Lesions Characterized by Osteoid Deposition and Nonaggressive Radiology Located on Bone Surface

Definition and Synonyms

Osteochondroma, also known as exostosis or osteocartilaginous exostosis, is characterized by a cartilage-capped bony outgrowth containing a marrow cavity with continuity to the underlying bone.

Historical Background

Osteochondromas are the most common benign bone tumors. The tumors occur exclusively in bones of endochondral origin and thus predominantly arise from the metaphysis of long bones, especially those around the knee and in the proximal humerus. They commonly develop during childhood or adolescence, with a peak incidence in the second decade of life. Approximately 85% of osteochondromas are solitary. The remainder are seen as part of hereditary multiple osteochondroma (HMO), an autosomal dominant disease thought to be caused principally by germline loss-of-function mutations in either the EXT1 or EXT2 gene.

Incidence and Demographics

The reported incidence of osteochondromas in benign bone tumors is 33.4% and in chondrogenic tumors 32.8%, and osteochondromas represent 10.1% of all bone tumors. However, it is thought that the true incidence is much higher because many osteochondromas are small in size and asymptomatic and thus are not clinically detected or surgically removed. Most cases present in the first three decades of life (approximately 50% in the second decade), with a slight male predominance.

Localization and Clinical Manifestations

Osteochondromas develop exclusively in bones of endochondral origin and arise from the metaphyseal region near the growth plate of long, tubular bones, most commonly the distal femur, proximal tibia and fibula, and proximal humerus. The tumors occasionally develop in bones of ribs, scapula, and pelvis. They rarely involve the short, tubular bones of hands and feet. Many osteochondromas are asymptomatic and are found incidentally. Long-standing lesions may produce a large, hard mass; thus, patients may present with pain due to mechanical irritation, although not all lesions are painful. Common secondary complications include limitation of motion; impingement on nerves, vessels, or tendons; bursa formation; arthritis; and stalk fracture. Increasing pain and/or rapidly growing masses may indicate malignant transformation to secondary chondrosarcomas.

Radiologic Features and Gross Pathology

Radiologically, osteochondromas present as sessile, exophytic, or pedunculated bony masses with cartilage caps ( Figs. 7-1 and 7-2 ). Conventional radiographs are usually sufficient for diagnosis of these lesions. The cortex and medullary cavity of the lesions are continuous with the cortex and medulla of the adjacent native bone, respectively, which is typically appreciated by computed tomography (CT) ( Fig. 7-3 ). Magnetic resonance imaging (MRI) is helpful in determining the relationship of the lesions to adjacent structures and the thickness of the cartilage cap ( Fig. 7-4 ).

A bursa may develop over an osteochondroma (bursa exostotica) and is usually attached to the perichondrium of the cap. The bursa may become inflamed, with accumulation of a large amount of fluid (bursitis), thus resulting in gradually increasing pain. A thick cartilage cap with infiltration into surrounding soft tissues may raise the question of malignant transformation.

The gross pathologic features usually recapitulate the radiologic findings. A surgically resected specimen is typically a bony mass with a smooth, glistening, bluish gray cartilage cap ( Fig. 7-5 ). On cross section, a rim of cortical bone and central medullary bone can be appreciated, similar to that seen in normal bone. The cartilage cap is usually thin, and its thickness decreases with age. A thick and irregular cap (>2 cm) may be indicative of malignancy but can be seen in benign lesions in skeletally immature individuals.

Histopathology

On low-power view, osteochondromas typically have three layers: perichondrium, cartilage, and bone ( Fig. 7-6 ). The surface perichondrium (not seen over the normal articular cartilage) is continuous with the periosteum of the parental bone. The underlying hyaline cartilage, similar to normal articular cartilage, undergoes endochondral ossification simulating the growth plate, thus creating trabecular bone that is surrounded by marrow adipose tissue and rare hematopoietic elements. This is continuous with the medullary canal of the underlying bone ( Fig. 7-7 ).

Compared with enchondromas of long bones, the cartilage of osteochondromas typically shows increased cellularity and a greater number of binucleated chondrocytes. Other secondary changes, such as irregular calcification and myxoid degeneration, may be present, especially in larger, long-standing lesions. Significant nuclear atypia, mitotic figures, and necrosis are typically not seen.

Differential Diagnosis

Markedly increased cellularity, along with significant nuclear atypia, discernible mitotic activity, and tumor necrosis, should raise concern for secondary chondrosarcoma. Rarely, dedifferentiated chondrosarcoma may develop in an osteochondroma. However, distinguishing osteochondroma from low-grade secondary chondrosarcoma is difficult based on purely histologic grounds and should be made by a multidisciplinary approach.

Genetics

Cytogenetic alterations involving 8q22-24.1, where the EXT1 gene is located, are found in approximately 56% to 78% of HMO cases and up to 80% of sporadic osteochondromas, whereas cytogenetic abnormalities involving the EXT2 gene (11p12-p11) are less frequent and are only seen in HMO cases (21% to 44%). HMO is inherited in an autosomal dominant manner, with an estimated penetrance of 96%. About 10% of affected individuals develop HMO as the result of a de novo mutation.

The cell origin in osteochondroma is thought to be the proliferating chondrocyte of the growth plate. The EXT gene products, exostosin-1 and exostosin-2, are transmembrane glycoproteins involved in biosynthesis of heparan sulfate proteoglycans, which are the key modulators of endochondral ossification. A mixture of wild-type and heparan sulfate–mutated chondrocytes are present in the cartilage cap of osteochondromas. Most mutations in the EXT1 or EXT2 genes in HMO patients are thought to result in a truncated or nonfunctional protein. Loss of heparan sulfate may give the chondrocyte a proliferative advantage, thus resulting in the loss of polarity and leading to altered hedgehog signaling. The double-hit mutation model was proposed for the formation of osteochondromas. Based on this model, the chondrocytes harboring mutations causing disturbed hedgehog signaling lose polarity and grow out through a defective bony collar.

The molecular genetic testing for EXT genes includes fluorescence in situ hybridization (FISH; for larger deletions) and sequence analysis (for small intragenic deletions/insertions and missense, nonsense, and splice site mutations).

Treatment and Prognosis

Osteochondromas usually stop growing at the time of growth plate closure. Treatment is generally unnecessary for asymptomatic lesions. If the tumor is causing pain or neurologic symptoms due to compression, a complete excision at the base is curative.

The risk of malignant transformation in solitary osteochondromas increases as the number and size of the osteochondromas increases. Sessile lesions are more likely to transform into sarcoma than pedunculated tumors. The estimated risk of malignant transformation to a secondary chondrosarcoma is about 1% for solitary osteochondromas and 5% to 30% in patients with HMO.

Definition and Synonyms

Bizarre parosteal osteochondromatous proliferation (BPOP) is characterized by a rapidly growing bony mass involving the surface of bone, usually affecting the small, tubular bones of the hands and feet. It was first described in 1983 by Nora and colleagues ; thus, it is also known as Nora lesion.

Historical Background

BPOP is typically small but has aggressive features on imaging studies and worrisome findings histologically. It was originally thought to be a reactive process; however, recent cytogenetic studies have identified a nonrandom molecular signature t(1 : 17)(q32;q21), thus supporting its neoplastic nature.

Incidence and Demographics

BPOP can occur in individuals of all ages but is more commonly seen in younger adults, with a peak incidence in the third and fourth decades of life. Men and women are equally affected.

Localization and Clinical Manifestations

BPOP most commonly involves the proximal and middle phalanges, metacarpals, and metatarsals, and it rarely occurs in the long bones, skull, and jaw. Swelling or mass with or without pain is the most common clinical presentation. The mass seems to grow rapidly over weeks or months. A history of trauma is typically absent.