A fibrodysplasia ossificans progressiva patient with a rare missense mutation in ACVR1 detected on 18F-FDG PET/CT.

Fibrodysplasia ossificans progressiva (FOP) is an exceedingly rare human genetic disorder characterized by the progressive and incapacitating formation of ectopic bone outside the skeleton. We report a case of FOP patient with mutations within the ACVR1 gene (c.982G>A; p.G328R). 18F-FDG positron emission tomography/computed tomography (PET/CT) was carried out for disease assessment. Previous studies have shown increased FDG uptake in regions of heterotopic ossification (HO) in FOP. However, in our study, the PET/CT features demonstrate that active ossificans exhibit increased 18F-FDG uptake, whereas end-stage ossifications do not. Collectively, 18F-FDG PET/CT emerges as a prospective approach to evaluate medication efficacy in the early stages, directing early intervention and pharmacological management of FOP before ossifications formation.

Challenges in Diagnosing Fibrodysplasia Ossificans Progressiva: A Case Report.

CASE: A 5-year-old boy presented with multiple bony swellings in the dorsal spine region, restricted left shoulder movement, and a previous misdiagnosis of hereditary multiple exostoses (HMEs) resulting in unnecessary excision of the right scapular lesion. Clinical examination revealed hallux valgus, brachydactyly, and limited neck movement. Radiography and computed tomography confirmed a diagnosis of fibrodysplasia ossificans progressiva (FOP). CONCLUSION: This case report underscores the importance of accurate diagnosis and differentiation between FOP and HME. Hallux valgus, brachydactyly, and restricted neck movement suggested FOP. It is paramount for orthopaedic surgeons to exclude rare disorders before performing any interventions. Biopsies or resections of bone formation areas should be avoided for patients with FOP.

The terminal period findings of late-diagnosed fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant rare disease characterized by foot deformities and concomitant heterotopic ossifications. Theoretically, in the absence of early diagnosis and medication, the patient's outcome will be poor. The patients are usually diagnosed at an early age. Hence, encountering a non-treated and terminal-period patient is rare. Our case was unique because it showed the clinical picture and atypical radiological distribution of a 20-year-old, terminally ill untreated female patient. She had hallux valgus, heterotopic ossifications and multiple osteochondromas that were detected in the right clavicula, the posterior arch of the 9th rib, the bilateral tibia and fibula. Atypically, heterotopic ossifications were not present in the soft tissues of the neck. Hand deformity, cardiac anomaly, or mental retardation was not observed. It was a sporadic case. The presentation with neurological symptoms was also atypical.

Synthetic CT Assessment of Lesions in Children With Rare Musculoskeletal Diseases.

Imaging modalities such as computed tomography (CT) are critical for monitoring musculoskeletal abnormalities in children with rare diseases. However, CT exposes patients to radiation, which limits its utility in the clinical setting, particularly during longitudinal evaluation. Synthetic CT is a novel, noncontrast, and rapid MRI method that can provide CT-like images without any radiation exposure and is easily performed in conjunction with traditional MRI, which detects soft-tissue and bone marrow abnormalities. To date, an evaluation of synthetic CT in pediatric patients with rare musculoskeletal diseases has been lacking. In this case series, the capability of synthetic CT to identify musculoskeletal lesions accurately in 2 rare disease patients is revealed. In Case 1, synthetic CT, in agreement with routine CT, identified an intraosseous lesion in the right femoral neck in a 16-year-old female with fibrous dysplasia, whereas standard-of-care MRIs additionally revealed mild surrounding edema-like bone marrow signal. For Case 2, synthetic CT applied to a 12-year-old female with fibrodysplasia ossificans progressiva revealed heterotopic ossification present along the cervical spine that had caused the fusion of multiple vertebrae. Our evaluation of synthetic CT offers important insights into the feasibility and utility of this methodology in children with rare diseases affecting the musculoskeletal system.

Fasciitis ossificans: imaging features, histology, and differential diagnosis.

AIM: To describe the imaging features of fasciitis ossificans and its histopathological features. MATERIALS AND METHODS: Using a word search of existing pathology reports at the Mayo Clinic, six cases of fasciitis ossificans were identified. The clinical history, histology, and available imaging of the affected area were reviewed. RESULTS: Imaging consisted of radiographs, mammograms, ultrasound images, bone scintigraphs, computed tomography (CT), and magnetic resonance imaging (MRI) images. All cases demonstrated a soft-tissue mass. The characteristic MRI appearance was a T2 hyperintense enhancing mass with surrounding soft-tissue oedema. Peripheral calcifications were seen on radiographs, CT, and/or ultrasound. Histological sections showed distinct zonation, with nodular fasciitis-like zones of myofibroblastic proliferation, which merged with osteoblasts that rim the ill-defined trabeculae of woven bone and became continuous with the mature lamellar bone surrounded by a thin layer of compressed fibrous tissue. CONCLUSION: Imaging features of fasciitis ossificans are that of an enhancing soft-tissue mass located within a fascial plane with prominent surrounding oedema and mature peripheral calcification. Imaging and histology are that of myositis ossificans but occurring within the fascia. It is important that radiologists are aware of the diagnosis of fasciitis ossificans and appreciate its similarity to myositis ossificans. This is particularly important in anatomical locations with fascias but no muscle. Given the radiographic and histological overlap between these entities, nomenclature that encompasses both could be considered in the future.

Most Fractures Treated Nonoperatively in Individuals With Fibrodysplasia Ossificans Progressiva Heal With a Paucity of Flareups, Heterotopic Ossification, and Loss of Mobility.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder with episodic and progressive heterotopic ossification. Tissue trauma is a major risk factor for flareups, heterotopic ossification (HO), and loss of mobility in patients with FOP. The International Clinical Council on FOP generally recommends avoiding surgery in patients with FOP unless the situation is life-threatening, because soft tissue injury can trigger an FOP flareup. Surprisingly little is known about flareups, HO formation, and loss of mobility after fractures of the normotopic (occurring in the normal place, distinct from heterotopic) skeleton when treated nonoperatively in patients with FOP. QUESTIONS/PURPOSES: (1) What proportion of fractures had radiographic evidence of union (defined as radiographic evidence of healing at 6 weeks) or nonunion (defined as the radiographic absence of a bridging callus at 3 years after the fracture)? (2) What proportion of patients had clinical symptoms of an FOP flareup because of the fracture (defined by increased pain or swelling at the fracture site within several days after closed immobilization)? (3) What proportion of patients with fractures had radiographic evidence of HO? (4) What proportion of patients lost movement after a fracture? METHODS: We retrospectively identified 36 patients with FOP from five continents who sustained 48 fractures of the normotopic skeleton from January 2001 to February 2021, who were treated nonoperatively, and who were followed for a minimum of 18 months after the fracture and for as long as 20 years, depending on when they sustained their fracture during the study period. Five patients (seven fractures) were excluded from the analysis to minimize cotreatment bias because these patients were enrolled in palovarotene clinical trials (NCT02190747 and NCT03312634) at the time of their fractures. Thus, we analyzed 31 patients (13 male, 18 female, median age 22 years, range 5 to 57 years) who sustained 41 fractures of the normotopic skeleton that were treated nonoperatively. Patients were analyzed at a median follow-up of 6 years (range 18 months to 20 years), and none was lost to follow-up. Clinical records for each patient were reviewed by the referring physician-author and the following data for each fracture were recorded: biological sex, ACVR1 gene pathogenic variant, age at the time of fracture, fracture mechanism, fracture location, initial treatment modality, prednisone use at the time of the fracture as indicated in the FOP Treatment Guidelines for flare prevention (2 mg/kg once daily for 4 days), patient-reported flareups (episodic inflammatory lesions of muscle and deep soft connective tissue characterized variably by swelling, escalating pain, stiffness, and immobility) after the fracture, follow-up radiographs of the fracture if available, HO formation (yes or no) as a result of the fracture determined at a minimum of 6 weeks after the fracture, and patient-reported loss of motion at least 6 months after and as long as 20 years after the fracture. Postfracture radiographs were available in 76% (31 of 41) of fractures in 25 patients and were independently reviewed by the referring physician-author and senior author for radiographic criteria of fracture healing and HO. RESULTS: Radiographic healing was noted in 97% (30 of 31) of fractures at 6 weeks after the incident fracture. Painless nonunion was noted in one patient who sustained a displaced patellar fracture and HO. In seven percent (three of 41) of fractures, patients reported increased pain or swelling at or near the fracture site within several days after fracture immobilization that likely indicated a site-specific FOP flareup. The same three patients reported a residual loss of motion 1 year after the fracture compared with their prefracture status. HO developed in 10% (three of 31) of the fractures for which follow-up radiographs were available. Patient-reported loss of motion occurred in 10% (four of 41) of fractures. Two of the four patients reported noticeable loss of motion and the other two patients reported that the joint was completely immobile (ankylosis). CONCLUSION: Most fractures treated nonoperatively in individuals with FOP healed with few flareups, little or no HO, and preservation of mobility, suggesting an uncoupling of fracture repair and HO, which are two inflammation-induced processes of endochondral ossification. These findings underscore the importance of considering nonoperative treatment for fractures in individuals with FOP. Physicians who treat fractures in patients with FOP should consult with a member of the International Clinical Council listed in the FOP Treatment Guidelines ( https://www.iccfop.org ). LEVEL OF EVIDENCE: Level IV, therapeutic study.

Painful and restricted hip due to myositis ossificans circumscripta of the pectineus muscle after pelvic fracture: A case report.

RATIONALE: Myositis ossificans circumscripta (MOC) is a rare disorder that causes heterotopic bone formation in soft tissues. It usually occurs after trauma and affects large muscles of the extremities. MOC of the pectineus muscle is extremely rare and has not been reported to be treated surgically. PATIENT CONCERNS: A 52-year-old woman presented with left hip pain and dysfunction 4 months after a traffic accident that caused pelvic and humeral fractures and cerebral hemorrhage. DIAGNOSES: Radiological imaging revealed isolated ossification of the left pectineus muscle. The patient was diagnosed with MOC. INTERVENTIONS: The patient underwent surgical resection of the ossified pectineus muscle followed by local radiation and medical therapy. OUTCOMES: At 12 months postoperatively, she was asymptomatic and had normal hip function. No recurrence was observed on radiography. LESSONS: MOC of the pectineus muscle is a rare condition that can cause severe hip dysfunction. Surgical resection combined with radiation and anti-inflammatory drugs can be an effective treatment option for patients who do not respond to conservative management.

Progressive osseous heteroplasia in a 5-year-old boy with a novel mutation in exon 2 of GNAS: a case presentation and literature review.

BACKGROUND: Progressive osseous heteroplasia (POH) is a rare genetic condition that causes progressive ossification. This usually results from an inactivating mutation of the paternal GNAS gene. Herein, we report a case of POH caused by a novel mutation in exon 2 of the GNAS gene. CASE PRESENTATION: A 5-year-old Chinese boy was referred to our hospital for a growing mass in his right foot. Although laboratory findings were normal, radiographic imaging revealed severe ossification in his right foot and smaller areas of intramuscular ossification in his arms and legs. A de novo mutation (c.175C > T, p.Q59X) in exon 2 of the GNAS gene was identified, prompting a diagnosis of POH. We conducted a systematic literature review to better understand this rare disease. CONCLUSION: We have discovered that a de novo nonsense mutation in exon 2 of GNAS can lead to POH. Our literature review revealed that ankylosis of the extremities is the primary clinical outcome in patients with POH. Unlike other conditions such as fibrodysplasia ossificans progressiva (FOP), patients with POH do not experience respiratory failure. However, much remains to be learned about the relationship between the type of GNAS gene mutation and the resulting POH symptoms. Further research is needed to understand this complex and rare disease. This case adds to our current understanding of POH and will contribute to future studies and treatments.

The Efficacy of CT Temporal Subtraction Images for Fibrodysplasia Ossificans Progressiva.

PURPOSE: To evaluate the usefulness of CT temporal subtraction (TS) images for detecting emerging or growing ectopic bone lesions in fibrodysplasia ossificans progressiva (FOP). MATERIALS AND METHODS: Four patients with FOP were retrospectively included in this study. TS images were produced by subtracting previously registered CT images from the current images. Two residents and two board-certified radiologists independently interpreted a pair of current and previous CT images for each subject with or without TS images. Changes in the visibility of the lesion, the usefulness of TS images for lesions with TS images, and the interpreter's confidence level in their interpretation of each scan were assessed on a semiquantitative 5-point scale (0-4). The Wilcoxon signed-rank test was used to compare the evaluated scores between datasets with and without TS images. RESULTS: The number of growing lesions tended to be larger than that of the emerging lesions in all cases. A higher sensitivity was found in residents and radiologists using TS compared to those not using TS. For all residents and radiologists, the dataset with TS tended to have more false-positive scans than the dataset without TS. All the interpreters recognized TS as useful, and confidence levels when using TS tended to be lower or the same as when not using TS for two residents and one radiologist. CONCLUSIONS: TS improved the sensitivity of all interpreters in detecting emerging or growing ectopic bone lesions in patients with FOP. TS could be applied further, including the areas of systematic bone disease.

Extra-skeletal osteosarcoma: a review.

Extra-skeletal osteosarcoma is a rare malignant soft tissue sarcoma which can cause a diagnostic challenge due to its non-specific presentation and soft tissue mineralisation, thus potentially mimicking conditions such as myositis ossificans. This review will outline the demographics, clinical presentation, key imaging features, differential diagnosis, management and outcomes of extra-skeletal osteosarcoma and serve as a reference to radiologists and other clinicians involved in the care of patients with soft tissue tumours and tumour-like lesions.

The natural history of fibrodysplasia ossificans progressiva: A prospective, global 36-month study.

PURPOSE: We report the first prospective, international, natural history study of the ultra-rare genetic disorder fibrodysplasia ossificans progressiva (FOP). FOP is characterized by painful, recurrent flare-ups, and disabling, cumulative heterotopic ossification (HO) in soft tissues. METHODS: Individuals aged ≤65 years with classical FOP (ACVR1R206H variant) were assessed at baseline and over 36 months. RESULTS: In total, 114 individuals participated; 33 completed the study (mean follow up: 26.8 months). Median age was 15.0 (range: 4-56) years; 54.4% were male. During the study, 82 (71.9%) individuals reported 229 flare-ups (upper back: 17.9%, hip: 14.8%, shoulder: 10.9%). After 84 days, 14 of 52 (26.9%) imaged flare-ups had new HO at the flare-up site (mean new HO volume: 28.8 × 103 mm3). Mean baseline low-dose whole-body computed tomography (excluding head) HO volume was 314.4 × 103 mm3; lowest at 2 to <8 years (68.8 × 103 mm3) and increasing by age (25-65 years: 575.2 × 103 mm3). The mean annualized volume of new HO was 23.6 × 103 mm3/year; highest at 8 to <15 and 15 to <25 years (21.9 × 103 and 41.5 × 103 mm3/year, respectively) and lowest at 25 to 65 years (4.6 × 103 mm3/year). CONCLUSION: Results from individuals receiving standard care for up to 3 years in this natural history study show the debilitating effect and progressive nature of FOP cross-sectionally and longitudinally, with greatest progression during childhood and early adulthood.

Scalp Nodules and Deformed Great Toes: Omens of Fibrodysplasia Ossificans Progressiva.

ABSTRACT: We report a case of fibrous scalp nodules and bilateral hallux valgus in an infant who one decade later was diagnosed with a rare life-threatening genetic disease.

Intense 68Ga-FAPI Uptake in a Patient With Myositis Ossificans: Mimicking Bone Malignancy.

ABSTRACT: A 72-year-old man presented with right hip pain, difficulty in walking, and a mass in his right hip for 3 months. CT suggested osteonecrosis of the right femoral head and a mass in the right hip with calcification. A malignancy was suspected, and the patient was subsequently enrolled in the clinical trial of 68Ga-FAPI. 68Ga-FAPI PET/CT showed a mass in his right hip with intense FAPI activity. It was also highly suggestive of malignancy. The pathological examination after right-hip surgery confirmed the diagnosis of myositis ossificans.