Fibrous cortical defect with bizarre nuclear features

CASE REPORT

Fibrous Cortical Defect With Bizarre Nuclear Features Randall D. Craver,MD, Stephen Heinrich, MD, andJoseph Mirra, MD A femoral neck fibrous cortical defect with typical radiographic features had bizarre nuclear features on histological examination. Recognition of the benign radiographic appearance, similar bizarre features of accompanying macrophages, and paucity of mitoses led us to consider this a pseudoanaplastic ischemic or degenerative change in an old fibrous cortical defect. Because the biological behavior was not known with certainty, we closely followed this case. After 25 months, there has been no recurrence or regrowth. The close cooperation between the pathologist and other disciplines facilitates recognition of these pseudoanaplastic lesions and development of treatment strategies for lesions of unknown or uncertain biological behavior.

Ann Diagn Pathol 1: 26-30, 1997. Copyright © 1997 by W.B. Saunders Company Index Words: Pseudoanaplasia, pseudosarcoma, fibrous cortical defect

HE CHANGES of nuclear hyperchromasia and leomorphism, histological hallmarks of malignancy, can also be typically found in certain benign lesions, such as the neurilemmoma and after radiation. Less frequently, it can be found in benign bone lesions leading to the designation ofpseudomalignancy orpseudoanaplasia, and probably represents ischemia. Nuclear hyperchromasia and pleomorphism in an otherwise typical fibrous cortical defect in the femoral neck of a 21-year-old woman at first suggested malignancy. However, the sparse mitoses and similar nuclear changes in accompanying macrophages suggested pseudoanaplasia. With no further therapy, there has been no recurrence or regrowth after 25 months. We describe the radiographic and histological features of this lesion with pseudoanaplasia, and discuss why we initially considered this lesion benign, the differential diagnosis, and our clinical approach to this lesion, which, at the beginning, we were uncertain of its biological behavior.

Case Report

This 21-year-old woman complained for 6 months of activity-limiting progressive anterior hip pain that radiated into the lateral distal thigh. Past history included asthma, previous pneumonias, acute hepatitis (12 years previously), and allergies to penicillin, sulfa drugs, and codeine. Thigh pain was elicited with internal and external rotation, and proximal, lateral, and anterior palpation. Left hip, knee, and ankle movement were normal. No masses, lymphadenopathy, neural or vascular abnormalities were present. 26

Radiographs demonstrated a well-delineated, intracortical, femoral neck 5 × 1.5 cm wedge-shaped lesion with sclerotic borders (Fig 1), without a permeative pattern of destruction. Computerized tomography and magnetic resonance imaging confirmed a markedly sclerotic intracortical lesion with only 2 to 3 mm of expansion into the medullary canal, but even this medullary extension was surrounded by sclerotic bone (Figs 2 and 3). The differential diagnosis at time of biopsy included a fibrous cortical defect, nonossifying fibroma, aneurysmal bone cyst, and osteoid osteoma. It was believed that a malignancy was unlikely. An incisional biopsy using a lateral approach created a cortical window, and currettings were obtained. Pathology Grossly, the bone was thickened, and the accompanying soft tissue was tan-to-yellow. Microscopically, the bone had numerous pagetoid cement lines with occasional osteoclasts. The marrow was sparsely cellular, contained spindle cells with markedly pleomorphic hyperchromatic nuclei, with irregularly clumped and distributed chromatin. There were occasional prominent

From the Departments of Pathology and Orthopaedics, Louisiana State University ]ffedical Center and Children's H~spital, New Orleans, LA; and University of California Los Angeles, OrthopaedicHospital, Los Angeles, CA. Address reprintrequeststo Randall D. Craver,MJ), DepartmentofPathology, Children'sHospital, 200 Henry ClayAve, New Orleans,LA 70118. Copyright © 1997by W.B. Saunders Company 1092-9134/97/0101-0004505.00/0

Annals of Diagnostic Pathology, Vol 1, No 1 (October), 1997: pp 26-30

Fibrous Cortical Defect With Bizarre Nuclei

27 Discussion

Figure 1. Lateral radiograph of the proximal femur reveals an intracortical radiolucency with benign features.

nucleoli, intranuclear pseudoinclusions of cytoplasm, and a moderate amount of eosinophilic cytoplasm (Fig 4), without a distinct organizational pattern. A single normal mitosis was present. There was no necrosis, neoplastic osteoid, or cartilage. Foamy histocy-tes with fine cytoplasmic granules also demonstrated similar nuclear enlargement, hyperchromasia, and pleomorphism (Fig 5). These latter cells stained strongly with CD68, a macrophage marker, but the spindle cells did not stain. There was no trapping of cortical or lamellar bone or infiltration into the Haversian canals. There was a discrepancy between nuclear anaplastic features, which suggested malignancy, and the low cellularity, sparse mitoses, and the imaging studies, which suggested benignancy. Because the accompanying macrophages demonstrated similar nuclear change, we interpreted the nuclear features as "pseudoanaplastic," probably caused by ischemia, and categorized the lesion as a pseudoanaplastic "ancient" fibrous cortical defect. Postoperatively, the case was followed by serial radiographs. There was slow resolution of the lesion, with gradual disappearance of the pain. At 25 months after biopsy, only a cortical scar remains on radiographs.

Fibrous cortical defects are usually found incidentally in young children or adolescents; typically are 1 to 3 cm in maximum dimension; are eccentric, juxta, or intracortical; metaphyseal to metadiaphyseal in location; are longer than they are wide; have a lucent center and peripheral border of sclerosis; are composed of variably cellular fibrous tissue; and usually spontaneously resolve. 1 Persistence with proliferative extension into the medullary cavity represents transition of a fibrous cortical defect into a nonossifying fibroma.l,2 There are many examples of soft tissue pseudosarcomas, such as nodular fasciitis, proliferative myositis, and myositis ossificans. These have well-defined clinical, imaging and histological characteristics, but may be confused for malignancy based on cellularity, nuclear hyperchromasia, and failure to recognize the distinct pattern by the unwary pathologist. Pseudosarcomas of the bone are also described, but are less common. An example is pseudomalignant osteoblastoma,3 which, although histological features are described, the diagnosis still requires clinical and radiological support. Much more common in bone pathology is the malignancy masquerading as a benign process because of normalization of the nuclei and the lack of appreciation of the aggressive nature demonstrated by imaging studies.

Figure 2. Tl-weighted coronal magnetic resonance image of the proximal femur shows the space-occupying lesion replacing the marrow with a rim of reactive bone around it.

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Craver, Heinrich, a n d Mirra

Figure 3. Computerized tomographic evaluation shows an intracortical geographic radiolucency with sclerotic bone at the margin. This pattern of destruction suggests a benign lesion,

Figure 4. Within the marrow space are several large cells with pleomorphic hyperchromatic nuclei.

Fibrous Cortical Defect With Bizarre Nuclei

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Figure 5. Foamyhistiocytes demonstrate similar pseudoanaplastic nuclear changes.

Clues to benignancy in this case were multiple. The chronic changes of the radiograph did not correlate with the anaplastic cytological features of the nuclei. Most tumors (including osteosarcomas) with this degree of anaplasia pursue an aggressive course, reflected radiographically by permeative or moth-eaten bone destruction. In this case, only one mitosis was found, and it was normal. Most anaplastic tumors are mitotically active with abnormal forms. This lesion's cellularity was low. Most anaplastic tumors have high cellularity. Other aggressive malignant features such as entrapment of normal bone, permeation of the Haversian canals, and necrosis were also absent. Finally, and perhaps most importantly, the nuclear changes were not restricted to the spindle cells, but also affected resident macrophages. The differential diagnosis in this woman included intracortical osteosarcoma. These lesions typically have a radiolucent center, an intense periosteal reaction, no thick rind of sclerosis on the intracortical surface, permeation of the Haversian canals, and demonstrate abundant sclerotic osteoid, all with a conspicuous lack of nuclear atypia.4-7Fracture callus may mimic a sarcomatous process, usually in the florid reparative phase, and may be superimposed on other benign (and malignant) lesions. 8 This lesion was most likely an old, "ancient," fibrous

cortical defect, with generalized nuclear changes reflecting ischemic degeneration. Similar degenerative pseudoanaplastic lesions have been encountered in other bony lesions---osteoblastomas,3 aneurysmal bone cysts, 1chondromyxoid fibromas, 9 giant cell tumors, 1 and chondroblastomas. 1° Pseudoanaplasia may also follow radiation, a factor not present in this woman. Because initially there was some uncertainty about the biological behavior, we chose to follow this case closely. If the lesion was malignant, then, most likely based on the abnormal nuclear features, it would be of higher grade, and it would recur quickly. With close follow-up, recurrence would be detected early before development of metastasis, and essentially no advantage would be lost by waiting. Close observation saved her from further debilitating surgery and complications of chemotherapy for a benign lesion. In summary, we describe a lesion with a benign radiographic appearance with pseudoanaplastic cytological nuclear features. We were able to treat this pseudoanaplastic tumor conservatively because of the communication among the pathologist, radiologist, and orthopedic surgeon. This allowed close clinical and radiographic follow-up for a lesion that, at the time, the biologic had unknown behavior. This close cooperation was rewarded by an optimal patient outcome.

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Craver, Heinrich, and Mirra References

1. Mirra JM: Bone Tumors: Clinical, Radiologic, and Pathologic Correlation. Philadelphia, PA, Lea & Febiger, 1989, pp 692-719, 1302, 979-980 2. Magliato HJ, Nastri A: Non-osteogenic fibroma occurring in the ilium. Report ofa case.J Bone Joint Surg (Am) 1967;49:384-386 3. MirraJM, Kendrick RA, Kendrick RE: Pseudomalignant osteoblastoma versus arrested osteosarcoma. A case report. Cancer 1976;37: 2005-2014 4. Jaffe HL: Intracortical osteogenic sarcoma. Bull Hospital Joint Dis (Orthop Inst) 1960;21:189-197 5. KyTiakos M: Intracortical osteosarcoma. Cancer 1980;46:25252533.

6. Picci P, Gherlinzoni F, Guerra A: Intracortical osteosarcoma: Rare entity or early manifestations of classical osteosarcoma? Skeletal Radiol 1983;9:255-258 7. Vigorita VJ, Ghelman B, Jones J, et al: Intracorticai osteosarcoma. AmJ Surg Pathoi 1984;8:65-71 8. Kahn LB, Wood FW, Ackerman LV: Fracture callus associated with benign and malignant bone lesions and mimicking osteosarcoma. AmJ Clin Pathol 1969;52:14-24 9. Zillmer DA, Dorfman HD: Chondromyxoid fibroma of the bone: Thirty-six cases with clinicopathologic correlation. Hum Pathol 1989; 20:952-964 10. Kurt AM, Unni KK, Sim FH, et al: Chondroblastoma of bone. Hum Pathol 1989;20:965-976