A transitional variant of a T-lymphoproliferative malignancy. Two cases of cutaneous T-cell lymphoma co-expressing E and Fc gamma receptors with final leukaemic transformation.

2 cases of malignant T-lymphoproliferative disease are reported. The proliferating cell was a large blast expressing E and Fc gamma receptors but no helper or suppressor phenotypes and no SmIg. Skin infiltrates were the dominant clinical sign with conspicuous perivascular aggregations of T, E, Fc gamma lymphocytes, though both patients initially had disseminated disease with mild lymphadenopathy, splenomegaly and, in case 2, also hepatic infiltrations. Accordingly, DNA measurements on skin biopsies, taken early in the course, showed a dominating hypotetraploid clone (case 1) and a pronounced population in S-phase (case 2). The patients were alive for 6 and 2 yr, respectively, with a final fatal course of about 6 months duration involving a rather sudden progression of the skin infiltrates, increasing lymphadenopathy and splenomegaly, leukaemic transformation of the neoplastic T, E, Fc gamma lymphocyte and practically no response to cytostatic treatment.

Prediction of survival in adults with acquired Bi- or pancytopenia.

In a retrospective study of 44 adults with acquired bi- or pancytopenia without evidence of any causal disorder, the survival curve suggested the existence of a subgroup of short survivors, mainly with aplastic anaemia, with death within 4 months. The initial values of 14 single clinical, blood and bone marrow variables were significantly associated with survival less than 4 months. Stepwise multiple logistic regression analyses identified 2 combinations of variables displaying significant simultaneous associations with short survival: (i) increased % of non-myeloid bone marrow cells and haemorrhagic manifestations initially; (ii) increased % of non-myeloid marrow cells, circulating erythroblasts and no history of any drug exposure. The predictive capacities of a resulting estimate of the probability of short survival and of previously introduced prognostic indices were approximately equal. The frequency of a correct prediction of a survival shorter than 4 months was in the range of 0.71-0.78 and that of longer survival in the range of 0.74-0.94.

Spongy lymphoid myelofibrosis as a predictor of hairy cell leukaemia or a variant of hairy cell leukaemia without hairy cells?

8 patients with clinical and haematological features suggestive of hairy cell leukaemia are described. During their initial illness morphologic and cytochemical evidence of hairy cell leukaemia were lacking in all but 2 patients. A common highly characteristic histopathologic finding was reticulin fibrosis in the bone marrow, present in all patients at first presentation. The term spongy lymphoid myelofibrosis is proposed for such cases, which may represent a variant type of hairy cell leukaemia or an early stage of the disease.

Two additional cases of coexisting polycythaemia vera and chronic lymphocytic leukaemia.

2 patients with coexistent polycythaemia vera and chronic lymphocytic leukaemia are described. A 61-year-old man presented with an increased packed cell volume (PCV) and a leucoerythroblastic blood picture, which was reversible upon treatment, neutrophil leucoytosis, bone marrow lymphocyte infiltration and splenomegaly, and subsequently developed lymphomas, blood lymphocytosis and thrombocytosis. The second case was a 58-year-old female presenting with increased PCV and leucocyte alkaline phosphatase score. She later had neutrophil leucocytosis, thrombocytosis, lymphocytosis, lymphomas and splenomegaly. These cases, together with 6 cases published by others, suggest that an association exists between the two diseases.

Malignant centroblastic-histiocytic lymphoma of the skin.

A mixed B-cell type centroblastic lymphoma with extraordinarily many histiocytes in a 68-year-old man is reported. Multiple skin tumours were the only clinical manifestation during the first 5 months. The disease then progressed to the lymph nodes, spleen, and parenchymal organs, but the bone marrow remained unaffected until death, 11 months after the onset of signs. C3d receptors were the only surface markers of the centroblasts. The histiocytes were normal with respect to morphology, muramidase staining, and Fc and C3b receptors. This highly unusual spread from skin to lymphoid and parenchymal organs is discussed in the light of lymphoid cell kinetics.

The applicability of simple blood and bone marrow variables in prediction of acute leukaemia in patients with acquired bi- or pancytopenia.

A retrospective study of 44 patients presenting with acquired bi- or pancytopenia (B/PC) and no evidence of any causal disorder was carried out. 12 patients developed acute non-lymphoblastic leukaemia after 2-51 months. Compared to the nonleukaemic subjects the preleukaemic patients at the onset of B/PC had significantly higher counts of myeloblasts and other myelopoietic cells in the bone marrow, more cellular marrows due to more dense cellularities of all compartments, higher blood granulocyte and monocyte counts, more pronounced anisocytosis, and in some cases a small number of circulating myeloblasts. A stepwise multiple logistic regression analysis identified 3 combinations of variables displaying significant simultaneous association with subsequent leukaemic transformation. Among these the combination of marrow myeloblast percentage and blood granulocyte count might be applicable to early prospective identification of patients with preleukaemic B/PC.

Quantitation of complement C3b and C3d surface receptors on neoplastic IgM positive B lymphocytes.

C3b and C3d complement receptors on the surface of mononuclear cells from blood, lymph nodes, and spleens were investigated in twenty-nine CLL patients and in eight patients with non-Hodgkin malignant lymphoma. Compared with a normal material, especially the lymphoid tissues but also the blood of the patients contained a high number of C3d receptor positive lymphocytes with a strong expression of C3d receptors per cell. The majority of the cells with high C3d receptor expression also had SmIgM. The number of C3b receptor positive cells was decreased in the patients but the C3b receptor expression per cell was normal.

Radiotherapy versus radiotherapy plus chemotherapy in stages I and II Hodgkin's disease. A prospective, randomized study by the Danish National Hodgkin Study Group, LYGRA.

In a multi-centre study in which data from all Danish Hodgkin patients have been registered since 1971, all patients in supradiaphragmatic stages I or II, as confirmed by staging laparotomy, were randomized to either radiotherapy (RT) to supra- and infradiaphragmatic lymph node regions (total nodal irradiation, TNI), or RT to a mantle field followed by 6 cycles of MOPP combination chemotherapy (RT+CT). Interim results up to July 1979, when 237 patients had entered the study, showed a treatment failure rate of 19/117 in the TNI group and 4/120 in the RT+CT group (P less than 0.05). 19 of the 23 relapsing patients were under the age of 40, and 14 in the TNI group and 3 in the RT+CT group belonged to stage II. 13 patients had nodular sclerosis, 9 had mixed cellularity and 1 had lymphocytic predominance histology. 12 of 19 relapsing patients in the TNI group had hilar or mediastinal involvement as against 51 of the 117 patients in the entire group. Most of the TNI failures could be retreated, and as yet there is no difference in the overall survival.

Acute myeloblastic leukaemia in sarcoidosis treated with methotrexate.

A 60-year-old man with sarcoidosis of skin and knee joints was treated with prednisone and methotrexate (MTX). A total of 590 mg MTX was given over two periods each of 3 months duration. 4 1/2 years after the first MTX dose he developed acute myeloid leukaemia. Only one more case of acture myeloid leukaemia following MTX treatment for a benign disease has been described, and until further cases have been reported the correlation might be considered a matter of simple coincidence.

Procarbazine-induced skin reactions in Hodgkin's disease and other malignant lymphomas.

A total of 44 patients with Hodgkin's disease and 23 patients with non-Hodgkin malignant lymphoma were treated with MOPP-combination chemotherapy. 4 patients with Hodgkin's disease and 8 with non-Hodgkin lymphoma developed urticaria or maculo-papular rash. This frequency of hypersensitivity reactions is higher than that expected from the few cases reported in the literature.

Megathrombocytopenia associated with glomerulonephritis, deafness and aortic cystic medianecrosis.

Macrothrombocytopenia associated with glomerulonephritis and deafness has only been reported in a few patients since it was first described in 1972. We present a patient with macrothrombocytopenia, glomerulonephritis, progressive uraemia and progressive sensorineural deafness associated with cystic medianecrosis of the ascending aorta and malformation of the aortic valves. The patient had consistently low platelet counts but no clinical signs of a defect haemostasis. The giant platelets were characterized by their size, averaging 11 micron in diameter, elaborate maze-like membrane formations, abundance of microtubules, and the total absence of very dense granules.

Unique eosinophil granules in a case of T-cell lymphoma.

A 41-year-old man developed intense itching without visible cutaneous changes, epigastric pressure pain, and a slight intolerance to alcohol. He was found to have persistent blood eosinophilia. The eosinophil granulocytes were of abnormal appearance in the light microscope: larger than normal, the nuclei were multilobulated (4-6 lobes), the cytoplasm contained atypical, large granules, ample glycogen, and up to 12 vacuoles. In the electron microscope too the eosinophil granules were entirely atypical, having an electron-dense matrix, often with a light central inclusion body which was inhomogeneous, having longitudinally oriented structures with a periodicity of about 10 nm. These findings are quite contrary to normal eosinophil granules. Enzymic studies of cytoplasmic enzymes from the granulocytes revealed a greatly reduced content of eosinophil cationic proteins, whereas 5 (7) other enzymes were present in a normal or slightly reduced quantity. The phagocytic capacity of the eosinophils against latex particles was normal. The patient developed generalized lymphomas, histologically very malignant, of the convoluted, acid phosphatase positive cell type (T-cell lymphoma). Sub-population studies of lymphocytes from a lymph node revealed 58% TE cells, while the remainder were B cells. At death, 3-1/2 years after the onset of symptoms, severe endomyocardial fibrosis was found. The thymus could not be identified. It is concluded that lymphomas should be described on the bais of clinical, histological, and histochemical criteria as well as studies of lymphocyte sub-populations and that the highly unusual eosinophil granulocytes still deserve particular attention. The endocardial fibrosis is assumed to have been due to substances liberated from the eosinophil cells.

A case of T-cell lymphoma with Sézary cells in the blood and bone marrow accompanied by peripheral T and B lymphocytosis.

A case of T-cell lymphoma occurred in a man, aged 66, whose symptoms started as itching and the appearance of 1-2 cm indurated plaques with central pustules on the skin of the trunk and face. A few months later generalized lymphomas and splenomegaly were present. Investigations of the lymphocytic subpopulations in situ in fresh frozen sections of lymphomas and skin showed only T cells. Samples of blood and bone marrow disclosed lymphocytosis and Sézary cells. Both T and B lymphocytes were definitely increased in the blood. The value of tissue studies in analyzing lymphocytic subpopulations is emphasized as a differential diagnostic aid in classifying lymphomas. A relationship between the T-cell neoplasia and the T and B lymphocytosis to mycosis fungoides and the Sézary syndrome is discussed.

Splenectomy in chronic lymphocytic leukaemia.

In a retrospective study it was endeavoured to evaluate the effects of splenectomy in chronic lymphocytic leukaemia (CLL) characterised by splenomegaly. The material comprises 42 patients subjected to the operation in the course of the past 20 years. In the majority the spleen weighed more than 1000 g. The main indication for splenectomy was anaemia, while in 9 cases it was thrombocytopenia and in 14 cases hypercatabolism. Splenectomy is followed by a pronounced increase in the venous haemoglobin level and platelet count to higher values which have been recorded for up to 3 years after the procedure. In cases where data were available, there has been weight gain and a falling basal metabolic rate. Splenectomy is effective especially in cases predominated exclusively by splenomegaly, but even in cases with marked extrasplenic manifestations, splenectomy often greatly reduces the need for prednisone and cytostatics. Increasing hepatomegaly and lymphomas were not more common after splenectomy than in a control series, and the incidence of infections was not increased after the operation. For comparison, 37 non-splenectomised patients with splenomegaly were assessed. X-radiation of the spleen seems to be insufficient, since usually it has to be repeated. Splenomegaly does not decrease spontaneously and rarely after treatment with prednisone/cytostatics. The findings indicate that splenectomy of patients with CLL and increasing splenomegaly should be performed more often and presumably also earlier than recommended in the literature.

Mu-chain disease in a case of chronic lymphocytic leukaemia and malignant histiocytoma. II. Immunochemical studies.

Agarose gel electrophoresis of serum from the eleventh case of mu-chain disease (mu-CD) showed two distinct abnormal bands due to free light chains and kappa-complexes with other serum proteins. This caused diagnostic difficulties on conventional immunoelectrophoresis, and crossed immunoelectrophoresis with intermediate gel is demonstrated as a superior tool for investigation of mu-CD. A simple rocket immunoelectrophoresis method foe mu-CD screening is also shown. The mu-CD protein had alpha-2-mobility and a part of the protein carried kappa-determinants probably due to secondary binding. Preparative ultracentrifugation and size chromatography on serum demonstrated that the mu-CD protein was present in serum in several sizes, the smallest being a dimer of mu-chains. Due to scarcity of material the abnormal protein could not be characterized further.