Skeletal Radiol (1992) 21:64-67

Skeletal Radiology

Case report 710 Peter J. Strouse, M.D. 1, Burton I. Ellis, M.D. 1, Louis Z. Shifrin, M.D. 2, and Ajay R. Shah, M.D. 3 Departments of 1 Diagnostic Radiology and Medical Imaging, 2 Orthopedic Surgery, and 3 Pathology, Henry Ford Hospital, Detroit, Michigan, USA

Fig. 1. Lateral view of right leg and anteroposterior view of left leg demonstrate slightly expanding lytic lesions superimposed on a diametaphyseal sclerosis with coarsened trabeculae. Round calcific opacities in soft tissue are suggestive of phleboliths (white arrows). Healing pathological fractures through large lytic lesions are seen bilaterally (black arrows) Fig. 2. Lateral and anteroposterior views of the distal end of the left femur and proximal ends of the tibia and fibula show metaphyseal sclerosis with coarsened trabeculae in the femur and tibia and, to a lesser extent, the fibula. A lytic lesion in the distal end of the femur demonstrates cortical breakthrough (arrows) Fig. 3. An isotope bone scan (anterior and posterior images) demonstrates bilateral, symmetrical uptake in the distal ends of the femora and throughout both tibiae. Facial uptake is due to dental disease Fig. 4. A computed tomography (CT) scan shows a lyric lesion in the proximal segment of the right tibia. Note the frank cortical breakthrough and an associated soft-tissue mass protruding into the leg (arrow). Less prominent changes are evident on the left at this level

9 1992 International Skeletal Society

P.J. Strouse et al. : Case report 710

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Fig. 5. A Tranverse magnetic resonance (MR) image (TR500/TE20) of the lower limbs demonstrates extensive replacement of the normal fatty marrow with low signal soft tissue. The anterior tibial cortex is not identifiable on the left. B Coronal MRI (TR500/TE20) demonstrates extensive marrow replacement and areas of frank cortical breakthrough (arrows). C Transverse MRI (TR2500/TE80) of the distal ends of the femora demonstrates a high signal lesion extending into the anterior soft tissues of the left thigh (arrows)

Clinical information A 36-year-old white man presented with a 1-year history of intermittent bilateral shin pain and pretibial swelling. The onset of symptoms was associated with jogging; he was forced to abandon his jogging and curtail his work as a musician due to the symptoms. He had been seen at other institutions and treated symptomatically. The patient's past medical history was noncontributory. Physical examination of the lower extremities demonstrated mild pretibial swelling. Soft-tissue masses were palpable along the anterior tibial surfaces. These were non-mobile, not attached to the skin, and not warm to touch. Minimal tenderness was noted. The skin was not affected. Neurologic and vascular exams were unremarkable. Laboratory studies were normal with the exception of a slightly elevated alkaline phosphatase level (133 IU/I), a Westergren erythrocyte sedimentaAddress reprint requests to: Peter J. Strouse, M.D., Department Of Diagnostic Radiology and Medical Imaging, Henry Ford Hospital - K3, 2799 W. Grand Boulevard, Detroit, MI 48202, USA

tion rate (51 ram/h), and a very mild anemia (hemoglobin 13.4 g/dl). Radiographs of the lower extremity (Figs. 1, 2) demonstrated extensive abnormality of the distal ends of the femora and tibiae, bilateral and symmetrical in distribution. A sclerotic medullary pattern with coarsened trabeculae was seen with multiple superimposed lytic areas, particularly in the midtibiae. The lytic lesions were generally well defined, although some had a multilocular appearance. Endosteal scalloping, slight fusiform expansion, and areas of frank cortical breakthrough were identified. A few round calcified opacities in the soft tissues adjacent to the left tibia were suggestive of phleboliths (Fig. 1). Lesser changes were seen in the fibulae bilaterally. The proximal segments of the femora, ankles, and feet were normal. A chest radiograph and skeletal survey showed no additional abnormalities. A technetium 99m methylenediphosphonate (99mTc-MDP) bone scan (Fig. 3) demonstrated intense, bilateral, symmetrical uptake in the distal femora and throughout both tibiae. This corresponded to the areas of radiographic abnormality.

A C T scan o f the legs (Fig. 4) demonstrated multiple lyric areas with frank cortical breakthrough within the tibial and distal femora. Soft-tissue masses were identified, protruding from the bony lesions. An M R I scan of the lower extremities (Fig. 5) demonstrated extensive abnormality of the medullary cavity of the distal ends of the femora and tibiae bilaterally. The abnormality was predominantly o f low signal intensity of Tl-weighted sequences, consistent with replacement of the normal native fatty marrow (Fig. 5 A, B). Mixed signal intensity was seen on T2-weighted sequences, with high intensity areas of the intramedullary process extending through the cortical surfaces into the anterior soft tissues (Fig. 5 C). During the work-up, the patient developed bilateral pathological fractures of the tibiae. Radiographs demonstrated transverse fractures through large lytic lesions in both tibiae (Fig. 1). Histology: Percutaneous core biopsies of the left tibia and pretibial soft tissues distant from the site o f fracture were obtained from two separate lytic lesions. Soft, friable, yellowish material was found within the medullary canal.

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Diagnosis: Symmetrical eosinophilic granuloma of the lower extremities (proven) and Erdheim-Chester disease (probable) Histological examination of multiple tissue fragments showed numerous histiocytes in a background of eosinophils, lymphocytes, plasma cells, and rare multinucleated giant cells (Fig. 6). Immunohistochemical studies using the avidin-biotin complex method on the monoclonal S-100 antibody revealed strong positive reaction on Langerhans-type histiocytes. The findings were consistent with eosinophilic granuloma.

Discussion In 1953, Lichtenstein coined the term "histiocytosis-X" to unify eosinophilic granuloma (EG), LettererSiwe disease (LSD), and HandSchfiller-Christian disease (HSC) as a spectrum of disease [6]. Recently, the term "Langerhans cell histiocytosis" (LCH) has been proposed as a more accurate pathological de-

P.J. Strouse et al, : Case report 710 scriptor, since the Langerhans cell is a histological feature common to these entities [3]. The Langerhans cell, originating from the marrow, is normally found as an epidermal dendritic cell. Its distinguishing characteristic is the presence of cytoplasmic Birkbeck granules, revealed as rodshaped or "tennis racket"-shaped profiles ultrastructurally. The proliferative bony lytic lesion typically reveals numerous Langerhans cells admixed with eosinophils, lymphocytes, plasma cells, and occasionally multinucleated histiocytes. Numerous neutrophils may be present areas of necrosis. In the healing lesion there is often a sparsity of Langerhans cells. This may warrant the use of immunohistochemical staining with monoclonal proteins such as S-100 and T6 to confirm the presence of the Langerhans cell and therefore aid in the diagnosis of LCH [3]. EG is generally a disease of childhood. It most frequently presents as a solitary lesion [5]. Multiple lesions are infrequent. To our knowledge, symmetry of lesions has not been reported. EG may occur at any bony

Pathological study

Fig. 6. Left tibial and pretibial soft-tissue biopsy ( x 25) reveals numerous histiocytes with abundant eosinophilic cytoplasm seen admixed with eosinophils, lymphocytes, and plasma cells. Monoclonal antibody to S-100 reveals strong positivity to Langerhans-type histiocytes (arrows, inset, x 100). The findings are typical of eosinophilic granuloma

site; skull, mandible, spine, rib, and long bones are most frequently affected. The lesions generally are wellcircumscribed and lytic, but aggressive lesions are not rare. HSC is a chronic, slowly progressive form of LCH, typically involving the reticuloendothelial system. Occasionally, it is fulminant [7]. HSC has a characteristic onset at 5-10 years of age. The classic triad of diabetes insipidus, exophthalmos, and "geographic skull" is only occasionally seen. Radiographically, the lesions are similar to those of EG but often multiple and widely disseminated. The skull is the most frequent site of skeletal involvement. LSD is an acute, fulminant form of LCH with a poor prognosis. It primarily affects children and infants under 3 years of age [7]. Skeletal lesions were once rare with LSD. With more effective treatment regimens, they are now seen in more than half of those surviving longer. Lesions are usually multiple; a predilection for the skull and mandible exists. The radiographic characteristics of EG vary with the location involved. Long bone lesions are usually diaphyseal, less frequently metaphyseal, and rarely epiphyseal. Lesions originate within the medullary cavity with lytic destruction, gradually expanding the medullary cavity and resulting in endosteal scalloping of the cortex. Periosteal reaction may be seen. Lesions may break through the cortex, producing a soft-tissue mass [11]. Our patient presented with extensive bilateral abnormality of the distal ends of the femora, tibiae, and to a lesser extent fibulae, as demonstrated by multiple imaging modalities. Biopsy at two sites demonstrated classic EG. Although radiographic characteristics of the individual lytic lesions are consistent with EG, a thorough search of the literature did not reveal a similar distribution of abnormality symmetrically involving the lower extremities. The radiographic findings are by no means diagnostic of EG. Differential diagnostic considerations would include adamantinoma, fibrous dysplasia, chronic osteomyelitis, tuberculous and fungal osteomyelitis, and Erdheim-Chester disease.

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P.J. Strouse et al. : Case report 710 Adamantinoma is a rare, locally aggressive malignancy of controversial pathogenesis. It occurs most frequently in the 2nd to 5th decades. Often a history of trauma is given. A predilection for long bones exists with 80% 85% of cases involving the tibia. The characteristic tibial lesion is a locally expanded, intramedullary, osteolytic, mid-diaphyseal lesion with thinned cortex and negligible periosteal reaction [10]. Interspersed areas of reactive sclerosis may be present. Concurrent fibular involvement may be seen [4]. Bilaterality virtually excludes adamantinoma in this case. Fibrous dysplasia is a developmental abnormality of bone-forming mesenchyme in which the osteoblasts fail to undergo normal morphologic differentiation. Some 7 0 % - 8 0 % is monostotic, in which tibial involvement is relatively common, while 2 0 % - 3 0 % are polyostotic; however, axial locations are favored. Long bone lesions are intramedullary and predominantly diaphyseal. Lesions are usually radiolucent with a " g r o u n d glass" appearance. They are well-defined, often with a rim of reactive sclerosis or thickened adjacent cortex. Local expansion produces a fusiform bulge. The cortex is intact unless there is fracture or infection. The bones are weak, allowing for bowing deformity and predisposing to fracture [13]. Chronic pyogenic osteomyelitis may produce extensive osteolytic and osteoselerotic changes. Tuberculous and fungal osteomyelitis may produce multiple osteolytic lesions. Bilaterally symmetric disease is unlikely. Erdheim-Chester disease (ECD, also known as lipid granulomatosis) typically affects the distal lower extremities symmetrically. It has been stated by some to be a variant of Langerhans cell histiocytosis [2, 14]. The radiological features o f ECD are characteristic and not inconsistent with the findings in our patient: symmetric lesions of long bones, especially the lower extremities, with diffuse diaphyseal-metaphyseal sclerosis and relative sparing of the epi-

physes [2]. The axial skeleton is generally spared. Lytic lesions occur in a substantial minority; however, no patient has demonstrated lytic lesions as extensively as our patient. To date, 32 cases of histologically proven ECD have been reported [2, 8]. An additional case [14] demonstrated radiographic changes of ECD but was histologically diagnosed as EG. All 20 patients for whom race was reported with ECD have been white, as was our patient, and the majority were male, as was our patient. Age ranged from 16 to 78 years. Clinical manifestations are variable and nonspecific and range from an asymptomatic focal process to progressive fatal illness with multisystem involvement [12]. Of the 32 reported cases 28 had bilateral distal lower extremity involvement; in several, this was the sole site of involvement. Successful reversal of progressive involvement of bone or other structures has not been reported. The clinical picture, in conjunction with symmetric involvement of the lower extremities associated with a component of sclerotic change sparing the epiphysis suggest the probable coexistence of ECD in this case, although biopsy p r o o f is not available. Histologically in ECD one sees irregular trabecular thickening in cortical and cancellous bone, marrow fibrosis, and yellow areas of lipid granulomata. Foamy histiocytes laden with cholesterol are seen in the intertrabecular spaces. Lymphocytes, plasma cells, and an occasional eosinophil are intermingled with the histiocytes [12]. All four cases of classic ECD immunohistochemically tested for S-100 protein have been negative [i, 8, 9]. The histology of ECD and L C H are thus distinct. However, lesions of HSC eventually may become lipidized, collagenized, and scarred, resembling the pathology of ECD [5]. In summary, we present a case of symmetrical E G of the lower extremities in a 36-year-old man. Several entities are considered in the differential diagnosis. However, many of the features bear a striking resemblance

to ECD, which probably coexists in this case. A link between the two entities, E G and ECD, has been suggested by others [2, 14]. Future experience may confirm this hypothesis.

References

1. Alper MG, Zimmerman LE, La Piana FG (1983) Orbital manifestations of Erdheim-Chester disease. Trans Am Ophthalmol Soc 81:64 2. Brower AC, Worsham F, Dudley AH (1984) Erdheim-Chester disease: a distinct lipidosis or part of the spectrum of histiocytosis. Hematol Oncol Clin NA 1:75

3. Favara BE, Jaffe R (1986) Pathology of Langerhans histiocytosis. Hematol Oncol Clin NA 1 : 75 4. Freiberger RH, Bullough PG (1976) Case report 8: adamantinoma of tibia. Skeletal Radiol 1:112 5. Jaffe HL (1972) Metabolic, degenerative, and inflammatory disease of bone and joints. Lee & Febiger, Philadelphia, p 535 6. Lichtenstein L (1953) Histiocytosis X. Integration of eosinophilic granuloma of bone, "Letterer-Siwe disease" and "Schfiller-Christian disease" as related manifestations of a single nosologic entity. Arch Pathot 56: 84 7. Mickelson MR, Bonfiglio M (1977) Eosinophilic granuloma and its variations. Orthop Clin North Am 8:933 8. Miller RL, Sheeler LR, Bauer TW, Bukowski RM (1986) Erdheim Chester disease: case report and review of the literature. Am J Med 80:1230 9. Molnar CP, Gottschalk R, Gallagher B (1988) Lipid granulomatosis: ErdheimChester disease. Clin Nuc Med 13:736 10. Moon NF, Mori H (1985) Adamantinoma of appendicular skeleton - updated. Clin Orthop 204:215 11. Nauert C, Zornova J, Ayala A, Harle T (1983) Eosinophilic granuloma of bone : diagnosis and management. Skeletal Radiol 10:227 12. Resnick D, Greenway G, Genant H, Brower A, Haghighi P, Emmett M (1982) Erdheim-Chester disease. Radiology 142:289 13. Resnick D, Niwayama G (1988) Diagnosis of bone and joint disorders, 2nd edn. W.B. Saunders, Philadelphia, p 4057 14. White RJ, Doherty PW, Liepman M, Woda B (1988) Langerhans cell histiocytosis with the radiographic findings of Erdheim-Chester disease. AJR 150:869