Malignant lymphoma of mucosa associated lymphoid tissue: a new etiology of amyloidosis.

Non Hodgkin Malignant lymphomas (NHML) of mucosa associated lymphoid tissue (MALT) are known to have multiple involvement of the digestive tract. We report one case, presenting with an infiltrative process of the jejuno-ileum, associating lymphoplasmacytoid proliferating cells and amyloidosis. The plasmacytoid cells expressed Alpha and scarce Mu heavy chains, and lambda light chain. Lympho-epithelial lesions were more obvious at the second site of involvement, in the gastric mucosa. The amyloid substance was negative with the Amyloid A component antibody and gave a background noise with Alpha, Mu and lambda chains. No similar report of amyloidosis associated with MALT NHML has been found in the literature.

Histological discrimination of idiopathic inflammatory bowel disease from other types of colitis.

AIMS: To assess the value of histology in diagnosing inflammatory bowel disease (IBD) in colorectal biopsy specimens. METHODS: Retrospective, double blind evaluation of colorectal biopsy specimens from 41 patients with colitis (28 with ischaemic colitis and 13 with acute self-limited colitis) and 84 patients with IBD (42 with Crohn's disease and 42 with ulcerative colitis). RESULTS: The features distinguishing IBD from other forms of colitis included distorted architecture, lymphocyte and plasma cell infiltrate, excess of polymorphonuclear leucocytes, polymorphonuclear cryptitis, crypt abscesses, and basal lymphoid aggregates. The features discriminating between Crohn's disease and ulcerative colitis included an irregular or villous surface, distorted architecture, decrease in mucus content, and polymorphonuclear cryptitis. Using multivariate analysis, 90% of patients with Crohn's disease and 71% of those with ulcerative colitis were correctly classified, the former being strongly defined by epithelioid granulomas, microgranulomas and isolated giant cells, and the latter best defined by an irregular or villous surface, decrease in mucus content and crypt atrophy. CONCLUSIONS: Examination of colorectal biopsy specimens is a reliable method for diagnosing IBD. In the absence of epithelioid granulomas, microgranulomas and isolated giant cells a diagnosis of Crohn's disease is based on the absence of histological criteria favouring ulcerative colitis. The histological spectrum of indeterminate colitis remains to be clarified.

[Extrapulmonary mycobacterial infection with multiple cold abscesses]. / Infection extrapulmonaire à mycobactéries avec abcès froids multiples.

We report one case of extrapulmonary mycobacterial infection, in the absence of HIV infection, singular by a clinical presentation simulating a tumor, associating a bulky intrahepatic mass, an abscess of the psoas, multiple intracerebral lesions, and an obstructive intracardiac mass of the right ventricle, which required a surgical resection. We comment the type of the mycobacterium involved and the hepatic and cardiac localisations, since macronodular hepatic abscesses are rare, and cardiac abcesses, exceptional.

[Intraductal mucin-secreting tumors of the pancreas. Nosologic discussion of two cases of villous tumor of Wirsung's duct and a case of mucinous ductal ectasia]. / Les tumeurs mucosécrétantes intracanalaires du pancréas. Discussion nosologique à propos de deux cas de tumeur villeuse du canal de Wirsung et d'un cas d'ectasie canalaire mucineuse.

Intraductal mucin-producing tumors of the pancreas are rare, recently described tumors; they have a better prognosis than usual ductal carcinomas of the pancreas. We report two cases of villous tumor of the main pancreatic duct and one case of mucinous ductal ectasia, with histochemical and immunohistochemical study.

[Botryoid rhabdomyosarcoma of the cervix. Clinico-pathologic study of a case]. / Rhabdomyosarcome botryoïde du col utérin. Etude anatomo-clinique d'un cas.

The botryoid rhabdomyosarcoma of the cervix is a rare tumour occurring in young woman or during genital activity. It mainly causes vaginal bleeding or appears as a polypoid grape-like mass with a gelatinous cut-surface. The diagnosis is based on the presence of a submucosal cambium layer and a rhabdomyoblastic differentiation, corresponding to an intracytoplasmic double cross-striation. Metaplastic cartilaginous islands are sometimes observed. The immunostaining ensures the muscular origin of the tumour, characterized by the expression of actin and desmin. Apart from mullerian adenosarcomas, the main differential diagnosis is represented by the benign polypoid formations of the cervix: the genital rhabdomyoma and the fibroblastic lesion, called fibro-epithelial polyp with atypical stroma. The treatment actually includes both chemotherapy and surgery which is often limited to a conization.

Flow cytometric DNA analysis of 20 bronchopulmonary neuroendocrine tumours.

Deoxyribonucleic acid (DNA) content of bronchopulmonary neuroendocrine tumours was measured by flow cytometry in order to investigate correlations between ploidy, S-phase fraction (SPF) and two histological classifications (World Health Organization (WHO), Warren and Gould), and clinical staging. A paraffin-embedded technique was used on 20 surgical specimens. Cases comprised (according to the classification of Warren and Gould) 7 carcinoids, 3 well-differentiated neuroendocrine carcinomas (WDNC), 6 intermediate neuroendocrine carcinomas (INC), and 4 small cell neuroendocrine carcinomas (SCNC). DNA aneuploidy was demonstrated in 3 out of 7 of the carcinoids, 3 out of 9 of the WDNCs and INCs, and 2 out of 4 of the SCNCs. A variable SPF was found in each group, except for the SCNCs which showed a constantly high SPF. In our small series, no correlation was noted between high SPF or aneuploidy and metastases. In conclusion, we observed no diagnostic value of malignancy for DNA aneuploidy. The SCNC group appeared to be an homogeneous group according to the SPF compared to the small cell carcinoma (SCC) group of the WHO classification. This and the prognostic incidence of high SPF need to be further studied.

Comparative quantitative study of Ki-67 antibody staining in 78 B and T cell malignant lymphoma (ML) using two image analyser systems.

Total Ki-67 stained area percentage was studied in 32 B and 46 T malignant lymphomas (ML) using two different image analyser systems (TAS, Leitz; SAMBA TM 2005, TITN) respectively. The total Ki-67 area percentage was highly correlated to the number of Ki-67 positive cellular profiles (B-ML, r = 0.93; T-ML, r = 0.88), indicating that area percentage is a reliable alternative method to the manual cell counting. Image analysis allows quicker measurements, appropriate to large and strictly lymphomatous regions. The cell image processor (SAMBA TM 2005, TITN) linked to a color video camera was more suitable for immunohistochemical sections and allowed more automated and faster measurements than the texture analyser (TAS, Leitz) linked with a black and white camera. Alkaline phosphatase technique with fast red as chromogen was more suitable for the detection of Ki-67 stained area by thresholding than peroxidase technique with aminoethylcarbazol or with diaminobenzidine as chromogens. Significant differences were found between low and high grade in B and T ML according to the Kiel classification (mean values +/- SD of 7.7 +/- 3.8% and 16.6 +/- 6.2% in B-ML and of 10.2 +/- 7.9% and 25.6 +/- 16.3% in T-ML respectively). In follicular B-ML, considering follicular areas only, values were comparable to high grade ML; angioimmunoblastic-lymphadenopathy-like (AILD-type) T-ML belonging to low grade ML showed similar values to pleomorphic T-ML with medium and/or large cells belonging to high grade ML.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative study of KI-67 antibody staining in 46 T-cell malignant lymphomas using image analysis.

Image analysis with a SAMBA 2005 (ALCATEL-TITN, Co) was used to quantify the Ki-67 stained area percentage in 46 T-cell malignant lymphomas (T-ML), classified according to the updated Kiel classification. This parameter demonstrated correlation with the number of Ki-67-positive cellular profiles (r = 0.88, P less than 0.001) and was more reproducible than cell counting. A significant difference was found between low and high grade T-ML (mean values +/- SEM respectively of 10.20 +/- 1.82 per cent and 25.63 +/- 3.15 per cent). The most interesting findings were that: (1) AILD-type T-ML showed an intermediate proliferation rate (15.55 +/- 2.72 per cent) between pleomorphic T-ML with medium and with large cells (respectively 12.53 +/- 3.64 per cent and 22.43 +/- 3.46 per cent), both of which belong to the high grade malignancy group. This finding is in accordance with the poor prognosis of this subtype despite its classification in the low grade malignancy group. (2) Subclassification of the pleomorphic MLs according to the predominance of small, medium or large cells, demonstrated significant differences between these three subtypes. However, the great overlap of values between pleomorphic T-ML with medium and with large cells, seems to indicate that the subclassification of these two subtypes is less valid. (3) A wide range of values with overlap was observed in AILD-type ML, in pleomorphic with medium or large cells and in lymphoblastic T-ML: for these T-ML with variable survival courses, the Ki-67 area percentage, one parameter of proliferative activity, appears worth studying as a prognostic factor.

Quantitative study of KI-67 antibody staining in non-Hodgkin's lymphomas using image analysis.

In sections from 32 B malignant lymphomas (ML), the total KI-67 stained area was compared to the number of KI-67 positive cells in order to demonstrate the reliability of using image analysis to quantify the proliferative activity. The total KI-67 area percentage correlated highly with the number of KI-67 positive cellular profiles (r = .93). Significant differences were found between low- and high-grade ML according to the Kiel classification (mean values +/- SD, respectively, of 7.7 +/- 3.81% and 16.6 +/- 6.23%), and between low-, or intermediate- and high-grade ML only, according to the International Working Formulation. Within the Working Formulation, the statistical analysis grouped the diffuse large cell subtype of intermediate grade with the immunoblastic high-grade subtype. A wide range of KI-67 area percentage values was noted, particularly in follicular ML; for these follicular ML, considering follicular areas only, values were comparable to high-grade ML (14.8 +/- 6.60%). In conclusion, the KI-67 area percentage is a reliable alternative method to manual cell counting, and image analysis allows quicker measurements appropriate to large and strictly lymphomatous areas, using a greater number of cells than in manual cell counting.

[Acute malignant myelofibrosis. Report of 3 cases]. / Myélofibrose aiguë maligne. Rapport de trois cas.

This report describes three cases of acute malignant myelofibrosis characterized by pancytopenia, absence of splenomegaly, bone marrow fibrosis with an immature cell proliferation and rapidly fatal outcome. The authors investigated the origin of blast cells with the use of immunohistochemical markers on paraffin embedded material with anti-factor VIII, BNH9 and anti-lysozyme. They studied the expression of megakaryoblastic, erythroblastic and myeloblastic differentiation in these cells. They demonstrated the heterogeneity of blast cells which are capable of differentiating along the three hematologic cell lines. The morphometric study showed the mutilating or systematized character of myelofibrosis. The increase in reticulin fiber density compared with normal bone marrow was not significantly different from two other types of myelofibrosis. It would be interesting to correlate a quantitative parameter with the course of this disease in order to evaluate the prognosis and the treatment.

Histopathological study of bone marrow biopsies in 30 cases of T-cell lymphoma with clinical, biological and survival correlations.

Forty-five bone marrow (BM) biopsies have been studied in 30 T-cell malignant lymphoma (ML). According to the updated Kiel classification, these ML comprised 12 low grade ML and 18 high grade ML. BM involvement was not significantly more frequent in low grade ML (41.6 per cent) than in high grade (33.3 per cent). This involvement was discovered in 85 per cent of the cases at the time of diagnosis. A correlation was found between BM and other visceral localizations for histological type in all cases. Infiltrates principally showed a nodular pattern in low grade and a diffuse pattern in high grade ML. Hematopoietic hyperplastic reaction was frequent (66.6 per cent) not correlated to involvement. Clinical staging showed extensive spreading. Our patients had an overall median survival of 40 months, worse in high grade ML (median: 19 months) than in low grade ML (41 months) but not statistically different (p = 0.25). Extranodal localizations are a significant criteria for poor prognosis (p = 0.018). Among them, BM involvement appears to be the most significant criteria (Cox model, p = 0.006). Patients with BM localization had a median survival of 9 months contrasting with 40 months in patients without BM localization (p = 0.007). Thus, BM biopsy is useful for the diagnosis of patients with T-ML and essential to establish the prognosis.

[Peripheral T-cell malignant lymphomas. Clinical, morphologic and developmental features in 22 cases]. / Lymphomes malins T périphériques. Aspects cliniques, morphologiques et évolutifs de 22 cas.

Peripheral T-cell lymphomas (PTCL) represent a new subset of malignant lymphomas, which demonstrates a marked morphological, immunological and clinical diversity. They seem to have a worse prognosis globally than B-cell lymphomas. The main clinical characteristics and outcome of PTCL are analysed in this series of 22 cases. The majority of patients had an advanced disease (stages III and IV; 55 percent) and constitutional symptoms (59 percent) at presentation; extranodal localizations were particularly frequent (41 percent). Three patients presented with isolated or predominant spleen enlargement and fever. According to the updated Kiel classification, there were 7 low-grade PTCL and 15 high-grade PTCL. Phenotypic analysis on fresh frozen tissue was available in 16 cases, showing a predominant helper/inducer phenotype (CD4+, CD8-). The complete remission rate was 76 percent for the whole population, but the median of global survival was only 40 months. The few patients who received radiation therapy and subsequently relapsed did not relapse in the irradiated fields, which suggests that radiotherapy might be included in the therapeutic strategy, the best modalities of which remain to be defined.

[Fatal hemoptysis during bronchial aspergillosis with multiple pulmonary artery aneurysms]. / Hémoptysie fatale au cours d'une aspergillose bronchique par anévrysmes artériels pulmonaires multiples.

Aspergillosis with fatal outcome are usually pulmonary invasive aspergillosis with or without dissemination, developed in patients with severe immunosuppression. We report a fatal case of bronchial necrotizing aspergillosis in a young woman with diabetes mellitus, who developed similar lesions to "Semi-invasive Aspergillosis", so-called "Chronic Necrotizing Pulmonary Aspergillosis". This aspergillosis was complicated by large pulmonary artery aneurysms requiring an hemostatic lobectomy. These aneurysms, secondary to the bronchial lesions, contrast with infectious aneurysms (so-called mycotic) secondary to septic embols. They differ from Rasmussen's aneurysms, due to tuberculosis, by their size, fusiform shape and extent. Lesions of vessels' walls and parietal fungal invasion in the vicinity of an endo-bronchial aspergilloma explain the vascular rupture. The multiplicity of these aneurysms, showed on C T Scan, is responsible for death by post-surgical recurrence of hemoptysis.

Quantitative study of centrolobular hepatic fibrosis in alcoholic disease before cirrhosis.

In an attempt to determine the importance of perivenular fibrosis (PVF) in alcoholic liver disease, we studied 71 liver biopsies using histological grading and a morphometric method. The histological grading used 7 variables which allowed us to classify the patients into 7 groups: controls, patients without alcoholic hepatitis but with steatosis, steato-fibrosis, portal fibrosis and patients with mild, moderate, or severe alcoholic hepatitis. The quantitative analysis examined 3 parameters: (1) The inner diameter of the terminal hepatic veins (THV). (2) The thickness of the THV rims, related to perivenular fibrosis (PVF). (3) Centrolobular fibrosis (CLF) which represented the association of perivenular and perisinusoidal centrolobular fibrosis. No changes in the inner diameter of the terminal hepatic veins was observed for the different groups except in the case of severe alcoholic hepatitis. This fact indicated the absence of veno-occlusive lesions in early stages of mild and moderate alcoholic disease. In severe alcoholic hepatitis, THV were destroyed by centrolobular scars and most of them were indistinguishable and unmeasurable. Of the 26 cases with steatosis (with or without portal fibrosis) only two cases with steatofibrosis showed perivenular fibrosis. In contrast, a significant increase in PVF and in CLF appeared in patients with alcoholic hepatitis. CLF is easier to quantify and more significative than PVF. Thus, it seems to us that CLF is a better indicator of the intensity of sclerosis and of the risk of developing cirrhosis than PVF alone.

Angio-immunoblastic lymphadenopathy (AIL) or T-cell malignant lymphoma of AIL-type. A histopathological, immunohistochemical and ultrastructural study of 8 cases.

Eight cases of AIL-type T-cell malignant lymphoma are reported. The clinical symptoms are the same as those described in AIL: fever, malaise, weight loss, skin rashes, polyadenopathy, and splenomegaly. However, some differences can be noted: the absence of hepatomegaly in all cases but one, the absence of polyclonal hypergammapathy in all cases but one, and predominance in females. The lymph node modifications comprise diffuse infiltrations of lymphoid cells with irregular nuclei and pale cytoplasm, associated with a large number of immunoblasts and plasma cells. Some eosinophilic granulocytes and epithelioid cells can be seen. Hyperplasia of the vessels and remnants of follicles, sometimes with proliferation of follicular dendritic cells, are prominent features. The immunolabelling study demonstrates the presence of an important T-cell population all expressing a high predominance of CD 4 phenotype. These findings are in accordance with those published in Europe and in contrast with those of some of the Japanese cases, particularly the first patients published by Shimoyama et al. The differential diagnosis with AIL is based on the presence of clusters of mainly large cells with a pale cytoplasm, on the loss of expression of one T cell marker, as in 3 cases of our series, and on the presence of a high percentage of lymphoid cells engaged in the mitotic cycle as demonstrated with the Ki 67 monoclonal antibody. However, to draw a clear cut difference between AIL-type T-cell lymphoma and AIL considered as a prelymphomatous dysimmune lymphadenopathy, only the demonstration of cytogenetic abnormalities, as in one of our cases or of rearrangement of the genes coding for beta and/or gamma chain of the antigen receptor of T-cell are valuable criteria. The follow-up of our series is not long enough to appreciate the prognosis. Three patients died, one from a glioma. All the other cases, treated with polychemotherapy show total remission with an evolution of 10 to 39 months.

[Malignant peripheral T-cell lymphomas: morphologic and immunopathologic bases of the classification proposed by Lennert and Suchi]. / Les lymphomes malins T périphériques: bases morphologiques et immunopathologiques de la classification proposée par K. Lennert et T. Suchi.

In the last few years advances in immunopathology have demonstrated the T cell origins of some malignant lymphoma (ML). Histopathological criteria have been suggested for classifying several varieties of T cell ML. Peripheral T cell ML are the result of proliferation of T cell lymphocytes with markers which distinguish between the enhancing-inducer and suppressor-cytotoxic forms. The diagnosis is made from the appearances of the cell, the presence of vascular hyperplasia and associated lesions. The numbers of small, medium and large cells and clinical follow-up of these tumors have provided a means of distinguishing between low and highly malignant tumors. Some peripheral T cell ML have associated lesions due to the secretion of lymphokines which give characteristic histopathological appearances (lympho-epithelioid T cell ML, AIL type T cell ML). The authors discuss the respective places of each variety of peripheral T cell ML in Lennert and Suchi's classification which is an extension of that proposed by Kiel, and their prognostic signification.