Fibrous Dysplasia - Yohan Parulian Sinaga.pptx

Fibrous Displasia

1. Fibrous Dysplasia: Recent Developments and Modern Management Alternatives Yohan Parulian Sinaga

2. Identitas Nama : Amri Fahrizal Usia : 13 tahun Jenis Kelamin : Laki-laki Pekerjaan : Buruh (Ayah) Pendidikan : SMP No. RM : 02245340

3. Anamnesis April 2020 April 2024 Keluhan Utama : Nyeri pada lengan bawah kanan Pasien mengalami patah tulang di lengan atas kanan terjatuh saat bermain sepakbola , belum terindentifikasi adanya kelainan patologis pada pemeriksaan rontgen . Kemudian pasien dipasang gips di RS Bantul oleh spesialis Orthopaedi . Setelah beberapa bulan kemudian keluhan membaik dan dinyatakan sembuh Pasien mengalami bengkak pada lengan kanan setelah menangkis pukulan dari teman pasien . Pasien tidak dibawa ke RS untuk penanganan keluhan tersebut . Bengkak kemudian hilang .

4. Anamnesis Juni 2024 Keluhan Utama : Nyeri pada lengan bawah kanan 10 jam SMRS pasien jatuh bertumpu pada lengan kanan saat bermain bola. Pasien dibawa ke RSUD Bantul ditemukan adanya patah tulang dan kecurigaan adanya tumor tulang . Pasien dirujuk ke RSS untuk tatalaksana lanjutan . Riwayat demam (-), penurunan berat badan (-), gusi berdarah (-), nyeri pada anggota gerak sebelumnya (-)

5. ANAMNESIS Riwayat Penyakit Dahulu : Alergi (-), asma (-), tumor (-), penyakit paru (-), riwayat patah tulang sebelumnya (+) Riwayat Penyakit Keluarga : Keluhan serupa (-), HT (-), DM (-), penyakit jantung (-), alergi (-), asma (-)

6. PEMERIKSAAN FISIK Keadaan Umum : Baik , compos mentis Tanda Vital : TD : 135/90 mmHg Nadi : 82 x/ menit VAS : 4-5 Rr : 18 x/ mnt Suhu : 36.8 o C SpO2 : 99% Status Generalis : Kepala : konjungtiva anemis (-/-) , sklera tidak ikterik Leher : JVP tidak meningkat Thorax I : Simetris , ketinggalan gerak (-) P : Vokal Fremitus kanan = kiri P : Sonor kanan = kiri A : Vesikuler +/+, ronkhi -/-, wheezing -/- Abdomen I : Flat A : Peristaltik (+) Normal P : Timpani ( + ) P : Supel , nyeri tekan (-)

7. Pemeriksaan Fisik Status Lokalis antebrachii dextra : Look: Swelling (+), deformity (-), wound (-) Feel : Tenderness (+), mass (-), NVD (-) Move : Limited due to pain Status Lokalis antebrachii dextra : Look: Swelling (+), deformity (-), wound (-) Feel : Tenderness (+), mass (-), NVD (-) Move : Limited due to pain

8. Durante operasi ( Curettage, Open biopsy, Frozen Section, ORIF ) Incision design Sample obtained

9. HASIL LABORATORIUM Lab Normal 13/06/24 14/06/2024 19/06/2024 Eritrosit 4.00 – 5.40 4.97 - 4.26 Hb 12.0 – 15.0 13.7 - 11.8 Hematokrit 35.0 – 49.0 40.5 - 34.7 Leukosit 4.50 – 11.50 7.0 - 13.4 Neutrofil 50 – 70 55.6 - 84.6 Limfosit 18.0 – 42.0 2.28 - 9.7 Monosit 2.0 – 11.0 0.69 - 5.1 Eosinofil 1.0 – 3.0 0.12 - 0.0 Basofil 0.0 – 2.0 0.01 - 0.1 Trombosit 150 – 450 208 - 210 Albumin 3.40 – 5.00 4.29 - 3.78 ALP 116-468 - 405 - Lab Normal 13/06/24 SGOT 10 – 50 25 SGPT 10 – 50 10 BUN 6 – 20 13 Kreatinin 0.67 – 0.17 0.81 GDS 74 – 106 108 APTT 25.1 – 36.5 33.9 PPT 9.4 – 12.5 10.4 INR 0.90 – 1.10 1.22 Na 136 – 145 139 K 3.5 – 5.1 3.6 Cl 98 – 107 104 HBsAg NR NR

10. X-Ray Thorax PA (13/06/2024)

11. X-Ray Antebrachii Dextra (AP/LAT) (13/06/2024)

12. Sidik Tulang (14/06/2024)

13. X-Ray Antebrachii dextra (AP/LAT) (19/06/2024) X-Ray Antebrachii dextra (AP/LAT) (19/06/2024)

14. Biopsi Proksimal Radius Kanan ( Potongan Beku ) (19/06/2024)

15. Biopsi Middle Third Radius Kanan (19/06/2024)

16. Imunohistokimia per jenis antibody (10/07/2024)

17. Close pathologic fracture of middle third of the right radius ulna due to susp Fibrous dysplasia post Tumor Excision, Open Biopsy amd ORIF 8 weeks ago at Sardjito General Hospital. DIAGNOSIS

18. FIBROUS DYSPLASIA

19. INTRODUCTION CLASSIFICATION ETIOLOGY CLINICAL PRESENTATION TREATMENT & PROGNOSIS CONCLUSION

20. Introduction DEFINITION A benign lesion, presumably developmental in nature, characterized by the presence of fibrous connective tissue with a characteristic whorled pattern and containing trabeculae of immature non lamellar bone. Waldron 1985. Reeds definition : fibrous dysplasia is an arrest of bone maturation in woven bone with ossification resulting from metaplasia of a non specific fibro-osseous type. Can diagnosed incidentally or in association with certain symptoms. The true incidence and prevalence are uncertain, but it is estimated to comprise 5-7% of all benign bone lesions. No gender predilection The most common sites of involvement are the femur, tibia, craniofacial bones, and ribs.

21. Etiology

22. Pathogenesis GNAS encodes Gs α, a cAMP pathway-associated G-protein subunit. Loss-of-function mutations of the GNAS gene result in a constitutionally inactive Gs α and has been found in several disorders of the endocrine system (e.g., pseudohypoparathyroidism). Gain-of-function mutations on the other hand, lead to the constitutive activity and abnormally increased cAMP signaling and leads to the phenotype of fibrous dysplasia.8 The primary role of Gs α is to couple G-protein receptors to adenylyl cyclase, which in turn promotes receptor stimulated production of intracellular cAMP and a subsequent downstream of effects. Mutations in the GNAS (guanine nucleotide-binding protein/α-subunit) gene is responsible for the development of fibrous dysplasia. GNAS encodes Gs α, a cAMP pathway-associated G-protein subunit. The primary role of Gs α is to couple G-protein receptors to adenylyl cyclase, which in turn promotes receptor stimulated production of intracellular cAMP and a subsequent downstream of effects. The normal Gs α, in its inactive state, forms a heterotrimer with Gsβ and Gsδ subunits, with GDP bound to its binding site. Exchange of GDP for GTP activates the Gs α subunit, which dissociates from the trimer and activates adenylyl cyclase to form cAMP from ATP. Loss-of-function mutations of the GNAS gene result in a constitutionally inactive Gs α and has been found in several disorders of the endocrine system (e.g., pseudohypoparathyroidism).7 Gain-of-function mutations on the other hand, lead to the constitutive activity and abnormally increased cAMP signaling and leads to the phenotype of fibrous dysplasia.8 Two missense mutati ns have been implicated in the majority of patients: Arg201 and Gln227,9 which are

23. Pathogenesis

24. CLASSIFICATION

25. EVERSOLE 2008 CLASSIFICATION 1. Bone dysplasias a. Fibrous dysplasia i . Monostotic ii. Polyostotic iii. Polyostotic with endocrinopathy (McCune-Albright) iv. Osteofibrous dysplasia b. Osteitis deformans c. Pagetoid heritable bone dysplasias of childhood d. Segmental odontomaxillary dysplasia 2. Cemento -osseous dysplasias a. Focal cemento -osseous dysplasia b. Florid cemento -osseous dysplasia 3. Inflammatory/reactive processes a. Focal sclerosing osteomyelitis b. Diffuse sclerosing osteomyelitis c. Proliferative periostitis 4 . Metabolic Disease: hyperparathyroidism 5 . Neoplastic lesions (Ossifying fibromas) a. Ossifying fibroma b. Hyperparathyroidism jaw lesion syndrome c. Juvenile ossifying fibroma i . Trabecular type ii. Psammomatoid type d. Gigantiform cementomas

26. CLINICAL PRESENTATION

27. CLINICAL PRESENTATION Equal in males & females. Commonly-3-15yrs Polyostotic-asymptomatic before 10 years . Monostotic-asymptomatic -20-30 years.

28. MONOSTOTIC FORM 70%-80% of fibrous dysplasia. Occurs in rib, femur , tibia, craniofacial bones and humerus Pain or pathologic fracture, Bone deformity less severe, Painless swelling

29. POLYOSTOTIC FORM

30. Craniofacial Fibrous Dysplasia

31. Clinical presentation M onostotic lesions - Asymptomatic and diagnosed incidentally on radiographs taken for unrelated symptoms. - Diagnosed in the second or third decades of life. - The femur is the most common site of involvement. McCune-Albright syndrome (MAS) - Diagnosed the earliest, typically during the first decade of life. - The classic presenting symptoms are nonorthopaedic , most commonly signs of precocious puberty (e.g., vaginal bleeding). Polyostotic lesion U sually present at an earlier age with pain, limp, deformity, or fractures. Complications, including fractures and deformity Hip function is reasonably preserved in most cases, and despite mild leg length discrepancy (LLD), function tends to be minimally impaired

32. INVESTIGATION

33. X-ray Fibrous dysplasia presents as an intramedullary, well-defined, and mildly expansile lytic lesion Often involves the diaphysis and metaphysis, and the epiphysis seems to be spared Margins are well-defined, sclerotic borders may be present, and mild endosteal scalloping can occur The characteristic ‘ground-glass’ appearance is the result of a homogenous fibro-osseous matrix replacing the normal trabecular woven bone

34. Other Investigations MRI CT Scan Bone survey Bone scan Laboratory studies Biopsy

35. CT Scans CT scans demonstrate the extent of the disease, the degree of cortical thinning, and associated deformities better than plain radiographs. CT is most valuable for preoperative planning of FD-related deformities, especially in the proximal femur.

36. MRI MRI appearance of FD is very typical. There is a hypointense or intermediate signal on T1- weighted images, a hyperintense or intermediate signal on T2-weighted images, and heterogeneous enhancement on contrast-enhanced images. MRI is also important in the differential diagnosis and to evaluate extra-osseous involvement in cases where malignant degeneration is suspected.

37. Bone Survey A skeletal survey is highly sensitive in determining the extent of skeletal involvement. In this study, routinely perform a low-dose lower extremity imaging for all newly identified fibrous dysplasia. And not routinely scan upper extremity lesions, but that is a case-by-case decision.

38. Radionucleotide bone scintigraphy Primary reports of PET/CT in FD were promising, but further studies showed a high false-positive rate, and multiple cases of FD mimicking malignancy/metastasis

39. Laboratory

40. Biopsy A biopsy is essential in the diagnosis of tumor. Open biopsy was once considered the gold standard due to its accuracy rate of 98%. Core biopsy is preferred because there is less risk of local contamination . This is important in patients who may have limb-sparing surgery. CT-guided biopsy is as accurate as open biopsy in diagnosing musculoskeletal tumors

41. Histopathology Proliferating fibroblasts in a compact stroma of interlacing collagen fibres. Irregular bony trabeculae scattered throughout lesion. Chinese character shaped. Trabeculae usually coarse woven bone Lesions rich in spindle shaped fibroblasts with a swirled appearance within the marrow space Lesional bone fuses directly with normal bone at the periphery

42. Histopathology Woven bone Lamellar bone Monotonous pattern-calcification-FD differs from haphazard mixture of woven, lamellar bone & spheroid particles-ossifying fibroma & cemento -osseous dysplasia.

43. Differential Diagnosis

44. PROGNOSIS Prognosis-good Although-bad outcomes-more frequently among young patients or with polyostotic forms.

45. Malignant transformation 0.4% - 4% Osteosarcoma Fibrosarcoma Chondrosarcoma 28% - seen in radiated- Radiotherapy contraindicated ….

46. TREATMENT

47. TREATMENT

48. Observation Most upper extremities lesions , and monostotic lower extremity lesions with little minimal fracture risk , are amenable to nonoperative management. The frequency in which patients should be re-evaluated and lesions reimaged depends on age, the extent of the lesion, and the presence of angular deformities or any symptoms.

49. Pharmacologic Management In polyostotic disease, pain is a common symptom, which ranges from intermittent and mild to chronic and severe. Management with acetaminophen or NSAIDs are the first line of treatment and can be very successful. Currently, the food and drug administration (FDA) considers FD an off-label indication for bisphosphonate treatment. Pain management and high bone turnover (as measured by serum biomarkers) in polyostotic fibrous dysplasia are the main indications for bisphosphonate treatment. More recently, the receptor activator of nuclear factorkB ligand inhibitor denosumab has been evaluated in polyostotic FD patients with pain refractory to bisphosphonate treatment. The results have been promising, with half the patients reporting complete elimination of pain.37

50. Surgery The main indications for surgery in fibrous dysplasia include recalcitrant bone pain, impending or pathologic fracture, progressive skeletal deformity, and concern for malignancy Some of the key factors to be considered:

51. Some of the key factors to be considered:

52. Surgery ( Conventional plates and screws ) The challenge is that nonlocking plates act by converting insertional torque into compression forces. In the deficient fibro-osseous tissue of FD, this will only lead to screw pull-out and subsequent fixation failure Plate and screw constructs in fibrous dysplasia: 1) Titanium alloy is preferred over stainless steel due to a more similar modulus of elasticity to normal bone. 2) Locking plates and screws are recommended over compression screws to act as an internal fixator. 3) The longest plate that spans the whole bone should be selected, which is particularly important in polyostotic disease. There are many reports of a small plate acting as a stress riser, leading to a fracture at the plate-bone junction. 4) In general, the maximum number of screws should be used. The mechanism of failure in locking plates is a simultaneous pull-out of the whole plate screws construct. A higher number of screws adds to the total pull-out strength

53. Surgery ( Intramedullary devices ) Intramedullary devices are the gold-standard for fixation in fibrous dysplasia because of their load-sharing Fixation alone has been successful in reducing pain and the risk of fracture, but could be combined with curettage and grafting if deemed necessary. Isolated curettage and bone grafting has produced poor results, with frequent resorption of the graft, fractures, and the need for re-operation.

54. Surgery (Correction of the Proximal Femoral Deformity) The extent of disease, age of the patient, and high mechanical loads acting on that region, are the main drivers towards the so-called Shepherd’s crook deformity.

55. Shepherd’s crook deformity

56. Surgery The authors recommend that the proximal femur osteotomy be performed after the starting point for the intramedullary implant is secured (lateral entry nails are preferred). Then, the osteotomy should be provisionally fixed with a 1/3 tubular locking unicortical plate to minimize the need for tight bone clamps Ideally, the correction is achieved with a single proximal level osteotomy via wedge resection. Adding another proximal level osteotomy makes it very challenging to secure the reduction. These distal level osteotomies can be safely done percutaneously without a wedge resection.

57. CONCLUSION Fibrous dysplasia is a lesion of bone commonly affecting the younger age group. It shows similarities with other fibro osseous lesions clinically, radiological & histopathologically . Hence through knowledge about these lesions is necessary for proper diagnosis & treatment plan.

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