A 25-year-old woman presented with a firm mass in her left lateral pelvis. Although she had noticed the mass 5 years earlier, it became much more prominent after a recent planned weight loss of 70 pounds. She felt pain in the area of the mass when lying on her side, but she did not experience any weakness, paresthesias, or numbness. Her past medical history was significant only for hypertension. Family history was negative for bone diseases.

Physical exam revealed a bony mass that was immovable and attached to her left iliac wing. The mass was approximately 7 cm in greatest dimension. She felt mild pain with extremes of abduction and adduction of her left hip. Her lower extremity sensation, pulses, reflexes, and strength were all within normal limits.

A radiograph showed a mushroom-shaped bony excrescence joined to the iliac wing by a broad stalk (Figure 1). Computed tomography confirmed this and showed that the mass did not have a fibrous capsule (Figure 2). Subsequently, the patient underwent surgical removal of the suspicious bone lesion. Postoperatively there was no evidence of erosion or destruction of the surrounding bone; however, mild atrophy and effacement of the adjacent gluteal muscle were present.

The gross specimen consisted of 2 fragments of bony tissue with irregular cartilaginous surfaces that measured 7.0 × 5.0 × 4.8 cm and 6.0 × 4.5 × 3.5 cm (Figure 3). The cut section revealed trabeculated bone covered with a thin layer of cartilage and several nodules of focal calcification. Microscopic examination demonstrated a disorganized cartilaginous cap overlying a zone of chondro-osseous transformation. The chondrocytes within the cap displayed nuclei that varied in shape and size relative to each other. Most importantly, no distinct atypia was noted (Figure 4).

What is your diagnosis?

Osteochondromas represent the single largest group of benign bone tumors. Comprised of an outgrowth of cortical and medullary bone capped with cartilage, they usually present before the age of 20. They may arise in the epiphyseal regions of the distal femur, proximal humerus, and proximal tibia. However, they do not occur in the craniofacial bones. Radiographically and grossly, osteochondromas have a classic mushroom shape with a narrow to broad stalk attaching the osseous base to the parent bone. The cartilage cap is smooth, with an irregularly knobby surface that covers this osseous base to a depth ranging from 0.1 to 3.0 cm, all of which is enclosed in a transparent periosteum.1 Microscopically, they demonstrate a moderately disorganized cartilage cap composed of chondrocytes, with nuclei varying from normal up to 5 times the normal size and occasionally displaying moderate nuclear atypia. A barely visible layer of fibrous periosteum overlies the cap. The cartilage generally abuts the underlying bone in a manner reminiscent of an epiphyseal plate, but islands of chondrocytes are often found trapped within the bone after ossification of the pseudoepiphyseal plate progresses. Typically, the thickness of the cartilaginous cap is inversely proportional to the patient's age.1,2 

Although the diagnosis of this disease is straightforward, controversy continues to surround the etiology, the pathogenesis, and indeed, even the classification of the osteochondroma. The classical theories presented over the last 100 years describe it as a skeletal dysplasia or epiphyseal malformation, in which displaced growth-plate cartilage penetrates a defect in the periosteum and grows at an acute angle to the longitudinal axis of the developing parent bone, away from the nearest joint. In addition, some cases include decreased stature and bowed long bones, and these theories postulate that growing osteochondromas sequester a large enough population of chondrocytes that the normal epiphyseal plate loses some of its osteogenic potential, resulting in shorter bones. The common thread that runs through these theories is the assumption that multiple, otherwise-normal chondrocytes participate in the initial formation of osteochondromas.3 

However, contrary to this assertion, recently emerged molecular and genetic data cast doubt on a mechanical or structural etiology, instead favoring a neoplastic explanation. Mutations in the EXT family of putative tumor suppressor genes have been implicated in the pathogenesis of osteochondromas. The 2 principle genes involved are EXT1 and EXT2, which encode a heterodimeric polymerase responsible for the addition of heparan sulfate onto proteoglycans.4 Loss of heterozygosity studies show that these genes are not functional in tumor cells and also reveal that the tumors arise from a clonal expansion of a single parent cell, which is a definitive feature of neoplasia.3 

In addition, osteochondromas share several features of other established neoplastic lesions, such as tumors of the colon. Like colorectal polyps, an autosomal dominant inherited multiple form exists, known as hereditary multiple exostoses; the lesions occur randomly at predisposed sites; they often demonstrate architectural disorder or nuclear atypia; and the potential for malignant transformation, specifically chondrosarcoma, exists.3 

Although this comparison is compelling, at least 2 important problems remain. First, the lifetime risk of malignant transformation in hereditary multiple exostoses is only 0.5% to 5%, compared to a near 100% risk of transformation to colorectal cancer in familial adenomatous polyposis. Second, and more important, unlike other tumors and contrary to the current definition of neoplasia, most osteochondromas cease growing and ossify at the end of puberty, indicating that their growth mechanisms do indeed respond to hormonal regulation and so are ultimately controllable.5 

Fechner
,
R. E.
and
S. E.
Mills
.
Tumors of the Bones and Joints.
Washington, DC: Armed Forces Institute of Pathology; 1993. Atlas of Tumor Pathology; 3rd series, fascicle 8
.
Bullough
,
P. G.
Cartilage-forming tumors and tumor-like conditions.
In: Orthopedic Pathology. London: Mosby-Wolfe; 1997:353–357
.
Porter
,
D. E.
and
A. H. R. W.
Simpson
.
The neoplastic pathogenesis of solitary and multiple osteochondromas.
J Pathol
1999
.
188
:
119
125
.
Duncan
,
G.
,
C.
McCormick
, and
F.
Tufaro
.
The link between heparan sulfate and hereditary bone disease: finding a function for the EXT family of putative tumor suppressor proteins.
J Clin Invest
2001
.
108
:
511
516
.
Bovée
,
J. V. M. G.
and
P. C. W.
Hogendoorn
.
Re: review article entitled ‘The neoplastic pathogenesis of solitary and multiple osteochondromas.’.
J Pathol
2000
.
190
:
516
517
.

Author notes

Corresponding author: Aiman Zaher, MD, Department of Pathology, Medical College of Ohio, School of Medicine, 3000 Arlington Ave, Toledo, OH 43615-2598 ([email protected])