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The Clinical Presentations And Diagnostic Procedures In Multiple Myeloma (Plasma Cell Dyscrasias)

Updated on January 21, 2014

Multiple Myeloma Manifestations


A General Overview

These include a group of disorders mainly characterized by

  1. Uncontrolled proliferation of antibody producing cells and
  2. Secretion of a structurally homogenous gammaglobulin or its polypeptide chains- the ‘M’ component.

Traditionally, multiple myeloma, Waldenstrom’s macroglobulinemia, heavy chain diseases, benign monoclonal hypergammaglobulinemia and amyloidosis are included in this group, though Waldenstrom’s macroglobulinemia and heavy chain diseases are actually lymphoid dyscrasias.

Characteristic protein abnormalities form the hallmark of these disorders. Increased concentrations of structurally homogenous proteins- myeloma or macroglobulinemia components (called M proteins)- are diagnostic.

Multiple Myeloma

This is the most common disorder among the group of plasma cell dyscrasias. Myeloma is a malignant tumour arising from the plasma cells. The tumour may arise unicentrically or multicentrically from the bone marrow or as localized tumours in other sites.

Myeloma is a clonal disorder arising from one abnormal clone of plasma cells, secreting only the same type of immunoglobulin- monoclonal myeloma. Rarely, myeloma proteins may be biclonal. Any of the immunoglobulins- IgG and its subclasses, IgA, IgM, IgE and IgD or their light chains Kappa or Lambda- may be produced in large amounts. The abnormal immunoglobulins are produced without antigenic stimulation and the normal immunoglobulins are reduced. Hence infections are common. Rarely abnormal immunoglobulins may not be secreted- non secretory myeloma.


There is gross hyperplasia of the plasma cells and these almost fill the bone marrow, eroding into bone and leading to pathological fractures. Proliferation of the plasma cells may take a diffuse pattern (myelomatosis) or may be localized and nodular (myeloma). The plasma cells show abundance of cytoplasm, with foamy vacuoles and many of them may be multinucleated (myeloma cells). Signs of nuclear immaturity may be evident. Due to increased cell turn over serum uric acid level is elevated. Primary type of amyloidosis occurs in some cases. The Bence- Jones proteinuria, amyloidosis and hyperuricemia lead to renal damage resulting in renal failure.

Mobilisation of calcium from bones causes hypercalcemia, hypercalciuria and nephrocalcinosis. Hyperviscosity syndrome may develop due to the presence of abnormal immunoglobulins. The signs of hyperviscosity include weakness, anorexia, impairment of cerebral circulation leading to neurological deficits, and retinal abnormalities. This is more pronounced in IgA myeloma.

Invasion of the bone marrow by plasma cells may caused myelophthysic anemia, leucopenia and thrombocytopenia. In the majority of cases, plasma cells occur in small numbers in peripheral blood and can be demonstrated in the buffy coar. In a few, large number of plasma cells and plasmablasts (showing nucleoli) appear in the peripheral blood when the condition may be termed plasma cell leukemia.

X-ray Of Myeloma Patient


Clinical features

This disease is seen in the middle and older age groups, majority of cases being between 50 and 70 years. It is mostly predominant in males. The onset is insidious with symptoms of vague ill health, back pain, aches and pains, arthralgia and progressive anemia. Some cases may be detected by investigation of asymptomatic subjects. In the advanced cases, anemia and thrombocytopenia develop.

Bone changes

Vertebrae, sternum, ribs, skull and clavicles show characteristic osteolytic changes. Localised bony or soft tissue swellings may be detectable over these sites. In some, the disease presents abruptly with the onset of pathological fractures in an otherwise healthy subject. Vertebral compression may result in reduction in height of the individual and compressive myelopathy. Other neurological manifestations develop due to demyelination, amyloid peripheral neuropathy, carpal tunnel syndrome and rarely cranial nerve palsies.


Splenomegaly occurs in 20%, hepatomegaly in 40%. Lymphadenopathy and involvement of organs like thyroid, adrenal, ovaries, testes, lung, pleural, pericardium, skin and others in a smaller proportion of cases. Infections like pneumonia and herpes zoster are more common.

Renal failure may present as insidious onset of azotemia, which is made out on investigation, or it may occur acutely with renal shut down due to tubular obstruction. Contrast radiography (IVP) may precipitate renal failure due to dehydration.


Normocytic normochromic anemia is present and neutropenia and thrombocytopenia may develop later. The peripheral blood smear shows marked rouleaux formation which reflects the high ESR. Plasma cells may be seen in small numbers. Presence of numerous plasma cells suggests plasma cell leukemia.

Multiple Myeloma Symptomatology



Myeloma should be suspected in any elderly person presenting with vague rheumatic symptoms, pains and deformity over the spine. Neurological symptoms, pathological fractures, unexplained anemia and recurrent infections should alert the physician to the possibility of myeloma. Investigations are absolutely essential to diagnose the condition and assess the extent of the disease. Presence of a very high ESR (often above 100 mm in 1 hour) should suggest the possibility of myeloma, if other more common causes can be excluded.


X-rays of the skull, long bones, pelvis, ribs, and vertebrae reveal characteristic punched out lesions. One or several vertebrae may be affected. The bone lesions are usually localized. Despite the bone lesions, plasma alkaline phosphatase is normal.

Bone marrow examination is diagnostic. Material aspirated from any site is usually diagnostic, but in case of doubt aspiration must be done from an area of radiological abnormality. Normally, the proportion of plasma cells range from 2 to 10%. Rarely, it may rise even up to 20%. In myeloma, the number of plasma cells is considerably increased and the plasma cells show morphological abnormality.

Electrophoretic studies

Demonstration of paraprotein by electrophoresis and determination of the immunoglobulin type by immune-electrophoresis or diffusion techniques help to confirm the diagnosis and type the myeloma.

Serial measurement of the paraprotein level helps to assess progress since its level reflects the tumour load. Assessment of renal function by blood urea, creatinine, uric acid and glomerular filteration rate are essential to indicate the prognosis and plan therapy.

Differential diagnosis of multiple myeloma includes multiple bony secondaries from carcinoma of the prostate, adrenals, breast, thyroid and other organs. In this condition, the protein abnormalities are absent or only minimal. Biopsy from these sites may be rewuired to confirm the diagnosis. Eosinophilic granuloma of bone or other lipidoses like Hand-Schuller Christian disease and Neimann-Pick’s disease may produce multiple lytic lesions in the skull.

© 2014 Funom Theophilus Makama


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    • married2medicine profile image

      Funom Theophilus Makama 3 years ago from Europe

      Woow! Thanks a whole lot for ur comment. I will go through this piece of info you have tabled.