1: Arch Orthop Trauma Surg. 2007 Jan 3

Low-grade central osteosarcoma mimicking fibrous dysplasia: a report of two cases.

Muramatsu K, Hashimoto T, Seto S, Gondo T, Ihara K, Taguchi T.

Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan, muramatu@yamaguchi-u.ac.jp.

Low-grade central osteosarcoma is an unusual variant of conventional osteosarcoma. We present here two rare cases of low-grade central osteosarcoma resembling fibrous dysplasia. A 24-year-old woman diagnosed as fibrous dysplasia was treated with intra-lesional excision and curettage of the tumor but tumor recurred at 4 months after surgery. Distal femoral en-bloc resection was performed followed by arthroplasty with mega-prosthesis of the knee. A 57-year-old man diagnosed as central osteosarcoma was treated with wide excision of the tumor, followed by reconstruction with the vascularized fibula graft combined with an autogenous irradiated bone graft. Because of the difficulty in distinguishing low-grade central osteosarcoma from a benign lesion, open biopsy is needed to obtain a large tumor sample. Careful clinical and pathological evaluation is required to obtain a definite diagnosis. The treatment of low-grade central osteosarcoma is en-block resection with wide surgical margins.

2: Skeletal Radiol. 2006 Jul 1

Dedifferentiated high-grade osteosarcoma originating from low-grade central osteosarcoma of the fibula.

Kenan S, Ginat DT, Steiner GC.

Department of Orthopedic Surgery, New York University-Hospital for Joint Diseases, New York, NY, USA.

Low grade central osteosarcoma is a distinct, rare low grade malignant neoplasm characterized histologically by a spindle cell proliferation associated with trabecular bone formation. This tumor usually carries a good prognosis. However, it has the potential to recur, dedifferentiate, and metastasize subsequent to surgical treatment. In extremely rare occasions, LGCOS presents with areas of dedifferentiation upon initial patient evaluation. In this report we describe one such case affecting the fibula of a 39-year-old female, presenting with pain. Initial biopsy demonstrated a high-grade osteosarcoma. No areas of LGCOS were seen histologically. Following biopsy the patient received 3 months of chemotherapy at a different institution. However, the patient continued to exhibit symptoms. X-rays indicated a very aggressive tumor in the diaphysis of the proximal fibula, MRI revealed soft tissue involvement. The tumor and surrounding soft-tissues were excised en bloc at our institution. Microscopically, the lesion consisted of high-grade osteosarcoma as well as an underlying LGCOS that involved the cortex and medullary cavity of the fibula. The two histological components of the tumor were sharply delineated from one another. No chemotherapy effect was appreciated histologically or clinically. Eight months following the surgery, the patient died from lung metastases. This is the third documented case of dedifferentiated LGCOS at initial presentation. This case reveals that the low-grade component was also evident on preoperative radiographs.

3: Skeletal Radiol. 2005 Aug;34(8):490-3

Low-grade central osteosarcoma of the rib.

Yamaguchi T, Shimizu K, Koguchi Y, Saotome K, Ueda Y.

Department of Pathology, Koshigaya Hospital, Dokkyo University School of Medicine, Minami-Koshigaya 2-1-50, 343-8555, Koshigaya, Saitama, Japan. takehiko@dokkyomed.ac.jp

We report a case of low-grade central osteosarcoma of the rib, mimicking fibrous dysplasia protuberans or parosteal osteosarcoma. A 13-year-old boy presented with a densely ossified exophytic tumor in the left sixth rib. The surgically resected rib revealed an ossified tumor that had developed within bone and had formed an exophytic mass. Microscopic examination revealed parosteal osteosarcoma-like low-grade central osteosarcoma. Low-grade central osteosarcomas rarely affect the rib, and exophytic tumor formation is also rare. This tumor required differentiation from fibrous dysplasia protuberans and parosteal osteosarcoma because of its clinical presentation.

4: Pathol Res Pract. 2004;200(6):439-45

Molecular analysis of p53, MDM2 and H-ras genes in low-grade central osteosarcoma.

Park HR, Jung WW, Bertoni F, Bacchini P, Park JH, Kim YW, Park YK.

Department of Pathology, Hallym University, Anyang, Republic of Korea.

Low-grade central osteosarcoma is an uncommon form that is characterized by a long premorbid history, and is compatible with prolonged survival after treatment. However, molecular abnormalities are rare in low-grade central osteosarcomas, whereas p53 mutations occur in approximately 20% of conventional high-grade osteosarcomas. In this study, 21 cases of low-grade central osteosarcoma were analyzed for mutations of the p53 gene, amplification of the MDM2 gene, and mutations of the H-ras gene using formalin-fixed, paraffin-embedded materials. We also examined the expression of p53, MDM2, and p21WAF1 protein immunohistochemically and assessed the proliferation activities using the monoclonal antibody MIB-1. One case (4.7%) showed strong p53 immunoreactivity, whereas p53 gene mutations were not detected at all. Seven cases (33.3%) showed immunoreactivity for MDM2 protein. As for gene alterations, MDM2 amplification was found in four cases (19.0%). p21WAF1 expression was detected in 12 cases (57.1%). MIB-1-LI showed very low levels in all the cases and no significant correlation with p53 or MDM2 immuno-reactivity. None of the tumors showed H-ras mutations. In conclusion, the number of p53 gene alterations in low-grade central osteosarcomas is lower than that in conventional high-grade osteosarcomas. MDM2 alterations and p21WAF1 expression might be involved in the tumorigenesis of low-grade central osteosarcomas

5: Mod Pathol. 2004 Mar;17(3):288-91.

Central low-grade osteosarcoma with pagetoid bone formation: a potential diagnostic pitfall.

Franchi A, Bacchini P, Della Rocca C, Bertoni F.

Department of Human Pathology and Oncology, University of Florence, Florence, Italy. Franchi@unifi.it

Central low-grade osteosarcoma is an uncommon form of osteosarcoma, which is often difficult to distinguish from benign bone lesions. We reviewed the radiographic studies, the histologic material and the clinical records of two patients with central low-grade osteosarcoma that closely simulated the histologic appearance of Paget's disease of bone. The patients were two women aged 46 and 53 years. Radiologically, they presented a large ill-defined densely sclerotic lesion involving the proximal tibia. Both lesions only focally presented the conventional histologic appearance of central low-grade osteosarcoma, with a proliferation of fibroblast-like cells embedded in a dense collagenous stroma and irregular anastomosing tumor bone trabeculae. The most striking feature was the presence of extremely thickened irregular plates of bone with an irregular mosaic pattern of cement lines that closely resembled that of Paget's disease of bone. One patient, who had been initially treated for Paget's disease for 7 years, experienced disease progression. At resection of proximal tibia, there was evidence of dedifferentiation to high-grade osteosarcoma. After 2 months, she developed local recurrence that was treated with above-knee amputation, followed by chemotherapy. She died with multiple lung metastases 4 months later. The other patient is alive 9 months after wide tumor resection. These cases further expand the spectrum of central low-grade osteosarcoma, and underscore the diagnostic difficulties in separating central low-grade osteosarcoma from benign bone diseases, which may lead to delay in diagnosis, inadequate treatment, and eventually to dedifferentiation. Recognition of this variant of central low-grade osteosarcoma is based on the aggressive radiologic appearance and on adequate tumor sampling for histologic examination.