Page 399 - Textbook of Pathology, 6th Edition

5. Liver, spleen involvement. Involvement of the liver iii) increased β-2 microglobulins and other globulins in urine 383
and spleen by myeloma cells sufficient to cause and serum.
hepatomegaly, and splenomegaly occurs in a small 9. POEMS syndrome is seen in about 1% cases of myeloma
percentage of cases. and includes simultaneous manifestations of polyneuro-
pathy, organomegaly, endocrinopathy, multiple myeloma
Clinical Features and skin changes.
The clinical manifestations of myeloma result from the effects
of infiltration of the bones and other organs by neoplastic Diagnosis
plasma cells and from immunoglobulin synthesis. The The diagnosis of myeloma is made by classic triad of features:
principal clinical features are as under: 1. Marrow plasmacytosis of more than 10%
1. Bone pain is the most common symptom. The pain usually 2. Radiologic evidence of lytic bony lesions
involves the back and ribs. Pathological fractures may occur 3. Demonstration of serum and/or urine M component.
causing persistent localised pain. Bone pain results from the There is rise in the total serum protein concentration due
proliferation of tumour cells in the marrow and activation of to paraproteinaemia but normal serum immunoglobulins (IgG,
osteoclasts which destroy the bones. IgA and IgM) and albumin are depressed. Paraproteins are
2. Susceptibility to infections is the next most common clinical abnormal immunoglobulins or their parts circulating in CHAPTER 14
feature. Particularly common are bacterial infections such plasma and excreted in urine. About two-third cases of
as pneumonias and pyelonephritis. Increased susceptibility myeloma excrete Bence Jones (light chain) proteins in the
to infection is related mainly to hypogammaglobulinaemia, urine, consisting of either kappa (κ) or lambda (λ) light chains,
and partly to granulocyte dysfunction and neutropenia. along with presence of Bence Jones paraproteins in the serum.
3. Renal failure occurs in about 25% of patients, while renal On serum electrophoresis, the paraprotein usually appears
pathology occurs in 50% of cases. Causes of renal failure in as a single narrow homogeneous M-band component, most
myeloma are hypercalcaemia, glomerular deposits of commonly in the region of γ-globulin (Fig. 14.27). Most
amyloid, hyperuricaemia and infiltration of the kidney by frequent paraprotein is IgG seen in about 50% cases of
myeloma cells. myeloma, IgA in 25%, and IgD in 1%, while about 20%
4. Anaemia occurs in about 80% of patients of myeloma and patients have only light chains in serum and urine (light chain
is related to marrow replacement by the tumour cells myeloma). Non-secretory myeloma is absence of M-band on
(myelophthisis) and inhibition of haematopoiesis. serum and/or electrophoresis but presence of other two
5. Bleeding tendencies may appear in some patients due to features out of triad listed above. Though the commonest
cause of paraproteinaemias is multiple myeloma, certain
thrombocytopenia, deranged platelet function and other conditions which may produce serum paraproteins
interaction of the M component with coagulation factors. need to be distinguished. These are as under:
6. Hyperviscosity syndrome owing to hyperglobulinaemia may
Monoclonal gammopathy of undetermined significance
produce headache, fatigue, visual disturbances and (MGUS) Disorders of Leucocytes and Lymphoreticular Tissues
haemorrhages.
7. Neurologic symptoms occur in a minority of patients and Waldenström’s macroglobulinaemia
are explained by hyperviscosity, cryoglobulins and amyloid Benign monoclonal gammopathy
deposits. B-cell lymphomas
8. Biochemical abnormalities. These include the following: CLL
i) hypercalcaemia due to destruction of bone; Light chain disease
ii) hyperuricaemia from necrosis of tumour mass and from Heavy chain disease
uraemia related to renal failure; and Cryoglobulinaemia.

Figure 14.27 Serum electrophoresis showing normal serum pattern (A), as contrasted with that in benign polyclonal gammopathy (B) and in
monoclonal gammopathy (C), typical of plasma cell myeloma.