CD5+ leukemic monocytoid B-cell lymphoma and lymphocytic lymphomas.
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Aged↗
Biomedical subjects
F Menestrina
Publications and source records attributed to F Menestrina.
A CD5+ leukemic lymphoma with monocytoid features: an unusual B-cell lymphoma mimicking hairy-cell leukemia.
A case of lymphoma presenting with features shared by hairy cell leukemia (HCL) and its variant, intermediate lymphocytic lymphoma (ILL) and monocytoid B-cell lymphoma (MBCL) is described. Clinical presentation and the morphological findings observed in peripheral blood and in bone marrow biopsy suggested an HCL; however, the tartrate-resistant acid phosphatase negativity of peripheral blood lymphocytes, the histologic pattern observed in the spleen, and the immunophenotyping of peripheral blood, spleen and bone marrow neoplastic lymphocytes (expression of CD5 and lack of CD25), were strongly against this hypothesis. The clinical course was aggressive. This report emphasizes the concept of the equivocal presentation of some 'low-grade' B-cell lymphomas. It is further pointed out that, even with complete and exhaustive morphological and immunological analyses, atypical cases may be encountered.
Aged↗
Constitutive expression of tenascin in T-dependent zones of human lymphoid tissues.
Tenascin is a major extracellular matrix glycoprotein that can interfere with the action of fibronectin by inhibiting cell adhesion and spreading. Although tenascin is able to exert important immunomodulatory activities on T and B cells and macrophages, little is known about its distribution in different lymphohemopoietic tissues. In this study we have analyzed tenascin immunoreactivity on cryostat and paraffin sections of normal and pathological lymphoid tissues using two different monoclonal antibodies. We demonstrated strong tenascin expression in all peripheral lymphoid tissues, whereas it was barely detectable in the thymus and in bone marrow. In reactive lymph nodes, tenascin was mainly found in T-dependent zones, forming a variably close-woven reticular network corresponding to fibroblastic reticulum cells and blood vessels basal laminae, showing a partial co-localization with fibronectin. In B-dependent zones, tenascin was restricted to blood vessels. Using double-marker analysis, we performed a thorough study comparing tenascin expression in different compartments of lymphoid microenvironments. Tenascin network appeared much thicker in chronically stimulated tissues, where CD4+ lymphocytes with "memory" phenotype (CD45RO+/CD45RA-) were predominant, and at sites of ongoing inflammation. In particular, a striking increase of tenascin was observed in sarcoid lymph node, as well as in myasthenic hyperplastic thymuses. In addition, tenascin can be abnormally synthesized in tissue involved by various types of lymphomas, including Hodgkin's disease and hairy cell leukemia.
Bone Marrow↗
Immunohistochemical detection of microenvironmental abnormalities in lung biopsies from patients with sarcoidosis.
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Antigens, CD↗
Detection of calbindin-D immunoreactivity in human follicular dendritic cells.
The calcium-binding protein calbindin-D (28 kD) has been analysed immunohistochemically in different human lymphoid tissues. Combined immunohistochemical staining showed that calbindin-D (28 kD) is expressed by only a proportion of dendritic cells within the light zone of germinal centres, where antigens in the form of immune complexes are trapped and presented to B lymphocytes. All other cell types including macrophages, interdigitating cells, and various lymphocyte populations were negative. The expression of calbindin-D in this functionally relevant subset of follicular dendritic cells could have a role in the regulation of proliferation and selection of memory B-cells by modulating the concentration of calcium ions. Calbindin-D may be a useful marker for analysing in situ the phases of follicular development in different physiological and pathological conditions.
Calbindins↗
Association of Epstein-Barr virus genome with mixed cellularity and cellular phase nodular sclerosis Hodgkin's disease subtypes.
Association of Epstein-Barr virus (EBV) genome with Hodgkin's disease (HD) histological subtypes was investigated using the polymerase chain reaction (PCR). A highly significant association of EBV genome with the mixed cellularity (MC) subtype (10 positive out of 15 cases; 66%) was observed, suggesting a possible etiopathogenetic role of EBV in the induction of this subset. By contrast, a markedly lower frequency of association with EBV genome was found in nodular sclerosis (NS) (12 positive out of 46 cases; 26%) and in nodular lymphocytic predominance (NLP) (0 positive out of 5 cases) HD subtypes. In addition, in the NS series, the presence of EBV genome was mainly restricted to the 'cellular phase' NS subset. This finding strengthens the possibility, suggested by clinico-pathological features and survival rates, that 'cellular phase NS' is a disease more akin to MC than to typical NS HD.
Genome, Viral↗
Transbronchial biopsy in sarcoidosis: the role of immunohistochemical analysis for granuloma detection.
In this study 27 transbronchial biopsy specimens obtained from patients with clinical and/or laboratory features suggestive for sarcoidosis were analysed with conventional morphology and immunohistochemistry comparing the sensitivity and reproducibility of the two methods. A limited panel of monoclonal antibodies recognizing epitopes resistant to conventional fixation and embedment procedures were used (CD45R0, CD68, anti-cheratin, anti-collagen IV). All specimens were independently observed by two different pathologists. On the basis of the recognition of bona-fide noncaseating granulomas, 9 cases were uniformly judged as positive, 10 cases as negative, but 8 cases were considered doubtful. Immunohistochemical analysis reliably demonstrated the presence of epithelioid cells in 3 of these cases and absence in 5. These data suggest that the use of a limited immunohistochemical analysis can significantly improve histological diagnosis of sarcoidosis on small transbronchial biopsies using conventional routine material.
Antigens, CD↗
Evidence of c-myc gene abnormalities in mediastinal large B-cell lymphoma of young adult age.
Six cases of mediastinal large B-cell lymphoma (MLCL) with sclerosis were analyzed for the presence and patterns of c-myc and bcl-2 loci rearrangements, and for the presence of Epstein-Barr virus DNA sequences by Southern blot hybridization, c-myc gene alterations were found in three of six cases. Two cases showed the presence of mutations or small rearrangements at the 3' end of the first exon. The c-myc gene abnormalities found in these two cases are similar to those observed in the translocation 8;14 of the endemic Burkitt's lymphomas or in its variants t(2;8) and t(8;22). A third case showed a major rearrangement of c-myc gene, with truncation within its first intron, similar to those observed in sporadic Burkitt's and in acquired immunodeficiency-associated lymphomas. None of the cases displayed bcl-2 gene rearrangements or contained viral sequences. Our data suggest a possible role for a translocation-mediated c-myc activation in the pathogenesis of MLCL. Conversely, bcl-2 gene and Epstein-Barr virus do not appear to be involved in the pathogenesis of these peculiar lymphomas. The association between c-myc structural modifications and MLCL also seems to be of relevance in light of the peculiar tendency of this tumor to involve unusual extranodal site (eg, kidney), reminiscent of the spreading attitude of Burkitt's limphomas.
Adult↗
Immunohistochemical characterization of sarcoid granuloma: differentiation antigens and adhesion molecules.
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Antigens, Differentiation↗
Immunohistochemical differentiation of follicular lymphoma from florid reactive follicular hyperplasia with monoclonal antibodies reactive on paraffin sections.
In this study monoclonal antibodies which recognize lymphoid-associated antigens on paraffin sections (LN1, MB2, L26, MT2, UCHL1) have been evaluated to assess their usefulness in the distinction between reactive and neoplastic lesions of lymphoid follicles. Thirty-three follicular lymphoma samples and 36 reactive samples (lymph nodes and tonsils) were analyzed. MT2 appeared as the most valuable immunophenotypic marker as emerged from a comprehensive quantitative evaluation of 2329 reactive follicles and 2288 neoplastic follicles performed on MT2 immunostained sections. MT2-positive follicles were found in all lymphoma samples but one. Overall 1908 of 2288 neoplastic follicles were judged as positive whereas no follicles with comparable strong MT2 immunoreactivity could be found in non neoplastic samples. These latter showed weak MT2 positivity only in about 10% (224/2329) of reactive follicles. This study confirms that MT2 follicular positivity can be considered a reliable marker of follicular neoplasia, although negative results ought to be considered with caution. The detection of centrofollicular cells outside the germinal centers, which is considered a reliable criterion of follicular neoplasia, was highly improved by LN1 immunostaining. On the other hand pan-B antibodies such as L26 and MB2 were less informative because of the large number of B-lymphocytes observed in interfollicular areas of nonneoplastic samples.
Adult↗
Expression and gene rearrangement of the T-cell receptor in human thymomas.
Human thymomas are epithelial neoplasms frequently associated with an exuberant lymphoid component. This mixture of epithelial cells and lymphocytes closely mimicks the organization of normal thymic cortex. However, it is not known whether thymocytes in thymoma express the T-cell receptor (TCR) for the antigen. We have analyzed the molecular configuration of TCR genes and their phenotypic expression in eight thymomas. In all we detected polyclonal rearrangements of TCR genes and cytoplasmic expression of TCR molecules in most thymocytes, thus indicating that rearranged TCR genes in thymomas are functioning genes. In addition, these findings suggest that the epithelial component of thymomas, even if neoplastic, is still capable of directing thymocyte differentiation.
Adolescent↗
Small-cell neuroendocrine carcinoma of the ampullary region. A clinicopathologic, immunohistochemical, and ultrastructural study of three cases.
We report the clinicopathologic, immunohistochemical, and ultrastructural features of three small-cell neuroendocrine carcinomas of the ampullary region of the duodenum. All patients were men; their ages were 51, 62, and 66 years. The therapy consisted of pancreatoduodenectomy. All patients died of the disease; median survival was 10 months from the diagnosis. The histological appearance was identical to pulmonary and extrapulmonary small-cell carcinoma. The neuroendocrine differentiation was demonstrated ultrastructurally by the presence of dense-core granules, and by the positive immunoreaction for neuron-specific enolase and Leu-7 in each case. One case expressed a focal positivity for chromogranin A (PHE-5) and argyrophilic granules. The same case showed the presence of neurofilaments on frozen material. Neurofilament proteins could not be demonstrated in any case in paraffin sections. Neoplastic cells exhibited cytoplasmic immunostaining for cytokeratins (CAM 5.2) in all cases. In one case, a large number of neoplastic cells (60-70%) exhibited nuclear Ki-67 positivity. We postulate that the disease's histogenesis was from epithelial stem cell expressing both epithelial and neuroendocrine characteristics. The clinical behavior of small-cell neuroendocrine carcinomas of the ampullary region appears to be extremely aggressive, with early metastases and fatal outcome.
Adenocarcinoma↗
Multimarker immunohistochemical staining of calgranulins, chloroacetate esterase, and S100 for simultaneous demonstration of inflammatory cells on paraffin sections.
Mac387 monoclonal antibody (MAb) recognizes two calcium binding, myeloid-associated proteins, now termed calgranulins, expressed at high levels by neutrophils and monocytes. Calgranulins are related to migration inhibitory factor (MIF) and are lost in a few days from monocytes differentiated in vitro. This marker is therefore potentially useful to analyze macrophage heterogeneity and turnover in tissue sections. In this study, we developed an immunohistochemical multimarker technique, including calgranulin demonstration, suitable for analyzing different inflammatory cells on paraffin-embedded material. The technique was carried out in subsequent steps demonstrating (a) naphthol AS-D chloroacetate esterase (CAE); (b) S100 immunoreactivity using a rabbit antibody in peroxidase-antiperoxidase (PAP) staining; and (c) Mac387 immunoreactivity using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. CAE staining was introduced in this method to distinguish Mac387+/CAE- macrophages from Mac387+/CAE+ neutrophils, and Mac387-/CAE+ mast cells. S100 protein is strongly expressed within lymphoid tissues by dendritic accessory cells and was then applied to distinguish these cells from S100-macrophages. We have also verified the possibility of reducing the staining time for this time-consuming procedure by use of microwave irradiation. The technique was applied to a representative variety of normal and pathological samples to assess its usefulness for study of cell heterogeneity. Our results showed the multimarker technique to be highly informative in the study of inflammatory lesions (e.g., rheumatoid arthritis, sarcoid and cat-scratch granulomas, dermathopathic lymphadenopathy), and is of wide potential value as an aid to histopathological diagnosis of several diseases.
Antibodies, Monoclonal↗
Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients.
We report the clinical findings of 21 consecutive patients affected by mediastinal large B-cell lymphoma with sclerosis. This type of lymphoma is a recently described histopathologic entity characterized on clinical grounds by distinctive features, which, according to our series, can be summarized as follows: young age (median, 30 years; range, 15 to 42 years), prevalence of females over males (15 v six), rare occurrence of superficial lymph node enlargement (three of 21 patients), and involvement of unusual extranodal sites (kidney six, adrenal cortex two patients). The clinical course appears to be closely related to treatment. In fact, complete remission (CR) was not obtained in the six patients submitted to conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus bleomycin (CHOP-Bleo) regimens until 1985, as opposed to 13 CRs reached in the 15 patients subsequently treated with more aggressive regimens after 1985 (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B], 12 patients; methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone [M-BACOD], two patients; and vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate, and prednisone [F-MACHOP], one patient; plus involved-field radiotherapy, 10 patients). Among the 13 patients who achieved a CR, only one relapse was observed at 10 months. The median overall survival of complete responders after an observation period of 11 to 69 months has not yet been reached, and the event-free survival curve indicates that 90% of patients who achieve CR may be potentially cured.
Adolescent↗
Increased levels of soluble interleukin-2 receptor in non-Hodgkin's lymphomas. Relationship with clinical, histologic, and phenotypic features.
In this study the authors investigated the serum levels of the released soluble form of interleukin-2 receptor (sIL-2R) in patients with non-Hodgkin's lymphomas (NHLs). Data were evaluated in relationship to the morphologic and immunophenotypic heterogeneity of NHL at diagnosis and in progressive advanced diseases. Increased sIL-2R levels were found in most cases, when compared with levels observed in healthy controls. No obvious statistical correlation has been observed between sIL-2R values in different NHL subtypes as defined by current classifications. On the other hand, major significance was related to the extent of the disease. Very high values, comparable to those observed in hairy cell leukemia, were observed in a number of large cell NHLs complicating low-grade B-cell lymphoproliferations and in a single case of T-cell Kil+ NHL. The authors' findings suggest that the detection of sIL-2R in NHL may represent a good marker in improving risk assignment of single cases and/or for monitoring remissions and exacerbations during the treatment of cases with very high levels at diagnosis. Nevertheless, the observed overlap between groups on an individual case basis can render the clinical application of this marker problematic.
B-Lymphocytes↗
T-cell-rich B-cell lymphoma.
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B-Lymphocytes↗
Immunohistochemistry in bone marrow diagnosis.
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Bone Marrow↗
Serum levels of soluble interleukin-2 receptor in hairy cell leukaemia: a reliable marker of neoplastic bulk.
In hairy cell leukaemia (HCL), the strong membrane expression of the Tac antigen, corresponding to the p55 chain of the interleukin-2 receptor (IL-2R), is associated with the presence in the serum of high levels of a soluble form of the same molecule (sIL-2R). Previous observations that therapy-induced clinical and haematologic improvement in HCL is accompanied by a progressive decrease of sIL-2R suggest a possible correlation between sIL-2R levels and tumour burden. To verify this hypothesis, we monitored the variation of sIL-2R values in 13 non-splenectomized HCL patients admitted for treatment with recombinant interferon alpha-2. The data were correlated with the estimated weight of bone marrow (BM) and spleen infiltration, which in these patients almost entirely account for the tumour mass. The regression analysis test showed a direct correlation between sIL-2R values and both BM neoplastic involvement (r = 0.63) and spleen tumour mass (r = 0.76). In addition, the correlation was further improved (r = 0.86) when sIL-2R values were correlated with the total neoplastic mass, as calculated by the sum of spleen and BM neoplastic tissue weight. These data indicate that the detection of sIL-2R in HCL is a reliable non-invasive marker of tumour burden, which can be regarded as an additional useful tool for monitoring treatment response.
Adult↗