Osteochondroid Lesions of Soft Tissue

INTRODUCTION

Bone or cartilage formation occurs in a wide variety of soft tissue lesions. Benign osseous, chondroid, or osteochondroid metaplasia is an occasional feature in many benign and malignant tumors, examples of which include calcifying aponeurotic fibroma (see Chapter 2), lipoma (see Chapter 15), fibromatosis (see Chapter 2), ossifying fasciitis (see Chapter 3), synovial sarcoma (see Chapter 10), sclerosing epithelioid fibrosarcoma (see Chapter 10), and liposarcoma (see Chapter 16). Divergent differentiation to osteosarcoma or chondrosarcoma can occur in malignant peripheral nerve sheath tumors (MPNSTs) (see Chapter 10), dedifferentiated liposarcoma (see Chapters 5 and 16), mesothelioma (see Chapter 5), and sarcomatoid carcinomas. This chapter includes those lesions in which such changes are the principal or sole form of differentiation. Extraskeletal myxoid chondrosarcoma is a translocation sarcoma without cartilaginous differentiation and is considered in Chapter 21. The differential diagnosis is summarized in Table 19.1.

TUMORS FORMING BONE

These include reactive and neoplastic conditions, and their diagnosis often requires clinical and radiologic information in addition to careful histologic assessment.

FIBRO-OSSEOUS PSEUDOTUMOR OF THE DIGITS

Clinical Features

Fibro-osseous pseudotumor is a benign, reactive zonal lesion, similar to myositis ossificans (MO), which occurs in the digits, often with a history of repetitive manual activity or trauma. Unlike MO, it chiefly involves the dermis or subcutaneous tissue and adjacent fibrous structures,¹ has a slight predilection for women,²,³ and involves a slightly older age group.²,⁴ The lesion usually occurs in the fingers, most commonly the proximal

phalanx of the index or middle fingers, and small numbers occur in the toes. It may rarely occur in nondigital sites such as the wrist. The usual presenting feature is a localized, often painful and erythematous mass in soft tissue that is not connected to the adjacent bone. Radiologically, there is randomly distributed lesional calcification. Complete local excision is usually curative.

TABLE 19.1 Differential Diagnosis of Osteochondroid Lesions

	Typical Clinical Features	Microscopic Features	Ancillary Investigations
Myositis ossificans	Young adults, proximal extremities or trunk Usually intramuscular and often history of trauma	Zonal pattern Highest cellularity in early stage Spindle and stellate fibroblasts resembling nodular fasciitis centrally Vascular or myxoid stroma with inflammation and extravasated erythrocytes Transition zone of active bone formation Peripheral layer of well-formed bone	Fibroblastic cells SMA+, occasionally desmin+
Fibro-osseous pseudotumor	Adults, digits; infrequently nondigital sites such as wrist Dermis or subcutis May have history of trauma	Variably cellular fascicles of spindle cells in myxoid stroma, similar to nodular fasciitis Focal irregular bony trabeculae with osteoid and osteoblastic rimming May display zoning pattern but less organized than in myositis ossificans	Variably SMA and calponin+
Ossifying fibromyxoid tumor	Subcutaneous circumscribed nodule	Cords of small rounded glomus like cells in fibromyxoid stroma About 80% have partial or complete rim of mature bone in capsule, extending long septa Atypical variants can have intratumoral osteoid and rarely spindle cells	S100 protein+, GFAP+, desmin±, SMA±, CK+ rarely
Extraskeletal osteosarcoma	Older adults	Atypical osteoblasts producing malignant osteoid and bone	Similar immunoprofile to skeletal counterpart (e.g., osteocalcin and osteonectin+)
	May occur at sites of previous irradiation Deep soft tissue of extremities, retroperitoneum	Surrounding tumor varies in morphology but most resemble pleomorphic sarcoma Atypical mitoses Calcification, mature bone, and atypical cartilage can be present	Can show divergent differentiation with variable muscle marker, S100 protein, and CK+
Ossifying synovial sarcoma	Young adults, often ankle or foot, slowly growing	Irregular distribution of mature bone spicules within tumor Can be biphasic or monophasic but are often the latter that can be only sparsely cellular Frequent mast cells Metaplastic bone can also be seen within fibrous septa	CK+, EMA+, bcl-2+, CD909+, S100 protein+, TLE1+
Lipoma with metaplastic bone	Usually superficial well-circumscribed masses in adults (some intramuscular, rarely retroperitoneal)	Resembles mature fat with variation in adipocyte size Mature-type bone	MDM2−, CDK4−, no MDM2 amplification, HMGA2 fusions
Schwannoma with metaplastic bone	Adults, superficial or deep, head and neck, limbs, retroperitoneum, posterior mediastinum	Circumscribed, fibrous capsule Spindle cells with wavy nuclei in palisades or patternless patterns Inflammatory cells, hyalinization Mature-type bone	S100 protein+ (diffuse) Peripheral rim of EMA+ perineurial cells
Soft tissue chondroma	Adults, extraosseous, and extra-articular sites, hands and feet	Lobules of mature hyaline cartilage, with clusters of chondrocytes Atypia and normal mitoses can be present, but more mature and sparsely cellular areas elsewhere identify lesion as benign	S100 protein+ in chondroid areas
Synovial chondromatosis	Adults Synovium of joints, bursae, and tendon sheaths Most common in large joints (e.g., knee and hip) Rarely in soft tissue adjacent to, but without communication with, the joint Has potential for malignant transformation to chondrosarcoma	Variably cellular nodules and islands of hyaline cartilage, present within the synovial membrane Atypia, mitoses, and ossification can be present	S100 protein+ in chondroid areas
Extraskeletal mesenchymal chondrosarcoma	Young adults Head and neck, extremities Exclude metastasis from extraosseous site	Biphasic morphology Hypercellular sheets of primitive small cells with round, ovoid, or spindled nuclei Discrete or intermingled islands of variably differentiated hyaline cartilage Hemangiopericytic vascular pattern	Small cell component CD99+ Cartilaginous component S100 protein+ t(8;8)(q21;q13.3), HEY1-NCOA2 fusion
Lipoma with metaplastic cartilage	Usually superficial wellcircumscribed masses in adults (some intramuscular, rarely retroperitoneal)	Resembles mature fat with variation in adipocyte size Well-differentiated cartilage	MDM2−, CDK4−, no MDM2 amplification, HMGA2 fusions
Atypical lipomatous tumor with metaplastic osteochondroid differentiation	Deep tumors of adults >50 y	Adipose tissue with scattered enlarged hyperchromatic nuclei, often found in fibrous septa Mature-type bone	MDM2+, CDK4±, p16+, MDM2 gene amplification
Myxoid liposarcoma with metaplastic osteochondroid differentiation	Deep soft tissues of extremities of young adults Often metastasizes to other soft tissue sites as well as to lungs	Monotonous small uniform spindle or round cells with abundant (myxoid) or minimal (round cell) myxoid matrix Rich network of delicate vessels becomes inconspicuous in round cell liposarcoma Lipoblasts	S100 protein+ in some cases t(12;16) (q13;p11) or t(12;22) (q13;q12) with FUS-DDIT3 or EWSR1-DDIT3 fusion
Malignant peripheral nerve sheath tumor with divergent osteochondroid differentiation	M > F In neurofibromatosis type 1 or sporadic, axial or in limbs Origin in nerve or neurofibroma	Elongated spindle cells, wavy or buckled nuclei Variably cellular and myxoid, fascicular pattern Nuclei wavy, buckled, or lanceolate Palisading, neuroid whorls, vascular wall involvement, collagenous “rosettes”	S100 protein+ focally, occasional GFAP+
Dedifferentiated liposarcoma with divergent osteochondroid differentiation	Older adults, large retroperitoneal tumor, recurrences frequent M > F	Low-grade dedifferentiation: cellular fascicles with mild pleomorphism High-grade dedifferentiation: pleomorphic undifferentiated sarcoma, or myofibrosarcoma-like Malignant osteochondroid or rhabdomyosarcomatous elements Well-differentiated liposarcomatous component present or absent	MDM2+, CDK4+ P16+, MDM2, CDK4 amplified on fluorescence in situ hybridization+ Variable desmin, SMA, CD34

Pathologic Features

Fibro-osseous pseudotumor is macroscopically fairly well circumscribed, although the surface can be ulcerated. It can display a “zonal” pattern of immature spindled areas admixed with more mature areas showing osteoid metaplasia. The features are similar to those of MO but tend to be less well organized, and generally, the bone is more randomly distributed (Fig. 19.1, e-Fig. 19.1). There is an irregular multinodular growth pattern with variably cellular fascicles of spindle cells with minimal to mild atypia within myxoid stroma (Fig. 19.2, e-Figs. 19.1 and 19.2) reminiscent of nodular fasciitis. Mitotic figures can be abundant. All cases show at least focal irregular bony trabeculae with osteoid formation and osteoblastic rimming,³ with occasional osteoclast-like giant cells (e-Fig. 19.3), and a component of cartilage is sometimes seen (e-Fig. 19.4). Importantly, there is no significant atypia, which helps to exclude osteosarcoma.

Ancillary Investigations

The spindle cells show variable positivity for smooth muscle actin and calponin and are negative for S100 protein, desmin, and h-caldesmon.

FIGURE 19.1 Fibro-osseous pseudotumor. This is an ill-defined lesion in the dermis and subcutis with a cellular spindle cell background and focal bone formation.

FIGURE 19.2 Fibro-osseous pseudotumor. Irregular trabeculae of bone are formed within plump fasciitis-like spindle cell stroma.

MYOSITIS OSSIFICANS

Clinical Features

MO is a rare lesion that can occur at any age, although chiefly affects young adults, with a predilection for males. It is a localized, reactive, self-limiting lesion that generally matures over several weeks to form a peripheral bony rim. It is a reactive process, but its clinical features of rapid growth and histologic features of hypercellularity, mitotic activity, and sometimes focal atypia can mimic malignancy, particularly osteosarcoma. Patients present with a rapidly growing mass at any site, but typically the proximal extremities or trunk. The lesion is separate from bone, and usually within skeletal muscle, but sometimes occurs in or extends into subcutaneous tissue. Patients are typically physically active and often have a history of trauma. The radiologic features reflect the stage of development of the lesion. When fully developed, they usually show a circumscribed lesion with peripheral lacy bone deposition, in contrast with extraskeletal osteosarcoma (EO) where the bone formation is more frequently in the center of the tumor. After time, the lesion may remain stable or undergo resorption, with some lesions regressing completely. Recurrence is rare if the lesion is completely excised.

Pathologic Features

Grossly, lesions are circumscribed and of variable size. There is a spectrum of microscopic features, but characteristically, the lesion is composed of fibroblasts and osteoblastic elements that form bone with a “zonal”
pattern (Figs. 19.3 and 19.4, e-Figs. 19.5 and 19.6). The appearance varies according to the stage of development. The lesion is most cellular in its earliest stage. The central aspect of the lesion resembles nodular fasciitis, with loosely fascicular or patternless arrays of spindle and stellate fibroblasts and myofibroblasts with vesicular nuclei and small nucleoli
(see e-Figs. 19.5 and 19.6). There is no significant atypia unlike in EO. Mitotic figures can be frequent, although atypical ones are not seen. The stroma is myxoid and vascular (see Fig. 19.4, e-Fig. 19.6), with variable chronic inflammation, extravasated erythrocytes, and fibrinoid material. Osteoclast-like giant cells can be present (see e-Fig. 19.6) as well as damaged muscle fibers. There is a transition zone with active bone formation, with trabeculae of woven bone with osteoblastic rimming, and sometimes admixed areas of hyaline cartilage (Fig. 19.5, e-Fig. 19.7). Peripherally, the lesion comprises a layer of well-formed bone (e-Fig. 19.8), initially of woven appearance and later remodeled to lamellar bone. A thin layer of fibrous tissue usually surrounds the lesion. Eventually, the cellular areas within the center become more fibrotic and paucicellular (e-Fig. 19.9) and undergo ossification. In the latest stages, the lesion comprises bone with hematopoietic or fatty marrow.

FIGURE 19.3 Myositis ossificans. The tumor typically has a zonal pattern, with a peripheral rim of more mature bone and a central loose spindle to stellate cell element with metaplastic bone formation.