Vascular Tumors Unraveling a Rare Genetic Disorder

Case Presentation A 19-year-old female presented with multiple soft, bluish, painless swellings on both hands and feet. The onset of these swellings occurred at the age of 5 years and has since gradually increased in size. There was no history of similar lesions in any family members. On physical examination, multiple soft, compressible subcutaneous bluish nodules were observed on both thumbs [Figure 1], multiple toes, and on the heel of the right foot. Local site ultrasound examination demonstrated multiple hypoechoic lesions in the subcutaneous plane in the hands and feet at the site of the swellings. These lesions showed internal vascularity on color Doppler of a slow-flow type. X-rays of both hands and feet showed multiple radiolucent, expansile, and multiloculated osteolytic lesions in the phalanges and metacarpals of both hands and feet, along with destruction of the respective joint spaces, valgus deformity of the left ring finger, and soft tissue shadows corresponding to the swellings. Cortical thinning and endosteal scalloping were also observed, with few areas of complete absence of cortex [Figure 2].Figure 1: (a) Soft, compressible, subcutaneous bluish nodule observed on the right thumb (b) Multiple soft, compressible, subcutaneous bluish nodules were observed on the heel of the right footFigure 2: (a) Multiple radiolucent, expansile, and multiloculated osteolytic lesions in the phalanges and metacarpals of both hands (green arrow), along with destruction of the respective joint spaces (yellow arrow), valgus deformity of the left ring finger (pink arrow), and soft tissue shadows corresponding to the swellings (blue arrow). Cortical thinning and endosteal scalloping (black arrow) were also observed, with few areas of complete absence of cortex (red arrow). (b) Similar lesions were observed in both feetWhat is the diagnosis? Diagnosis Maffucci syndrome with enchondromas and venous malformations. Discussion Maffucci syndrome is a rare genetic disorder characterized by the distinct presence of multiple enchondromas and vascular tumors or malformations. It was first described in 1881, and less than 200 cases have been reported in literature since then.[1] It has been recently linked to somatic mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes. It usually appears before puberty, mostly at the age of 4–5 years, and has no sexual or ethnic predisposition. However, 25% of the patients present at birth or within 1 year of birth.[2] The common presenting features are asymmetric leg contracture, swelling of the hands and feet (vascular malformations), and occasionally fracture of the affected parts.[2] Bony lesions mostly appear in the metaphyses of short tubular bones such as metacarpals and phalanges of hands (89.3%), infrequently in the short tubular bones of feet (35.7%) and long tubular bones of upper and lower limbs.[3] Generalized mesodermal dysplasia occurs when the bone grows and enlarges in length, but the cartilage lags and grows asymmetrically, resulting in enchondroma formation. Hence, multicentric radiolucent areas with significant cortical thinning are the pathognomonic sign on X-ray.[3] Longitudinal strips and honeycombs can form at the center or sides of the bones, along with cystic transparent areas. Vascular lesions occur in the form of deep hemangiomas, spindle cell hemangiomas, venous, or rarely lymphatic malformations.[1] Hemangiomas occur at a rate of 32% in the hands and 23% in the feet. These lesions generally present as soft bluish or bluish-red nodules, as seen in our patient. Cutaneous lymphangioma circumscriptum has also been reported,[4] representing another aspect of mesodermal dysplasia in Maffucci’s syndrome. Currently, there is no unified criteria for diagnosing Maffucci syndrome, and is largely a clinical diagnosis. Histopathological examination of the vascular lesions can be performed if needed. Maffucci syndrome can result in a variety of complications, including pathological fractures, skeletal deformities, vascular overgrowth, limb-length discrepancies, and malignant transformations.[2] Malignant transformations occur at a rate of 52%–57% in Maffucci syndrome. Chondrosarcomas account for 30% of the malignant lesions in Maffucci syndrome.[3] Phleboliths can also form, which appear as distinct round calcifications in soft tissues on X-ray and are prone to forming micro-thrombi.[3] Maffucci syndrome must be differentiated from other enchondromatosis like Ollier disease.[3] Ollier disease is characterized by unilateral enchondromas and the absence of hemangiomas. Other differentials include blue rubber bleb nevus syndrome, in which the vascular lesions are rubbery, soft, tender, hemorrhagic, easily compressible, and promptly refill after compression. Enchondromas are not a feature of blue rubber bleb nevus syndrome.[5] Gorham Stout syndrome is another differential diagnosis in which only vascular malformations are observed, along with massive osteolysis of long bones.[6] The main aim of the management of Maffucci syndrome is symptomatic relief and early recognition of the disease to prevent the complications. For complications like vascular overgrowth, enlarged enchondromas, and limb-length discrepancies, surgical correction and removal of enchondromas is the only treatment possibility. At present, no effective treatment for vascular lesions of Maffucci syndrome is available. Sirolimus, a mammalian target of rapamycin inhibitor, has been used with varying results in reducing the progression and symptoms of vascular anomalies. However, further research must be performed to determine its full effectiveness.[7] Sclerotherapy may also be tried. Due to the risk of malignant transformation, regular follow-up is an absolute necessity. A multidisciplinary approach involving orthopedic surgeons, geneticists, and radiologists is crucial for comprehensive management. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.