Waldenström macroglobulinemia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Waldenström macroglobulinemia is a rare blood cell cancer characterized by an excess of abnormal white blood cells in the bone marrow. These abnormal cells have characteristics of both white blood cells (lymphocytes) called B cells and more mature cells derived from B cells known as plasma cells. These abnormal cells with both lymphocyte and plasma characteristics are known as lymphoplasmacytic cells. Due to these cells, Waldenström macroglobulinemia is classified as a lymphoplasmacytic lymphoma. In Waldenström macroglobulinemia, these abnormal cells produce excess amounts of IgM, the largest of a type of protein known as an immunoglobulin; the overproduction of this large protein contributes to the condition's name (macroglobulinemia).

Waldenström macroglobulinemia usually begins in a person's sixties and is a slow-growing (indolent) cancer. Some affected individuals have elevated levels of IgM and lymphoplasmacytic cells but no symptoms of the condition; in these cases, the disease is usually found incidentally by a blood test taken for another reason. These individuals are diagnosed with smoldering (or asymptomatic) Waldenström macroglobulinemia. It can be many years before a person with the condition develops noticable signs and symptoms.

The most common signs and symptoms to first appear in people with Waldenström macroglobulinemia are weakness and extreme tiredness (fatigue) caused by a shortage of red blood cells (anemia). Affected individuals can also experience general symptoms such as fever, night sweats, and weight loss. Some people with Waldenström macroglobulinemia develop a loss of sensation and weakness in the limbs (peripheral neuropathy). Doctors are unsure why this feature occurs, although they speculate that the IgM protein attaches to the protective covering of nerve cells (myelin) and breaks it down. The damaged nerves cannot carry signals normally, leading to neuropathy.

Other features of Waldenström macroglobulinemia are due to the accumulation of lymphoplasmacytic cells in different tissues. For example, accumulation of these cells can lead to an enlarged liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy). In the bone marrow, the lymphoplasmacytic cells interfere with normal blood cell development, causing a shortage of healthy blood cells (pancytopenia).

Several other signs and symptoms of Waldenström macroglobulinemia are related to the excess amounts of IgM. Increased IgM can thicken blood and impair circulation, causing a condition known as hyperviscosity syndrome. Features related to hyperviscosity syndrome include bleeding in the nose or mouth, blurring or loss of vision, headache, dizziness, and confusion. In some affected individuals, IgM and other immunoglobulins react to cold temperatures to form gel-like clumps that block blood flow in areas exposed to the cold, such as the hands and feet. These clumped proteins are referred to as cryoglobulins, and their clumping causes a condition known as cryoglobulinemia. Cryoglobulinemia can lead to pain in the hands and feet or episodes of Raynaud phenomenon, in which the fingers and toes turn white or blue in response to cold temperatures. The IgM protein, along with another protein called amyloid, can build up in organs and interfere with their normal function. This buildup causes a condition called amyloidosis. Organs that are typically affected by amyloidosis include the heart, kidneys, liver or spleen. Affected individuals can experience weakness, fatigue, shortness of breath, irregular heartbeat, or joint pain.

ORPHANET DEFINITION A rare indolent B-cell non-Hodgkin lymphoma, characterized by the infiltration of monoclonal lymphoplasmacytic cells in the bone marrow and the production of serum immunoglobulin M (IgM) monoclonal protein.

Causes

From: MedlinePlus Genetics, National Library of Medicine

Due to these cells, Waldenström macroglobulinemia is classified as a lymphoplasmacytic lymphoma. The most common signs and symptoms to first appear in people with Waldenström macroglobulinemia are weakness and extreme tiredness (fatigue) caused by a shortage of red blood cells (anemia). Other features of Waldenström macroglobulinemia are due to the accumulation of lymphoplasmacytic cells in different tissues.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Not inherited

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Annual incidence: 1-9 / 1 000 000; Europe; Value and class. Annual incidence: 1-9 / 100 000; France; Value and class. Annual incidence: 1-9 / 1 000 000; United States; Value and class. Annual incidence: 1-9 / 1 000 000; United Kingdom; Value and class.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Leukemia · Very frequent (99-80%)

A cancer of the blood and bone marrow characterized by an abnormal proliferation of leukocytes.

Lymphoma · Very frequent (99-80%)

A cancer originating in lymphocytes and presenting as a solid tumor of lymhpoid cells.

Monoclonal immunoglobulin M proteinemia · Very frequent (99-80%)

Presence of a monoclonal immunoglobulin M protein in the serum.

Abnormality of neutrophils · Frequent (79-30%)

A neutrophil abnormality.

Gingival bleeding · Frequent (79-30%)

Hemorrhage affecting the gingiva.

Hypercoagulability · Frequent (79-30%)

An abnormality of coagulation associated with an increased risk of thrombosis.

Normocytic anemia · Frequent (79-30%)

A kind of anemia in which the volume of the red blood cells is normal.

Pallor · Frequent (79-30%)

Abnormally pale skin.

Other findings in the same source

From: Orphanet

Additional reported features include Vertigo (Frequent (79-30%)); Respiratory insufficiency (Frequent (79-30%)); Abnormal retinal vascular morphology (Occasional (29-5%)); Anorexia (Occasional (29-5%)); Ataxia (Occasional (29-5%)); Congestive heart failure (Occasional (29-5%)); Cryoglobulinemia (Occasional (29-5%)); Cutis marmorata (Occasional (29-5%)); Diarrhea (Occasional (29-5%)); Elevated erythrocyte sedimentation rate (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Elderly

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Not inherited

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Annual incidence: 1-9 / 1 000 000; Europe; Value and class. Annual incidence: 1-9 / 100 000; France; Value and class. Annual incidence: 1-9 / 1 000 000; United States; Value and class. Annual incidence: 1-9 / 1 000 000; United Kingdom; Value and class.

Which doctor should you see?

The suggested department for discussing Waldenström macroglobulinemia is Oncology, with a oncologist and relevant organ specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics; Relevant organ specialist / Surgical Oncology as indicated.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Has the exact tumour type been confirmed, and is staging relevant?
• What is the goal of each proposed treatment option?
• How will side effects, daily function and supportive care be addressed?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Waldenström macroglobulinemia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.