DOI: 10.1148/rg.284075173
RadioGraphics 2008;28:1215-1220
© RSNA, 2008
Best Cases from the AFIP
Adamantinoma of the Tibia and Fibula with Cytogenetic Analysis1
Morgan D. Camp, MD,
Ryan K. Tompkins, MD,
Suzanne S. Spanier, MD,
Julia A. Bridge, MD, and
Charles H. Bush, MD
1 From the Departments of Radiology (M.D.C., R.K.T., C.H.B.) and Pathology (S.S.S.), University of Florida and Shands Hospital, 3450 Hull Rd, Gainesville, FL 32609; and the Department of Pathology, Nebraska Medical Center, Omaha, Neb (J.A.B.). Received August 15, 2007; revision requested September 10 and received October 23; accepted October 25. J.A.B. supported in part by a UNMC College of Medicine Educational Support Grant.
Address correspondence to M.D.C. (e-mail: mocamp1{at}yahoo.com).
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History
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An 18-year-old woman presented with worsening pain in her left shin and calf after local trauma. After the injury, she was unable to bear weight on the limb. She reported a 1-year history of intermittent, crampy left shin pain, which worsened with activity and occasionally awoke her at night. Physical examination revealed a tender contour deformity along the anterior left tibia.
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Imaging Findings
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Radiography of the lower leg revealed a mildly expansive, mixed lytic, and sclerotic lesion involving a long portion of the mid to distal tibial diaphysis (Fig 1a, 1b). There was no cortical breakthrough, periosteal reaction, or soft-tissue mass seen. There was, however, a subtle lucent lesion in the distal fibular diaphysis (Fig 2a).
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Figure 1a. (a, b) Anteroposterior (a) and lateral (b) radiographs of the left tibia and fibula demonstrate an elongated multilocular lesion with no periosteal reaction or cortical breakthrough. Note the endosteal scalloping (arrow); cortical remodeling; and the narrow zone of transition, which correlates with the indolent nature of the lesion. (c) Photograph of the tibia sectioned in the parasagittal plane shows the neoplasm filling the medullary canal and expanding the cortex, especially where the endosteal scalloping is most prominent (arrow). The hemorrhagic area in the center of the mass corresponds to the biopsy site.
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Figure 1b. (a, b) Anteroposterior (a) and lateral (b) radiographs of the left tibia and fibula demonstrate an elongated multilocular lesion with no periosteal reaction or cortical breakthrough. Note the endosteal scalloping (arrow); cortical remodeling; and the narrow zone of transition, which correlates with the indolent nature of the lesion. (c) Photograph of the tibia sectioned in the parasagittal plane shows the neoplasm filling the medullary canal and expanding the cortex, especially where the endosteal scalloping is most prominent (arrow). The hemorrhagic area in the center of the mass corresponds to the biopsy site.
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Figure 1c. (a, b) Anteroposterior (a) and lateral (b) radiographs of the left tibia and fibula demonstrate an elongated multilocular lesion with no periosteal reaction or cortical breakthrough. Note the endosteal scalloping (arrow); cortical remodeling; and the narrow zone of transition, which correlates with the indolent nature of the lesion. (c) Photograph of the tibia sectioned in the parasagittal plane shows the neoplasm filling the medullary canal and expanding the cortex, especially where the endosteal scalloping is most prominent (arrow). The hemorrhagic area in the center of the mass corresponds to the biopsy site.
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Figure 2a. (a) Collimated anteroposterior radiograph of the distal left tibia and fibula reveals the distal extent of the tibial mass. An ill-defined, lucent lesion (arrow) with surrounding reactive bone in the distal fibular diaphysis is also seen. (b) Gross pathologic photograph of the distal fibula, sectioned in the parasagittal plane, shows the focal fibular lesion (arrow), which corresponds with the abnormality seen on radiographs.
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Figure 2b. (a) Collimated anteroposterior radiograph of the distal left tibia and fibula reveals the distal extent of the tibial mass. An ill-defined, lucent lesion (arrow) with surrounding reactive bone in the distal fibular diaphysis is also seen. (b) Gross pathologic photograph of the distal fibula, sectioned in the parasagittal plane, shows the focal fibular lesion (arrow), which corresponds with the abnormality seen on radiographs.
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Magnetic resonance (MR) imaging showed an 18-cm multilobulated lesion, which was centered longitudinally in the mid to distal tibial diaphysis. The lesion was slightly hyperintense relative to muscle on T1-weighted images, was hyperintense relative to muscle on short inversion time inversion recovery (STIR) fat-suppressed images, and enhanced homogeneously with intravenous administration of gadodiamide. The extensive intramedullary component of the neoplasm replaced the bone marrow (Fig 3). Furthermore, enhancing tissue was visualized within the remodeled cortex (Fig 4). The 3-mm fibular lesion was localized in the anterior cortex and showed signal intensity similar to that of the tibial lesion.
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Figure 3a. Axial T1-weighted (a) and sagittal STIR (b) MR images demonstrate the multilobulated, longitudinally oriented mass in the left tibia that is obliterating the medullary cavity. Note the circumferential cortical involvement and that the mass is displacing the medullary cavity by intracortical expansion. These findings closely correlate with the appearance of the sectioned tibia (cf Fig 2b), where the yellow marrow is displaced by the neoplastic tissue. There is no cortical breakthrough, soft-tissue masses, or satellite lesions
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Figure 3b. Axial T1-weighted (a) and sagittal STIR (b) MR images demonstrate the multilobulated, longitudinally oriented mass in the left tibia that is obliterating the medullary cavity. Note the circumferential cortical involvement and that the mass is displacing the medullary cavity by intracortical expansion. These findings closely correlate with the appearance of the sectioned tibia (cf Fig 2b), where the yellow marrow is displaced by the neoplastic tissue. There is no cortical breakthrough, soft-tissue masses, or satellite lesions
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Figure 4a. Axial T1-weighted MR images of the left tibia before (a) and after (b) administration of contrast material demonstrate homogeneous enhancement of the tibial mass, which is causing extensive cortical remodeling. Note the intracortical, enhancing neoplastic tissue (arrow).
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Figure 4b. Axial T1-weighted MR images of the left tibia before (a) and after (b) administration of contrast material demonstrate homogeneous enhancement of the tibial mass, which is causing extensive cortical remodeling. Note the intracortical, enhancing neoplastic tissue (arrow).
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A three-phase technetium 99m (99mTc) methylene diphosphonate radionuclide bone scan study demonstrated focal, increased radiotracer uptake in the tibial lesion on flow, blood pool, and delayed images. No other abnormalities were seen on the bone scan (Fig 5). Interestingly, no increased uptake was seen within the fibular lesion, which was likely due to its small size.
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Figure 5. Delayed 99mTc methylene diphosphonate bone scan demonstrates a vertically oriented region of increased radiotracer uptake, which corresponds to the left tibial mass. No other lesions were seen on the whole-body scintigraphic images.
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Pathologic Evaluation
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Results of an incisional biopsy of the tibial lesion demonstrated adamantinoma. Macroscopic inspection revealed a white to pale yellow neoplasm, which had a firm to gritty texture. The neoplasm filled the medullary cavity and appeared to be contained by an intact cortex. The tumor was 18 cm in length and up to 2.2 cm in width. It was well delineated, with its proximal extent 5.3 cm distant to the surgical margin (Fig 1c). In the sectioned fibula, there was a 3-mm area of a pale-gray soft tissue with ill-defined cortical thickening (Fig 2b). There was no tumor present in the soft tissues.
Findings from the microscopic examination confirmed that the tibial neoplasm was contained by a cortex of actively remodeling bone. Remnants of the original cortex were found deep within the medullary canal, a finding consistent with an intracortical origin (Fig 6). The tissue of the lesion consisted of epithelial elements in various patterns embedded in a benign fibrous background (Fig 7). There was a zonal architecture, in which mature, nonneoplastic reactive tissues were found predominantly in the periphery of the lesion, and the diagnostic epithelial tissues were toward the center. The neoplastic epithelial tissue was positive for cytokeratins (Fig 7).
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Figure 6. Photomicrograph (original magnification, x100; hematoxylin-eosin [H-E] stain) of the tibial neoplasm demonstrates a cortical remnant trapped deep within the medullary cavity, a finding consistent with an intracortical origin. Note the resorption by osteoclasts along the lower border (arrow).
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Figure 7. Photomicrograph (original magnification, x100; H-E stain) of the tibial neoplasm shows scattered nests (arrowhead) and islands (arrow) of the diagnostic epithelial cells on a fibrous background, an appearance that illustrates the spindle cell pattern. Photomicrograph (insert, with original magnification, x100) of a representative island of epithelial cells was positive for cytokeratin AE 1/AE 3 staining.
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Cytogenetic Analysis
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Conventional cytogenetic analysis on a representative sample from the tibia revealed extra copies of chromosomes 7, 10, 12, 13, 19, and 21 in the primary clone with additional structural abnormalities in three subclones. (Fig 8). Thirteen analyzed metaphase cells were karyotypically normal (1).
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Figure 8. Representative karyotype from the tibia demonstrates extra copies of chromosomes 7, 10, 12, 13, and 19 (short arrows). Note that chromosomes 19 and 21 are translocated (long arrow). Cytogenetic analysis: 52,XX,+7,+10,+12,+13,+19,+21[3]/51, sl,der(16)t(16;21)(p13.3;q11.2), –21[2]/51,sl,der(17) t(17;21)(p12;q11.2), –21[1]/50,sl,der(19)t(19;21) (p13.3;q11.2), –21[1].
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Discussion
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Adamantinoma was first observed in the shaft of an ulna in 1900 by Maier (2), who believed it was a carcinoma. The name adamantinoma was actually given by Fisher (3) in his report of a tibial neoplasm that was microscopically similar to the adamantinoma of the jaw. Adamantinoma represents less than 0.5% of malignant bone tumors (4). It is a low-grade malignancy and has a strong predilection for the tibia and fibula of patients in the second and third decades of life, but the age range extends from 3 to 74 years (5,6).
At imaging, adamantinoma appears as a well-circumscribed, slightly expansile lesion, usually with a narrow zone of transition, a finding consistent with its indolent nature. It is often multilocular, with sclerosis and lysis seen in a "soap bubble" pattern (7). The lesion is typically oriented longitudinally along the anterior tibial diaphysis, with an average length of 10 cm (4,7). Synchronous fibular involvement has been reported in 5%–10% of cases (4,6), and cortical breakthrough is seen in 15% of cases (5).
MR imaging is the best modality for delineating the extent of adamantinoma in the medullary cavity, soft tissues, and satellite lesions. These tumors typically demonstrate intermediate signal intensity relative to muscle on T1-weighted images and intensity similar to that of fat on T2-weighted images obtained without fat saturation. Static-enhanced images demonstrate intense homogeneous enhancement within the lesion. In a study of 22 patients with adamantinomas, 27% demonstrated multicentricity within the same bone, which was best visualized on MR images (8).
At microscopic examination, adamantinoma is composed of neoplastic epithelial cells within an osteofibrous stroma. The epithelial cells are consistently reactive to cytokeratins (9,10). Many adamantinomas have a zonal architecture in which the diagnostic epithelial elements are concentrated toward the center of the neoplasm and the fibroblastic tissue occupies the periphery. Therefore, peripheral tissue samples may not include the diagnostic epithelial elements of the tumor (11).
Although it is usually indolent, adamantinoma can be aggressive. Risk factors for a more malignant course include: male sex, young age at presentation, a short duration of symptoms, pain at initial presentation, and a local recurrence (5,6). In a series of 70 patients who underwent wide, local limb-sparing resections at 23 cancer centers, the local recurrence rate was 19% and the mortality rate was 13% (12). Radiation therapy and chemotherapy are of limited use (4). Long-term follow-up is required to screen for late metastases. In our patient, a below-the-knee amputation was performed, and computed tomography (CT) of the chest performed at the 19-month follow-up examination demonstrated no metastatic disease.
The primary differential diagnosis for adamantinoma of a long bone includes osteofibrous dysplasia and differentiated adamantinoma.
Osteofibrous dysplasia, described by Companacci (13) in 1976, occurs almost exclusively within the diaphyseal cortex of the tibia or fibula of infants and children under the age of 10 years. Most patients present with painless enlargement of the tibia, a finding usually associated with anterior bowing or a pathologic fracture. On radiographs, osteofibrous dysplasia is characterized by areas of eccentric cortical lucency and expansion, which may appear as a focal lucent area or as multiple "bubbles." At microscopic examination, the lesion is composed of fibrous tissue that contains bone trabeculae bordered by osteoblasts arranged in a zonal pattern, with the most mature spicules at the periphery (13). Epithelial cells are not seen with routine H-E staining, but in most cases isolated epithelial cells may be detected with cytokeratins (4,10,14,15). These lesions have little tendency to progress; in fact, they frequently spontaneously regress. If they are resected before the patient reaches 5 years of age, the lesions tend to recur. In patients older than 10 or 12 years of age, however, most lesions stabilize or regress (13,16). In most large series, the prognosis is good (4,13,14,16,17).
Differentiated adamantinoma , also known as osteofibrous-like or juvenile adamantinoma, is a term that was introduced by Czerniak et al (9) in 1989 to describe a group of eight tumors culled from a review of 25 cases of adamantinoma. These tumors were distinguished by the patient’s age (20 years or younger); their strictly intracortical location; and the uniform predominance of an osteofibrous dysplasia–like tissue, which contained only small nests of epithelial cells that were visible with H-E staining (9). Although the majority of these tumors appear to have a benign course (4), there are at least two well-documented cases in which adamantinoma evolved from thoroughly curetted lesions that were initially diagnosed as osteofibrous dysplasia–like adamantinoma (11,18). In a third patient, whose resected tumor was diagnosed as differentiated adamantinoma, there was radiographic progression over a 4.5-year period (19).
Because of the overlapping clinical demographics, radiologic findings, microscopic characteristics, and immunohistochemical properties, the notion of a spectrum of fibro-osseous lesions has been suggested. In this scheme, adamantinoma is on the malignant end of a continuum relative to differentiated adamantinoma, which is in the middle, and osteofibrous dysplasia, which is on the benign end (14,15,16,18,20). Some unresolved issues are the relationship of these lesions to one another, whether osteofibrous dysplasia can progress to adamantinoma, and whether osteofibrous dysplasia and differentiated adamantinoma represent regression of adamantinoma (9,18). In this regard, the cytogenetic evidence linking these lesions is most interesting: Extra copies of one or more of chromosomes 7, 8, 12, 19, or 21 have been found in all but one case of adamantinoma and in one case of differentiated adamantinoma (18,19). Extra copies of one or more of these same chromosomes (except for chromosome 19) have been found in osteofibrous dysplasia (20). In addition to trisomy 19, certain structural abnormalities, including translocation, inversion, and marker chromosomes, have been reported in adamantinoma and in differentiated adamantinoma, but not in osteofibrous dysplasia. These findings suggest that adamantinoma is more karyotypically complex than osteofibrous dysplasia. It is conceivable that the expansion of an abnormal clone might lead osteofibrous dysplasia to progress to adamantinoma (19).
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Acknowledgments
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The authors thank Robert Foss for his work in producing the photographs and photomicrographs of the tumor used in the manuscript.
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Footnotes
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Abbreviations: H-E = hematoxylin-eosin, STIR = short inversion time inversion recovery
Editor’s Note.—Everyone who has taken the course in radiologic pathology at the Armed Forces Institute of Pathology (AFIP) remembers bringing beautifully illustrated cases for accession to the Institute. In recent years, the staff of the Department of Radiologic Pathology has judged the "best cases" by organ system, and recognition is given to the winners on the last day of the class. With each issue of RadioGraphics, one or more of these cases are published, written by the winning resident. Radiologic-pathologic correlation is emphasized, and the causes of the imaging signs of various diseases are illustrated.
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References
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- Ishida T, Iijima T, Kikuchi F, et al. A clinicopathological and immunohistochemical study of osteofibrous dysplasia, differentiated adamantinoma, and adamantinoma of long bones. Skeletal Radiol 1992;21(8):493–502.[Medline]
- Campanacci M, Laus M. Osteofibrous dysplasia of the tibia and fibula. J Bone Joint Surg Am 1981;63 (3):367–375.[Abstract/Free Full Text]
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- Hazelbag HM, Wessels JW, Mollevangers P, van den Berg E, Molenaar WM, Hogendoorn PC. Cytogenetic analysis of adamantinoma of long bones: further indications for a common histiogenesis with osteofibrous dysplasia. Cancer Genet Cytogenet 1997;97(1):5–11.[CrossRef][Medline]
- Kanamori M, Antonescu CR, Scott M, et al. Extra copies of chromosomes 7, 8, 12, 19, and 21 are recurrent in adamantinoma. J Mol Diagn 2001;3(1): 16–21.[Abstract/Free Full Text]
- Bridge JA, Dembinski A, DeBoer J, Travis J, Neff JR. Clonal chromosomal abnormalities in osteofibrous dysplasia. Cancer 1994;73(6):1746–1752.[CrossRef][Medline]
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History
Imaging Findings
