Lesion of the Right Proximal Tibia in a 12-Year-Old Boy (2004)

LEARNING OBJECTIVES On completion of this study, the reader should be able to: differentiate benign fibrous lesions from malignancies on the basis of radiographic presentation and histology, describe the histologic basis of multifocal lesions, plan appropriate therapy on the basis of the histologic diagnosis. A ×12-year-old boy was referred for evaluation of a painless swelling at the right tibia without any history of trauma. His medical history was insignificant. The swelling first had been noticed 5 months before. Conservative treatment with nonsteroidal antiinflammatory drugs and cryotherapy was done because of progression of the swelling; however, the patient did not respond to this treatment. Physical examination showed a 3×3 cm solid, immovable resistance at the right proximal lateral tibia. There was warmth without erythema in this area. Motoric, sensorial, and vascular status were normal. The knee had full ROM. The patient did not have constitutional symptoms such as fever, night sweats, or weight loss. There was no inguinal lymphadenopathy. Blood tests including differential blood count, electrolytes, lactate dehydrogenase, uric acid, coagulation, and liver and kidney parameters were normal. The blood sedimentation rate was 10 to 20. Plain radiographs and MRI scans were obtained (Figs. 1–3). Based on the history, physical examination, and laboratory and imaging studies what is the differential diagnosis?FIGURE 1.: A–B. (A) Anteroposterior and (B) lateral radiographs of the right tibia.FIGURE 2.: A–B. Magnetic resonance imaging scans reveal (A) low signal intensity on T1-weighted and (B) marked contrast enhancement on T2-weighted images.FIGURE 3.: Magnetic resonance imaging scan in the transversal plain.RADIOGRAPHIC INTERPRETATION Anteroposterior and lateral radiographs of the right tibia show a well-defined multilobulated lucency approximately 3.5 cm in maximal diameter, which is located at the proximal metaphyseal-diaphyseal junction. The lateral and anterior cortex of the tibia shows endostal scalloping with ill-defined lucency of compact bone in this area. A soft tissue mass can be identified anteriorly (Fig. 1). On the MRI scans, a well-defined multilobulated lesion can be delineated, showing an inhomogeneous shape with low-signal intensity on T1-weighted images, mixed hypointensity and hyperintensity on T2-weighted images and marked contrast enhancement with sparing of round, cyst-shaped areas on T1-weighted images (Fig. 2). The surrounding bone marrow is normal, in particular no edema is present. There is broad extension of tumor into the anterior soft tissues forming a broad-based extraskeletal tumor mass approximately 3 cm in diameter (Fig. 3). DIFFERENTIAL DIAGNOSIS Ewing sarcoma Lymphoma Adamantinoma Osteofibrous dysplasia Nonossifying fibroma Aneurysmal bone cyst Histiocytosis An incisional biopsy was done for histologic analysis (Fig. 4).FIGURE 4.: A–B. Photomicrograph of the resected specimen. (A) Stain, Hematoxylin and eosin; magnification, ×100. (B) Immunohistochemistry Lu 5, magnification, ×100).Based on the history, physical examination, laboratory and imaging studies, and histologic findings, what is the diagnosis and how should this lesion be treated? See page 267 for diagnosis and treatment. HISTOLOGIC EVALUATION The histologic examination showed a biphasic tumor with many epithelial elements within spindle-shaped mesenchymal stroma. The most frequent pattern consisted of basaloid nests with a peripheral layer of cells positioned perpendicular to the inner masses of cells. The surrounding stroma was rich of collagen fibers with rare capillaries. There was fluent transition between fibrous netlike pattern and tumor areas with high cell density. The epithelial cells are strongly positive for cytokeratin and for the epithelial markers anticytokeratin antibody CAM 5.2 and the antipancytokeratin antibody MNF 116, vimentin, and immunhistochemistry Lu 5 (Fig. 4A–B). DIAGNOSIS The histologic evaluation revealed a classic adamantinoma with different patterns of the epithelial nests within a fibrous stroma. TREATMENT AND DISCUSSION Adamantinoma, first described by Fischer4 in 1913, is an extremely rare bone tumor, representing less than 1% of all malignant bone tumors.13 Fischer reported that the tumor was somewhat similar to a more common odontogenic adamantinioma of the jaw bone. However, despite histologic similarity, there was no proof that the jaw bone and the long bone adamantinioma have a similar histiogenetic origin. The last review published in 1986 reported that there were approximately 200 well-documented cases in the literature.15 The typical history of the lesion is that of a slow-growing, locally destructive tumor that may continue for years before it is diagnosed. The tumor is of low-grade malignancy5,6 in terms of biologic aggressiveness (long duration of symptoms) and it affects predominantly the tibia or fibula or both. Synchronously involvment of tibia and fibula is seen in approximately 50% of patients.3 The tumor also may develop in the ulna, femur, humerus, radius, and rib.19 Classic adamantinoma typically affects patients older than 20 years, occasionally occurs in patients between 10 and 20 years, and very rarely is seen in children younger than 10 years.3 Classic adamantinoma is locally aggressive and has a high rate of recurrence after local excision.3,15 Metastasis of adamantinoma has been reported in 15% to 20% involving a long bone16,23,24 with the common sites of secondary spread being the inguinal nodes, lung, or other bones.10,15,16 Widespread metastasis is very uncommon.24 In two series of 200 patients analyzed by Moon14 and Moon and Mori,15 29 patients died of metastatic disease. Their average survival time was 5.4 years, with a range from 5 months to 22 years. For the diagnosis, benign and malignant lesions have to be considered. In addition to the current differential diagnosis that included nonossifying fibroma, aneurysmal bone cyst, histiocytosis, osteofibrous dysplasia, Ewing’s sarcoma, and lymphoma also unicameral bone cysts, giant cell tumors, and eosinophilic granulomas comprise the majority of such lesions. Cystic lesions in childhood usually are benign. A nonossifying fibroma is one of the most common fibrous lesions in the tibia. Nonossifying fibroma is an excentric osseous lesion and always has a clear connection to the corticalis. The border to the bone marrow is polycyclic, the cortex of the bone is thinned and occasionally may show a bowing of the affected cortex. The typical location of nonossifying fibroma is in the metaphysis. If the defect is large nonossifying fibromas also can be found in the diaphysis. Ritschl et al.18 described that the location of nonossifying fibroma is in the axial extension of the attachment of tendons or tendonlike structures at the perichondrium of the epiphyseal cartilage. In the current patient, the tumor is located in the diaphysis, centric in the AP and lateral projections and without typical cortical thinning. Instead a cortical breakthrough is present. Aneurysmal bone cyst also can be located in the metaphysis or diaphysis. Two forms of aneurysmal bone cyst can be seen radiologically. The subperiostal form occurs usually in the metaphysis and the diaphysis, and the central aneurysmal bone cyst almost always occurs in the metaphysis. Despite its central location aneurysmal bone cysts are located excentrically and have a connection to the corticalis in one plane (AP or lateral) and often show an aneurysmatic aspect. Magnetic resonance imaging scans reveal fluid-fluid levels in most cases even in the solid forms of aneurysmal bone cyst. Histiocytosis or eosinophilic granuloma occurs as an osteolytic lesion that affects spongiosa and corticalis. They usually are seen central but an eccentric location is possible. The osteolysis is homogeneous, the configuration is round to polycyclic. The borders are well-defined so that in the current case the radiologic evaluation and the patient age would confirm the diagnosis. On MRI scans, histiocytosis or eosinophilic granuloma is surrounded by bone marrow edema, which was not seen in the current case. Ewing’s sarcoma and lymphoma are malignant lesions that show a destructive osseous pattern, such as infiltration, cortical erosion or periostitis. On MRI scans, a mixed signal “bowl of fruit” or storiform appearance with signs of hemorrhage is common. Extensive perifocal bone marrow edema and a large soft tissue component usually are present. The radiographic, histologic, and clinical findings show similarities in osteofibrous dysplasia, osteofibrous dysplasialike adamantinoma, and classic adamantinoma2,3 (Table 1). Osteofibrous dysplasia and osteofibrous dysplasialike adamantinomas (differentiated adamantinoma)3 are confined to the cortex in most patients, whereas in patients who have classic adamantinoma, soft tissue or intramedullary involvement is observed regularly.6,7 Classic adamantinoma is characterized by an abundance of tumor cells and a destructive growth pattern radiographically. Cystic and sclerotic areas are visible. Radiographs show sharply outlined, radiolucent areas that may be multiple and separate within the same bone. Adamantinoma typically affects patients older than 20 years, but occasionally may occur during the first two decades of life. The involved bones usually are the tibia, the fibula or both, but involvement of other long bones or skeletal sides has been reported. Immunohistochemistry reveals a predominance of cytokeratin cytokeratin positive cells. Metastasis is possible.3,5,6Table 1: Differences Between Classic Adamantinoma, Differentiated Adamantinoma, and Osteofibrous DysplasiaDifferentiated adamantinoma is characterized histologically by a predominance of an osteofibrous dysplasialike pattern with a small, inconspicuous component of epithelial tumor elements. Immunhistochemistry shows scattered elements positive for cytokeratin. On radiographs, differentiated adamantinoma usually are intracortical, often multicentric, with cystic and sclerotic areas and occurs before the age of 20 years. Followup data suggest no metastatic potential.3 When technically feasible, wide en bloc resection and reconstruction is considered to be the procedure of choice for the treatment of classic and differentiated adamantinoma.5,6,20 Osteofibrous dysplasia shows no epithelial cells and the radiographically appearance always is intracortical. It affects only the long bones, usually during the first decade of life. The treatment is conservative or intralesional resection. According to the radiographic appearance, adamantinomas can be divided into two major groups: intracortical or with radiologic evidence of complete cortical disruption and involvement of the medullary cavity. In the tibia, involvement of the anterolateral cortex and the presence of a moderate to severe bowing deformity are typical. Dorfman and Czerniak3 suggested that the differentiated type of adamantinoma and the osteofibrous dysplasia may represent different stages of the same process, namely a reparative mechanism transforming the intracortical adamantinoma into a osteofibrous dysplasia. Other authors also suggested that osteofibrous dysplasia, differentiated adamantinoma, and classic adamantinoma are part of the same morphologic spectrum.6,7,11,21 These differences should be taken into account when the biopsy specimen is interpreted. However, focal expansion into the surrounding tissue should be a warning signal because the more the tumor progresses, the more aggressive it becomes.4 The histogenesis of adamantinomas is a matter of continous debate. The bone neoplasm is striking because of its morphologic diversity, which mimics various primary and metastatic bone and softtissue lesions.23 The low prevalence of the lesion, which accounts for only 0.1% to 0.3% of all primary bone tumors and the paucity of long-term followup data have made predictions of clinical behavior difficult but today adamantinomas are regarded as a slow-growing, locally destructive tumor with a high recurrence rate after local excision.3,5,6 Cytogenetic studies revealed translocation in tumor tissue. It is evident that adamantinomas of long bones present complex chromosomal abnormalities with multiple translocations and some extra chromosomes.1,12,20 The origin of those cells with epithelial phenotype still is unknown, although several reports gave information to the histologic, immunhistochemic, and biologic characteristics of the tumor.3,6,17,18 The histiologic patterns of adamantinoma are extremely variable within each case and among cases. Basic patterns are: basaloid, spindle, tubular, and squamoid.3 Classic adamantinoma tumor cells of basaloid, spindle, tubular, and squamoid patterns are consistently strongly positive for keratin.9 The fibrous stroma and the bone trabeculae of the differentiated adamantinoma (osteofibrous dysplasialike) pattern are negative for keratin; however, small nests of epithelial cells and tubular structures scattered in the stromal tissue are strongly positive for keratin. The classic adamantinomas are characterized microscopically by the abundance of tumor cells and a frequent mixture of several histologic patterns. The pattern of the differentiated adamantinomas never dominates the histologic picture. The treatment of adamantinoma is controversial. Although a few patients have been reported to respond to radiotherapy15 several authors recommended surgical treatment of the lesion.5,6,23 Intralesional and marginal treatments such as curettage or excision without a border of normal tissue usually are unsuccessful and often lead to recurrence. Wide excision was recommended as the treatment of choice8,16,22 but amputation also is recommended because of the malignant potential of this tumor especially in cases of local recurrences, failures of reconstruction, or lesions with large soft tissue component.5 The current authors think that initial treatment should be wide excision when technically feasible and that all patients should have long-term followup for the potential development of metastatic disease. In the current case, wide local resection left a gap of 12 cm, which presented a difficult reconstructive problem in a major weightbearing bone. Reconstruction options included a segmental prosthesis, an intercalary allograft, and ipsilateral or contralateral, vascularized or nonvascularized fibular grafts. A wide excision was done covering the previous biopsy tract. For reconstruction of the bone defect, the ipsilateral vascularized fibular and the contralateral nonvascularized fibula were used. The ipsilateral fibula was mobilized on its vascular pedicle and transferred into the defect. The ends of the graft were placed within the medullary canal in telescope fashion reconstructing the tibial length. A plate was applied laterally with two screws above the defect and three screws below the defect. The contralateral fibula was added medially by impacting the proximal part inside the medullary canal and applying the distal end to the tibial cortex by screw fixation. Homologious spongiosa were added. After surgery, a long leg cast was applied. Five months after surgery, the cast was replaced by a brace. The patient wore this brace permanently and gradually progressed to partial weightbearing. At 7 months followup, the patient was asymptomatic and had advanced healing of the defect without any obvious sign of recurrence.