Esther Aghai

Primary hepatic lymphoma presenting as symptomatic immune thrombocytopenic purpura

A 33‐year old Arabian man presented with idiopathic thrombocytopenic purpura that did not respond to steroid treatment or splenectomy. A routine liver scan performed after splenectomy showed a large mass in the liver. Four years later, massive gastrointestinal bleeding led to an emergency laparotomy, which revealed well‐differentiated lymphocytic lymphoma extending from the liver to the fundus and lesser curvature of the stomach. A partial gastrectomy was performed. With chemotherapy the liver mass resolved and the platelet counts have normalized for the past 30 months.

Reduced natural killer activity in patients with Fanconi's anemia and in family members

Natural killer (NK) activity was measured in the peripheral blood of a family with Fanconis anemia (FA) and compared to normal controls. One of two children with FA, and 6 of 11 family members had reduced NK activity (less than 30% with an E:T ratio of 25:1) compared to none of 40 controls (p less than 0.001). On retesting 5 of 8 family members and both children with FA had reduced endogenous NK activity compared to 0 of 5 controls (p less than 0.02). The number of NK cells determined by Leu 11b antibody was not reduced in any of the family members. Augmentation with interleukin-2 (IL-2) and alpha interferon (IFN) in those with low endogenous activity was variable. Three demonstrated no response to the 2 immunomodulators, while the 4 others increased to low normal levels. We conclude that some patients with FA and their apparently healthy relatives have reduced NK activity, which appears to be secondary to an intrinsic cell defect.

Increased spontaneous secretion of IL-6 from B cells of patients with B chronic lymphatic leukaemia (B-CLL) and autoimmunity

We studied B cells from 18 patients with B‐CLL, six of them with autoimmune haemolytic anaemia, for spontaneous secretion of IL‐6. Our aim was to determine whether the increased incidence of autoimmune disease found in B‐CLL patients is associated with enhanced spontaneous IL‐6 secretion. IL‐6 was measured by the effect of B cell supernatants on the proliferation of an IL‐6 dependent plasmacytoma cell line T1165. The highest IL‐6 values (7.4±1.8 U/ml) were measured in supernatants derived on day 3 of culture from lymphocytes of the six patients with B‐CLL and concomitant autoimmune disease. The maximal IL‐6 values for 10 patients with B‐CLL only were 2.8±0.3 U/ml and for 10 age‐matched controls, 0.8±0.3 U/ml (P < 0.01, each group compared with the other). We conclude that there is an association between B‐CLL, autoimmune disease and the spontaneous in vitro secretion of IL‐6. Further studies are needed to determine whether the IL‐6 secretion plays a role in the pathogenesis of autoimmune disease in patients with B‐CLL.

Multiple myeloma in the geriatric patient

Consecutive patients with multiple myeloma were studied. The clinical characteristics and survival of 17 patients aged 75 years or more were compared to 42 patients younger than 75 years of age. Of the patients older than 75 years, 14/17 (82%) died in less than 12 months compared to only 11/42 (26%) of those under 75 years old (P < 0.001). Multivariate analysis showed that both age and hemoglobin were significant predictors of survival (P < 0.012 and P < 0.002, respectively) explaining 34.6% of the variance (r = 0.588, P < 0.000), whereas the extent of bone lesions, the presence of more than 50% plasma cells in the bone marrow, the amount of serum monoclonal protein, functional class, and the Salmon and Durie staging system did not significantly add to the analysis. We conclude that the factors that best predict prognosis are hemoglobin levels, and age at pressentation. Different approaches including more appropriate chemotherapeutic regimes and comprehensive geriatric assessment with improved supportive treatment need to be developed for the geriatric patient with multiple myeloma.

Increase in the suppressor-inducer T cell subset in multiple myeloma and monoclonal gammopathy of undetermined significance.

Summary The expression of CD4 (helper‐inducer). CD8 (suppressor‐cytotoxic) and CD4 subpopulations (2H4 and 4B4) were studied in patients with multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS) and in healthy controls. The percentages of CD4 + cells and CD8 + cells among total T cells were not different between the three groups studied. However the percentage of CD4 + cells of the suppressor‐inducer type (CD4 + 2H4 +) was 53 ± 9% in patients with MGUS, and 51 ± 9% in those with MM. comrpared to 46 ± 5 in the controls (P=0.033 and P= 0.07 respectively). A significant negative correlation between serum polyclonal IgM and the percentage of CD4 + 2H4 + cells was found in patients with MM but not in those with MGUS. No difference was found in the percentage of CD4+4B4+ (helper CD4+ cells) between the various groups. These findings suggest that the elevation of the suppressor‐inducer subset occurs prior to clinical manifestations of MM, perhaps as an immune response to the malignant clone. The existence of elevated proportions of CD4 suppressor‐inducer cells was associated with the hypogammaglobulinaemia observed in patients with MM. Since no hypogammaglobulinaemia was present in those with MGUS, additional factors are needed to explain the influence of the CD4 + 2H4 + cells on the production of immunoglobulins.

Accelerated Phase of Chronic Myeloid Leukemia Presenting with Hypercalcemia and a Mediastinal Mass

A patient with chronic myeloid leukemia developed hypercalcemia as a presenting sign of the accelerated phase of the disease. Ultrasound of the neck showed a large hypodense mass connected to the thyroid gland, which was thought to be a parathyorid tumor and the cause of the hypercalcemia. Histology of the surgically removed mass revealed a chloroma. The patient’s course was complicated by respiratory failure and metastatic calcinosis of the lung, an unusual finding in hypercalcemia of short duration.

Fulminant Bilateral Cerebellar Syndrome in a Patient with Chronic Lymphocytic Leukemia

A 55 year old patient with chronic lymphocytic leukemia (CLL) and long-standing excessive lymphocytosis developed a rapidly progressive neurological syndrome. Differential diagnosis focused on two rate neurological complications in this disease: direct brain infiltration by leukemic cells versus progressive multifocal leukoencephalopathy (PML). Tissue diagnosis was not available. Two cerebro-spinal fluid examinations performed during the presence of the acute neurological symptoms were normal. Computed tomography (CT) showed low density lesions without enhancement and no mass effect within the left cerebellum. Magnetic resonance imaging scan (MRI) demonstrated multiple hyperintense areas in the brain stem, right and left cerebellum and right capsula interna, suggestive of demyelinative process. In our opinion these findings were compatible with the diagnosis of PML, but biopsy was not performed. Because of the different therapeutic approach in these two conditions, we feel that tissue diagnosis is warranted in patients with CLL who develop a rapidly progressive central nervous system complication in the presence of normal CSF.

T-cells of multiple myeloma patients triggered by the autologous mixed lymphocyte reaction suppress polyclonal immunoglobulin synthesis

To elucidate the possible role of T‐cells of patients with multiple myeloma (MM) in the suppression of polyclonal immunoglobulin synthesis. T‐cells with and without prior activation by the autologous mixed lymphocyte reaction (AMLR) were added to normal immunoglobulin (Ig)‐secreting cultures. The suppression induced by AMLR‐activated T‐cells from patients with MM was compared to that induced by AMLR‐activated T‐cells from apparently normal controls. The addition of 10% unstimulated autologous T‐cells from patients with MM resulted in minimal suppression of IgG synthesis (87 ± 19% of baseline values for patients and 115 ± 21% for controls, no significant difference). The suppression sharply increased when T‐cells were preactivated by AMLR and then added in the same concentration to the IgG‐secreting cultures (38 + 12% of baseline values for patients compared to 106 + 14% for controls, P < 0.05). AMLR cultures were performed in the presence of adherent monocytes and after their depletion. The T‐cell suppressor effect on normal IgG synthesis was unchanged after monocyte depletion. T‐cells preactivated in the AMLR from patients with MM sharply suppress in vitro polyclonal IgG synthesis, and the activation of these suppressor T‐cells is not dependent on the presence of monocytes.

Hodgkin disease: malignancy, inflammation and abnormal immunity.

The effect of Hodgkin disease cells on the surrounding environment is complex. In the light of recent findings on growth factors and oncogenes a hypothesis on Hodgkin disease is presented. The interrelation of three main features of Hodgkin disease: malignancy, inflammation and abnormal immunity may be explained by the local secretion of platelet-derived growth factor like substances and interleukin-1 like substances by malignant Hodgkin disease cells.

Scintigraphic evaluation of a patient with hemangiosarcoma : labeled red blood cell imaging is nondiagnostic

Perfusion vascularity mismatch is characteristic of liver cavernous hemangiomas. The large blood volume and slow perfusion are responsible for this pattern. Often a large lesion demonstrate «cold» areas within the hemangioma, which are explained by slow or absent perfusion due to localized thrombosis. The authors present a polyvinyl-chloride worker with a large liver lesion whose Tc-99m RBC scintigraphy was consistent with cavernous hemangioma with a «cold» area. The lesion was diagnosed at surgery as hemangiosarcoma. It is concluded that malignant vascular lesions of the liver cannot be differentiated from the benign lesions by RBC imaging alone, because they may demonstrate similar patterns