Overview

Maffucci syndrome, a rare, non-hereditary disorder, primarily affects the bones and skin, leading to multiple enchondromas (benign cartilage tumours) and haemangiomas (benign blood vessel tumours). Named after Italian pathologist Angelo Maffucci, who first described the condition in 1881, this syndrome manifests in childhood and progresses throughout life, often resulting in significant complications and requiring careful management. 

This article delves into the soft tissue manifestations of Maffucci syndrome, exploring its pathophysiology, clinical presentation, diagnosis, and management.

Pathophysiology

Maffucci syndrome arises from somatic mutations, typically in the IDH1 or IDH2 genes, involved in cellular metabolism. These mutations are not inherited but occur spontaneously. The genetic alterations lead to abnormal cell proliferation and differentiation, resulting in the characteristic enchondromas and hemangiomas. The soft tissue manifestations, primarily hemangiomas, are critical in diagnosing and managing the syndrome due to their potential complications and impact on the patient's quality of life.

Clinical presentation

Hemangiomas

Hemangiomas in Maffucci syndrome are benign vascular tumours that can appear anywhere on the body, although they are most commonly found on the hands and feet.¹ 

These lesions are usually present at birth or develop in early childhood and grow proportionally with the child. They can vary in size and appearance, ranging from small, red, and superficial to large, deep, and have a blue-purple colour. Types of hemangiomas:

• Capillary hemangiomas: These are small, superficial lesions that often appear as red spots on the skin. While generally not problematic, they can occasionally cause discomfort or bleeding if traumatised
• Cavernous hemangiomas: Larger and deeper than capillary hemangiomas, these lesions can cause more significant issues, including pain, swelling, and, in some cases, compression of nearby structures, leading to functional impairment
• Mixed hemangiomas: These contain both capillary and cavernous components, exhibiting characteristics of both types

Other soft tissue manifestations apart from hemangiomas, Maffucci syndrome can lead to other soft tissue anomalies, including lymphangiomas (malformations of the lymphatic system), soft tissue enchondromas, and fibromas (benign fibrous tumours). These manifestations contribute to the overall complexity of the syndrome and require a comprehensive diagnostic approach.

Diagnostic approach

Diagnosing Maffucci syndrome involves a combination of clinical evaluation, imaging studies, and histopathological examination.³ 

The presence of multiple enchondromas and hemangiomas typically prompts further investigation.

Clinical evaluation

A thorough clinical evaluation is the first step, focusing on the characteristic skin lesions and skeletal abnormalities. A detailed medical history, including the age of onset and progression of symptoms, is essential. Physical examination should include a careful inspection and palpation of the skin and soft tissues to identify and characterise hemangiomas.

Imaging studies

• Radiography: X-rays are useful for detecting enchondromas, which appear as radiolucent areas (darker areas)  within the bones. They help in assessing the extent of skeletal involvement and identifying potential complications such as fractures or malignant transformation
• Magnetic resonance imaging (MRI): MRI is the preferred modality for evaluating soft tissue lesions, providing detailed information about the size, location, and nature of hemangiomas. It can also help differentiate between benign and malignant lesions
• Ultrasonography: This non-invasive imaging technique is particularly useful for assessing superficial hemangiomas. It can provide information about the vascularity and depth of the lesions

Histopathological examination

Biopsy and histopathological examination of the lesions can confirm the diagnosis. Hemangiomas show characteristic findings, such as proliferating blood vessels and, in some cases, thrombosis or fibrosis. Enchondromas typically display hyaline cartilage with characteristic cytological features.

Complications

The soft tissue manifestations of Maffucci syndrome can lead to several complications, affecting the patient's overall health and quality of life.

Pain and functional impairment

Large or deep hemangiomas can cause significant pain and discomfort. When located near joints or in weight-bearing areas, they can interfere with mobility and daily activities. Compression of nerves or blood vessels by these lesions can lead to additional complications, including neuropathy and vascular insufficiency.

Bleeding and ulceration

Superficial hemangiomas are prone to bleeding, especially if traumatised. In some cases, they can ulcerate, leading to infection and further complications. Proper wound care and preventive measures are essential to minimise these risks.

Malignant transformation

While the risk of malignant transformation in hemangiomas is low, enchondromas in Maffucci syndrome carry a significant risk of developing into chondrosarcoma, a malignant cartilage tumour. Regular monitoring and prompt intervention are crucial to detect and manage malignancies early.

Psychosocial impact

The visible and often disfiguring nature of hemangiomas can have a profound psychosocial impact on patients, especially children and adolescents. They may experience social stigma, low self-esteem, and emotional distress. Psychological support and counselling are important components of comprehensive care.

Management

Management of Maffucci syndrome is multidisciplinary, involving dermatologists, orthopaedic surgeons, radiologists, and other specialists. The approach is tailored to the individual's symptoms, lesion size and location, and overall health.

Observation and monitoring

For asymptomatic or minimally symptomatic lesions, observation and regular follow-up may be sufficient.⁴ This approach includes periodic clinical evaluations and imaging studies to monitor the lesions' progression and detect any complications early.

Medical management

• Pain management: Analgesics and anti-inflammatory medications can help manage pain associated with hemangiomas and enchondromas. In some cases, corticosteroid injections may be beneficial for reducing inflammation and pain
• Sclerotherapy: This minimally invasive procedure involves injecting a sclerosing agent into the hemangioma, causing it to shrink. Sclerotherapy is particularly useful for cavernous and mixed hemangiomas
• Laser therapy: Laser treatment can be effective for superficial hemangiomas, reducing their size and improving cosmetic appearance. Multiple sessions may be required for optimal results

Surgical intervention

Surgery is often necessary for symptomatic or complicated lesions. The type and extent of surgery depend on the lesion's size, location, and impact on function.

• Excision: Surgical removal of hemangiomas or enchondromas may be indicated for large, symptomatic, or cosmetically concerning lesions. Complete excision is preferred to minimise recurrence
• Debulking: In cases where complete excision is not feasible, debulking procedures can reduce the lesion's size and alleviate symptoms
• Reconstructive surgery: For extensive or disfiguring lesions, reconstructive surgery may be necessary to restore function and appearance. This can involve skin grafting, tissue flaps, or other reconstructive techniques

Rehabilitation and support

Rehabilitation, including physical and occupational therapy, can help patients regain function and improve mobility.⁵ 

Psychological support and counselling are also important, addressing the emotional and social challenges associated with the syndrome.

Summary

Maffucci syndrome, though rare, presents significant clinical challenges due to its complex soft tissue manifestations. Hemangiomas, the primary soft tissue lesions, can lead to pain, functional impairment, bleeding, and psychosocial issues. 

Early diagnosis, regular monitoring, and a multidisciplinary approach to management are essential to mitigate complications and enhance the quality of life for affected individuals. 

Ongoing research and advances in medical and surgical treatments continue to improve outcomes for patients with this challenging syndrome.