Case 3 -

Enchondroma Scott Kilpatrick

Clinical History: The patient is a 35-year-old male with a painful lytic lesion involving the middle phalanx of his right ring finger. Diagnosis: Enchondroma. Enchondroma (EC) is a benign hyaline cartilage neoplasm arising within the medullary canal of a bone. Most are solitary, but multiple bone involvement (enchondromatosis) occurs rarely. EC may arise at any age, but the majority occurs between the second and fourth decades of life. There is no gender bias. The most common anatomic location is the small tubular bones of the hands and feet, followed by the proximal humerus and distal femur. [1] Involvement of the pelvis, scapula and vertebral spine are extraordinarily rare. In the small tubular bones of the hands and feet, patients complain of soft tissue swelling, sometimes associated with pain and pathologic fracture. Enchondromas within the long bones are usually asymptomatic, incidental findings. Radiologically, EC are generally well-marginated, metaphyseal/diaphyseal lesions with variable amounts of mineralization, arranged in punctate, ring, or arc-type patterns. In the small tubular bones, they are often expansile and show cortical erosion and thinning; conversely, EC of the long bones show minimal bone expansion without endosteal erosion. Soft tissue extension is never present. Morphologically, EC displays sharply-marginated lobules of mature, hypocellular hyaline cartilage, at least partially surrounded by shells of mature, lamellar bone. [2] Individual chondrocytes are uniform, small, and evenly-distributed or arranged in small clusters. Occasional binucleated cells may be observed. Mitotic figures are virtually never seen. Myxoid change within the hyaline cartilage matrix may be focally present but should never be a prominent. The degree of acceptable cellularity and chondrocyte atypia within EC arising from the small tubular bones of the hands and feet is significantly higher than that observed in the extremity long bones. Consequently, hypercellularity is not a reliable feature for distinguishing digital EC from digital chondrosarcoma. Extension into soft tissues or permeation of medullary bone is diagnostic of chondrosarcoma. [3] Immunohistochemistry is not helpful in the differential diagnosis of EC. Cytogenetic analysis has revealed mostly diploid tumors with occasional structural anomalies, most involving chromosome 6 and 12. [4] The vast majority of EC are cured by simple curettage. Local recurrences are rare. Enchondromatosis (Ollier's disease) represents a developmental disorder, characterized by the presence of multiple EC, preferentially affecting the small tubular bones of the hands and feet. Rarely, it is associated with soft tissue and visceral hemangiomas (Maffucci's syndrome), frequently localizing to the same extremity. [5] Most patients develop clinical manifestations at a younger age than those seen with the solitary form of the disease. The severity of the disease is variable, ranging from involvement of a single extremity to multifocal, widespread disease with severe osseous deformities. Most examples of enchondromatosis are sporadic (non-hereditary), but rare examples appear familial with an autosomal dominant inheritance pattern. Radiographically, lesions of enchondromatosis resemble those observed with solitary EC; however, the tumors may be intramedullary, subperiosteal, or intracortical. Compared to solitary EC, enchondromatosis shows significantly greater cellularity and cytologic atypia. The hemangiomas of Maffucci's syndrome may present as capillary, cavernous, or spindle cell subtypes. [5] The diagnosis of chondrosarcomatous transformation is heralded by the presence of significant myxoid changes, permeation of medullary bone, and/or cortical destruction with soft tissue extension. The prognosis of enchondromatosis is dependent on the extent and severity of the underlying disease. Malignant transformation occurs in 15-30% of cases, usually in the form of a low grade chondrosarcoma. [6, 7] Chondrosarcoma (CS) may arise as a primary condition (conventional or classic CS) or be secondary to a precursor lesion (e.g. EC or osteochondroma). Most patients are between the 5th and 7th decades of life at clinical presentation. There appears to be slight male predominance. The pelvis is the most common anatomic site, followed by the proximal long bones of the extremities, especially the femur and humerus. Unlike EC, the small tubular bones of the hands and feet are rarely involved. Patients with CS usually complain of localized pain, often of a long duration. Radiologically, CS generally appear variably calcified with poor margination. Within the long bones, CS arises within the metaphysis or diaphysis, frequently showing areas of bone expansion, cortical thickening, and/or endosteal erosion. Varying amounts of punctate and ring-like calcified densities are present in the majority of tumors, although purely lytic examples occasionally occur. Periosteal reaction is observed in only about 20% of patients; however, soft tissue extension is present in up to 50% of cases. [8] Conventional CS is a pure hyaline cartilage tumor, but the morphologic features depend, in part, on the histologic grade of the tumor. CS are graded via a 3-tiered system, based predominantly on cellularity (which is inversely related to quantity of matrix) and to a lesser extent on nuclear features. Despite being the most common, grade 1 CS represent one of the most challenging diagnoses in bone pathology. The tumors are generally composed of confluent sheets of well-developed hyaline cartilage with mild to moderate cellularity, overlapping degrees of cellularity observed with EC. [10] Individual chondrocytes may be seen solitarily and in small clusters but generally show only minimal atypia with slightly enlarged, hyperchromatic nuclei. Bi-nucleated chondrocytes may be observed, but these cells may also be seen in EC. Perhaps the most helpful diagnostic feature for CS is the presence of permeation of cortical and/or medullary bone. [2, 3] Permeation is defined as the presence of lobules of hyaline cartilage that infiltrate and replace portions of medullary and/or cortical bone, entrapping residual lamellar bone within the cartilaginous matrix. In contrast, EC exhibit nodules of hyaline cartilage clearly separated from the main tumor mass, virtually always at least partially encircled by a shell of lamellar bone, without such bone entrapped in its matrix. [3] The presence of myxoid change tends to be more prominent in CS than in EC. Tumor necrosis, high cellularity, and mitotic activity are features usually seen in higher grade lesions and are generally not helpful in the differential diagnosis of grade 1 CS and EC. Permeation of tumor into adjacent soft tissues is generally required to establish a diagnosis of grade 1 CS of the digits. It is absolutely essential that clinical and radiographic correlation be undertaken. Within the long bones and limb girdles, grade 2 CS are easily recognized as malignant. The tumors are moderately cellular and tend to show greater nuclear atypia and pleomorphism. Nevertheless, the hyaline cartilage matrix remains well-differentiated and clearly recognizable. Rare grade 3 tumors are highly cellular with a tendency toward spindling of the tumor cells; hyaline cartilage differentiation tends to be less well developed. Mitotic figures are easily detected. [8] The main differential diagnosis in the later includes chondroblastic osteosarcoma. Among small biopsy cases lacking diagnostic osteoid, chondroblastic osteosarcomas show increased cellularity at the periphery of the cartilaginous lobules and greater nuclear atypia compared to most CS. The most important prognostic indicator is histologic grade. Bjornsson et al. documented a 5-year survival rate of approximately 89% in patients with grade 1 CS, while patients with grade 2 and 3 tumors had a reported 5-year survival rate of 53%. [8] CS arising in the digits are far less likely to metastasize than those occurring more proximally. [9] Surgical resection is the treatment of choice; however, curettage with adequate follow-up may be employed for phalangeal lesions, especially if amputation would cause significant functional impairment. [9] A higher risk of local recurrence is significantly associated with inadequate surgical margins. Approximately 10% of patients develop dedifferentiated chondrosarcoma, a lethal complication. Ostrowskit ML, Spjut HJ. Lesions of the bones of the hands and feet. Am J Surg Pathol 1997;21:676-690. Mirra JM, Gold RG, Downs J, et al. A new histologic approach to the differentiation of enchondroma and chondrosarcoma of the bones: a clinicopathologic analysis of 51 cases. Clin Orthop 1985;201:214-237. Ogose A, Unni KK, Swee RG, et al. Chondrosarcoma of the small bones of the hands and feet. Cancer 1997;80:50-59. Gunawan B, Weber M, Bergmann F, et al. Clonal chromosome abnormalities in enchondromas and chondrosarcomas. Cancer Genet Cytogenet 2000;120:127-130. Fanburg JC, Meis-Kindblom JM, Rosenberg AE. Multiple enchondromas associated with spindle-cell hemangioendotheliomas: an overlooked variant of Maffucci's syndrome. Am J Surg Pathol 1995;19:1029-1038. Liu J, Hudkins PG, Swee RG, et al. Bone sarcomas associated with Ollier's disease. Cancer 1987;59:1376-1385. Sun BT, Swee RG, Shives TC, et al. Chondrosarcoma in Maffucci's syndrome. J Bone Joint Surg [Am] 1985;67:1214-1219. Bjornsson J, McLeod RA, Unni KK, et al. Primary chondrosarcoma of long bones and limb girdles. Cancer 1998;83:2105-2119. Bovee JVMG, van der Heul RO, Taminiau AHM, et al. Chondrosarcoma of the phalanx: a locally aggressive lesion with minimal metastatic potential. Cancer 1999;86:1724-1732.