Sclerotic bone lesions caused by non-infectious and non-neoplastic.pptx

sclerotic bone lesions caused by a variety of conditions that are not involved in metastatic conditions.

1. Sclerotic bone lesions caused by non-infectious and non-neoplastic diseases: a review of the imaging and clinicopathologic findings Skeletal Radiology (2021) 50:847–869

2. Introduction Bone sclerosis is defined as the abnormal increase in osseous density on radiographs or CT and it may be focal, multifocal, or diffuse A good set of differential diagnoses for sclerotic bone lesions is essential for rendering a timely and accurate diagnosis This article aims to review the non-infectious and non-neoplastic causes of bone sclerosis by highlighting their radiological profile, etiopathogenesis, and relevant important clinical findings The diseases have been broadly divided into congenital and developmental, depositional, and metabolic disorders

3. Imaging strategy Radiographs are the main screening tool for bone disorders lesions are picked up incidentally on DEXA scan, CT, MRI many non-malignant processes associated with an increased turnover like degenerative lesions, infarcts, trauma, and infection can mimic metastatic disease on Tc99m-MDP planar scintigraphy 18F-NaF PET/CT -not just in metastatic disease, but also in assessing osteonecrosis and bone viability, Paget’s disease, and renal osteodystrophy. Patients with unexplained extremity pain can also benefit from PET/CT Planar bone scintigraphy - determine the presence of additional lesions and their distribution

4. Congenital and development disorders

5. Camurati -Engelmann disease also called progressive diaphyseal dysplasia, is an autosomal dominant disorder multifocal or diffuse osseous sclerosis, particularly of the long bones of the limbs mutation in transforming growth factor-beta 1 (TGFB1) resulting in decreased osteoclastic resorption and increased osteoblastic formation TGFB1 also inhibits myogenesis and adipogenesis, leading to a reduction in muscle and fat usually presents in adolescents with bone pain Progressive symmetrical diaphyseal hyperostosis of the lower limbs is seen in 94–98% mc location pelvis and skull base multifocal or diffuse (bilaterally symmetrical) endosteal bony sclerosis and periosteal involvement with uneven cortical thickening and increased diameter Bone scintigraphy shows increased uptake with Tc99m-MDP

6. Osteopetrosis group of rare, heritable disorders ranging from asymptomatic to fatal in infancy failure of osteoclast differentiation or function classified into three forms: Infantile malignant autosomal recessive osteopetrosis (ARO), intermediate autosomal recessive osteopetrosis (IRO), and Autosomal dominant osteopetrosis (ADO) - negative mutations of the ClCN7 gene, commonly known as Albers- Schönberg disease ADO type I (generalized increase in bone mass) and ADO type II (sclerosis of the axial skeleton) ADO presents with fractures, scoliosis, osteoarthritis of the hip joint, and osteomyelitis—particularly affecting the mandible

7. The typical radiological findings include diffuse sclerosis (“marbled appearance”) of the axial and appendicular bones, modeling defects at the metaphyses of long bones giving rise to an undertubulation and funnel-like appearance - “Erlenmeyer flask” deformity “sandwich vertebra” sign Bone-in-bone appearance of the phalanges and vertebrae bones show marked hypointensity on T1-weighted (T1W) and T2-weighted (T2W) images patients present at a younger age, the bony margins are sharp without coarsened trabeculations, and vascular calcifications and brown tumors are absent

8. Pyknodystosis also known as osteopetrosis acro- osteolytica or Toulouse-Lautrec syndrome characterized by osteosclerosis and short stature rare autosomal recessive lysosomal storage disorder caused due to a mutation in the lysosomal enzyme cathepsin K, leading to defective osteoclast-mediated bone turnover a classic “drumstick” appearance of terminal phalanges of hands and feet due to the resorption of distal tufts (acro-osteolysis) dolichocephaly with patent fontanelles, frontal or occipital bossing of the head, hypoplastic maxilla, and an excessive obtuse angle of the mandible

9. severe teeth crowding, grooved palate, and delayed exfoliation of deciduous teeth dwarfism and multiple fractures Radiographically closely resembles cleidocranial dysplasia Wide-angled mandible, acro-osteolysis, and sclerosis of the terminal phalanges absent in cleidocranial dysplasia. DEXA scans show marked increased bone density, mainly in the trabecular bone. MRI reveals normal cortical thickness with an increase in trabecular bone within the medullary cavity high incidence of pituitary hypoplasia and cerebral demyelination

10. Osteopathia Striata or Voorhoeve disease, is a rare disorder of the secondary spongiosa failure of remodeling of mature bone diagnosed incidentally in childhood or adulthood cranial nerve palsies and mild mental retardation in addition to characteristic bone changes dense, linear striations are seen, usually in the diaphysis and metaphysis of long and tubular bones, in the areas of rapid growth. The iliac bones, if involved, demonstrate a “fan-like” appearance due to the striations

11. Ribbing disease Multiple diaphyseal sclerosis (MDS) resembles CED rare benign bone dysplasia characterized by endosteal and periosteal bone growth in the diaphyses of long bones tibia and femur being most commonly affected disease is seen to progress slowly and then stabilize fusiform widening of the diaphyseal portion of the long bones, caused due to thickening of the cortex with narrowing of the medullary cavity A three-phase Tc99m-MDP bone scan is helpful in the diagnosis Bone marrow edema may also be seen, probably from superimposed stress/disease activity

12. Key imaging features: Unilateral or bilateral long bone diaphyseal sclerosis with periosteal and endosteal new bone formation causing fusiform widening of the diaphysis. Associated bone marrow edema and periostitis in females after puberty who may be asymptomatic or present with deep boring pain

13. Osteofibrous dysplasia rare, congenital fibroosseous disease, also referred to as ossifying fibroma of the long bones intracortical lesion of unknown pathogenesis and almost exclusively affects the tibia or fibula. Histologically, OD resembles adamantinomas and shows woven bone trabeculae lined with osteoblasts, cellular proliferation of fibroblast-like cells, and a “zonal” architectural pattern intermediate signal intensity on T1 and intermediate to high signal intensity on T2 Well-marginated cortical-subcortical lytic-sclerotic lesion with painless tibial bowing in prepubescent children, sometimes associated with pathological fractures.

14. Fibrous dysplasia abnormal proliferation of fibrous tissue interspersed with normal or immature bone mutation at chromosome 20 leading to alteration of the alpha subunit of the stimulatory G protein, preventing the maturation of progenitor cells presents in the first two decades of life with painless bony enlargement lesions are intramedullary and commonly affect the femur, tibia, skull and facial bones, and the pelvis polyostotic form has a more serious prognosis and can be associated withMcCune -Albright syndrome Monostotic affects only femur Craniofacial FD presents in childhood, before 5 years of age, and may rarely be associated with malignant degeneration

15. Geographic ground-glass lesion with mild cortical thickening and long bone bowing deformity, very rarely involving the epiphysis

16. Melorheostosis or Leri’s disease is a sclerosing bone disorder characterized by a defect in endochondral and intramembranous ossification often shows a sclerotome distribution with the long bones of the lower extremities being more commonly affected than the upper extremities sclerosis on only one side of the cortical bone, with linear and segmental distribution, which projects over the medullary space giving the classical “dripping candle wax” appearance Osteoma-like, myositis ossificans like, and osteopathia striata–like patterns involvement of soft tissues or intra-articular compartment may also be observed

17. Osteopoikilosis also known as spotted bone disease autosomal dominant sclerosing dysplasia characterized by multiple, periarticular deposits of compact lamellar bone known as enostosis or “bone islands” in the spongiosa An inactivating mutation in the LEMD3 gene leads to defective endochondral ossification and the abnormal bone deposits asymptomatic and are diagnosed incidentally A quarter of the cases present as part of Bushke Olendorf syndrome, in which osteopoikilosis is associated with dermatofibrosis lenticularis disseminate

18. Multiple, small, discrete sclerotic lesions are seen in the periarticular regions on radiographs, typically at the ends of short bones The small bones of the hands and feet are most commonly involved and some lesions may exhibit trabeculated margins lesions may be confused with osteoblastic metastasis but demonstrate high density similar to cortical bone

19. Key imaging features: Bilateral periarticular well-defined sclerotic lesions with high density similar to bony cortex, mostly diagnosed incidentally

20. Depositional disorders

21. Gaucher disease rare autosomal recessive lysosomal storage disorder with various visceral (hepatosplenomegaly), hematological , and osseous manifestations Skeletal lesions are more common in type I disease remodelling failure, bone infarcts, avascular necrosis, lytic lesions, osteosclerosis, and pathological fractures due to osteopenia or osteoporosis mainly seen in the long bones and vertebrae Local swellings in the bones called gaucheromas may also be present Marrow infiltration exhibits low signal intensity on T1W, non-fat-suppressed T2W, and T2W sequences as compared to the subcutaneous fat

22. Osteonecrosis is seen as a geographic area of increased signal with demarcated margins on T2W images Quantitative chemical shift imaging on MR is the most sensitive quantitative method for evaluating the bone marrow and can be used to assess the disease burden CT imaging can show patchy sclerosis of trabeculations and bone infarcts Tc99-sulfur colloid is taken up by normal bone marrow and, therefore, the uptake is reduced in areas of pathological infiltration Tc99-sestamibi accumulates in the areas of Gaucher cell infiltration and is therefore a direct measure of pathology Tc99m-MDP can also help to differentiate between osteomyelitis and bone crisis

23. Mastocytosis rare disorder of mast cell proliferation and subsequent infiltration into skin, bone marrow, and organs such as the spleen, liver, lymph nodes, and gastrointestinal tract spontaneous mutations in the KIT gene that codes for a receptor in the stem cell factor (SCF), resulting in SCF-independent proliferation and activation of mast cells The release of vasoactive substances such as histamine leads to systemic mastocytosis that presents with symptoms, such as urticaria pigmentosa, flushing, syncope with hypotension, headache, nausea, vomiting, diarrhea , and bronchospasms These lesions are usually seen in the axial skeleton, proximal ends of long bones, and the pelvis. The axial skeleton usually shows diffuse involvement, whereas focal lesions can occur both in axial and appendicular skeleton

24. Findings may resemble diffuse metastatic disease leading to incorrect diagnosis and management Bone scintigraphy findings correlate well with the severity and progression of systemic mastocytosis T1W MRI is very sensitive for marrow involvement, seen as a loss of the normal high signal of medullary fat on T1-weighted imaging which can be homogenous or non homogenous sclerotic lesions appear hypointense on both T1- and T2-weighted images, similar to other sclerotic diseases Key imaging features: Bilateral mixed osteolytic-sclerotic lesions in the appendicular and axial skeleton in a patient with non-specific symptoms of mast cell degranulation, hepatosplenomegaly, and abdominal lymphadenopathy

25. Hypervitaminosis D Vitamin D toxicity may be endogenous, related to increased concentration of 1,25(OH)2 vitamin D or, more commonly, exogenous, characterized by serum 25-hydroxyvitamin D levels higher than 150 ng/ml Skeletal manifestations are largely due to the subsequent hypercalcemia usually manifests as metastatic calcification, particularly in the periarticular soft tissues, joint capsule, and bursae. Children may present with metaphyseal band-like thickening and sclerosis due to calcifications of the cartilage and thickening of cortical bone

26. Renal Osteodystrophy musculoskeletal abnormalities seen in patients with chronic kidney disease and includes the findings of osteomalacia and secondary hyperparathyroidism, i.e., osteosclerosis, soft tissue, and vascular calcifications Additional complications of dialysis destructive spondyloarthropathy, infections, and osteonecrosis intracortical lucencies , blurring of cortical margins, scalloping of bony margins, and acro osteolysis can be seen The middle phalanges of second and third fingers are typically affected with subperiosteal bone resorption, usually along the radial aspects

27. Lytic, demarcated, central, or eccentric lesions usually in the pelvis, femur, ribs, and facial bones represent osteoclastomas (brown tumors), which are typical for primary HPT but are more commonly seen in ROD Osteosclerosis, occurring due to osteoblastic stimulation, is frequently seen in patients of ROD and may be the sole manifestation. It mainly affects the axial skeleton, commonly the spine, ribs, clavicle, and pelvis “Rugger Jersey” appearance of vertebra Key imaging features: Ill-defined bony margins, patchy bony sclerosis, findings of osteomalacia , secondary hyper parathyroidism with multi-focal bone resorptions, brown tumors , Rugger-jersey spine, soft tissue, and vascular calcifications.

28. Fluorosis ingestion of high levels of fluoride, most significantly through water About half of the daily-ingested fluoride gets deposited into calcified tissue and gets incorporated into hydroxyapatite crystals leading to a reduction in the mechanical competence and quality of bones. Ingestion of fluoride in excess of 1.5 mg/L over a long period of time is associated with dental and skeletal fluorosis Dental fluorosis or mottling of teeth occurs Ossification of the interosseous membrane and iliolumbar and sacrotuberous ligaments The bony changes are most marked in the axial skeleton, mainly in the spine, pelvis, and ribs

29. Other findings include osteopenia, trabecular blurring, intermittent growth lines, diaphyseal widening, and ossification of soft tissues—primarily the posterior longitudinal ligament, and enthesophytes at tendon, ligament, and muscle attachments Periosteal proliferation is common, especially around the ribs Osteosclerosis is common when small doses of fluoride are taken over long periods with normal calcium intake, whereas osteoporotic form is observed in children with a higher body load of fluoride Key imaging features: Bilateral patchy bony sclerosis, enthesopathy, ligament, and periosteal bony proliferation and ossification of spinal ligaments in endemic areas

30. Paget’s disease or osteitis deformans is the second most common bone disease in adult population characterized by abnormal or excessive remodeling of bone progresses through 3 main phases: the lytic phase, the mixed phase, and then the inactive blastic phase in which most of the sclerosis and bone enlargement transpire often asymptomatic and the disease is diagnosed incidentally on radiograph Lesions are typically asymmetric, polyostotic, and commonly seen in the axial skeleton, with the spine and pelvis being most commonly involved In osteolytic stage, “blade of grass” sign can be seen with a sharp lytic border of the lesion, e.g., in tibia; or a geographic lytic lesion of the skull vault. Osteosclerosis in the late, inactive blastic phase is seen as a trabecular and cortical thickening of bone, e.g., thickening of the ilio-pectineal line in the pelvis

31. Transverse fatigue fractures, called “banana fractures,” and bowing deformities may be seen. Thickening of the inner calvarial table, leading to an enlargement of the diploic spaces (“Tam-o’-shanter” sign) focal areas of “cotton-wool” osteosclerosis may be seen when the skull is involved Key imaging features: Blade of grass sign, geographic lytic lesion, cotton-wool osteosclerosis, trabecular and cortical thickening with bone expansion, and banana fractures in middle-aged and old patients

32. Erdheim Chester disease rare, multisystemic, non Langerhans cell histiocytosis characterized by xanthomatous or xanthogranulomatous infiltration of tissues by foamy histiocytes etiology is uncertain but considered to be non infectious and non-genetic most common initial manifestation is symptomatic or asymptomatic osteosclerosis of long bones with patients presenting with bone pain, usually around the knees and ankles 50% of the patients present with extraskeletal features as neurologic, cardiovascular, ophthalmologic manifestations, and skin, kidney, and retroperitoneal involvements Patients may also have diabetes insipidus or panhypopituitarism when the CNS is involved Diagnosis is based on a widely accepted radiological and histological criteria

33. bilateral symmetric diametaphyseal osteosclerotic lesions, cortical thickening with a reduced corticomedullary cavity Tc99m bone scintigraphy illustrates symmetric and abnormally strong uptake at the distal ends of long bones 18F-Fluorodeoxyglucose positron emission tomography CT (FDG PET/CT) is the modality of choice for follow-up imaging MR imaging is primarily useful in the evaluation of the neurologic manifestations with dural and ocular lesions Soft tissue lesions are heterogeneously hyperintense on T2W imaging and homogenously hypointense on T1W imaging

34. Key imaging features: Bilateral symmetric diametaphyseal osteosclerotic lesions, cortical thickening with a reduced corticomedullary cavity, patchy mixed T2 signal in periarticular locations of both knees, soft tissue masses around dura, kidney, and orbits

35. Sickle cell disease autosomal recessive red cell disorder characterized by abnormal sickling of red blood cells due to the presence of red blood cells with hemoglobin S Musculoskeletal complications include acute manifestations such as bony infarcts with vaso -occlusive crises and osteomyelitis, and chronic issues like osteoporosis and osteonecrosis Hand-foot syndrome, or sickle cell dactylitis, is seen in about half the children with sickle cell disease layered deposit along the inner surface of the cortex appearing as a “bone-in-bone” Vertebral findings called “Lincoln log” or “H-shaped” deformities seen due to endplate microvascular occlusion and over growth of the surrounding, non-damaged areas

36. SCA is also the most common cause of hip AVN in children. The “double-line sign” consisting of a hyperintense inner inflammatory response inside a low signal intensity reactive bone interface is well seen on T2W imaging Eventually, these lesions develop sclerosis, subchondral collapse, significant osteoarthritic changes, and flattening of the articular areas Key imaging features: Bilateral, nearly symmetric patchy osteosclerosis, epiphyseal and medullary infarcts, H-shaped vertebrae, and cardiomegaly in young patients

37. Myelofibrosis a chronic myeloproliferative disorder characterized by progressive bone marrow fibrosis, inefficient hematopoiesis, and reduced survival more prevalent in older ages with 65 years being the median age at diagnosis Myelofibrosis can be classified as primary (earlier termed “idiopathic”) or secondary, developing from essential thrombocythemia or polycythemia vera. Dysregulated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling Osteosclerosis is the imaging hallmark of myelofibrosis. It is most commonly seen in the axial skeleton and the metaphyseal ends of the femur, humerus, and tibia

38. In the spine, “sandwich vertebra” appearance may be seen due to increased radiodensity at the superior and inferior margins osteopenia on skeletal surveys and eosinophilia in mastocytosis can help differentiate the two Bone sclerosis in myelofibrosis also lacks the irregular appearance of the lesions seen in osteopetrosis, Paget’s disease, and sickle cell disease, in which the increased density is due to bone infarcts Other features such as hepatomegaly, splenomegaly, and lymphadenopathy can also be noted Key imaging features: Bilateral nearly symmetric osteosclerosis without substantial architectural distortion, hepatosplenomegaly, and lymphadenopathy in middle-aged and old patients

39. Medullary bone infarcts osteonecrosis in the medullary cavity of the metaphysis or diaphysis of long bones. Predisposing causes include alcoholism, Gaucher disease, sickle cell anemia, decompressions sickness, collagen vascular diseases, and steroid use About half of the cases show multifocal disease, which is usually accompanied by multiple foci of epiphyseal avascular necrosis Findings could be non-specific and appearances may range from ill-defined radiolucencies to classic appearance of a well-defined “shell-like” sclerosis— mottled bone rarefaction with mild reactive sclerosis lesions typically show irregular well-defined sclerotic margins and calcifications surrounding the necrotic segment

40. characteristic appearances as described above include the “double line sign” seen on T2W images and a geographic “ maplike ” rim of low signal intensity Occasionally, a central region of low signal intensity may be observed due to marrow fibrosis or sclerosis Key imaging features: Shell-like peripheral sclerosis, double-line sign, central fatty change of the lesion.

41. Conclusion a wide spectrum of non-infectious and nontumorous pathologies can cause osteosclerosis. Knowledge of key clinical and radiological features of such lesions can aid in rendering an accurate and confident diagnosis, which can lead to timely and appropriate management