There are a number of plasma cell and lymphoplasmacytic neoplasms characterized by specific damaging effects of a paraprotein rather than by the more usual features of a lymphoid neoplasm [1,2]. Sometimes the haematological and pathological features would lead to a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) if it were not for the effects of the paraprotein. In other patients, there is an overt neoplasm at the onset but, in addition, the damaging effects of a paraprotein are apparent. An overt neoplastic condition may emerge some years later in patients in whom none was apparent at onset. The words ‘primary’ or ‘essential’ are sometimes used when there is no overt associated neoplasm, for example ‘primary amyloidosis’ or ‘essential cryoglobulinaemia’.
The main clinical features are those resulting from the specific effects of the paraprotein in an individual condition [1–7]. These are summarized in Table 27.1. Patients with polyneuropathy, organomegaly (hepatomegaly, splenomegaly, lymphadenopathy), endocrinopathy, M-protein and skin (POEMS) syndrome may not have all the manifestations. Mandatory diagnostic criteria are polyneuropathy and a monoclonal M band together with one or more major criteria (Castleman disease, osteosclerotic lesions, elevated VEGF) and one or more minor criteria (organomegaly, endocrinopathy, skin changes, thrombocytosis, extravascular volume overload) . Alpha heavy chain disease is a form of MALT lymphoma (see Chapter 9).
Table 27.1Syndromes resulting from synthesis of a monoclonal paraprotein. |Favorite Table|Download (.pdf) Table 27.1 Syndromes resulting from synthesis of a monoclonal paraprotein.
|Condition ||Type of paraprotein ||Pathological effects ||Clinical effects |
|Light-chain associated-amyloidosis ||Complete immunoglobulin or Bence Jones protein; 70%–80% of paraproteins have λ light chains ||Amyloid deposition in many tissues ||Heart failure, hepatomegaly, tongue enlargement, malabsorption, peripheral neuropathy, renal failure or nephrotic syndrome |
|Light-chain- or light- and heavychain-deposition disease ||About 80% of paraproteins have κ light chains ||Light-chain deposition in kidneys ||Renal failure or nephrotic syndrome, much less often hepatic, cardiac or adrenal involvement |
|Cryoglobulinaemia (type I or type II) ||Paraprotein that is either a cryoglobulin or forms an immune complex that is a cryoglobulin (in the case of an IgM paraprotein with antibody activity to IgG) ||Precipitation of cryoglobulin in blood in cold conditions ||Vasculitis, purpura, impaired peripheral circulation |
|Cold haemagglutinin disease ||IgM paraprotein with anti-I activity ||Agglutination of red cells by a cold agglutinin in cold conditions ||Cold-induced haemolytic anaemia (intravascular haemolysis and haemoglobinuria) |
|POEMS syndrome ||Usually IgGλ or IgAλ || ||Peripheral neuropathy, hepatomegaly, splenomegaly, lymphadenopathy, endocrine organ failure and skin thickening |
|Acquired angiooedema ||A cryoglobulin, cold agglutinin or immune complex of an anti-idiotype antibody and the paraprotein to which it is directed ||Consumption of C1 esterase inhibitor ||Angiooedema |
Haematological and pathological features
Haematological and pathological features also differ, according to the characteristics ...