Space plasma physics: space experiments with particle accelerators.

Electron and plasma beams and neutral gas plumes were injected into the space environment by instruments on Spacelab 1, and various diagnostic measurements including television camera observations were performed. The results yield information on vehicle charging and neutralization, beam-plasma interactions, and ionization enhancement by neutral beam injection.

Exercise for improving balance in older people.

BACKGROUND: Diminished ability to maintain balance may be associated with an increased risk of falling. In older adults, falls commonly lead to injury, loss of independence, associated illness and early death. Although some exercise interventions with balance and muscle strengthening components have been shown to reduce falls it is not known which elements, or combination of elements, of exercise interventions are most effective for improving balance in older people. OBJECTIVES: To present the best evidence for effectiveness of exercise interventions designed to improve balance in older people living in the community or in institutional care. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (Feb 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to February 2006), EMBASE (1980 to February 2006), other databases and reference lists of articles. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials testing exercise interventions designed to improve balance in older people were included. We excluded trials of interventions targeting individuals with specific conditions in order not to broaden the scope of this review too widely. Trials were included where participants were randomised to receive the following: a single exercise intervention or a multiple exercise intervention and a control group (usual activities or attention or recreational activity). Trials comparing two or more exercise interventions and a control group were also included. DATA COLLECTION AND ANALYSIS: Three pairs of members of the review team independently assessed trial quality and extracted data. For each trial, relative risk and 95% confidence intervals were calculated for dichotomous outcomes, and mean differences and 95% confidence intervals calculated for continuous outcomes. Where appropriate, results of comparable groups of trials were pooled and 95% confidence intervals calculated. MAIN RESULTS: For the 34 included studies there were 2883 participants at entry. Statistically significant improvements in balance ability were observed for exercise interventions compared to usual activity. Interventions involving gait; balance; co-ordination and functional exercises; muscle strengthening; and multiple exercise types appear to have the greatest impact on indirect measures of balance. There was trend towards an improvement in balance with cycling on a static cycle. However, there was limited evidence that effects were long-lasting. AUTHORS' CONCLUSIONS: Exercise appears to have statistically significant beneficial effects on balance ability in the short term but the strength of evidence contained within these trials is limited. Many of these mainly small studies demonstrated a range of methodological weaknesses. The failure across the included studies to apply a core set of standardised outcome measures to determine balance ability restricts the capacity to compare or pool different trials from which firm conclusions regarding efficacy can be made. Further standardisation in timing of outcome assessment is also required as is longer term follow-up of outcomes to determine any lasting effects.

Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma.

BACKGROUND: Cyclophosphamide is an established bladder carcinogen, but few studies have examined the relationship between dose and effect. The largest analysis to date included only seven cases of bladder cancer. No investigation has estimated the risk of kidney cancer. PURPOSE: The purpose of this study was to quantify the risk of bladder and kidney cancer following cyclophosphamide therapy. METHODS: Within a cohort of 6171 two-year survivors of non-Hodgkin's lymphoma (NHL), 48 patients with secondary cancer of the urinary tract were identified and matched to 136 control subjects with NHL who did not develop a second malignancy. Detailed information on chemotherapeutic drugs and cumulative dose received was collected for all subjects. Radiation dose to the target organ was estimated from individual radiotherapy records. Evaluations of the risk of second cancer as a result of treatment with cyclophosphamide alone, radiation alone, or both therapies were made relative to those patients who were exposed to neither treatment modality. RESULTS: A significant 4.5-fold risk of bladder cancer (95% confidence interval [CI] = 1.5-13.6) followed therapy with cyclophosphamide, and risk was dependent upon cumulative dose. Among patients who received a total amount of cyclophosphamide of less than 20 g, a nonsignificant 2.4-fold risk of bladder cancer was apparent. Significantly elevated sixfold (95% CI = 1.3-29) and 14.5-fold (95% CI = 2.3-94) risks of bladder malignancy followed cumulative doses of 20-49 g and 50 g or more, respectively (P value for trend = .004). Radiotherapy given without cyclophosphamide was associated with a nonsignificant increased risk of bladder malignancy. Excess bladder cancer risk following treatment with both radiotherapy and cyclophosphamide was as expected if individual risks were summed. Neither radiotherapy nor cyclophosphamide was associated with excesses of kidney cancer. CONCLUSIONS: Cyclophosphamide-related bladder cancer is dose dependent. For patients given cumulative doses between 20 and 49 g, the absolute risk of bladder cancer is on the order of three excess cancers per 100 NHL patients after 15 years of follow-up. At cumulative doses of 50 g or more, the excess risk increases to approximately seven excess bladder cancers per 100 NHL patients. IMPLICATIONS: The strong dose-response relationship and high absolute risk of bladder cancer underscore the importance of limiting the cumulative dose of cyclophosphamide to what is required to achieve therapeutic end points. The risk of secondary bladder malignancy and other late sequelae of therapy must be carefully weighted against the curative gains provided by cyclophosphamide. Moreover, long-term side effects of therapy that might be acceptable in cancer treatment may need to be re-evaluated for patients with non-neoplastic disorders.

Risk of leukemia following treatment for non-Hodgkin's lymphoma.

BACKGROUND: There have been few evaluations of the risk of acute nonlymphocytic leukemia (ANLL) following therapy for non-Hodgkin's lymphoma (NHL). Further, the relationship between cumulative dose of cytotoxic drug, radiation dose to active bone marrow, and the risk of ANLL following NHL have not been well described. PURPOSE: Our purpose was to examine the risk of ANLL in relationship to all prior treatment for NHL. METHODS: Within a cohort study of 11,386 2-year survivors of NHL, 35 case patients with secondary ANLL were identified and matched to 140 controls with NHL who did not develop ANLL. The primary eligibility criteria for the cohort included a diagnosis of NHL as a first primary cancer from January 1, 1965, through December 31, 1989; age 18 through 70 years at the time of initial diagnosis; and survival for 2 or more years without the development of a second invasive primary malignancy. Detailed information on chemotherapeutic drugs and radiotherapy was collected for all patients. Standard conditional logistic regression programs were used to estimate the relative risk (RR) of ANLL associated with specific therapies by comparing the exposure histories of case patients with individually matched controls. RESULTS: Significant excesses of ANLL followed therapy with either prednimustine (RR = 13.4; 95% confidence interval [CI] = 1.1-156; P trend for dose < .05) or regimens containing mechlorethamine and procarbazine (RR = 12.6; 95% CI = 2.0-79; P < .05). Elevated risks of leukemia following therapy with chlorambucil were restricted to patients given cumulative doses of 1300 mg or more (RR = 6.5; 95% CI = 1.6-26; P < .05). Cyclophosphamide regimens were associated with a small, nonsignificant increased risk of ANLL (RR = 1.8;95% CI = 0.7-4.9), with most patients receiving relatively low cumulative doses (< 20,000 mg). Radiotherapy given at higher doses without alkylating agents was linked to a nonsignificant threefold risk of ANLL compared with lower dose radiation or no radiotherapy. CONCLUSIONS: Our results suggest that prednimustine may be a human carcinogen, with a positive dose-response gradient evident for ANLL risk. The low, nonsignificant risk of leukemia associated with cyclophosphamide was reassuring because this drug is commonly used today. Despite the excesses of ANLL associated with specific therapies, secondary leukemia remains a rare occurrence following NHL. Of 10,000 NHL patients treated for 6 months with selected regimens including low cumulative doses of cyclophosphamide and followed for 10 years, an excess of four leukemias might be expected.

Changes in diagnosis of non-Hodgkin's lymphomas over time.

The question is raised as to whether changes in criteria for the diagnosis of non-Hodgkin's lymphomas, both clinical and pathological, have changed over the past four decades in sufficient scale to create a spurious increase in the apparent incidence of this grouping of disease. In the decade of the 1970s refinement in histomorphological criteria for the diagnosis of Hodgkin's disease resulted in as many as 10-15% of cases which previously would have been diagnosed as Hodgkin's disease being diagnosed instead as non-Hodgkin's lymphoma. Other considerations, including distinction of non-Hodgkin's lymphomas from leukemias and plasma cell myelomas, and recent recognition of angioimmunoblastic lymphadenopathy and extranodal "pseudolymphomas" as variant forms of non-Hodgkin's lymphoma, appear to have added only marginally to the total of reported cases. It is concluded that the increase in reported incidence of non-Hodgkin's lymphoma cannot be explained on the basis of changes in diagnostic criteria.

Clinical correlates of distinct immunophenotypic and histologic subcategories of lymphocyte-predominance Hodgkin's disease.

Histologic and paraffin immunohistologic studies were carried out on 32 patients with lymphocyte-predominance Hodgkin's disease (LPHD) seen from 1970 through 1982. While nodular histology was accurately predictive of B-cell phenotype (Leu M1 -/L26+), diffuse histology corresponded to either B-cell or Hodgkin's (Leu M1 +/L26-) phenotype, not invariably predictable even when attention was paid to subtle paragranuloma cytology. Clinical characteristics were compared between histologic (diffuse v nodular) and immunophenotypic (Leu M1 +/L26-, Hodgkin's phenotype, v Leu M1 -/L26+, B-cell phenotype) subgroups. Ten patients have since died, and the median follow-up of the living patients was 14 years (range, 6 to 31). Of the several clinical parameters compared, only axillary nodal presentation was strongly associated with both B-cell phenotype and nodular histology, while male predominance related more to B-cell phenotype than nodular histology. No significant difference in overall survival or relapse rate was apparent among either the histologic or the immunophenotypic subgroups. However, very late but salvageable relapses were associated with nodular histology. The incidences of secondary malignancies and death from Hodgkin's disease (HD) were also comparable between the subgroups. Although difference in clinical presentation may exist, neither the histologic nor the immunophenotypic subcategories of LPHD could be demonstrated to correlate with differences in clinical outcome.

Patterns of failure in primary testicular non-Hodgkin's lymphoma.

Patterns of failure were analyzed in 30 patients with testicular non-Hodgkin's lymphoma: 16 had stage IE disease, ten had stage IIE, and four had stage IV. After orchiectomy, two of the 16 patients with stage IE disease received no additional therapy, one received multiagent chemotherapy, and 13 received pelvic and para-aortic radiation. Twelve patients with stage IE disease had progression, and the median time to progression was 12 months. Of the 14 patients with extratesticular involvement (stage IIE or IV), one (stage IV) received no treatment after orchiectomy, three (stage IIE) received para-aortic and pelvic radiation, and ten (seven stage IIE and three stage IV) received multiagent chemotherapy with or without radiation. Eight of the patients with stage IIE or IV disease had progression, and the median time to progression was 11 months. Widespread extranodal progression was observed in 17 of the 20 patients who had progression. The tendency of testicular lymphoma for early systemic progression suggests a need for multiagent chemotherapy in initial management.

Leukemia following low-dose total body irradiation and chemotherapy for non-Hodgkin's lymphoma.

PURPOSE: Low-dose total body irradiation (TBI) is used to treat non-Hodgkin's lymphoma (NHL) and several other malignancies. Large volumes of bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae. PATIENTS AND METHODS: A cohort of 61 2-year survivors of NHL treated initially with low-dose TBI was monitored for second cancer occurrence. Data on primary and subsequent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed. RESULTS: Thirteen second primary cancers occurred. Four patients developed acute nonlymphocytic leukemia (ANLL), which represents a relative risk (RR) of 117 (95% confidence interval [CI], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (MDS). All five patients with secondary hematologic malignancies subsequently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight solid tumors were observed (RR = 2.0; 95% CI, 0.9 to 4.0). The 15-year cumulative risks of all second cancers and secondary ANLL were 37% and 17%, respectively. CONCLUSIONS: Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated with low-dose TBI in combination with CMT including alkylating agents. Based on these results, approximately eight to nine excess ANLLs might be expected to occur among 100 NHL patients treated with low-dose TBI and salvage treatment and followed-up for 15 years.

New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia.

PURPOSE: To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia. PATIENTS AND METHODS: We studied a cohort of 3, 182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age- and sex-matched general population. Risks factors were evaluated using Poisson regression. RESULTS: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P <.001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR = 6.5), unrelated or HLA-disparate related donor (RR = 7. 5), T-cell-depleted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1). CONCLUSION: Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers.

Splenectomy for Felty's syndrome. Clinicopathological study of 27 patients.

The major clinical and pathological features and the long-term follow-up of 27 patients with Felty's syndrome who were treated with splenectomy for sever granulocytpenia and for acute, chronic, or recurrent infection were studied. Granulocyte counts rose within days in most patients, although slow responses and transient granulocytopenia did occur; only 12% of the patients had persistent or recurrent granulocytopenia. Infections resolved promptly in 77% of the patients, more slowly in the remainder, and only one patient had new problems of infection after aplenectomy. Splenic enlargement, present in all but one case, was attributable to expansion of the sinusoidal pulp. The most substantial pathological features of immune stimulation included germinal center hyperplasia and prominent clusters of plasma and preplasma cells within sinuses.

A novel highly differentially expressed gene in wheat endosperm associated with bread quality.

Analysis of gene expression in developing wheat seeds was used to identify a gene, wheat bread making (wbm), with highly differential expression (~1000 fold) in the starchy endosperm of genotypes varying in bread making quality. Several alleles differing in the 5'-upstream region (promoter) of this gene were identified, with one present only in genotypes with high levels of wbm expression. RNA-Seq analysis revealed low or no wbm expression in most genotypes but high expression (0.2-0.4% of total gene expression) in genotypes that had good bread loaf volume. The wbm gene is predicted to encode a mature protein of 48 amino acids (including four cysteine residues) not previously identified in association with wheat quality, possibly because of its small size and low frequency in the wheat gene pool. Genotypes with high wbm expression all had good bread making quality but not always good physical dough qualities. The predicted protein was sulphur rich suggesting the possibility of a contribution to bread loaf volume by supporting the crossing linking of proteins in gluten. Improved understanding of the molecular basis of differences in bread making quality may allow more rapid development of high performing genotypes with acceptable end-use properties and facilitate increased wheat production.

Angiofollicular lymph node hyperplasia (Castleman's disease).

This review provides a comprehensive assessment of angiofollicular lymph node hyperplasia (ALNH) or Castleman's disease including pathogenesis, clinical presentation, histomorphologic and immunophenotypic findings, laboratory results, treatment, and prognosis. A division of ALNH into clinically relevant subtypes provides a framework for the consideration of the disorder. A comprehensive search of the medical literature involving ALNH using Medline was performed. Reports judged to be significant for the understanding of the disorder were analyzed and their findings incorporated into this review. ALNH is divided into localized/unicentric ALNH and generalized/multicentric ALNH due to the profound clinical differences seen between these variants. Localized/unicentric ALNH is separated by clinical and histomorphologic criteria into hyaline-vascular (HV) and plasma-cell (PC) subtypes. Generalized/multicentric ALNH may be divided by clinical criteria into generalized/multicentric ALNH without neuropathy (non-neuropathic) and generalized/multicentric ALNH with neuropathy (POEMS-associated or neuropathic). The dichotomy between these two subtypes is not absolute, with considerable clinical overlap occurring among patients presenting with generalized disease. Immunophenotypic and molecular probe studies demonstrate clonal B-cell lymphocyte populations in some cases, particularly those with generalized/multicentric ALNH. However, the finding of clonal populations is of no value in predicting malignant clinical progression. We conclude that using this division of ALNH, patients presenting with symptoms and histomorphology consistent with ALNH can be subdivided into the appropriate category of ALNH. Localized or unicentric disease, either HV or PC subtype, has an excellent prognosis with surgery being curative in the majority of cases. Generalized or multicentric disease indicates a poor prognosis with short survival, with the neuropathic variant possessing resistance to steroids and chemotherapy and a corresponding worse prognosis.

Computer-assisted stereotaxic biopsy for the diagnosis of primary central nervous system lymphoma.

Primary CNS lymphoma was diagnosed in 13 patients after stereotaxic biopsy of indeterminate intracerebral mass lesions. Two patients also had laser extirpation of CT-visible tumor. The group consisted of 10 men and 3 women, aged 17 to 81 (mean, 55 years; median, 60 years). The lesions on CT were characteristically hyperdense, homogeneously contrast-enhancing, and associated with mild to moderate mass effect. Five patients had more than one lesion visible on CT. Complete staging procedures for occult systemic lymphoma were negative in all 13 patients. The majority (eight) of the tumors were of the diffuse, large-cell type. Five biopsy specimens underwent special immunostaining as a supplemental diagnostic effort. Two patients with small lymphocytic tumors demonstrated features consistent with T cell phenotype. Two patients with diffuse, large-cell tumors were confirmed as B cell phenotype by monotypic immunoglobulin light chain content. Primary CNS lymphomas represent a treatable group of primary brain tumors. Because of their tendency to develop in deep cerebral regions, they are often inaccessible to conventional neurosurgical techniques. We propose that stereotaxic neurosurgery can provide safe and accurate diagnosis, which is a prelude to planning comprehensive management.

Anaplastic plasma cell myeloma and immunoblastic lymphoma. Clinical, pathologic, and immunologic comparison.

To test whether highly anaplastic myeloma and immunoblastic lymphoma are truly identical disease processes, simultaneous series were compared in respect to cytomorphologic features, immunoglobulin content or secretion, clinical and laboratory findings, and patient survival. Although the series partially overlapped in each studied feature, different trends served to distinguish them. Of the 14 patients with myeloma, all were dead at two years, whereas six of the 22 patients with lymphoma were disease-free at 35 to 78 months. Only 50 percent of patients with myeloma received intensive chemotherapy, whereas all 19 patients with stage III or IV lymphoma received such therapy. Myelomas secreted predominantly IgA heavy chain rather than IgG and lambda light chain rather than kappa. Lymphomas contained predominantly IgM rather than IgG and kappa rather than lambda. There were no IgM myelomas and no IgA lymphomas. The shorter survival of patients with the extremely anaplastic form of myeloma, as compared with patients who had immunoblastic lymphoma, may relate, in part, to prior therapy for previous lower grade myeloma; however, intrinsic differences in the nature of these two disease processes are reflected in their disparate immunologic characteristics.

Malignant lymphoma of plasmablastic identity. A neoplasm with both "immunoblastic" and plasma cellular features.

A solitary extramedullary lymphoid neoplasm had characteristics of plasma cell precursors or plasmablasts. Conventional microscopic study classified this tumor as a diffuse large cell lymphoma of "immunoblastic sarcoma" type. Immunologic cell surface markers could not be detected, but cytoplasmic immunoglobulin G (IgG)-kappa was demonstrated by immunoperoxidase technic, and IgG was present in the supernatant of the tumor tissue culture. The distinction between lymphoid and plasma cellular neoplasms is made.

American Burkitt's lymphoma: a clinicopathologic study of 30 cases. II. Pathologic correlations.

Thirty cases of malignant lymphoma, undifferentiated, Burkitt's type are reviewed. An older median age and a predominance of presentation in abdominal and pelvic sites rather than in the jaw distinguishes this series of American patients from those reported from endemic regions in Africa. Bone marrow involvement invariably consisted of massive infiltration recognizable in smear, clot and biopsy preparations. Involvement of the central nervous system or bone marrow was always associated with short survival. In all eight long-term survivors lymphoma was apparently confined to a single site at presentation. At autopsy, the most consistent finding was widespread multiorgan involvement without predilection for lymphoreticular structures. The histologic appearance of the tumor changed after chemotherapy, varying from diffuse necrosis within 48 hours of initial therapy to extreme pleomorphism of tumor cells after 9 months of therapy. In one patient, there was almost complete absence of lymphoma at autopsy in an organ site shown clinically to have been extensively involved by tumor prior to treatment. The diagnostic and therapeutic implications of these findings are discussed.

American Burkitt's lymphoma: a clinicopathologic study of 30 cases. I. Clinical factors relating to prolonged survival.

The presenting clinical characteristics and the results of therapy in 30 cases of American Burkitt's lymphoma are described. Five patients presented with localized disease. The abdomen was the most frequent site of involvement (19 cases). Serum lactic dehydrogenase (LDH) levels closely correlated with extent of tumor mass. Of the 22 patients treated with large doses of parenteral cyclophosphamide, complete remission was achieved in 13 (59 per cent). Of these only four have had a relapse, all within 12 months of treatment. The remainder are alive, free of disease and have not received any treatment for up to 80 months or more. The site and volume of tumor mass predicted for prolonged survival. None of the six patients with bone marrow or central nervous system involvement remained tumor-free. A complete remission was achieved in 8 of 9 patients with presenting LDH levels of less than 700 IU/ml and they have remained free of disease, whereas only 4 of 13 patients with LDH levels greater than 700 IU/ml had a complete response and 3 of these had a relapse within 12 months. In six cases, the massive tumor regression following chemotherapy was associated with serious metabolid consequences including hyperkalemia (six cases), hypocalcemia, hyperphosphatemia (one case) and lactic acidosis (one case). There were four sudden deaths in less than 48 hours after chemotherapy; two of these were attributable to hyperkalemia. In all cases therw were large tumor masses and/or elevated serum LDH levels.

Infectious mononucleosis mimicking a B cell immunoblastic lymphoma associated with an abnormality in regulatory T cells.

An elderly woman is described with infectious mononucleosis in whom cervical node biopsy was interpreted as showing immunoblastic lymphoma. Concomitant reactive lymphocytosis, Epstein-Barr virus serologic results consistent with an acute infection, and demonstration of polyclonal B cell infiltration of other tissues argued against intervention. Defective in vitro T cell responses were demonstrated during the acute phase of Epstein-Barr virus infection. Infectious mononucleosis has rarely been reported as mimicking a non-Hodgkin's lymphoma. At 18 months, our patient's course has been typical for infectious mononucleosis with no evidence of disseminated malignancy.

Polymicrobial cholangitis and Kaposi's sarcoma in blood product transfusion-related acquired immune deficiency syndrome.

Before presenting to the Mayo Clinic, a 24-year-old white woman had received 35 transfusions of blood products over a 72-hour period in February 1981. Two and one half years later, the diagnosis of polymicrobial cholangitis (Cryptosporidium, Candida albicans, and Klebsiella pneumoniae) was established. Further evaluation demonstrated profound helper T lymphocyte suppression, disseminated Mycobacterium avium-intracellular infection with mycobacteremia, and Kaposi's sarcoma of lymphoid tissue, confirming a diagnosis of acquired immune deficiency syndrome (AIDS). This case represents an unusual infectious complication of AIDS. Additionally, this is believed to be the first report of Kaposi's sarcoma occurring in a patient with AIDS associated with blood product transfusion.

Radiotherapeutic management of primary thyroid lymphoma.

The purpose of this study was to evaluate the radiotherapeutic management of 38 patients, with malignant lymphoma of the thyroid, seen at the Mayo Clinic between 1965 and 1979. There were 8 males and 30 females with ages ranging from 34 to 90 years (mean age of 65 years). A tissue diagnosis was made in all patients and tissue was available for reclassification under the "Working Formulation" in 31 of the 38 patients. Twenty-six patients had intermediate grade histology, four low grade and one indeterminate. Twenty patients were clinical Stage IE, 14 patients Stage IIE, one patient Stage IIIE, one patient Stage IV and two patients were unstaged. All patients were treated with approximately 4000 rad megavoltage irradiation (range 2400-6000 rad) to the neck only (10 patients) or neck and mediastinum (28 patients). Twenty patients received subdiaphragmatic radiotherapy and four patients received adjuvant chemotherapy. Median follow-up was 56 months with minimum follow-up of 30 months. Overall disease-free survival at five years was 59%. Of 14 patients who experienced a recurrence, 10 (71%) failed in two or more sites. The most common site of failure was in para-aortic lymph nodes. One year survival following recurrence was 29%; however, four of six patients receiving salvage therapy survived at least two years. Patients receiving radiation treatment to the neck and mediastinum and those with no gross residual disease at the initiation of radiotherapy were less likely to develop a recurrence. Patients receiving a planned break during the course of therapy did not have reduced overall disease-free survival. However, 4 of 20 patients (20%) who received split course therapy failed within the radiation fields compared to 2 of 18 patients (11%) who had no treatment break. Only 1 of 4 patients (25%) receiving adjuvant chemotherapy survived one year. Side effects of radiotherapy were minimal. We believe the radiotherapeutic management of clinical Stage IE and IIE primary thyroid lymphoma should include treatment of the neck, axillae and mediastinum to a dose of approximately 4000 rad using a continuous course technique. Additionally, gross total removal of the disease surgically may be beneficial.