Paget Osteosarcoma Research Articles

Disappearing hemipelvis: Low grade osteosarcoma, an unusual and poorly described variant of Paget’s Sarcoma

Paget’s sarcomatous transformation is a rare and potentially fatal complication of Paget’s disease. Histologically, it is typically described as a high-grade and extremely aggressive malignancy. We present an unusual radiographic series from a patient diagnosed with a low-grade Paget's osteosarcoma, a very rare and poorly described variant of the disease.

Osteosarcoma in Asian Populations Over the Age of 40 Years: A Multicenter Study.

Elderly patients with osteosarcoma (OSA) are no longer uncommon; however, many questions remain regarding this population. We investigated the clinicopathological characteristics and prognostic factors of OSA in an Asian population over the age of 40 years. This was a multi-national, multi-institutional study by the Eastern Asian Musculoskeletal Oncology Group (EAMOG). A total of 232 patients were enrolled (116 males and 116 females), with a median age of 50 years at diagnosis; 25 (10.8 %) patients exhibited initial metastasis. Median follow-up was 52 months for survivors. We observed 102 osteolytic and mixed radiographic findings for 173 lesions. Histological subtypes other than osteoblastic type were frequent. Radiation-associated OSA was seen in seven patients, with a 5-year overall survival (OS) of 16.7 %. No Paget's OSA was observed. High-grade spinopelvic OSA was seen in 29 (12.5 %) patients. The 5-year OS was 59.4 % in patients without initial metastasis and 45.2 % in patients with spinopelvic OSA. While surgery and initial metastasis were common prognostic factors for OS, chemotherapy was not. Histologic response to neoadjuvant chemotherapy was poor in 61 of 83 patients. This study revealed distinct clinicopathological features of OSA patients over 40 years of age compared with younger patients, such as the high incidence of axial tumors, common osteolytic and mixed radiographic findings, the high frequency of unusual histologic subtypes, and poor prognosis. Contrary to Western elderly patients with OSA, there was no Paget's OSA in this study, which may result in a lower incidence of secondary OSA. Prognostic factor analyses demonstrated chemotherapy did not influence OS.

Osteosarcoma of the spine: experience in 26 patients treated at the Massachusetts General Hospital

Background context Because of the low incidence, treatment recommendations for spinal osteosarcoma are guided by the results of small series and case reports. Many include patients who presented for treatment over the course of three to four decades. Purpose The goal of this investigation was to report the treatments, results, and overall survivorship of 26 patients treated for osteosarcoma of the spine at a single institution. Study design Retrospective prognostic series (Level III evidence). Patient sample Twenty-six patients treated at a single center for osteosarcoma of the spine over a 26-year period. Outcome measures Estimation of patient survival, local recurrence, and the presence of metastatic disease. Methods We performed a retrospective review of cases of osteosarcoma involving the spine treated at our institution between 1982 and 2008. Medical charts, radiology reports, pathology reports, and operative notes were reviewed for all patients. Available imaging studies were also reviewed. The log-rank test was used to compare baseline differences between groups. Survivorship analysis was performed using Kaplan–Meier methodology. The effect of Paget osteosarcoma, type of resection, presence of local recurrence, tumor size, surgical margins, and metastases on overall survival were also investigated using the log-rank test. Results Twenty-six patients were included for review in this study. Twenty individuals were treated surgically, and 24 were treated with radiation with a mean dose of 62.2 Gy (range 20–84.7 Gy). Twenty-five patients received chemotherapy. Of those treated surgically, seven received en bloc resection. The median overall survival for all patients in our series was 29.5 months (standard error 14.7, 95% confidence interval 0.6–58). Local recurrence developed in 7 patients (27%), and metastasis occurred in 16 individuals (62%). Patients with Paget osteosarcoma had worse overall survival (p<.001). Conclusions Results presented here confirm a poor prognosis for patients with spinal osteosarcoma. Although combination therapies, including surgery, chemotherapy, and high-dose radiation, achieve adequate short-term survival, the 5-year mortality rate remains high.

Paget's osteosarcoma and post-radiation osteosarcoma: secondary osteosarcoma at Middlemore Hospital, New Zealand

To review the clinical and histological features of our cases of Paget's osteosarcoma and post-radiation osteosarcoma. A search through the files of the New Zealand Bone and Soft Tissue Tumour Registry was performed, patients were identified and the relevant details were collated. Thirty-one cases of Paget's osteosarcoma and eight cases of post-radiation osteosarcoma were identified. Patients with Paget's osteosarcoma were aged between 48 and 67 years, predominantly female, and axial and appendicular skeleton were equally affected. The outcome was known in 29 cases, with a median survival of 7.25 months and 5 year overall survival of 10%. Patients with post-radiation osteosarcoma were aged between 17 and 68 years, equally male or female, and axial and appendicular skeleton were equally affected. Index lesions included benign or malignant osseous and non-osseous conditions. The average age at diagnosis of the index lesion was 30.1 years and the average latent period was 13.5 years. The outcome was known in all eight cases, with a median survival of 33 months and 5 year overall survival of 38%. Paget's osteosarcoma and post-radiation osteosarcoma are examples of secondary osteosarcoma. The former affects elderly patients, and has a poor prognosis and response to treatment. The later affects a wide age group, and has a prognosis and response to treatment comparable with primary osteosarcoma.

Immediate Reconstruction of Oncologic Hemipelvectomy Defects

Soft tissue and bony tumors of the pelvis are rare, but when they occur, treatment presents both an oncologic surgical and a reconstructive challenge. After reconstruction, soft tissue defects can be large and there is usually exposed bone and/or joint. A retroperitoneal abdominal wall defect may also be present. Flap mobilization is generally necessary to eliminate dead space and cover the exposed bone, viscera, and/or prosthetic orthopedic material. We performed immediate reconstruction on 11 patients after radical pelvic resections for tumor. Eleven cases of radical pelvic resection and immediate reconstruction were identified during the period from 1992 to 2002 at University Hospital, Newark, New Jersey. All patients were treated by both the orthopedic oncology and plastic surgery teams. A retrospective review of office charts and hospital records was performed. Data were gathered regarding the following: tumor type and oncologic history, extent of resection, reconstructive modality, complications, and outcome. All patients underwent radical resection of pelvic masses depending on the tumor type and location. Tumor types included chondrosarcoma (6), Paget osteosarcoma (1), giant cell tumor (1), metastatic uterine carcinoma (2), and invasive squamous cell carcinoma arising in a chronic decubitus ulcer (1). The reconstructive procedures performed were the following: rectus abdominus flaps (6), gluteus maximus musculocutaneous flaps (3), and thigh fillet flaps (2). The retroperitoneal defects were repaired with primary tissue approximation of the surrounding available musculature. Additionally, Gore-Tex mesh was used in 2 cases, tensor fascia lata was used in 2 cases, and acellular dermal matrix in 1 case. Blood loss for the combined procedures ranged from 400 mL to 1400 mL. The follow-up period in this series ranged from 24 to 114 months. Complications included skin flap loss with subsequent infection (1), local cellulitis controlled with antibiotics (1), regional recurrence (2). The postoperative course was uneventful for the remainder of the cases. Soft tissue reconstructions after extensive pelvic resections always present as complex reconstructive problems. Reconstruction is dictated by the size of the defects and by tissue availability. The extent and type of resections vary according to tumor size and location. In our experience, local pedicled muscle-based flaps, if available, usually provide adequate tissue mass to eliminate dead space, cover the extent of the wound, and close the retroperitoneal defect. Microvascular tissue transfer is always an option but was reserved in our series for cases with no suitable local alternative.

Primary tumors of the thoracic skeleton.

From 1975 to 1990, eighty-nine primary tumors of the thoracic skeleton; ribs, sternum, scapula, clavicle, and thoracic spine, were treated. Forty-four tumors (49%) were benign lesions. Forty-five tumors were malignant and were proportionately distributed amongst the five sites. The most common malignancies were Ewing's sarcomas, chondrosarcomas, plasmacytomas, osteogenic sarcomas, and lymphomas. All patients with Ewing's sarcomas were treated with combination chemotherapy, surgical resection, and radiation therapy for those with residual disease after surgery. Only one patient has died of disease. Patients with primary chondrosarcomas were treated by surgery alone and all are free of disease or have died without disease. Patients with solitary plasmacytomas or primary lymphomas of bone were treated with radiation therapy initially. Half the patients developed systemic disease. The patients with osteogenic sarcomas included several with radiation induced lesions and Paget's osteosarcoma and all but one died of disease.

Sporadic Amplification of the MYC Gene in Human Osteosarcomas

The MYC proto-oncogene has been shown to be overexpressed in several types of sarcomas, including some osteosarcomas. In most cases, the overexpression is due to gene amplification. The total number of osteosarcoma patients studied, however, remains too small to derive any conclusions regarding the true prevalence and the possible clinical significance of MYC gene amplification. To address the issue more thoroughly, we studied 27 specimens from 25 patients with high-grade osteosarcoma (16 primary, 11 metastatic; 11 adult, 14 pediatric) for MYC gene alterations by Southern blot analysis. Two of 27 specimens (7%) showed MYC gene amplification: a primary fibrohistiocytic osteosarcoma of the femur in a 37-year-old man showed threefold amplification, and a primary Paget's osteosarcoma of the tibia in a 60-year-old man showed fourfold amplification. None of the specimens tested showed MYC gene rearrangement (zero of 27) or activating point mutations at the PvuII site in MYC exon-1 (zero of 26). Hence, the MYC gene is amplified in a subset of osteosarcomas. The possible clinical or biological significance of MYC gene amplification in osteosarcoma may warrant further investigation.

Survival and Management Considerations in Postirradiation Osteosarcoma and Paget??s Osteosarcoma

Postirradiation and Paget's osteosarcomas are high-grade malignancies. The five-year survival was only 10% in recent experience at the author's institution. Progressive pain is an important clinical feature in both conditions. Careful roentgenographic studies demonstrate cortical destruction and a soft-tissue mass in virtually all patients. Metastasis was present in 25% of both groups of patients at presentation. In contrast to previous series, more than 80% of the patients with postirradiation osteosarcoma had had irradiation for malignant entities and more than 70% had been treated with modern radiotherapy regimens (cobalt-60 or linear accelerator). Twice as many patients with postirradiation osteosarcoma were evaluated and treated in the 1980s than in the previous decade. The initial indication for irradiation often was carcinoma of the breast, uterus, or cervix, or lymphoma. Two-thirds of the patients had progressive disease that was not controllable within six months after diagnosis. Early detection may be the only effective means of improving survival with postirradiation or Paget's osteosarcoma. These patients require lifelong follow-up evaluations.

Effect of calcitonin treatment on osteoclast counts in Paget's disease of bone.

Histological and biochemical changes during calcitonin treatment have been studied in 15 patients with Paget's disease of bone. For each patient, osteoclast counts were made by the same observer on serial needle biopsies of diseased bone from the posterosuperior iliac spine. Serial estimations were also made of the serum alkaline phosphatase and urinary hydroxyproline excretion. A total of 66 biopsies was examined (ranging from two to seven per patient). Osteoclast populations and the biochemical measurements were log normally distributed. During calcitonin treatment there was a statistically significant decrease in: (1) the total osteoclast count per square millimetre; (2) the number per square millimetre of osteoclasts in resorption cavities on the trabecular surface; (3) the relative proportion of osteoclasts sited in resorption cavities compared with total osteoclasts; (4) the serum alkaline phosphatase level; (5) 24-hour urinary hydroxyproline excretion. On stopping treatment there was a statistically significant increase in all of these histological and biochemical values except that the proportion of osteoclasts in resorption cavities remained low. The trabecular cement line pattern remained abnormal during and after treatment in all biopsies examined, and complete suppression of osteoclast activity was not observed. One of the patients developed a Paget's osteosarcoma while on calcitonin therapy.