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Actually, radiation-therapy indications in non-Hodgkin's lymphoma tends to decrease in favour of exclusive chemotherapy, especially in aggressive localized diseases. In this situation, PET scan imaging would be a promising tool to identify candidates to complementary radiotherapy after initial chemotherapy. To decrease long-term morbidity, radiation doses and treated volumes should be as small as possible. New radiation technologies could contribute to reduce this risk as well. However, there are still indications for radiotherapy. Radiation therapy could be delivered with curative-intent in localized indolent non-Hodgkin's lymphoma and could be helpful in symptom relief in advanced or relapsed indolent lymphoma.

Hodgkin's and non-Hodgkin's lymphomas are frequent and represent a heterogenic group of haematologic diseases. Prognostic factors allow to classify patients into homogeneic risk groups, to adapt treatment proposal to disease's risk and, in some cases, to avoid over-treatment. For all lymphomas, the first step is to determine the stage of the disease in Ann Arbor's classification, using physical examination, radiological and functional imaging. However, this classification is not optimal to predict disease evolution. Specific scores corresponding to the histological subtype of the lymphoma have been determined: IPI (international prognostic index) for aggressive lymphomas, FLIPI (follicular lymphoma international prognostic index) for indolent lymphomas and IPS (international prognostic score) for advanced Hodgkin's lymphomas. Functional imaging by PET (position emission tomography) is of prognostic significance in aggressive and Hodgkin lymphomas to evaluate early response to treatment, before autografting and at the end of the treatment. Several kinds of molecular prognostic markers have been studied: circulating rates of proteins, over expression of genes, presence of specific cells in the tumour... But these factors are not yet used in clinical practice, as they have not been validated on large cohorts and their interactions with other prognostic factors and between them are not well known. Although molecular biology has made some recent progress, only classical prognostic factors (physical examination, radiological and functional imaging) are used by now.

In France, adolescents (15-20 years) with non Hodgkin's lymphoma (NHL) are referred either to paediatric or to adult onco-haematological departments. According to data obtained from regional tumour registries (covering about 10% of France), their 5 year survival rate was 59% whereas it was 87% for children (< or =14 years) treated for NHL during a similar period of time. We reviewed the management of NHL either by the paediatricians or the onco-hematologists for adults. The categories of NHL that are reviewed and whose clinical and biological characteristics are presented are: Burkitt, lymphoblastic and large cell, either B or anaplastic. This review shows that, in most series, outcome was better in children than in adults. This raises the reasons of this difference: is it due to the different therapeutic approaches, to different tolerance of chemotherapy, to different biology within the same histological type ? Further studies specific to the adolescents are needed to better know the biology of their lymphoma and to determine the best therapeutic approach.

Non Hodgkin lymphoma represent about 5% of childhood cancer. They are the third most common group of cancers in children and adolescents, after cerebral tumours and leukemias. They differ from adult lymphomas as they are all high grade tumours, always diffuse and often associated with extra-nodal diseases. Three main histological subtypes predominate: Burkitt, lymphoblastic and anaplastic large cell lymphomas. As the clinical progression is growing fast and treatment different between the 3 subtypes, the diagnosis must be rapidly done and with accuracy.

Hematodermic CD4/CD56 neoplasm is a recently described entity. This name has been initially proposed by the French Study Group on Cutaneous Lymphomas which established the primary anatomoclinical and pathogenic and cytogenic bases of the disease in 1999. This descriptive and provisional name allowed conceptualizing the entity by its main clinical and phenotypical characteristics. The first case in the literature goes back to 1994. Since that time, several other cases have been published. The expression of CD56 led most of the authors to propose an NK-cell lineage origin. In the last WHO classification of lymphomas, the entity was indexed under the name of "blastic NK-cell lymphoma". However, the authors underlined that there were currently no clues to the etiology of blastic NK-cell lymphoma and that the precise lineage of this disease was still unresolved. At the clinical level the main characteristics of the disease are the skin tropism and the occurrence of a leukemic phase at any time during the course of the disease. The median age is 59 but pediatric cases do exist. At the morphological level skin biopsy shows a monomorphous cell proliferation simulating a pleomorphic T cell cutaneous lymphoma. The diagnosis is based on phenotypic criteria which require frozen tissue. Currently, the main characteristics are the expression of CD4 and CD56 antigens while the main defined lineage specific markers are negative (B-cell, T-cell, NK-cell and myeloid-cell lineages). The origin of the tumor cells still remains uncertain but the plasmacytoid dendritic cell is presently a very serious candidate. The tumor cells share a great phenotypical homology and particularly the expression of the CD123 antigen. Functional homologies have also been demonstrated with tumor cells in vitro. Outcome of CD4/CD56 hematodermic neoplasms is very bad. The median time of survival is 14 months irrespective of the treatment given. Conventional chemotherapies used for the treatment of aggressive lymphomas or acute myeloid leukemias are quickly inefficient.

Main strategies used as first line treatment of aggressive lymphoma are the subject of this review. The evolution of histopathlogical classifications is reviewed and the concept of aggressive lymphoma is given. General principles of chemotherapy treatment and main prognostic factors that direct therapeutic decisions are described. The treatment modalities of localized and advanced disease are detailed, as well as the role of high-dose therapy with hematopoietic support. Finally, the major impact of immunotherapy based on the monoclonal anti-CD20 antibody is envisaged.

Different histopathologic classifications have been used in the study of malignant lymphomas. The clinical relevance (reproducibility, prognostic value) has not been precisely studied. The "non-Hodgkin's lymphoma classification project" has been organized to study a cohort of 1,403 cases in 9 sites around the world consisting of consecutive patients seen between 1988 and 1990 in order to have a good follow-up. The reproducibility of the up-dated Kiel and the ILSG (REAL) classifications between the 5 visiting expert hematopathologists was pretty good, at least 85% for the majority of the entities. According to survival curves, the lymphomas can be stratified in 4 different groups. Comparison with the international prognostic index demonstrate that for therapeutic strategy both histopathology and index should be used. The results bring a good support to the project of the WHO to propose the first international classification of lymphomas based on both forme classifications.

In this retrospective study (1986-1996), a series of 250 immunocompetent patients (SFNC series) with primary malignant lymphoma of the central nervous system is reviewed and the lymphomas redefined using the REAL (Revised European-American classification of Lymphoid neoplasms) and the modified Kiel classifications. All the tumors available for review were classic diffuse non-Hodgkin's lymphomas. Thirty-eight were unclassifiable due to small size and artifacts in the specimens. Eight cases were of T-cell type (3.7%). The 212 others cases were B-cell type. According to the REAL classification, the high majority was diffuse large cell (62%). Following the modified Kiel classification percentage of cases categorized as low and high grade of malignancy were 22.4% and 77.6% respectively.

The pathological material of 35 patients with Hodgkin's disease lymphocyte-depletion type (type 4) is reviewed with an immunohistochemistry study on paraffin-embedded sections. The new pathologic data are compared with clinical features. These 35 patients are 4.7% of 742 previously untreated patients managed in this institution from 1960 to 1991. The diagnosis of 31 of the 35 patients was rectified, 17 to non-Hodgkin's lymphoma (12 unclassifiable and five anaplastic Ki-1 positive) and 14 to another type of Hodgkin's disease (six nodular sclerosis and eight mixed cellularity). In four cases, the pathologic material was neither sufficient nor satisfactory to allow a clear-cut distinction between Hodgkin's disease and non-Hodgkin's lymphoma. The analysis of clinical data before and after pathological revision did not show any difference in clinical features, either between Hodgkin's disease "type 4" and other types (1, 2 or 3) or between cases with Hodgkin's disease and those with non-Hodgkin's lymphoma. There is, however, a significant male predominance for Hodgkin's disease versus non-Hodgkin's lymphoma (P = 0.029, exact Fisher test), and B symptoms in non-Hodgkin's lymphomas (P = 0.056), whereas B symptoms are commonly seen in advanced stages of Hodgkin's disease. It is emphasized that all Hodgkin's disease of lymphocyte-depletion type should be reviewed and discussed before any treatment, and this diagnosis actually means non-Hodgkin's lymphoma or other types of Hodgkin's disease.

Non-Hodgkin's lymphomas are malignant tumours of lymphotic tissue. They predominantly involve the lymph nodes but may affect all organs. The distribution of lymphomas is summarized in the Ann Arbor classification into two types of extranodal tumours: localized primary lymphomas and secondary lymphomas expressing a disseminated disease. The most frequent sites of secondary lymphomas are the bone marrow and the liver, while those of primary lymphomas are the digestive tract and the E.N.T. region. The diagnosis is complicated by the clinical polymorphism of extranodal lymphomas, particularly when the tumour is located in regions such as the brain, where histological samples are difficult to obtain. The prognosis does not rest on the multiplicity of clinical presentations but exclusively on the histology and size of the tumoral mass. Only cerebromeningeal and cutaneous lymphomas require special treatments.

The term malignant lymphoma (ML) covers several lymphoid tumoral diseases of varying aggressiveness. Nowadays, histopathology makes it possible to individualize entities corresponding to cellular types well defined by their cytology, their selective invasion of certain lymph node compartments, their immunophenotype and sometimes their cytogenetic and molecular markers. Some of these entities are not yet known to non-specialists. Mantle cell-derived malignant lymphoma, monocytoid B-cell lymphoma, low-grade MALT type malignant lymphoma, large mediastinal cell malignant lymphoma and large anaplastic cell malignant lymphoma are examples of these entities, each of them having its own clinical manifestations.

Classifications of malignant lymphomas (ML) are aimed at separating different morphological entities that can be recognized by histopathologists and anatomico-clinical entities that are useful to clinicians. With these classifications, entities with different proliferative and disseminating potential can be distinguished, and the effects of treatment on the various types of ML can be compared. The advances expected in the near future will be due to techniques which are already known and will provide information on the proliferative power of lymphoma cells, on the significance of chromosomal abnormalities, on hyperexpression of certain cytokines or expression of certain adhesion molecules, and on the role played by the presence of the genome of some viruses in tumoral cells. Yet the most important advances in this field will perhaps be due to hitherto unknown techniques or to not yet imaginable new research lines.

The authors list the reasons which make it important and useful to classify non-Hodgkin's malignant lymphomas (ML) and discuss the criteria of a convenient classification. They also describe the principles of updated Kiel's classification and the various entities recognized. These entities are divided into type B and type T ML, each type in turn being divided into low malignancy, high malignancy and rare forms.

The aim of this prospective study was to assess the frequency of gastroduodenal involvement during initial staging of extradigestive non Hodgkin's lymphoma. One hundred and one patients (64 men and 37 women; mean age 57.7; range 22-77 years) underwent an upper digestive endoscopy with multiple biopsies before any treatment. The origin of lymphoma was nodal in 76 cases and extranodal in 25 cases. Biopsy specimens were taken from all gross lesions; when the mucosa was considered as normal, biopsy specimens were obtained from the corpus, the antrum, and the duodenum. Endoscopy was normal in 37 patients; nevertheless in 4/37 patients, biopsies revealed lymphoma infiltration. In 64 patients, endoscopy showed macroscopic anomalies: biopsies were negative in 47 patients and showed lymphoma involvement in 17 patients. The involvement site was the corpus of the stomach (11 cases), the antrum (9 cases), and the duodenum (9 cases); lesions were multifocal in 10/21 patients. The association of several types of lesions was noticed in 5 patients. Lesions included volcano-like craters (8 cases), large folds of brain-like appearance (4 cases), tumors greater than 3 cm (3 cases), gastric ulcers (3 cases), erosive gastritis (3 cases), and erythematous duodenitis (2 cases). Overall, 21 of 101 patients (20.8 percent) had positive biopsies, 17 with endoscopic lesions and 4 without. Only 5/21 patients presented upper gastrointestinal symptoms. Staging of the lymphoma changed to Stage IV in 11 patients (4 stage I, 4 stage II and 3 stage III) (10.9 percent) after gastrointestinal involvement was documented. Gastroduodenal involvement is not related to initial site (nodal or extranodal), stage of extension or grade of malignancy of the lymphoma.

A patient aged 65 years was observed to have successive adenomegalic syndromes over a period of 4 years, with variable histological appearances. A right cervical adenopathy had the histological appearance of a simple antigenic-stimulation lesion. Three years later, a right inguinal adenomegaly presented all the histological criteria of angioimmunoblastic adenopathies, without, however, any humoral immunity disturbance. Two months later, a biopsy of a palatine tumour confirmed the diagnosis of an immunoblastic sarcoma. The condition then became generalized as a lymphoblastic type of diffuse lymphosarcoma, and autopsy one year later showed the presence of a pleomorphic lymphosarcoma in several lymphoid formations. This case serves as a basis for discussing the concept of angio-immunoblastic adenopathy; the result of various antigenic aggressions or the early stage of a haematosarcoma. It also clearly demonstrates the sometimes contingent characteristics and difficulties in classification of haematosarcomas.

New methods helpful in the classification of lymphoid and monocytoid leukaemias and haematosarcomas have recently become available. Among the most valuable procedures have been those detecting immunological markers and the ultrastructural analysis permitted by convention and scanning electron microscopy. The results of these studies, taken together with a meticulous morphologic examination on Giemsa smears allow a more subtle classification on these neoplasias. Among the most interesting points, one can list: a) The description of macroglobulinemic proplasmocytic leukaemia; b) The observation that all the prognostic parameters in the four types of common acute lymphoid leukaemia (ALL) (prolymphocytic, microlymphocytic, macrolymphocytic, prolymphoblastic) such as age, tumour mass (or leucocytosis are related to the cytological type); T marker may be found in all these types, except for the prolymphoblastic one; c) T or B immunoblastic acute lymphoid leukaemias have been described as a fifth type of ALL; d) The lymphosarcomas which can be histologically nodular (composed of B cells) or diffuse (composed of cells presenting B, T or no markers) can be cytologically prolymphocytic or lymphoblastic (or lymphoblastoid) if they are nodular, prolymphocytic, lymphoblastic, or immunoblastic if they are diffuse; true (African) Burkitt's lymphosarcomas (BLS) must be distinguished from all the pseudo (non-African) Burkitt's lymphosarcomas which have been described elsewhere and which are either immunoblastic or lymphoblastic (oid) lymphosarcomas with a few macrophages; e) The diagnosis of reticulosarcoma which was in the past abusively carried out (because of confusion with immunoblastic lymphosarcoma) is based on the presence of many reticluins fibers at histological examination and on the cytological aspect of the cells on smears (the distinction of those cells with immunoblasts is easy).

The approach to non hodgkins malignant lymphomas (NHML) has changed in recent years, notably because of advances in pathological evaluation due to histo-immuno-labelling leading to a more accurate classification. Such pathology being relatively common in the cervical facial region, with a figure of 10 to 25%, this report concerns the personal experience of the authors based upon 65 cases treated in the department between 1975 and 1985.