You are in: eMedicine Specialties > Orthopedic Surgery > NEOPLASMS Telangiectatic OsteosarcomaArticle Last Updated: Jan 18, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 7
  Author: Nirag C Jhala, MD, MBBS, MIAC, Associate Professor, Department of Pathology, University of Alabama School of Medicine; Consulting Staff, Department of Pathology, University of Alabama Hospitals and Birmingham VA Medical Center Nirag C Jhala is a member of the following medical societies: American Society of Cytopathology, Biomedical Engineering Society, College of American Pathologists, International Academy of Cytology, and United States and Canadian Academy of Pathology Coauthor(s): Gene P Siegal, MD, PhD, Director, Division of Anatomic Pathology, Professor, Departments of Pathology and Surgery, University of Alabama at Birmingham; Donald Hackbarth, MD, FACS, Director of Musculoskeletal Oncology, Associate Professor, Department of Orthopaedic Surgery, Medical College of Wisconsin; Stuart Wong, MD, Assistant Professor, Department of Medicine, Section of Hematology/Oncology, Froedert Memorial Lutheran Hospital; Vinod B Shidham, MD, FRCPath, FIAC, Associate Professor, Director of FNAB Service, Director of Cytopathology Fellowship Training Program, Coeditor-in-chief of CytoJournal, Department of Pathology, Medical College of Wisconsin Editors: Miguel A Schmitz, MD, Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports Medicine Clinic; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Sean P Scully, MD, PhD, Professor, Department of Orthopedics, University of Miami; Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital; Harris Gellman, MD, Consulting Surgeon, Broward Hand Center, Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine Author and Editor Disclosure Synonyms and related keywords: primary malignant bone tumor, osteosarcoma variant, lytic mass lesion in long bone metaphysis INTRODUCTIONSection 2 of 7
  Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. When first recognized, telangiectatic osteosarcoma was proposed to be a distinct clinical and pathologic entity.1 On the basis of subsequent findings that provided a better understanding of the condition's presentation and prognostic implications, telangiectatic osteosarcoma should be considered a variant of osteosarcoma. Telangiectatic osteosarcoma appears as a painful, radiographically lytic mass lesion in the metaphyseal portion of the long bones. It is characterized by dilated, blood-filled vascular spaces lined by malignant osteoblasts. These osteoblasts are separated by fibrous septa, which contain the malignant cells, multinucleated giant cells, and tumor osteoid. FrequencyAs an uncommon variant of osteosarcoma, telangiectatic osteosarcoma accounts for 0.4-12% of all osteosarcomas.2, 3, 4, 5 EtiologyBecause of the rarity of this lesion, the etiologic factors that promote malignant transformation have not been extensively investigated. Telangiectatic osteosarcomas are presumed to originate from transformed osteoblasts or from stem cells that are of mesenchymal derivation. Results from transmission electron microscopic examination show that, in addition to undifferentiated osteoblastlike and fibroblastlike tumor cells, angiosarcomatous elements may be observed in this malignant bone tumor. Endothelial, cell-like structures, including pinocytotic vesicles, tight intercellular junctions, fine fibrils, and Weibel-Palade bodies, are seen in the cytoplasm of these cells.6 Such observations suggest that telangiectatic osteosarcoma may be derived from multipotential mesenchymal cells, with possible differentiation along various pathways.7 Familial occurrence has been reported at least once.8 In all cases of telangiectatic osteosarcoma, familial genetic changes may be responsible, but other causes are more likely. Molecular and cytogenetic studies are necessary to resolve these issues.9 ClinicalThe clinical presentation of telangiectatic osteosarcoma closely resembles that of conventional osteosarcoma. However, local pain, soft-tissue masses, and fractures are the most common presenting symptoms and signs.5, 10 Patient sex and age Telangiectatic osteosarcoma occurs in a male-to-female ratio of 2:1. Although disease can be found in patients aged 3-71 years, it rarely occurs in persons older than 25 years. Most patients present when they are aged 10-20 years. Site of lesions Telangiectatic osteosarcoma lesions are usually osseous, but extraosseous lesions have been reported. In the long bones, these tumors usually occur in the metaphyseal region within the medullary cavity. As the tumors expand and destroy the cortex, blowout fractures may occur. These lesions may also occur in a diaphyseal location.11 The distribution pattern of telangiectatic osteosarcomas in the long bones is as follows12: Telangiectatic osteosarcomatous differentiation has been reported in parosteal osteosarcoma,17 in dedifferentiated chondrosarcoma arising in the background of osteochondroma,18 in association with aneurysmal bone cysts,19, 20 and in osteitis deformans. Telangiectatic osteosarcoma also has been noted to arise in extraosseous soft tissues in the forearm, thigh, and popliteal fossa.21 Although rare, telangiectatic osteosarcomatous differentiation has been seen in cases of malignant phyllodes tumor of the breast22 and in cases of ovarian sarcoma.23 WORKUPSection 3 of 7
Imaging Studies
Histologic FindingsThe use of fine-needle aspiration biopsy and the pathologic evaluation of tissue sections obtained during surgery in the diagnosis of telangiectatic osteosarcoma have been reviewed.3, 4, 24 Fine-needle aspiration biopsy The examination of samples obtained at fine-needle aspiration biopsy reveals sheets of highly polymorphous cells. The cells include spindled cells reminiscent of fibroblasts, as well as round or oval malignant cells. Multinucleated cells also are frequently identified. Nuclear hyperchromasia, nuclear membrane irregularity, and prominent nucleoli are noted in the malignant cells. Increased mitotic activity may be noted as well. The cytoplasm is variable and granular. Although fine-needle aspiration results, in conjunction with highly suggestive clinical and radiographic findings, may be of value in determining the malignant nature of the underlying process, they are not the mainstays in the diagnosis of telangiectatic osteosarcomas. Rather, core-needle or conventional biopsy permits a definitive diagnosis of telangiectatic osteosarcoma. Gross appearance of the resected tumors The tumors, which may be 10-20 cm in diameter, have the appearance of a hemorrhagic mass. An aneurysmal bone cyst is often suspected. Sometimes, these lesions have multicystic channels filled with blood that correspond to the radiographic appearance of fluid-filled spaces. A solid, fleshy, sarcomalike appearance is not appreciated in these lesions. Microscopic features Malignant cells are noted in a background of blood and necrotic debris. Because the pleomorphic hyperchromatic malignant cells may be diluted in the necrotic and hemorrhagic background, a careful examination to recognize these elements is imperative. Blood lakes, rather than endothelium-lined spaces, are present. In some cases, an osteoid matrix may not be visualized except within the septal walls, which may be thin and difficult to find. In such cases, a characteristic radiographic appearance, when correlated with a careful microscopic search for features suggestive of malignancy, helps in the correct interpretation of the findings.25 In some cases, low-power examination reveals a morphologic pattern that is reminiscent of an aneurysmal bone cyst (see Image 1). A potential trap is created by a radiologic impression of an aneurysmal bone cyst and the characteristic gross features of that cyst. However, examination of the cyst lining reveals overt malignant cells, often with increased mitotic activity (see Image 2). These cells may lie adjacent to the benign osteoclastic giant cells. In some cases, these giant cells are numerous, and the tumor mimics a giant, cell–rich osteosarcoma (see Image 3). Unlike an aneurysmal bone cyst, telangiectatic osteosarcoma has an osteoid matrix that is delicate and lacelike in appearance. Also, the stroma between the dilated vascular spaces often contains malignant cells. Role of pathologists A high degree of suspicion is necessary with a purely destructive lesion of the long bones in adolescents. Examinations of bone tumors and tumorlike conditions have been reviewed.9 Briefly, in the resected specimen, the size and location of the tumor and the extent of disease should be noted. The involvement of the resected margins and of the vessels, nerves, skin, and soft tissues along the biopsy tract should be included in the report. After preoperative chemotherapy, the resected specimen should be mapped, and multiple sections representing the complete face of the bone should be obtained to document the amount of necrosis and viable tumor in the specimen. This observation is particularly important, because the amount of necrosis has strong prognostic significance and affects the subsequent management of telangiectatic osteosarcoma. Tumor necrosis in more than 95-98% of the resected specimen is considered a good response to chemotherapy.26 Staging
TREATMENTSection 4 of 7
Medical TherapyAdvances in diagnosis and chemotherapeutic regimens have improved the prognosis of patients with telangiectatic osteosarcoma.5, 27, 28, 29 Because of neoadjuvant chemotherapy, the continuous disease-free survival for patients with telangiectatic osteosarcoma is similar to or better than that for persons with conventional osteosarcoma.27, 28, 30 Regarding the choice of chemotherapeutic agents, the treatment of telangiectatic osteosarcoma is similar to that of high-grade osteogenic sarcomas. Reported below are 2 protocols that are used specifically for the treatment of telangiectatic osteosarcoma. Although no standard recommendations for chemotherapy in telangiectatic osteosarcoma exist, generalizations can be made regarding the modern treatment of this disease. Preoperative chemotherapeutic agents can be administered intravenously or intra-arterially for 2-6 cycles. Chemotherapy should include at least 2 of the following drugs: doxorubicin, methotrexate, cisplatin or carboplatin, and ifosfamide.31 For adjuvant chemotherapy, 2-6 cycles of the same drugs are used. However, non–cross-reacting drugs may be selected for use in patients with a poor response to neo-adjuvant chemotherapy. As always, and particularly in the case of rare diseases such as telangiectatic osteosarcoma, experimental treatment options that advance scientific knowledge and ensure high-quality patient care should be considered. Chemotherapeutic approach A Two cycles of intravenous methotrexate are administered over 6 hours, beginning on days 1 and 21. This agent is followed by citrovorum factor or leucovorin rescue, and, after 9 days, by the continuous intra-arterial cisplatin for 72 hours. Surgery follows, and, depending on the tumor response (good vs poor), further neoadjuvant therapy may be continued. Postoperative chemotherapy for patients who have a good response may include at least 3 cycles of intravenous doxorubicin for 2 days. On day 21, intravenous methotrexate is infused over 6 hours, followed by citrovorum factor or leucovorin rescue. Continuous intra-arterial cisplatin administration follows this course on day 28 for 72 hours. Such cycles are administered beginning on days 1, 49, and 105, at least. For patients who have a poor response, (ie, tumor necrosis in <95% of the tumor in the resected specimen), 5 cycles of intravenous doxorubicin are administered for 2 days. On day 21, a combination of bleomycin, cyclophosphamide, and intravenous dactinomycin is administered for 2 days. Chemotherapeutic approach B Preoperative chemotherapy involves 2 cycles of intravenous methotrexate over 6 hours, followed by citrovorum factor or leucovorin rescue. This is followed by the administration of cisplatin on day 7 for 72 hours. After 48 hours of cisplatin therapy, the patient should receive intravenous doxorubicin for 8 hours. The second cycle begins on day 28, and surgery follows this cycle. If the response to chemotherapy is good, as determined by the amount of tumor necrosis in the resected specimens, at least 3 cycles of intravenous doxorubicin may be administered for 2 consecutive days in a 4-hour period on each day. This step is followed by intravenous methotrexate administered over 6 hours on the 21st and 27th days, followed by citrovorum factor or leucovorin rescue and intra-arterial cisplatin infusion for 72 hours. This course is repeated after 17 days for at least 2 additional cycles. For patients with a poor response to the initial neoadjuvant chemotherapy, 4 cycles of intravenous doxorubicin is administered for 2 consecutive days in a 4-hour period each day. On day 21, ifosfamide plus mesna is intravenously infused for 5 consecutive days in 90 minutes. This step is followed with intravenous methotrexate administered over 6 hours on day 42 and then citrovorum factor or leucovorin rescue. On day 48, a combination of cisplatin, as given preoperatively, and etoposide (VP16) is administered in 1-hour infusions on 3 days. This cycle is repeated after 19 days for at least 2 cycles. The addition of doxorubicin to preoperative neoadjuvant therapy results in a continuous disease-free survival rate of 82% at a follow-up of 2-7 years (mean, 4 y). This rate is significantly better than is the continuous disease-free survival rate of 61% in conventional osteosarcomas treated with the same chemotherapeutic protocol. The Children's Oncology Group and its precursor organizations, the Pediatric Oncology Group (POG) and the Cancer Strategies Group (CSG), have been pioneers with regard to studies to establish standardized neoadjuvant chemotherapeutic protocols for the treatment of osteosarcomas.32 Because chemotherapeutic protocols are continually evolving, a knowledgeable investigator should always be consulted before such therapy is initiated. Surgical TherapyThe surgical management of telangiectatic osteosarcoma depends on the tumor's location, the stage of the disease, and the tumor's response to neoadjuvant chemotherapy. The primary goal of surgery is the complete resection of the tumor, using wide margins. With the success of current neoadjuvant chemotherapeutic protocols, this goal is usually achieved. However, cases in which the major neurovascular structures are involved or a pathologic fracture has occurred usually require wide excision or radical amputation to completely resect the primary tumor. Margins that are intralesional, marginal, or less than wide result in unacceptably high local recurrence rates that may indicate lower disease-free survival rates. In limb-salvage procedures, the type of reconstruction depends on the primary tumor's location, the structures being resected, the patient's age and activity level, and the surgeon's experience.33 The resultant function of the patient with a salvaged limb should be determined by using standard Musculoskeletal Tumor Society functional outcome assessments. The local recurrence of disease after limb-salvage procedures is usually treated with wide excision or radical amputation to achieve local control of the disease. Preoperative DetailsInitial staging studies should include standard radiography, whole-body technetium-99m (99mTc) methylene diphosphonate (MDP) bone scanning, CT scanning of the chest, and MRI of the primary tumor. MRI scans should include not only the tumor but also the joint proximal to and the one distal to the tumor to detect any skip metastases. After these studies, biopsy is performed in close consultation with the musculoskeletal oncologic surgeon and the radiologist, as well as with the surgical pathologist and/or the cytopathologist. A sample can be obtained by means of open biopsy, fine-needle aspiration biopsy, or core-needle biopsy, with image guidance used as indicated. The biopsy incision or tract must be placed so that its site can be resected en bloc at the time of definitive surgery. Therefore, the musculoskeletal oncologic surgeon must be involved in the initial biopsy. After the preoperative portion of neoadjuvant chemotherapy, the tumor stage is reassessed to determine the effect of the chemotherapy on the local extent of the disease and the presence of any distant metastatic disease. The staging system used by musculoskeletal oncologic surgeons is the surgical staging system that Dr Enneking introduced, which is advocated by the Musculoskeletal Tumor Society. Most telangiectatic osteosarcomas are stage IIB, that is, high-grade, extracompartmental lesions. Some patients present with distant metastatic disease; their tumors are stage IIIB. Intraoperative detailsThe margins of surgical excision may be evaluated with intraoperative frozen-section examination as indicated. Postoperative detailsAfter successful resection with limb-salvage methods or amputation, the patient should be closely monitored for recurrence of the tumor and for distant metastatic disease. Standard radiographs should be obtained to assess local recurrence. CT scans of the chest and bone scans are periodically obtained to assess distant metastatic disease. OUTCOME AND PROGNOSISSection 5 of 7
Historically, local recurrence has been found to be more common than metastasis.27, 12, 5 With the use of preoperative chemotherapy, however, this observation is probably changing. Telangiectatic osteosarcomas have vascular spread and therefore, similar to conventional osteosarcomas, metastasize to the bones and lungs.27, 12 MULTIMEDIASection 6 of 7
REFERENCESSection 7 of 7
Telangiectatic Osteosarcoma excerpt Article Last Updated: Jan 18, 2008 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
