"X marks the spot": The skeletal manifestations of Langerhans cell histiocytosis in the paediatric age group

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1 "X marks the spot": The skeletal manifestations of Langerhans cell histiocytosis in the paediatric age group Poster No.: C-2847 Congress: ECR 2010 Type: Educational Exhibit Topic: Pediatric Authors: A. M. Hutchings, R. Chowdhury, S. J. Thomas, A. Thomson ; Portsmouth/UK, Southampton/UK Keywords: Langerhans cell histiocytosis, bone lesions, children DOI: /ecr2010/C-2847 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 47

2 Learning objectives 1. To provide a brief overview of the clinicoradiological spectrum of Langerhans cell histiocytosis (LCH). 2. To appreciate the varied appearance of skeletal disease, or eosinophilic granuloma, the most common manifestation of LCH in children. 3. To recognise common sites of bony involvement in LCH and distinguish form important differential diagnostic possibilities. Background Langerhans cell histiocytosis (LCH), is a rare disease complex affecting young people with a diverse clinical and radiological presentation, which can often prove a diagnostic challenge to both clinicians and radiologists alike. Previously termed Histiocytosis X, the X indicating an unknown cause, this spectrum of disease is currently considered a disorder of immune regulation and is characterised by the idiopathic proliferation of histiocytes, specifically the hallmark Langerhans cell, and granuloma formation. [1,2] The clinical symptoms of LCH depend on the site and extent of involvement. Localised osseous LCH may be clinically occult, but usually presents with pain and swelling of less than two months duration. Patients may have low-grade fever, elevated inflammatory markers and a normocytic anaemia, resulting in clinical confusion with infection.[1] The disease may be focal or systemic and the most common sites affected include the skeleton, lung, CNS, liver, thymus, skin and lymph nodes.[2,3] LCH encompasses three classic clinical syndromes, which are considered to be clinical variations of the same disease[1,2]: 1. Eosinophilic granuloma: localised benign form, isolated to bone Page 2 of 47

3 majority are monostotic, less frequently polyostotic usually present in 5-15 year olds most favourable prognosis associated[4] 2. Hand-Schuller-Christian disease: chronic disseminated disease, characterised by multifocal bone lesions and extraskeletal involvement of the reticuloendothelial system (RES) classic triad of: skull lesions,exophthalmos and diabetes insipidus usually seen in patients 1-5 years old 3. Letterer-Siwe disease: disseminated involvement of the RES with an acute fulminant clinical course multiple visceral organs involved usually occurs within first 2 years of life least favourable prognosis associated[5] Eosinophilic granuloma(eg) is by far the most common manifestation of this disease spectrum, accounting for approximately 70% of cases of LCH[1], however the variability of presentation of musculoskeletal LCH contributes towards the diagnostic difficulty this entity can pose for the clinical radiologist. Biopsy is usually indicated for diagnostic confirmation.[6] Although the natural history for most lesions is of gradual healing, curettage and grafting are sometimes indicated to accelerate the healing process. Occasionally, internal fixation for stability is required. Chemotherapy is used for multisystemic disease.[6] Imaging findings OR Procedure details The radiologic appearance of osseous LCH depends on the site of involvement and phase of disease. In the early stages, bony lesions may have an aggressive pattern of osteolysis with: permeative appearance wide zone of transition laminated periosteal reaction possible. Page 3 of 47

4 In later stages, lesions have a more benign appearance with: well-defined sclerotic margins narrow zone of transition mature or absent periosteal reaction.[3] SKELETAL DISTRIBUTION: Solitary LCH can occur in any bone, although there is a predilection for the flat bones, with more than 50% occurring in the skull, mandible, ribs and pelvis. Skull: most frequently involved calvarium > skull base, especially parietal Page 4 of 47

Fig.: AP skull radiograph of a 6 month old depicting multiple well-defined "punched-out" lytic lesions involving the cranial vault, some of which have

5 Fig.: AP skull radiograph of a 6 month old depicting multiple well-defined "punched-out" lytic lesions involving the cranial vault, some of which have coalesced resulting in a typical geographic or map-like appearance. References: A. M. Hutchings; Radiology, Portsmouth Hospital NHS Trust, UK, Page 5 of 47

Fig.: Lateral skull radiograph of the same patient demonstrating multiple lytic lesions affecting the calvarium, with a parietal predominance. References: A. M.

6 Fig.: Lateral skull radiograph of the same patient demonstrating multiple lytic lesions affecting the calvarium, with a parietal predominance. References: A. M. Hutchings; Radiology, Portsmouth Hospital NHS Trust, UK, temporal bone is the most commonly involved basal skull site (petrous ridges and mastoids) Page 6 of 47

7 Fig.: AP skull radiograph of a 9 month old infant demonstrating erosion of the left skull base due to a lesion centred on the mastoid region of the left temporal bone. The diagnosis of LCH in this region is often delayed as clinical features mimic those of otomastoiditis. Page 7 of 47

8 References: A. M. Hutchings; Radiology, Portsmouth Hospital NHS Trust, UK, Fig.: Axial CT image of the petrous temporal bones of a 3 year old demonstrates a large lytic lesion on the right with extensive destruction of the mastoid process and lateral petrous region. The external auditory meatus and middle ear cavity are also involved. Otologic involvement is more common in patients with multisystemic disease and can lead to deafness. References: A. M. Hutchings; Radiology, Portsmouth Hospital NHS Trust, UK, involvement of the orbital wall is common and often results in proptosis Page 8 of 47

9 Fig.: AP skull radiograph of a 3 year old demonstrates well-defined calvarial lytic lesions situated in the right parietal and occipital bones. Closer inspection reveals asymmetry of the orbits with loss of definition of the left lateral orbital margin, due to a third lytic lesion situated within the lateral orbital wall. Page 9 of 47

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11 Fig.: AP skull radiograph of the same patient taken 2 years later demonstrates evidence of healing in the calvarial lesions. The occipital lesion has undergone sclerosis and is now barely visible. The left lateral orbital wall defect persists. typically, round well-demarcated "punched out" osteolytic lesions characteristic bevelled edge or double contour due to uneven destruction of the outer and inner cranial tables a residual bony fragment may be contained within a lytic lesion, so called "button sequestrum" or "bull's eye" lesion periosteal reaction usually absent may be an associated soft tissue mass, demonstrated on CT and MRI, which typically enhances following intravenous contrast administration [1,3] Page 11 of 47

12 Fig.: The classic "bevelled edge" appearance of calvarial lesions is demonstrated on this axial CT image, due to unequal involvement of the inner and outer tables. There is an associated extracranial soft tissue mass. Page 12 of 47

13 Fig.: The same axial CT image displayed in soft tissue windows demonstrates the extracranial soft tissue mass associated with the osteolytic parietal lesion. Page 13 of 47

Fig.: Axial contrast-enhanced CT image of a 3 year old shows a right-sided large occipital soft tissue mass associated with an osteolytic lesion of the underlying calvarium, which extends

14 Fig.: Axial contrast-enhanced CT image of a 3 year old shows a right-sided large occipital soft tissue mass associated with an osteolytic lesion of the underlying calvarium, which extends intracranially. A similar lesion is seen within the ipsilateral petrous temporal bone, which extends into the posterior fossa and is seen to contain two hyperdense foci, representing bony sequestra. Both these soft tissue masses demonstrate diffuse enhancement on this post-contrast study. Mandible: alveolar bone destruction gives typical "floating teeth" appearance Page 14 of 47

15 often associated with soft tissue swelling similar finding may be seen in maxilla [1,3] Ribs: often geographic or permeative osteolysis periosteal reaction often associated with a pathological fracture extrapleural mass can result from soft tissue extension [1] Page 15 of 47

16 Fig.: AP chest radiograph depicts a well-defined lytic lesion in the posterolateral aspect of the left 8th rib in this 13 year old boy. There is focal expansion of the rib with thickening of the inferior cortex. Page 16 of 47

$Fig.: Sagittal reformatted CT image of a 6 year old reveals a pathological fracture$

17 Fig.: Sagittal reformatted CT image of a 6 year old reveals a pathological fracture associated with a well-defined osteolytic lesion in the left 7th rib. Page 17 of 47

18 Fig.: Sequential sagittal reformatted CT image of the same patient demonstrates the well-defined lucent lesion with mild focal expansion and a sclerotic rim. The pathological fracture is seen to breach the superior cortex of the rib on this slice. Page 18 of 47

$Increased tracer uptake relates to the underlying bony lesion, but may also relate to an underlying pathological fracture in some cases.$

19 Fig.: Technetium 99M-MDP radionuclide bone scan depicts the same lesion pictured above on plain film in a 13 year old. Increased tracer uptake relates to the underlying bony lesion, but may also relate to an underlying pathological fracture in some cases. Pelvis: supraacetabular region most frequently involved Page 19 of 47

20 Fig.: AP abdominal radiograph of a 9 month old infant demonstrates several large confluent lucent lesions in the left ilium. The supra-acetabular region is most commonly involved in pelvic LCH. In this case there is a lateral cortical breach associated with the lesion in this region, representing a pathological fracture. Page 20 of 47

21 References: A. M. Hutchings; Radiology, Portsmouth Hospital NHS Trust, UK, Fig.: AP pelvic radiograph of the same patient taken 3 years later shows clearer definition of the left iliac lesions due to a thin sclerotic rim. The previous pathological fracture has now healed and the cortex appears thickened. References: A. M. Hutchings; Radiology, Portsmouth Hospital NHS Trust, UK, other common sites include the iliac wings, ilium adjacent to the SI joints and ischiopubic rami iliac lesions can be mistaken for bowel gas with time, iliac lesions become well defined +/- sclerotic margin[1] Page 21 of 47

22 Fig.: AP pelvic radiograph of a 13 year old depicts an ill-defined lucent lesion in the right iliac blade. These lesions are easily mistaken for superimposed bowel gas shadows. This particular lesion was missed initially and the diagnosis delayed until 3 years later following development of a new symptomatic SIJ lesion (see below). Page 22 of 47

23 Fig.: AP pelvic radiograph of the same patient taken 3 years later due to a presenting complaint of right hip and buttock pain. There is destruction of the right ilium adjacent to the sacro-iliac joint. The lesion previously seen in the right iliac blade has healed and is now barely discernible, although on careful inspection its thin sclerotic margin can be detected on this film. Long bones: femur is most common site, followed by the humerus and tibia usually situated in the diaphysis or, less commonly, in the metaphysis epiphyseal involvement rare can cross the growth plate, although rare initially produces small ill-defined area of medullary destruction which may then enlarge with resultant endosteal scalloping Page 23 of 47

24 cortical erosion and soft tissue production may be seen in progressive lesions variable amounts of periosteal reaction, usually lamellated, with or without pathological fracture confluent lesions give rise to "hole-within-a-hole" appearance as lesions mature, they become more well-defined and develop a sclerotic margin remodelling of bone can impart expanded appearance, especially if preexistent soft tissue extension or extensive lamellated periosteal reaction present Page 24 of 47

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26 Fig.: Lateral femur radiograph of a 6 year old depicts a diaphyseal medullary lucency, with endosteal scalloping and subtle periosteal reaction seen anteriorly. Page 26 of 47

Fig.: AP and lateral lower leg radiographs demonstrate a well-defined lytic lesion within the tibial metaphysis which displays endosteal scalloping, cortical thickening, periosteal reaction and

27 Fig.: AP and lateral lower leg radiographs demonstrate a well-defined lytic lesion within the tibial metaphysis which displays endosteal scalloping, cortical thickening, periosteal reaction and "hole-within-a-hole" appearance. Fig.: AP and lateral lower leg radiographs of the same patient several months later, following treatment with chemotherapeutic agents. The tibial lesion has decreased significantly in size with in-filling and sclerosis seen as part of the healing response. The bone now displays normal cortical thickness, with almost complete bony remodelling evident. Page 27 of 47

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29 Fig.: Axial PD-fat saturated MR image of the leg of a 6 year old demonstrates the marrow replacing process within the medullary cavity of the femoral diaphysis, with endosteal scalloping, cortical thickening and periosteal reaction. Page 29 of 47

30 Fig.: AP radiograph of the left humerus in an 11 month old child depicts a large lytic lesion with marked expansion of the mid and distal humeral diaphysis, Page 30 of 47

31 cortical thinning and a lamellated periosteal reaction, particularly prominent towards the proximal aspect of the lesion. Several smaller lucencies seen within the distal diaphysis give rise to the so-called "hole-within-a-hole" appearance. Fig.: Radiograph of the humerus of the same patient as above taken 1 year later. The extensive lytic lesion has undergone in-filling and is no longer apparent, with just a few residual sclerotic foci remaining in the distal diaphysis. The bone has undergone extensive remodelling and now displays a normal cortical thickness. Page 31 of 47

32 Spine: mainly involves vertebral bodies posterior element involvement less common thoracic spine > lumbar spine > cervical spine anterior wedging or more commonly, uniform vertebral collapse termed vertebra plana with "coin-on-edge" appearance intervertebral disc spaces preserved or slightly widened (useful to differentiate from vertebral osteomyelitis) associated epidural extension or paraspinal mass may be seen on CT or MRI partial / almost complete reconstitution of vertebral body height is usual pattern of healing, although some residual compression deformity usually persists. [1,2,3] Page 32 of 47

33 Fig.: Lateral thoracic spine radiograph depicts a uniform collapse of the T7 vertebral body, a typical vertebra plana. LCH is the commonest cause of vertebra plana in children. Page 33 of 47

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35 Fig.: AP thoracic spine radiograph of a different patient with a T6 vertebra plana. Page 35 of 47

36 Fig.: Lateral thoracic spine radiograph of the above patient taken several months later depicts the known T6 vertebra plana and also a new T3 lesion, with a resultant increased thoracic kyphosis. Page 36 of 47

37 Fig.: Midline sagittal T2-weighted MR image of the above patient depicting the T6 vertebra plana, with preservation of the adjacent intervertebral disc architecture and signal return. Page 37 of 47

Fig.: Midline sagittal T2-weighted MR image of the same patient several years later depicts multiple consecutive vertebrae plana involving the T3 to T8 vertebrae.

38 Fig.: Midline sagittal T2-weighted MR image of the same patient several years later depicts multiple consecutive vertebrae plana involving the T3 to T8 vertebrae. There is a marked thoracic kyphosis as a result of this with subsequent degenerative intervertebral disc changes. The spinal cord is stretched over the kyphotic apex, however displays normal signal return with no evidence of oedema. Page 38 of 47

39 Atypical features: rare locations of eosinophilic granuloma include the clavicles, sternum, fibula and small bones of the hands and feet Fig.: Obliqued and AP radiographs of the right foot in a patient with an old eosinophilic granuloma of the distal 1st metatarsal. There is a long-standing Page 39 of 47

40 modelling deformity with a well-defined central lucent lesion which has a thin sclerotic rim. Other unusual features include: crossing of growth plate to involve epiphysis or apophysis involvement of the posterior elements of the spine intracortical and primary soft tissue lesions soft tissue calcification fluid-fluid level (may be due to haemorrhage within the lesion or a secondary aneurysmal bone cyst) [2] DIFFERENTIAL DIAGNOSIS: The differential diagnosis of lesions in the acute aggressive-appearing osteolytic phase of LCH includes: osteomyelitis Ewing's sarcoma leukaemia lymphoma. Chronic more benign-appearing lesions may resemble the following: healing metastases intraosseous haemangioma fibrous dysplasia giant cell tumour aneurysmal and simple bone cysts enchondroma non-ossifying fibroma.[3] Page 40 of 47

41 Acute skull lesions also need to be distinguished from metastases and leptomeningeal cysts. As the lesions start to heal and develop surrounding sclerosis, the differential includes epidermoids, meningocoele and chronic osteomyelitis.[3] LCH is the commonest cause of a vertebra plana in a child, however, the differential diagnosis includes: metastases lymphoma trauma Gaucher's disease haemangioma.[3] ROLE OF IMAGING MODALITIES: once a clinical diagnosis of LCH is made, further investigation involves the detection of other bony lesions via radiographic skeletal survey or bone scintigraphy these two techniques are complementary in the primary work up of LCH of the bone, although a single modality may suffice in follow-up imaging CT is useful to delineate the extent of osseous destruction and demonstrate soft tissue involvement CT-guided biopsy is often used to establish diagnosis in spinal LCH MRI is excellent in demonstrating bone marrow involvement and associated soft tissue mass or inflammation in LCH of the bone [1,2,3] Page 41 of 47

$pathological rib fracture. A further focus of increased activity is seen at the right sacro-iliac joint which correlates to a new focus of active disease seen on pelvic radiographs.$

42 Fig.: Tc99M-MDP radionuclide bone scan of a 13 year old boy with polyostotic LCH depicting increased tracer uptake in left 8th rib corresponding to the site of an eosinophilic granuloma and pathological rib fracture. A further focus of increased activity is seen at the right sacro-iliac joint which correlates to a new focus of active disease seen on pelvic radiographs. He presented with right hip pain and the rib lesion was an incidental finding during primary work-up investigations. Page 42 of 47

Fig.: Coronal T1-W MR image of the arm of an 11 month old who had an extensive eosinophilic granuloma of the humeral diaphysis demonstrated on plain film.

43 Fig.: Coronal T1-W MR image of the arm of an 11 month old who had an extensive eosinophilic granuloma of the humeral diaphysis demonstrated on plain film. MRI is superior in demonstrating the extent of soft tissue involvement. There is a large soft tissues mass with extensive inflammatory change surrounding the humerus, the posterior aspect of which is shown in this image. This was not clearly demonstrated on the radiographs. Page 43 of 47

44 Fig.: Coronal STIR MR image of the pelvis of a 13 year old shown to have a small focus of active disease of the right ilium adjacent to the SIJ. This image illustrates the effectiveness of MR in demonstrating bone marrow oedema, as evidenced by the increased signal intensity seen within the right iliac wing, which may be considerably more extensive than the underlying lesion itself. Page 44 of 47

Fig.: Surface rendered reconstruction of a craniofacial CT performed in a 2 year old with polyostotic disease illustrates the superior capability of CT in

45 Fig.: Surface rendered reconstruction of a craniofacial CT performed in a 2 year old with polyostotic disease illustrates the superior capability of CT in demonstrating the extent of bony destruction. The left lateral orbital wall destruction is far more apparent than on the radiograph (depicted earlier). Page 45 of 47

46 Conclusion Imaging plays an important role in the diagnosis and staging of LCH. The varied nature of bony lesions in both site and appearance as well as the potential for multisystemic involvement makes this an important disease entity for the radiologist to recognise and consider in the differential of both aggressive and non-aggressive bony lesions. Personal Information Dr Alexandra Hutchings Specialist Registrar Department of Radiology Queen Alexandra Hospital Southwick Hill Road Portsmouth PO6 3LY United Kingdom References 1. Stull MA, et al. From the archives of the AFIP; Langerhans Cell Histiocytosis of Bone. RadioGraphics (1992); 12: Azouz EM, et al. Langerhans' cell histiocytosis: pathology, imaging and treatment of skeletal involvement. Paediatric Radiology (2005); 35: Page 46 of 47

47 3. Kilborn TN, et al. Manifestations of Langerhans cell histiocytosis: A review of the clinical and radiological findings. Clinical Radiology (2003); 58(4): Titgemeyer C, et al. Pattern and course of single-system disease in Langerhans cell histiocytosis data from the DAL-HX 83- and 90-study. Med Pediatr Oncol (2002); 37(2): Kilpatrick SE, et al. Langerhans' cell histiocytosis (histiocytosis X) of bone. A clinicopathologic analysis of 263 pediatric and adult cases. Cancer (1995); 76(12): Arkader A, et al. Primary musculoskeletal Langerhans cell histiocytosis in children: an analysis for a 3-decade period. Journal of Pediatric Orthopaedics (2009); 29(2): Page 47 of 47

CT assessment of acute coalescent mastoiditis.

CT assessment of acute coalescent mastoiditis. Poster No.: C-1794 Congress: ECR 2010 Type: Educational Exhibit Topic: Head and Neck Authors: A. Thomson, S. J. Thomas, A. Hutchings, E. Tilley; Portsmouth/UK