Definition

Lipoma is a rare primary tumor of bone composed of mature adipose tissue. Lipomas involving bone are divided into three types: intramedullary (intraosseous), intracortical/subperiosteal, and parosteal. Lipomas involving synovial tissue are described in Chapter 20.

Incidence and Location

Lipomas of bone are extremely rare; fewer than 50 cases are described in the literature.

Radiographic Imaging

Radiographically, intramedullary lipoma is seen as a lytic lesion with trabeculation (Figs. 16-1 and 16-2). Bone expansion with a thinned but intact cortex may be present (Fig. 16-2). Central, niduslike calcification is a frequent radiographic feature of intramedullary lipoma (Figs. 16-2 and 16-3). Magnetic resonance imaging may show no discernible signal alteration because lipoma is composed of mature adipose tissue with signal characteristics similar to normal fatty marrow (Fig. 16-1). Lipomas with extensive fat necrosis may appear as low signal density lesions with signal void in areas of calcifications (Fig. 16-4).

The gross appearance of lipoma is that of a well-circumscribed, lobular mass of adipose tissue (see Fig. 16-2).

Microscopic Findings

Histologically, lipomas consist of mature adipose tissue and do not differ from ordinary lipomas of soft tissue (Fig. 16-4). The presence of fat necrosis with dystrophic calcifications, which correspond to the central, niduslike opacity seen radiographically, is frequently seen (Figs. 16-3 and 16-4).

Liposarcoma of bone is one of the rarest of primary bone tumors.^39–48 In 1982, Addison and Payne accepted only six examples of this entity in bone from previously published reports.²⁴ The patients ranged in age from 15 to 53 years but usually had symptoms during the third and fourth decades of life. Reported cases of intraosseous liposarcoma involved the major long tubular bones, such as the femur, tibia, and humerus.

Radiographic Imaging

Radiographic features are nonspecific and show a bone-destructive process indicative of a malignant tumor.

Microscopic Findings

Microscopically, liposarcomas in bone represent high-grade pleomorphic or round-cell (signet-ring) lesions. Some of these tumors may have features of myxoid liposarcoma.

Differential Diagnosis

The high-grade pleomorphic liposarcoma should be differentiated from malignant fibrous histiocytoma. In the evaluation of adipose tissue and differentiation of intraosseous lesions, the presence of residual nonneoplastic tissue of fatty marrow infiltrated by a nonlipomatous tumor should be ruled out before the lesion is classified as a liposarcoma. It is our impression that at least some of the cases previously reported as primary liposarcomas of bone would be currently classified as malignant fibrous histiocytomas.

Clinical Behavior

Approximately 50% of patients who were reported to have primary liposarcoma of bone had metastases after amputation.

Definition

Vascular-cartilaginous hamartoma is a rare and distinct clinical, radiologic, and pathologic entity that presents at birth or early infancy as an expansile intraosseous lesion involving the central portion of one or more ribs.

Incidence and Location

McLeod and Dahlin⁵⁶ reported nine cases from the Mayo Clinic’s consultation files. The lesion typically involves the chest wall and most likely originates within the ribs.^49–59

Gross Findings

The gross findings of these tumors are those of smooth, well-circumscribed, red-brown masses that arise from the surface of the rib. The cut surface is marked by the presence of many dilated channels filled with blood. These spaces are separated by a friable, red-brown stroma that contains variable amounts of gritty, shiny, white, cartilaginous tissue.

Radiographic Imaging

Radiographically vascular-cartilaginous hamartoma presents as an expansile lesion of the rib. Magnetic resonance imaging typically shows signal enhancement in T2-weighted images corresponding to the high water content in both cartilaginous and vascular components of the lesion (Figs. 16-6 and 16-8).

Microscopically, these lesions show a mixture of cellular fibrous tissue that contains many blood-filled, endothelial-lined vascular spaces; numerous islands of randomly distributed mature hyaline cartilage; and reactive new bone (Figs. 16-6 and 16-7). The cartilage islands represent well-developed nodules of cartilaginous tissue that are well demarcated from the surrounding vascular component and occasionally form irregular clusters. The vascular component is similar to conventional hemangioma and may contain large, highly cellular areas composed of spindle cells forming narrow vascular channels. The spindle-cell areas may show prominent mitotic activity, but atypical mitoses are absent. Larger-caliber vessels are also present and may form clusters mimicking common (cavernous) hemangioma. Vascular-cartilaginous hamartoma frequently shows features of superimposed secondary aneurysmal bone cyst.^49,54–56 In fact, aneurysmal bone cyst features can dominate the lesion. Some of the lesions may contain coalescent nodules of mature hyaline cartilage that obscure the spindle and vascular component of the lesion (Fig. 16-9).

These rare lesions are benign and may be cured by en bloc excision of the mass in continuity with the involved rib. Rapid enlargement of the lesion can be clinically observed if vascular-cartilaginous hamartoma is complicated by a superimposed aneurysmal bone cyst.^49,54–56

Definition

Melanotic neuroectodermal tumor of infancy is a rare, distinctive neoplasm that frequently affects children younger than age 1 year. The tumor is composed of nests of cells that have melanin pigment and is also referred to as retinal anlage tumor, melanotic progonoma, or melanotic ameloblastoma.

Incidence and Location

Melanotic neuroectodermal tumors usually involve the maxilla or mandible but also occur in the soft tissue, the epididymis, and the mediastinum or may present as intracranial (dural or brain) masses.^{60,62–64,67–69,71,72,79,80,82,85} They may present as lesions in the long bones. The lesion can be clinically associated with increased levels of catecholamines and urinary excretion of vanillylmandelic acid.^61,70

Radiographic Imaging

Radiographically, the tumor presents as a well-demarcated, lytic bone lesion.^63,72,80 The preoperative diagnosis can be suspected radiographically if the lesion presents in typical locations—the maxilla or mandible—in a child during the first year of life.

Gross Findings

The lesion is fibrous and tan, brown, or black, depending on the proportion of the pigmented component.

Microscopic Findings

Microscopic features are characteristic and consist of two basic cell populations: small neuroblastic cells and larger, melanin-containing epithelial cells arranged in a distinct architectural pattern.^{65,66,73–78,81} The tumor cells form nests within a predominantly fibrous stroma. The nests are delineated by epithelial, pigment-containing cells (Figs. 16-10 to 16-14). The central portion of these structures with alveolar or tubular arrangements is filled by small, loosely arranged neuroblastic cells in a neurofibrillary matrix (Fig. 16-13, B to D). The neuroblastic cells occasionally form larger, more diffuse areas in which epithelial alveolar structures are loosely distributed. This may create a more disorganized pattern of neuroblastic cells and solid ephithelial proliferations. The presence of heterologous elements (i.e., mesenchymal spindle cells and woven bone) has also been described but is extremely rare.⁸³

The tumor cells, particularly the epithelial pigment–containing cells, are positive for keratin and occasionally positive for epithelial membrane antigen and the HMB-45 marker. In addition, both components (i.e., small neuroblastic cells and epithelial cells) are positive for neuron-specific enolase and Leu-7 and occasionally are positive for synaptophysin. Glial fibrillary acidic and S-100 proteins may be focally positive in a small-cell neuroblastic component. This immunohistochemical pattern is consistent with the postulated neuroectodermal derivation of these tumors.^{73,84,86,92,81}

Treatment and Behavior

Melanotic neuroectodermal tumors of infancy generally behave as benign lesions, but local recurrence is possible. In addition, approximately 6% of patients develop distant metastases. The development of distant metastases cannot be correlated with any specific microscopic features, the distribution of DNA ploidy, or tumor proliferation parameters.

Definition

Perivascular epithelioid cell tumor (PEComa) is a rare distinct neoplasm of bone made up of epithelioid clear cells rich in glycogen and characterized by coexpression of muscle and melanocytic markers. This term has been applied to an expanding family of tumors that are presumed to originate from microscopically and phenotypically unique perivascular epithelioid cells, although there is no known normal cellular counterpart to these cells, and precursor lesions for PEComas have not been identified.^{88–91,99,101} It includes angiomyolipoma (both renal and extrarenal), lymphangiomyomatosis, clear cell sugar tumor of the lung, and a variety of spindled and epithelioid neoplasms involving various organs, soft tissue, and bone with a similar phenotype.^{88,92,93,96,98,100,105,108–110,114,116} The unifying concept proposed for this family of tumors evolved over the past century and was developed by identifying unique clear cell features as well as the smooth muscle and melanocytic characteristics of the tumor cells. A distinct type of benign clear cell tumor referred to as clear cell sugar tumor was described in the lung in 1963 by Liebow and Castleman.¹⁰⁷ The name refers to the clear cytoplasm of the cells, which is rich in glycogen. Despite their epithelioid appearance, the clear cells are negative for epithelial markers and exhibit distinctive coexpression of muscle and melanoma markers.^{88,89,97,100,105,106,112,115} The same immunophenotypic features are also present in a subset of cells in lymphangiomatosis and angiomyolipoma. On the basis of the common and distinctive phenotype, Bonetti et al, Pea et al, and Zamboni et al defined a family of lesions characterized by the presence of this peculiar cell type, the perivascular epithelioid cell (PEC), and designated the group of tumors with similar features as PEComas.^88,89,90,118 These tumors have also been referred to as PEST (primary extrapulmonary sugar tumors).¹¹⁴ Patients with one or more of the PEC family of lesions may have the tuberous sclerosis complex. The tuberous sclerosis complex is typically associated with angiomyolipomas and lymphangiomyomatosis, but PEComas in other anatomic sites can develop in this syndrome.⁹¹ Two-step inactivation of the TSC1 and TSC2 genes activating the Rheb/mTOR/p70S6K pathway underlie the development of PEComas in tuberous sclerosis.^101,117 Comparative genomic hybridization studies of PEComas disclose frequent losses and gains of multiple chromosomes, implicating major chromosomal rearrangements.¹¹¹ Some PEComas show rearrangements of the transcription factor E3 (TFE3) gene and overexpression of the TFE3 protein immunohistochemically.^{87,95,104,113}

Incidence and Location

Our experience is restricted to four cases of primary clear cell sugar tumor of bone seen in consultation. These presented in the calcaneus of a 9-year-old boy, the humerus of a 10-year-old girl, the patella of a 29-year-old man, and the proximal phalanx of the middle finger of the left hand in a 33-year-old woman. One of the cases showed a clonal cytogenetic abnormality consisting of reciprocal chromosomal translocation t(X;2) (q11-12; q34-35).

Radiographic Imaging

Radiographic features are nonspecific and consist of a well-demarcated lucent lesion with a trabeculated appearance and sclerotic margins (Figs. 16-15 and 16-16). In general, the tumors arise in skeletal sites that are relatively rare for primary bone tumors.