儿童综述骨化肌颜

REVIEW Myositis ossificans circumscripta: a paediatric case and review of the literature Annalisa Micheli & Sandra Trapani & Ilaria Brizzi & Domenico Campanacci & Massimo Resti & Maurizio de Martino Received: 1 August 2008 /Accepted: 8 December 2008 /Published online: 8 January 2009 # Springer-Verlag 2008 Abstract Myositis ossificans circumscripta (MOC), char- acterised by non-neoplastic heterotopic bone formation in soft tissue and skeletal muscle, is rare in children. At onset, it is difficult to distinguish MOC from a musculoskeletal infection or neoplasm, particularly in absence of trauma, and a biopsy is frequently required. We describe an 11- year-old boy with MOC in his thigh. At admission, minor local trauma was referred, and clinical examination revealed a tender and painful mass in the left thigh. Hypothesising a periarticular infection, a wide-spectrum antibiotic and an anti-inflammatory drug were given. The magnetic resonance imaging revealed an enlarged mass with marked enhancement of the lesion and a central, irregular non-enhanced area due to necrosis. After inci- sional biopsy, the histopathological examination found immature osteoblasts inside striated muscle fibres, as well as proliferating fibroblasts, which are all compatible with MOC, thereby ruling out infection or malignancy. The CT scan showed calcified deposits arranged in a ring, thus confirming MOC; a radiological follow-up was suggested to detect the lesion’s maturation. Three months after diagnosis, surgical excision was performed. The post- operative period was uneventful. Six months later, the child was in good condition, with no signs of recurrence. In the literature, 57 paediatric cases have been described; most of these had an acute course, required excision and then had a favourable evolution. Our case study confirms the good prognosis of MOC and underlines how this benign condition should be considered in children presenting a tender and painful soft-tissue swelling. Keywords Myositis ossificans circumscripta . Children Abbreviations MO Myositis ossificans FOP Fibrodysplasia ossificans progressiva PHO Progressive osseous heteroplasia MOC Myositis ossificans circumscripta MRI Magnetic resonance imaging CT Computed tomography Introduction Myositis ossificans (MO) is a rare benign disorder characterised by a non-neoplastic heterotopic bone forma- tion in soft tissue and skeletal muscle [17]. It can be divided into three types: myositis ossificans progressiva (fibrodys- plasia ossificans progressiva, FOP, OMIM no. 135100), which is a hereditary and severe generalised form leading to diffuse heteropic ossification, throughout exacerbations precipitated by trauma; MO without a history of trauma (non-traumatic or pseudomalignant MO), which may follow after burns, haemophilia, paraplegia or poliomyeli- tis; and finally, MO circumscripta (MOC) or traumatica, which is related to an evident and direct trauma [17]. The latter form is the most common MO, representing 60–75% of the cases [17]. It can be observed at any age, but the highest incidence is reported in adolescents and young Eur J Pediatr (2009) 168:523–529 DOI 10.1007/s00431-008-0906-8 A. Micheli (*) : S. Trapani : I. Brizzi :M. Resti :M. de Martino Department of Paediatrics, University of Florence, Anna Meyer Children’s Hospital, Viale Pieraccini, 24, Florence, Italy e-mail: annalisa_micheli@yahoo.it D. Campanacci Orthopaedic-Oncology Unit, Careggi Hospital, Florence, Italy adults, while it is rare in children younger than 10 years [17, 23]. MOC mainly affects extremities, either limbs or arms. It occasionally involves other sites, such as the temporal muscle [27], abdominal muscles [25, 35] or paravertebral muscles [31, 33]. Many hypotheses have been proposed concerning its aetiology, but major injury (e.g. fractures and dislocation) or minor repeated trauma are considered the most common causes [11, 15, 17]. MOC presents as a painful soft-tissue mass, which can be easily confused with malignant lesions such as osteo- sarcoma and soft-tissue sarcoma. Thus, diagnosis of this condition may be difficult and requires radiological and/or histological findings [17]. We present a new paediatric case of MOC localised in the thigh and report the literature review. Case report A previously healthy 11-year-old Caucasian boy was referred to our hospital because of a painful mass in the distal part of his left thigh and restricted range of motion (above all, reduced extension of the left knee). His past history revealed that he had often played football in the previous months. Moreover, the child referred that he had fallen against sea rocks 1 month before. At admission, clinical examination revealed a tender, painful and warm mass in the posteromedial area of the distal left thigh and a low-grade fever. No other skeletal anomaly, such as adactyly, microdactyly, ankylosis of the interphalageal joint, clinodactyly or pseudoesostosy, was observed at admission. There were no external signs of injury. Laboratory tests revealed a normal erythrocyte sedimen- tation rate, slightly increased C reactive protein, normal white blood cell counts, lactate dehydrogenase and alkaline phosphatase. Antistreptolysin-O and anti-DNase B titres were within the normal range. A plain knee X-ray, performed 3 weeks after injury, did not show any alteration besides soft-tissue swelling. Musculoskeletal ultrasound showed an inhomogeneous (hypoechogenic) enlargement of soft tissue (sized 40×38×35 mm), local- ised posteriorly at the lower extremity of the left thigh. The first orthopaedic consultant hypothesised a periartic- ular infection; therefore, the patient received a wide- spectrum antibiotic treatment (oxacillin and ceftriaxone) and an anti-inflammatory drug (ibuprofen) for suspected cellulitis. A few days later, magnetic resonance imaging (MRI) was performed. The MRI revealed an enlarged mass with overthrowing structure inside the gastrocne- mious muscle (sized 65×50×40 mm), suggesting a soft- tissue (muscle) neoformation. Post-contrast images showed a strongly enhancing soft-tissue lesion with a central, irregular, hypointense area and diffuse enhance- ment of the surrounding muscle. As the lesion could not be correctly identified, an incisional biopsy was performed. The histopathological examination showed immature osteoblasts inside oedematous, striated muscle fibres and proliferating fibroblasts, without malignant cells (Fig. 1). These features were considered compatible with MOC. A new orthopaedic consultation was performed, and a radiological follow-up was suggested in order to detect the lesion’s maturation. An initial computed tomog- raphy (CT) scan showed a peripheric ossification of the lesion, thus further confirming MOC (Fig. 2a). One month later, a plain X-ray showed marked calcifi- cation in the muscle and periosteal reaction; a CT scan control demonstrated increased peripheric ossification with focal central radiolucency (immature unmineralised central area), with a zonal organisation (Fig. 2b). The child underwent a clinical and radiological follow-up. Surgical treatment was planned for about 3 months after diagnosis, given the lesion’s evolution. At a further CT scan, the mass was better defined and more ossified than in the previous one (Fig. 3). At surgery, a firm mass involving the medial gastrocnemious insertion on the femur was excised with marginal surgical margins. The histological examination of the mass confirmed myositis ossificans without any malignancy. The post-operative period was uneventful and the patient was discharged. Six months later, the patient was in good condition; he showed a complete recovery of his knee’s range of motion. At the time of writing, there is no sign of recurrence. Fig. 1 Histology in case: proliferating fibroblasts admixed with immature osteblasts production with a regular architectural pattern inside striated muscle fibres 524 Eur J Pediatr (2009) 168:523–529 Discussion MOC is a benign, heterotopic bone formation [11, 17]. It is relatively rare, but it must be kept in mind in the differential diagnosis of a tender, soft-tissue swelling (osteosarcoma and soft-tissue sarcoma). Moreover, when the disease occurs in a periarticular location, it may also be mistaken for inflammatory arthritis. MOC may develop after a fracture, dislocation or even minor trauma to the soft tissues, probably following the release of periostal cells and growth factors into muscle. Contrary to its name, MOC is not strictly an inflammatory process. Traumatic injury might be followed by inflammation, which precedes the fibroproliferative response. In fact, MOC is essentially a proliferative mesenchymal response to an initiating injury to the soft tissue, not necessarily to the muscle, which leads to localised ossification. In the first week, richly vascular- ised, proliferative fibroblastic cells are prominent. These primitive mesenchymal cells, with high mitotic activity, can mimic malignancy on biopsy. With maturation of the lesion, which is variable, a typical zonal pattern develops with three distinct zones: (1) the centre consists of rapidly proliferating fibroblasts with areas of haemorrhage and necrotic muscles, (2) the intermediate or middle zone is characterised by osteoblasts with immature osteoid forma- tion and islands of cartilage due to enchondral ossification, (3) the peripheral zone is composed of mature bone, usually well separated from the surrounding tissue by myxoid fibrous tissue. Then, by the third to fourth week, calcifica- tions and ossifications appear inside the mass; by the sixth to eighth week, a well-organised cortical bone with cortex and marrow space formation develops at the periphery [1, 29]. This new bone continues to mature, so that by 6 months, a dense ring of compact bone has developed with a central core of lamellar bone [5, 26]. New bone formation is the result of increased vascularity and metabolism, plus an excess of calcium brought to the injured part due to hyperaemia subsequent to the injury. MOC is rarely described in childhood. So far, to the best of our knowledge, 57 cases have been reported in the literature. The MEDLINE database was searched for the key words “myositis ossificans” and “children”; additional Fig. 3 Tridimensional CT scan control, 3 months later, demostrate a well-defined and highly ossified mass, which is attached to the cortex by a short sessile base Fig. 2 a CT scans show the ossified mass inside the gastrocnemious muscle with a peripherical ossification of the lesion. b A CT scan control, 1 month later, demonstrated an increased peripheral ossifica- tion with focal immature non-mineralised central area, with a zonal organisation Eur J Pediatr (2009) 168:523–529 525 words used in further queries included “fibrodysplasia ossificans progressiva”. In Table 1, the epidemiological, clinical and diagnostic data of all paediatrics cases published from 1958 to 2007, including the present case, are summarised [1–3, 8–10, 13, 14, 17–22, 28, 29, 32–34]. Regarding gender, no sex predilection was found, as already stated by Nuovo et al. [29]; although, in adulthood, MOC is more frequently described in males [8, 12, 24, 30]. Most of the cases are adolescents, and only six patients are younger than 5 years. The most common sites for MO are the large muscle groups of the thigh and the arm. Twenty- seven patients, including our case, developed MOC in the lower limbs, and 18 at the upper limbs. More rarely, it can occur at any other anatomical site, such as the temporal muscle [27], neck [6], scapula [29], hand [10], para- vertebral muscles [31, 33] or abdominal wall [1, 25, 35]. A positive history of trauma was reported in only 14 paediatric patients. In one of these, the lesion occurred after arthroscopy [2]. Traumatic history was, however, specifi- cally negative in 13 cases. In 31 cases, a previous trauma is not mentioned. However, absence of a reported prior injury does not necessarily exclude the presence of MOC since trauma may have been forgotten and/or not recollected unless explicitly asked for [17]. The clinical history of our patient revealed that he usually played football. Moreover, he referred a minor trauma which had recently occurred. The absence of a history of trauma initially can be misleading and prevent the inclusion of MOC into the differential diagnosis. This is well demonstrated by the alternative terms “pseudomalignant MO” or “tumour of soft tissue” also used for this lesion in the literature [11, 24, 26]. In the early stage, children present increasing pain and swelling that can suggest soft-tissue infection, as in our case, or tumour [24]. High fever is usually absent. Moderate serological inflammatory signs have been only rarely reported [9, 17]. In the later stages, pain and swelling eventually diminish. A correct diagnosis of MOC especially at onset may be difficult. However, differentiating MOC from malignant neoplasm is imperative. In the earlier stages, when peripheral ossification is absent or incomplete, the appear- ance of a mass may suggest osteosarcoma, synovial sarcoma or fibrosarcoma. Although when ossification is complete, periosteal and parosteal sarcoma must be considered in the differential diagnosis. The differential diagnosis should also include various benign conditions, such as post-traumatic periostitis, osteomyelitis, tumoural calcinosis and osteochondroma [1, 20]. Furthermore, in its early stage, MOC could be confused with FOP; however, FOP generally affects infants, while MOC is extremely rare under 10 years. Furthermore, FOP initially involves the toes, which are usually spared in MOC, and frequently includes skeletal anomalies, such as adactyly, microdactyly, clinodactyly and pseudoexostosis, which are not observed in MOC. Lastly, FOP progresses with a dissemination of fibro-osseous masses in multiple sites, producing severe disability. Progressive osseous heteroplasia (OMIM no. 166350) is another genetic condition involving soft tissue and extension into skeletal muscle that could be mistaken for MOC. In the literature, the initial most frequent clinical misdiagnoses were tumour, specifically osteosarcoma in seven cases and soft-tissue sarcoma in one and osteomye- litis in four children. Other provisional diagnoses were lymphadenitis in two cases and FOP in one. In our case, the initial diagnosis was cellulitis. The most important radiographic hallmark of MOC is the presence of so-called zonal phenomenon. On a plain X-ray, this phenomenon is characterised by a central radiolucent area, indicating immature bone formation, and by a peripheral dense zone of mature ossification. In addition, a thin radiolucent cleft separates the ossified mass from the adjacent cortex. These features could help to differentiate this condition from juxta-cortical osteosarco- ma, which may appear very similar. MRI findings are almost non-specific, as well, in that it may demonstrate lesion before the appearance of calcifications. On MRI imaging, MOC appear as a relatively well-defined, inho- mogeneous soft-tissue mass. In fact, in its early stages, only an isointense nodule can be distinguished from the surrounding muscles in T1-weighted images, which en- hance contrast at its periphery in T2-W [15, 34]. Only in the later stages are MRI findings consistent with MO. De Smet et al. highlight a low-signal intensity rim on T1-W and T2-W images as an important, common finding that reflects the beginning of peripheral ossification. However, these patterns are not specific to MOC, as they have also been noted in benign neoplasms, haematomas, abscesses and malignant tumours [13, 26]. In MRI, extensive muscle oedema without bone marrow and cortical abnormalities are considered uncommon in neoplasms and infections [16]. Hanna et al. presented a case of subacute MOC in the quadriceps. T1-weighed MR images showed an inhomoge- neous mass with signal intensity that was slightly higher than the surrounding muscle and with a well-defined low- signal intensity rim corresponding to peripheral ossifica- tion. T2-weighed MR images showed markedly increased central signal intensity [20]. In agreement with Hanna’s case, in our patient, a strongly enhancing soft-tissue lesion with central irregular hypointense area and diffuse en- hancement of the surrounding muscle was present. The pathological criteria establishing the diagnosis of MOC are based on this lesion’s characteristic pattern of maturation. The CT appearance of MOC has been well described [20, 26]. CT usually shows a rim of mineralisation around the lesion after 4–6 weeks. Even when densely mineralised 526 Eur J Pediatr (2009) 168:523–529 Table 1 Epidemiological, clinical and diagnostic data of all the paediatric cases with MOC published from 1958 to 2007 Authors [ref] Sex Age y.m Site Trauma Clinical diagnosis Radiological diagnosis Biopsy Ackerman 1958 [1] F 6.5 Thigh Nr Nr Nr MO Ackerman 1958 [1] F 12 Thigh Nr Nr Nr MO Ackerman 1958 [1] F 15 Abdominal muscle Nr Nr Nr MO Angervall 1969 [in 9] F 9 Axilla Nr Nr Nr Nr Angervall 1969 [in 9] F 13 Hip Nr Nr Nr Nr Valentin 1969 [in 9] M 14 Knee Nr Nr Nr Nr Dickerson 1971 [14] F 5 Nr Yes Nr Nr Nr Norman 1970 [in 9] M 13 Shoulder Nr Nr Nr MO Paterson 1970 [in 9] M 7 Thigh Nr Nr Nr Nr Paterson 1970 [in 9] M 15 Knee Nr Nr Nr Nr Faure Vialas 1975 [in 9] M 8.5 Axilla Nr Nr Nr MO Goldman 1976 [18] F 11 Shoulder Nr Nr Nr MO Wilkes 1976 [34] M 2.11 Deltoid Yes Nr Nr MO Goldman 1976 [18] F 11 Shoulder No OS Calcified mass with parosteal bone formation MO Goldman 1976 [18] M 15 Hip Nr OS Ossified mass MO Tredget 1977 [32] M 15 Arm Yes Nr MO Nr Tredget 1977 [32] M 11 Thigh Yes Nr MO Nr Ogilvie Harris 1980 [in 9] F 13 Nr Nr Nr Nr Nr Ogilvie Harris 1980 [in 9] M 13 Nr Nr Nr Nr Nr Ogilvie Harris 1980 [in 9] M 14 Nr Nr Nr Nr Nr Ogilvie Harris 1980 [in 9] F 15 Nr Nr Nr Nr Nr Ogilvie Harris 1980 [in 9] M 8 Nr Nr Nr Nr Nr Ogilvie Harris 1980 [in 9] M 10 Nr Nr Nr Nr Nr Ogilvie Harris 1980 [in 9] F 15 Nr Nr Nr Nr Nr Valette 1985 [in 9] M 14 Axilla Nr Nr Nr MO Pazzaglia 1986 [in 9] M 0.1 Thigh Nr Nr Nr MO Ducloyer 1988 [in 9] F 14 Thigh Nr Nr Nr MO Ducloyer 1988 [in 9] F 7 Thigh Nr Nr Nr Nd Ducloyer 1988 [in 9] M 3.5 Thigh Nr Nr Nr MO Rooser 1989 [in 9] M 15 Thigh Nr Nr Nr MO Sellami 1990 [in 9] M 8 Thigh Nr Nr Nr Nr Hanna 1990 [20] M 12 Thigh Yes OS Calcification within the mass MO Nuovo 1992 [29] F 8 Arm No OS Surface OS review: MO Parosteal OS Nuovo 1992 [29] M 1 Arm Yes OM Juxta-cortical lesions osteogenesis imperfecta (upon review) Post- traumatic ossification Nuovo 1992 [29] M 14 Tibia No Nr Periosteal bone reaction Nr Nuovo 1992 [29] F 11 Hip No L Avulsion fracture. No “zoning” in subsequent films MO review: reparative changes Nuovo 1992 [29] F 5 Thigh Nr Child abuse or OM MO with periosteal reaction Nr Nuovo 1992 [29] F 11 Scapula Nr Nr MO Nr Nuovo 1992 [29] F 16 Knee No Nr Cortical defect distal femur Parosteal OS versus callus Eur J Pediatr (2009) 168:523–529 527 on CT, this rim is much less evident on MRI. Mature lesions may show diffuse ossification, with corresponding regions of decreased signal intensity on all MRI pulse sequences [26], whereas CT findings may also confirm separation of the lesion from adjacent bone [20]. Further- more, CT scan allows follow-up on the calcification stages. In our case, the CT scan showed that the mass was attached to the cortex by a short sessile base with adjacent periosteal reaction. This alteration has already been reported in other cases of post-traumatic MO [20]. Biopsy is indicated for cases not showing MOC’s typical radiographic zonal ossification pattern [21]. In our case, MRI was done first, and so, the findings were non-specific. Biopsy was necessary for the diagnosis to rule out infection or malignant tumour. Some reports suggest that MRI may be the first-choice diagnostic option and thereby may avoid