CORRECT DIAGNOSIS:

Maffucci Syndrome

DISCUSSION:

Maffucci syndrome is a rare congenital disorder characterized by the presence of multiple enchondromas and vascular malformations. With fewer than 200 cases reported worldwide, this condition manifests in early childhood and typically progresses until puberty. It is notable for its equal prevalence among all ethnic groups and genders, with a median age of diagnosis around 11 years. The syndrome predominantly affects the extremities, especially the upper limbs, although it can also present with cephalic lesions that may lead to severe neuro-ophthalmologic complications.

In our patient, the presence of multiple, well-defined enchondromas—benign cartilaginous tumors arising from the medullary cavity of bones—was suspected. These tumors can lead to complications such as pain, deformity, and limited range of motion. Importantly, there is a significant risk (approximately 25%-30%) of malignant transformation of these enchondromas into osteosarcoma or other malignancies, which represents one of the most severe complications associated with the syndrome.

The underlying genetic basis of Maffucci syndrome is associated with sporadic somatic mutations in the NADP+ dependent isocitrate dehydrogenase 1 (IDH1) or IDH2 genes.  These mutations play a critical role in the pathogenesis of the syndrome, distinguishing it from similar conditions. For instance, enchondromatosis can occur in two settings: Ollier’s disease, which lacks the vascular malformations seen in Maffucci syndrome.

Diagnosis is primarily based on a detailed medical history, comprehensive physical examination, and radiologic assessment. In our case, imaging studies revealed soft tissue hemangioma with calcifications, irregular skeletal expansion, thinning of the cortex, and endosteal scalloping, further supporting the diagnosis of Maffucci syndrome. Whole-body MRIs are recommended to monitor for asymptomatic chondrosarcomas, which may develop in patients with this syndrome.

Microscopically, enchondromas are characterized by “islands of intramedullary hyaline cartilage surrounded by marrow fat,” while chondrosarcomas exhibit “diffuse cartilaginous replacement (invasion) of the marrow,” leading to the complete entrapment of host lamellar bone trabeculae. Despite the utility of radiographs and MRI, both modalities have limitations in assessing low-grade cartilage lesions, with low-grade chondrosarcomas showing a significantly higher incidence of distinctive MRI findings.

TREATMENT:

CONCLUSION:

Maffucci syndrome is a complex and rare condition that poses significant challenges in diagnosis and management. Our patient’s clinical presentation exemplifies the typical features of the syndrome, emphasizing the need for thorough evaluation and a multidisciplinary approach. Close clinical follow-up is crucial for patients with Maffucci syndrome due to the risk of malignant transformation of enchondromas into chondrosarcomas, necessitating vigilant monitoring and timely intervention.

While current treatment options include sirolimus, further studies are needed to characterize its efficacy specifically in Maffucci syndrome. Additionally, the potential benefits and risks of IDH1/2 inhibitors remain unknown; however, these agents could potentially lead to a reduction in tumor growth or lower the risk of cancer progression within enchondromas. This possibility has yet to be explored, likely due to the rarity of the condition. Nevertheless, for patients experiencing severe manifestations of Maffucci syndrome or those progressing to malignancy, these agents may offer therapeutic benefits worth investigating.

Understanding the clinical features, potential complications, and the importance of coordinated care is essential for optimal patient management. Continued research into the genetic and molecular mechanisms underlying Maffucci syndrome will be crucial for developing targeted therapies and improving outcomes for affected individuals.

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