Feature
Benign lesions
Malignant lesions
Pattern of growth
Pushing
Infiltrative
No extension or penetration into surrounding bone
Permeation and destruction of surrounding bone
Borders of lesion
Well circumscribed
Ill-defined, moth-eaten
Sclerotic rim or “rind” separates lesion from adjacent bone
Infiltration of adjacent host bone
Periosteal reaction
Absent or solid
Complex (“onion skin” or “hair on end”)
Codman’s triangle
A microscopically useful and clinically relevant way of classifying lesions of bone is based on evidence of matrix production. In general, destructive processes in the skeleton can be divided into those that show evidence of matrix production, both radiographically and microscopically, and those that do not. The former are further subdivided based on the type of matrix produced, i.e., osteoid, chondroid, chondromyxoid, or myxoid matrix, or fibrous stroma. Matrix producing lesions of bone and soft tissue can be non-neoplastic or neoplastic, and benign or malignant.
In cytologic specimens, matrix is best appreciated in air-dried, modified Giemsa-stained preparations, and is often readily apparent at scanning power. Osteoid appears as irregular fragments of opaque, intensely metachromatic stroma, often arrayed in branched or interlacing cords or strands. The edges of the fragments may be sharply defined or have a frayed, fibrillar appearance. Variable numbers of benign or malignant osteoblasts are present within and/or at the periphery of the fragments. Fibrous matrix is also metachromatic, and varies from dense and opaque to pale and finely fibrillar or wispy. Fragments can be large or small, and have well-defined, smooth edges or be frayed and irregular. The fragments may be acellular or have variable numbers of benign or malignant spindle cells of fibroblastic or myofibroblastic origin embedded within the stroma. Due to biochemical and staining similarities, acellular or relatively hypocellular fragments of dense collagen may be difficult or impossible to distinguish from osteoid. Chondroid, chondromyxoid, and myxoid matrices, like osteoid, are intensely metachromatic, but in contrast to osteoid, often occur in large, sheet-like fragments or clumps. The matrix can appear opaque, or have a fibrillar or filmy quality, and the borders are often relatively well defined. The fragments can be acellular, or have variable numbers of benign or malignant cells embedded in the stroma. Because these matrices are essentially identical, the principal feature that distinguishes the various chondroid, chondromyxoid, and myxoid lesions from each other is the type(s) of benign or malignant mesenchymal cells associated with the matrix.
5.2.1 Osteoid Producing Lesions
A number of lesions of bone produce osteoid and its mineralized end product, woven bone. Production of lamellar bone, which is the mature, highly organized matrix of the skeleton, is seen only in osteoma and enostosis (bone islands). Osteoid is the unmineralized, protein matrix produced by osteoblasts. This matrix consists of type I collagen (approximately 90 %) and a number of non-collagenous proteins, including osteocalcin, osteopontin, osteonectin, and various growth factors. The morphologic separation of osteoid from fibroblastic collagen is often qualitative; however, this distinction is important diagnostically. Fibroblastic collagen is laid down by flattened or spindle shaped fibroblasts and has a distinctly fibrillar, longitudinal arrangement. In contrast, osteoid forms irregular, amorphous masses that have a hard, waxy quality. Osteoid appears bright magenta in air-dried, modified Giemsa-stained smears, and green-blue in wet-fixed, Papanicolaou-stained preparations. Osteoblasts, that may be benign or malignant, become entrapped in the matrix, creating a lacy, interwoven pattern. The major osteoid producing lesions of bone that are encountered in the pediatric population are listed in Table 5.2.
Table 5.2
Osteoid producing lesions of bone
Benign lesions | Malignant lesions |
|---|---|
Osteoblastoma | Osteosarcoma |
Osteoid osteoma | Conventional |
Fracture callus | Surface (parosteal, periosteal, high grade) |
Telangiectatic | |
Aneurysmal bone cyst with reactive bone formation | Small cell |
Low grade central |
5.2.1.1 Osteoblastoma
Clinical Features
Osteoblastoma (OB) is a rare benign neoplasm, accounting for approximately 1 % of primary bone tumors. Most patients are less than 30 years old, with a peak incidence in the second decade of life. Patients typically present with local pain.
Location
OB may arise in any portion of the skeleton, but has a distinct predilection for the axial skeleton, particularly the spine.
Radiographic Appearance
OB is typically intramedullary, although occasional intracortical examples occur. In long bones, OB arises in the metaphysis, whereas vertebral OB is usually located in the posterior elements. OB produces a uniform, sharply circumscribed, expansile lesion that is usually radiolucent. Periosteal reaction is generally absent. Calcification of the matrix may be present or absent radiographically.
Cytological Features
FNA yields moderately cellular smears composed of a polymorphous population of benign mesenchymal cells, and irregular fragments of osteoid and woven bone [7, 8]. Osteoblasts, osteoclasts, and fibrovascular stroma comprise the mesenchymal elements. Osteoblasts are plump, round, or polygonal cells with well-defined cellular borders, abundant cytoplasm, and eccentric, round nuclei with evenly dispersed chromatin and a single, round, often prominent nucleolus. The osteoblasts occur as individually dispersed cells or in rows “rimming” the fragments of osteoid. Individually dispersed, true osteoclasts are also present, and characteristically exhibit variation in size, shape, and number of benign nuclei. Benign spindle cells of fibroblastic and endothelial origin are arrayed within irregular fragments of fibrous stroma, and also occur singly. The background is usually bloody, reflecting the richly vascular nature of OB.
Differential Diagnosis
Differential diagnostic considerations include osteoid osteoma, fracture callus, and osteosarcoma. Usually, these entities can be distinguished from each other based on imaging characteristics. Moreover, neither osteoid osteoma nor fracture callus is likely to undergo FNA. Occasionally OB has an aggressive appearance on imaging studies, raising concern for osteosarcoma. However, the cytologically benign appearance of the cells in OB helps to distinguish this entity from osteosarcoma.
Pearls
Occasional OBs have atypical cytological features that may lead to misdiagnosis as osteosarcoma, particularly when combined with an aggressive radiologic appearance. Because osteosarcoma is the most common primary bone tumor in the second decade of life and is far more common than OB irrespective of the patient’s age, histologic evaluation of tumors with atypical features is imperative to avoid misdiagnosis and guide appropriate treatment.
5.2.1.2 Osteoid Osteoma
Clinical Features
The majority of cases of osteoid osteoma (OO) occur in the second decade of life. OO is usually associated with marked pain that is worse at night and relieved with aspirin.
Location
OO may arise in any portion of the skeleton, and almost always involves cortical bone. Occasional subchondral and intramedullary lesions occur.
Radiographic Appearance
The characteristic radiographic appearance of intracortical OO is that of a well-circumscribed, lytic lesion surrounded by excessive sclerosis and reactive bone formation. The central lytic region, termed the nidus, is almost always less than 1 cm in diameter and by definition, less than 2 cm. Although periosteal new bone formation is characteristic, a true periosteal reaction is absent.
Cytological Features
To our knowledge, cytologic diagnosis of OO by FNA has not been reported. The diagnosis is usually apparent from the clinical history and radiographic findings, and this, combined with the characteristic intracortical location and extensive peripheral sclerosis, makes aspiration of OO highly unlikely.
5.2.1.3 Conventional Osteosarcoma
Clinical Features
Osteosarcoma (OS) is the most common primary malignant tumor of bone and more than 60 % of patients present in the second decade of life. While most osteosarcomas are sporadic, there is an increased incidence of this tumor in patients with hereditary retinoblastoma, Li–Fraumeni syndrome, and Rothmund–Thomson syndrome. Secondary or post-irradiation osteosarcoma may also occur in childhood. Primary conventional osteosarcoma is 1.5 times more frequent in males than females. The usual presenting symptom is pain with or without swelling that can be present for weeks or months. Pathologic fractures are present in 5–10 % of patients.
Location
OS has a predilection for the metaphyseal portion of long bones, particularly the distal femur, proximal tibia, and proximal humerus.
Radiographic Appearance
OS characteristically appears as a large, poorly defined, infiltrative, metaphyseal lesion arising in the medullary bone and extending through the cortex to form a large soft tissue mass. A periosteal reaction, usually of the hair on end, sunburst or onion skin type, and Codman’s triangle are present. Lesions are usually mixed lytic and blastic, the latter feature reflecting matrix production. Occasionally, OS is purely lytic.
Cytological Features
OS has a spectrum of cytologic appearances, reflecting the histologic variability of these neoplasms [7, 9–11]. FNA of conventional OS yields variably cellular smears, depending on the amount of matrix within the area sampled. Aspirates are composed of varying proportions of malignant osteoblasts, spindle cells and bizarre, multinucleated tumor giant cells (Fig. 5.1a). In addition, scattered osteoclast-like giant cells are often present. The malignant cells show considerable anisocytosis, nuclear pleomorphism, and increased nuclear to cytoplasmic ratios. Nuclei are characterized by absolute enlargement, irregular contours, coarsely clumped chromatin, and prominent, irregular nucleoli. The malignant cells occur as individually dispersed elements, in irregular aggregates, and in association with osteoid or other matrix (Fig. 5.1b).
Fig. 5.1
Conventional osteosarcoma , osteoblastic subtype (a. Papanicolaou stain, medium power; b. Diff-Quik stain, medium power). Osteosarcoma is composed of obviously malignant osteoblasts and spindle cells, with occasional bizarre multinucleated giant cells and osteoclastic giant cells. The cells occur singly and in loosely cohesive clusters (a). Marked anisocytosis and nuclear pleomorphism are evident in this example of osteosarcoma. Magenta-colored matrix is present between and around some of the tumor cells in the cluster (b).
The amount of osteoid varies considerably, and may dominate the smears or be exceedingly scant and focal. Osteoid can be distinguished from dense collagen in the air-dried, modified Giemsa-stained smears by its amorphous, lace-like quality in combination with the presence of entrapped or individually dispersed malignant cells reminiscent of osteoblasts. In cases lacking these features, osteoid may be difficult or impossible to distinguish from dense collagen. In addition to osteoid, chondroid and fibrous matrices may be present in aspirates from chondroblastic [12] and fibroblastic OS, respectively (Fig. 5.2).
Fig. 5.2
Conventional osteosarcoma , chondroblastic subtype (Papanicolaou stain, medium power). Irregular fragments of chondroid matrix are present in this smear comprised of highly pleomorphic, overtly malignant cells.
Differential Diagnosis
The overtly malignant nature of these tumors is usually apparent thereby limiting differential diagnostic considerations, particularly when osteoid is evident. In the absence of convincing osteoid, cytologic distinction from chondrosarcoma and fibrosarcoma may be difficult or impossible [12].
Pearls
Preparation of a cell block can be helpful for identifying osteoid matrix (Fig. 5.3). In osteoid poor tumors, an immunoperoxidase stain for SATB2 can help to confirm the osteoblastic origin of the neoplasm; however, other immunoperoxidase stains are not helpful as OS can be positive for a variety of mesenchymal, as well as epithelial markers. Cytogenetics reveals a numerically and structurally complex karyotype and may help to distinguish OS from tumors characterized by recurrent translocations.
Fig. 5.3
Conventional osteosarcoma (Cell block, H&E stain, high power). Cell block preparations can help to confirm the presence of osteoid, which may be inconspicuous in smears. Delicate osteoid with focal evidence of calcification is evident between and around cells in this fragment of tissue from an osteosarcoma.
5.2.1.4 Other Variants of Osteosarcoma
Although a detailed discussion of the different variants of OS is beyond the scope of this chapter, cytopathologists should be aware of these entities.
Small Cell Osteosarcoma
This variant of OS comprises less than 2 % of OS and, as the name implies, is composed of small round cells. Osteoid matrix can be exceedingly scant, and rare examples may also have focal chondroid matrix. The cytologic features of small cell OS are considerably different from those of other types. Aspirates are composed of small round or ovoid cells with scant cytoplasm, oval to elongate nuclei with finely dispersed or clumped chromatin, and very high nuclear to cytoplasmic ratios. Nuclear pleomorphism is present, but may not be marked. Cells occur singly and in cohesive fragments. When osteoid is scant or absent in aspirate smears, small cell OS may be mistaken for Ewing sarcoma or metastasis from a pediatric small round cell tumor. Immunoperoxidase stains and fluorescent in situ hybridization for EWSR1, FOXO1, and SS18(SYT) can be helpful for excluding these entities.
Telangiectatic Osteosarcoma
This variant, which comprises less than 4 % of OS, is a high grade intramedullary tumor with prominent intralesional blood-filled spaces and scant evidence of osteoid formation. Radiographically, these lesions are purely lytic with extensive destruction of bone and often, soft tissue extension. Aspirates are usually bloody and may have a paucity of diagnostic malignant cells, thereby mimicking aneurysmal bone cyst or a vascular lesion.
Low Grade Central Osteosarcoma
This rare variant, which comprises 1–2 % of OS, lacks the marked nuclear pleomorphism that characterizes conventional OS. Tumors are composed of hypocellular fibrous tissue with variable amounts of osteoid and woven, or occasionally lamellar, bone, and due to the bland appearance of the malignant cells, may be confused with fibrous dysplasia. This variant typically progresses more slowly than conventional OS and has a better prognosis. Low-grade central osteosarcomas have also been shown to have MDM2 amplifications, which can help to distinguish it from benign mimics.
Juxtacortical Osteosarcomas (Parosteal, Periosteal, and High Grade Surface)
These tumors originate from the periosteal surface of the bone and typically grow outward as well as into the cortex, with minimal or no involvement of the underlying medullary bone. High grade surface OS accounts for less than 1 % of OS and is morphologically and biologically indistinguishable from conventional OS. In contrast, parosteal and periosteal OS are characterized by slow growth and have a better prognosis than conventional OS. Parosteal OS accounts for approximately 4 % of OS and is characterized by a proliferation of spindle cells within a predominantly fibrous stroma with well-formed bony trabeculae in parallel array. The spindle cells tend to show minimal cytologic atypia. Periosteal OS comprises less than 2 % of OS and usually appears as a lytic lesion with scalloping of the outer cortex. This variant of demonstrates abundant cartilaginous matrix. The cytologic features are those of an intermediate grade malignant neoplasm.
5.2.1.5 Fracture Callus
On occasion, an early or incipient fracture can mimic a sarcoma both clinically and pathologically. In addition, benign as well as malignant lesions of bone can lead to pathologic fracture, and the presence of fracture callus can make interpretation of the FNA or small biopsy difficult. For these reasons and to avoid false positive diagnoses, it is important that one be familiar with the pathology of fracture callus.
In an acute fracture, there are hemorrhage, variable tissue damage, and necrosis of adjacent bone and marrow. The hematoma and necrosis stimulate rapid proliferation of mitotically active, spindled mesenchymal cells that appear atypical. After approximately 1 week, primitive osteoid and chondroid matrices are produced by the cells of the callus. This early osteoid and chondroid is disorganized and at this stage, is most likely to be confused with an OS. By the second week, the osteoblasts begin to appear in single rows along the periphery of osteoid, a phenomenon known as “osteoblastic rimming.” The osteoblasts are plump and uniform, and appear to be at the same maturational stage. The islands of cartilaginous matrix show gradual transition to osteoid at their periphery (chondro-osseous bone). The orderly arrangement of osteoblasts in rows, the uniformity of the cells, and the gradual transition from one matrix type to another without a change in the appearance of the cells distinguish this process from sarcoma.
As evident from the previous discussion, the features of fracture callus in FNA vary with age of the fracture. Aspirates from acute fractures may contain old blood, spicules of necrotic lamellar bone, fragments of necrotic tissue, and highly atypical spindled mesenchymal cells occurring singly and in irregular fragments. In maturing fractures, fragments of osteoid, chondroid, and eventually chondro-osseous bone are also present, while the number of primitive spindled mesenchymal cells decreases. Preparation of a cell block can help to distinguish fragments of fracture callus from more ominous lesions.
5.2.2 Chondroid Producing Lesions
Cartilaginous tumors of the skeleton are a major source of diagnostic difficulty, in both cytologic and histologic specimens. This is due, in part, to the tremendous amount of overlap in the morphologic spectrum of these lesions [13]. But in addition, considerable histologic variation often exists within a single tumor. In lesions that are deemed malignant, grading is sometimes difficult and is more subjective than in other neoplasms. Fortunately, differentiating low grade lesions with minimal risk of metastasis from high grade lesions is usually not a problem, and clinically, is the most relevant distinction.
It is critically important to include the clinical data, particularly the presence or absence of pain, and the radiographic findings in the evaluation of cartilaginous tumors. The plain films provide crucial information regarding the bone involved and the pattern of growth, both of which are important predictors of benign or malignant behavior. Tumors of the pelvis, axial skeleton and proximal ends of long bones are more likely to behave in a malignant fashion than lesions in the distal extremities and tubular bones of the hands and feet. When different patterns of growth are evident, the radiographic studies also guide the selection of the most appropriate area of the lesion to sample. Heavily calcified areas are more likely to be benign or low grade, whereas purely lytic areas usually represent a higher grade malignancy. The major chondroid producing lesions of bone are listed in Table 5.3.
Table 5.3
Chondroid producing lesions of bone
Benign lesions | Malignant lesions |
|---|---|
Enchondroma | Chondrosarcoma |
Grade I, II, & III | |
De-differentiated | |
Mesenchymal | |
Osteochondroma | Secondary low grade chondrosarcoma arising within osteochondroma |
Periosteal chondroma (Juxtacortical chondroma) | Periosteal osteosarcoma |
Periosteal chondrosarcoma | |
Chondromyxoid fibroma | Myxoid chondrosarcoma |
Chondroblastoma | Clear cell chondrosarcoma |
Synovial chondromatosis | |
Fracture callus |
5.2.2.1 Enchondroma
Clinical Features
Enchondroma (EC) is a common benign bone tumor that occurs over a broad age range. Most solitary lesions in the pediatric population present in the second decade of life, whereas those associated with enchondromatosis syndromes manifest in infancy or early childhood. Most of the solitary tumors are asymptomatic and are incidental findings, or present after pathologic fracture. In contrast, enchondromatosis syndromes (Ollier disease, Maffucci syndrome) are characterized by multiple enchondromas involving multiple sites. The resulting skeletal deformities and symptoms vary depending on the sites involvement. Enchondromatosis is also associated with increased risk of malignant degeneration of EC.
Location
The most common location of EC is in the tubular bones of the hands. EC is also seen in the proximal humerus, proximal femur, distal femur and other locations, particularly in enchondromatosis.
Radiographic Appearance
EC arises in the medullary space, usually in the metaphysis. Most solitary lesions are small, lytic, and expansile, with well-demarcated borders. Calcifications, that are described as rings, flocculent, fluffy, or popcorn-like, are characteristic and often, abundant. Cortical destruction or a soft tissue mass is unusual, and should raise the possibility of malignancy.
Cytological Features
FNA of enchondroma yields paucicellular smears dominated by mature cartilaginous matrix (Fig. 5.4). The benign chondroid has a filmy or granular quality, appears bright magenta to purple in air-dried, modified Giemsa-stained and blue-green to blue-gray in Papanicolaou-stained preparations. Fragments of matrix occasionally have a lobulated appearance that recapitulates the histologic pattern. Embedded in the matrix are variable numbers of uniform, round or ovoid cells, usually within lacunar spaces. Cells have small, round, dark nuclei without nucleoli. Nuclear detail is typically difficult to discern. Binucleated cells are rare. Multinucleated forms and mitotic figures are absent. Cells occur singly, as doublets, or occasionally as clusters within the lacunae. Individually dispersed cells may also be identified. Foci of calcification within the matrix are often, but not always, evident. In contrast to EC arising in other sites, digital EC often shows hypercellularity and cytologic atypia.
Fig. 5.4
Enchondroma (Diff-Quik stain, medium power). Irregular fragments of hyaline-type cartilage are present in this aspirate from a digital enchondroma. Although the cellularity is mildly increased, cytologic atypia is absent.
Differential Diagnosis
The major differential diagnostic consideration is low grade chondrosarcoma. Because hypercellularity and mild cytologic atypia are characteristic of digital EC, it is important not to overinterpret these findings as indicative of malignancy in lesions arising in the fingers and toes. Regardless of site, both significant myxoid degeneration and necrosis should be absent, and if present, should arouse suspicion of malignant transformation. Table 5.4 summarizes the features that help to distinguish enchondroma from low grade chondrosarcoma.
Table 5.4
Useful features for distinguishing enchondroma from low grade chondrosarcoma
Feature | Enchondroma | Low grade chondrosarcoma |
|---|---|---|
Binucleated cells | Occasional (EC < LCS) | Occasional to frequent (LCS > EC) |
Cellular morphology | Small, bland cells | Larger, “plump” cells |
Don’t fill lacunar space | Tend to fill lacunae | |
Atypia absent or minimal except in digital EC | Mild atypia | |
Nuclear morphology | Small, round nuclei | Larger, round nuclei |
± evenly dispersed open chromatin | ||
Dark, pyknotic-appearing nuclei, chromatin detail absent | ||
± small nucleoli | ||
Pattern of growth | Well circumscribed | Infiltrative |
Usually surrounded by a rim of trabecular bone | Invades/surrounds host bone | |
Lobulated architecture | Erodes and destroys cortex | |
Architecture is less organized | ||
Skeletal location | Small bones hand and feet, long bones especially femur and humerus | Pelvis, axial skeleton, proximal long bones |
Clinical history | Painless, usually asymptomatic | Usually painful (± night or rest pain) |
Most often discovered incidentally or after pathologic fracture |
Pearl
The radiographic appearance of EC is often diagnostic and treatment is curettage; thus, these lesions are rarely sampled by FNA.
5.2.2.2 Chondromyxoid Fibroma
Clinical Features
Chondromyxoid fibroma (CMF) is a very rare benign bone tumor. The vast majority of patients are between 5 and 30 years of age at presentation. CMF is usually asymptomatic, but may present with long standing, intermittent pain. When lesions occur in the small bones of the hand or feet, local swelling may be noted.
Location
CMF most often arises in the lower extremities, particularly the proximal tibia.
Radiographic Appearance
CMF is an eccentric, metaphyseal, lytic lesion with sharply circumscribed, sclerotic margins. The borders typically have a scalloped appearance. Cortical thinning is typical and may be marked. If present, cortical expansion is usually minimal. Periosteal reaction is absent.
Cytological Features
FNA of CMF yields mildly to moderately cellular smears composed of fragments of chondromyxoid matrix admixed with stellate, spindled, and round cells [14]. The stellate and spindled cells may be mildly pleomorphic, with variably shaped nuclei and finely clumped to dark chromatin. Binucleated and multinucleated forms may be identified. The stellate and spindled cells appear to float in the chondromyxoid matrix, and also occur as individually dispersed elements. Variable numbers of uniform, small, round to ovoid cells that are morphologically similar or identical to chondroblasts are also present, either singly or in small clusters. These cells have dense, well-defined cytoplasm and relatively uniform, round to ovoid nuclei with pale, finely dispersed chromatin. Nuclear grooves or convolutions may be seen. Mitotic figures are absent. The chondromyxoid matrix has a watery or filmy quality, and appears magenta or pale purple in air-dried modified Giemsa-stained smears and pale blue-green or gray-blue in Papanicolaou-stained preparations.
Differential Diagnosis
Differential diagnostic considerations include chondromyxoid fibroma-like conventional osteosarcoma and a chondrosarcoma. In contrast to CMF, these entities have aggressive radiographic appearances and are characterized by a greater degree of cytologic atypia.
5.2.2.3 Chondroblastoma
Clinical Features
Although chondroblastoma occurs over a wide age range, approximately 75 % of patients present in the second decade of life. CB is rare in patients less than 10 years old. Patients typically present with gradually increasing pain of long duration. Swelling and decreased range of motion may occur, but are usually late symptoms.
Location
CB is most often located in the proximal humerus, distal femur, or proximal tibia.
Radiographic Appearance
CB is located within the epiphysis or apophysis. Lesions are small, lytic defects with sharply circumscribed, sclerotic borders. Speckled calcifications may be present.
Cytological Features
FNA of CB yields variably cellular smears dominated by small, mononuclear cells occurring singly and in small clusters, admixed with osteoclast-like giant cells and fragments of chondroid matrix (Fig. 5.5) [15, 16]. The mononuclear cells have dense cytoplasm, sharp cytoplasmic borders, and eccentric, round to oval nuclei with finely dispersed chromatin, and absent or inconspicuous nucleoli. Nuclei often have longitudinal grooves or convolutions. The fragments of chondroid matrix are typically small, have an amorphous or fibrillar quality, and may be calcified. Cellular aggregates in which matrix surrounds individual mononuclear cells in a “chicken-wire” pattern, with or without calcification, may be present and are virtually diagnostic of this entity.
Fig. 5.5
Chondroblastoma (a. Papanicolaou stain, high power; b. Cell block, H&E stain, high power; c. Cell block, DOG1 immunoperoxidase stain, high power). Chondroblastoma is comprised of mononuclear cells admixed with multinucleated giant cells. The cells occur singly and in small loosely cohesive aggregates. Nuclei in the mononuclear cells are ovoid with finely dispersed chromatin, small nucleoli, and nuclear grooves (a). The cell block shows mononuclear cells with nuclear grooves interspersed with multinucleated giant cells (b). An immunoperoxidase stain for DOG1 is positive in a subset of the mononuclear cells in this cell block preparation (c). (Image of DOG1 immunoperoxidase stain courtesy of Dr. Jeffrey Goldstein).
Differential Diagnosis
The main differential diagnostic consideration is giant cell tumor of bone (GCT). Although GCT can occur in the pediatric population, it is more common in skeletally mature individuals. In contrast to CB, mononuclear cells of GCT lack nuclear grooves and their nuclei resemble those of the multinucleated giant cells. In addition, the giant cells in GCT typically have many more nuclei (sometimes greater than 50) than those of CB. The mononuclear cells in CB are positive for DOG1, a feature that can help to confirm the diagnosis (Fig. 5.5).
Pearl
Cell block preparations can help to demonstrate the characteristic chicken-wire calcifications.
5.2.2.4 Chondrosarcoma
Clinical Features
Chondrosarcoma (CS) usually occurs in patients older than 40 years of age, and is rare in persons under 20 years of age. Usually, there is a history of pain that may be of long duration. Rest pain or night pain is not uncommon. CS may be primary, or arise in a previously benign lesion, such as osteochondroma or enchondroma. Patients with osteochondromatosis or enchondromatosis are at increased risk for secondary CS. Mesenchymal chondrosarcoma (MCS) is a rare variant of CS, comprising 3–10 % of tumors, and has a uniformly dismal prognosis. MCS tends to occur at a younger age than conventional CS, with a peak incidence in the second and third decades of life.
