Lymphohistiocytic T-cell lymphoma (anaplastic large cell lymphoma CD30+/Ki-1 + with a high content of reactive histiocytes).

We describe 13 cases of a peculiar lymphoid tumour containing very large numbers of reactive histiocytes. The tumours occurred in young patients (mean age 14.8 y) who presented with systemic symptoms and superficial lymphadenopathy. Microscopic examination revealed a diffuse effacement of lymph node structure due to the presence of histiocytes intermingled with a variable number of anaplastic large lymphoid cells. The latter, in some cases, were isolated, while in others they were arranged in clusters or were diffusely present in residual sinuses. The large anaplastic cells expressed the activation markers CD30 (Ki-1), CD25 (interleukin-2 receptor), CD70 (Ki-24) and Ki-27, as well as varying combinations of T-associated molecules. The histiocytes expressed lysozyme and the CD11b (C3bi-R), CD11c (p150, 95) CD14, CD68 (KPI) and Ber-Mac3 antigens. Double staining with the antibody Ki-67 demonstrated that the proliferating components were the CD30-positive cells and not the histiocytes. T-cell receptor beta gene rearrangements were shown in three cases tested. The patients responded well to aggressive chemotherapy and nine are still alive, eight in complete remission. It is suggested that the tumour represents a well-defined clinico-pathological entity originating from activated T-lymphocytes.

Mantle zone lymphoma: a morphometric comparison with centrocytic and immunocytic lymphomas and reactive secondary follicles.

Nuclear size and shape of lymphoid cells were evaluated morphometrically in the mantle zone lymphoma, immunocytic lymphoma, and centrocytic lymphoma, and were compared with those of reactive secondary follicles. Shape factors (forms Ar, Ell, Pe, and Dia) have been used to quantitatively define the most frequent nuclear profiles. One of the testing sets consisted of the nuclei of the light, dark, and mantle regions of reactive nodes, as well as those of the centrocytic lymphoma, immunocytic lymphoma, and the mantle-fashion growth lymphoma. Another testing set was made up of only the three types of lymphoma and was used for evaluating the variability of shapes within these groups by means of a pattern recognition algorithm. The content of reactive T lymphocytes was assessed in all cases by immunohistochemistry. The results of transforming centroid values into geometric shapes by computer modelling indicated that only minor geometric differences existed between the a priori qualitatively chosen nuclear types and those modeled a posteriori by computer. All the nuclear types were found in each of the reactive regions and in each of the lymphomas. However, highly significant differences of distribution were detected among the three categories of lymphoma and between each reactive region and each lymphoma. The cases of centrocytic lymphoma showed constant findings in terms of nuclear composition, while lymphomas with mantle-fashion growth and the examples of immunocytic lymphoma showed significant variability. These observations confirm that the centrocytic lymphoma represents a distinct entity, although its normal counterpart is still unknown, and question the view that the immunocytoma and the mantle zone lymphoma correspond to homogenous categories of non-Hodgkin's lymphomas. In addition, since all the qualitatively and quantitatively detected nuclear types were found in all the reactive regions and in all the lymphomas, albeit with different distributions, it has to be assumed that only numerical differences exist among the various lymphomas and the reactive regions.

Ultrastructural and immunohistochemical contribution to the histogenesis of human cardiac myxoma.

The ultrastructural features of 8 human cardiac myxomas were analyzed and correlated with immunohistochemical data, with the aim to clarify the characteristics of the cell lines involved in the tumor genesis. Immunohistochemical studies were performed to detect the presence and the distribution of intracytoplasmic filaments (vimentin, desmin, actin, myosin) as well as myoglobin and factor VIII-related antigen, albumin, and lysozyme. Eighty percent of myxoma cells were simultaneously positive for vimentin, desmin, and actin, whereas 30% of them stained with antifactor VIII and antivimentin antibodies. The submicroscopic analysis revealed two main cell populations: (1) one composed of stellate-shaped cells with scanty organelles and sparse hyaloplasmic filaments scattered throughout the myxoid stroma and forming a loose network with their projections; (2) another one included cells with more cytoplasmic organelles, intermediate filaments, and myofilaments arranged either singly or in both solid and hollow cord-like structures. Our results support the hypothesis that cardiac myxoma may originate from a reserve multipotent mesenchymal cell able to differentiate more or less completely along two major evolutional lines: myoid and endothelial. The tumor tissue thus seems to be involved in vessel formation, suggesting a growth pattern akin to that manifested in other forms of endocardial pathological reactivity in which reserve mesenchymal cells are engaged.

Essential mixed cryoglobulinemia, type II: a manifestation of a low-grade malignant lymphoma? Clinical-morphological study of 12 cases with special reference to immunohistochemical findings in liver frozen sections.

Twelve patients with clinical and laboratory findings typical of essential mixed cryoglobulinemia, type II (EMC II) underwent multiple liver and bone marrow biopsies. In 9 of 12 cases (all hepatitis B surface antibody-negative), routine histology revealed patent infiltration of liver portal tracts, lobules and sinusoids by small lymphocytes provided with cytological characteristics closely resembling those of the LP immunocytoma of the Kiel classification. At immunophenotyping on frozen sections, these elements expressed the CD22 antigen (marker of B cells) and bore the same type of immunoglobulin (IgM/k = 8, IgM/lambda = 1) as the monotypic component in the serum. Furthermore, in 7 of 9 patients repeated bone marrow needle biopsies showed multiple foci of infiltration by plasmacytoid cells, often with paratrabecular location. In the remaining 3 cases (all hepatitis B surface and core antigen-positive), liver biopsies were consistent with a diagnosis of cirrhosis (two) or chronic active hepatitis (one). In two of them, however, Jamshidi needle biopsy evidenced bone marrow infiltrates quite similar to those observed in the other group. On the basis of these findings, the authors discuss the hypothesis that most EMC II are substained by a low-grade malignant lymphoma.

Primary multilobated B cell lymphoma of the kidney: report of two cases.

Two cases of multilobated B cell lymphoma primarily involving the renal parenchyma are reported. The rarity of the finding and the utility of immunohistochemical analysis are pointed out.

In situ immunocytochemical staining of cell colonies growing in plasma clot.

The procedures involving the growth of cell colonies in semi-solid media, such as methyl cellulose or agar, provide a score of colony-forming-units (CFUs) by means of morphology, and allow the application of cytochemistry. However, a better characterization of the growing cells by employing monoclonal antibodies is impaired by the medium itself. Plasma clot is a possible alternative, allowing immunofluorescence as well as immunoenzymatic techniques. We have developed a staining procedure which can be performed using both peroxidase- or alkaline phosphatase-conjugated reagents; the colonies, growing in plasma clot, can be stained in situ, without transferring the cells. In this paper we report on the study of six different cell lines stained by immunocytochemical techniques with appropriate monoclonal antibodies.

Histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi's lymphadenitis). Morphological and immunohistochemical study of eight cases.

Eight examples of histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi's lymphadenitis) are described. They occurred in young or middle-aged women who usually complained of latero-cervical lymphadenopathy. Serology revealed significant titres for Epstein-Barr virus and Yersinia enterocolitica serogroup 9 in one of eight and one of six tested. All patients fully recovered within 2 months. On histological examination of the lymph nodes large foci of infiltration were observed in the cortex and/or paracortex: they consisted of variable numbers of small lymphocytes, immunoblasts, macrophages and so-called plasmacytoid T-cells; granulocytes were absent. Necrotic changes varied from single pyknotic cells to extensive areas of necrosis. Immunohistochemistry showed that within the lesion the number of macrophages was inversely proportional to the number of peripheral T-lymphocytes and 'plasmacytoid T-cells'. The latter displayed a phenotype (CD4+, CD10+, CD45+) which, in the absence of macrophage-associated antigens, seemed in keeping with their supposed lymphoid nature. In seven cases peripheral T-lymphocytes predominantly expressed the cytotoxic/suppressor phenotype, while in one remaining case a mild predominance of the helper/inducer subset was observed. In the areas with less extensive tissue necrosis, numerous T-immunoblasts expressed both markers of activation and the proliferation-associated nuclear antigen Ki-67. The results of the present study expand the spectrum of our knowledge and allow speculation as to the biology of this disease.

Growth fraction in human brain tumors defined by the monoclonal antibody Ki-67.

The monoclonal antibody Ki-67, which reacts with cells in the active part of the cell cycle, was used to evaluate immunocytochemically the growth fraction in 22 primary brain neoplasms. The percentage of labelled cells reflected the histological grade of malignancy of each neoplasms. High percentage of Ki-67-positive cells were observed in one choroid plexus carcinoma (60%), one primary melanoma of meninges (40%), three medulloblastomas (40%-50%), one anaplastic astrocytoma and six glioblastomas (10%-40%). One ependymoma had 7% positive cells. Rare positive cells (1%) were present in one pilocytic astrocytoma and one ganglioglioma. Except one negative case, the meningiomas (five cases) had values of positivity ranging from 1% to 6%. Two acoustic schwannomas were negative. These results suggest that immunocytochemical staining with the Ki-67 may be a useful method for measuring the growth fraction in brain neoplasms.

A clinical-immunological evaluation of AIDS cases and related syndromes.

The clinical features of our cases demonstrated some of the already known characteristics of the variable spectrum of HIV infection. DA are the most important risk category in Italy. 10% of the ARC cases evolved into AIDS during a 12-month follow-up, on average. The most frequent OI in our AIDS cases were PCP, C. albicans esophagitis and chronic mucocutaneous ulcers. An high percentage of neurologic involvement from HIV was observed, and malignancies were encountered in AIDS (3 KS and 1 undifferentiated B lymphoma) as well as in ARC (1 Hodgkin's lymphoma). Statistically, significant worsening of the immunologic situation is evident as the disease progresses from LAS to AIDS. Activated B lymphocytes represent most of the cells of the germinal center during the hyperplastic stage of lymphadenopathy. Reversal of the T4/T8 ratio appears early during the initial stage of lymphadenopathy and is due to a decrease of CD4 and a relative increase of CD8. Also, destruction of the follicular dendritic cells is an early feature which becomes more evident as the disease advances and the lymph node evolves toward progressive involution. Activated B-lymphocyte augmentation with polyclonal Ig secretion appears to be related to T-independent B stimulation by coinfection such as CMV, EBV and HBV. The increase of cytotoxic/suppressor lymphocytes seems to be partly related to the excessive activation of B lymphocytes and partially directed to the cells infected by HIV or coated with its proteins (6,7,8,9). The destruction of follicular dendritic cells has been interpreted not only as a killer effect of the virus but also as a result of the intervention of CTL sensitized to the cells containing the virus (10,11). Their destruction may contribute to the impaired recognition of soluble antigen which is one of the main features of the immune deficiency of HIV infection (9,13,16).

Lymphoblastic lymphoma in adolescents and adults. Clinical, pathological and prognostic evaluation.

Sixty-four adult patients with lymphoblasts lymphoma (LB) identified according to Kiel Classification were analyzed retrospectively. Three distinct clinical presentations were identified: prevalent abdominal disease (29 pts = 45.3%), prevalent mediastinal disease (14 pts = 21.9%) and prevalent superficial node involvement (21 pts = 32.8%). On histological grounds, the patients with abdominal disease were mainly associated to "Burkitt like" cell lymphoma (55%); patients with mediastinal disease to convoluted cell type (58%); and those with superficial node disease to unclassified cell type (48%). Immunological studies showed a significant correlation between mediastinal disease and T phenotype (P = 0.0011), abdominal disease and B phenotype (P = 0.00042), and between superficial node disease and non-B non-T phenotype (P = 0.00024). Survival was independent of the type of clinical presentation and protocol employed but was correlated with the stage (P less than 0.0005), symptoms (P less than 0.025), bulky disease (P less than 0.025) and bone marrow involvement (P less than 0.025). Furthermore the response to therapy was strongly correlated with prognosis (P less than 0.0001) with 34.5 months median survival for complete responders, 9 months for partial responders, and 3 months for non-responders. Four patients underwent bone marrow transplantation (three autologous and one allogeneic BMT in a patient in leukemic phase); three of them are still in CR (18, 22, and 27 months from the transplant) while one patient had an early relapse and died 3 months later.

The value of lymph node biopsy in patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex (ARC): a morphological and immunohistochemical study of 90 cases.

The morphological and immunohistochemical findings in lymph nodes of nine patients with the acquired immunodeficiency syndrome (AIDS) and 81 patients with the AIDS-related complex (ARC) are presented. Three basic histological patterns were observed: follicular hyperplasia (29 cases), mixed hyperplasia (49 cases) and lymphocyte depletion (12 cases). While the first two variants were detected in typical ARC patients, lymphocyte depletion was always associated with AIDS. Immunohistochemistry on frozen sections showed that the number of B-cells varied throughout the series, being higher in the follicular type and significantly lower in the lymphocyte depletion nodes. The content of T-lymphocytes of the helper/inducer (T4) phenotype was reduced in all instances; this reduction was more pronounced in the germinal centres in follicular hyperplasia, while it involved all compartments of the node in the mixed and lymphocyte depletion types. In contrast the cytotoxic/suppressor (T8) subset was increased in the follicular and mixed hyperplasias only. Partial disintegration of the dendritic network in at least some of the follicles could be demonstrated in all lymph nodes. In the follicular and mixed hyperplasias there was a high number of proliferating B-cells in the germinal centres. Our data indicate the usefulness of grading the changes occurring in lymph nodes of patients with ARC and AIDS, and allow speculation as to the pathophysiology of these conditions.

Solitary plasmacytoma of the bone in a case of Hodgkin's disease.

This report describes a case of solitary plasmacytoma of the bone which occurred in a 35-year-old male 3 years after mantle field irradiation for Hodgkin's disease, nodular sclerosing, stage IA. The possible significance of this rare association is discussed.

Neoplastic and reactive follicles within B-cell malignant lymphomas. A morphological and immunological study of 30 cases.

Thirty cases originally diagnosed as B-cell lymphomas, either LP immunocytoma, centrocytic (Cc), or centroblastic-centrocytic (Cb/Cc), containing follicular structures of an uncertain nature were critically reviewed using both morphological criteria and immunological techniques. In particular, they were tested by conventional antisera for detection of immunoglobulins in paraffin sections and also, in the 5 cases in which frozen material was available, by a panel of monoclonal antibodies. At the first histological evaluation the cases were divided into two groups. Group A consisted of 12 examples which showed homogeneous features and, because of the neoplastic nature of the follicular structures, could be classified as follicular centroblastic-centrocytic lymphomas with marked plasmacellular differentiation. Group B comprised 18 cases which at onset of disease revealed a mantle-fashion growth around reactive-appearing follicles formed by polytypic germinal centre cells. On closer examination, however, this group appeared heterogeneous: 13 cases displayed cytological and immunological findings consistent with the diagnosis of Cc and usually contained polytypic plasma cells; 5 cases were examples of LP immunocytoma consisting of monotypic elements only. Therefore, the so-called mantle-zone lymphoma does not appear to be an entity.