EXPECTATIVAS DE LOS POBLADORES DEL DISTRITO DE MAÑAZO SOBRE LA ACTIVIDAD

Ten Ghanaian patients have been described in this study who could clearly be diagnosed as splenic lymphoma with villous lymphocytes (SLVL). They had splenomegaly, lymphocytosis and typical circulating lymphocytes with polar villi. The monoclonal nature of SLVL was confirmed by a combination of factors such as serum paraproteins, restricted immunoglobulin light chain expression and clonal rearrangements of the immunoglobulin genes. A further twenty patients partially fulfilled current criteria for SLVL by having splenomegaly and at least 3 0% villous lymphocytes in their peripheral blood. However, monoclonality could not be demonstrated in the majority of these individuals and they did not have a marked lymphocytosis. These 3 0 patients, who comprise groups A and B, were selected from a group of 93 patients with splenomegaly due to various causes, predominantly HMS or African 'CLL'.

African CLL - a misnomer

The existence of SLVL in tropical West Africa may partly explain why 'CLL' in Africa has been reported to be associated

cell lymphoma, such as SLVL. The frequency of classical CLL with lymphadenopathy, hypogammaglobulinaemia and CD5+ lymphocytes in West Africa is not known. The realisation that SLVL in Ghana may be mistaken for CLL has important management implications. Normal first-line treatment for CLL includes chlorambucil although this may not be readily available in tropical countries. Chlorambucil is not appropriate treatment for SLVL which instead, responds well to splenectomy. Thus in the case of these two disorders it is essential to make the correct diagnosis.

Differentiation of SLVL from CLL in this study

This study shows that although diagnoses of SLVL and CLL in Ghana are both made in the presence of splenomegaly they can be distinguished by differences in lymphocyte morphology. Typical villous lymphocytes are present in Ghanaian patients with SLVL but not with CLL. SLVL is shown to predominantly affect women over 4 0 years (table 1) and has similar symptomatology to CLL (table 3), patients either complaining of generalised symptoms or splenic discomfort. Anaemia is common in both SLVL and CLL and the white count usually exceeds 10 x 10^/1. However, the peripheral blood lymphocyte count tends to be lower in these Ghanaian patients with SLVL than in CLL.

greater than the local, normal mean. Almost every patient tested had a polyclonal increase in gamma globulins and, superimposed on this, about 2 0% of cases had a paraprotein band in their serum. Although there are no large studies of immunoglobulin levels in African CLL, raised gammaglobulins are not a common feature of lymphproliferative neoplasms. CLL in particular, is usually associated with immune suppression rather than with increased gamma globulins. Monoclonal IgM bands have been reported in 5% of B-CLL and 10% of lymphocytic lymphomas in North America [Alexanian 1975]. This frequency of raised IgM is one hundred times higher than in normal populations and other cancers.

The majority of lymphocytes in cases of CLL in Europe and North America are positive for antibodies for CDS. There is a paucity of data on the lymphocyte phenotype in African CLL and information from Caucasian CLL cases cannot necessarily be extrapolated to CLL in tropical Africa. In view of the different demographical and clinical features of CLL in these two geographical areas it is possible that they are in fact different entities. I have demonstrated by surface marker studies that SLVL in Ghana is a B-cell disorder negative for antibodies to the CDS determinant. In addition the study identified in group D | a case of B-lyn^hoproliferative

In Essien's study of CLL in Nigeria [1976], 63% of patients with CLL died within 3 months of presentation and 90% had died by 3 years despite the administration of "appropriate chemotherapy". 15% died from infection and 3.3% had lymphoblastic transformation. 2 patients who had white counts <50 X l o ’/l were considered to be "in remission" 5 and 7 years after initial treatment with chlorambucil. I also found the course of SLVL to be variable with 6 patients out of 30 with over 30% villous lymphocytes dying during the period of the study, usually from infections.

Differentiation of SLVL from HMS in this study

As with CLL, this study shows that both SLVL and HMS affect women more than men but SLVL tends to occur in a slightly older age group (table 1) . Clinically, HMS and SLVL proved difficult to distinguish; SLVL patients seem to have a greater tendency to develop moderate lymphadenopathy and, on average, have larger spleens than patients with lower numbers of villous lymphocytes (figure 11) . These variations are not helpful in the diagnosis of individual patients. Both SLVL and HMS present with non-specific symptoms and hepatosplenomegaly (table 3). Jaundice due to acute haemolysis appears to be more common among HMS patients, particularly those who are pregnant

[Hamilton 1966], than in SLVL patients.

HMS and SLVL and I have demonstrated that the total white blood count is usually raised in SLVL and associated with a significantly greater degree of bone marrow involvement than HMS. Nevertheless, 8-7 0% of African HMS patients may show a blood and bone marrow lymphocytosis [Lowenthal et al 1980, Bryceson et al 1976]. This phenomenon of lymphocytosis in HMS has not described from other parts of the world. IgM levels in HMS are stated to be at least 2 SD above the local normal mean in the diagnostic criteria published in 1981 [Fakunle]. My findings generally confirmed this but it was also noted that such elevations of IgM were not confined to HMS; markedly raised IgM levels were also found in patients with SLVL and splenomegaly due to other causes. These findings support those of DeCock et al [1986] who looked specifically at the IgM criterion by comparing two groups of Kenyan patients with HMS. They found no clinical difference between those with IgM concentrations 2SD above the local normal mean and the rest and concluded that it was "unreasonable" to consider this degree of IgM increase as essential for the diagnosis. Studies from Malawi [Molyneaux et al 1979] and Uganda [Ziegler et al 1973] have also found that HMS is underdiagnosed if the 2SD IgM criterion is a prerequisite. Raised IgM levels are therefore not specific for HMS and so the usefulness of this criterion in the diagnosis of HMS needs to be re-evaluated. An

Until this study was carried out there was very little data published on the lymphocyte phenotype in HMS. I have found that the lymphocyte surface antigen determinants in HMS and SLVL patients with normal lymphocyte counts are no different from those in the normal population. One of the major distinguishing features between SLVL and HMS proved to be that SLVL shows evidence of monoclonality, such as immunoglobulin light chain restriction and immunoglobuin gene rearrangements, whereas in HMS the lymphocytes are polyclonal.

Susceptibility to infections

Although some patients in this study have only been followed for a few years it is clear that the course of SLVL is variable, some patients succumbing to infections shortly after presentation and others remaining asymptomatic for long periods. Infections, which were the terminal event in most of the patients who died during this study, are the most common cause of death generally in developing countries. There is no evidence from my work that patients with SLVL and other causes of splenomegaly are particularly prone to infections either as a result of splenic hypofunction or hypogammaglobulinaemia.

The natural history of HMS in Papua New Guinean patients has been described by Crane [1981]. The patients progressed from being minimally disabled to being completely incapacitated as the spleen enlarged. A suprisingly high mortality rate of 63% in 18 years was found [Crane 1986a] amongst a group of 148

Watuts with untreated HMS from Papua New Guinea; most of these deaths were due to infections. Not suprisingly, reports in the literature about the infection risks in HMS are contradictory because infections are such a common cause of death even amongst previously healthy individuals in developing countries. An impaired neutrophil response to pyogenic infection has been observed in HMS patients [Hewlett and Pitchnmoni 1987] manifest by an abnormally slow reduction in temperature after treatment for pneumonia despite normal resolution of radiological abnormalities [Awunor-Renner 1979].