Maffucci's syndrome—The result of neural abnormalities? Evidence of mitogenic neurotransmitters present in enchondromas and soft tissue hemangiomas

Background. Maffucci's syndrome (MS) is distinguished by the enigmatic association of benign cartilaginous bone tumors and soft tissue hemangiomas. Methods. This study was conducted to define the distribution of nerves and neuropeptides around these tumors. Results were measured by quantitative image analysis of immunohistochemical staining. Four types of tissues were compared: connective tissues around normal muscles, solitary hemangiomas, MS hemangiomas, and MS enchondromas (the last two from a single patient). Results. The number of nerves was found to be quadrupled in both types of hemangiomas as compared to normal connective tissue. A unique feature of MS tissues is the presence of an increased number of nerve fibers not only in the lesions but also in histologically normal margins of resection surrounding the lesions. Furthermore, hemangiomas of both types were found to contain a significantly higher number of calcitonin gene‐related peptide‐, substance P‐, and methionine enkephalin‐positive fibers than did normal muscle or its related fibroconnective tissue. These neuropeptides are mitogens, and their presence stimulates the growth of the abnormal blood vessels. Enchondroma fragments from an MS patient contained numerous methionine enkephalin‐positive nerves. This neuropeptide is known to act as a growth factor in cartilage proliferation. Conclusions. A neural abnormality of the neuropeptidergic nervous system seems to relate to the abnormal tumors seen in MS.