Hyperlipoproteinemia

* A number of fibrous lesions involving bone display almost identical histologic appearances yet may represent either reactive or neoplastic conditions, resulting in a confusing nomenclature and possible diagnostic confusion. We report the case of a young man with no significant previous medical history who presented with a painful lesion in the left shoulder, which consisted almost entirely of xanthomatous material. We discuss the possible differential diagnosis of this lesion and why benign fibrous histiocytoma is the preferred terminology for this lesion. To our knowledge, this is the first reported case of a benign fibrous histiocytoma involving the acromion in an adult.

(Arch Pathol Lab Med 2002;126:599-601)

The histogenesis and classification of fibrohistiocytic lesions involving bone and containing an admixture of fibrous tissue, foam cells, and giant cells are confusing and include several overlapping entities, such as metaphyseal fibrous defect, nonossifying fibroma, fibrous cortical defect, fibroxanthoma, and benign fibrous histiocytoma (BFH) of bone. Some of these entities are considered to be either developmental abnormalities or degenerative changes, while others are considered to be neoplasms. These lesions, although displaying a similar range of histologic features, differ in their skeletal distribution and location, as well as in their age of presentation.

The histologic appearances can vary from polymorphous lesions to those showing a predominantly storiform, fibrous pattern of growth with rare multinucleated giant cells, to those lesions consisting predominantly of xanthic material. Some authors consider these latter xanthomatous lesions as neoplastic under the broad category of BFH, while others favor a "primary" xanthoma of bone as a separate reactive entity.1,2 A review of 70 cases of BFH of bone found only 1 previously reported case involving the scapula.1 However, the original diagnosis in this case was that of a nonossifying fibroma of bone, and no clinical details (including the age of the patient) were provided.3 We describe a benign bone lesion in an adult patient; the tumor consisted of a mass of foam cells and scanty fibrous tissue with no giant cells or cholesterol clefts and presented in this unusual location.

REPORT OF A CASE

The patient was a 45-year-old man who presented with a 3month history of pain affecting both shoulders, primarily in the right side, but also involving the left side. He worked as a manual laborer and described the pain as being aggravated by his daily work. He had also recently begun weight lifting as a hobby. Physical findings were confined to the right shoulder and included some local tenderness, but no limitation in movement. Because of the vague symptoms in the left shoulder, a radiograph of both shoulders was performed and revealed a 16-mm cyst with a sclerotic margin in the mid-acromion process of the left scapula; the cyst appeared to be benign (Figure 1). The right shoulder showed possible osteolysis of the distal end of the clavicle, which may have been related to the history of recent weight lifting. A bone scan performed soon after showed increased uptake in the right acromioclavicular joint, but no evidence of activity in the left scapula. No computed tomographic or magnetic resonance imaging scans were performed.

The patient was observed for a period of 8 months with continuing symptoms but no change in size of the cyst. He underwent surgery, which revealed a small cyst filled with yellow mucoid material and some fatty tissue prolapsing into the cyst. The fluid was aspirated and the lesion curetted free of any soft tissue. The space was packed with a bone graft, and the patient was discharged with no further complications.

PATHOLOGIC FINDINGS

The material submitted consisted of the aspirated cyst contents and tiny fragments of bone and soft tissue. The fluidlike material did not contain any refractile or crystalline material and showed only scattered foam cells with no accompanying inflammatory infiltrate. The fragment of bone was slightly thickened but otherwise unremarkable. Small areas of attached soft tissue consisted of sheets of uniform foam cells with abundant vacuolated cytoplasm and clear cytoplasmic borders lying in a background of small fibrovascular septations. No features of multinucleation or atypia were seen. No mitotic activity was identified. No giant cells or diffuse areas of fibrous tissue were seen in the material submitted for examination. No hemosiderin pigment was identified, although the material had been decalcified prior to staining. Small aggregates of bland lymphocytes were present at the periphery of the tissue, and erosion of newly formed bone by the lesion was seen (Figures 2 and 3). The cells were negative for 5100 (Dako Diagnostics, Mississauga, Ontario, Canada) and positive for HAM-56 (anti-human macrophage; Dako), indicating a histiocytic origin.

COMMENT

The Armed Forces Institute of Pathology's fascicle on tumors of the bones and joints defines BFH as "a tumor of fibroblasts and mono- or multinucleated cells that resemble histiocytes. Lipid-filled cells may be conspicuous and occasionally are the major component. The term xanthoma or fibroxanthoma is often given to the latter lesions which (we) consider to be within the broad category of benign fibrous histiocytoma."1 Although masses of cholesterol, foam cells, and giant cells are often seen as secondary or degenerative findings in many bone lesions, the underlying or "primary" lesion can be radiologically or histologically identified in most cases. The differential diagnostic possibilities include lesions, both nonneoplastic and neoplastic lesions, such as Erdheim-Chester disease, sinus histiocytosis with massive lymphadenopathy, giant cell tumor of bone, eosinophilic granuloma, malignant fibrous histiocytoma, or metastatic renal cell carcinoma. In generalized lesions, underlying hyperparathyroidism requires exclusion. In children, another possibility is a nonossifying fibroma or fibrous cortical defect.

Bertoni et al2 proposed the term primary xanthoma of bone for those cases in which no apparent underlying condition can be identified and the predominant finding is a collection of foam cells. The authors considered these lesions to be nonneoplastic in origin and not variants of BFH, a lesion they consider requiring a spindle cell component with clinical and radiographic evidence of a low-grade neoplasm.2 The clinical, radiological, and histologic features of these 2 entities are very similar, with a recurring theme being the varying proportions of the histologic elements considered in the diagnosis. Pain is a common presenting complaint in the majority of reported cases of BFH and was also the presenting feature in 6 of the 8 patients in 1 study; these 6 patients reported pain either as a presenting complaint or as a feature associated with a pathologic fracture.1,4 Pain was reported in 13 of the 21 "primary xanthoma" cases described by Bertoni et al.2 Destouet et als reported a case of fibrous histiocytoma (fibroxanthoma) of a cervical vertebra and included 21 additional cases in a literature review of BFH. These cases had a wide age range and a number of original diagnoses, including xanthoma or xanthofibroma; however, clinical details, including follow-up data, were unavailable in many.5 Citing a definition by Dahlin, the authors chose to include in their review those lesions having the histologic features of a nonossifying fibroma but occurring in skeletal sites other than the metaphyses of long bones as examples of BFH.6 They also questioned whether these lesions were true tumors of bone or a reactive process.5

The lesions in BFH are described as lytic, most with sharply defined margins and a sclerotic rim.4 The lesions are small and most commonly involve the flat bones, especially the pelvis, although the femur was also a common site in the series reported by Clarke et al4 and by Fechner and Mills.1 The pelvic bones were involved in 8 of the 22 cases reviewed by Destouet et al,5 and in only 2 cases did the lesion involve a long bone. The lesion presented around the knee joint in all 7 cases of BFH described by Bertoni et al7 in a 1986 series from the Instituto Rizzoli, 3 in the tibia and 2 each in the distal femur and fibula, sites usually associated with giant cell tumors of bone.7 Only 1 of the 21 cases classified as xanthomas and reported later by Bertoni et al from the Mayo Clinic involved the femur, and 3 cases also involved the skull, a site not previously reported in other series.2-4 The most frequently reported sites were the pelvic bones or ribs.2 In long bones, the metaphysis, epiphysis, or diaphysis may be involved. Cortical expansion and soft tissue invasion have been reported only rarely.1 The lesions are always solitary in distribution and showed characteristic findings on computed tomographic and magnetic resonance imaging scans in another small series of 3 lesions involving the femur.8 These characteristics included computed tomographic findings of lytic destruction and well-defined marginal sclerosis and T1-weighted magnetic resonance images of the same signal intensity as skeletal muscle.8

Pathologic findings include the gross description of the cyst contents as being clear to hemorrhagic in color and the curetted fragments as having a yellowish appearance.1,2,4 The lesions usually display the characteristic admixture of fibrous tissue, sometimes arranged in a storiform pattern together with foam cells and multinucleated giant cells. The relative proportions of these tissues vary widely, accounting for the different terms used in the final diagnosis. Bertoni et al2 attempted to exclude from their 1988 series any lesions showing definite histologic evidence of "metaphyseal fibrous defect, benign fibrous histiocytoma, aneurysmal bone cyst, simple bone cyst, fibrous dysplasia, osteomyelitis, histiocytosis X, a storage disease, hyperlipoproteinemia, or giant cell tumor." Multinucleated giant cells were a common feature in all 21 cases, as was iron pigment, and 7 of the cases showed a lymphocytic infiltrate.2 In distinction, the case reported by Destouet et all showed only rare multinucleated giant cells.

Most BFHs are treated with curettage and bone grafting. Three of the 8 cases in the series reported by Clarke et al4 recurred locally, leading to amputation in 2 cases. In contrast, none of the 21 cases reported as xanthomas by Bertoni et al2 recurred. No histologic features appear to predict recurrence, although predominantly fibrous lesions may be difficult to distinguish from low-grade fibrosarcoma. Another entity, which may cause diagnostic difficulty, is giant cell tumor of bone. In one study, 3 of 5 lesions of long bones originally diagnosed as BFH were reclassified as giant cell tumor when small foci of typical giant cell tumor were found on review.9 Extensive sheets of foamy macrophages have been described in cases of giant cell tumor of bone, as well as those cases presenting with extra-articular disease.10

Sampling adequate amounts of tissue is crucial to any histologic diagnosis and may well be the cause of much of the diagnostic confusion associated with these entities. It is possible, although considered unlikely, that the lesion in this case was incompletely removed and that the pathologic findings are unrepresentative, with the fibrous and giant cell components being difficult to aspirate or curette out and therefore absent in the examined material. The possibility of degenerative xanthic changes in a simple bone cyst was also considered in this case, but it was discounted owing to the clinical and radiological features and relatively abundant amounts of foam cells present.

In summary, it is difficult to clearly and reliably distinguish differences between the clinical, radiological, and pathologic findings of BFH and primary xanthoma because the summarized data in the literature include cases with a number of different diagnoses or cases with incomplete or missing information.1,2,4 Our patient presented with the typical clinical and radiological features of a BFH involving the scapula and histologically showed a lesion consisting predominantly of nests of bland foam cells with a slightly fibrous stroma, resulting in the final descriptive diagnosis of a fibroxanthoma.1 We consider this entity to be part of the morphologic spectrum of BFH of bone and not meriting a separate designation as a primary xanthoma of bone.

References

1. Fechner RE, Mills SE. Tumors of Bone and Cartilage. Washington, DC: Armed Forces Institute of Pathology; 1993:161-163. Atlas of Tumor Pathology, 3rd series, fascicle 8.

2. Bertoni F, Unni K, McLeod RA, Sim FH. Xanthoma of bone. Am J Clin Pathol. 1988;90:377-384.

3. Huvos AG. Bone Tumors: Diagnosis, Treatment, and Prognosis. Philadelphia, Pa: WB Saunders Co; 1979:297-306.

4. Clarke BE, Xipell JM, Thomas DP. Benign histiocytoma of bone. Am J Surg Pathol. 1985;9:806-815.

5. Destouet JD, Kyriakos M, Gilula LA. Fibrous histiocytoma (fibroxanthoma) of a cervical vertebra: a report with a review of the literature. Skeletal Radiol. 1985;5:241-246.

6. Dahlin DC. General aspects and data on 6,221 cases. In: Bone Tumors. 3rd ed. Springfield, III: Charles C Thomas; 1978:116-136.

7. Bertoni F, Calderoni P, Bacchini P, et al. Benign histiocytoma of bone. J Bone joint Surg Am. 1986;68:1225-1230.

8. Hamada T, Ito H, Araki Y, Fujii K, Inoue M, Ishida 0. Benign fibrous histiocytoma of the femur: review of three cases. Skeletal Radiol. 1996;25:25-29.

9. Matsuno T. Benign fibrous histiocytoma involving the ends of long bone. Skeletal Radiol. 1990;19:561-566.

10. Somerhausen N, Fletcher CDM. Diffuse-type giant cell tumor: clinicopathologic and immunohistochemical analysis of 50 cases with extraarticular disease. Am] Surg Pathol. 2000;24:479-492.

Denis Macdonald, MD; Victor Fornasier, MD; Richard Holtby, MD

Accepted for publication September 4, 2001.

From the Departments of Anatomical and Clinical Pathology (Dr Macdonald) and Surgery (Dr Holtby), Sunnybrook & Women's College Health Sciences Centre, Toronto, Ontario; and the Department of Laboratory Medicine, Division of Pathology, St Michael's Hospital, Toronto, Ontario (Dr Fornasier).

Reprints: Denis Macdonald, MD, Departments of Anatomical and Clinical Pathology, Sunnybrook & Women's College Health Sciences Centre, Women's College Campus, 76 Grenville St, Toronto, Ontario, Canada M5S 1B2 (e-mail: denis.macdonald@swchsc.on.ca).

Copyright College of American Pathologists May 2002
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