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Biomedical subjects

R Volpe

Publications and source records attributed to R Volpe.

At least 91 records · Page 5Linked to original sources

Immunoglobulin and T cell receptor gene rearrangements and in situ immunophenotyping in lymphoproliferative disorders.

We investigated for rearrangements of the immunoglobulin (Ig) heavy and light chain genes and of the T cell receptor gamma (TCR gamma) and beta (TCR beta) genes 45 biopsy samples from a variety of lymphoproliferative disorders. They were diagnosed histopathologically and immunophenotypically as non-Hodgkin's lymphomas (NHLs) of the B cell type (19 cases), NHLs of the T cell type (3 cases), NHLs of "undetermined" cell type (3 cases), atypical lymphoid proliferation (1 case) and AIDS-related lymphadenopathies with florid polyclonal follicular hyperplasia (19 cases). A monoclonal proliferation of B cells was shown by DNA analysis in all 19 B cell NHLs. In two immunohistologically determined T cell NHLs (both diagnosed as mycosis fungoides) the cells had rearrangements of TCR beta gene, whereas in the third case (lymphoblastic NHL) the cells had rearrangements of Ig heavy chain and TCR gamma and TCR beta genes. None of the B cell NHLs exhibited TCR gamma and TCR beta gene rearrangement bands. All the "undetermined" cell NHLs demonstrated rearrangements of Ig heavy chain gene associated with the germ line TCR gamma and TCR beta genes; in two cases light chain gene rearrangements were also found. The atypical lymphoid proliferation, in which the differential diagnosis was between a reactive or malignant process, and two out of 19 cases of florid polyclonal follicular hyperplasia showed a clonal B cell population by DNA analysis. This study indicates that there was a strong correlation between the rearrangements of specific genes and the immunophenotype of the NHL; moreover, DNA analysis of tissue biopsy specimens from phenotypically "undetermined" cell NHLs and from equivocal lymphoid proliferation using Ig and TCR gene probes yielded an answer in the cases analyzed. The significance of clonal B cell expansions found in two AIDS-related lymphadenopathies should be interpreted with caution.

AIDS-Related Complex↗

Dipeptidylaminopeptidase IV activity in T lymphocyte subsets in B cell non-Hodgkin's lymphomas.

The total T cell population and T cell subsets in ten lymph nodes with reactive lymphoid hyperplasia (RLH) and 23 specimens (21 lymph nodes, one stomach, and one small bowel) involved by histologically and immunohistologically diagnosed B cell non-Hodgkin's lymphomas (NHLs) were determined by reactivity with monoclonal antibodies Leu 4-CD3, Leu 3-CD4, and Leu 2-CD8 in cytospin preparations from cell suspensions. T cell populations were also investigated for the coexpression of dipeptidylaminopeptidase IV (DAP IV) activity, which was visualized simultaneously with cell surface immunostaining by a combined cytochemical and immunocytochemical method. The mean absolute percentage of Leu 4-CD3+ (total T) and Leu 3-CD4+ cell populations was significantly lower in B cell NHL cases than in RLH cases (35% v 54%, P less than .001; 29.5% v 44.4%, P less than .01). No difference in the mean absolute percentage of the Leu 2-CD8+ T cell subset was found between the RLH cases and the B cell NHL cases classified as other than category A as described by the Working Formulation (WF) of NHLs. The relative percentage of Leu 4-CD3+ and Leu 2-CD8+ cells coexpressing DAP IV reactivity was lower in B cell NHL cases than in RLH cases (27.3% v 39.5%, P less than .05; 13.5% v 24.4%, P less than .10). There was no difference in the proportion of Leu 3-CD4+ cells expressing DAP IV reactivity between the NHL and RLH groups (34.5% v 36.1%). Since the mean relative percentage of Leu 2-CD8+ cells expressing DAP IV reactivity in the B cell NHL group in the other than category A according to the WF was lower than that of the RLH group (12.5% v 24.4%), and whereas the mean absolute percentage of total Leu 2-CD8+ cells was similar in the two groups (16.6% and 16.6%), a possible defective role of this Leu 2-CD8+ DAP IV+ subset, at least in B cell NHLs in the other than category A according to the WF, may be hypothesized.

Antibodies, Monoclonal↗

Intermediate lymphocytic lymphoma encompassing diffuse and mantle zone pattern variants. A distinct entity among low-grade lymphomas?

Intermediate lymphocytic lymphoma has been operationally included among low-grade lymphomas, but few clinical data appeared to support definitely such an inclusion. The clinicopathologic features of 13 out of 14 cases of intermediate lymphocytic lymphoma either encompassing diffuse or mantle-zone pattern variants (ILL or MZL, respectively), diagnosed by conventional histology according to established criteria, are reported. Frozen section immunophenotypic analysis was also performed in 10 cases and enzyme studies were done in five. The 14 cases formed 6.9% of 203 non-Hodgkin's lymphomas (NHL) histologically diagnosed over a 2-year period. Among the 13 cases studied, there were nine males (five with ILL and four with MZL) and four females (one with ILL and three with MZL). Median age was 59 years. Splenomegaly (46%), high stage diseases (100%), involvement of bone marrow (92%) and peripheral blood (38%), and diffusion to and/or involvement of extranodal sites (38%), all were common findings at presentation. The 34 low-grade NHL of the total series classified according to the Working Formulation did not significantly differ from the ILL/MZL group in terms of frequency of involvement of bone marrow (69%) and peripheral blood (56%) as well as diffusion to and/or involvement of extranodal sites (26%). In ILL/MZL, therapy modalities were not uniform and the short follow-up time precluded firm conclusions on prognosis. Immunohistology demonstrated that ILL/MZL diagnosed by adequate morphologic criteria is a fairly homogeneous entity, also sharing most of its consistent immunological features with low-grade NHL. Thus, ILL/MZL is a relatively frequent and consistently recognizable clinical and pathological entity that may deserve a distinct place among NHL according to the Working Formulation. Proper clinical studies are needed to establish on a firmer basis the prognosis and optimal treatment of ILL/MZL.

Adenosine Triphosphatases↗

Non-familial hemophagocytic lymphohistiocytosis.

A case of non-familial hemophagocytic lymphohistiocytosis (HLH) is described. The patient had a chronic course being alive and doing relatively well 3 years since onset. The specific pathological features of this disorder are discussed with emphasis on the fact that a remarkable loss of lymph node structure is sustained by a mature lymphohistiocytic infiltrate. Erythrophagocytosis is assessed as an important but not specific finding. Lymphocyte depletion is an important feature of the lesion. The presence of overlapping features in HLH, infection-associated hemophagocytic syndrome (IAHS) and X-linked recessive lymphoproliferative syndrome (XLS) is emphasized.

Child, Preschool↗

A method for routine approach to laryngeal and hypopharyngeal surgical specimens by whole organ sections in the horizontal plane.

A procedure of pathological analysis of laryngopharyngeal specimens by whole organ sections in the horizontal plane was developed and evaluated. The use of a fast decalcifying and fixative solution allowed both an easier sectioning of the whole organ and thin (5-6 microns) histological whole organ sections of laryngo pharyngectomy specimens. The complete procedure required 5 to 10 days for each case. A preliminary examination of 39 surgical laryngopharyngectomy specimens with laryngeal or hypopharyngeal carcinomas showed that most of the normal structures were histologically identifiable on whole organ horizontal histological sections. The data of the local neoplastic spread related to the main sites of origin were in accordance with the results obtained by other studies using whole organ sections in the coronal or vertical planes. In conclusion, with this procedure it is possible to obtain, in a reasonably short time, thin histological horizontal whole organ sections allowing an adequate and complete assessment of the microscopic characteristics of the tumor and of the tridimensional relationships of the neoplasm with the host organ; moreover, by this procedure pathological data may be compared with preoperative CT or MR scans in patients with laryngeal and hypopharyngeal carcinomas.

Histocytochemistry↗

A combined cytochemical and immunocytochemical method for simultaneous visualization of cytoplasmic enzyme reactivity and cell surface antigens in cell suspensions.

Immunocytochemical methods were used in combination with enzyme cytochemistry to visualize simultaneously cytoplasmic enzyme reactivity (for dipeptidyl[amino]peptidase [DAP IV], acid phosphatase [AcP], chloroacetyl esterase [CAE]) and cell surface antigens (Leu-3a, Leu-4, Leu-14, Leu-M1, OKT4, OKT8, OKB7) in cytospin preparations from cell suspensions of human reactive lymphoid tissues (four lymph nodes and three tonsils). Different fixative solutions were tested. Enzyme and immunocytochemical reactions were carried out in different orders of sequence to establish which was the better direction for the combination of the two methods. The following immunocytochemical methods were tested: three stages, avidin-biotin complex, peroxidase-antiperoxidase, alkaline phosphatase-antialkaline phosphatase (APAAP) (using both peroxidase and alkaline phosphatase as labeling enzyme). Acetone or buffered formalin acetone gave the best results both for cytochemical and immunologic reactions. DAP IV and AcP reactivities could be visualized only when cytochemical reactions were performed before immunocytochemistry. CAE reactivity could be demonstrated either before or after immunocytochemistry. Cell surface antigens could be demonstrated with most immunocytochemical methods: however, the APAAP method was preferred for its sensitivity and effectiveness when combined with enzyme cytochemistry. By this approach, cells expressing only immunologic markers and cells expressing only cytochemical markers could easily be distinguished from those coexpressing both markers, because cytochemistry and immunocytochemistry could be combined without affecting the reactivity of each marker, and the reaction products did not hamper the interpretation of preparations.

Antigens, Surface↗

Monocytoid B-cell lymphoma with bone marrow and peripheral blood involvement at presentation.

A case of malignant lymphoma showing in a lymph node the characteristic morphologic features of the so-called monocytoid B-cell lymphoma (MBCL) is described. This case differs from the reported cases in the literature because atypical cells were observed in the bone marrow biopsy and marrow and peripheral blood smears that were obtained from the patient, a 61-year-old man, during the staging procedures. Lymphocyte surface marker studies on peripheral blood by flow cytometry and DNA analysis revealed a monoclonal population of lambda-positive lymphocytes. The immunophenotype of MBCL cells was studied both in paraffin-embedded lymph node sections by immunoperoxidase method and in peripheral blood by flow cytometric analysis; the cells expressed the SIg with lambda light chain restriction and the HLA-DR antigen; they also had positive results for B-cell-associated antigens, including LN1, LN2, CD 20, CD 22, CD 19, CD 9 but not CD 21, CD 24, and CD 10, T-cell-associated antigens and monocytic markers. In addition, they had negative results for CD 25, CD 38, PCA-1. This report emphasizes that in MBCL, peripheral and marrow involvement may occur at presentation analogous to other low-grade B-cell lymphomas. The immunophenotypic characteristics of MBCL cells, though not pathognomonic, are considered to be helpful in differentiating them from circulating cells of other B-cell lymphomas.

Antigens, Differentiation, B-Lymphocyte↗

Non-Hodgkin's lymphoma in the elderly: a retrospective evaluation of toxicity related to aggressive vs. conservative treatments.

The outcome of 70 elderly patients aged 65 years or more (median, 71 years) with non-Hodgkin's lymphoma (NHL) treated between 1973 and 1981 with aggressive (AM) or conservative modalities (CM) was retrospectively evaluated. A significantly higher incidence of lethal and severe toxicity was observed in patients treated with AM than in those treated with CM (32% vs 3%, p less than 0.01), with 10% treatment related deaths in the AM group. Only 56% of the deaths were attributed to NHL; other major causes were treatment-related deaths, infection and cardiac diseases. No significant difference in response and survival was found between AM and CM groups (complete remission rates were 35% vs 42%, and 10 year survival rates were 31% vs 19%, respectively), but the prevalence of stages III-IV in patients treated with AM makes these results meaningless. Prospective randomized trials with AM vs CM are clearly needed in elderly patients with advanced unfavorable NHL.

Aged↗

Expression of Leu-8 surface antigen in B-cell lymphomas. Correlation with other B-cell markers.

Using in situ immunohistological analysis, expression of Leu-8 and its correlation with other B-cell markers were investigated in 21 selected lymphomas of different categories, each one expressing its own typical immunophenotype. These categories included eight follicular centroblastic/centrocytic (CB/CC) lymphomas, eight intermediately differentiated lymphocytic lymphomas (ILL)/mantle zone lymphomas (MZL), and five lymphocytic lymphomas (LL) associated with chronic lymphocytic leukaemia (CLL). Four reactive lymph nodes and three tonsils were also studied using double immunolabelling procedures. Cell suspensions were also performed in three CB/CC and four ILL/MZL cases. Leu-8 was consistently expressed in ILL/MZL and LL but it was absent in most (7/8) CB/CC lymphomas. In reactive tissues, the Leu-8-positive B cells were strictly confined to the mantle zones. A close association emerged between Leu-1 (CD5) and Leu-8, both being present in ILL/MZL and LL but absent in CB/CC. A consistent lack of association was found between Leu-8 or CD5 antigens and common acute lymphoblastic leukaemia antigen (CD10) and BA-2 (CD9) antigen, whereas Leu-8 and CD5 were strictly associated with surface IgD. Reactivity with Leu-8 provides a means of distinguishing between CB/CC and ILL/MZL. Furthermore, shared immunoreactivity for Leu-8 in ILL/MZL and LL may represent a potential clue to the still uncertain cellular derivation of LL/B-CLL.

Antigens, Differentiation, T-Lymphocyte↗

Heterogeneous immunostaining patterns of follicular dendritic reticulum cells in human lymphoid tissue with selected antibodies reactive with different cell lineages.

A comparative immunohistologic study of the cell density and distribution pattern of follicular dendritic reticulum cells (DRCs) within their follicular microenvironments (germinal centers and mantle zones) was performed by immunoperoxidase technique with a selected panel of antibodies either operationally specific for DRCs (DRC-1) or reported as having additional immunoreactivity with DRCs (antibodies to B- and T-cells, leukocytes, monocytes/macrophages, desmosomal components, and S-100 protein). Twenty-five biopsy specimens, including reactive lymph nodes and tonsils as well as normal spleen tissue, were analyzed. Serial frozen sections were tested either with single antibodies or paired monoclonal reagents in double-labeling procedures. Our results consistently indicated that DRCs positive for Leu M3 and BA-2 antibodies were confined to the central portion of germinal centers, whereas DRCs immunoreactive for S-100 protein and desmoplakin 1 and 2 were localized mostly in the central and pericentral portion of germinal centers. All the DRCs extending from the central portion of germinal centers to the mantle zones were labeled with DRC-1 and, unexpectedly, with OKB7 antibodies. Other immunostainings, such as those for HLA-DR antigens, common leukocyte antigen, and Leu 3a, were not contributory in defining topographic differences of DRCs within the follicle. The consistent heterogeneity of the labeling patterns appears to suggest a possible in situ immunophenotypic grouping of DRCs, and the concept of their possible heterogeneity appears to be corroborated.

Antibodies, Monoclonal↗

Dendritic reticulum cell pattern as a microenvironmental indicator for a distinct origin of lymphoma of follicular mantle cells.

Follicular dendritic reticulum cells (DRCs) are known to be normally present in primary follicles and both follicular centres and mantle zones of secondary follicles of peripheral lymphoid tissue. Involved frozen biopsy tissue specimens from eight cases of intermediate lymphocytic lymphoma/mantle zone lymphoma (ILL/MZL); eight cases of follicular centre cell lymphomas (FCCL) of the centroblastic/centrocytic type; and seven cases of well-differentiated lymphocytic lymphoma (WDLL) consistent with chronic lymphocytic leukaemia (CLL) were analysed immunohistologically with R4/23 (DRC-1) monoclonal antibody reactive with 'bystander' DRCs. As opposed to FCCL and most WDLL/CLL cases, the DRCs consistently formed a loose, ill-defined meshwork with a radiating or blurred outline in all MZL cases and one ILL. On the basis of the observed findings as well as from those reported in literature, the hypothesis is proposed that ILL/MZL originates from the follicular mantle zone and represents a distinct lymphoma entity owing to its peculiar immunostaining pattern of DRCs that allows it to be separated from both FCCL and WDLL/CLL. Moreover, the absence of DRCs in the microenvironment of other B-cell malignancies such as prolymphocytic leukaemia and hairy cell leukaemia, analogously with most CLL cases, would speak in favour of their different--possibly extrafollicular--compartment of origin within lymphoid tissue.

Dendritic Cells↗

Study of AIDS-related lymphadenopathy in the intraparotid and perisubmaxillary gland lymph nodes.

Salivary gland lymph node involvement is rare in patients at risk for AIDS. Intraparotid and perisubmaxillary gland lymph node biopsies from 2 intravenous drug abusers serologically positive for human immunodeficiency virus (HIV) affected by persistent generalized lymphadenopathy (PGL) were also analyzed immunohistologically. We found hypervascular reactive lymphoid hyperplasia with prevalence of suppressor T-cells within follicular centers often lacking surface IgD-positive mantle zone cells and showing disruption of the network of dendritic reticulum cells revealed with DRC-1 and anti-S-100 protein antibodies. Within the nodes there were numerous cysts lined by metaplastic squamous epithelium/positive for epithelial membrane antigen and containing numerous lymphocytes positive for leukocyte common antigen, macrophages positive for alpha 1 -antichymotrypsin, and Langerhans cells positive for OKT6. Salivary gland lymph nodes are immunohistologically similar to those of other sites in PGL and their increased epithelial metaplastic component containing cells involved in the immune response might represent an exuberant reaction to HIV infection.

AIDS-Related Complex↗

Superficial extending carcinoma of the larynx.

Superficial extending carcinoma of the hypopharynx is a recently recognized form of carcinoma regarded as a possible pharyngeal counterpart to early gastric cancer and superficial esophageal carcinoma. In this study we report the radiological, clinical, and pathological features of three carcinomas of the larynx, which show architectural and histopathological features similar to those previously described in superficial extending carcinoma of the hypopharynx. These cases were singled out from a series of 37 consecutive laryngectomy specimens of primary infiltrating laryngeal carcinomas that were uniformly studied by means of a whole-organ sections technique. Pathologically, these cases showed a clearly invasive growth through the basal membrane into the lamina propria and an entire or predominant, extensive, superficial type of spread; infiltration of underlying muscle or gland structures was restricted to a few microscopic foci, regardless of the presence of lymph node metastases. The present study demonstrates that infiltrating carcinomas with a preferential superficial type of growth may also be encountered in the larynx. Differences between the histological features of these carcinomas of the larynx and the histopathological spectrum of so-called early laryngeal cancer are emphasized.

Aged↗

Clinical and laboratory findings at presentation in persistent generalized lymphadenopathy vs malignant lymphoma.

The purpose of this study is to compare the clinical and laboratory findings at presentation of 38 intravenous drug abusers with pathologically documented persistent generalized lymphadenopathy and 50 patients with biopsy proven malignant lymphoma (30 Hodgkin diseases, 20 non-Hodgkin's lymphomas) not related to acquired immunodeficiency syndrome, all aged 40 years or less and consecutively seen and evaluated with a similar clinicopathological approach since May 1984 in a single institution, Centro di Riferimento Oncologico, Aviano, Italy. Our results document that, although pathology is the decisive diagnostic tool, selected clinical and laboratory findings may contribute to a better differentiation of persistent generalized lymphadenopathy from malignant lymphoma not related to acquired immunodeficiency syndrome. Therefore, young patients presenting with generalized lymphadenopathy, apparently not related to known groups at risk for acquired immunodeficiency syndrome, should be evaluated also according to a protocol which includes the detection of symptoms, signs, and laboratory data that are known to be significantly increased among patients with persistent generalized lymphadenopathy.

Adult↗

Heterogeneous in situ immunophenotyping of follicular dendritic reticulum cells in malignant lymphomas of B-cell origin.

The phenotype of follicular dendritic reticulum cells (DRC) was analyzed with monoclonal antibodies (DRC-1, OKB7, BA-2, Leu-M3, and antidesmoplakin 1 and 2) in 28 frozen biopsy specimens of both morphologically and phenotypically analyzed B-cell lymphomas and 21 normal or reactive controls. The former included 15 follicular center cell lymphomas (FCCL), four intermediately differentiated lymphocytic lymphomas (ILL), four mantle zone lymphomas (MZL), and five well-differentiated lymphocytic lymphomas (WDLL). In controls, DRC-1+ and OKB7+ DRC were localized in both follicular centers (FC) and mantle zones (MZ), but BA-2+ and Leu-M3+ DRC were confined to FC only. FCCL were usually accompanied by DRC-1+, OKB7+, and BA-2+ DRC, and either lost or maintained positively with Leu-M3 from case to case. By contrast, MZL consistently lacked BA-2+ and Leu-M3+ DRC, and was associated with DRC-1+ and OKB7+ DRC only. Desmoplakin-positive DRC occurred in variable proportions in both FCCL and MZL. As opposed to FCCL and MZL, all WDLL and all but one of the ILL (associated only with DRC-1+, OKB7+, and desmoplakin+ DRC) did not show any DRC as identifiable with the antibody panel used. Remarkably, the difference in the distribution of BA-2+ and Leu-M3+ DRC in the normal FC and MZ appears to be maintained in their neoplastic counterparts (FCCL and MZL) also. Such a difference represents an example of the possible interactions between lymphoma cells of different phenotype and their microenvironment, as portrayed by phenotypically heterogeneous DRC.

Antibodies, Monoclonal↗

Effectiveness of a rapid immunohistologic method for tumor cell origin analysis.

A rapid immunohistologic method is described to analyze the possible cell origin of a given neoplasm during surgery by using selected examples of monoclonal and polyclonal antibodies (anti-cytokeratins, anti-vimentin, anti-leukocyte common antigen, and anti-keratin). This rapid (26-28 min) procedure, consisting of a two-step immunoperoxidase method, did not differ in terms of intensity and specificity of the immunoreaction from the control procedure for which conventional longer times of incubation and washing were used. The results demonstrate the feasibility and effectiveness of the procedure.

Antibodies, Monoclonal↗

Splenic irradiation in chronic lymphocytic leukemia. A 10-year experience at a single institution.

A group of 38 patients with a median age of 70 years and chronic lymphocytic leukemia (CLL) were treated using a cobalt 60 U or a 6-MeV linear accelerator. A direct field or two opposite fields covered the palpable spleen area in most patients. 100 cGy were administered weekly for a total dose of 10 Gy, given over 10 weeks. The stage arrangement (according to Rai) for the 32 evaluable patients was as follows: Stage I: 11 patients, Stage II: nine patients, Stage III: three patients, and Stage IV: nine patients. Patients in Stages I and II were treated when symptomatic. Twenty-five patients (78%) achieved hematologic response (HR), defined as normalization of the differential leukocyte count, of the total blood cell count, and of bone marrow infiltration. However, no complete response according to the standard criteria of response has been obtained. The median response time of HR was 7 months (range, 1.5 months to greater than 120 months). The overall median survival time from the start of splenic irradiation (SI) was 40 months. More than 50% splenomegaly reduction was obtained in 63% of patients, whereas no benefit was verified in the lymphadenopathy. The incidence of second tumor was 29%. Fourteen patients benefited from a further 21 SI cycles. SI does not result in a complete remission and therefore cannot modify the course of CLL. This treatment is most advisable for elderly patients with predominant bone marrow lymphocytosis, for patients with previous extensive chemotherapy or radiotherapy, and for patients with poor marrow reserve. Moreover, because of the absence of toxicity subsequent treatment is not compromised.

Aged↗