Hodgkin's disease in a national and hospital population: trends over 20 years.

The aim of the study was to investigate the incidence rate and time trends in a national registry population of Hodgkin's disease (HD) and the effects of selection in a hospital population. A national registry population of all HD patients from Norway and a hospital population of HD patients treated at the Norwegian Radium Hospital (NRH) were studied retrospectively from 1971 to 1993. The incidence of non-Hodgkin's lymphomas (NHL) in Norway increased steadily from 1961 in contrast to a stable incidence pattern for HD before 1980 and a decreasing incidence since 1980. Due to improved diagnostic tools after 1980, an increasing proportion of patients previously diagnosed as lymphocyte depleted and unclassified HD were classified as NHL. As these histologies are dominant in older patients, the incidence of older patients with HD and the total population of HD have decreased since 1980. As a result, the proportion of young adults with a favourable histology has increased. These changes may partly explain the increased patient survival observed both in the national and the hospital population. The hospital population comprised 92% of patients aged 15-39 years, 80% of patients aged 40-59 years and 53% of patients aged > 60 years in the national population. The selection of younger patients in the hospital material may explain a higher survival rate as compared with the national population.

Isolation and characterization of heparin from human mastocytoma tissue.

Polysaccharide was isolated from human spleen mastocytoma by proteolytic digestion, precipitation with cetylpyridinium chloride, digestion with chondroitinase ABC, and ion-exchange chromatography on DEAE-cellulose. The final product (0.7 mg per g of starting material, MW 8000) behaved like standard heparin on ion-exchange chromatography and on electrophoresis, and contained D-glucuronic acid, L-iduronic acid, D-glucosamine and sulfate in the proportions expected for heparin. Affinity chromatography on antithrombin-Sepharose separated a distinct high-affinity fraction (4-5% of the total material). Structural analysis of this fraction showed that about 10% of the D-glucosamine residues were N-acetylated, the remainder N-sulfated. The anticoagulant activity of the isolated heparin was 71 B.P. units per mg (whole-blood system), or 30 units per mg (anti-thrombin and chromogenic substrate). 205 and 10-15 units per mg (chromogenic assay) were found for high and low affinity fractions, respectively. These results demonstrate conclusively the occurrence of heparin in a human tissue.

Karyotyping of a hematologic neoplasia developing shortly after treatment for cerebral extragonadal germ cell tumor.

Hematologic malignancies may be associated with mediastinal extragonadal germ cell tumors. It may be that the hematologic malignancy is a part of the natural history of the teratoma, one germ cell tumor line being able to differentiate into hematological cells, or the hematologic malignancy is related to the treatment, or the two malignancies develop independently. Cytogenetic analysis of bone marrow from a patient with a germ cell tumor in the brain and the almost simultaneous appearance of a hematologic neoplasia showed a rearranged karyotype in that all 15 analyzed cells had the same karyotype: 50,XY, +X, +del(1)(p21), +10, +11, -12, +der(12)t(12;?)(q?;?). Our findings were consistent with the interpretation that the hematologic malignancy was derived from the germ cell tumor.

Small cell pleomorphic T-cell lymphoma presenting with cutaneous vasculitis.

The association between cutaneous vasculitis and lymphoproliferative disease has been increasingly recognized. We report a female patient who presented with cutaneous vasculitis which was due to a small cell pleomorphic T-cell lymphoma. In spite of aggressive therapy, she died two years after onset of disease. The clinical picture of vasculitis associated with lympho-proliferative disease is addressed with particular emphasis on symptoms and signs suggesting malignancy rather than vasculitis appearing in concert with well-defined connective tissue disorders.

[Visceral leishmaniasis (kala-azar)]. / Visceral leishmaniasis (kala azar).

Visceral leishmaniasis is a serious zoonosis which has very rarely been diagnosed in Norway. We report a case of visceral leishmaniasis in a Norwegian patient, and present an up-to-date review of the disease. We conclude that this disease should be considered even in Scandinavian patients if the appropriate symptoms and signs are present and there has been possibility of exposure. Simple blood tests and serum electrophoresis are of considerable value. If possible, the protozoa should be demonstrated by microscopy of bone marrow aspirate. We also discuss the identification of the parasites in bone marrow biopsy, which should be performed in pancytopenic patients. The diagnosis should be confirmed by culture or a serological test.

Hexagonal crystals in the bone marrow in patients with myeloproliferative disease and preleukaemia.

In epoxy resin-embedded bone marrow biopsies from 238 cases of myeloproliferative disease and preleukaemia, crystalline inclusions were found in the bone marrow cells of 24 (10.1%), most often in patients with acute myeloproliferative disease (23%). By light microscopy the crystals were easily recognized after Giemsa staining, lying within the cytoplasm of bone marrow macrophages. By electron microscopy the hexagonal crystals were encountered chiefly within secondary lysosomes of the macrophages, but also within immature myeloid cells in one of the two cases studied. In the latter a tight-fitting membrane around the crystals suggested that they were of lysosomal origin and represented a form of abnormal granulation. We suggest that the presence of crystals in myeloid cells represents a kind of abnormal granula formation in the neoplastic cells. In the macrophages the crystals lodge in secondary lysosomes, probably after phagocytosis of crystal-bearing non-viable myeloid cells. The accumulation of crystals in lysosomes indicates resistance to degradation.

T-zone lymphoma with predominance of 'plasmacytoid T-cells' associated with myelomonocytic leukaemia--a distinct clinicopathological entity.

In this paper we present a further case of a new clinicopathological entity combining a rare type of non-Hodgkin lymphoma with a myelomonocytic leukaemia. The characteristic feature of the lymphoma is massive infiltration of the T-zones of lymph nodes by plasmacytoid cells originally described by Lennert in non-specific lymphadenitis. Two lymphoma cases of this type have recently been published, by Müller-Hermelink et al. who named the cells 'plasmacytoid T-cells' (PTC), and by Prasthofer et al. These three cases have similar clinical and pathological features and appear to form a distinct clinicopathological entity. In contrast to the two previously published cases the present lymphoma also contained irregular lymphoid cells accompanying the PTC in the lymph node lesion and focally infiltrating the bone marrow. An accumulation of polytypic IgG positive plasma cells was observed in the remaining lymph node follicles. Immunohistological analysis with a range of monoclonal antibodies showed the PTC of our case to be CD5(T1)+, CD4(T4)+, CD3(T3)-, CD8(T8)-, CD2(T11)-, and CD25(TAC)-, but HLA-DR+ and transferrin receptor positive. The nature of this peculiar lymphoid lesion and its relationship to myelomonocytic leukaemia are discussed.

A 10-year experience with splenectomy in patients with malignant non-Hodgkin's lymphoma at the Norwegian Radium Hospital.

BACKGROUND: Splenectomy is a major surgical intervention that has many implications for patients with malignant non-Hodgkin's lymphoma. As debated during the last few decades, the therapeutic benefit must outweigh the surgical risk and the loss of cellular immunity. A more liberal attitude toward splenectomy developed during the years 1980-1990 at the Norwegian Radium Hospital, as illustrated by the higher number of operations performed in the last 5 years (21 patients) compared to the first 5 years (14 patients). METHODS: A 10-year retrospective review of the effects and side effects of splenectomy in 35 patients with malignant non-Hodgkin's lymphoma was performed, based on information obtained from the patient files at the authors' institution. RESULTS: Clinical Stage IV disease was found in 29 patients (83%), and B symptoms in 15 patients (43%). At diagnosis, 26 patients (74%) had splenomegaly, and 8 patients (23%) had primary splenic lymphoma. The surgical mortality was 2.9%, and the morbidity was 37%. Infection was the most common complication, occurring in seven patients (20%). Pneumococcal vaccination had been performed in 13 patients, and the frequency of septicemia and pneumonia tended to be higher during follow-up in unvaccinated patients (not significant). Blood counts returned to normal during the first postoperative month in 18 of 25 patients (72%) who had cytopenia. After splenectomy, a durable remission was achieved in five patients (14%) who did not receive subsequent treatment. CONCLUSIONS: Splenectomy has the potential to relieve local symptoms, correct cytopenias, and modify the disease course in patients with malignant non-Hodgkin's lymphomas, even in advanced stages, at the cost of an acceptable operative risk.

Appearance of trabecular bone in the femoral neck (Singh index). Relation to vertebral bone mass post mortem.

In 89 consecutive cases trabecular bone mass of the second or third lumbar vertabra was subjectively estimated in post mortem specimens, using frontal section 1 cm in thickness. The trabecular appearance of the femoral neck (Singh index) at radiography and the thickness of the femoral cortical bone were also determined. Agreement between vertebral bone mass and either of the two radiologic indices was present in only two thirds of the cases, and most often these indices underestimated the presence of vertebral osteoporosis. The results indicate that neither of these radiologic indices can be used for clinical guidance of the diagnosis of vertebral osteoporosis in the individual case.

Immunologic subsets in B cell lymphomas defined by surface immunoglobulin isotype and complement receptor--their relationship to survival.

Cell surface marker profiles were studied on cell suspensions from monoclonal B cell lymphomas. Surface immunoglobulin (sIg) was examined in 178 cases, whereas combined data with sIg and receptors for complement (C3) were available in 99/178 cases. The results showed that B cell lymphomas can be divided into distinct immunological subsets according to surface marker expression. Whereas some histologic subgroups (diffuse centroblastic/centrocytic, centrocytic, immunocytoma) (Kiel classification) consisted of few immunological subtypes, others were more heterogeneous (follicular centroblastic/centrocytic, centroblastic, lymphocytic). By combining immunological and histological subgroups, more than 40 phenotypes could be identified; this diversity most likely reflects, the heterogeneity of the B cell compartment. As part of the same study the prognostic significance of cell marker phenotypes was examined. Survival analysis undertaken on 149/178 patients did not uncover any significant relationship between type of heavy or light chain expression, C3 receptor expression and clinical outcome. Our data do not confirm recent findings that the type of immunological phenotype may be of prognostic significance.

Detection of bone marrow metastases in small cell lung cancer patients. Comparison of immunologic and morphologic methods.

An immunocytochemical method, involving four monoclonal antibodies (MAbs) previously selected for their specific binding to small cell lung cancer (SCLC) cells in human bone marrow, was used for detection of bone marrow metastases in 81 patients with diagnosed SCLC. This procedure was compared with two routine morphologic methods with regard to diagnostic efficiency and sensitivity. Bone marrow involvement was found in 26 patients (32%), one of which had limited disease according to conventional clinical criteria. Eight of the positive cases were exclusively diagnosed by immunocytochemistry, whereas the histologic and cytologic methods separately identified two patients each. Immunocytochemistry had a detection level of tumor cells in the mononuclear cell fraction of approximately 1-2%, whereas no patients with less than 10% immunocytologically detectable tumor cells were diagnosed by cytomorphologic examination of bone marrow aspirates. Evidence was obtained that the diagnostic efficiency of any method increased with the number of samples examined. Of the four MAbs used, the anti-NCAM antibody, MOC-1, labeled tumor cells in all immunologically positive patients, and in all but one of these patients all cytologically confirmed tumor cells were stained. The antibodies MOC-31, which recognize a cluster-2 antigen, and NrLu10 bound nearly all tumor cells in most cases, whereas MLuC1 only diagnosed tumor cells in a fraction of the patients. The results show that the immunocytochemical application of these antibodies is superior to morphologic techniques in detecting SCLC bone marrow metastases. Further use of the method might provide prognostically and therapeutically useful information.

Extramedullary plasmacytomas and solitary plasma cell tumours of bone.

We describe clinical features and treatment results in 25 patients with solitary osseous (SOP) and 18 patients with solitary extramedullary plasmacytoma (EMP). 41 patients were treated with high-voltage radiotherapy, median 40 Gy in 20 fractions. Surgery was part of the treatment in 21 and chemotherapy in 5 patients. The median age in both groups was 56 years, with a preponderance of males. Myelomatosis developed in 10 SOP and 2 EMP patients, and this development did not correlate with the presence or absence of an M-component at the time of diagnosis of plasmacytoma. The estimated 5- and 10-y survival was 87% and 76% without a statistical difference between SOP and EMP groups. The patients in the SOP group usually died from myelomatosis while EMP patients died from other causes.

[Non-Hodgkin's lymphoma in the gastrointestinal tract]. / Non-Hodgkins lymfom i gastrointestinaltractus.

The gastrointestinal tract is the predominant site of extranodal non-Hodgkin's lymphoma. We present a summary of our recommendations as regards treatment. To avoid serious complications, such as perforation and/or bleeding, surgical resection should be considered before chemotherapy or radiation therapy. The laparotomy gives an opportunity to perform an exact staging procedure, including biopsy from the primary site and the lymph nodes. We recommend that gastrointestinal malignant lymphomas should be referred to medical centers with special competence in this field.

Bone-marrow MR imaging before and after autologous marrow transplantation in lymphoma patients without known bone-marrow involvement.

PURPOSE: To study lumbar bone marrow by means of MR imaging before and after bone-marrow transplantation in lymphoma patients. Particular emphasis was paid to heterogeneity and to focal manifestations, i.e. appearances that could simulate tumor. MATERIAL AND METHODS: Twenty-two patients who were disease-free for a minimum of 30 months after transplantation were studied in 107 MR examinations. Two radiologists visually evaluated coronal T1-weighted and short inversion time inversion-recovery (STIR) images. RESULTS: T1-weighted images demonstrated a more heterogeneous marrow after transplantation than before it. Sharply defined focal low signal intensity areas appeared on this sequence in 5 (23%) of the 22 patients at between 21 and 60 weeks after transplantation. The mean age of these 5 patients was 48.4 years (range 42-54 years). The difference in age between these 5 patients and the remaining 17 patients, who had a mean age of 33.4 years (range 14-51 years), was statistically significant (p < 0.01, Student's t-test, 2-sided test). CONCLUSION: Sharply defined focal low signal intensity areas may be seen on T1-weighted images of bone marrow in patients who are in complete remission after transplantation, particularly in those aged over 40-45 years.

Stage I high-grade non-Hodgkin's lymphoma.

We report long-term survival and prognostic factors in 252 patients with stage I high-grade lymphoma. Median patient age was 64 years and 49% of patients had extranodal lymphoma. Premenopausal women had less risk of extranodal lymphoma than older women or males (p < 0.002). Disease specific 5 and 15 years' survival in patients < 64 years was 83% and 76%, respectively; compared to 54% and 46% in patients > 64 years of age. Age, non-centroblastic histology, B-symptoms, and increased serum lactate dehydrogenase (LDH) were independently negative prognostic factors (p < 0.01), while extranodal, testicular, or bulky ( > 6 cm) lymphoma presentation were of no prognostic significance. A radiation dose of 40 Gy in 2 Gy fractions to the primary site prevented in-field relapse in 159 of 173 irradiated patients (92%) and only three of 173 patients (1.7%) had local relapse in the absence of systemic dissemination.

[Giant cell anaplastic anemia]. / Storcellet anaplastisk lymfom.

The Ki-1-antibody was raised against a cell-line of Hodgkin-cells, and reacts with most Hodgkin- and Reed-Sternberg-cells. By use of this antibody a new entity of non-Hodgkin's lymphomas has been identified; the anaplastic large cell lymphoma. We report our experience from studying 16 such tumours diagnosed during the period October 1986 to February 1988. In three cases the anaplastic large cell lymphoma appeared in patients who presented Hodgkin's disease as well. Of 15 cases studied using frozen section immunohistochemistry, ten showed T-, one B-, and one monocyte/macrophagephenotype, whereas three cases presented a mixed T-, B- and monocyte/macrophagephenotype. All cases showed a high proliferative activity as evaluated by presence of activation antigens. In paraffin sections six of 16 cases expressed epithelial membrane antigen (EMA). In 13 cases EMA, leucocyte common antigen (LCA) and Ber-H2 (a Ki-1-antibody) reactivity was compared in paraffin and frozen sections. The EMA reactivity was of nearly equal intensity in paraffin and frozen sections, while the reactivity of LCA and Ber-H2 was significantly reduced in paraffin sections, implying only partial preservation of the antigens. Clinically, most cases were in an advanced (III and IV) stage by the time of diagnosis. Of 14 actively treated patients, nine went into complete and two into partial remission, while three patients did not respond. Six patients are dead, five after less than one year. The coexistence of anaplastic large cell lymphoma and Hodgkin's disease and the common Ki-1 (CD30) antigen expression in these tumours suggest a possible histogenetic relationship.

[Diagnosis and treatment of solitary plasmacytoma]. / Diagnostikk og behandling av solitaere plasmacytomer.

Solitary plasmacytomas are rare tumours. We report our experience from 25 solitary osseous and 18 solitary extramedullary plasmacytomas. 41 patients were given high voltage radiotherapy, usually 40 Gy in 20 fractions. Two patients with extramedullary plasmacytoma developed generalized disease, while ten patients with osseous plasmacytoma developed myelomatosis. Extramedullary plasmacytomas are usually cured by adequate local treatment, while in solitary osseous plasmacytomas the prognosis is more dubious.

Enlargement of the thymus following chemotherapy for non-seminomatous testicular cancer.

The thickness of the largest thymic lobe at computed tomography (CT) was measured retrospectively in 21 relapse free patients who had undergone chemotherapy for non-seminomatous testicular cancer. CT was performed at initial staging, at completion of chemotherapy and 3 to 12 months later. Enlargement of the thymus occurred in 7 patients, one of whom had a reduced thymic size at the first two examinations after chemotherapy. A temporary reduction was detected in another patient in whom the original thymic size was regained 19 months after start of chemotherapy. The mean age of the group with thymic enlargement was 21 years compared with a mean age of 28 years in the group with no increased size. The age difference between the two groups was significant (p less than 0.05, Mann-Whitney U test). To reduce the number of explorative thoracotomies the frequent occurrence of thymic enlargement after chemotherapy for non-seminomatous testicular cancer should be kept in mind.

Bone marrow examination in Hodgkin's disease.

Bone marrow aspiration and biopsy was performed as part of routine staging in 425 patients with primary Hodgkin's disease. Only seven patients were found to have bone marrow disease by biopsy and only four by aspiration. All these patients had B symptoms and stage III or IV before bone marrow examination. Bone marrow infiltration did not influence treatment decision and there was no association between bone marrow findings and outcome of the disease.

[Human T-cell lymphotrophic virus type I and T-cell lymphoma]. / Humant T-cellelymfotropt virus type I og T-cellelymfom.

Human T-cell lymphotropic virus type I is an oncogenic retrovirus, endemic in Southwestern Japan, the Caribbean, some parts of Africa and Central and South America. The virus is etiologically associated with adult T-cell leukemia/lymphoma and a myelopathy called tropical spastic paraparesis or HTLV-I associated myelopathy. Transmission of the virus is almost identical to that of HIV. The latency period before onset of clinical symptoms can last from a few years (tropical spastic paraparesis) up to several decades (adult T-cell leukemia/lymphoma). Four different clinicopathological subtypes of the T-cell neoplasia are known, and in this article we describe two patients with the subtype lymphoma.