Introduction

Osteosarcoma is the most common malignant primary bone tumor in children, adolescents, and young adults. Telangiectatic osteosarcoma is an uncommon subtype of osteosarcoma accounting for less than 4% of all cases of osteosarcoma.1 It is characterized by distinctive radiographic, pathologic features, and prognostic implications. Radiologically and microscopically, it mimics aneurysmal bone cyst. The common sites involved are femur, tibia, and humerus a distribution similar to conventional osteosarcoma.2 These tumors mostly originate from metaphysis. Clinically, the tumor presents as a painful lytic mass lesion involving metaphysis of long bones often with pathological fracture. On imaging, it shows cystic spaces filled with blood and separated by thin septa.

In this retrospective study, we review the clinical characteristics and treatment outcome of 13 cases of telangiectatic osteosarcoma treated at our tertiary cancer center.

Objectives

The objective of this article was to study the clinical characteristics and treatment outcome of patients with telangiectatic osteosarcoma.

Methods

Thirteen patients were diagnosed with telangiectatic osteosarcoma in the department of medical oncology at a tertiary cancer center in India during a 12-year period. All were above 15 years of age. The details of clinical presentation, diagnosis, treatment, and survival were noted from medical records.

Treatment Protocol

The treatment protocol for all patients included chemotherapy and surgery. Standard chemotherapy consisted of two to three cycles of preoperative chemotherapy and three to four cycles of adjuvant chemotherapy following surgery for a total of six cycles. The regimen used was IAP regimen (ifosfamide 1.3 gm/m² on days 1–3, doxorubicin 60mg/m² on day 1, and cisplatin 100 mg/m² over 3 days) every 3 weeks. Adjuvant chemotherapy was administered 2 to 3 weeks after surgery. Limb-salvage surgery (LSS) was performed in most patients with the principle of tumor eradication through a wide resection margin.

Results

The details of the 13 cases are summarized in Table 1.

In our series, the median age was 20 years (range: 15–51 years); there were nine males and four females. All patients presented with pain and swelling of the involved site. The sites of involvement were lower end of femur (4), proximal humerus (4), upper tibia (2), proximal femur (1), rib (1), and distal ulna (1). All except one were nonmetastatic at presentation. One patient had bilateral lung metastasis at presentation. Four patients had elevated serum lactate dehydrogenase (LDH) (mean LDH: 597 u/L) and three had elevated serum alkaline phosphatase (ALP) (mean ALP: 326 u/L). The mean hemoglobin of the group was 12g/dL, and the mean white blood cell count was 8514/mm³. The patient with metastatic disease had significant anemia (hemoglobin: 5.5 g/dL). Radiographs showed expansile lytic lesions in all cases (Fig. 1A and B). Magnetic resonance imaging (MRI) scan showed an expansile lesion at metaphyseal region of the involved bone with periosteal reaction, associated soft tissue component, and multiple blood-filled cavities (Fig. 2A & B). On imaging, all except one patient had involvement of the metaphysis, four had associated pathological fracture, six had extension of the lesion into the diaphysis, and one had intra-articular extension. Two patients gave previous history of pathological fracture of femur and open reduction with internal fixation when presented to us with pain at surgical site. On imaging, one patient had lesion at the site of fracture and the other had lesion at fracture site as well as bilateral lung metastasis.

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Fig. 1: (A) X-ray showing expansile lytic lesion involving the upper end of left humerus (red arrow). (B) X-ray of the same patient after wide excision and reconstruction (red arrow).

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Fig. 2: (A) Magnetic resonance imaging (MRI) scan of the left shoulder, axial sections, T2-weighted images showing an expansile lesion at metaphyseal region of the humerus with associated soft tissue component and multiple blood-filled cavities (red arrow). (B) MRI scan of the same patient after neoadjuvant chemotherapy showing treatment response (red arrow).

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All patients had a confirmed histological diagnosis of telangiectatic osteosarcoma. Histopathological examination of the biopsy specimens showed large cystic spaces filled with blood. Neoplasm was composed of atypical cells arranged diffusely, having eosinophilic cytoplasm and oval-to-spindle hyper chromatic pleomorphic nuclei, and had osteoid formation. Mitosis was increased (Fig. 3).

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Fig. 3: Histopathological examination of the specimen showing neoplasm composed of atypical cells arranged diffusely, having eosinophilic cytoplasm and oval to spindle hyper chromatic pleomorphic nuclei and with osteoid formation.

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Out of 13 patients, only 10 patients with nonmetastatic disease took treatment. Six patients received neoadjuvant chemotherapy (NACT) with IAP regimen followed by limb salvage surgery. The LSS procedure consisted of wide excision and endoprosthetic reconstruction. One patient had received three cycles of chemotherapy elsewhere and underwent above knee amputation (AK amputation) as limb was not salvageable. Of the seven patients who received NACT, five patients had more than 90% necrosis on histopathology examination of the resected specimen and two patients had 60 to 70% necrosis. The patients with ulnar lesion and rib lesion underwent wide excision only and received six cycles of adjuvant chemotherapy. Patient number 8 with tibial lesion underwent AK amputation in view of large lesion, received four cycles adjuvant chemotherapy, and had prolonged neutropenia and herpes zoster infection. He developed solitary lung metastasis after a disease-free survival (DFS) of 17 months, underwent lobectomy, and is now in remission at 51 months. Patient no 4 developed surgical site infection post operatively and was treated with debridement and excision of the sinus tract. This patient developed metastatic disease after a DFS of 14 months. Currently, eight patients are alive in remission at a median follow-up of 50 months (range: 18–138 months). The 3-year DFS and overall survival were 66.7 and 88.9%, respectively (Fig. 4).

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Fig. 4: Kaplan–Meier curve showing progression-free survival (PFS) and overall survival (OS) at 3 years.

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Discussion

Telangiectatic osteosarcoma is a rare highly malignant bone tumor accounting for 2 to 125 of all tumors in the appendicular skeleton.23 This primary bone osteosarcoma commonly affects children, adolescents, and young adults. The mean age at presentation of these tumors is 17.5 years (range: 15–20 years) and males are affected twice as frequently as females.1 In our series, the median age was 20 years and sex distribution were similar to published literature. The sites commonly affected are the fast-growing metaphysis of long tubular bones. The most common site of origin is the distal femoral metaphysis (42%) followed by proximal tibia (17%), proximal humerus (9%) and proximal femur (8%).1 Rare sites of involvement are scapula, ribs, sternum, spine, pelvis, skull bones, and mandible. Extraosseous involvement is very rare.4 The distribution was similar in our series also.

Clinically, the presentation of telangiectatic osteosarcoma is similar to conventional osteosarcoma. Local pain, soft tissue swelling, and sometimes pathological fractures are the common presentations.1 Four out of 13 patients in this series presented with pathological fracture. Two patients in our series (patient nos. 6 and 13) underwent surgery for pathological fracture suspecting aneurysmal bone cyst. Radiologically, telangiectatic osteosarcoma is characterized by an expansile lytic lesion with a permeative destructive growth pattern. Being a rapidly growing tumor, it expands the cortex with cortical disruption and minimal or no periosteal new bone formation. Radiologically, this mimics an aneurysmal bone cyst.56

Telangiectatic osteosarcoma is presumed to originate from transformed osteoblasts or mesenchymal stem cells.1 Histologically, telangiectatic osteosarcoma is composed of cystic spaces often filled with blood resembling aneurysmal bone cyst. These are separated by fibrous septa populated by malignant cells, multinucleated giant cells, and tumor osteoid.1 The pattern of spread of telangiectatic osteosarcomas is similar to conventional osteosarcoma and metastasize to the bone and lungs.7 Matsuno et al proposed the following criteria for the diagnosis of telangiectatic osteosarcoma.8

• Radiologically, the lesion is lytic destructive with no appreciable sclerosis

• Grossly, it is a cavitatory lesion with little solid tumor mass and no area of sclerosis

• Microscopically, the tumor consists of single or multiple cystic cavities containing blood or necrotic tissue, traversed by septa composed of anaplastic appearing cells.

• Malignant cells may be found at the periphery and osteoid production is minimal.

The baseline imaging studies include plain radiographs, MRI of the primary site, and computed tomogram of the chest and technicism ⁹⁹ bone scan. The MRI of primary site should include the proximal and distal joints to detect skip metastasis. The differential diagnosis includes aneurysmal bone cyst, Ewing's sarcoma, and Langerhans cell histiocytosis.

Advances in diagnosis and chemotherapy have improved the outcome of patients with telangiectatic osteosarcoma and are similar to or better than conventional osteosarcoma.79 The treatment is similar to that of conventional osteosarcoma with NACT and limb sparing surgery when possible.10 The chemotherapeutic regimens used are same and the common agents are cisplatin, ifosfamide, doxorubicin, and methotrexate. The surgical management of telangiectatic osteosarcoma depends on the site of the tumor, stage of disease, and the response to NACT. The goal of surgery is always complete resection of tumor with wide margins by limb sparing surgery. However, when neurovascular structures are involved or when there is pathological fracture, radical amputation may be required. In our series, seven patients underwent limb sparing surgery and two amputations.

Survival rates of telangiectatic osteosarcoma with the current chemotherapy protocols are in the range of 65% at 5 years.11 In a study on 24 patients with telangiectatic osteosarcoma of the extremities by Bacci et al, at a median follow-up of 74 months, 20 remained free of disease and there was no local recurrence.10 They observed that there was significantly better histologic response to chemotherapy (96 vs. 68% good response) and disease-free survival (83 vs. 58%) in these patients when compared to those with conventional osteosarcoma treated with the same protocol. In our series, of the seven patients who received NACT five patients had a percentage necrosis more than 90 percentage similar to the study by Bacci et al.10 In another study on 28 patients with telangiectatic osteosarcoma of the extremities treated with NACT, good histologic response was seen in 89%, and 23 patients remained disease free at a mean follow-up of 5 years.7 Another study by Weiss et al reported event-free survival and overall survival at 5 years similar to other types of osteosarcomas.12 In the present series, eight patients were alive at 36 months and currently eight patients are alive at a median follow-up of 50 months (range: 18–138 months). A review on treatment outcome in telangiectatic osteosarcoma is summarized in Table 2.

Conclusion

Telangiectatic osteosarcoma is a rare variant of osteosarcoma often presenting with pathological fractures. The treatment is similar to conventional osteosarcoma with good outcome.