Overview

What is tumoral calcinosis?

Tumoral calcinosis or hyperphosphatemic familial tumoral calcinosis is an inherited disease which means it runs in families. It is a rare condition caused by a genetic mutation that causes a high amount of phosphate in your blood. It is diagnosed mostly in people of African and Middle Eastern descent, however, recent research shows other ethnicities can also be affected.¹

A person suffering from this condition will have a lot of calcium and phosphate in their blood, which will continue to accumulate in soft tissues and form a noncancerous mass (benign tumour).²

Types of tumoral calcinosis

There are three types of calcinosis, depending on which gene is affected:

• Hyperphosphatemic familial tumoral calcinosis which is the most common type. In this form, the FGF23 gene is mutated.
• Normophosphatemic tumoral calcinosis: manifests in a patient as kidney failure and can lead to hyperparathyroidism. This type has a mutation in the SAMD9 gene.
• Hyperphosphatemic-hyperostosis syndrome (HHS) is caused by a mutation in 2 genes GALNT3 and FGF23 and results in increased bone growth and the formation of noncancerous lesions.³

Causes of tumoral calcinosis

Genetic mutations and inherited disorders

Tumoral calcinosis can be caused by two different mutations:

• a mutation in the FGF23 Gene itself.
• mutation in genes that regulate its production - GALNT3 and KL genes

The FGF23 gene is essential as it tells the kidneys what amount of phosphate should be absorbed from the blood. Hence, if it’s mutated, the kidneys will not absorb enough phosphate from the blood. Consequently, that leads to phosphate accumulation and its binding with calcium, resulting in lumps within soft tissues, especially near the joints.

Secondary causes

Chronic kidney disease

In hemodialysis patients may develop what is called calcinosis as a result of chronic kidney failure. It is a rare condition which leads to an increased amount of phosphate and calcium in our blood, resulting in hyperphosphatemia and the formation of a mass in tissues.

Hyperparathyroidism

When hyperparathyroidism becomes severe, a high amount of calcium is accumulated which leads to kidney failure and consequently to calcinosis as well as increased phosphate and calcium levels in the blood.

Metabolic disorders 

Some metabolic disorders which affect calcium and phosphate metabolism also can lead to hypercalcemia and hypocalcemia or hypophosphatemia and hypophosphatemia.⁴

Risk factors

Tumoral calcinosis is an autosomal recessive disease which means it will affect you only if you inherit two copies of the mutated genes from both of your parents. If each of your parents is a carrier, they have only one copy of the affected gene, therefore will not show any signs or symptoms.

The chances of being affected are as follows:

• One to four of no gene mutation
• One to four of developing tumoral calcinosis
• One to two of being a carrier only without any symptoms³

Commonly affected regions (periarticular areas)

As a result of the gene mutations, calcium and phosphate build up in our soft tissues to form lumps underneath the skin near joints such as:

• Hip 
• Elbow 
• Shoulder 
• Foot 
• Spinal cord

Symptoms and signs

The patient will start experiencing visible signs and symptoms when they begin to feel pain as a result of formed lumps around joints. This can manifest as:

• Musculoskeletal pain
• Inability to move the affected joints
• Painless lumps that are tender to touch
• Pain and discomfort around the joints
• Swelling and limited range of motion
• Formation of tumour-like nodules
• Erosion of adjacent bone
• Functional impairment⁴

Diagnosis

To diagnose this condition a doctor such as your GP, they will perform a general examination of your body and asks about family history of any diseases. Then they may ask to do some tests and diagnostic imaging to confirm the presence of tumoral calcinosis.

The imaging procedures used are usually:

• X-ray
• CT scan
• MRI³

This is typically done to take a deeper look at bones and surrounding tissues which can help identify any lumps or masses that could have formed near the joints.

Laboratory tests can also be performed and these are:

• Measurement of calcium and phosphate levels in the blood
• Biopsy to confirm calcinosis and to rule out other conditions

Treatment and management 

Choosing which type of treatment will be used in this case depends on:

• Type of the disease - if it is first hyperphosphatemia tumoral calcinosis or secondary tumoral calcinosis due to the presence of kidney failure or hyperparathyroidism.
• The size and site of lesions formed surrounding the joints.
• Stage of the pathology³

After examination, there are two types of treatment available: medical or surgical treatment.

When is the medical treatment recommended over the surgical one?

Doctors use this approach of treatment when:

• Patients have secondary tumoral calcinosis as surgery can be dangerous and not effective. This is true especially when there is kidney failure or hyperparathyroidism as it may slow the healing process and can lead to infection and profound complications. Therefore, making a surgical excision is considered the last option.
• It can be used in combination with surgical treatment for better results in more severe stages of the disease.
• The patient is in the active stages of the disease. In this case, it is more effective because recurrence of the lumps post-surgical removal is high. 

Surgical treatment can be more successful in a quiescent stage when the mass is fully calcified, encased in fibrous tissue and the ion exchange process is hidden so depletion of the phosphate fails.³

Non-surgical treatment

Following non-surgical treatments are available:

• Phosphate-binding medication which decreases the amount of phosphate in the blood.
• Phosphate binders with acetazolamide which decrease the levels of phosphate in the blood. It works by blocking the absorption of phosphate into your blood which is then processed by the kidneys and removed in urine.
• Going on a low phosphate diet to control phosphate and calcium levels.

Surgical treatment

During surgical treatment the lumps or noncancerous masses around joints are removed and then a biopsy of the lesion is taken to confirm tumoral calcinosis. Sometimes during the surgical excision, the removal may be only partial due to the large size of the lesion. This still provides relief from the pain, although there is a higher risk of lumps recurrence and hence may require further excisions in the future. 

Complications of surgical intervention

The surgery may lead to recurrent infection and postoperative seroma, which may result in slower healing and secondary infections. In the case of only partial excision, follow-up surgeries may be needed if there is a recurrent infection, ulceration and/or functional impairment.

Summary

Tumoral calcinosis (hyperphosphatemic familial tumoral calcinosis) is a rare inherited disorder characterized by high phosphate levels in the blood. Typically, the condition leads to the formation of benign tumours containing calcium deposits in soft tissues, particularly near joints. There are various types of tumoral calcinosis caused by different genetic mutations. Common symptoms include musculoskeletal pain, joint immobility, and the development of tender lumps near affected joints. Diagnosis involves laboratory examinations such as biopsy and imaging procedures such as X-ray. Recommended treatment is based on the type and stage of the disease. Non-surgical options include the use of phosphate-binding medications and dietary adjustments, while surgical procedures may be necessary to remove the lumps. However, surgery may come with complications such as infections and recurrence of the lumps, particularly in cases of partial lump excision. The treatment of tumoral calcinosis is tailored to the individual patient's condition and considers factors like disease progression and potential complications.