Malignant lymphomas in Japanese AIDS patients.

Seven non-Hodgkin's malignant lymphomas (MLs) were found in 25 Japanese AIDS (acquired immune deficiency syndrome) patients who died at two hospitals in Tokyo. All of these MLs originated from extranodal organs including the brain (three cases), skin (two cases) liver and adrenal gland. B cell markers were demonstrated in all of them. Epstein-Barr virus (EBV) capsid antigen (EBVCA) was demonstrated in 5/7, nuclear antigen (EBNA) in 2/2, the W fragment of EBV DNA by in situ hybridization in 5/7 and the same fragment by PCR in 6/7, indicating high association of these MLs with EBV. The adult T cell leukemia/lymphoma (ATL), endemic in south-west Japan and known to have a high association with HTLV-I, was not found in this series. The incidence of ML among the present AIDS cases is higher than in any other autopsy reports from western countries, although statistical analysis did not show this to be significant in comparison to some of these reports at a level of p less than 0.05. In spite of apparent higher incidence, the histopathologic and immunophenotypic characteristics of AIDS-associated MLs in Japan are in accordance with those in western countries.     

Malignant lymphomas in Korea

A retrospective histological study of 540 malignant lymphomas diagnosed at the Department of Pathology of the Seoul National University from 1976 through 1986 is presented. Malignant lymphoma is the 10th most common malignant tumor in Korea, comprising 3.07% of all malignancy during period of study. Among malignant lymphomas non-Hodgkin's lymphoma accounted for 82% and accordingly the Hodgkin's disease was for 18%. The most common type of non-Hodgkin's lymphoma was diffuse histiocytic lymphoma of Rappaport. Follicular lymphoma was very rare, comprising only 2.3%. T-cell lymphoma accounted for 9.6% of non-Hodgkin's lymphomas, the most frequent type being lymphoblastic lymphoma. Immunoblastic sarcoma and mycosis fungoides were occasionally seen but there was no case of pleomorphic adult T-cell lymphoma. Among Hodgkin's diseases, mixed cellularity type was the most common type, and nodular sclerosis type was relatively rare.     

Malignant lymphomas with primary bone manifestation

18 malignant lymphomas with initial manifestation in bone were selected from the Bone Tumor Registry of Westfalia at the Münster Institute of Pathology where they had been documented between 1975 and 1985, and evaluated under clinical, radiological and histological aspects. Non-Hodgkin lymphomas were reclassified according to the Kiel nomenclature. Paraffin-embedded material was subjected to immunohistochemical analysis in order to assess the features that could add to the correct characterization of these lymphomas, and to their differentiation from other round cell tumors of bone. Non-Hodgkin lymphomas (NHL) were more common in the collective than Hodgkin's lymphomas (HL). Of 13 NHL, 2 were of low, 11 of high-grade malignancy. The former comprised one centrocytic and one centroblastic/centrocytic, the latter 7 centroblastic, 2 immunoblastic, and 2 lymphoblastic lymphomas. Seven NHL patients with localized tumors survived up to 11 years (mean survival span: 6 yrs) after local therapy (radiation and/or resection). Another NHL patient, however, had multiple bone lesions, and died within a year. Analysis for leukocyte common antigen was positive in 9/12 NHL cases, reaction with Ki-B-3, a marker of B-lymphocytes, was positive in 7/12 cases. No lymphoma cells were found to react positively with lysozyme, alpha 1-antitrypsin, or alpha 1-antichymotrypsin. It is concluded that localized lymphomas of bone respond well to appropriate local therapy; immunohistochemical investigation may be useful to characterize the true cellular origin of these tumors, and may help to differentiate them from other round cell tumors of bone.     

Malignant lymphomas associated with immunodeficiency states

An increased incidence of malignant lymphomas is common to all types of immunodeficient patients whether they be of the natural or constitutionally occurring type, acquired as in acquired immunodeficiency syndrome (AIDS) or of iatrogenic origin as in organ transplantation. Although there is some degree of heterogeneity, the most characteristic feature of these immunodeficient states is alteration of T-cell cytotoxic function. The malignant lymphomas show a variety of relatively common features, notably: rapid onset following the appearance of the immunodeficient state, a high degree of clinical aggressiveness, and a tendency to present in extranodal sites, particularly the central nervous system (CNS) and gastrointestinal tract. The tumors are almost invariably of B-lymphocytic cell origin and while the histologic classifications reflect some diversity, the vast majority of tumors are described as Burkitt-like or diffuse large cell type. There appears to be a high degree of correlation with a preceding fulminant Epstein-Barr virus (EBV) infection resulting in marked B-cell lymphoproliferation in the absence of effective T-cell control. Initially, the B-cell proliferation is clearly polyclonal and reactive in nature, although as time evolves, there appears to be selection of oligoclonal and even monoclonal cell populations. Such cells are latently infected with EBV and may express EBV nuclear protein two and latent membrane protein, which are characteristically seen in proliferating B-lymphocytes in response to growth transformation by EBV. While desoxyribonucleic acid (DNA) probes may continue to demonstrate multiple lymphoid clonal populations, it is hypothesized that the hyperproliferative state favors genetic alterations which select out a single malignant clone. This transformed clone is evidenced by expression of a translocated, activated c-myc oncogene and decreased evidence of EBV nuclear protein two and latent membrane protein, that is, characteristics of Burkitt's lymphoma. Other large cell malignant lymphoma phenotypes may show similar findings. While most studies have continued to suggest that EBV plays a key role in the development of non-Hodgkin's lymphoma (NHL) of AIDS patients, some recent studies have suggested a less dominant role. Therefore, further exploration of the world of molecular biology will be needed to demonstrate whether other factors, namely additional viruses and/or oncogenes play a similar or significant role in the lymphomas of immunodeficient patients.     

Malignant lymphomas with a follicular growth pattern

Given the pivotal role of the B-cell follicle in B-cell proliferation, and the fact that the follicle centre has the highest proliferation fraction of any structure in the body, it would be reasonable to expect that the potential for the development of aberrant (neoplastic) growth within it would be relatively high, especially when compared to other lymphoid compartments. However, in all current lymphoma classifications only one entity, namely follicular lymphoma, is acknowledged as having any relation to the follicle. As knowledge of the immunophenotype and function of the normal follicle has increased, it has become evident that many lymphomas, including some examples of Hodgkin's disease, are related to the B-cell follicle and as a consequence manifest a follicular growth pattern. This has implications for the pathogenesis of these tumours and may point the way to novel therapeutic options.     

Malignant lymphomas of the nasal cavity and Waldeyer's ring--clinicopathologic and immunohistochemical study.

The clinicopathologic and immunohistochemical finding of 10 cases of nasal non-Hodgkin's lymphoma (NHL) and 23 cases of Waldeyer's ring NHL were studied. Immunohistochemically, nasal NHL expressed T-cell markers exclusively, whereas the NHL of Waldeyer's ring were of both T-cell (56.5%) and B-cell lineages (43.5%). Angioinvasiveness by tumor cells was exclusively noted in the T-lineage lymphomas. Epithelial hyperplasia, epitheliotropism by tumor cells, and extensive invasion of adjacent normal tissue were more prominent in T-cell lymphomas than in B-cell lymphomas. T-lineage lymphomas showed distant extranodal spread pattern involving the skin, soft tissue, stomach, spleen, and the liver, whereas B-lineage lymphomas tended to localize in the lymph nodes. The survival rate of Nasal NHL was similar to that of Waldeyer's ring NHL. Although not statistically significant because of small sample numbers, immunophenotype, histologic groups of monomorphic lymphoma, and stage had prognostic importance. In general, T-lineage lymphomas presented with a higher stage than B-lineage lymphomas (p < 0.05)-and overall survival was poor. Stage I disease showed a much more favorable prognosis than stage II disease. Monomorphic lymphomas had a shorter survival than polymorphic reticulosis (PR) or lymphomas with features of PR. This result in conjunction with the morphologic transition between them suggested that monomorphic lymphoma may represent the most advanced stage in the spectrum of PR, lymphoma with features of PR, and monomorphic lymphoma.     

Malignant lymphomas of the nasal cavity and paranasal sinuses

Summary The incidence of malignant lymphomas in the nasal cavity and paranasal sinuses was found tobe 0.17% of all malignant lymphomas and 0.44% of all extranodal malignant lymphomas registered in the Kiel Lymph Node Registry from 1972 to 1987. Fifty-nine cases of malignant lymphoma presenting in the nasal cavity and paranasal sinuses were investigated with morphological and immunological methods. The median age of the patients was 64.5 years, with a female predominance (m:f=0.87:1). In the 59 cases a marked preponderance of B-cell lymphomas was found (centroblasticn=15, immunoblasticn=8, Burkitt's lymphoman=6, Immunocytoman=3, centrocyticn=1, centroblastic/centrocyticn=1, plasmacyticn=11); only a small number (n=5) was of T-cell lineage (pleomorphic types). Nine further cases could not be assigned with certainty to either the T or B cell system. Angiocentricity with infiltration and destruction of vessel walls by tumour cells was demonstrated only in the T-cell lymphomas; the B-cell lymphomas, in contrast, of ten surrounded and compressed blood vessels with intact endothelium. No similarity to malignant lymphomas of mucosa associated lymphoid tissue, such as those in the gastrointestinal tract, was detected.     

Malignant lymphomas of the skin (clinico-morphological parallels)

On the basis of clinico-morphological analysis of 104 patients with malignant skin lymphomas (MSL) they are subdivided into two groups: epidermotropic (mycosis fungoides, prolymphocytic and lymphoblastic MSL with sinuous nuclei, histiocytic MSL) and non-epidermotropic (prolymphocytic MSL with roundish nuclei, microlymphoblastic and immunoblastic MSL). The former group differs from the latter by the involvement of the epidermis, with hyperplasia of keratinocytes and the disturbance of their differentiation, penetration of tumour cell into the epidermis and by the composition, type and localization of the proliferate. Epidermotropic MSL were much more frequent, affected younger persons, had a longer duration, more widespread skin involvement with polymorphic eruptions. Non-epidermotropic MSL were characterised by the appearance of single tumours of the skin and early generalization.     

Malignant lymphomas in the acquired immunodeficiency syndrome. Additional evidence for a B-cell origin

An increased incidence of high-grade malignant non-Hodgkin's lymphomas has been reported in homosexual men. This phenomenon appears to represent another facet of the acquired immunodeficiency syndrome (AIDS). Histologically, the majority of these lymphomas have been small noncleaved cell lymphomas or immunoblastic lymphomas, subtypes most commonly associated with a B-cell phenotype, but immunologic data supporting this have been limited. Using a plastic embedding technique, we have examined a series of 31 malignant lymphomas, including nine from the central nervous system (CNS), in patients with AIDS or at high risk for AIDS. All 31 of the lymphomas were positive with one or more of the following B-cell markers: HLA-DR/la, Pan B, Leu 12, Leu 14, and IgM. All 31 were negative for the pan-T reagent Leu 4 and myeloid-macrophage markers (Leu M1, nonspecific esterase). In addition, seven of the nine CNS lymphomas showed strong plasma membrane staining for adenosine triphosphatase, a B-associated marker. These findings provide strong immunologic evidence for a B-cell origin in the lymphomas of AIDS.     

Malignant lymphomas of the nasal cavity and paranasal sinuses. A clinicopathologic and immunohistochemical study.

The clinicopathologic and immunohistological features of 20 Japanese patients with non-Hodgkin's lymphomas (NHLs) limited to the sinonasal area were studied using a broad panel of T- and B-cell markers on paraffin-embedded and fresh frozen tissue. All cases showed a diffuse growth pattern. Nine cases were B-cell lymphomas (immunoblastic n = 4, centroblastic n = 3, immunocytoma n = 1, centrocytic n = 1), and nine were T-cell lymphomas (pleomorphic medium and large cell n = 8, angioimmunoblastic n = 1). In two cases, the cell lineage could not be determined. No morphologic features of angiocentric/angiodestructive lymphoproliferative lesions or lymphoepithelial lesions in ductal or glandular epithelium were seen in our series. Eight (89%) of the nine T-cell tumors and four (44%) of the nine B-cell neoplasms involved both the nasal cavity and paranasal sinuses. Six of the nine T-cell neoplasms showed a clinical presentation of rhinitis, whereas all of the B-cell neoplasms showed tumor masses in the nasal cavity and/or paranasal sinuses. The two-year survival rate for T-cell lymphomas was poorer than that for B-cell lymphomas. The five-year survival of patients with NHLs involving both the nasal cavity and paranasal sinuses was also poorer than that of patients in whom NHLs were limited to the nasal cavity.     

Malignant lymphomas in HIV-seropositive patients. Frequency,features, and prognosis. Report on 31 cases

Summary In a random HIV-seropositive population, malignant lymphomas were diagnosed in 31 patients, of whom 24 (77%) had non-Hodgkin lymphoma (NHL) and 7 (23%) Hodgkin lymphoma (HL). The prevalence of NHL among AIDS patients was 8% (23/279 cases), with a prevalence of 17% among autopsied patients (16/96 cases). No patient with HL had AIDS at the time of diagnosis. In 7 of 23 AIDS patients with NHL (30%) the diagnosis was made only post mortem; among these were all 5 patients with primary CNS NHL. Median survival from the time of diagnosis was 1 month for patients with NHL and 3 months for those with HL. In individual patients, survival for several years may be possible with chemotherapy. Certain patients with NHL appear to benefit from intensive chemotherapy with a combination of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOPB protocol). Appropriate, therapeutic strategies taking into account the patients' individual conditions, including the overall prognosis, urgently requires development. Metastatic CNS involvement, which was the primary cause of death in 5 of 11 patients with NHL (45%) receiving chemotherapy, represents a serious limitation to successful treatment.Abbreviations AIDS acquired immunodeficiency syndrome - CB centroblastic - CDC Centers for Disease Control - CHOP cyclophosphamide, doxorubicin, vincristine, prednisone - CMV cytomegalovirus - CNS central nervous system - COPBLAM cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, procarbazine - COPP/ABVD cyclophosphamide, vincristine, prednisone, procarbazine/doxorubicin, bleomycin, vinblastine, darcarbazine - CR complete remission - CT computerized tomography - ELISA enzyme-linked immunosorbent assay - HIV human immunodeficiency virus - HL Hodgkin lymphoma - IT intrathecal - IMVP16 ifosfamide, methotrexate, etoposide - KC Kiel classification - MACOP-B methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin - ML malignant lymphoma - NHL non-Hodgkin lymphoma - OI opportunistic infection - PCP Pneumocystis carinii pneumonia - PD progressive disease - PR partial remission - RT radiation therapy - WBC white blood cells - WF Working Formulation     

Malignant lymphomas in Gabon (equatorial Africa): a morphologic study of 72 cases.

A retrospective morphologic analysis was conducted on 72 malignant lymphomas collected in Gabon, a country of the equatorial area in Africa. Non-Hodgkin's lymphomas (NHLs) were by far the most frequent type of lymphoma, representing 67 cases (93%); only five patients (7%) had Hodgkin's disease. Non-Hodgkin's lymphomas were classified according to two modern systems (Kiel and Working Formulation). The age distribution of NHL patients was bimodal, with the highest peak in the 0 to 14 years age group (these cases were almost exclusively associated with Burkitt's lymphomas), and with the second highest peak in the 55 to 64 years age group. The male to female ratio was 2.5:1, and the overall median age was 44 years. According to the Working Formulation, the NHL cases were composed of one follicular lymphoma (1.5%), 55 diffuse lymphomas (82%), and 11 miscellaneous lymphomas (16.5%). Burkitt's lymphoma was the most frequent NHL (17 cases; 25.4%), followed by diffuse large cell lymphoma (15 cases; 22.4%) and immunoblastic lymphoma (nine cases; 13.4%). Consequently, high-grade NHL formed the largest group (28 cases; 42%), intermediate-grade NHL formed the next largest group (21 cases; 31.3%), and low-grade NHL formed the smallest group (seven cases; 10.4%). These data are compared with series from developed and developing countries, and the observed differences in distribution of the histologic subtypes of malignant lymphoma are discussed.     

Malignant, non-Hodgkin's lymphomas in Trypanosoma cruzi-infected rabbits treated with nitroarenes

Use of 2-nitroimidazole, 5-nitrofuran and 5-nitroimidazole compounds in T. cruzi-infected rabbits resulted in a reduction in duration of parasitaemia in comparison with untreated, infected rabbits. The chronic myocarditis associated with Chagas' disease was not, however, prevented in nitroarene-treated rabbits; lymphocytic infiltrates associated with cardiac cell lysis, in the absence of parasites in situ, were present in both treated and untreated rabbits. The carcinogenic effect of each trypanocidal nitroarene used in this study was also assessed. Administration of nitroarenes to rabbits resulted in the appearance of solid tumours in 37.8 per cent of animals that received drug therapy. Untreated, control rabbits in this series did not show tumour growth. Furthermore, malignant, mixed-cell type, non-Hodgkin's lymphomas were seen in 32.4 per cent of the treated rabbits. It seems that a direct relationship could be present between the presence of the nitro group, the trypanocidal cytotoxicity and the prevalence of tumours. Benznidazole cleared up parasitaemias in the shortest time and was associated with 41.6 per cent of lymphoma growths, whereas MK-436 required twice as much time to clear blood parasites, and showed lymphomas in 25 per cent of experimental rabbits. The demonstration of a high prevalence of malignant tumours in addition to the chronic myocarditis of Chagas' disease in nitroarene-treated rabbits is important since indiscriminate use of such compounds currently used to treat T. cruzi infections in man could increase the risk of lymphoma.