGECs was low in pSS patients and in controls. Treatment with IFN-alpha, IFN-gamma and TNF-alpha + IFN-gamma increased the level of BAFF mRNA in pSS patients (the mean increases were 27-fold, 25-fold and 62-fold, respectively) and in controls (mean increases 19.1-fold, 26.7-fold and 17.7-fold, respectively), with no significant difference between patients and controls. However, in comparison with that at baseline, stimulation with IFN-alpha significantly increased the level of BAFF mRNA in SGECs of pSS patients (p = 0.03) but not in controls (p = 0.2), which suggests that SGECs of patients with pSS are particularly susceptible to expressing BAFF under IFN-alpha stimulation. Secretion of BAFF protein, undetectable at baseline, was significantly increased after IFN-alpha and IFN-gamma stimulation both in pSS patients (40.8 +/- 12.5 (+/- SEM) and 47.4 +/- 18.7 pg/ml, respectively) and controls (24.9 +/- 8.0 and 9.0 +/- 3.9 pg/ml, respectively), with no significant difference between pSS and controls. Immunocytochemistry confirmed the induction of cytoplasmic BAFF expression after stimulation with IFN-alpha and IFN-gamma. This study confirms the importance of resident cells of target organs in inducing or perpetuating autoimmunity. Demonstrating the capacity of SGECs to express and secrete BAFF after IFN stimulation adds further information to the pivotal role of these epithelial cells in the pathogenesis of pSS, possibly after stimulation by innate immunity. Our results suggest that an anti-BAFF therapeutic approach could be particularly interesting in pSS.
Gene expression analysis of target organs might help provide new insights into the pathogenesis of autoimmune diseases. We used global gene expression profiling of minor salivary glands to identify patterns of gene expression in patients with primary Sjögren's syndrome (pSS), a common and prototypic systemic autoimmune disease. Gene expression analysis allowed for differentiating most patients with pSS from controls. The expression of 23 genes in the IFN pathways, including two Toll-like receptors (TLR8 and TLR9), was significantly different between patients and controls. Furthermore, the increased expression of IFN-inducible genes, BAFF and IFN-induced transmembrane protein 1, was also demonstrated in ocular epithelial cells by quantitative RT-PCR. In vitro activation showed that these genes were effectively modulated by IFNs in salivary gland epithelial cells, the target cells of autoimmunity in pSS. The activation of IFN pathways led us to investigate whether plasmacytoid dendritic cells were recruited in salivary glands. These IFN-producing cells were detected by immunohistochemistry in all patients with pSS, whereas none was observed in controls. In conclusion, our results support the pathogenic interaction between the innate and adaptive immune system in pSS. The persistence of the IFN signature might be related to a vicious circle, in which the environment interacts with genetic factors to drive the stimulation of salivary TLRs.
We report the case of a 67-year-old man presenting with an isolated 3 cm mass of the pancreatic tail revealed by weight loss. Distal pancreatectomy and splenectomy were performed. Microscopically, the tumor filled the main pancreatic duct, extending into the smaller ducts and was associated with a minor adenocarcinomatous invasive component. The intraductal tumor showed a cribriform pattern, atypical cells without mucus and a MUC1+, MUC2-, MUC5AC- phenotype, all characteristics of intraductal tubular carcinoma, a new entity described by Japanese authors. The differential diagnosis and its relationship with intraductal papillary-mucinous tumors are discussed.
The normal counterpart of the neoplastic B cells in Burkitt lymphoma (BL) is still unclear. Based on immunoglobulin gene rearrangement studies, some authors suggest an origin from germinal center cells and others from memory B cells. However, most of these studies rely on cell lines or on a small series of cases. To help clarify the cell of origin of BL, semi-nested polymerase chain reaction (PCR) was performed to amplify the VDJ rearrangements of the immunoglobulin heavy chain (V(H)) genes, and the resultant amplificates were sequenced for comparison with known germline V(H) segments. The results of this approach revealed that all cases (15 endemic BL [eBL], 10 sporadic BL [sBL], and 6 AIDS-related BL) harbor mutated V(H) genes, with different mutation ranges among the 3 types of BL. The eBL and AIDS-related forms showed considerably higher mutation rates than the sBL form (5.1%, 5.4%, and 1.5%, respectively). The mutations in eBL and AIDS-related BL also showed signs of antigen selection, whereas no signs of antigen selection were found in sBL. Finally, after subcloning the amplificates, sequence analysis revealed no signs of ongoing mutations in any of the cases analyzed. Given that one of the main differences between eBL and AIDS-related BL on the one hand and sBL on the other hand is the association with Epstein-Barr virus (EBV), we compared EBV-positive and EBV-negative BLs independently of their geographic origin and HIV status. The differences in the number of somatic mutations and antigen selection were even more evident when this approach was used. According to our molecular results, it appears that EBV-positive and EBV-negative BL may originate from 2 distinct subsets of B cells, pointing to a particular role for the germinal-center reaction in the pathogenesis of these tumors. The different types of C-MYC translocation reported in BL may also be related to the different stages of B-cell maturation.
Angiomyofibroblastoma of the male genital tract is a rare tumor with only 20 cases reported in the literature to date. We report three cases in males aged from 23 to 44 years. They presented with painless inguinal, scrotal and perineal masses, ranging from 3 to 8 cm in diameter. On microscopic examination the tumors were composed of small spindle cells without atypia in a fibrous and myxoid stroma. There were scattered mononuclear inflammatory cells around capillaries. Immunohistochemical studies showed positive staining of the tumor cells for vimentin, and weak reactivity for CD34, bcl-2, CD99, EMA and CD117. Some tumor cells expressed estrogen receptors in all three cases, and progesterone receptors in only one case. There was no recurrence with a follow-up ranging form 12 to 21 months. Angiomyofibroblastoma of the male genital tract is a benign often hormone-dependent tumor. Its histogenesis is still unclear. It has to be distinguished from aggressive angiomyxoma and myxofibrosarcoma.
Amputation neuroma of the common bile duct after surgery is a rare and mostly asymptomatic lesion. A 60-year old patient presented with obstructive jaundice three months after a cholecystectomy for symptomatic gallstones. Imaging investigations showed common extrahepatic bile duct stenosis. Surgical resection of the stricture with biliodigestive anastomosis was performed. Histological examination of the surgical specimen revealed an amputation neuroma. Despite its rarity, amputation neuroma of the common bile duct should be considered in patients with post-cholecystectomy syndrome following liver or extrahepatic bile duct surgical procedures.
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Pancreatic haemangiomas in infants are rare. Seven cases have been reported in the literature to date. We report two new cases. One of our cases had antenatal diagnosis and was associated with atypical portal vein thrombosis. The diagnosis was obtained by percutaneous biopsy without complication. For both cases, regression was observed without treatment.
We report an atypical case of congenital erythroleukemia in a child born with hepatosplenomegaly and abnormal liver tests. The initial peripheral blood cell count showed anemia and hyperleukocytosis with erythroblastosis that disappeared 1 week later. During the next 5 weeks, no blasts were found in the blood, and less than 5% were found on 2 successive bone marrow aspirates. The infant died of hepatic failure. The suspected diagnosis on a premortem liver biopsy was confirmed by an autopsy that showed a blastic infiltration in many organs. These cells expressed only erythroid markers glycophorin A and C. Rearrangement of the myeloid lymphoid leukemia gene was not found by fluorescence in situ hybridization. The main differential diagnoses include metabolic diseases, Langerhans histiocytosis, Pepper syndrome, transient myeloproliferative disorder, and leukemoid reactions. Although some of these can be excluded by the pathologist, others require a multidisciplinary confrontation: clinical, biologic, genetic, and pathologic examinations.
Infantile or congenital choriocarcinoma is a very uncommon complication of gestational choriocarcinoma. We report such a case with fatal outcome in a 3-week-old newborn, admitted for a hemorrhagic syndrome. Lungs, liver and brain masses were discovered and suggested an angiomatous process. The diagnosis was made later on gingival biopsy with necropsic confirmation. The mother's B-HCG level was elevated. She had asymptomatic pulmonary nodules and a uterine mass. This case report highlights characteristic but non specific clinical findings leading to the diagnosis. Chemotherapy must be undertaken as soon as possible to be effective. It is also necessary to assay maternal serum B-HCG when infantile choriocarcinoma is disclosed.
Osseous metaplasia is rare in tumors of the gastrointestinal tract. We report the case of a 76-year-old man presenting with an adenocarcinoma of the transverse colon containing osseous tissue. Calcifications were seen on the abdominal CT-scan. Pathogenesis of the osseous metaplasia is still unknown.
We report a unique, previously unreported pancreatic tumor with hepatoid differentiation associated with serous microcystic adenoma in a 70-year-old man. These two lesions localized, respectively, at the body and the tail of the pancreas, were found incidentally on abdominal ultrasonography. Serum alpha-fetoprotein was not increased and no hepatic lesion was displayed on computed tomography. A subtotal pancreatectomy with splenectomy was performed. The patient is alive and well 12 months after resection. Pathological examination showed a very unusual encapsulated solid tumor with hepatocytic differentiation, bile production and immunoreactivity for hepatocyte paraffin-1 antibody. The tumor cells were negative for endocrine (neuron-specific enolase, chromogranin A, synaptophysin) and acinar (amylase, trypsin) markers. Ultrastructurally, zymogen and neurosecretory granules were absent. The features of the tumor were almost indistinguishable from those of hepatocellular adenoma; therefore, we believe that this solid hepatoid tumor may represent a variant of pancreatic adenoma. Recognition of this entity is important because the only reported pancreatic hepatoid tumors to date have been malignant. The main differential diagnoses include hepatoid ductal adenocarcinoma, hepatoid acinar cell carcinoma, primitive hepatoid endocrine tumor, and metastatic hepatocellular carcinoma.
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Infantile pancreatic vascular tumors are very unusual and are described with an old and imprecise terminology. We report two new cases in 2 and 4 months old children, the first one associated with Kasabach-Merritt syndrome, the second revealed by cholestasis. The histology diagnosis was kaposiform hemangioendothelioma and juvenile capillary hemangioma respectively. Outcome was favourable after selective embolization for one and biliary derivation for the other. These case reports show that infantile vascular pancreatic tumors form a heterogeneous group. Most of them would be in fact kaposiform hemangioendothelioma with a benign behavior, in contrast with aggressive growth for retroperitoneal localizations.
Groove pancreatitis is a rare form of segmental chronic pancreatitis which is localized within the head of the pancreas, the duodenum and the common bile duct. Symptoms are due to common bile duct stenosis or duodenal stenosis. Radiologically, there is a pancreatic mass, which hinders differential diagnosis with pancreatic carcinoma. We report here a case of groove pancreatitis observed in a 41-year-old man treated by pancreatoduodenectomy. Histological features of the groove scar were noted. Our case and cases reported in the literature lead to hypotheses concerning the pathogenesis and clinical, biological, and radiological features suggestive of the diagnosis.