Introduction

Maffucci syndrome is also known as Kast syndrome, hemangiomatosis chondrodystrophica, or enchondromatosis Spranger type II. It is a congenital, non-hereditary (not inherited by offspring) rare disease with a prevalence of less than 1 in 100000.^1,2

Multiple benign cartilaginous tumours (enchondromas) and benign vascular overgrowths (hemangiomas) are characteristic of Maffucci syndrome. Around 400 cases worldwide have been reported, limiting knowledge of the disorder. There is no definitive agreement on the pathogenesis and treatment for this disease. However, non-hereditary mutations in isocitrate dehydrogenase 1 and 2 genes are related to this disease. Understanding how the diagnosis of this condition is crucial for proper disease management and patient care.^3,4,5

Diagnosis

Clinical presentation

The symptoms start before puberty, usually between the ages of 4 and 5. They are characterised by multiple (more than three) enchondromas and hemangiomas.^2,6

Enchondromas

Enchondromas are a hallmark of Maffucci syndrome and Ollier disease. They are benign cartilaginous tumours originating inside the bones (medulla of bones), generally in the extremity of large bones (an essential area for bone growth). It usually presents bilaterally and asymmetrically. They can cause a variety of symptoms, such as:²

• Multiple swellings on the extremities
• Deformity around the joints
• Limitations in joint mobility that could develop into a loss of joint function
• Backbone deviation
• Bones shortening
• Leg-length discrepancy
• Gait problems
• Pain in the affected area

Common locations affected:¹

• Humerus
• Pelvis
• Tibia
• Femur
• Ulna
• Radius
• Fibula

Complications of enchondromas:⁷

• Facial asymmetry
• Cranial nerve palsies due to endochondral compression
• Short stature
• Pathological fractures

Vascular anomalies

Vascular anomalies usually appear at 4 to 5 years of age, mainly affecting the hands. The most common type is hemangiomas. Hemangiomas are abnormal clusters of blood vessels that appear as blue or purple spots on the skin that become pale after being compressed. They are often found in the skin (dermis) and just under the skin (subcutaneous fat) near enchondromas. On the contrary, they can also appear in internal organs and mucous membranes like the brain, eyes, and gastrointestinal tract. More than 50 % of hemangiomas are present in the hands and feet, and around 15% have visceral vascular anomalies.^2,7,8,9,10

Complications of hemangiomas:^8,10

• Pain
• Swelling
• Calcified vessels or Phleboliths – calcifications in soft tissue that can be seen on X-rays, that could also predispose to form microthrombi

Cancer

People who suffer from Maffucci syndrome are susceptible to both skeletal and non-skeletal cancer. There is an overall rate of malignancies of 23%, at the mean age of 40, for malignant transformation. The most frequent type of cancer is chondrosarcoma and some of the patients will develop vascular cancer with a rare occurrence of brain cancer.^2,8

Chondrosarcoma

Chondrosarcoma is the more frequent type of cancer found in Maffuci syndrome. It develops from enchondromas in around 50% of the patients at a median age of 30. They have a good prognosis with around 90% of patients surviving five years. ² Features that raise the suspicion of malignancy:¹¹

• New pain
• The location in the sternum, ribs, spine, pelvis, or scapula
• More than 5 cm in size
• Thinning of more than two-thirds of the bone's outer layer or, less critically, over two-thirds of the lesion's length
• An irregular lesion shape with poorly defined edges
• Spontaneous fractures through the lesion
• A change in the lesion's shape

Imaging signs indicating a higher grade of cancer:

• Involvement of nerves or blood vessels
• A mass in the soft tissue
• Irregular or widespread bone destruction
• Bone expansion
• Cortical bone destruction
• Aggressive bone response without an underlying pathological reaction

Other types of malignant tumours that may arise with Maffuci syndrome:^2,4

• Intrahepatic cholangiocarcinoma
• Acute myeloid leukaemia
• Glioma
• Oral squamous cell carcinoma

Investigations

Imaging

Several imaging techniques are used to visualise the enchondromas and hemangiomas to diagnose Maffucci syndrome. Also, due to the high risk of cancer, it is recommended to look for early detection of malignancies such as chondrosarcomas.²

X-rays

X-rays are often the first imaging test used because they show characteristics of enchondroma within the bones that differentiate it from other diseases. Also, doctors recommend having X-rays of every single enchondroma to provide a baseline for future comparison. X-rays can show:^1,11,12

• Small (less than 5 cm) dark spots inside bones on X-rays
• Can have a pattern like "arc and rings" on X-rays
• Well-defined areas within the bones that appear darker on X-rays
• Lesions that have a medullary connection to underlying bone
• Fractures

CT scans

CT scans show a more extensive view of the lesion, helping to identify subtle fractures. Brain and abdominal CT scans are recommended for patients with neurological and abdominal symptoms.^1,11

MRI scans

Magnetic resonance imaging (MRI scans) is a highly effective diagnostic method because it offers a detailed view of bone and soft tissue structures including the cartiliges. A whole-body MRI scan should be obtained to assess all bones, rule out possible tumours, and assess vascular anomalies in the visceral organs. MRI is the recommended imaging method for an early detection of chondrosarcoma. Its ability to see soft tissue allows it to detect soft tissue malignancies such as ovarian and pancreatic cancer. Also, in contrast to X-rays and CT scans, MRI poses no radiation exposure.^2,13

Biopsy

A biopsy is vital in diagnosing different diseases and malignant tumours. However, due to the tumours’ diverse shapes and stages present in one region of the affected area, it is not recommended to use a biopsy to rule out for example cartilage tumours in Maffucci syndrome. Some areas of the tumour could have benign tissue, making an inadequate diagnosis and treatment. Hence, for accurate diagnosis, the biopsy must encompass not just the complete tumour but also the adjacent bone to evaluate for signs of locoregional infiltration.¹¹

Genetic tests

Genetic testing is possible to rule out other disorders associated with enchondromas and exostoses, such as:²

• Metachondromatosis
• Multiple exostoses types 1 and 2
• Spondyloenchondrodysplasia with immune dysregulation
• Spondylomegaepiphyseal-metaphyseal dysplasia

The recommended genes that should be tested:²

• PTPN11
• EXT1
• EXT2
• ACP5
• NKX3-2
• IDH1
• IDH2

Treatment

Treatment for Maffucci syndrome will depend on the lesion type (enchondroma and hemangiomas) and malignancy.

Enchondromatosis

Surgical treatment is mainly recommended when there are symptoms and pathological fractures. However, other indications prefer surgical treatment:^14,15

• Limb-length discrepancies
• A bone deformity that affects daily activities
• Gait disturbances
• Suspicion of malignant transformation
• Cosmetic deformity
• Oversised enchondromas

Vascular lesions

There is no approved treatment for vascular lesions, however surgical treatment is recommended in vascular overgrowths. Some other recommended treatments are:^4,16

• Sirolimus
• Sclerotherapy
• Surgical resection
• Radiotherapy
• Embolisation
• Chemotherapy

Follow-up

The follow-up guidelines of Maffucci syndrome depend on the age, location, and size. Thus the following:²

In children:

• Clinical screening every 6 to 12 months
• Radiographs of lesions every 2 to 3 years to track

In adults:

• Clinical screening every 12 to 24 months
• Radiographs of lesions every 2 to 3 years to track

FAQs 

What is the first step in diagnosing Maffucci syndrome (MS)?

The diagnosis includes a whole-body MRI to assess all affected bones, determine the type of bone and cartilage tumours, and check for any vascular anomalies in internal organs.

Is there a treatment for MS?

Yes, however it depends on the location and size of lesions. 

How often should children with MS be screened?

Children should have a clinical screening every 6-12 months and plain X-rays of known lesions every 2-3 years to detect growth abnormalities that may need surgical treatment.

What is the recommended surveillance for adults with MS?

To detect and treat any malignant transformation early, adults should have a clinical examination every 12-24 months and plain X-rays of known lesions every 2-3 years, depending on the location of the enchondroma.

What is the recommended plan for suspected of chondrosarcoma?

If chondrosarcoma is suspected, an MRI is recommended. It is the best imaging method for distinguishing between enchondroma (benign cartilage tumour) and low-grade chondrosarcoma.

Is a biopsy necessary for diagnosing chondrosarcoma?

Yes, a biopsy may be necessary to confirm the diagnosis of chondrosarcoma.

What if an enchondroma is more significant than 5-6 cm?

A yearly clinical examination and a whole-body MRI are recommended if an enchondroma is more extensive than 5-6 cm.

Summary

Maffucci syndrome, also called Kast syndrome, is a rare, non-hereditary disease affecting fewer than 1 in 100,000 people. It is characterised by multiple benign cartilaginous tumours (enchondromas) and benign vascular growths (hemangiomas). Symptoms usually appear between ages 4 and 5, and they include swelling, joint deformities, and pain. Individuals with Maffucci syndrome have an increased risk of certain malignancies, especially chondrosarcoma. 

Diagnosing the syndrome involves imaging techniques like X-rays, CT scans, and MRIs along with biopsies and genetic testing to identify associated disorders to detect tumours. Treatment may include surgery depending on type of lesions and other therapies for vascular anomalies. Follow-up guidelines differ for children and adults, focusing on screening and tracking lesions over time.