Overview

Tumoral calcinosis (TC) is a rare disorder that usually affects children and young adolescents. It is characterised by the presence of calcium lesions in periarticular soft tissues. Due to its rarity it presents with unique diagnostic and management challenges. In this article TC will be briefly presented as well as the unique considerations of the syndrome in the pediatric cases.

Introduction

Tumoral calcinosis, which is also known as hyperphosphatemic familial tumoral calcinosis (HFTC) or Teutschlaender disease, is a rare, usually genetic condition that results in increased phosphorus and calcium levels. The increase of these minerals is caused due to the altered metabolism of phosphate, which leads to its rise (hyperphosphatemia). Consequently, calcium is deposited in and around the joint (periarticular) soft tissue areas, forming benign (non-cancerous) masses (lumps).^4,15 TC’s varieties include the following:

Primary 

It is caused by genetic mutations in genes (e.g., SAMD9, GALNT3, FGF23) affecting the metabolism of phosphate, resulting in phosphate buildup and the formation of calcium deposits. While the most common type of this category is HFTC, there are two less common types: the hyperphosphatemia-hyperostosis syndrome (HHS) and normophosphatemic tumoral calcinosis (NFTC) types. HHS’s unique characteristics include excess bone formation and benign bone masses. NFTC is a severely painful type that causes life-threatening skin infections due to calcium deposit formation.^5,6,9,10

Secondary 

The most common condition that can lead to secondary TC is chronic kidney disease (CKD) and hemodialysis. This is due to the disturbance of the calcium-phosphate metabolism. However, other conditions, such as hyperparathyroidism and scleroderma, have been noted to accompany TC.^1,2

Signs and symptoms

The typical sign is the appearance of palpable lumps of various sizes near one or more joints, usually around the hip, elbow, or shoulder. These usually develop in early childhood or adolescence, but may also occur in adults. In addition, patients may experience:

• Decreased range of motion of the affected joints (limited movement)
• Pain or tenderness due to the pressure of structures surrounding the affected joints (secondary pain)
• Swelling in the affected joints due to the presence of masses
• Ulceration of skin around the affected joints leading to the oozing of thick, white, paste-like fluid, i.e., exudation of chalky fluid (extremely rare)^13,15

Diagnosis

Diagnosis is usually established through clinical examination, but imaging studies may be performed in order to assess for masses or other issues. These include:

• X-Ray: circular, ‘cloud-like’ calcification around the joints 
• CT scan: decreased metabolic activity resulting in restricted growth (homogeneity) or calcium lines may be visible, resembling cysts (sedimentation sign)
• MRI: may demonstrate different levels of fluid density (fluid-fluid levels)¹⁴
• Bone scan: may reveal absorption of the injected radionuclide (tracing element) by the calcified lesion 

In extremely difficult cases, a biopsy may be done so that a diagnosis is reached, but it is generally avoided due to the fear of infection. It must also be noted that some blood tests may be performed to assess parathyroid function and other markers.^10,13

Treatment

The aim of the treatment is to relieve the symptoms, prevent complications, and control the phosphate levels. Management is both pharmacological and non-pharmacological and depends on the lesion type, size, and symptoms it causes.

Distinctive paediatric considerations 

Even though tumoral calcinosis is a rare condition, it should be wise to take into account the unique impact it can have on children.

Impact on growth

When calcified lesions are formed, they can interfere with the normal development of the skeletal system. This can affect the physical development of the child and result in limited movement of the respective bone or joint.

Diet restrictions

Phosphate dietary restrictions are necessary to manage the condition. However, challenges can arise. Phosphorus is necessary for bone growth as well as energy metabolism, and for this reason, a tailored dietary plan is essential to avoid growth issues. In addition, poor adherence can occur as the foods children usually prefer (e.g., meat, dairy products, chocolate) should be limited, leading to altered caloric intake, meal dissatisfaction, or nutritional deficiencies. Consult a registered dietitian and a healthcare provider to discuss the necessary lifestyle adjustments and gain further information.

Surgery and recurrence risk

Even though surgery is a common treatment method of the disorder, it must be approached carefully in children due to growth disturbance or damage that may be caused. Furthermore, recurrence is possible with long-term monitoring being essential. Parents should be informed accordingly regarding the implications of the disease.

Psychological impact

Visible masses can affect children’s self-esteem as well as psychosocial development. Prompt diagnosis and initiation of treatment can help minimise the emotional burden of the condition.^8,12

FAQs

Who is most commonly affected by TC?

It affects both males and females equally, but it most commonly occurs in Black and Middle Eastern people.^4,10

What are the complications of TC?

Complications of tumoral calcinosis are rare but increase the risk of serious health issues, like cerebrovascular accidents (strokes) and myocardial infarctions (heart attacks), because it affects the blood vessels as well as the brain. Some other problems it can cause include:

• Teeth problems: swollen roots (also known as bulging), hard pulp, thistle-shaped roots^4,7
• Diaphysitis: long bone inflammation (e.g., femur, humerus)³
• Vascular calcifications: calcium deposits in the blood vessels¹¹
• Hyperostosis: extreme bone enlargement
• Angioid retinal streaks: lines in the eyes that are caused bydamage to the inner eye membrane called Bruch’s membrane¹⁵

Can TC be mistaken for other conditions? 

Due to its rare occurrence and similarity of symptoms with other conditions, tumoral calcinosis can be mistaken for other conditions. Some of these include:

• Calcific tendinitis: calcium builds up in the tendons, whereas in TC, the build-up occurs in the soft tissue around the joints.
• Calcinosis universalis: widespread build-up of calcium in the skin, muscles, and connective tissue, whereas in TC the build-up is localised.
• Calcific myonecrosis: calcium builds up inside the muscle after trauma, whereas in TC, it develops in the soft tissue around the joints in the absence of trauma or injury.
• Gout: uric acid crystals are developed in the joints (usually in the big toe), and sudden pain is present, unlike in TC, where pain is absent and the crystals are formed of calcium phosphate. 
• Myositis ossificans: bone is formed after trauma inside the muscles or soft tissues and causes pain, unlike in TC, where crystals are formed and pain is usually absent.^13,14

Can TC be prevented?

Speak to a genetic counsellor if you plan on conceiving. Preimplantation genetic diagnosis (PGD) can be used to identify embryos that do not carry mutated genes and place them through in vitro fertilisation (IVF) into the female reproductive system.¹⁵

What is the prognosis for a child with TC?

Regular monitoring by a healthcare professional to check for new or recurring growths is advised, but the disorder doesn’t commonly cause serious issues. Most individuals lead active and full lives.⁸

Can TC lumps become malignant?

No, because TC lesions aren’t tumours.¹⁵

When should I contact my healthcare provider?

Call your healthcare professional if you experience any TC symptoms or notice a lump you can touch (palpable).¹⁵

Summary

Tumoral calcinosis (TC), also known as hyperphosphatemic familial tumoral calcinosis (HFTC) or Teutschlaender disease, is a rare disorder characterised by calcium build-up in periarticular soft tissues. It affects mostly children and young adolescents. It is the result of genetic mutations or secondary to other conditions, usually from chronic kidney disease (CKD). Symptomatology includes palpable lumps, limited range of motion, swelling, and skin ulceration. Diagnosis includes clinical examination and imaging. Treatment focuses on managing the symptoms through drug administration, surgery, diet alteration, and observation. In children, TC impacts growth and may cause nutritional deficiencies, rendering a personalised diet necessary. It must also be noted that surgery risks are considered, and psychological support must be taken into consideration. Lastly, complications exist but are very uncommon.