A Case Report of Progressive Paget Disease Mimicking a Malignancy: A Second Episode 21 Years Later.

Paget osteosarcoma is a rare but serious complication of Paget disease requiring immediate management before further malignant transformation. This case report examines the progression of a previously reported case of Paget disease with atypical pseudotumor manifestation, mimicking osteosarcoma over a 21-year time lapse. After presenting with substantial pain and elevated alkaline phosphatase levels, imaging proved extensive bony expansion of the lesion with high-grade trabecular and cortical thickening and extraosseous soft-tissue extension, prompting the need for biopsy to rule out Paget sarcoma. The atypical features of the pseudotumor's development helps distinguish key radiographic and clinical criteria for malignant development.

The Dilemma of Balance between Benefits and Losses for Chondromyxoid Fibroma-like Osteosarcoma in Thoracic Spine with Azygos Tumor Thrombosis: A Case Report.

Background: Chondromyxoid fibroma-like osteosarcoma (CMF-OS) is an extremely rare subtype of osteosarcoma, its clinical data are scarce, and our understanding of it is far from sufficient. As it has few typical imaging manifestations, it is not uncommonly misdiagnosed clinically. Azygos vein thrombosis is also a rare entity, and there is a big controversy over treatments for it. Case presentation: Herein, we report a case of CMF-OS that occurred in the spine, coincidently, azygos vein thrombosis was found. A young male patient came to our clinic because of continuous back pain, and a neoplastic lesion was suspected in the thoracolumbar vertebrae. The pathological results of the biopsy showed a low grade of osteosarcoma, and chondromyxoid fibroma-like osteosarcoma was the primary diagnosis. Since the tumor cannot be en-bloc resected, he received palliative decompression surgery, followed by radio and chemotherapy. Azygos vein tumor thrombosis was not treated and, unfortunately, he died of heart failure caused by the thrombus migrating from the azygos vein to the right atrium. Before the palliative decompression surgery, both the patient and the clinical team were trapped in the dilemma of how big a surgery should be carried out to maximize the benefits of this patient. Results and complications: CMF-OS is indeed more aggressive than its pathological sections suggest. Guidelines for osteosarcoma should be followed. Furthermore, it is important to recognize the danger of tumor thrombosis in the azygos vein. Preventive measures have to be performed in a timely manner to avoid catastrophic results.

Three, dynamic variants of ST segment elevations in a patient with osteosarcoma and cardiac metastasis.

In the right clinical setting, ST segment elevation (STE) on electrocardiogram (ECG) is most concerning for acute injury due to transmural myocardial ischemia. This frequently points to significant epicardial coronary artery disease, mandating emergent cardiac intervention. In rare cases, cardiac metastases may cause transient STE. We present a case of a 28-year-old male patient with metastatic osteosarcoma with STE in three different ECG territories over ten months. Several transient, dynamic patterns of STE were noted: anteroseptal leads concerning for acute injury with reciprocal ST depressions in inferior leads, lateral leads, inferior leads with reciprocal ST depression in lateral leads, followed by STE again in lateral leads. Given the patient's young age, absence of cardiac history or symptoms, personal preference, bleeding risk, and cancer prognosis, cardiac catheterization was never pursued. We present this case to remind providers to include metastatic cancer in the differential diagnosis of STE on ECG, and that these changes can be dynamic.

Second Primary Malignancies of the Bones and Joints: More Common than Expected in Osteosarcoma Patients.

BACKGROUND: Osteosarcoma is the most common primary bone tumor in children, adolescents, and young adults. Second primary malignancies (SPMs) are a potential serious long-term event that can occur in osteosarcoma survivors. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results 18 database was queried for all osteosarcoma cases from 2000 through 2015. Standardized incidence ratio (SIR) and absolute excess risk (AER) of SPM per 10,000 persons (AER) relative to representative population-level data were calculated across for various anatomic locations. RESULTS: In total, 3438 patients with osteosarcoma were identified. Of these patients, 79 (2.3%) developed SPMs, with an SIR of 2.84 (95% confidence interval [CI] 2.35 to 3.39, P < 0.0001) and an AER of 44.96. The most common SPMs were tumors of the bones or joints (SIR 73.07, CI, 38.90 to 124.94, P < 0.0001, AER 7.48), tumors of soft tissues including the heart (SIR 15.19, CI, 5.58 to 33.07, P < 0.0001, AER 3.27), and leukemia (SIR 22.28, CI, 15.03 to 31.80, P < 0.0001, AER 16.74). CONCLUSION: The overall incidence of SPMs in osteosarcoma survivors was significantly higher than would otherwise be expected for this population. Considering the occurrence and targeting surveillance for SPM in the osteosarcoma patient population is warranted.

Osteosarcoma emboli presenting as chronic thromboembolic pulmonary hypertension in a child.

A 13-year-old girl presented with hypoxemia during adjuvant chemotherapy for an osteosarcoma of the left distal femur. She underwent an amputation complicated by a post-operative pulmonary embolism (PE). Three months post-operatively, she was admitted to hospital with severe hypoxemia and diagnosed with pulmonary hypertension on echocardiogram in the context of extensive bilateral PE on computed tomography. She was planned for elective pulmonary thromboendarterectomy, but rapidly deteriorated requiring emergent surgery. At the time of surgery, she was found to have extensive tumor emboli throughout both pulmonary arteries. She recovered well post-operatively but died 2 months later from progressive disease.

Secondary osteosarcoma associated with osteofibrous dysplasia: a case report.

Secondary osteosarcoma is a rare complication of primary malignancies and benign bone lesions. There are various types of diseases that cause secondary osteosarcoma. A 15-year-old male presented at our medical center complaining of pain and redness in the right lower leg. He had been diagnosed with osteofibrous dysplasia in the right tibia when he was 2 years old and since then had been followed up. Although he had a pathological fracture of the right tibia at the age of 7, his fracture healed with a plaster cast and did not require surgery. At the time of the patient's last visit, a radiograph revealed a periosteal reaction as well as erosion of the bone cortex. Magnetic resonance imaging revealed an infiltrative area in the soft tissue surrounding the osteofibrous dysplasia lesion in the tibia. Consequent to pathological examination (through bone biopsy), the patient was diagnosed with secondary osteosarcoma. The patient underwent chemotherapy and extensive resection with liquid nitrogen. He has been progressing satisfactorily after the operation. The present case is the first report of secondary osteosarcoma associated with osteofibrous dysplasia. During the long-term follow-up of osteofibrous dysplasia, oncologists should be aware of the possibility of secondary osteosarcoma.

Patient-reported neurocognitive function in adult survivors of childhood and adolescent osteosarcoma and Ewing sarcoma.

PURPOSE: Little is known regarding long-term neurocognitive outcomes in osteosarcoma and Ewing sarcoma (EWS) survivors despite potential risk factors. We evaluated associations among treatment exposures, chronic health conditions, and patient-reported neurocognitive outcomes in adult survivors of childhood osteosarcoma and EWS. METHODS: Five-year survivors of osteosarcoma (N = 604; median age 37.0 years) and EWS (N = 356; median age 35.0 years) diagnosed at < 21 years from 1970 to 1999, and 697 siblings completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire and reported chronic health conditions, education, and employment. Prevalence of reported neurocognitive difficulties were compared between diagnostic groups and siblings. Modified Poisson regression identified factors associated with neurocognitive difficulties. RESULTS: Osteosarcoma and EWS survivors, vs. siblings, reported higher prevalences of difficulties with task efficiency (15.4% [P = 0.03] and 14.0% [P = 0.04] vs. 9.6%, respectively) and emotional regulation (18.0% [P < 0.0001] and 15.2% [P = 0.03] vs. 11.3%, respectively), adjusted for age, sex, and ethnicity/race. Osteosarcoma survivors reported greater memory difficulties vs. siblings (23.5% vs. 16.4% [P = 0.01]). Comorbid impairment (i.e., ≥ 2 neurocognitive domains) was more prevalent in osteosarcoma (20.0% [P < 0.001]) and EWS survivors (16.3% [P = 0.02]) vs. siblings (10.9%). Neurological conditions were associated with worse task efficiency (RR = 2.17; 95% CI = 1.21-3.88) and emotional regulation (RR = 1.88; 95% CI = 1.01-3.52), and respiratory conditions were associated with worse organization (RR = 2.60; 95% CI = 1.05-6.39) for EWS. Hearing impairment was associated with emotional regulation difficulties for osteosarcoma (RR = 1.98; 95% CI = 1.22-3.20). Patient report of cognitive difficulties was associated with employment but not educational attainment. CONCLUSIONS: Survivors of childhood osteosarcoma and EWS are at increased risk for reporting neurocognitive difficulties, which are associated with employment status and appear related to chronic health conditions that develop over time. IMPLICATIONS FOR CANCER SURVIVORS: Early screening, prevention, and treatment of chronic health conditions may improve/prevent long-term neurocognitive outcomes.

Risk of venous thromboembolism and major bleeding in the clinical course of osteosarcoma and Ewing sarcoma.

BACKGROUND: Patients with osteosarcoma (OS) and Ewing sarcoma (ES) are considered to have a high venous thromboembolism (VTE) risk, although the exact incidence and prognostic impact are under-researched in general as well as in relevant age groups. AIMS: To study the impact of VTE and major bleeding (MB) in OS and ES patients, subdivided in children, Adolescents Young Adults (AYAs; aged 18-39) and older adults. METHODS: Retrospective single-center chart review in 519 OS and 165 ES patients treated between 1980 and 2018. Patients were followed from sarcoma diagnosis until an outcome of interest (VTE, MB) or death occurred. Cumulative incidences were estimated with death as competing risk. Cox models were used to determine prognostic impact. RESULTS: Five-year cumulative incidences of VTE were 12 % (95%CI 9.1-15) for OS and 6.7 % (95%CI 3.5-11) for ES patients, mostly happening in patients ≥18 years; the most frequent VTE presentation was catheter-related upper-extremity thrombosis (OS: 18/65, ES: 7/11). Five-year cumulative incidences for MB were 5.8 % (95%CI 4.0-8.1) in OS and 5.4 % (95%CI 2.5-9.8) in ES patients. 192 OS and 77 ES AYAs were included, who faced similar VTE and MB incidences as older adults. In OS, VTE and MB were both associated with mortality (adjusted HRs 2.0 [95%CI 1.4-2.9] and 2.4 [95%CI 1.4-4.0], respectively), whereas in ES this association was only present for MB (aHR 3.4 [95%CI 1.2-9.6]). CONCLUSIONS: VTE is a frequent complication in adult OS and to a lesser extent in ES patients, while the rate of MB was comparably high in both sarcoma types.

Primary hyperparathyroidism and sarcoma: A case report and literature review.

ABSTRACT: The relationship between primary hyperparathyroidism (PHPT) and bone sarcoma is debatable, especially after wider use of teriparatide treatment, concerns have intensified on the issue. Extensive search in English literature revealed 10 cases reported having PHPT and sarcomas. Besides, three cases of bone sarcoma occurring after teriparatide treatment had been reported. Hereby, we report a 51-year-old woman with a prolonged history of PHPT. She was diagnosed with chondrosarcoma 9 years after refusal and lack of treatment for PHPT. She was cured surgically for both chondrosarcoma and parathyroid adenoma at 1-year interval. So far, large cohorts did not show an increase in the incidence of bone sarcomas in PHPT. Several case observations, including the current one, as well as data from in vitro and rat studies, pointed out prolonged parathormone exposure, may be a risk for bone sarcomas. Under these circumstances, a safer attitude on individual basis would be the prevention of prolonged parathormone exposures.

Individualized combination therapies based on whole-exome sequencing displayed significant clinical benefits in a glioblastoma patient with secondary osteosarcoma: case report and genetic characterization.

BACKGROUND: The incidence of osteosarcoma as a secondary neoplasm in glioblastoma patient is extremely rare. The genetic characteristic still remains unclear until now. CASE DESCRIPTION: We reported a 47-year-old female patient with multiple intracranial disseminations and infiltrations (splenium of the corpus callosum and lateral ventricular wall) of a rapid progressive glioblastoma underwent occipital craniotomy and total resection of all the enhancing lesions. Whole-exome sequencing and pathological examination revealed glioblastoma, IDH1 wild type, PTEN deficient, TERT mutated, NF1mutated, MGMT unmethylated. After surgery, the patient received combined therapeutic regimen of TTFields (tumor-treating fields) plus pembrolizumab plus temozolomide and TTFields plus everolimus, which displayed significant clinical benefits. During the combined therapeutic course, an extremely rare secondary malignant neoplasm occurred, femur MR and pathological detection of biopsy tissue demonstrated osteosarcoma. The result of whole-exome sequencing revealed 7 germline mutated genes (EPAS1, SETD2, MSH3, BMPR1A, ERCC4, CDH1, AR). Bioinformatic analysis showed the two germline mutations (MSH3 and ERCC4) induced deficiency in the DNA repair machinery, which resulting in the accumulation of mutations and may generate neoantigens contributing to the development of a secondary osteosarcoma in this case. CONCLUSION: Individualized combination therapies based on whole-exome sequencing displayed significant clinical benefits in this case. Germline MSH3 and ERCC4 mutation may induce a secondary osteosarcoma in glioblastoma patients.

Primary Osteosarcoma of Left Atrial Appendage in a Patient with Rheumatic Heart Disease.

Primary cardiac osteosarcoma is extremely rare, with all arising from the atrium, right ventricle, and cardiac valve, according to previous reports. We report a case of primary osteosarcoma of the left atrial appendage in a patient. We present a process of preoperative misdiagnosis, intraoperative confirmed diagnosis, and complete resection.

The Management of an Open Biopsy Tract Site Infection and Ulceration in the Setting of Osteosarcoma.

Biopsy site infection in the setting of osteosarcoma is a potentially devastating complication. We present the case of a 16-year-old adolescent girl with a distal femur osteosarcoma who developed an open biopsy site ulceration and infection after initiation of neoadjuvant chemotherapy. This was treated with careful local excision of the ulcerated biopsy site and systemic antibiotic therapy throughout the duration of her chemotherapy course. She subsequently underwent wide resection of the tumor en bloc with a generous ellipse around the biopsy scar and reconstruction with cemented knee megaprosthesis. No recurrence of either infection or malignancy was observed. This case represents the successful treatment of a biopsy site ulceration and infection in a patient with osteosarcoma and may merit adoption in future instances of this complication.

Metastatic osteosarcoma bowel perforation secondary to chemotherapy-induced tumour necrosis.

Osteosarcoma is the most common paediatric and adolescent primary bone malignancy and is highly chemosensitive. Gastrointestinal metastases from osteosarcomas are rare. Bowel perforation secondary to chemotherapy is a potential serious complication reported in ovarian, colorectal and haematological malignancies. We report the first documented case of chemotherapy-mediated bowel perforation in an osteosarcoma patient with gastrointestinal metastases. A man in his 20s, with a history of resected osteosarcoma in remission, presented with abdominal pain. A computed tomography (CT) scan demonstrated a large calcified intrabdominal mass (15×13×9 cm) consistent with new peritoneal disease. After one cycle of palliative ifosfamide and etoposide chemotherapy, he developed a large bowel perforation and neutropenic sepsis consequently requiring resection of the perforated mass. Chemotherapy-induced bowel perforation is a rare but serious complication that should be considered in patients with osteosarcoma, and other chemosensitive malignancies, with intra-abdominal metastases. Recommencement of systemic therapies after bowel complications must be assessed cautiously on a case-by-case basis.

Metastatic osteosarcoma tumor thrombus in a Cavalier King Charles Spaniel presenting with dyspnea.

A six-year-seven-month-old female neutered Cavalier King Charles Spaniel was referred for the investigation of progressive dyspnea and hyphema in the right eye with secondary glaucoma. Previous medical history included a high-grade soft tissue spindle cell sarcoma removed from the cranial sternal region one year before. On presentation at the referral hospital, the dog was tachypneic and dyspneic. The heart rhythm was regular and there was a soft left-sided systolic murmur. Echocardiography identified the presence of a mass significantly occluding left heart inflow, with no other lesions identified. Thoracic radiographs documented a localized alveolar pattern within the left caudal lung lobe. The size of the heart and pulmonary vessels were within normal limits, indicating a non-cardiogenic alveolar pattern. Given the clinical presentation of dyspnea and high index of suspicion of intra-cardiac neoplasia, the dog was considered to have a grave prognosis and therefore euthanized. Post-mortem gross and histopathologic examination revealed the presence of a metastatic osteosarcoma tumor thrombus in the left atrium and pulmonary vein, metastatic osteosarcoma infiltrating the myocardium, lungs, the uveal tract of the right eye, and both adrenal glands. Whitney grade II myxomatous changes were noted on the mitral and tricuspid valve leaflets. This report describes an unusual intra-cardiac tumor thrombus in a dog presenting with dyspnea. Cavalier King Charles Spaniels presenting with dyspnea often raise suspicion for myxomatous mitral valve disease. However, as demonstrated in this case, other more unusual causes of dyspnea should also be considered in the absence of classic clinical findings.

Bone Health in Osteosarcoma at Presentation and Its Impact on Cancer Treatment: A Case Series of 3 Pediatric Patients.

Osteosarcoma is the most common pediatric malignant bone tumor. Concomitant osteoporosis has typically been attributed to oncologic therapy. The present case series is aimed to describe 3 patients who presented with osteoporosis or osteopenia before, or early in, their oncology treatment. In our patients, bone health and its complications had significant impacts including pain, reduced mobility, prolonged admission, and delays in recovery. Our patients experienced improvement with resection of their primary tumor and with bisphosphonate infusion. Future studies are required to determine the prevalence osteoporosis at presentation of osteosarcoma and the role of bisphosphonates.

Relaxin inhibits 177Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathway.

177Lu-EDTMP (Ethylenediamine tetramethylene phosphonic acid) is the most used radioactive agent for pain palliation in bone cancer patients. The present study aims to study the impact of relaxin-2 on the 177Lu-EDTMP associated cell toxicity and death in osteosarcoma cells. MG63 and Saos-2 cells were cultured with 177Lu-EDTMP (37 MBq) for 24 h with and without pretreatment of recombinant relaxin 2 (RLXH2) for 12 and 24 h. 177Lu-EDTMP associated cellular deterioration and death was determined by LDH, MTT, and trypan blue dye assays. ELISA-based kit was used to determine apoptotic DNA fragmentation. Western blotting was used to determine expression levels of apoptotic-related signalling pathway proteins like bcl2, poly(ADP-ribose) polymerase (PARP), and MAPK (mitogen-activated protein kinase). Our results found that RLXH2 counters 177Lu-EDTMP associated cellular toxicity. Similarly, RLXH2 was able to counter 177Lu-EDTMP induced cell death in a concentration and time--dependent manner. Furthermore, it was found that RLXH2 treatment prevents apoptosis in 177Lu-EDTMP challenged cells through activation of the notch-1 pathway in a concentration- and time-dependent manner. We reported that RLXH2 significantly declined cellular toxicity and apoptosis associated with 177Lu-EDTMP in MG63 and Saos-2 cells through the notch-1 pathway.

Juvenile dermatomyositis in Thai children: Retrospective review of 30 cases from a tertiary care center.

BACKGROUND: Juvenile dermatomyositis is a rare condition, but it is the most common idiopathic inflammatory myopathy in pediatric patients. AIM: To study the clinical manifestations, investigations, treatment, clinical course, and outcomes of juvenile dermatomyositis in Thai children. METHOD: This retrospective study included juvenile dermatomyositis patients treated at Siriraj Hospital, a 2,300-bed national tertiary referral center in Bangkok, Thailand, from 1994 to 2019. RESULTS: Thirty patients (22 females and 8 males) were included with a female to male ratio of 2.7:1. Median age at diagnosis was 5.1 years (range, 2.6-14.8 years). Median duration of illness before diagnosis was 6.5 months (range, 0.3-84.0 months). Acute and subacute onset occurred in the majority of patients. Presenting symptoms included muscle weakness in 27/30 (90%), skin rash in 26/30 (86.7%), muscle pain in 17/26 (65.4%), and arthralgia in 4/18 (22.2%) of patients. Dermatologic examination revealed Gottron's rash, heliotrope rash, and periungual telangiectasia in 25/30 (83.3%), 21/30 (70.0%), and 15/24 (62.5%) of patients, respectively. Interestingly, scalp dermatitis was found in 8/21 (38.1%) of patients. The most commonly used treatment regimen in this series was a combination of prednisolone and methotrexate. During the median follow-up of 3.1 years (range, 0.0-18.5 years), only one-third of patients were seen to have monocyclic disease. Extraskeletal osteosarcoma at a previous lesion of calcinosis cutis was observed in one patient at 12 years after juvenile dermatomyositis onset. LIMITATIONS: This was a retrospective single-center study, and our results may not be generalizable to other healthcare settings. Prospective multicenter studies are needed to confirm the findings of this study. CONCLUSION: juvenile dermatomyositis usually poses a diagnostic and therapeutic challenge, which can be compounded by the ethnic variations in the clinical presentation, as observed in this study. Asian patients tend to present with acute or subacute onset of disease, and arthralgia and/or arthritis are less common than in Caucasian patients. Scalp dermatitis is not uncommon in pediatric juvenile dermatomyositis patients. An association between juvenile dermatomyositis and malignancy, though rare, can occur.

Patient-derived iPSCs link elevated mitochondrial respiratory complex I function to osteosarcoma in Rothmund-Thomson syndrome.

Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma, small stature, skeletal anomalies, sparse brows/lashes, cataracts, and predisposition to cancer. Type 2 RTS patients with biallelic RECQL4 pathogenic variants have multiple skeletal anomalies and a significantly increased incidence of osteosarcoma. Here, we generated RTS patient-derived induced pluripotent stem cells (iPSCs) to dissect the pathological signaling leading to RTS patient-associated osteosarcoma. RTS iPSC-derived osteoblasts showed defective osteogenic differentiation and gain of in vitro tumorigenic ability. Transcriptome analysis of RTS osteoblasts validated decreased bone morphogenesis while revealing aberrantly upregulated mitochondrial respiratory complex I gene expression. RTS osteoblast metabolic assays demonstrated elevated mitochondrial respiratory complex I function, increased oxidative phosphorylation (OXPHOS), and increased ATP production. Inhibition of mitochondrial respiratory complex I activity by IACS-010759 selectively suppressed cellular respiration and cell proliferation of RTS osteoblasts. Furthermore, systems analysis of IACS-010759-induced changes in RTS osteoblasts revealed that chemical inhibition of mitochondrial respiratory complex I impaired cell proliferation, induced senescence, and decreased MAPK signaling and cell cycle associated genes, but increased H19 and ribosomal protein genes. In summary, our study suggests that mitochondrial respiratory complex I is a potential therapeutic target for RTS-associated osteosarcoma and provides future insights for clinical treatment strategies.