Non-Hodgkin's lymphoma with large multilobated cells mimicking tonsillar carcinoma.
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Publications and source records attributed to C D Baroni.
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The presence of Epstein-Barr virus antigens and genome was studied in lymph nodes from HIV + patients affected by PGL. Cryostat sections from 50 lymph nodes of HIV + patients were immunostained with EBV-VCA (viral capsid antigen), EBV-EA (early antigen) and p24 HIV major core protein monoclonal antibodies. In situ hybridization was performed using a biotin conjugated EBV DNA probe; the reaction product was demonstrated by immunohistochemical method. As positive controls, EBV producer B95-8 and HIV infected H9 cell lines were used. The majority of patients had circulating EBV antibodies mainly directed against the viral capsid antigen and only in few cases against early antigens. Positivity for HIV p24 protein was detected in 43 out of 50 lymph nodes within the germinal centers with a reticular pattern. Only 2 out of 50 lymph nodes presented very few positive cells for EBV antigens and none expressed detectable EBV genome. Our results suggest that EBV cellular expression does not correlate with serum positivity; furthermore the absence of EBV antigens and genome at tissue level might indicate that EBV is not directly involved in the pathogenesis of PGL.
We report a unique case of primary myxoid chondrosarcoma in the posterior mediastinum. This lesion clinically mimicked a neurogenic tumor due to its location and dumbbell appearance. The histogenesis of this tumor is discussed and a skeletal origin from the thoracic vertebrae is suggested. It is concluded that myxoid chondrosarcoma has to be distinguished for the differential diagnosis among the long list of myxoid tumors arising in the posterior mediastinum.
Monoclonal antibodies (MAbs) against two non-cross-reacting antigens of human IL-1 beta (Vhp20 and BRhC3) and human TNF alpha (B154.2 and B154.7) were applied to identify cytokine-containing cells in tissue sections and in cell suspensions. IL-1 beta- or TNF alpha-positive cells were not present in immunostained cytocentrifuge smears prepared from freshly isolated peripheral blood leukocytes, spleen, and lymph node cells. After 18 hours of culture with bacterial endotoxin (LPS), 80% to 90% of blood monocytes, 30% of spleen macrophages, and 2% to 28% of lymph node macrophages were strongly positive for IL-1 beta with either of the MAbs. Furthermore, 25% to 35% of blood monocytes and 6% to 60% of lymph node macrophages were stained for TNF alpha. Cells positive for IL-1 beta or TNF alpha were extremely rare in sections of normal thymus, spleen, and lymph nodes. Immunoreactivity for IL-1 beta or TNF alpha was frequently observed in sections of granulomatous lymphadenitis (N = 11). IL-1 beta or TNF alpha staining was confined to the epithelioid macrophages forming the granuloma, and the intensity of TNF alpha reactivity was generally stronger. The high frequency of cytokine-containing cells in this pathologic condition was confirmed in a cell suspension study showing that 20% of epithelioid macrophages were weakly positive for IL-1 beta and 80% were strongly positive for TNF alpha. The presence of cytokine-containing cells was investigated in cryostat sections of several nonlymphoid organs with normal histologic appearance. IL-1 beta reactivity was not observed in any of the tissues. TNF alpha reactivity was frequently demonstrated in isolated macrophages embedded in the interstitial connective tissue.
The histological alterations seen in HIV-related lymphadenopathy have been described with different terms by different authors. In order to facilitate comparisons of results from various laboratories, a group of pathologists of the European Lymphoma Study Group (later the European Association for Haematopathology) have proposed a histological classification for the evaluation of HIV related lymphadenopathy. Most observers agree that the morphological and immunohistochemical alterations in the follicles (germinal centres) are the most conspicuous and earliest changes seen. The follicular alterations were therefore used as the basis for the proposed classification. In addition, some features occasionally seen were also included, i.e. angioimmunoblastic hyperplasia, multicentric Castleman-like lesions, and vascular lesions, especially pretumorous and tumorous stages of Kaposi's sarcoma. The proposed classification was used by the members of the group of a collection of lymph nodes compiled from the various centres. The classification was shown to be reproducible and to have clinical relevance in staging of the patients. The prognostic relevance as to the survival of the patients has to be further substantiated by follow-up studies. The proposed classification offers a common terminology for the alterations previously described by different terms by various authors.
The morphological, ultrastructural and immunophenotypic properties of Histiocytosis-X (H-X) cells were investigated in a lymph node involved by Letterer-Siwe (L-S) disease. H-X cells were T6+ (CD1a), S-100+, T4+ (CD4) and HLA-DR+; in addition they were consistently T11+ (CD2) and were stained by antibodies directed against receptors for transferrin (T9), C3bi (OKM-1/CD11b), IgG-Fc (Leu-11/CD16) and Interleukin-2 (IL-2R/CD25). On immunostained cytosmears, T6+ cells were highly polymorphic and a prominent fraction (45%) showed immature morphology, characterized by lymphoid appearance. Cells expressing macrophage markers (ANAE, AACT, Leu-M3/CD14, PAM-1) were 10-fold fewer than T6+ cells and did not show a lymphoid morphology. At TEM level, H-X cells were characterized by poor content of LC granules and by the presence of myelin-like laminated bodies and of lysosome-like dense bodies. The immunophenotypic properties of H-X cells were compared to those of epidermal Langerhans cells (LCs) and of LCs present in lymph nodes of three cases of dermatophatic lymphadenitis. Epidermal LCs were T6+/HLA-DR+, and sometimes faintly T4+. Lymph node LCs were T6+, S-100+, T4+, HLA-DR+, and showed the same variety of surface receptors detected in H-X cells; furthermore, in a case with massive infiltration of the paracortex by T6+ cells, lymph node LCs were faintly T11+ and some of the T6+ cells had lymphoid aspect. Our findings suggest that the H-X cell population of L-S disease is not homogeneous, but is composed of discrete cell subsets with distinctive antigenic and morphological traits closely resembling those of cells of LC lineage at different maturational stages.
Signet ring cell lymphoma is a non-Hodgkin's lymphoma, characterized by neoplastic lymphoid signet ring cells very similar to epithelial mucin producing cells. We describe here a case of signet ring cell lymphoma in which the immunophenotypic markers of signet ring cells parallel those of plasma cells, being intensively T10+ (CD 38), weakly HLA-DR+, and To15 (CD 22) and T200 (CD 45) negative. The morphologic and immunohistochemical features of the case and the main differential diagnosis are preceded by a review of the literature.
Monoclonal antibodies (MAb) anti-HIV core and envelope proteins and in situ hybridization, using cDNA HIV probe, were employed to determine which lymph node cells in LAS patients express viral antigens and viral nucleic acids. The results have been correlated with the histologic phases of LAS and with the germinal center lysis detected using DRC-1 MAb directed against follicular dendritic reticulum cells (FDRC). Viral antigens occasionally were detected on high endothelial cells of paracortical venules and frequently on germinal center FDR accessory cells; this last finding correlates well with the extent of FDRC lysis and of CD4+ and CD8+ lymphocyte infiltration in germinal centers. HIV replication, detected by in situ hybridization, was observed in mononucleated cells present in T and B areas and, in one case, in flat endothelium.
The presence of human immunodeficiency virus (HIV, or HTLV-III) genome sequence was investigated by means of in situ hybridization in cryostat sections of lymph nodes from lymphadenopathy syndrome (LAS) patients. The technique employed involved the modification of the DNA probe by chemical insertion of an antigenic sulfone group in cytosine moieties and the visualization of DNA by a double-antibody immunohistochemical reaction. The hybrid formation was revealed in five out of ten cases: in all positive samples, HIV was mainly observed in the cytoplasm of lymph node cells. The method of in situ hybridization described in the present paper is specific and has some advantages if compared with other techniques based on the use of DNA probes labelled with radioisotopes or biotin by nick translation.
Immunostaining of frozen sections from a mediastinal T lymphoblastic lymphoma (T-LL) revealed the existence of two neoplastic cell populations characterized by different degrees of maturation. Several large nodules of 3A1+/T11+/T9+ T6-/T4-/T8-/T3- lymphoid cells, resembling normal early thymocytes, were surrounded by 3A1+/T11+/T9+/T6+/T4+/T8+/T3- cells resembling normal cortical thymocytes. The junctional area between early and cortical lymphocytes was occupied by numerous Leu-M3+/PAM-1+/DR+ reticular macrophages which were also characterized by J5 reactivity. Cytokeratin+/keratin+ epithelial cells were absent. Immunostaining of paraffin sections and of cytocentrifuge smears obtained from tumour cell suspensions revealed that a consistent percentage (8%) of neoplastic lymphoblasts were S-100+. Our findings are consistent with a cortical T-LL presenting areas of dedifferentiated cells or, alternatively, with an early T-LL whose cells were able to differentiate into cortical thymocytes, perhaps through the interaction with a specialized subset of J5+ macrophages.
The mononuclear phagocytic system is composed of cells which display a marked immunohistological heterogeneity. In the present study we have investigated the immunohistochemical and enzymatic features of macrophages and accessory cells present in human lymph nodes and spleen and, as control tissues, in thymus, liver, skin and heart. Our investigation has demonstrated that macrophages present in germinal centres display an immunophenotype different from that of macrophages populating T-dependent areas. Furthermore, cells lining lymph node sinuses and splenic sinusoids express endothelial and macrophage markers, and are able to modulate their immunophenotype according to different reactive conditions. These data suggest, on immunohistochemical grounds, that macrophages populating B- and T-dependent areas as well as sinuses of human peripheral lymphoid tissues, may modulate their immunophenotype according to environmental and antigenic influences.
Ten cases of non-Hodgkin's lymphomas, mainly composed of large multilobated cells, have been studied. Our results are consistent with the view that they represent a somewhat heterogeneous group of lymphoid tumours displaying different morphological, clinical and immunophenotypic features. In B-cell type the large multilobated cells were histologically characterized by prominent nucleoli and distinctly basophilic cytoplasm whereas in the T-cell type they had indistinct or small nucleoli and ill-defined weakly eosinophilic cytoplasm. These differential features between B- and T-cell type were confirmed by electron microscopy. From a clinical standpoint B-cell type was characterized by a constant involvement of lymphoid tissues (lymph nodes and/or Waldeyer's ring); T-cell type showed, on the contrary, a more frequent involvement of extra-lymphoid sites (mainly bone and subcutaneous tissues). Our study provides some morphological features that may be helpful for a correct differential diagnosis in this heterogeneous group of non-Hodgkin's lymphomas.
The epithelial, vascular and lymphoid components present in two cases of adenolymphoma (Warthin's tumour) were characterized by immunohistochemistry on frozen sections. Epithelial cells were positive for cytokeratin and keratin and were in close contact with numerous factor VIII related antigen-positive capillary vessels, running parallel to the epithelial basement membrane. The capillary vessels were in communication with high endothelial post-capillary venules which were often lined by HLA-DR-positive endothelial cells. The lymphoid tissue was organized in B-cell and T-cell areas. The B-cell areas consisted of B4+/To15+ B-lymphocytes admixed with DRC-1-positive follicular dendritic reticulum cells. The T-cell areas were mainly populated by T11+/T3+/T4+ lymphocytes admixed with some S-100+/HLA-DR+ interdigitating reticulum cells. Plasma cells and T8+ lymphocytes were more numerous in the proximity of the epithelium. Leu-M3+/PAM-1+ macrophages were scattered singly in the T-cell areas or were arranged in sinus-like structures around the epithelial cysts. The epithelial basement membrane, the vascular membrane and the fibrillar reticular stroma of the lymphoid tissue were immunoreactive for laminin and type IV collagen. The possibility is discussed that the accumulation of lymphoid tissue in Warthin's tumour is modulated by the epithelial cells, perhaps through their ability to organize a peculiar pattern of vascularization.
An intensive treatment program was developed to achieve durable remissions in a high proportion of previously untreated patients with advanced stages of diffuse high-grade non-Hodgkin's lymphoma (NHL). Fifty-six patients (15-68 years) received a course of F-MACHOP (5-fluorouracil, methotrexate, cytosine-arabinoside, cyclophosphamide, doxorubicin, vincristine, and prednisone) every 3-4 weeks for 6 courses. Cycle active drugs were sequentially administered to expose rapidly proliferating tumor cells to the synergistic effects of these agents throughout the cell cycle. Forty-three patients achieved complete remission (77%) and 80% of the complete responders are projected to be alive and disease-free at 4 1/2 years (median follow-up 33 months). Up to 70% of all patients are predicted to be alive at 5 years. Bulky tumor, "B"-symptoms and lymphoblastic histology were poor prognostic factors, particularly when associated with clinically detectable disease after three courses. Toxicity included transitory myelodepression in most patients (2 septic deaths). This protocol provides effective and tolerable therapy for the majority of patients with advanced stages of diffuse aggressive NHL.
Lymph nodes of patients with lymphadenopathy syndrome (LAS) are characterized by two main histological patterns: hyperplastic reactive (H) and regressive (R). In both conditions, the paracortex (PC) is markedly activated with presence of selectively Ia-1+ high endothelial venules. Using a monoclonal antibody for p24, the major core protein of HTLV3, we have immunohistochemically determined the distribution of p24+ cells in lymph nodes from 23 LAS patients' HTLV3-ab serologically positive. p24+ cells were demonstrated in 11 cases. Control nodes were negative. p24+ cells included high endothelial cells of PC postcapillary venules, large perivenular cells, large mono- or binucleated cells in PC and in GC, and few lymphocytelike cells. Our preliminary observations indicate that the majority of p24+ cells are high endothelial and accessory cells that may act either as virus reservoir or as antigen-presenting cells to T4 lymphocytes and to GC B cells. In addition, the positivity of high endothelial cells for p24 might help to explain their selective Ia-1+.
S-100 protein is an immunohistochemical marker for a subset of dendritic cells, the interdigitating reticulum cells (IDRCs), which are mainly located in T-dependent areas of lymphoid tissues. In the present study we have investigated the distribution of S-100-positive cells in lymph nodes, spleen, thymus and peripheral blood of normal subjects. Immunoreactivity for S-100 protein was demonstrated in large cells with dendritic morphology and in small lymphocyte-like cells present in the lymph node paracortex, thymic medulla, splenic periarterial lymphatic sheaths (PALS) and in peripheral blood. S-100-positive lymphocyte-like cells were frequently detected around high endothelial venules (HEV) and were present in numbers comparable to those of S-100-positive IDRCs. Immunoelectron microscopy confirmed the existence of positive cells with lymphoid morphology and revealed that the intracellular distribution of the immunoreaction product was similar in lymphoid and dendritic cells. Further characterization of S-100-positive cells demonstrated that both lymphoid and dendritic cells were unreactive with a large panel of monocytic and macrophage markers.
The p24 protein is the major core protein of LAV/HTLV III which is the putative agent of the lymphadenopathy syndrome. By the use of an anti-p24 monoclonal antibody we have studied the presence of LAV/HTLV III infected cells in 20 lymph nodes obtained from lymphadenopathy syndrome patients: 14 lymph nodes were characterized by prominent follicular hyperplasia consistent with the early phase of the syndrome and six lymph nodes presented marked regressive changes. Cells positive for p24 were detected in 8/14 lymph nodes with hyperplastic changes and in 1/6 lymph nodes with regressive changes. Positive cells were most often located in germinal centres and were mainly characterized by a lymphoid morphology. However, immunoreactivity for p24 protein was also occasionally observed in some histiocytic-like cells and in high endothelial cells of post-capillary venules, suggesting that these 'accessory cells' also play a role in the early phases of the lymphadenopathy syndrome.
We describe four lymph node based tumours in which numerous neoplastic cells and some mitotic figures were characterized by staining affinity for Lectin I of Ulex europaeus (UEA-I). The patients had no vascular or epithelial tumours and presented symptoms suggestive of a systemic lymphoproliferative disease. Histologically, the tumours were composed of large, cohesive, cells which were mainly located in the paracortex. UEA-I reactivity was more evident in the Golgi area and was present in large mononucleated cells often arranged to delimit vascular-like spaces. The neoplastic cells were weakly muramidase-positive in one case, and were ANAE+/AP+ in two other cases. Large dots of UEA-I reactivity were detected in S-100+/muramidase-negative Langerhans-like cells present in one case of Letterer-Siwe disease. UEA-I staining was consistently negative in 20 cases of B cell- or T cell lymphoma and in 9 other cases of histiocytic lymphoma. It is suggested that UEA-I+ tumours of the lymph nodes are part of a distinct subset of histiocytic malignancies whose neoplastic cells present some morphological and phenotypic properties normally associated with endothelial cells.