Reactive and Metabolic Conditions Simulating Neoplasms of Bone


Chapter 23

Reactive and Metabolic Conditions Simulating Neoplasms of Bone



Myositis Ossificans




Definition


Myositis ossificans is a reactive, self-limiting condition characterized by prominent heterotopic ossification. It predominantly occurs deep in soft tissue, and it undergoes zonal maturation. If the lesion is located in the vicinity of bone (i.e., involves the structures of the bone surface), a periosteal reaction contributes to its formation. This may alter the classic clinicopathologic presentation of the lesion. For this reason, we distinguish the classic (soft tissue) and bone surface forms of myositis ossificans (parosteal myositis ossificans) (Fig. 23-1). The pathogenesis of myositis ossificans is unknown, but it is generally considered a reactive process. Chromosome X inactivation analysis indicates that it is a polyclonal disorder, but some recent studies show rearrangement of the USP6 gene in a subset of myositis ossificans, which affects only a minor population of the stromal cells within the lesion.17,30




Incidence and Location


Myositis ossificans predominantly affects adolescents and young, athletically active adults. Typically, it develops at a site of clearly identifiable trauma, but in some cases, no history of injury can be obtained.1,4,5,16,22,24,26,29 The peak age incidence is during the second and third decades of life, and nearly 50% of patients with this diagnosis are in this age group. It is usually found deep in soft tissue within the muscles of the lower or upper extremities (Fig. 23-2). However, it may also involve fasciae, tendons, or subcutaneous tissue.12,13,15 Rare examples of intraabdominal myositis ossificans have been also reported.35 A lesion located deep in soft tissue may present radiographically and clinically as a lesion of the bone surface. Some lesions that originate in the parosteal soft tissue and do not involve the bone surface de novo may eventually, in the process of their evolution, adhere to the adjacent bone. This typically occurs in the later stages of the lesion’s evolution.



Most intramuscular lesions that involve deep soft tissue are located in the lower extremities, whereas more superficial lesions typically affect the upper extremities and occur more frequently in women than in men. A similar process seen predominantly in the acral parts has been designated fibroosseous pseudotumor of the digits. It is described in this chapter under the term florid reactive periostitis in the section on reactive lesions of the bone surface.


A peculiar form of heterotopic bone formation that resembles myositis ossificans occurs in comatose patients who have sustained head injuries.8 It is typically located in the soft tissue around the hip joints, but other major joints such as the shoulder area also can be affected. Heterotopic ossification of the soft tissue has also been described as a complication of many neurologic disorders, including tetanus, myelodysplasia, poliomyelitis, spinal cord injury, anoxic brain damage, and stroke.19,27,32,33 These lesions resemble myositis ossificans in the sense that the fundamental soft tissue reaction is that of heterotopic bone formation. However, they show no radiographic or microscopic evidence of a zonal architecture nor do they ultimately form a peripheral shell of bone.



Radiographic Imaging


Myositis ossificans has several ill-defined phases that may, to some extent, be identified on radiographs.7,9,14,21,31 These evolutionary phases follow an orderly time sequence and reflect maturation and then regression. Initially, radiographs show an ill-defined mass in the soft tissue. A well-developed zonal calcification pattern, characteristic of the mature lesion, is typically seen 4 to 6 weeks after an injury (Figs. 23-3 and 23-4). The mature phase of myositis ossificans presents radiographically as a well-demarcated, calcified mass. The calcifications are accentuated at the periphery of the lesion and may form a shell at its periphery (Figs. 23-3 to 23-5). Less evident faint, flocculent, irregular opacities, referred to as a dotted veil, can be seen much earlier. A regressive phase is associated with some reduction in size and increased mineralization at the periphery. Zonal architecture and mineralization pattern are particularly well documented by computed tomography and magnetic resonance imaging.7,14 T1-weighted images show shell-like signal void of the periphery of the lesion (Figs. 23-3 and 23-5). Central portions of the lesion show varying degrees of signal enhancement on T2-weighted images (Figs. 23-3 and 23-5).





Myositis ossificans developing in the vicinity of bone (parosteal myositis ossificans) can be accompanied by a periosteal new bone formation that typically has a multilayered onion-skin pattern (Figs. 23-4 and 23-6). The presence of a radiolucent cleft (space) that separates the lesion from the periosteum helps distinguish the lesions that affect the soft tissue from those that primarily affect a bone surface (Figs. 23-4 and 23-8).20,21 The lesion may show a focal attachment to the bone surface (see Fig. 23-6). In areas of attachment, especially in a lesion of long duration, it may be difficult to demonstrate a fibrous zone that separates the lesion from the adjacent cortex. However, even if there is radiographic evidence of attachment, microscopically there is usually a narrow fibrous zone that separates the lesion from the cortex. Occasionally, myositis ossificans presents as a convex lesion attached to the surface of the bone by a broad base (Figs. 23-7 and 23-8). Long-standing lesions show a linear pattern of mineralization at the periphery and may show a broad, bony stalk attached to the bone surface, which is fused with its cortex (Figs. 23-5, 23-9, and 23-10). This phase of myositis ossificans somewhat overlaps radiographically and microscopically with acquired osteochondroma or the so-called turret exostosis that is seen predominantly in the acral skeleton.







Myositis ossificans occasionally involves the soft tissues of the trunk or the head and neck region (Fig. 23-11). If these sites are involved in patients younger than age 20 years and especially if multifocal ossifications are present in the soft tissue, myositis ossificans progressiva (fibrodysplasia ossificans progressiva) must be ruled out.




Gross Findings


The gross appearance of myositis ossificans corresponds to the radiographic presentation of the lesion: a zonal architecture with a hemorrhagic, more cellular, center and a peripheral shell of reactive bone (Figs. 23-12 to 23-14). The outer surface of the reactive shell of the bone is more sclerotic and better delineated from the adjacent soft tissue than its inner surface. The inner border of the sclerotic rim merges imperceptibly with a softer, often hemorrhagic, center. The hemorrhagic center is seen in younger lesions. More mature, older lesions show tan, fibrous, sometimes prominently vascularized tissue. Myxoid or cystic changes are frequently seen in fully matured or regressing older lesions. Initially the shell of the bone is ill-defined and sparsely mineralized with a gritty consistency. At the other end of the spectrum are well-developed lesions that have a well-mineralized and clearly demarcated peripheral shell of bone, which requires decalcification for specimen processing. The lesions are typically less than 10 cm in size, and most are relatively small, measuring 3 to 6 cm.






Microscopic Findings


The distinct zonal architecture with predominantly peripheral heterotopic ossification is a hallmark of myositis ossificans (Figs. 23-12 to 23-14).1,2,3,6,11,16,18,31,34 This feature is most evident in mature, fully developed lesions at least 4 weeks old. The inner central portion of the lesion is composed of loose fibrovascular tissue. It resembles, to some extent, granulation tissue or a type of spindle-cell proliferation seen in nodular fasciitis (Fig. 23-15). Ultrastructural analyses show that the proliferating spindle cells in this process are myofibroblasts.25 Areas with ganglion-like giant mesenchymal cells that have prominent nucleoli, similar to those seen in proliferative myositis, also may be present. These usually are seen in younger, evolving lesions. Lesions with a predominance of these types of cells are sometimes referred to as proliferative fasciitis. Evidence of fresh and old hemorrhage with deposition of hemosiderin may be present. Prominent histiocytic and giant-cell reactions may also be seen and are usually concentrated in the areas of hemorrhage. Degenerated, entrapped skeletal muscle cells are seen focally. The peripheral parts of the lesion contain a network of reactive bone that shows prominent osteoblastic rimming (Fig. 23-15). The amount of osteoid and its maturation increases toward the periphery. Early lesions are dominated by florid stromal cell proliferations with nuclear atypia showing various stages of osteoid matrix deposition and mineralization (Figs. 23-16 and 23-17). Fully developed lesions are outlined by a clearly defined shell of mature bone. In well-developed lesions, progressive maturation from woven to lamellar bone may be identified under polarized light. The outer edges of the lesion are separated from the surrounding skeletal muscle by a loose fibrous capsule. Foci of metaplastic cartilage with enchondral ossification evolving into bone trabeculae may occasionally be seen (Figs. 23-18 and 23-19). Metaplastic cartilage is more likely to be present in deeply sited lesions and often corresponds to the areas of bone surface attachment (parosteal myositis ossificans). In this area a clear zonal architecture may be disturbed by a periosteal reaction that contains foci of cartilage. In such cases, metaplastic hypercellular cartilage can dominate the lesion focally. In areas of attachment to a bone’s surface, focal proliferation of bone and metaplastic cartilage can mimic the areas seen in florid reactive periostitis or bizarre osteochondromatous proliferation (Fig. 23-18) (also see the section on reactive lesions of the bone surface in this chapter). Early lesions may show less evident zonal architecture, and the level of cellularity can be very high. In such lesions, florid proliferation of spindle cells with giant cells may be the dominant feature.








Differential Diagnosis


Distinguishing myositis ossificans from extraskeletal osteosarcoma and osteosarcoma of a bone surface is of paramount importance.5,11,16,21,31 The zonal architecture in myositis ossificans is the single most important feature helpful in distinguishing this lesion from malignant bone-forming tumors. The zonal architecture of the lesion can be seen on radiographs and in gross and microscopic examinations and provides important clues to the correct diagnosis. The microscopic features of immature bone trabeculae with osteoblastic rimming and progression to more mature bone are not seen in osteosarcoma. Moreover, extraskeletal osteosarcomas involving soft tissue are usually high-grade lesions with obvious nuclear atypia. Atypical mitoses are not present in myositis ossificans.


It is occasionally difficult to distinguish parosteal myositis ossificans from osteosarcoma (parosteal and periosteal osteosarcoma) of a bone surface, especially when the lesion is located near the surface of a major long tubular bone of the lower extremities. Lesions located on the posterior aspect of the distal femoral shaft and superior to the popliteal fossa should be carefully evaluated because parosteal osteosarcoma frequently is found at this site. Parosteal myositis ossificans usually shows a clear zone of separation from the underlying cortical bone that can be seen on radiographs. Lesions that show wide, broad fusion with the underlying bone in this location should be considered suspicious. Microscopically, parosteal osteosarcoma has unique features of hypercellular, fibroblastic stroma and a network of relatively well-developed tumor bone. Paradoxically, the level of bone maturation in parosteal osteosarcoma often exceeds the level of bone maturation in myositis ossificans. The overall radiographic pattern of mineralization in parosteal osteosarcoma is different from that seen in myositis ossificans because parosteal osteosarcoma has a heavily mineralized central or basal portion that is fused with the underlying cortex.


The occasional presence of cartilage with hypercellularity and nuclear atypia may require differentiation between myositis ossificans and periosteal osteosarcoma. The overall radiographic appearance of periosteal osteosarcoma is different from that of myositis ossificans. Periosteal osteosarcoma is a true lesion of the bone surface and has an associated periosteal reaction that is usually in the form of perpendicular striations on the bone surface. In addition, true sarcomatous elements with direct tumor bone formation are a classic feature of periosteal osteosarcoma. Moreover, periosteal osteosarcoma shows a seamless fusion with the underlying cortex, which is relatively uniform over the entire length of the lesion.



Treatment and Behavior


Myositis ossificans is a benign, self-limiting condition. Conservative excision of the lesion is curative. This is best performed during the mature phase of the disease, when the lesion is well delineated and a mass is clearly identifiable. Incompletely excised lesions, especially those in the early phase of development, continue to grow for a limited period (several weeks to months). Eventually, these lesions stabilize and may undergo partial or complete regression.


Myositis ossificans is one of the rare extraskeletal conditions that may be complicated by a superimposed secondary aneurysmal bone cyst.2 Several reports on secondary malignant transformation in myositis ossificans are not convincing.10,23,28 Most likely, they represent lesions that were originally misdiagnosed and were de novo malignant lesion of the soft tissue.


A more recently published case by E. Konishi et al may represent an extremely rare true example of an osteosarcoma that has developed in association with a long-standing myositis ossificans.13



Myositis Ossificans Progressiva




Definition


Myositis ossificans progressiva (fibrodysplasia ossificans progressiva) represents an extremely rare, multifocal, generalized chronic progressive disease of heterotopic ossification within the body’s musculature and frequently shows a familial pattern of occurrence.38,41,42,57,63 It predominantly affects children during the first decade of life, primarily between birth and age 6 years.


Myositis ossificans progressiva is an autosomal dominant disorder caused by germline mutations of the activin A type 1 receptor (bone morphogenetic protein type 1 receptor) gene mapping to the 2q23-34 chromosomal region in both inherited and sporatic cases.58,59 The majority of patients carry a germline (617G→A; R206H) mutation in the glycine-serine (Gs) activation domain of the ACVR1 gene. Other less frequent mutations such as (1067G→A; G356D) also involving the ACVR1 gene have been identified.46,47 Another predisposing locus mapping to the 17q21-32 region with mutations of the noggin (NOG) gene may be involved in a subset of patients with myositis ossificans progressiva.45,55


It is postulated that the mutations of ACVR1 cause destabilization of the GS domain and permanently activate ACVR1, which in turn trigger exuberant ectopic chondrogenesis and osteogenesis, a hallmark of myositis ossificans progressiva. Upregulation of the RUNX2/CBFA1 gene in stromal cells of myositis ossificans progressiva increases the recruitment of chondroprogenitor and osteoprogenitor cells from the pool of uncommitted primitive mesenchymal cells.48 The resulting downstream deregulation of the bone morphogenetic protein network through the SMAD and MAPK kinase pathways causes ligand-independent activation of bone morphogenetic protein signaling and ligand-dependent hyper-responsiveness to bone morphogenetic protein stimulation.36,44,64 Animal model studies indicate that hematopoietic stem cells contribute to early phases of heterotopic ossification induced by BMP-4.51 Although the genetic defects causing fibrodysplasia ossificans progressiva are not completely understood, the clinical and animal models implicate mutations in bone morphogenetic proteins, their receptors, and activin receptor type IA (ACVR1) as well as mutations of the noggin (NOG) gene in the development of this disorder.56



Clinical Symptoms


Multifocal involvement of soft tissues, predominantly of the trunk, a progressive chronic clinical course, and a familial incidence and occurrence in young children distinguish this disease from the more common, localized, and solitary (posttraumatic) form of myositis ossificans.37,38,40,41,43,52,57


The first clinical manifestation is a localized, painful swelling in the soft tissue. The onset is often precipitated by a minor injury or an infectious disease. The lesion typically appears first within the muscles of the trunk (the back, shoulder, and paravertebral region). The head and neck region is also a frequent site of initial presentation. Lesions of the head and neck are most often located in the scalp and within the sternocleidomastoid muscle. As it progresses, the disease moves into the proximal parts of the extremities until it eventually involves their distal parts, which is typical of a more advanced, long-term process.40,41


The disorder is often associated with abnormalities of bone and joint formation that principally affect the acral skeleton.60 The changes predominantly consist of bilateral microdactyly and the absence of both thumbs and great toes. If great toes are present, they frequently show deviation (bilateral hallux valgus). Deafness and sexual infantilism can also be present.



Radiographic Imaging


On radiographs, the disorder presents as multifocal ossifications of soft tissue that progress to form a network of interconnecting bridges between adjacent bones and joints, causing ankylosis, muscle stiffness, and ultimately, heterotopic bone formation at the affected sites (Fig. 23-20).39,54,61,62




Microscopic Findings


The early lesions consist of multifocal proliferations of plump fibroblasts within the skeletal muscle, similar to those seen in fibromatosis. In fact, early lesions of myositis ossificans progressiva, especially in the sternocleidomastoid muscle, are often confused with juvenile fibromatosis. The lesions undergo mineralization and develop extensive bone metaplasia with formation of fusing bridges between adjacent bones and joints. The development of bone can be associated with cartilage metaplasia and can have features of enchondral ossification.53 The zonal architecture typical of common solitary myositis ossificans is not present (Fig. 23-21).



Pathogenetically, the disease has three main phases that somewhat parallel those of conventional solitary myositis ossificans. The first phase consists of a proliferation of loose fibroblastic cells that are somewhat similar to those seen in fasciitis or fibromatosis. In the second phase, thick collagen fibers appear among the fibroblasts before osteoid deposition, mineralization, and the metaplastic change into bone and cartilage. In the third (regressing) phase, there is some reduction in size, and maturation is identified by the network of lamellar bone and the formation of firm bridges among individual lesions and adjacent structures (articular ankylosis). Contrary to localized solitary myositis ossificans, this process is multifocal, and the ossifications develop in the centers of individual lesions rather than at their periphery.



Differential Diagnosis


Myositis ossificans progressiva should be differentiated microscopically from fibromatosis and the localized common form of myositis ossificans. The analysis of the entire clinical and radiographic picture is usually very helpful: occurrence during the first decade of life, initial involvement of trunk musculature, and presence of multifocal proliferations. Radiographic and microscopic evidence of bone formation helps differentiate the lesions from fibromatosis. In addition, the clinical differential diagnosis includes battered child syndrome, ectopic bone formation with multiple congenital anomalies, and pseudohypoparathyroidism.



Treatment and Behavior


Typically the disease is fatal and causes death after 10 to 15 years of prolonged progressive illness with transient spontaneous remissions.37,40,41,49,50,57,61 The fatal outcome frequently results from the progressive immobilization of the thorax, which causes severe respiratory insufficiency. Biopsy, trauma, and infections can exacerbate the process and lead to the development of new lesions.



Reactive Lesions of the Bone Surface


Periosteal (bone surface) reactive lesions that mimic primary neoplasms of bone occur in several distinct clinicopathologic settings and are designated as florid reactive periostitis, bizarre parosteal osteochondromatous proliferation, acquired osteochondroma (turret exostosis), and subungual (Dupuytren’s) exostosis.77,95,100 In the pathology literature concerning soft tissue, these lesions are designated descriptively as fibroosseous pseudotumors.76,78,97 Common to all these lesions is an initial hemorrhagic subperiosteal collection that often can be related to trauma.


The lesion undergoes organization referred to as maturation. Because of its peculiar localization, a periosteal reaction (i.e., new bone and cartilage of periosteal origin) participates in the process. Initially, spindle and giant cells, as well as hemorrhage with minimal bone and cartilage proliferation, dominate the lesion (florid reactive periostitis). Later, periosteal new bone formation and metaplastic cartilage proliferation are dominant elements (bizarre parosteal osteochondromatous proliferation, or Nora’s lesion). Finally, the focus of ossification matures with the formation of a bony base that is incorporated into the underlying cortex and that more peripherally is covered with a cartilaginous cap (acquired osteochondroma, turret exostosis, subungual exostosis).


All these lesions predominantly affect the phalanges of the hands and feet and have their peak incidence in the third and fourth decades of life (Fig. 23-22). They rarely involve the long tubular bones of the extremities. The bones of the forearm are more often affected than other long bones. In extremely rare instances, the lesions can involve other bones.



It is postulated that the radiologic and histologic features of these lesions depend on their stages of maturation and organization rather than on a distinct pathogenesis.107 The basic architectural features of these conditions are summarized in Figure 23-23. Although the radiographic and microscopic data of these conditions clearly overlap, recent cytogenetic studies have identified distinctive chromosomal rearrangements in subungual (Dupuytren’s) exostosis and bizarre parosteal ostechondromatous prolifereration (Nora’s lesion), which suggests that these lesions are in fact neoplastic and may evolve via different molecular mechanisms.79,86,94,101,108 Several reports indicate that Nora’s lesion is characterized by a clonal balanced translocation t(1;17)(q32; q21) or variant translocations involving 1q32 or t(1:17)(q42:q23) (Fig 23-24).79,94 Conversely, the cells in subungual exostosis carry a balanced clonal translocation t(x;6)(q13-14;q22).86,91,101,108 The chromosomal breakpoints of subungual exostosis cluster in 6q13-14 and Xq22 harboring the collagen genes CoL12A1 and COL4A5, respectively.101 The exact structure of putative chimeric gene(s) and their fusion transcripts in subungual exostosis are unknown at this time.




 
image

B, Partial karyogram showing reciprocal 1;17 translocation. Breakpoints are indicated by arrows. C, Three-color metaphase fluorescent in situ hybridization (FISH) using BAC probes 99A19 (green), 145I20 (red), and 351B8 (yellow). Signals from all three probes are present in the der(17)t(1;17), whereas the reciprocal der(1) has a signal from only the proximal probe 99A19. The insert presents only green signals to demonstrate the uneven split of 99A19. D, Split of BAC probe 219F9 (yellow). Signals are seen on der(1), der(17), and chromosome 17. Signals from the more proximal probe 243D13 (red) are present on der(17) and chromosome 17. The whole chromosome 1 paint probe (green) demonstrates the presence of chromosome 1 material. E, Interphase nucleus (case 1) showing a split in the 1q probes. Chromosome 1 is indicated by joined red and green signals (arrow), der(1) is indicated by a red signal (black arrowhead), and der(17) is indicated by a green signal (white arrowhead). F, Interphase nucleus showing a split in the 17q probes. Chromosome 17 is indicated by joined red and green signals (arrow), der(17) is indicated by a red signal (black arrowhead), and der(1) is indicated by a green signal (white arrowhead). G, Interphase nucleus (case 2a) showing fusion of the proximal 1q and distal 17q probes. The fusion and der(1) are indicated by joined red and green signals (arrow), chromosome 1 is indicated by a red signal (black arrowhead), and chromosome 17 is indicated by a green signal (white arrowhead). H, Normal tissue hybridized with the 1q probes, where red and green signals are seen together on chromosome 1 (arrows). I and J, FISH probes used for detecting breakpoints in chromosomes 1 and 17. BAC clones are represented by vertical lines. Probes that were split by the 1;17translocation are marked with stars, and those used in interphase FISH analyses are shown in bold type. Probes situated on the proximal side and on the distal side of the breakpoints are labeled red and green, respectively. The localization and size of BAC clones are given according to the UCSC Genome Browser and NCBI Map Viewer. (B-J, Modified and reprinted with permission from Nilsson M, et al: Human Pathol 35:1063–1069, 2004.)



Florid Reactive Periostitis


The term florid reactive periostitis was proposed by Spjut and Dorfman100 in 1981 to designate a rare lesion on the bone surface that most frequently affects the short tubular bones of the hands and, less commonly, the feet.80,82,96,103 The peak incidence is during the third and fourth decades of life. Nearly 70% of cases are diagnosed in patients between ages 20 and 40 years, at a mean age of 34 years. There is no sex predilection. The lesions usually involve the proximal and middle phalanges and less frequently, the metatarsals and the metacarpals but have also been reported in the long bones.68


Radiographically, there is a critical difference between these proliferations and ordinary cartilage-capped osteochondromas. There is no flaring out of the cortex of the adjacent bone or continuity of the central part of the lesion with the underlying osseous medulla, as is seen in typical osteochondroma. The lesion appears to arise from the surface of the bone without disturbing the architecture of the adjacent bony structure. The overall shape of the lesion is that of a pedunculated or, more often, flat cap attached to the bone surface (Fig. 23-25). Early lesions present as an ill-defined density of soft tissue that is attached to the bone surface and contains varying amounts of calcific material. Sometimes, rapid growth is noted over several days or weeks. Most symptoms are related to the mechanics of the lesion, such as discomfort from wearing shoes or pain when flexing digits.



The size of the lesions varies from 0.5 to 3.0 cm. Most lesions are grossly described as resembling osteochondromas because they have a bony matrix covered by cartilage. Microscopically, an irregular cartilage cap covers the outer surface of the lesion. The cartilage exhibits marked proliferative activity. The osteocartilaginous interface is irregular and strongly resembles a callus. Cartilage cells are numerous and have enlarged nuclei. Spindle-cell fibroblastic proliferation with giant-cell reaction and fresh hemorrhage can dominate the lesion focally.



Bizarre Parosteal Osteochondromatous Proliferation (Nora’s Lesion)


Bizarre parosteal osteochondromatous proliferation predominantly involving the bones of the hands and feet has been described by Nora et al.95 The peak age incidence is during the third and fourth decades of life, and the lesion predominantly affects the short tubular bones of the hands and feet.65,71,74,75,85,87,90,105 The peak age incidence and the anatomic sites involved closely overlap with those of florid reactive periostitis. In fact, the lesion is closely related to other reactive lesions of the bone surface and most likely represents an intermediate step between florid reactive periostitis and acquired osteochondroma that is either subungual or the so-called turret exostosis found on the shafts of phalanges and metacarpals.


Radiographically, Nora’s lesion presents as a well-delineated, cap-shaped lesion attached to the bone surface. Plain radiographs typically disclose a well-developed patchy or linear mineralization pattern (Figs. 23-26 and 23-27).




Prominent periosteal new bone and cartilage formation is a dominant feature of the lesion (Figs. 23-27 and 23-28). The cartilage shows hypercellularity, an open chromatin structure, and binucleated cartilage cells. In summary, the lesion exhibits striking architectural and cytologic atypia that may lead to the diagnosis of malignancy if microscopic features are evaluated without knowledge of the entire clinicoradiologic presentation. Despite pronounced cytologic atypia of both osseous and cartilaginous elements, a low power examination discloses a peculiar zonal architecture—the bony elements are located within the central/basal region, and the cartilage forms irregular, caplike structures toward the periphery. In some cases, a more organized, somewhat parallel arrangement of reactive bone trabeculae can be seen at low power magnification.




Acquired Osteochondroma (Turret Exostosis)


The term turret exostosis was proposed by Wissinger et al.106 in 1966 in reference to reactive lesions on the bone surface of the phalanges that they descriptively designated as ossifying hematoma of the phalanges.83,92 The clinicoradiologic features of this condition overlap with the two other reactive lesions of the bone surface described in this section: florid reactive periostitis and bizarre parosteal osteochondromatous proliferation.


Radiographically, acquired osteochondroma is typically well delineated and has a well-developed linear mineralization pattern at the base, which is fused with the cortex (Fig. 23-29). Microscopically, the lesion consists of an ossified core or base attached to the underlying cortex. The periphery of the lesion is covered by a cartilaginous cap.



Depending on the level of maturation of osseous and cartilaginous elements, the lesion may exhibit more or less architectural and cytologic atypia. Typically the zonal architecture is well developed; that is, it has cartilage at the periphery and bone at the base (Fig. 23-30). The proliferation of cartilage is less evident, and the cartilage cap is thinner and more regular and exhibits less cytologic atypia. In contradiction to ordinary osteochondroma or osteocartilaginous exostosis, the underlying cortex is intact, and there is no continuity between the center of the lesion and the medullary cavity of the affected bone. In summary, the microscopic features overlap with those of so-called subungual exostosis.




Subungual (Dupuytren’s) Exostosis


Subungual exostosis is an osteocartilaginous reactive lesion similar to acquired osteochondroma but arising from a distal phalanx.66,67,69,70,72,73,81,84,88,89,93,98,99,102,104 It was first described by Dupuytren in 1847 as a bony growth of the distal phalanx of the great toe.77 In fact, this is the most frequent location of the lesion. The peak incidence is in the second and third decades of life, at a mean age of 24 years. Nearly 80% of reported cases involve the great toe, and the remaining cases involve other toes. Subungual exostosis rarely involves the fingers.


The radiographic features are typical. Frequently, the exostosis arises from the dorsal aspect of the tip of the distal phalanx (Figs. 23-31 and 23-32). In mature, well-developed lesions, there is a clear trabecular pattern at the base that connects the lesion to the underlying phalangeal bone tuft. The peripheral parts of the exostosis have ill-defined margins and a hazy density in the soft tissue, which is the typical presentation of an early lesion. As these lesions mature, they develop calcification and trabecular patterns (compare photographs in Fig. 23-32).




In the early stages of development, the lesion consists of proliferating fibroblasts in direct continuity with the nail bed, where cartilaginous metaplasia can be seen (Figs. 23-33 and 23-34). The cartilage gradually undergoes calcification, increases in volume, and develops enchondral ossification. The areas of enchondral ossification gradually progress to woven bone and then lamellar bone. Eventually the bone forms the core, or base, of the lesion and is covered by a thick cartilaginous cap (Figs. 23-33 and 23-34). During evolution of the lesion, the continuity between the bony stalk and the underlying cortex is established. The cartilage cap may show striking cellularity with plump nuclei and binucleated and multinucleated chondrocytes. The surrounding proliferating fibrous tissue can be hypercellular, and it is composed of myofibroblasts. In the initial phase, the proliferation of cartilage contributes to the exophytic growth of the lesion. In later phases, an interconnecting network of mature lamellar bone dominates the lesion (Fig. 23-35). Limited biopsy samples taken from the periphery of the lesion may create the impression of a malignant cartilage tumor. The microscopic features of this condition should be evaluated with the clinicopathologic presentation: the anatomic site and radiographic features of a lesion at the bone surface. An associated infection can cause a considerably acute and chronic inflammatory infiltrate.


May 31, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Reactive and Metabolic Conditions Simulating Neoplasms of Bone
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