Bone-Forming Tumors

Clinical Features

Bone island (enostosis) is a benign, bone-forming tumor composed of cortical-type bone, which involves the medullary cavity. The true incidence is unknown as it is most commonly detected as an incidental radiographic finding. Its prevalence in pelvic bones and ribs has been reported to be 1.08% and 0.43%, respectively, and some investigators indicate that 3% to 4% of the population has a bone island in their skeleton. Bone islands have been identified in all age groups, although they are reported to be fairly uncommon in children and have no sex predilection. The pelvis, proximal femur, and ribs are the most frequently involved sites. Within tubular bones, they usually involve the epiphyses. Clinically, bone islands are asymptomatic, with only exceptional cases causing pain.

Osteopoikilosis is a syndrome that may be inherited in an autosomal dominant fashion and is caused by a loss-of-function mutation in the LEMD3 gene, which encodes a nuclear envelope protein involved in the regulation of the transforming growth factor beta (TGF-beta) and bone morphogenic protein (BMP) pathways. Some patients may also have melorheostosis and Buschke–Ollendorff syndrome. Clinically, the disorder is characterized by the presence of innumerable bone islands, which are bilateral, symmetric, and most frequently involve the metaphyseal and epiphyseal regions of tubular bones, carpal, and tarsal bones, and the flat bones of the proximal limb girdles. Radiographically, macroscopically, and histologically, they are identical to sporadic, solitary bone islands.

Radiologic Features

Bone islands have characteristic radiographic features. On plain films they appear as small, round, homogeneously radiodense lesions that have spiculated margins that merge with surrounding cancellous bone ( Fig. 16.1 ). The lesions, particularly those which are large in size, may abut or arise in association with the endosteal surface; however, they do not involve the cortex and do not elicit a periosteal reaction ( Fig. 16.2A ). On computed tomographic (CT) scans, bone islands appear identical to cortical bone ( Figs. 16.2B and 16.3 ). On magnetic resonance imaging (MRI), they have low signal intensity giving them a dark appearance and, on bone scan, they absorb little-to-no tracer and are referred to as “cold.”

Pathologic Features

Grossly, bone islands arise within the medullary cavity, are generally not much larger than 1 cm in diameter, and are hard, solid, and tan-white. Their periphery merges seamlessly into surrounding cancellous trabeculae.

Histologically, bone islands consist of cortical-type bone that is predominately lamellar, may be focally woven, and contains Haversian-like canals ( Fig. 16.4 ). The osteoblasts lining the bone surfaces are flat and quiescent, and the osteocytes are small and cytologically banal. Lesional bone at the periphery merges almost imperceptibly into pre-existing lamellar bone ( Fig. 16.5 ).

Differential Diagnosis

The most important differential diagnostic consideration is intramedullary well-differentiated osteosarcoma. In contrast to bone island, intramedullary well-differentiated osteosarcoma is infiltrative, the bone is usually trabecular rather than cortical, and the neoplastic matrix is surrounded by a monotonous population of proliferating spindle cells rather than a single layer of quiescent surface osteoblasts. While the distinction is usually a morphologic one, in small biopsies or samples with adjacent fibrosis, it could rarely be helpful to assess for the presence of MDM2 amplification by in situ hybridization (ISH) or immunohistochemistry (IHC), which is often seen in intramedullary well-differentiated osteosarcoma and not enostoses.

Another lesion that may enter the differential is an osteoblastic metastasis. In contrast to an enostosis, the newly formed bone in an osteoblastic metastasis is trabecular and generally surrounds islands of carcinoma cells that are cytologically malignant and morphologically different from the osteoblasts seen in bone islands.

Prognosis and Treatment

Bone islands usually do not require treatment, as they are indolent and typically asymptomatic. They may undergo remodeling, altering the radiographic appearance of the lesion; however, they do not undergo biologic transformation to a more aggressive process. Rare cases, particularly those presenting as larger lesions, may require biopsy to exclude a more aggressive neoplasm such as well-differentiated osteosarcoma or sclerotic metastasis. Lesions which are excised may rarely recur.

Clinical Features

Osteoma is a benign, bone-forming tumor that arises on the cortical surface. The majority of tumors are composed of mature, compact, cortical-type bone; however, rare cases may be composed of cancellous-type bone. They usually develop on the surface of the craniofacial skeleton and have a particular propensity to involve the bones of the paranasal and frontal sinuses and the orbit where they are found in 1% to 3% of the adult population. Rarely, osteomas are located in the vertebral column or the appendicular skeleton where they develop on the surfaces of long tubular bones. They have a slight male predilection and are typically diagnosed during mid-adulthood. Osteoma is usually solitary but may be multiple in a minority of cases. Importantly, the diagnosis of osteoma in a young patient or multiple osteomas should raise suspicion for the presence of Gardner syndrome, an autosomal dominant intestinal polyposis syndrome caused by mutations in the adenomatous polyposis coli (APC) tumor suppressor gene and associated with a predisposition for colorectal adenocarcinoma, osteomas, dental anomalies, epidermal inclusion cysts, congenital hypertrophy of the retinal pigment epithelium, and various soft tissue tumors.

Craniofacial osteomas are commonly asymptomatic and detected as incidental radiographic findings. Larger tumors, however, may cause cosmetic issues such as swelling and facial asymmetry in addition to symptoms secondary to sinus obstruction, including discharge and mucocele formation. Orbital osteomas can induce a variety of secondary symptoms, including dacryocystitis, exophthalmos, and diplopia. Tumors involving the spinal column may be complicated by spinal cord or nerve compression, and those developing in the extremities can present as a palpable, possibly painful, mass.

Radiologic Features

Osteomas are usually round-to-ovoid, uniformly radiodense, sharply demarcated, and have a broad base of attachment to the cortical bone surface ( Figs. 16.6 and 16.7 ). On CT and MRI, osteomas most often manifest as well-delineated, surface-based masses composed of cortical-type bone; however, the cancellous variant demonstrates characteristics of trabecular-type bone with intervening adipose tissue ( Fig. 16.8 ).

Pathologic Features

Grossly, most osteomas are 0.5 to 2.0 cm in diameter, round-to-oval, hard, tan-white, and merge seamlessly with the cortical bone from which they arise ( Fig. 16.9 ). Large lesions in the appendicular skeleton are frequently sessile and elongate ( Fig. 16.10 ).

Microscopically, the bone seen in osteomas is lamellar, or an admixture of lamellar and woven, bone that is cortical-like in appearance with perforating vascular channels similar to Haversian systems ( Fig. 16.11 ). In the cancellous variant, the core of the lesion consists of interconnecting, broad trabeculae of bone that are surrounded by fatty marrow. The cells that line the surfaces of the bone are flattened osteoblasts with small, elongate nuclei and sparse amounts of eosinophilic cytoplasm. The osteocytes are small and quiescent in appearance. Infrequently, especially in lesions that are in a stage of rapid growth, the osteoblasts can be large and polyhedral with prominent nuclei and a layer of loose fibrous connective tissue cuffing the adjacent bone.

Differential Diagnosis

Parosteal osteosarcoma can be clinically confused with osteoma, particularly when they are large and arise within the appendicular skeleton. Histologically, parosteal osteosarcoma is characterized by long, often parallel, trabeculae of woven bone (“streamers”) surrounded by sheets of proliferating spindle cells, which are absent in osteoma. In addition, parosteal osteosarcoma may contain neoplastic cartilage, a feature not present in osteoma. In small biopsies, or samples with adjacent fibrosis, it could rarely be helpful to assess for the presence of MDM2 amplification by ISH or IHC, which is often seen in parosteal osteosarcoma but not in osteoma.

Melorheostosis can resemble osteoma radiographically; however, in melorheostosis, the thickened cortex has the appearance of flowing or dripping candlewax rather than a discrete, ovoid or mushroom-shaped, cortically-based mass, although exceptions occur. Additionally, melorheostosis frequently involves more than one bone and may be associated with localized sclerotic lesions of the skin. In our experience, the bone in a bona fide osteoma and melorheostosis are virtually identical histologically and cannot be confidently distinguished from one another on histologic grounds alone.