Cortical dysplasia

Fibrous dysplasia is a benign disorder of bone in which proliferating fibrous tissue replaces the bony spongiosa. Cytologic atypia is generally not considered a feature of this proliferating tissue. We present a case of fibrous dysplasia with marked atypical nuclear changes consistent with degenerative or regressive changes. A 42-year-old man presented with an osteolytic lesion of the right iliac bone. Histologic study demonstrated a fibro-osseous lesion with woven bone trabeculae and bland-looking fibrous tissue. Several areas showed atypical cells with enlarged pleomorphic nuclei and bizarre features. There was no change in the nuclear-cytoplasmic ratio nor were mitotic figures identified. The differential diagnosis is discussed. When radiographic and other histologic findings suggest fibrous dysplasia, the atypical nuclear changes should not, by themselves, alter the diagnosis.

(Arch Pathol Lab Med. 2004;128:794-796)

Fibrous dysplasia (FD) is a common benign disorder of bone characterized by a tumorlike proliferation; the mass is almost always intramedullary and composed of fibrous tissue with an irregular pattern of osseous metaplasia. It may involve a single bone or multiple bones.1 Although FD is sometimes considered a true neoplasm of bone (in recognition of its presentation as a mass lesion), it is not a neoplasm; hamartomatous proliferation and localized failure of bone to mature from the woven to the lamellar form are theories that may account for FD.1-3

Although, when asymptomatic, FD can be discovered at any age, it usually begins prior to puberty, grows slowly, and tends to become quiescent after puberty.3 It commonly presents in radiographs as an incidental lucent lesion replacing the bony spongiosa, with well-defined and occasionally sclerotic margins. Histologically, it appears as a proliferation of thin wavy spicules of woven bone found in a bland, slightly to moderately cellular fibrous background. Bony trabeculae are usually not surrounded by osteoblasts. Unusual histologic features include foci of osteoblastic rimming, scattered trabeculae of lamellar bone, cystic degeneration, and highly cellular fibrous stroma. Cytologie atypia and more than just occasional mitoses are not features of FD.1-3

This article presents an unusual case of FD of bone with scattered foci of nuclear atypia with degenerative nuclear changes, which led to diagnostic problems.

REPORT OF A CASE

In June 1990, a 42-year-old man presented with a 2-year history of lower back pain. He had no history of trauma and the pain was not relieved by rest. Radiography of the pelvis showed a poorly circumscribed, osteolytic lesion in the anterior upper aspect of the right iliac bone. It was intramedullary and showed thinning and focal erosion of the overlying cortex (Figure 1, a). Computed tomography demonstrated cortical thinning and slight bony expansion without soft tissue extension (Figure 1, b). The radiographic findings were not specific. Results of a computed tomography of the thorax and other investigations were essentially normal. Open biopsy was performed. During surgery, a firm yellow-white to pink tissue was noted. This tissue was completely contained between the 2 cortices of the ilium. Because of diagnostic uncertainty, a definitive resection of the tumor with wide margins was performed. Stability of the right sacroiliac and hip joints was preserved. No further treatment was used. The patient recovered with minimal disability and has been well with no evidence of recurrence or metastatic disease for more than 12 years.

MATERIALS AND METHODS

The whole lesion, including its interface with the adjacent bone, was sectioned for histologic study. For light microscopy, 3- to 5-µm paraffin sections of formalin-fixed tissue were stained with hematoxylin-eosin. Retrospectively, 400 cases of fibrous dysplasia of bone in the files at Istituto Rizzoli (Bologna, Italy) were reviewed. Only cases that had been treated surgically and were histologically proven were included. The aim of this review was to investigate, using a large series of FD cases, the true incidence of this phenomenon, which may be overlooked in otherwise diagnostically obvious cases.

PATHOLOGIC FINDINGS

Grossly, the lesion was well defined from the surrounding bone and was tan with reddish hemorrhagic areas. Microscopic examination showed a paucicellular fibro-osseous lesion with randomly arranged, woven bone trabeculae and bland-looking, loosely textured, intervening fibrous tissue with thin capillary vessels (Figure 2, a). The delicate bone trabeculae were not surrounded by osteoblasts for the most part, but scattered foci of osteoblastic rimming were observed. Several areas showed atypical cells with enlarged, pleomorphic, hyperchromatic nuclei, sometimes multilobed, scattered singly or in clusters in the fibrous stroma and in the trabeculae; several of these nuclei had a bizarre aspect (Figure 2, b). The nuclei commonly showed vacuolization similar to that seen in bizarre nuclei of other benign lesions.4-6 There was no change in the nuclear-cytoplasmic ratio, because the cytoplasmic volume also increased. No mitoses, typical or atypical, could be identified in the numerous histologic slides (Figure 2, c and d). In summary, the histologic findings were those of FD with pseudomalignant cytologic features. A histopathologic diagnosis of FD with degenerative or regressive nuclear changes was made.

COMMENT

Fibrous dysplasia is a benign fibro-osseous lesion arising in an intramedullary location. Radiologically, it is usually a well-defined radiolucent defect with hazy opacity, classically described as "ground glass" or "frosted glass" in appearance, lacking a trabecular structure, with or without expansion of the cortex. The lesion may be sharply defined with a sclerotic rim or may lack perilesional sclerosis and fade into the adjacent normal bone. The periosteal surface may have a wavy appearance, but it is most often smooth and intact.1,3

Low-grade, intraosseous-type osteosarcoma (LGIOS) is a distinct variant of osteosarcoma in which the histology may be strikingly similar to that of FD.78 This low-grade malignant tumor is composed of spindle cells, with only minimal atypia, forming osteoid and bone. The differential diagnosis from FD is made by careful radiographic and histologic correlation. In LGIOS, radiologic features suggest a malignant nature (intramedullary extension, cortical violation, and soft tissue involvement); FD almost never has the appearance of malignancy.8 However, LGIOS sometimes appears with radiologic features suggesting a benign lesion,7 and FD can exhibit areas of cortical perforation, with or without cortical thinning (better appreciated on computed tomographic examination).9 Histologically, there may be focal areas showing an overlapping of morphologic features. However LGIOS, even if similar to FD, has a consistent infiltrating pattern. Permeation, extensive or minimal, among the peripheral host bony trabeculae, or entrapment of the host trabeculae at the edge of the tumor is always present. Occasionally, bone marrow infiltration may be present.7,8 Spindle cells in LGIOS are arranged in an interlacing pattern and have nuclear pleomorphism with few mitotic figures. They can be relatively sparse and show minimal hyperchromatism and variation in size and shape, or they can have nuclei slightly more hyperchromatic and pleomorphic.7 Lowgrade, intraosseous-type osteosarcoma is a hypocellular, very sclerotic tumor. Low-grade, intraosseous-type osteosarcoma is the main differential diagnosis in the present case.

Our case was characterized by unusual foci of marked nuclear hyperchromasia, suggesting a malignant neoplasm. Rigorous search for mitoses and an infiltrating pattern yielded negative results. Initially, a diagnosis of LGIOS was considered because of the focal nuclear hyperchromasia observed in the first biopsy. Microscopic evaluation of the definitive surgical specimen and radiologic studies showed the noninvasive, or nondestructive, nature of the lesion. We stress the focal nature of the atypical cells, lack of crisp nuclear details, and lack of mitotic figures in these cells in making a correct diagnosis. Conventional osteosarcoma shows a more aggressive spindle cell proliferation, permeation or evident invasion of the host bone, highly malignant atypical nuclei, and frequent mitoses.

To the best of our knowledge, nuclear atypia has not been described previously in FD. Furthermore, in the review of 400 cases of FD in our files, we were not able to find any atypia in the oval and/or spindle cells of the lesions. Nuclear changes associated with degeneration have been described in several other lesions, such as ancient schwannoma, neurofibroma, bizarre (or pseudomalignant) osteoblastomas, chondromyxoid fibroma, and bizarre leiomyoma of the uterus.2-6, 10 The nuclear changes seen in the present case were very similar to the degenerative atypical changes observed in the aforementioned lesions; the similarity extends to the absence of mitoses as well. The nuclei tended to be large and bizarre, appearing without alteration in the nuclear-cytoplasmic ratio, and they might appear vacuolated. This kind of bizarre appearance may also be seen after radiation. Wu et al10 proposed that the term pleoniorphism was more appropriate than cytologic atypia.

In summary, we report a case of FD with foci of marked nuclear atypical changes, as seen in other tumoral lesions. These changes were related to degenerative alterations, and they did not indicate aggressive or malignant behavior, although they could be mistaken for sarcomatous features. The atypia in FD of bone is indeed a very rare occurrence; therefore, it is probably of greatest relevance to those interested in musculoskeletal diseases. It represents an important finding, as it adds 1 more entity to the list of potential mimics of sarcoma.

References

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2. Fechner RE, Mills SE. Tumors of the Bones and joints. Washington, DC: Armed Forces Institute of Pathology: 1993. Alias of Tumor Pathology, 3rd series, fascicle 8.

3. Huvos AC. Bone Tumors: Diagnosis, Treatment, and Prognosis. 2nd ed. Philadelphia, Pa: WB Saunders; 1991.

4. Bahk WJ, Mirra IM, Sohn KR, Shin DS. Pseudoanaplastic chondromyxoid fibroma. Ann Diagn Pathol. 1998;2:241-246.

5. Cheung FMF, Wu WC, Lam CK, Fu YK. Diagnostic criteria for pseudomalignant osteoblastoma. Histopathology. 1989;31:196-200.

6. Moore CE, Putzi M, McClatchey KD, Terrell J. Ancient schwannoma of the posterolateral pharynx: a benign lesion commonly mistaken for sarcoma. Otolaryngol Head Neck Surg. 1997;117:S124-S128.

7. Bertoni F, Bacchini P, Fabbri N, et al. Osteosarcoma: low-grade intraosseous-type Osteosarcoma, histolugically resembling parosteal osteosarcoma, fibrous dysplasia, and desmoplastic fibroma. Cancer. 1993;71:338-345.

8. Kurt AM, Unni KK, McLeod RA, Pritchard DJ. Low-grade intraosseous osteosarcoma. Cancer. 1990;65:1418-1428.

9. Yao L, Eckardt JJ, Seeger LL. Fibrous dysplasia associated with cortical bony destruction: CT and MR findings. J Comput Assist Tomogr. 1994;18:91-94.

10. Wu CT, Inwards CY, O'Laughlin S, Rock MG, Beabout JW, Unni KK. Chondromyxoid fibroma of bone: a clinicopathologic review of 278 cases. Hum Pathol. 1998;29:438-446.

Franco Bertoni, MD; Luis Fernando Arias, MD; Marco Alberghini, MD; Patrizia Bacchini, MD

Accepted for publication February 26, 2004.

From the Department of Surgical Pathology, Istituti Ortopedici Rizzoli, Bologna, Italy (Drs Bertoni, Alberghini, and Bacchini); and University of Antioquia, Medellln, Columbia (Dr Arias).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Franco Bertoni, MD, Department of Surgical Pathology, Istituti Ortopedici Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy (e-mail: franco.bertoni@ior.it).

Copyright College of American Pathologists Jul 2004
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