Secretion of immunoglobulins and plasma proteins from the jejunal mucosa. Transport rate and origin of polymeric immunoglobulin A.

Parameters of secretion of IgA and several other plasma proteins from the jejunal mucosa were investigated in 11 individuals who had a normal distribution of Ig-containing cells in the lamina propria and in one patient who was totally deficient in jejunal IgA and IgM plasmacytes. Jejunal samples were collected during segmental gut perfusion. The following results were obtained: (a) The secretion of polymeric IgA (p-IgA, mean equals 217 micrograms/40 cm per min) exceeded those of albumin (132 micrograms), IgG (35 micrograms), and monomeric IgA (m-IgA, 15 micrograms, or 6.4% of total IgA). About 35% of IgA was IgA2 in the jejunal secretion, compared with approximately 23% in serum. This closely corresponds to the 35 and 24% of IgA2 plasmocytes in jejunal mucosa and peripheral lymph nodes, respectively. (b) For each protein, a relative coefficient of excretion (RCE) was calculated (jejunum to serum concentration ratio expressed relative to that of albumin). RCEs of 1.41 for orosomucoid, 1.0 for albumin, 0.83 for IgG, and 0.74 for IgE and, in the deficient patient, of 0.64 for m-IgA and 0.016 for IgM were obtained. This was inversely related to the molecular weight of these proteins and indicated their predominantly passive transport into the jejunum. However, in normal individuals, the RCE of transferrin (approximately 1.11 greater than 1, P greater than 0.05), alpha 2-macro globulin (approximately 0.77), m-IgA (approximately 1.98), and p-IgA (approximately 218) exceeded the value expected from simple seepage from plasma, thus pointing to an additional role of either local gut synthesis and/or active transepithelial transport. (c) Approximately 98% of p-IgA, approximately 99% of IgM, and approximately 68% of m-IgA in jejunal secretions were derived from local production in the gut wall, as determined by 125I-p-IgA specific activities and/or by comparison between the RCE values of the deficient patient to the values of controls. Therefore, the jejunal production of p-IgA (approximately 312 mg/d per 40 cm vs. approximately 54 mg/d from bile) contributes the majority of upper intestinal IgA in humans. The active transport of plasma p-IgA across the intestinal mucosa (approximately 0.08 mg/40 cm per kg per d) contributes less than 2% of the total amount of p-IgA (4.5 mg/kg per d) that is cleared daily from plasma.

Diffuse follicular lymphoid hyperplasia of the small intestine without primary immunoglobulin deficiency.

Three cases of follicular lymphoid hyperplasia extending to the whole length of small intestine are reported in three young adult patients of low economic status. The disease was revealed by chronic diarrhea with malabsorption and/or protein-losing enteropathy. In one patient, all transitional patterns were found between the hyperplastic follicles and a small intestinal multicentric centrocytic-centroblastic lymphoma. No abnormalities in humoral or cellular immunity were found in the three patients. In particular, serum immunoglobulins (except IgG in one case) and plasma cell populations of small intestinal lamina propria were normal. Diffuse follicular lymphoid hyperplasia of the small intestine in the absence of primary immunoglobulin deficiency appears to be a rare condition associated with (or leading to) intestinal malignant lymphoma in most cases. Patients usually belong to the same populations as those suffering from alpha-chain disease.

A primary immunoblastic T malignant lymphoma of the small bowel, with azurophilic intracytoplasmic granules. A histologic, immunologic, and electron microscopy study.

We report an aggressive primary T-immunoblastic lymphoma of the small intestine without blood involvement or associated celiac disease. Grossly, the tumor was composed of multiple disseminated ulcerated, infiltrating, or protuberant nodular lesions. Immunologic investigation showed that lymphoma cells were of peripheral (post-thymic) T-cell origin and expressed the phenotype associated with cytotoxic-suppressor subset (Leu4/CD3+, Leu9/CD7+, Leu2/CD8+, Leu11/CD16+, Leu 7/NKcells+, FcIgG+, HLA-DR+, anti-Tac/CD25+, Ki-1/CD30-, Leu1/CD5-, Leu5/CD2-, Leu3/CD4-). A particular morphologic feature of this case is the presence of numerous azurophilic granules within the lymphoma cells, identified as lysosomes by cytochemical and ultrastructural studies. In view of recent immunologic evidence that normal cytotoxic/suppressor T-cells selectively reside within the epithelium of the normal bowel and some of them contain azurophilic granules, it could be suggested that our patient's lymphoma represents a malignant counterpart of these lymphocytes. Furthermore, the aggressive character of this T malignant lymphoma (T-ML) could be related to the expression of T-cell activation markers HLA-DR and Tac/CD25 and the proliferation-associated antigen Ki-67 on a high proportion of tumor cells.

Comparison of budesonide and 5-aminosalicylic acid enemas in active distal ulcerative colitis.

BACKGROUND: Budesonide is a new corticosteroid with high topical anti-inflammatory activity but little systemic effect. The aim of the present study was to compare the efficacy and safety of budesonide enema (2 mg/100 mL) and 5-ASA enema (mesalazine 1 g/100 mL) given for 4 weeks in the treatment of active distal ulcerative colitis and proctitis. METHODS: Ninety-seven patients were studied in a multicentre single-blind randomized group-comparative trial. The primary efficacy variables were endoscopy and histopathology scores obtained at 0, 2 and 4 weeks. Clinical symptoms were the secondary efficacy variables. Haematology, chemistry and adverse events were the safety variables. RESULTS: Budesonide and 5-ASA enemas both resulted in a significant improvement in endoscopy and histopathology scores but no difference could be demonstrated between the two treatment groups. There was also a significant improvement of symptoms (number of bowel movements per day, quality of stools, presence of blood and mucus, and state of well-being) within both groups but no difference between the two treatment groups. The clinical remission rate at 4 weeks was, however, 38% for patients treated with budesonide enema but 60% for those treated with 5-ASA enema (P = 0.03). No adverse events attributed to the study drugs were recorded in either of the groups. CONCLUSIONS: Budesonide enema 2 mg/100 mL appears to be as efficient and well-tolerated as 5-ASA enema in the treatment of active distal ulcerative colitis and proctitis.

Primary B-cell gastric lymphomas of mucosa-associated lymphoid tissue. Histological and immunohistochemical study of ten cases on surgical specimens.

Ten cases of gastric mucosa-associated lymphoid-tissue B-cell lymphoma were studied on surgical specimens by histology and immunohistochemistry, with monoclonal and polyclonal antibodies for B- and T-cells. For the first time, percentage of centroblast-like cells was appreciated, using their LN1 positivity, by opposition to the negativity of centrocyte-like cells (LN2 immunoreactivity alone). Lymphomas were divided into four main groups: A) centrocyte-like cells; B) centrocyte-like cells and immunocytoma; C) centrocyte-like cells admixed to centroblast-like cells; and D) centrocyte-like cells, immunocytoma and at least 30% of centroblast-like cells. Group C was divided into 3 subgroups: C1 (rare centroblast-like cells); C2 (30-50% of centroblast-like cells); and C3 (predominant centroblast-like cells). Therefore low grade (A, B, C1) and high grade malignancy groups (C2, C3, D) were identified: this preliminary subdivision could be extended in larger series and applied to mucosa-associated lymphoid-tissue lymphoma from other sites. Furthermore, the possible prognostic significance of this subdivision could be evaluated by correlation with long term follow-up.

Peripheral T-cell lymphoma or Hodgkin's disease in a HIV seropositive patient: a histopathological study.

Malignant lymphomas occurring in patients with AIDS are usually derived from the B-cell lineage while T-cell malignant lymphomas are very rare in these patients. We report a HIV seropositive 29-year-old homosexual man in whom cervical lymph node biopsy showed an atypical lymphoproliferative process. On morphological and paraffin section immunohistochemical grounds the possibility of Hodgkin's disease (HD) mixed cellularity was initially suggested, but frozen section immunohistochemical studies revealed that the cellular infiltrate exhibited an aberrant pan T immunophenotype and consequently the diagnosis of peripheral T-malignant lymphomas (T-ML) was made. However, genotypic studies would be required to definitely confirm this diagnosis, in such cases. In our case, varying numbers of small and medium-sized cells were positive for both Leu 3/CD4 and Leu 2/CD8 whereas some large cells reacted only with Leu 3/CD4 antibody. Some medium-sized, large and giant cells showed cytoplasmic positivity for Leu M1/CD15. Furthermore, the positivity of many large and giant cells with the activation markers BerH2/CD30, Ki-1/CD30, Tac/CD25 and HLA-DR suggested an activation state for these cells. Our findings emphasize the usefulness of frozen section immunohistochemical methods in order to investigate the spectrum of lymphoid malignancies occurring in HIV seropositive patients, and confirm results of previous studies which stressed the diagnostic difficulties that may appear in distinguishing HD from peripheral T-ML.

Immunohistochemical detection of cell proliferation in gastric carcinomas with the monoclonal antibody Ki-67. A study of 24 cases.

The proliferative activity in 24 gastric carcinomas was determined by an immunohistochemical method using monoclonal antibody Ki-67 (ABC method). Immunostained nuclei were counted by two observers through a Nachet NS 1000 image numeriser. Three grades were defined according to stained nuclei percentage (proliferation index Pi = percentage of cells engaged in cellular cycle outside Go): grade 1 (Pi < 20%); grade 2 (20% < Pi < 40%); grade 3 (Pi > 40%). About 60% of tumours were in grade 1 and 10% in grade 3. No correlations were observed between Pi and the following parameters: histological differentiation; parietal extension; presence or absence of metastasis. These results may be compared to the two other available studies of Ki-67 antibody in gastric cancers. Our study also showed a heterogeneous distribution of immunostained nuclei, within each single tumour and from one tumour to another, which has been noted in one previous study and in a similar one we made on colorectal carcinoma. This heterogeneity is the consequence of the variability of carcinomatous cell proliferative activity; an important biological factor in the evaluation of tumoral process. The proliferative activity in gastric carcinomas provides an estimation of tumour dynamics that might be a prospective criterium for tumoral process evaluation.

Chronic cholestasis and macronutrient excess in patients treated with prolonged parenteral nutrition.

The mechanism of chronic cholestasis observed during prolonged parenteral nutrition remains unclear. We studied liver function tests in 18 consecutive gastroenterological adult patients submitted to 18 mo (median; range 6-66 mo) of parenteral nutrition. Seven patients (group B) developed a cholestatic nonobstructive jaundice, culminating after 3 mo, (1-4 mo) whereas 11 patients (group A) did not develop chronic abnormalities on liver function tests during parenteral nutrition. Liver biopsies obtained at 4 mo (3-6 mo) in 6 group B patients demonstrated bile duct proliferation in the portal area, with extensive fibrosis, cholestasis, and focal necrosis of hepatocytes. Initial intakes of calories, fat, and protein were higher (p less than 0.01) in group B than in group A patients and, when reduced, were associated with reversal of jaundice and improvement in liver function tests and histological findings. These data suggest that the development and course of cholestasis are influenced by excess parenteral intake of protein and mixed-energy sources.

Stereotactic biopsy diagnosis of primary non-Hodgkin's lymphoma of the central nervous system. A histological and immunohistochemical study.

We report 29 cases of primary non-Hodgkin lymphomas (NHL) of the Central Nervous System (CNS), 26 of which were diagnosed by stereotactic biopsy and 3 by autopsy. In seven cases the patients were affected by AIDS. Histological examination of this series revealed 15 cases of immunoblastic lymphoma, 12 cases of centroblastic lymphoma, 1 case of lymphoplasmacytic immunocytoma and 1 case of unclassified high grade lymphoma. By immunohistochemistry the B-cell origin of lymphoma cells was demonstrated in 28/29 cases. Eight cases were assigned to the B-cell lineage by demonstration of monotypic surface or cytoplasmic immunoglobulin or of the B-cell phenotype CD22+, CD2-, CD3-, CD5-. In twenty cases the B-cell nature of lymphoma was identified by positivity with two or more anti-B monoclonal antibodies (LN1LN2MB2) and negativity by the anti-T monoclonal antibody UCHL1. The histologically unclassified case was a peripheral T-NHL (CD1-, CD2+, CD3-, CD5+, CD22-). We conclude that histological and immunohistological evaluation of stereotactic biopsy specimens provides sufficient information for diagnosis and phenotypic characterization of primary NHL of the CNS. These lymphomas exhibit important predominance of high-grade malignancy histological types and are nearly always B-cell derived. In addition, we provide further evidence that the panel of monoclonal antibodies LN1, LN2, MB2, and UCHL1 is useful for immunophenotypic characterization of brain lymphomas when only paraffin embedded stereotactic biopsy tissue is available.

Primary T-cell malignant lymphoma of the central nervous system. Histological, immunohistochemical and ultrastructural study of a case.

Most primary malignant lymphomas (ML) of the central nervous system (CNS) are derived from B-cells, whereas T-malignant lymphomas (T-ML) primarily arising in the CNS are extremely rare. We report on a patient with a primary T-ML of the CNS localised in the posterior fossa. On the basis of histological, ultrastructural and immunohistochemical studies, this tumour was classified as a pleomorphic T-ML, medium and large cell type with peripheral helper/inducer T-cell phenotype (CD 1-, CD 2+, CD 3+, CD 5+, CD 7-, CD 4+, CD 8-, CD 19-, CD 22-, UCHL 1+/CD 45 RO, L 26-/CD 20, LN 1-/CDW75, LN 2-/CD 74, MB 2-). Furthermore, the positivity of the markers CD 25 and HLA-DR on many medium-sized and large lymphoma cells suggests activation of these cells. The nuclear marker of proliferative activity Ki-67 was expressed in some large cells, whereas the natural killer cell-related markers CD 16 and Leu 7/CD 57 did not react with lymphoma cells. This study emphasises the value of extensive immunohistochemical investigations on frozen and paraffin sections in order to identify and characterize the T-cell malignancies, particularly in their rare CNS location.

Nucleolar organizer regions (NORs) staining and proliferating cell nuclear antigen (PCNA) immunostaining in mucosa-associated lymphoid tissue (MALT) gastric lymphomas.

Nucleolar organizer region-associated proteins (AgNOR) and proliferating cell nuclear antigen (PCNA) have been studied by means of a silver staining technique and immunohistochemistry, in paraffin-embedded, gastrectomy specimens of 12 low-grade and 13 high-grade gastric MALT lymphomas respectively. A significant difference was found between the AgNOR count and PCNA index of low-grade lymphomas (mean AgNOR count 2.5 and mean PCNA index 8.33%) and high-grade lymphomas (mean AgNOR count 8.67 and mean PCNA index 49.7%). It is suggested that both methods are useful adjuncts to histopathology for the distinction between low and high grade gastric MALT lymphomas. We also found heterogeneity in AgNOR counts and PCNA index among individual cases of either low or high grade MALT gastric lymphomas. This suggests that the AgNOR count and PCNA index is helpful in the individual approach of the proliferation rate of each tumour, a parameter of potential importance for predicting the biological behaviour of the tumour and the prognosis of the disease.

Comparison of cytologic examination of smears and histologic examination of tissue cores obtained by fine needle aspiration biopsy of the liver.

Biopsies of 30 consecutive suspected liver cancers were performed with 19-gauge fine needles having circumferentially bevelled tips that produced tiny tissue cores suitable for histologic study. The histologic results were compared with the cytologic results on aspirates obtained at the same time with 22-gauge Chiba needles. While cytologic examination of the aspiration smears produced better results than did histologic study of the tiny tissue cores, an improved overall accuracy of 86% was achieved with the combined cytologic and histologic results. The FNA core biopsy technique did not increase the complication rate.

[Undifferentiated carcinoma with lymphoid stroma (undifferentiated carcinoma nasopharyngeal type?). Optical, electron microscopical and immunofluorescence study (author's transl)]. / Carcinome indifférencié à stroma lymphoïde de la parotide (Carcinome indifférencié de type nasopharyngé ?). Etude en microscopie optique, életronique et en immunofluorescence.

A case of undifferentiated carcinoma with lymphoid stroma of the paired gland is reported in a chinese woman with positive Epstein-Barr virus serology. The histologic appearance of the tumor is very similar to undifferentiated carcinomas nasopharyngeal type (UCNT). Ultrastructural study reveals features of epidermoid differentiation. Immunofluorescence study shows numerous and predominant IgA plasma cells in the stroma. The relationship between this tumor and the benign lymphoepithelial lesions of the salivary glands are discussed. The present case and the review of the literature emphasize the morphological and epidemiological similarities between UCNT and undifferentiated carcinoma with lymphoid stroma of the salivary glands.

[Anatomo-pathological evolution of single-layer end-to-end digestive anastomoses. A study of 210 colonic anastomoses in rats from the 2d to the 180th day]. / Evolution anatomo-pathologique des anastomoses digestives bord à bord en un plan. Etude de 210 anastomoses coliques chez le rat du 2e au 180e jour.

Two hundred and ten left colonic single-layer end-to-end anastomoses (105 by extramucosal continuous suture, 53 by extramucosal interrupted sutures, 52 by total continuous suture) performed on 105 rats with microsurgical techniques using a slowly resorbed suturing material were examined histologically at nine different times between the 2nd and the 180th days. The histopathological evolution of the inflammatory granuloma, the granulation tissue, the reepithelialization process and the restoration of the smooth muscle layers are described. The rate and the amount of inflammation were found to differ between animals and three different types of evolution could be schematized. The differences could not be due to the suturing techniques since continuous and interrupted sutures gave the same results, but rather to the manner of treating the intestinal cut edges before and during suturing. The amount of inflammation was found to decrease with the operator's training.

[A case of diffuse inflammatory colonic pseudopolyposis caused by Crohn's disease]. / Un cas de pseudopolypose inflammatoire diffuse colique due à une maladie de Crohn.

Inflammatory pseudopolyposis of the colon is an uncommon anatomoclinical entity. It is generally associated with ulcerative colitis, Crohn's disease or schistosomiasis. We report a case of a pseudopolyposis in Crohn's disease involving the entire colon. This case was characterized by three particular facts: a) the pseudopolyps were composed of granulation tissues only, b) severe exudative enteropathy was the most important symptom, c) the endoscopic ablation of the polyps, performed for the first time in Crohn's disease pseudopolyposis, resulted in clinical and biological improvement.

[Peliosis hepatitis during intestinal lymphomatous polyposis treated with chemotherapy and radiotherapy. Regression after antibiotic therapy]. / Péliose hépatique au cours d'une polypose lymphomateuse intestinale traitée par chimiothérapie et radiothérapie. Régression après antibiothérapie.

We report a case of regressive peliosis hepatis, which occurred in a 55 year-old woman with diffuse intestinal lymphomatous polyposis in remission after treatment with chemotherapy and radiotherapy, and which was cleared after one month treatment with erythromycin. The Warthin-Sarry stain, performed to identify a specific agent such as Rochalimaea quintana and henselae, was negative, and the polymerase chain reaction technique could not be performed. Regressive cases of peliosis hepatis are rare, and 4 out of 7 have been reported after antibiotic treatment. Two of them were observed after an antibiotic regimen with erythromycin in patients with HIV disease, and the bacilli Rochalimaea quintana and henselae were identified in liver tissue with Warthin-Starry stain and polymerase chain reaction technique. The observation and the regressive cases recently reported elsewhere, suggest that appropriate antibiotic treatment should be proposed when peliosis hepatis occurs.

[Ileal duplication in adults. Value of 99m pertechnetate scintigraphy]. / Duplication iléale de l'adulte. Intérêt de la scintigraphie au 99m pertechnétate.

Duplications of the small bowel are an uncommon group of congenital malformations whose symptoms rarely occur in adults. We report the case of a 21 year-old man who suffered during four years from symptoms related to the ulceration of ectopic gastric mucosa in an ileal duplication (spontaneously resolving peritonitis, pelvic abscess, recurrent gastrointestinal bleeding and chronic abdominal pain). Radiological and endoscopic explorations and a first laparotomy failed to provide the diagnosis. 99m pertechnetate (99mTcO4) scintigraphy demonstrated ectopic gastric mucosa and guided the radiological detection of an ileal ulceration. Injection of 99mTcO4 during a second laparotomy located the ectopic gastric mucosa at the level of a tumefaction found on the mesenteric side of the terminal ileum. Duplication was only recognized at pathological examination of the ileal resection. This case emphasizes the need to evoke a duplication in clinical circumstances like those described in this patient as well as the usefulness of 99mTcO4 in the diagnosis of such a malformation.

[Primary biliary cirrhosis and sarcoidosis. Association or unique disease?]. / Cirrhose biliaire primitive et sarcoïdose. Association ou maladie unique?

The incontestable simultaneous occurrence of primary biliary cirrhosis and sarcoidosis is reported in a 40 year-old woman. The diagnosis of primary biliary cirrhosis was based on the association of intrahepatic cholestasis, increased serum IgM, high titer of antimitochondrial antibodies and hepatic histologic lesions. In six years the latter passed from bile duct destruction with fibrosis to cirrhosis with absence of bile ducts. The diagnosis of sarcoidosis relied on the presence of bilateral hilar lymphadenopathies, pulmonary infiltrate, tuberculoid granuloma without necrosis in an enlarged cervical lymph node and increased serum level of angiotensin conversion enzyme improved by steroid therapy. Such an association, only three other cases of which have been reported, suggests a link between the two diseases, which could be two localizations of a same physiopathological process.

[Multiple primary intraductal tumors of Wirsung's duct: demonstration of a relation between benign and malignant tumors]. / Tumeurs intra-canalaires primitives multiples du canal de Wirsung: démonstration d'une filiation entre tumeurs bénignes et malignes.

A case of multiple villous and, more rarely, tubulovillous adenomas of the main pancreatic duct, associated with a diffuse infiltrating adenocarcinoma of the pancreas in which evidence for a link between these lesions is supported by histopathologic features, is reported in a 53 year old patient. Clinical presentation included abdominal pain, weight loss and chronic diarrhea with steatorrhea related to pancreatic insufficiency. Retrograde endoscopic pancreatography showed a complete stenosis of the main pancreatic duct located 3 mm beyond the ampulla of Vater. CT scan showed an heterogeneous cephalic pancreatic tumor with extensive enlargement of the main pancreatic duct. After total pancreatectomy, recovery was maintained (follow-up 18 months). By analogy to colorectal tumors, a new pathologic classification of these rare neoplasms may be proposed.

[Intestinal involvement and exudative enteropathy in Waldenström's macroglobulinemia]. / Atteinte intestinale et entéropathie exsudative au cours de la macro-globulinémie de Waldenström.

The case of a 60 year old man in whom diarrhea, steatorrhea and protein losing enteropathy developed one year after the diagnosis of Waldenström's macroglobulinemia is reported. Histological study of multilevel peroral biopsies of the small bowel mucosa showed the following features: a) lymphangiectasia, b) intralymphatic and interstitial deposits composed of lipids and immunoglobulin M of the kappa type (as demonstrated by specific histoimmunofluorescence), c) a mild lymphoplasmocytoid infiltrate, corresponding to the location of Waldenström's macroglobulinemia. The patient died six months later, in spite of improvement of his digestive tract functional abnormalities by a low-fat diet. Sixteen cases of small intestinal involvement have been reported during the course of Waldenström's macroglobulinemia, of which only one showed features similar to those found in our case. Lymphangiectasia appear to be due to mesenteric lymph node involvement by the tumoral process, and/or to increased blood viscosity; in turn the lymphangiectasia seem to be responsible for steatorrhea and plasma protein losses, since in our case both lipids and the immunoglobulin M-kappa were shown to cross the villous epithelium by immunohistochemistry.