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Treatment of lymphoma.

Lymphomatous diseases (non-Hodgkin's) of children differ markedly from those of adults in histology, natural history, and response to therapy. Information obtained from treating adults with lymphoma cannot be applied to children with equal success; the progress in treating children has been slow. The following types of non-Hodgkin's lymphoma have been distinguished in children seen at the M. D. Anderson Hospital and Tumor Institute in the past 7 years: 1) diffuse undifferentiated lymphoma (Burkitt's lymphoma); 2) diffuse undifferentiated lymphoma (non-Burkitt's lymphoma lacking leukemic propensity); 3) diffuse poorly differentiated lymphocytic lymphoma (non-Burkitt's lymphoma with leukemic propensity (convoluted cell type); and 4) diffuse histiocytic lymphoma (histiocytic lymphoma). The interrelationships of age, sex, histology, and primary site are presented. The occurrence of mediastinal masses in non-Burkitt's tumor (convoluted cell type) is particularly striking. Therapeutic regimens designed for specific types of non-Hodgkin's lymphoma have improved the outcome of treatment in Burkitt's lymphoma, non-Burkitt's lymphoma (convoluted cell type), and histiocytic lymphoma (Stages I and II) as compared with treatment regimens used prior to 1967.

Adolescent

Involvement of the central nervous system in malignant lymphomas.

A retrospective histologic study of 145 consecutive autopsy cases of systemic malignant lymphomas (including lymphatic leukemias) was performed. The classification followed the Kiel Classification (Gérard-Marchant et al., 1974). There was an overall secondary CNS involvement in 26.2% of the total or in 30.4% of the non-Hodgkin's lymphomas including ALL, with intracranial lesions in 21.4 and 26.1%, respectively, and spinal epidural spread in 5.5 (5.1%). Peripheral nerve involvement was seen in almost 40% of the examined cases. Ten further cases were isolated ("primary") intracranial lymphomas without evidence of extraneural deposits or systemic lymphatic disease. The CNS complications in non-Hodgkin's lymphomas were diffuse meningeal and/or perivascular infiltration with or without invasion of the nervous parenchyma, and did not differ from those in CNS leukemia. Isolated solid mass lesions in the brain were only present in 7% of the secondary CNS lymphomas, but were seen in all instances of "primary" cerebral lymphomas. The incidence of CNS complications was highest in lymphoblastic lymphomas including ALL (39%), CLL (31%), immunocytic lymphoma (29%), less frequent in immunoblastic (18.7%), and centrocytic lymphomas (16.6%). No intracranial lesion was observed in centroblastic-centrocytic and centroblastic lymphomas which only produced epidural spread. Bone marrow involvement was present in 92.8% of the cases with secondary CNS lesions, and in 83.2% of the epidural lymphomas. Leukemic conversion, present in 44% of the total (52% with ALL), was demonstrated in 83.3% of the cases with secondary brain lesions, but was hardly combined with epidural spread. The histologic pattern of CNS lesions in non-Hodgkin's lymphomas and their frequent association with leukemic conversion suggest the importance of hematogenous dissemination rather than of direct spread from bone marrow or local manifestation in multisystem disease. Isolated ("primary") lymphomas of the CNS which are morphologically identical with the extraneural lymphomas may represent a primary, often lethal manifestation of a multisystem disease with or without secondary generalization.

Brain Diseases

[Retrospective analysis of the clinical relevance of the Kiel classification of malignant non-Hodgkin's lymphomas (author's transl)].

405 cases with non-Hodgkin's lymphomas have been diagnosed according to the Kiel classification and analysed retrospectively. 314 patients with non-Hodgkin's lymphomas of low-grade-malignancy (chronic lymphocytic leukemia, lymphoplasmacytoid, centrocytic, centrocytic, centroblastic-centrocytic lymphoma) manifested significantly higher median survival times than the 91 patients with non-Hodgkin's lymphomas of high-grade malignancy (lymphoblastic and immunoblastic lymphoma). Within the group of patients with low-grade malignant lymphomas distinct prognostic differences were found whereas survival times in patients with lymphoblastic or immunoblastic lymphomas were rather similar. The lymphoblastic lymphoma showed a bimodal curve of age distribution whilst all other lymphomas had a maximum of incidence in the seventh decade of life. Increased frequency of B-symptoms did not necessarily represent an unfavorable prognostic factor for the lymphoma entity concerned. Except for chronic lymphocytic leukemia the highest incidence of initial bone marrow involvement was seen in lymphoplasmacytoid, centrocytic and lymphoblastic lymphomas. Centrocytes have been observed in peripheral blood of patients with centrocytic and centroblastic-centrocytic lymphomas, even though lymphocytosis did not exist. Monoclonal hypergammaglobulinemia was found in only 43% of the sera from patients with lymphoplasmocytoid lymphoma. In this disease, it was possible to differentiate between a lymphonodal, a splenomegalic and an extranodal manifestation.

Age Factors

Lymphomas of the gastrointestinal tract: a study of 117 cases presenting with gastrointestinal disease.

A study was made of 117 patients who presented with gastrointestinal lymphoma. The occurrence was 48 in the stomach, 37 in the small intestine, 13 in the ileocecal region, two in the appendix and 11 in the large intestine. In six cases, multiple sites in the gastrointestinal tract were involved, but in five cases this appeared to be secondary to massive mesenteric or retroperitoneal lymph node disease. Using Rappaport's classification, diffuse histiocytic lymphoma was the most frequent histologic type and constituted 60% of the cases. Nodular lymphomas comprised 10% of the total, nodular poorly differentiated lymphocytic lymphoma forming the majority of this group. Ten of the lymphomas were undifferentiated, 5 of Burkitt's type and 5 non-Burkitt's type. Five were Mediterranean-type lymphomas associated with plasma cell infiltration of the adjacent mucosa, and only two cases of primary Hodgkin's disease were encountered. Two lymphomas could not be classified. Eight percent of the cases showed plasmacytoid changes and were classified as a distinct subgroup of the parent lymphoma rather than as examples of extramedullary plasmacytoma. Gastrointestinally lymphomas occurred most frequently during the fourth to seventh decades. However, nine lymphomas occurred in children younger than 16 years of age. In comparison to adults, the childhood lymphomas showed a number of notable differences with respect to sex distribution, site of involvement and histologic type. Information concerning the extent of the disease at the time of diagnosis was available in 75 cases. Of these, 49% of the lymphomas were confined to the affected viscus and 33% had associated regional lymph node involvement; the remaining 18% had mode widespread disease. In 44 patients information on the spread of disease was available and in 48% there was extra abdominal spread. Prognosis appeared to correlate best with the stage of the disease rather than the histologic type.

Adolescent

Malignant lymphomas of follicular center cell origin in man. I. Immunologic studies.

Lymphomas with histologic features indicating a follicular center cell (FCC) origin were analyzed from 26 patients of a group of 45 consecutive non-Hodgkin's lymphoma patinets whose tumors were studied for B- and T-cell characteristics. They were compared with benign, reactive lymphoid tissue from 14 patients. Cell suspensions from biopsy material, blood, or bone marrow were examined for surface Ig and for rosette formation with sheep erythrocytes (E rosettes). Of the 26 patients with FCC lymphomas, 22 had 40% or more Ig-bearing cells; all patients with FCC lymphoma tissues had 25% or less E rosette-forming cells. Cells from most FCC lymphomas of the cleaved type had surfac IgM; those from several FCC lymphomas had both IgM and IgD. Cells from lymphomas of noncleaved cell type had surface IgG or IgA. Light-chain analysis showed that cells from FCC lymphomas bore a predominant light-chain type, which indicated their monoclonal nature. Neoplastic cells from several FCC lymphomas synthesized the surface Ig which they bore. Reactive tissues usually contained fewer Ig-bearing and more E rosette-forming cells than FCC lymphomas; the Ig-bearing cells, with one exception, had a polyclonal distribution. Correlation of histologic and immunologic observations indicates that most lymphomas identified as FCC in origin by light micorscopic criteria mark as B cells with the use of immunologic techniques and that FCC lymphomas are the most common type of non-Hodgkin's lymphoma.

B-Lymphocytes

Nodular lymphoma: an ultrastructural study of its relationship to germinal centers and a correlation of light and electron microscopic findings.

This study describes the ultrastructural findings in 16 cases of nodular lymphoma, and compares these with normal germinal centers in order to determine the possible germinal center origin of the lymphomas. Long branching desmosome-associated dendritic reticulum cells, characteristic of germinal centers, were found in all 16 cases of nodular lymphoma. Desmosomes were observed only between dendritic cells and not between lymphoid cells, and they were seen in only 1 of 7 cases of diffuse lymphoma. Cells comprising the nodular lymphomas share cytologic features, such as nuclear blebs and marked nuclear indentations, with germinal center cells. It appears that nodular lymphomas have a close anatomical relationship to germinal centers, although their actual origin from these sites is not established by this study. They are composed of lymphoid cells; we have no evidence to confirm the view that nodular lymphomas are derived from dendritic cells. Light and electron microscopic findings have been compared in order to establish the nature of large "histiocyte-like" cells in the nodular lymphomas. Many of these cells appear to represent transformed lymphocytes rather than histiocytes. They are more numerous in so-called mixed "histiocytic" lymphocytic lymphomas than in poorly differentiated lymphocytic lymphomas, which otherwise are ultrastructurally similar. This study casts doubt upon the existence of a mixed lymphocytic and histiocytic lymphoma within the spectrum of the nodular lymphomas, and indicates that a cytologic continuum exists between cells interpreted as poorly differentiated lymphocytes and those heretofore identified as histiocytes.

Adult

Non-Hodgkin's lymphomas: an ultrastructural study correlating morphology with immunologic cell type.

Ultrastructural studies were performed on 40 B-cell and 14 T-cell lymphomas of non-Hodgkin's type (NHL). Most B-cell lymphomas were comprised of neoplastic cells with morphologic features compatible with a follicular center cell origin. Dendritic reticulum cells and their desmosome-associated processes, characteristic of germinal centers, were observed in all 11 cases of nodular poorly differentiated lymphocytic lymphoma and in one of two cases of nodular "histiocytic" lymphoma, but were not identified in the lymphomas with a diffuse growth pattern. Desmosomes were observed between dendritic reticulum cells and were not found between lymphoid cells. Large neoplastic cells comprising lymphomas of "histiocytic," mixed lymphocytic "histiocytic," and "undifferentiated" types were characterized ultrastructurally and immunologically as lymphoid cells. Malignant lymphomas of well and moderately well differentiated lymphocytic types (7 cases) revealed B-cell markers, and represented a distinct homogenous group of neoplasms, with electron microscopic features most closely resembling follicular cuff lymphocytes. T-cell malignancies included lymphoblastic lymphomas (3 cases), large cell ("histiocytic") lymphomas (4 cases), lymphoepithelioid cell ("Lennert's") lymphomas (2 cases), mycosis fungoides (3 cases) and diffuse poorly differentiated lymphocytic lymphomas (2 cases). A consistent finding in the T-cell proliferations was the presence of small and/or large lymphoid cells with extremely irregular and/or convoluted nuclei, which occurred in varying proportions and with variable degrees of nuclear complexity. The nuclear irregularity evident in the neoplastic T cells was distinguishable from that observed for lymphoid cells of B-cell lymphomas. In comparing the cytoplasmic features of the T- and B-cell neoplasms ultrastructurally, the only distinguishing feature was the presence of well developed granular endoplasmic reticulum with dilated cisternae, i.e., plasmacytoid features, predictive of a B cell origin.

Adolescent

Differential diagnosis of malignant and benign cutaneous lymphoid infiltrates: a study of 57 cases in which malignant lymphoma had been diagnosed or suspected in the skin.

Clinical and histopathologic findings were reviewed in 57 cases in which there had been a diagnosis or suspicion of malignant lymphoma in the skin other than mycosis fungoides. Patients were included only if 1) extracutaneous tissue satisfactory for lymphoma classification was available, or 2) there was no evidence of extracutaneous involvement after a minimum of five years. Thirty-five patients had systemic lymphoma; in eight of these that disease first became manifest in the skin. There were two patients with typical lymphomatoid papulosis and one with a somewhat similar but solitary lesion which did not recur after excision; we have termed the latter a "solitary lymphomatoid papule." The remaining 19 cases without extracutaneous involvement were regarded as benign lymphoid hyperplasia. Clinically, the cutaneous lesions of malignant lymphoma were difficult to distinguish from those of lymphoid hyperplasia; only lymphomatoid papulosis was distinctive. Histologically, it was found that a definite diagnosis of malignant lymphoma (other than mycosis fungoides) could be made in the skin when three criteria were fulfilled: 1) exclusive presence or marked preponderance of medium-sized or larger lymphocytes, 2) absence of preferential involvement of the upper dermis, and 3) absence of extensive epidermal infiltration. These criteria were met in 21 cases of lymphoma. In both cases of lymphomatoid papulosis, the infiltrate was predominantly composed of large lymphocytes but was primarily limited to the upper dermis. The "solitary lymphomatoid papule" contained a similar cell population and involved the full thickness of the dermis; however, it displayed a prominent intraepidermal component. Fourteen cases of malignant lymphoma and all cases of lymphoid hyperplasia were characterized by a mixture of lymphocytes of varying size or a predominance of small lymphocytes. Nine cases of lymphoid hyperplasia exhibited at least one of three findings not observed in lymphoma; these findings were 1) germinal centers, 2) marked paucity of medium-sized lymphocytes in comparison to both small and large lymphocytes, and 3) sharp margination between adjacent groups of small and large lymphocytes. Aside from one case of small lymphocytic lymphoma which showed deep subcutaneous extension, the remaining cases (13 malignant and 10 benign) could not be reliably differentiated from each other by skin biopsy findings alone and were thus considered histologically indeterminate. The 13 lymphoma cases in this group were all of the small lymphocytic or follicular types; the failure of follicular lymphoma to exhibit a follicular pattern in the skin was a major impediment to its recognition in that location. The cutaneous infiltrates in all cases of large lymphocytic, Burkitt's, and lymphoblastic lymphoma were diagnostic of malignancy.

Adolescent

Human malignant lymphomas in vitro. Characterization of biopsy cells and establishment of permanent cell lines.

A series of 55 biopsies from different types of malignant lymphomas were characterized in short-term culture experiments and during prolonged growth in vitro. The majority of the lymphocytic lymphomas and half of the histiocytic lymphomas expressed surface immunoglobulin, either in monoclonal or polyclonal form, indicating B-lymphocyte derivation. No lysozyme production was noted in either type of lymphoma, giving further support to the notion that histiocytic lymphomas are not truly histiocytic. Production of beta2-microglobulin was higher in histiocytic than in lymphocytic lymphoma and Hodgkin's disease but did not significantly differ from the production observed in non-neoplastic lymph node disorders. Incorporation of 3H-thymidine varied greatly within each category of lymphoma; the highest mean labelling index was noted in histiocytic lymphoma, possibly reflecting the generally more malignant course in such cases. Epstein-Barr virus-associated nuclear antigen was observed in one case of Hodgkin's disease. Attempts to establish permanent tumor cell lines were successful only from two explants of lymphocytic lymphoma and one pleural effusion from histiocytic lymphoma. The two cell lines derived from lymphocytic lymphomas both exhibited B-lymphocyte characteristics. The histiocytic lymphoma line lacked lymphocyte markers, produced lysozyme and was found to be rich in cytoplasmic esterases. These features are consistent with a "true" histiocytic derivation of this line. Lymphoblastoid cell lines representing non-neoplastic EBV-carrying lymphocytes contaminating the biopsies were derived from 19 biopsies, with the highest frequency noted in cultures of biopsies from Hodgkin's disease. The tumor lines were all EBV-genome negative.

Antigens, Viral

Non-hodgkin's lymphomas in Saskatchewan: a clinicopathologic study.

In a retrospective clinical study of 208 previously untreated persons with non-Hodgkin's lymphomas the disorders were classified and staged according to the histopathologic criteria of Rappaport, Winter and Hicks and the Ann Arbor clinical staging classification.Nodular types constituted 22% and diffuse types 78% of the lymphomas. The nodular lymphomas were slightly more common in females and were clustered in the age range 30 to 90 years. The diffuse lymphomas were slightly more common in males; the age distribution was bimodal, with one peak in the age range 10 to 19 years and the other in the age range 60 to 69 years, but when the age distribution of the general population in which the lymphomas occurred was taken into account, the incidence of these lymphomas was found to be significantly higher (P < 0.001) in persons more than 69 years of age than in those 40 to 69 years of age.SURVIVAL CORRELATED WITH HISTOPATHOLOGIC TYPE: persons with nodular (follicular) lymphomas and diffuse lymphocytic well differentiated lymphomas had a significantly greater survival (P < 0.05) than those with other diffuse lymphomas. No significant difference in survival was noticed between persons with nodal and extranodal lymphomas.While Rappaport and colleagues' criteria are still very useful, it is important to recognize the nodular lymphoma as a specific entity requiring generally different management from diffuse lymphomas. Appreciation of the different biologic behaviour of the various lymphomas is important to clinicians planning therapy.

Adult

Familial lymphoma and genetic predisposition: an updated review.

BACKGROUND: Several factors contribute to the development of malignant lymphomas including environmental exposures, bacterial and viral infections, as well as familial and genetic factors. MAIN BODY: Numerous somatic variants are involved in lymphomagenesis, and an increasing number of germline variants predisposing patients to lymphoid neoplasm have been identified. Although most lymphomas arise sporadically, epidemiological studies have linked a familial history of lymphomas and other hematological tumors with an increased lymphoma risk. Although rare, familial clustering of malignant lymphoma is well documented, and the constellations suggest inherited risk factors. Recent technological advancements have improved our ability to identify genetic factors associated with lymphoma that overall lead to a better understanding of genetic susceptibility for these entities. In this context, we here provide a comprehensive perspective on lymphoma risk factors to support improved lymphoma risk assessment and testing. A dedicated clinical management could influence future advances in lymphoma therapies and might also prevent severe toxicity and secondary malignancies. However, to date, only few susceptibility genes for malignant lymphomas have been identified. Highly penetrant mutations in known genes cannot account for most of the excess in a polygenic and heterogenic disease such as cancer. High-throughput sequencing identifies pathogenic variants that may constitute most low-penetrance alleles. However, their detection requires many well-characterized cases and controls. In this review, we therefore also include a short discussion on a Swiss cohort where we prospectively collect and samples for genetic data from individuals with a family history of lymphoma. We are convinced that such an approach is more informative and feasible than a population-based project with unselected cases and aim to better inform both genetic counsellors and oncologists. CONCLUSION: Inherited genetic factors contribute to lymphoma risk in a subset of patients. Improved identification of susceptibility variants, particularly through family-based studies, may enhance risk assessment and inform personalized clinical management.

Humans

Non-Hodgkin's lymphomas: an immunohistochemical and histological study.

Immunohistochemical and histoogical studies have been performed on paraffin sections of 19 cases of non-Hodgkin's lymphoma (NHL). All the cases were lymphocytic in type and, on the basis of the National Lymphoma Investigation classification, 11 were follicular (six small, three mixed small and large, and two large cell types) and eight were diffuse (four intermediate, three poorly and one well-differentiated types). Marshall's metalophil method revealed a population of dendritic histiocytes in and around the follicles of follicular lymphomas. The distribution of the dendritic cells within the neoplastic follicles resembled the distribution of similar cells in reactive follicles, lending support to the concept of an origin for lymphoma follicles from their reactive counterparts. In the diffuse lesions the dendritic cells were large and more pleomorphic than in the follicular lesions, but these features were not so pronounced as those previously observed in Hodgkin's disease. The PAP sequence was used to demonstrate Ig, and as judged by the types of light and heavy chains in the lymphoma cells, the cases were divided into three groups: Group 1 (eight cases) in which the lymphoma cells contained monotypic Ig; Group 2 (six cases) in which monotypic Ig was probably present; and Group 3 (four cases) where no evidence of monotypic Ig secretion was found. Monotypic Ig was most commonly found in follicular lymphomas, mu kappa secretion being the most frequently identified combination of heavy and light chains. The majority of cases (73 per cent.) were thus clearly derived from B lymphocytes. However, the fact that monoclonality was evident in only a proportion of cases suggested that lymphomas may be polyclonal initially and proportion of cases suggested that lymphomas may be polyclonal initially and that monoclonality is a later development. In addition to the lymphoma cells, normal mature plasma cells containing a high concentration of intracellular Ig were present in all but one of the lesions. The Ig was polytypic, cells containing kappa and lambda chains being present in roughly equal numbers and gamma chains pre-dominating. Extracellular Ig (gamma, mu, kappa, lambda) was also present in many lesions. Collections of small non-lymphomatous lymphocytes were also present in all cases. In eight lesions these appeared to have polytypic surface Ig (mu, kappa, lambda). Dendritic cells mingled with these lymphocytes. Collections of small lymphocytes non-reactive for Ig were also present. These had no association with dendritic histiocytes and might have been T cells. It is concluded that in most cases immunohistochemistry alone provides an insufficient basis for the diagnosis of lymphoma and that disturbance of cellular morphology and tissue architecture remain the most useful criteria on which the diagnosis of lymphoma rests.

Adult

[Non-Hodgkin's malignant lymphoma. Retrospective study of 64 cases classified according to Kiel's and Rappaport's nomenclature].

64 cases of non-Hodgkin malignant lymphomas were the object of a retrospective study: these 64 cases were considered in terms of Kiel's and Rappaport's classifications. The stimultaneous study using the two classifications showed that entities defined in one of them do not correspond to entities defined in the other one. --This study allows us to define: 1) in Kiel's classification, a groupe of lymphomas of favorable prognosis, by opposition with a group of lymphomas of poor progonosis, all stages included; 2) in Rappaport's classification, a group of nodular lymphomas of favorable prognosis, for which the actuarial survival curves, all stages included, seem to accord with the anatomico-clinical data thus far published. Nevertheless, while nodular lymphomas can be identified as lymphomas of favorable prognosis, it does not seem possible to isolate, in Rappaport's classification, a group of lymphomas of poor prognosis by opposition with the favorable prognosis group. This study confirms that, to the morphological entity of the malignant centroblastic centrocytic follicular lymphoma, there corresponds a lymphoma of favorable prognosis whose median is 72 months, all stages included, for an average age of 57.5 years (this median is more than 180 months in the clinically localized stages). This morphological entity of Kiel covers 76 per cent of Rappaport's malignant nodular lymphomas. Nevertheless, 24 per cent of these same malignant nodular lymphomas are considered to be lymphomas of poor prognosis by Kiel and seem to appear as such in our study.

Adult

Surface markers and functional properties of non-Hodgkin's lymphoma cells in relation to histology.

Cells from 32 adult patients with non-Hodgkin's lymphoma were studied with respect to surface markers and functional properties in short-term culture. Twenty-six lymphomas were of B-cell origin, including all nodular and diffuse lymphocytic lymphomas. Three tumors were of T-cell origin (one histiocytic lymphoma and two undifferentiated lymphomas). In the remaining three cases (histiocytic lymphomas) the immunological nature of the tumor cells could not be determined. All reactivity to mitogenic stimuli of cells from B-cell lymphomas was due to residual normal T cells. In follicular lymphocytic lymphomas more reactive T cells prevailed among the malignant B cells than in diffuse lymphocytic lymphomas. Heterogeneity among B-cell lymphomas was indicated by differences in intensity of fluorescence with anti-Ig reagents and in stimulatory capacity in mixed lymphocyte culture. T-cell lymphomas were characterized by high percentages of T cells together with impaired responses to stimuli. The results of immunological studies correlated well with the histological classifications of Rappaport, Lukes and Lennert.

Adult

Non-Hodgkin's lymphoma in children.

The clinical and pathological features of 64 children with non-Hodgkin's malignant lymphoma seen between April 1962 and June 1973 are described. Forty-one children had diffuse, undifferentiated, non-Burkitt lymphoma (lymphoblastic lymphoma). They tended to be boys under 10 years of age and their median survival was 1 year. Almost one-third are surviving for 1-11 years, most in initial complete remission. Nineteen children had diffuse, poorly differentiated, histiocytic lymphoma. They tended to be boys more than 10 years of age, their median survival was only 6 months, and only the 3 patients with Stage I peripheral node tumour survived. Two children had nodular, lymphocytic, poorly differentiated lymphoma and 2 had lymphoma resembling the Burkitt type. From our clinical and pathological observations, we conclude that non-Hodgkin's malignant lymphomata in children cannot be separated from the acute lymphocytic, histiocytic and unclassified leukaemias by cytological or histological methods. What is called diffuse, undifferentiated, non-Burkitt type, or lymphoblastic lymphoma is actually acute lymphocytic leukaemia without apparent invasion of marrow and peripheral blood by neoplastic lymphocytes at time of diagnosis. What is termed diffuse, histiocytic lymphoma is acute histiocytic leukaemia without apparent infiltration of marrow and peripheral blood at initial presentation. One could say just as well that acute lymphocytic leukaemia is Stage IV lymphoblastic lymphoma and that acute histiocytic leukaemia is Stage IV histiocytic lymphoma. Further classification of lymphocytic and histiocytic cancers by newer functional, chemical and morphological methods should include both what is called lymphocytic or histiocytic leukaemia and what is called non-Hodgkin's lymphoma as one group of diseases, susceptible to subclassification by the new methods. We recommend that Stage I lymphocytic and histiocytic cancers be treated with local irradiation. Patients with Stages II-IV tumours should receive anti-leukaemic forms of therapy including prolonged multiple agent chemotherapy and preventive central nervous system irradiation. Staging laparotomy should be considered in patients with Stage I tumour in low cervical, axillary and inguinal nodes.

Adolescent

B and T cell lymphomas. Analysis of blood and lymph nodes in 87 patients.

B and T cell populations were studied in blood and neoplastic tissues from 64 untreated and 23 treated patients with non-Hodgkin's lymphoma. This study was undertaken primarily to evaluate the relation of B and T cell markers in various lymphomas to the currently accepted morphologic classifications and to determine the utility of various tissues in defining the cell of origin of a lymphoma. When histologically involved blood, bone marrow, lymph nodes or body fluids were studied, a B or T cell origin of the lymphoma was identified in 26 of 28 (68 per cent) patients. A B cell origin was found in 17 adults classified as having nodular (N) or diffuse (D) poorly differentiated lymphocytic lymphoma (PDLL). One lymphoma of T cell origin was observed in an adult with poorly differentiated lymphocytic lymphoma-diffuse (PDLL-D). In contrast, all cases of PDLL-D in children were T cell in origin. The origin of American Burkitt's (stem cell) lymphoma in two children was the B cell. When histologically involved blood was studied, a B or T cell origin was demonstrated in 10 of 21 (48 percent) adults. Evidence of a monoclonal proliferation of B lymphocytes in the blood was found two adults with more than 7 per cent lymphoma cells in Wright-Giemsa stained blood smears. When neoplastic lymph nodes were studied, the diagnosis of a B cell lymphoma was made in 8 of 12 (67 per cent) adults. Study of surface markers on malignant cells in cerebrospinal or serosal fluids frequently revealed a B or T cell origin of the lymphoma. B and T lymphocyte numbers in the blood did not correlate with immunoglobulin or skin test abnormalities. Abnormalities in circulating B or T cell percentages at diagnosis were a poor prognostic sign in patients with PDLL-D.

Adolescent

Histopathologic review of lymphoma cases from the Southwest Oncology Group.

Lymphoma Pathology Panel and Repository (LPPR) review of pathologic material from 354 patients registered on Southwest Oncology Group clinical trials substantiated the diagnosis of Hodgkin's disease (Lukes-Butler classification) in 175 (94%) of 186 cases and the diagnosis of non-Hodgkin's lymphoma (Rappaport classification) in 162 (96%) of 168 cases. However, complete agreement (type and subtype) between institutional and LPPR review diagnoses was found in only 66% of confirmed cases of Hodgkin's disease and in only 58% of confirmed cases of non-Hodgkin's lymphomas. In 26 (16%) of 160 cases of non-Hodgkin's lymphoma, the initial interpretation of pattern (nodular vs diffuse) differed: 20 (25%) of 81 nodular lymphomas had been thought to be diffuse and 6 (8%) of 79 diffuse lymphomas had been diagnosed as nodular. The frequency with which initial diagnoses were confirmed on LPPR review was highest for three subtypes of lymphoma: nodular sclerosis Hodgkin's disease (88%), diffuse histiocytic lymphoma (86%), and nodular lymphocytic lymphoma (78%); rates of confirmation for all other subtypes ranged from 13-50%. The results of this analysis emphasize the necessity of having pathologic review of all cases entered on major lymphoma studies so that comparability of cases can be assured and the results of those studies placed in proper perspective.

Hodgkin Disease

Immunologic and cytochemical cell markers in non-Hodgkin's lymphomas.

Lymph nodes were obtained from 28 patients with non-Hodgkin's lymphoma and 24 patients without hematologic malignancy. Cases of undifferentiated lymphoma, diffuse histiocytic lymphoma, diffuse and nodular mixed histiocytic-lymphocytic lymphoma, nodular poorly differentiated lymphocytic lymphoma, and diffuse well differentiated lymphocytic lymphoma were analyzed. Touch preparations were stained for nonspecific esterases, peroxidase, Sudan black B activity and with periodic acid-Schiff and Wright-Giemsa reagents. Mononuclear cell suspension from lymph nodes and, in some cases, peripheral blood were tested for spontaneous rosette formation with sheep erythrocytes and for the presence of surface immunoglobulin. The remainder of the lymph node was examined after staining with hematoxylin and eosin. Analysis of the lymphocyte surface markers indicated that 15 cases of various histologic types of lymphoma were B cell proliferations. However, three out of four cases of diffuse poorly differentiated lymphocytic lymphoma and one of seven cases of diffuse histiocytic lymphoma appeared to represent T cell neoplasia. Lymph nodes from four cases of lymphoma representing diverse histologic types were replaced by neoplastic cells devoid of discernible cell markers. In five cases, the distribution of cell surface markers in the malignant lymph node failed to differ from data obtained in the analysis of non-neoplastic lymph nodes. The study indicates that the histopathologic entities recognized in the currently employed classification of lymphoreticular malignancies are heterogeneous. Alterations in the distribution of cell surface markers in the peripheral blood from five of 12 patients indicated involvement prior to demonstrable morphologic evidence of peripheral blood involvement in four patients and bone marrow infiltration in two patients.

Adolescent