Benign extraosseous cartilaginous lesions are uncommon and usually present as tumor-like masses. In the past, the term soft part chondroma or extraskeletal chondroma was used arbitrarily for small, well-defined, solitary nodules of hyaline cartilage that are unattached to bone and occur primarily in the distal extremities (especially the fingers and hands). These lesions, however, must be distinguished from the cartilaginous rests of branchial origin (usually found in the soft tissues of the lateral neck in infants and small children), as well as from the metaplastic cartilage encountered in some benign lipomatous (chondro-osseous lipoma) and fibromatous (calcifying aponeurotic fibroma) neoplasms. They must also be distinguished from multiple cartilaginous nodules in the synovium (synovial chondromatosis), the myxochondroid metaplastic process that characteristically occurs in the plantar foot, and the cartilage found in myositis ossificans and its variants.
Chondrosarcomas also occur as primary soft tissue neoplasms, although much less often than primary chondrosarcomas of bone, and are essentially composed of only a single tumor type, mesenchymal chondrosarcoma . Although its name would seem to imply otherwise, there is little to no evidence of true chondroid differentiation in the distinctive translocation-associated sarcoma currently known as extraskeletal myxoid chondrosarcoma. Therefore, it is discussed in Chapter 35 , “Other Important Soft Tissue Neoplasms.”
Chondrosarcomas may arise from the synovium (sometimes secondary to synovial chondromatosis) and from the periosteum (periosteal chondrosarcoma). They also appear following radiation therapy or injection of radioactive material, usually after a latent period of many years. Rare examples of chondrosarcoma also occur in parenchymal organs. In some locations (e.g., bladder), they usually represent part of a carcinosarcoma.
This chapter also addresses soft tissue lesions with osseous differentiation, including myositis ossificans, fibroosseous pseudotumor of the digit, aneurysmal bone cyst, fibrodysplasia ossificans progressiva (FOP), and extraskeletal osteosarcoma, as well as other soft tissue lesions that may show matrix production, such as tumoral calcinosis and amyloidoma.
This chapter will not discuss rare heterotopic ossifications that occur after various types of soft tissue injury. These lesions have been described in surgical scars (particularly those of the abdomen), , in burns, in association with dislocations of the elbow and other joints, and total hip arthroplasty. Repeated minor soft tissue trauma is also the cause of the drill bone or shooter bone in the deltoid and pectoralis muscles, the rider bone in the adductor muscles of the thigh, and the shoemaker’s bone in the rectus muscle of the lower abdominal wall—all lesions rarely encountered today but repeatedly described in the earlier literature. In addition to these more deeply seated lesions, localized production of bone in the dermis and subcutis is not particularly rare. Such lesions may be solitary or multiple, and they can occur spontaneously or in connection with a variety of neoplastic (e.g., linear basal cell nevus, basal cell carcinoma, chondroid syringoma, calcifying pilomatricoma) and nonneoplastic (e.g., scars, acne, puncture wounds, injections, organizing hematomas, pseudohypoparathyroidism, dermatomyositis) etiologies. Many of these lesions have been reported as osteoma cutis , but they, too, seem to be products of metaplasia rather than neoplasia.
Extraskeletal Chondroma (Chondroma of Soft Parts)
Extraskeletal chondroma is a benign cartilaginous tumor that occurs predominantly in the hands and feet. Its variable histologic appearance can occasionally lead to a mistaken diagnosis of chondrosarcoma. There are two large series of this entity: 70 cases from the Mayo Clinic and 104 cases from the Armed Forces Institute of Pathology (AFIP) archives. More recently, subsets of soft tissue chondromas with features of “chondroblastoma-like” chondroma have been reported as examples of calcified chondroid mesenchymal neoplasm . , This proposed terminology is discussed later.
Clinical Findings
Extraskeletal chondromas occur primarily in the soft tissues of the hands and feet, usually with no connection to the underlying bone or tenosynovium. The most common site is the fingers, where more than 80% are found. Less frequent sites include the hands, toes, feet, and trunk; unusual cases have been described in the auricle, bladder, and fallopian tube, among others. Extraskeletal chondroma grows as a slowly enlarging nodule that seldom causes pain or tenderness. The tumor mainly affects adults 30 to 60 years old (with a slight male predominance) and is rare in children. Almost all are solitary, although bilateral cases have been reported. The association of pulmonary chondroma, epithelioid gastrointestinal stromal tumor, and extraadrenal paraganglioma is known as Carney triad (see Chapter 31).
Radiographically, soft tissue chondromas are well-demarcated and do not involve bone, although some tumors cause compression deformities or bone erosion. Discrete, irregular, ringlike, or curvilinear calcifications are often demonstrable ( Fig. 31.1 ).
Chondroma of Soft Parts.
A, Radiograph of left third finger, showing small soft tissue mass with foci of calcification. B, Chondroma of soft parts at base of right second finger. C, Intraoperative specimen of enucleated chondroma of soft parts.
Gross and Microscopic Findings
Extraskeletal chondromas are firm, well-demarcated, oval-round masses. Occasionally, they are soft or friable with focal cystic change. Almost all are small, seldom exceeding 3 cm in greatest diameter. They may be attached to the tendon or tendon sheath but do not involve the synovium. Microscopically, they vary in appearance. About two-thirds consist of mature hyaline cartilage arranged in distinct lobules with sharp borders ( Figs. 31.2 to 31.5 ). Some are altered by focal fibrosis ( fibrochondroma ) or ossification ( osteochondroma ); others show myxoid change ( myxochondroma ), sometimes together with focal hemorrhage. About one-third display focal or diffuse calcifications, which usually represent a late feature that may completely obscure the cartilaginous nature of the tumor and mimic tumoral calcinosis. With a granular, floccular, or crystalline appearance, the calcified material often outlines the contours of the chondrocytes in a lace-like pattern. The calcification tends to be more pronounced in the center than at the periphery of the lobule. Calcium pyrophosphate crystals may be seen but do not indicate systemic pseudogout. Calcification is often accompanied by cellular degeneration and necrosis, which accounts for the softened gross appearance of some of these tumors.
Cross section of chondroma of soft parts showing circumscription and multinodular growth pattern.
Chondroma of soft parts consisting of mature hyaline cartilage with nests of benign-appearing cells in lacunae.
Chondroma of soft parts with hypercellular zone at periphery of lobule.
Calcified Chondroma of Soft Parts.
Calcium deposits surround and partially replace cartilage cells.
A striking feature that occurs in about 15% of cases is a proliferation of epithelioid and multinucleated giant cells ( Figs. 31.6 and 31.7 ). This proliferation is most conspicuous at the tumor margin and along the interlobular vascular channels. There are also rare extraskeletal chondromas in which plump, immature-appearing cells are set in a myxoid background, thereby simulating a chondrosarcoma. In general, however, these tumors can be recognized as chondromas by the presence of more mature, less-cellular cartilaginous areas at the periphery. Other examples exhibit features that closely simulate those of chondroblastoma, with epithelioid chondrocytes and “lace-like” calcification.
Calcified chondroma of soft parts showing florid granuloma-like fibrohistiocytic reaction.
Mild atypia and nuclear enlargement within calcified chondroma (same case as Fig. 31.6 ).
As with normal chondrocytes, the cells of the extraskeletal chondroma are positive for S-100 protein. The matrix is rich in types I and III collagen, whereas types II and IV collagen seem to be reduced. Interestingly, like other chondrogenic tumors, this lesion consistently shows nuclear expression of ERG.
Clonal chromosomal abnormalities have been identified in some extraskeletal chondromas, including monosomy 6, trisomy 5, and rearrangements of chromosome 11. Sakai et al. described a rare case of extraskeletal chondroma with three clones, including t(6;12)(q12;p11.2), t(3;7)(q13;p12), and der(2)t(2;18)(p11.2;q11.2). More recently, FN1 gene fusions have been identified in soft tissue chondromas. In the study by Amary et al., 50% of tumors had FN1 rearrangement, and in the study by Liu et al., 80% (4 out of 5) of soft tissue chondromas tested showed FN1 rearrangement. The most common fusion partners are FGFR1/2 ; other fusion partners include MERTK and NTRK1 ; this is in contrast with synovial chondromatosis, where the most common fusion partner is ACVR2A .
Outcome
Although some of the chondroblastic or myxoid forms of extraskeletal chondroma cause concern because of their atypical cellular features, there is no evidence that these tumors behave differently from the well-differentiated forms composed of adult-type hyaline cartilage. Overall, up to 15% of cases recur locally. , It is noteworthy that transformation of extraskeletal chondroma to chondrosarcoma has never been encountered, although this is by no means rare with the chondroid lesions of bone. Local excision is the preferred mode of therapy.
Differential Diagnosis
Distinction from other benign lesions should not be difficult in most cases. Calcifying aponeurotic fibroma is characterized by short, bar-like foci of cartilaginous metaplasia in a dense, poorly circumscribed fibromatous background. It occurs in the hand rather than the distal portion of the digits and almost always affects patients younger than 25 years. Tumoral calcinosis may mimic a heavily calcified chondroma, but it lacks cartilage and usually shows a distinct histiocytic response to the calcified material. Giant cell tumor of tendon sheath has a more uniform cellular pattern and rarely has metaplastic cartilage or bone. Radiography usually allows distinction from periosteal or juxtacortical chondroma , as well as subungual osteochondroma. A small, well-circumscribed tumor located underneath the periosteum, periosteal/juxtacortical chondroma causes erosion of the underlying cortex, with ledges or buttresses at the margin of the tumor. In contrast to extraskeletal osteochondroma, subungual osteochondroma is characterized by cartilage overlying well-developed bone—features that also separate it from subungual exostosis, and bizarre parosteal osteochondromatous proliferation (BPOP). Tenosynovitis with psammomatous calcification tends to involve the fingers and toes, often in patients with a history of repetitive trauma, and shows distinctive psammomatous calcifications.
Another lesion in this differential diagnosis has been called “ myxochondroid metaplasia of the plantar foot .” Associated with variably painful soft tissue swelling, this lesion arises in patients of any age (including children) in the subcutaneous plantar soft tissues of the feet, sometimes also involving the toes. Histologically, it is characterized by a partially circumscribed, variably cellular proliferation of cytologically bland spindle cells deposited in a fibromyxoid stroma with occasional foci of chondroid metaplasia. The latter foci stain for both S-100 protein and ERG, consistent with true cartilaginous differentiation. These lesions do not locally recur, even with incomplete excision. This is likely a reparative/reactive process secondary to chronic mechanical stress. The lesion has also been recognized anecdotally at other anatomic sites with a similar clinical history.
Synovial chondromatosis differs from extraskeletal chondroma by its occurrence in joints (e.g., knee, hip, elbow, shoulder) and the formation of numerous small, cartilaginous or osteocartilaginous nodules of varying size. Attached to the synovial membrane of the joint, tendon sheath, or lining of the adjacent extraarticular bursa ( Figs. 31.8 to 31.10 ), these synovial nodules often become detached and are found as loose bodies in the joint space. Some are hypercellular with clustering of tumor cells and increased mitotic activity. Most become calcified or ossified and can be readily demonstrated by routine radiography as multiple small, discrete radiopaque bodies ( loose bodies or joint mice ). Nonmineralized loose bodies are demonstrable on arthrograms, computed tomography (CT) scans, bone scans, or magnetic resonance imaging (MRI) as multiple filling defects outlined by contrast material. As in extraskeletal chondromas, hypercellularity, binucleate cells, and nuclear atypia are compatible with a benign clinical course. However, rare instances of chondrosarcoma arising in synovial chondromatosis have been reported.
Conglomerate of variably sized nodules characteristic of synovial chondromatosis.
Synovial chondromatosis of left knee.
High-power view of synovial chondromatosis with nodule of metaplastic cartilage underneath synovium.
Soft tissue chondromas with myxoid change may occasionally be confused with extraskeletal myxoid chondrosarcoma (EMC). EMC, however, generally presents as a large, often-hemorrhagic mass of the deep, proximal soft tissues, and does not produce actual cartilage, or incite an osteoclast-like giant cell reaction. In challenging cases, demonstration of NR4A3 rearrangements by flourescence in situ hybridizaton (FISH) of next-generation sequencing will confirm the diagnosis of EMC.
Calcified Chondroid Mesenchymal Neoplasms
Calcified chondroid mesenchymal neoplasms (CCMN) is a recently proposed “umbrella” term for a group of mesenchymal tumors which share production of unusual calcified, often chondroid-appearing matrix and frequent FN1 -rearrangements. , Historically, the great majority of tumors reported as such have been classified as tenosynovial giant cell tumors with cartilage production, extraskeletal chondromas, tophaceous pseudogout, and “nonphosphaturic” phosphaturic mesenchymal tumors.
Although this is an interesting way to conceptualize these unusual neoplasms, the use of this term as a specific diagnosis seems to us to risk blurring some important differences between these entities. For example, cartilage-forming tenosynovial giant cell tumors are clearly of synoviocytic origin, and represent a distinct tumor type, now termed “chondroid synoviocytic neoplasm” (see Chapter 26). Many reported “CCMN” are indistinguishable from extraskeletal chondromas, , in particular the “chondroblastoma-like” variant, and it is difficult to see the benefit to pathologists or clinicians in renaming these benign tumors of chondrocytes. “Nonphosphaturic” phosphaturic mesenchymal tumors occur in patients without known phosphaturia, or in patients whose bone loss is ascribed to other causes; recognition of the distinctive morphologic features of these tumors in combination with FGF23 chromogenic in situ hybridization (CISH) can be critical in recognizing and treating otherwise-debilitating osteomalacia in these patients. , Thus, there is considerable value in attempting to apply a more specific label to tumors of these types, rather than simply “lumping” them as “CCMN.”
It also seems that the term “CCMN” requires both genetic and morphological refinement before it can be used as a specific diagnosis. For example, other FN1 -rearranged, calcified or chondroid tumors such as synovial chondromatosis and calcifying aponeurotic fibroma , are not currently included under the umbrella of “CCMN,” for obscure reasons. Some tumors which might be considered morphologically to fall in the “CCMN” spectrum lack FN1 -rearrangements, showing instead rearrangements of genes such as PDGFRA or TIMP3 . Finally, FN1 -rearrangements may be seen in tumors lacking any morphological features of “CCMN,” such as inflammatory myofibroblastic tumors. Putting all of this together, we do not believe that “CCMN” is yet ready to be used as a specific diagnostic term.
Acral Fibro-Chondro-Myxoid Tumor
Acral fibro-chondro-myxoid tumor (AFCTM) is a recently identified neoplasm with a distinct predilection for the distal extremities, characterized by a THBS1::ADGRF5 gene fusion in most cases. , Clinically, 66% of these tumors occur in the hands, with the remaining 34% arising in the feet. AFCTM typically presents as a well-demarcated, uni- or multinodular mass, comprising chondroid regions within a rich extracellular chondromyxoid stroma. Histologically, the tumor cells are arranged in rows or clusters, closely resembling myoepithelioma or chondroma; however, true cartilaginous differentiation is rarely observed ( Fig. 31.11 ). Immunohistochemistry reveals that most tumor cells express ERG and CD34, with approximately 70% showing positivity for SOX9. In contrast, S100 protein staining is negative or only patchy. While AFCTM has the potential for local recurrence, no cases of metastasis have been reported to date.
Acral fibrochondromyxoid tumor, presenting as a small, well-circumscribed mass on the finger ( A ). Fibromyxoid zone with cartilaginous metaplasia ( B ). High-power view of chondroid focus ( C ).
Mesenchymal Chondrosarcoma
Mesenchymal chondrosarcoma is a malignant cartilaginous tumor composed of two components: sheets of primitive mesenchymal cells and interspersed islands of well-differentiated hyaline cartilage. Because of the latter, mesenchymal chondrosarcoma has traditionally been considered a variant of chondrosarcoma. More recent data suggest that this is a translocation-associated sarcoma with unique features. Because of its prominent vascular pattern, several cases reported in the earlier literature were initially interpreted as “hemangiopericytoma with cartilaginous differentiation.” Mesenchymal chondrosarcoma is a rare tumor that occurs two to three times more often in bone than in soft tissue. It is a rapidly growing tumor with a high incidence of metastasis.
Clinical Findings
This neoplasm differs from other forms of chondrosarcoma by its preponderance in young adults 15 to 35 years old and its slightly more frequent occurrence in females. The tumor may also occur in young children and has been described as a congenital lesion. The principal anatomic sites of mesenchymal chondrosarcoma are the head and neck region (particularly the orbit), cranial and spinal dura mater, and occipital portion of the neck, followed by the lower extremities, especially the thigh. , Rare examples of this tumor have been described in virtually every anatomic site.
Orbital lesions tend to produce exophthalmos, orbital pain, blurring of vision, and headaches. Intracranial and intraspinal tumors are accompanied by vomiting, headaches, and various motor and sensory defects. Tumors in the extremities usually manifest as a painless, slowly enlarging mass, situated in the musculature. Metastasis from a primary mesenchymal chondrosarcoma of bone has mimicked a soft tissue tumor in reviewed cases. Therefore, a bone survey is essential, particularly when the tumor occurs in an unusual location. In most cases, radiography reveals a well-defined soft tissue mass, often with irregular radiopaque stipplings, arcs, flecks, or streaks due to focal calcification or bone formation in cartilaginous areas ( Fig. 31.12A ). CT scans, MRI, and angiography are helpful for outlining the tumor before surgical therapy.
Mesenchymal chondrosarcoma. Axial CT image shows a mineralized mass arising in the soft tissues of the pelvis ( A ). Grossly, the tumor has a fleshy cut surface with areas of calcifications ( B ).
Gross and Microscopic Findings
Grossly, mesenchymal chondrosarcoma presents as a multilobulated, circumscribed mass that shows considerable variation in size. Cut sections show a mixture of fleshy, soft, gray–white tissue with scattered foci of irregularly sized cartilage and bone ( Fig. 31.12B ). At times, there are also small areas of hemorrhage and necrosis.
Microscopically, mesenchymal chondrosarcoma exhibits a characteristic pattern that consists of sheets of undifferentiated round, oval, or spindle-shaped cells, typically with an abrupt transition to small, well-defined nodules of well-differentiated hyaline cartilage. The cartilage is frequently associated with central calcification and ossification ( Figs. 31.13 to 31.15 ). The undifferentiated cells range in appearance from round to oval to slightly spindled ( Figs. 31.16 to 31.17 ). In general, however, mesenchymal chondrosarcoma is a tumor of “stubby,” monotonous spindled cells, rather than truly round cells (as seen in Ewing sarcoma, for example). The neoplastic cells may be arranged in nests, sheets, or a classic pericytic pattern around the sinusoidal vessels. Solid cellular and richly vascular patterns may be present in different portions of the same neoplasm. The cartilaginous foci are usually well-defined, but there are also poorly circumscribed cartilaginous areas that gradually blend with the undifferentiated tumor cells. Spindle cell areas, with or without collagen formation, are present in some cases but are rarely a prominent feature.
Low-power view of mesenchymal chondrosarcoma with its characteristic bimorphic picture: islands of well-differentiated cartilage adjacent to sheets of small, undifferentiated tumor cells.
Demarcation between small, undifferentiated tumor cells and well-differentiated cartilage in mesenchymal chondrosarcoma.
Extraskeletal mesenchymal chondrosarcoma with secondary calcification of cartilage matrix.
A, Small round cells surround a prominent hemangiopericytoma-like vasculature in extraskeletal mesenchymal chondrosarcoma. B, Rounded cells have high nuclear/cytoplasmic ratio but more variability in nuclear shape than in classic Ewing sarcoma.
A, High-power view of small round cells surrounding collagen cores in extraskeletal mesenchymal chondrosarcoma. Subtle cartilaginous features can sometimes be seen within these areas. B, Spindling of primitive cells in extraskeletal mesenchymal chondrosarcoma.
Immunohistochemical Findings
In general, immunohistochemistry plays only a limited role in the diagnosis of mesenchymal chondrosarcoma. The cartilaginous portion of the tumor typically shows strong S-100 protein positivity, whereas only isolated cells in the undifferentiated areas express this antigen. SOX9, a transcription factor thought to be a master regulator of chondrogenesis, is consistently expressed by both the primitive round/spindled cells and cartilaginous areas in mesenchymal chondrosarcomas, although this marker is not widely utilized.
The round cells typically do not express keratins, but up to 35% show focal epithelial membrane antigen (EMA) staining. Desmin expression, along with aberrant expression of MyoD1 and less often myogenin, is seen in many mesenchymal chondrosarcomas, a potentially significant diagnostic pitfall when the differential diagnosis includes spindle cell/sclerosing rhabdomyosarcoma ( Fig. 31.18D ). Expression of these myogenic markers is likely related to the activation of the myogenic differentiation pathway by the HEY1::NCOA2 fusion protein.
Mesenchymal chondrosarcoma. Immunohistochemical stains showing positive staining for CD99 ( A ), NKX2.2 ( B ), NKX 3.1 ( C ) and MyoD1 ( D ).
In the absence of the cartilaginous foci, the undifferentiated areas may somewhat resemble other primitive round or spindle cell sarcomas, such as Ewing sarcoma. Although mesenchymal chondrosarcomas were initially thought to be CD99-negative, subsequent studies demonstrated expression of this antigen in >90% of cases. , ( Fig. 31.18A ). Similarly, NKX2-2, a nuclear marker found in almost all cases of Ewing sarcoma, is expressed in up to 75% of cases of mesenchymal chondrosarcoma. ( Fig. 31.18B ) However, FLI1, a marker found in many, but not all, cases of Ewing sarcoma, is typically negative.
There is some controversy regarding the utility of NKX3.1 in distinguishing mesenchymal chondrosarcoma from Ewing sarcoma. In our experience, NKX3.1 is positive in mesenchymal chondrosarcoma but negative in Ewing sarcoma ( Fig. 31.18C ).
Cytogenetic and Molecular Genetic Findings
A recurrent HEY1::NCOA2 [t(8;8)(q21;q13)] fusion has been consistently identified in mesenchymal chondrosarcoma. This fusion event appears to be specific to mesenchymal chondrosarcoma. A single case with IRF2BP2::CDX1 fusion has been reported. Mutations in IDH1 and IDH2 are not seen, distinguishing this tumor from central and periosteal chondrosarcomas. Methylation profiling has been reported to reliably identify mesenchymal chondrosarcoma.
Outcome
Mesenchymal chondrosarcoma is a fully malignant tumor that pursues an aggressive clinical course and metastasizes in a high percentage of cases. Nakashima et al. reported 5- and 10-year survival rates of 54.6% and 27.3%, respectively. Similarly, in a more recent survey of 107 patients, 5- and 10-year survival rates were 55% and 43.5%, respectively. The principal metastatic site is the lung. Lymph node metastasis is extremely rare. Several patients have followed a protracted clinical course with late metastases, but there do not seem to be clinical or pathological predictors of indolent or aggressive disease. The presence of metastatic disease and increased tumor size were found to be the only predictive factors of survival. Combined radical surgery and chemotherapy or radiotherapy appear to be the treatments of choice.
Differential Diagnosis
Although typical mesenchymal chondrosarcomas pose no particular diagnostic problem, recognition of this tumor may be difficult with small biopsy or needle biopsy specimens that demonstrate only one of the two tissue elements. In particular, tumors without the cartilaginous element may be easily mistaken for Ewing sarcoma or poorly differentiated synovial sarcoma with a prominent hemangiopericytoma-like vascular pattern. Metaplastic cartilage may extremely rarely occur in poorly differentiated synovial sarcoma, but it is much less common than foci of calcification or bone. Careful search for a biphasic pattern or epithelial differentiation with antibodies for keratins or EMA may be helpful, but molecular analysis allows for a more definitive separation. Traditional immunohistochemical markers such as CD99, NKX2-2, and NKX3.1 do not reliably distinguish mesenchymal chondrosarcoma from Ewing sarcoma or even poorly differentiated synovial sarcoma, although more recently developed SS18:SSX fusion antibodies are quite synovial sarcoma-specific. As noted above, the finding of HEY1::NCOA2 fusion is specific to mesenchymal chondrosarcoma.
The distinction of mesenchymal chondrosarcomas showing expression of rhabdomyoblastic markers from spindle cell/sclerosing rhabdomyosarcoma may be extremely challenging, particularly if cartilage has not been sampled in a needle biopsy. The presence of calcifications radiologically should suggest mesenchymal chondrosarcoma. In difficult cases, next-generation sequencing for the HEY1::NCOA2 fusion may be required. FISH for NCOA2 rearrangement is not helpful, as subsets of rhabdomyosarcomas harbor NCOA2 rearrangements.
Other Neoplastic Bone Forming Soft Tissue Tumors
Myositis Ossificans (MO)/Fibroosseous Pseudotumor of the Digit (FOPD)/Soft Tissue Aneurysmal Bone Cyst (ST-ABC).
Myositis ossificans (MO) and fibroosseous pseudotumor of the digit (FOPD), previously thought to be traumatically induced, are now considered related entities that frequently harbor USP6 gene fusion. , In the latest WHO classification of soft tissue and bone tumors, these two lesions are grouped together. ST-ABC also harbors USP6 gene fusions and likely belongs to the same spectrum of lesions.
Clinical Findings.
MO is most often found in the musculature but can also occur in other tissues, including tendons and subcutaneous fat (sometimes referred to as panniculitis ossificans ). In contrast, FOPD typically arises in the fingers and less frequently the toes. , The initial complaint is pain or tenderness, followed by diffuse, doughy soft tissue swelling. Later, usually during the second or third week after onset, the swelling becomes more circumscribed and indurated, gradually changing into a distinctly outlined, firm to stony mass on palpation.
MO primarily affects young, vigorous, athletically active adolescents and adults, predominantly males. , However, it can also be found in older individuals and females. MO is rare in small children. In about 80% of cases, the lesion involves the limbs. In the lower extremity, the favored sites are the quadriceps and gluteus muscles; in the upper extremity, the flexor muscles, especially the brachialis muscle. MO has also been described in the head and neck, particularly in the masseter, temporalis, and sternocleidomastoid muscles. , Deep-seated lesions may involve both muscle and underlying periosteum and may also arise on the surface of bone (parosteal), mimicking a surface bone-forming tumor. , Rarely, similar lesions arise in the mesentery (heterotopic mesenteric ossification), usually in middle-aged to elderly men (median age: 49) who present with bowel obstruction following significant abdominal surgery or trauma. ,
FOPD usually presents as a painful, localized, fusiform, often erythematous swelling of the affected digit ( Fig. 31.19 ). It predominantly affects young to middle-aged adults and, unlike myositis ossificans, is more common in women. In four large studies of 93 cases, 54 were females and 39 males with an age range of 5–70 years. Seventy-eight arose in the fingers and 14 in the toes (one was reported to arise in the forehead). ,
Radiographs of fibroosseous pseudotumor of thenar eminence ( A ) and right ring finger ( B ).
ST-ABC is more common in females and has a wide age distribution. , The lower extremity is the most common location, and patients usually present with a painful, rapidly, or slow-growing mass without a history of trauma.
Radiographically, at the initial stage, plain films of MO show a slight increase in soft tissue density. Calcification is rarely seen before the end of the third week and initially presents as rather faint, irregular, floccular radiopacities (sometimes described as the “dotted veil pattern” of myositis ossificans). As the lesion progresses and becomes increasingly calcified, it presents as a well-outlined soft tissue mass that is most densely calcified at its periphery. Calcification becomes clearly apparent radiographically 4 to 6 weeks after the onset of the lesion, which progresses from the periphery toward the center of the process. However, even in late lesions the central core tends to remain uncalcified ( Figs. 31.20 and 31.21 ). The appearance of myositis ossificans on CT and MRI is quite characteristic and often leads to the correct diagnosis. FOPD usually shows a mass with calcifications and may or may not be attached to the underlying bone. ,
Myositis ossificans of popliteal fossa showing evidence of progressive ossification within 22-day period.
Radiograph of myositis ossificans ( arrow ) of upper thigh. The lesion had been present for 5 weeks.
ST-ABC can be solid or cystic on imaging, frequently with peripheral calcifications and perilesional edema ( Fig. 31.22A ). There is an imaging overlap with MO, but cystic changes with fluid-fluid levels would support the diagnosis of ST-ABC.
Soft tissue aneurysmal bone cyst. Radiograph showing a tumor with peripheral mineralization ( A ). Grossly, the tumor was blood filled and cystic with peripheral rim of bone ( B ). Low-power view showing the peripheral bone formation ( left ) and blood-filled cystic areas with thick walls ( C ).
Gross and Microscopic Findings.
Grossly, MO usually measures 3 to 6 cm when excised. They tend to be well-circumscribed and cut with a gritty sensation. They are white, soft, and somewhat gelatinous (or hemorrhagic) in the center and yellow-gray with a rough granular surface at the periphery. These findings correlate with the zonal pattern seen on light microscopy. FOPD has a similar gross appearance but is smaller in size. ST-ABC are usually larger, measuring 2–12 cm ; the only distinguishing feature is the presence of blood-filled spaces ( Fig. 31.22B and C ).
Histologically, MO is characterized by a zonal pattern that reflects different degrees of cellular maturation. This pattern is most conspicuous in lesions of 3 weeks or more duration ( Fig. 31.23 ). In these cases, the innermost portion of the lesion is composed of immature, loosely textured, often richly vascular fibroblastic/myofibroblastic tissue that closely resembles nodular fasciitis or granulation tissue ( Figs. 31.24 and 31.25 ). The constituent fibroblasts and myofibroblasts display a mild degree of cellular pleomorphism (but not hyperchromasia) and prominent mitotic activity. They are intermingled with a varying number of macrophages, chronic inflammatory cells, fibrinous material, and sometimes multinucleated giant cells. In addition, there may be prominent endothelial proliferation, focal hemorrhage, fibrin, and entrapped atrophic or necrotic muscle fibers.
Low-power view of myositis ossificans illustrating transition between fibroblastic ( lower right ) to osteoblastic stroma ( upper left ).
Central portion of myositis ossificans showing fibroblastic/myofibroblastic proliferation resembling nodular fasciitis.
Nonossifying area in myositis ossificans illustrating mats of glassy collagen that contains plump, reactive fibroblasts/myofibroblasts.
Peripheral to these areas is an intermediate zone in which the cells become condensed into poorly defined trabeculae that consist of a mixture of fibroblasts and osteoblasts, as well as varying amounts of osteoid that is separated by thin-walled, ectatic vascular channels ( Figs. 31.26 and 31.27 ). Farther toward the periphery, the osteoid increasingly undergoes calcification and evolves into mature lamellar bone ( Fig. 31.28 ). Islets of immature or mature cartilage may be present and precede bone formation. Characteristically, bone formation is most prominent at the margin of the lesion, often with rimming by a monolayer of osteoblasts that show little variation in size and shape. The bone is separated from the surrounding muscle tissue by a zone of loose, myxoid, or compressed fibrous tissue. The surrounding muscle often shows atrophic changes, sometimes together with a mild inflammatory infiltrate and a focal sarcolemmal proliferation. In some lesions, particularly those arising in the subcutaneous fat, the zonal pattern is absent or inconspicuous. Older lesions often consist of only mature lamellar bone together with interspersed fat cells, fibrous tissue, and thin-walled vascular spaces indistinguishable from osteoma.
Transition between fibroblastic and osteoblastic areas in myositis ossificans. Note how the two areas “stream” or seem to blend gradually.
Intermediate portion of myositis ossificans with transition from proliferating spindle-shaped cells to trabeculae of osteoid ( A ) lined by plump osteoblasts ( B ).
Low-magnification view of peripheral portion of myositis ossificans displaying zone of osteoid trabeculae rimmed by osteoblasts, underneath which a proliferation of spindle-shaped cells is present.
Histologically, FOPD closely resembles myositis ossificans but lacks its orderly zonal pattern. Instead, it consists simply of an irregular, often nodular mixture of loosely arranged fibroblasts and myofibroblasts, a prominent myxoid matrix, and deposits of osteoid rimmed by uniform osteoblasts ( Figs. 31.29 to 31.32 ). Multinucleated giant cells may be seen, and in some cases there is a mild lymphoplasmacytic infiltrate. ST-ABC has the histologic features of ABC arising in bone. It contains blood-filled cystic spaces that are lined by septa composed of spindle-shaped cells, osteoclast-type giant cells, and reactive bone formation, sometimes with a characteristic blue appearance. Although there might be some histologic overlap between MO and ST-ABC, we feel that ST-ABC and MO represent two distinct pathologic entities and that MO is typically solid and characterized by the zoning pattern.
Fibroosseous pseudotumor of right index finger showing peripheral zone of proliferating spindle cells and central zone of osteoid.
Fibroosseous pseudotumor with osteoblast-rimmed osteoid material and surrounding chondroid zone.
High-magnification view of fibroosseous pseudotumor with proliferation of spindle-shaped cells adjacent to trabecule of osteoid that resembles myositis ossificans.
