Common Diagnostic Dilemmas in Bone and Soft Tissue Surgical Pathology
Case 3 -
The patient is a 35-year-old male with a
painful lytic lesion involving the middle phalanx of his right ring finger.
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.  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.  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.  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.  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.  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.  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 (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. 
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.  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.
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.  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.  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%.  CS arising in the digits are far less likely to
metastasize than those occurring more proximally.  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.  A higher risk of local recurrence
is significantly associated with inadequate surgical margins. Approximately 10% of patients develop
dedifferentiated chondrosarcoma, a lethal complication.
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- 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.
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- 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.