Waldenström macroglobulinaemia

What is Waldenström macroglobulinaemia?

Waldenström macroglobulinaemia is a low-grade form of lymphoma in which cancerous B-cells in the bone marrow, lymph nodes and/or spleen produce excessive quantities of IgM antibodies (lymphoplasmacytic lymphoma). These antibodies, called paraproteins, are all identical and are detected in the blood circulation. Skin problems are uncommon in this condition but, when present, may be helpful in considering the diagnosis.

Who gets Waldenström macroglobulinaemia?

Waldenström macroglobulinaemia affects males a little more commonly than females, and usually in the age range 50–70 years (median age 63 years).

The most common presenting symptoms are:

• Weight loss
• Weakness
• Tiredness

Common signs are:

• Anaemia
• Enlarged lymph nodes
• Enlarged liver and/or spleen
• Intermittent bleeding from mucosa

The cause of Waldenström macroglobulinaemia is unknown.

Cutaneous manifestations of Waldenström macroglobulinaemia

The skin is affected in Waldenström macroglobulinaema in approximately 5% of patients and occurs in three general ways:

1. Effects of the large amount of IgM antibody (paraprotein) in the blood
2. Paraprotein that directly attacks the skin
3. Specific infiltrate of the abnormal B-cells in the skin

The most common of these is when there is so much paraprotein in the blood that it affects blood flow (hyperviscosity syndrome) and this can present as:

• Swelling of the feet
• Bleeding from the gums
• Purple spots on hands and feet (petechiae)

Sometimes the paraprotein is affected by cold (cryoglobulin) and can then cause:

• Hives on exposure to cold (cold urticaria)
• Blue fingers in the cold (acral cyanosis)
• Raynaud phenomenon
• Livedo reticularis
• Ulcers
• Purpura

If the paraprotein is deposited in the skin it can result in numerous ‘storage papules’ which are small skin-coloured or translucent bumps on the body, buttocks or outer (extensor) aspects of the limbs. These are usually not itchy.

When the paraprotein attacks the skin, it can cause blisters, hives or itchy bumps.

Specific infiltrates: In this rare skin presentation the cancerous B-cells form lumps in the skin that can range in size from small papules to large plaques. They have been described as red-brown to purple in colour, are usually not itchy and appear on the trunk, earlobes, face or legs. Symmetrical firm swelling and burning of the face, with a purple colour is considered characteristic. This usually develops several years after the diagnosis of Waldenström macroglobulinaemia has been made, but can be the presenting problem.

There have also been a number of other skin presentations reported in association with Waldenström macroglobulinaemia including:

• Schnitzler syndrome
• Amyloid
• Paraneoplastic pemphigus
• Xanthoma disseminatum
• Hives/urticaria

In general, the presence of skin lesions of any type does not appear to affect outcome in this condition which often does not require treatment.

How is Waldenström macroglobulinaemia diagnosed?

Waldenström macroglobulinaemia is diagnosed by:

• Blood test — serum protein electrophoresis detects a high level of IgM antibodies (paraprotein), and immunoelectrophoresis shows these are all the same (monoclonal)
• Urine test — Bence Jones proteins may be found
• Bone marrow biopsy — predominantly abnormal B-cells (lympho-plasmacytoid cells), which on further studies are all the same (monoclonal)

Skin biopsy may be helpful in some situations.

• Storage papules contain IgM deposits in the dermis which are eosinophilic on normal histology and stain with PAS but not with Congo Red dye.
• When blood vessels are blocked by the IgM deposits.
• When the paraprotein is attacking the skin, IgM can be detected in the skin by direct immunofluorescence studies.
• Papules and plaques due to specific infiltrates show a dense infiltrate of atypical monoclonal B-cells in the dermis.

Further investigations may be performed to assess the extent of the disease and presence of complications.