Gene P. Siegal

Fibro-osseous Lesions

Fibro-osseous lesion is a generic designation for a clinically diverse group of bone disorders in which the lesional tissue consists of large volumes of fibrous connective tissue, principally collagens type I and III, as well as an osseous component in the form of woven or lamellar bone or cementum with varying degrees of mineralization. These lesions exhibit nearly identical histomorphologic features, yet demonstrate widely ranging clinical behavior. The site-dependent morphology applies especially to fibro-osseous lesions, as some occur exclusively at a particular anatomic location (i.e., osteofibrous dysplasia and central ossifying fibroma). A specific diagnosis is crucial because the management differs substantially from no treatment to complete excision. It should be noted as well that entities undergo name changes over time, especially among fibro-osseous lesions. Thus, ossifying fibroma is a synonym for osteofibrous dysplasia in long bones, whereas ossifying fibroma of maxillofacial bones is commonly referred to as central ossifying fibroma. Other synonyms (or perhaps variants) of this entity include cementifying fibroma, cemento-ossifying fibroma, juvenile (active/aggressive) ossifying fibroma, and psammomatoid ossifying fibroma.

Fibrous and Fibrohistiocytic Lesions

Most tumors of fibrous and fibrohistiocytic origin generally produce collagen but do not form a mineralizing matrix, whereas high-grade tumors may have little to no matrix. Fibro-osseous lesions [fibrous dysplasia (FD) and osteofibrous dysplasia (OFD)] are composed of large volumes of fibrous connective tissue, principally collagens type I and III, as well as osseous areas. Fibrous and fibrohistiocytic lesions span the entire spectrum of clinical behaviors: benign, locally aggressive, and malignant. While with radiologic input, it is usually not difficult to distinguish the benign and malignant ends of the spectrum, some of these lesions have significant overlapping histologic features and necessitate incorporating clinical and demographic information to arrive at the correct diagnosis.

Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

This chapter is composed of rare primary mesenchymal tumors of bone that demonstrate various differentiation pathways, including those of myogenic, lipogenic, neural, and epithelial derivation. Metastatic carcinoma, by far the most common malignancy in the skeleton, and metastatic sarcoma to bone, a rare event, should be excluded before accepting the diagnosis of a primary bone neoplasm.

Reactive, Metabolic, and Developmental Conditions

This chapter covers several nonneoplastic, noninflammatory entities that are reactive, metabolic, or developmental in nature. Osteoarthritis almost exclusively affects weight-bearing joints and remains mostly idiopathic in nature, although frequently it also is a consequence of other conditions involving the joints and synovium. The metabolic and developmental conditions typically involve the skeleton systemically, although they may present as focal lesions (i.e., Paget disease and phosphaturic mesenchymal tumor).

Small/Round Cell Lesions

Small, round cell lesions encompass a broad spectrum of entities, including reactive and inflammatory processes, benign neoplasms, and malignant tumors. Osteomyelitis is among the most common nonneoplastic conditions and denotes an inflammation of bone and bone marrow, commonly caused by bacteria (pyogenic osteomyelitis), although it may be produced by any type of organism. The incidence of small, round cell tumors of bone is tightly linked to the age at presentation, with Ewing sarcoma/primitive neuroectodermal tumor (PNET) and Langerhans cell histiocytosis (LCH) being the most common entities in young individuals. In contrast, hematologic neoplasms (myeloma and lymphoma) constitute approximately 40 % of all bone tumors but occur almost exclusively in adults, especially elderly patients. Most entities included in this chapter are those of traditional small, blue, round cell tumors that produce minimal extracellular matrix, such as Ewing sarcoma/PNET and hematologic neoplasms, whereas others, such as LCH and Rosai-Dorfman disease, tend to be composed of mixed-cell populations. Several other tumors with small, round cell histomorphology, either those that occur primarily in bone (e.g., small cell osteosarcoma and mesenchymal chondrosarcoma) or metastases from other organs (e.g., neuroblastoma and most rhabdomyosarcomas), are discussed in other chapters.

Tumor-like Conditions

Many nonneoplastic conditions of bone may form mass lesions that clinically and/or radiologically mimic tumors. In this chapter, selective conditions commonly encountered in clinical practice are discussed.

Bone-Forming Tumors

Bone-forming tumors represent a broad spectrum of neoplasms that arise within or on the surface of bone and may rarely occur in extraskeletal sites. The hallmark of these tumors is that the neoplastic cells produce the organic components of bone or bone matrix that may or may not be mineralized. Osteoma is usually solitary but in rare cases may be multiple. The latter is seen typically in association with Gardner syndrome. Osteoid osteoma and osteoblastoma are terms used to describe benign bone-forming tumors with essentially identical histologic features, thus preventing their distinction from one another solely on histomorphologic grounds. They differ in size, anatomic sites, and clinical manifestations. Osteosarcoma is the most common primary malignant tumor of bone, exclusive of hematologic malignancies. Although the tumor may occur at any age with a slightly male predilection, it has a bimodal age distribution, with a propensity to develop predominantly in adolescents and young adults. This is followed by a smaller second peak in the elderly, frequently with conditions known to predispose to osteosarcoma, including Paget disease and prior radiation.

Metastases to and from Bone

Bone, lymph nodes, lung, and liver represent the most common sites of tumor metastasis. Meanwhile, metastatic tumor within bone is the most common type of malignant tumor involving bone. Carcinomas are much more likely than sarcomas to metastasize to bone. Virtually all types of carcinomas can metastasize to bone. The most common origins include breast, lung, prostate, thyroid, and kidney. In fact, certain solid tumors have a particular propensity to seed within bone (e.g., prostate cancer), a theory known as the “seed and soil” hypothesis proposed by Stephen Paget more than a century ago. Radiographically, bone metastasis most commonly is osteolytic and, less frequently, osteoblastic or mixed. Most lesions are mixed microscopically as a result of an active remodeling process. The use of immunohistochemistry has allowed pathologists to better identify the origins of many of these metastases, although a small proportion of cases remain “cancer of unknown primary origin” despite extensive radiologic and pathologic workup. Advances in molecular genetics are expected to narrow this category even further. The most common metastasis from bone is from osteosarcoma, and the most common site to which it spreads is the lungs. High-grade chondrosarcomas also may have distant metastases, which also usually occur, as do most sarcomas, in the lungs.

Cartilage-Forming Tumors

All tumors that engage in chondroid matrix production are traditionally grouped together, regardless of their histogenesis. Cartilage tumors account for most nonhematologic primary bone tumors and encompass a broad spectrum of lesions, ranging from completely benign to highly malignant. As in most types of bone tumors but in contrast to bone-forming tumors, benign cartilaginous lesions are far more common than malignant ones. As for all bone lesions, evaluation of cartilage tumors necessitates adequate correlation with radiographic and demographic findings. This is extremely important in differentiating chondromas from chondrosarcomas, because benign lesions may have worrisome cytohistologic features, and conversely, high-grade lesions may possess foci of benign-appearing cytologic characteristics.

Giant Cell-Rich Lesions

Although the vast majority of bone/joint tumors contain giant cells, this discussion of giant cell–rich lesions is limited to entities in which the giant cells are an essential lesional component: chief among these are giant cell tumors of bone, giant cell reparative granuloma, and aneurysmal bone cysts. Giant cell reparative granuloma was first described as a nonneoplastic lesion of gnathic bones in children and young adults. Thereafter, the concept of giant cell reparative granuloma of extragnathic sites (also known as giant cell reaction) has been widely recognized. Given the significant histologic overlap, many practitioners have merged giant cell reparative granuloma of extragnathic sites with the solid variant of aneurysmal bone cysts, and the neoplastic nature of these interchangeably termed entities has been supported by the identification of various translocations.