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Objective: To evaluate, via a multidisciplinary approach, a distinctive paleopathological condition believed to be fibrous dysplasia, found on a 19th/20th century skeleton from Certosa Monumental Cemetery, Bologna, Italy., Materials: A skeletonized cranium and mandible recovered from an ossuary in 2014., Methods: Pathological alterations were analysed by radiological examination, dental macrowear, histopathological and genetic analyses., Result: The skeleton is believed to be an adult male. Differential diagnoses include Paget's disease, McCune-Albright syndrome, osteochondroma and osteosarcoma. The radiographic findings, along with the solitary nature of the lesions, are strong evidence for the diagnosis of fibrous dysplasia (FD). Genetic analysis further revealed a frequency of ˜1% of mutant alleles with the R201C substitution, one of the post-zygotic activating mutation frequently associated with FD., Conclusions: The multi-analytical method employed suggests a diagnosis of monostotic form of FD. The diagnostic design incorporates multiple lines of evidence, including macroscopic, histopathological, and genetic analyses., Significance: Through the use of a multi-analytic approach, robust diagnoses can be offered. This case serves as one of the oldest examples of FD from an historical context. The genetic mutation detected, associated with FD, has not been previously reported in historical/ancient samples., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Osteosarcoma is the most common primary malignancy of bone, and typically occurs among children and adolescence. This study aims to evaluate treatment outcomes among children, adolescents and young adults with osteosarcoma over the three decades by the changes in the long-term relative survival., Methods: Osteosarcoma incidence and relative survival data from Surveillance, Epidemiology, and End Results (SEER) registries during 1984-2013 were analyzed. The survival differences over three decades, age, sex, race, and socioeconomic status (SES) were assessed by comparing Kaplan-Meier curves., Results: The overall incidence of osteosarcoma kept relatively stable with 0.4 per 100 000 in the three decades with the peak incidence occurring in the aged 10-19 group. The 10-year relative survival rate (RSR) increased from 57.7% to 61.0% in the three decades, with the greatest increase in the aged 0-9 group from 48.2% to 65.7%. The 10-year RSR improved from 54.1% to 61.5% in males, and from 62.4% to 63.0% in females, respectively, in the three decades. Furthermore, survival dramatically improved from 30% to 60% in the high-poverty group over the three decades., Conclusion: This study demonstrated that the overall incidence of osteosarcoma remained stable, with an improvement in survival in the three decades. The improved survival was greater in males than in females in the three decades. Furthermore, the survival significantly increased in high-poverty group, which was attributed to increasing improved health care system and patients with low finance can also have access to receiving effective and consistent treatment without distinction., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The famous poet Arthur Rimbaud (1854-1891) stopped writing poetry at 21 years and subsequently had a rather adventurous life mainly in the Arabic peninsula and Ethiopia. He died at 37 years, only a few months after the amputation of his right lower limb due to a developing tumor in the knee, which probably was an osteosarcoma in the lower third of the femur. His letters to his sister Isabelle suggest that he suffered from severe stump pain rather than phantom limb, but since he lived only shortly after surgery (he developed extensive carcinomatosis), one does not know whether a full phantom would have developed and how this would have affected his subsequent life., (© 2018 S. Karger AG, Basel.)

Objectives: The recent discovery of the earliest hominin cancer, a 1.7-million-year-old osteosarcoma from South Africa has raised the question of the origin of cancer and its determinants. We aimed to determine whether malignant and benign tumors exist in the past societies., Methods: A review of literature using Medline database and Google about benign and malignant tumors in prehistory and antiquity. Only cases with morphological and paraclinical analysis were included. The following keywords were used: cancer; paleopathology; malignant neoplasia; benign tumor; leiomyoma; myoma; breast cancer; mummies; soft tissue tumor; Antiquity., Results: Thirty-five articles were found in wich there were 34 malignant tumors, 10 benign tumors and 11 gynecological benign tumors., Conclusions: The fact that there were some malignant tumors, even few tumors and probably underdiagnosed, in the past may be evidence that cancer is not only a disease of the modern world. Cancer may be indeed a moving target: we have likely predisposing genes to cancer inherited from our ancestors. The malignant disease could therefore appear because of our modern lifestyle (carcinogens and risk factors related to the modern industrial society)., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Introducing the multidisciplinary paleoradiology research at the Institute of Diagnostic Imaging and Radiation Oncology of the Kaposvár University, highlighting the cases with potential central nervous system involvement--from the scanning methods to the 3D printing--in order to draw attention to the historical background and clinical aspects of certain pathological conditions., Methods: The authors developed the examination protocols for three different CT scanners. Among the examined archaeological remains cranial lesions were identified in 26 cases, from which 4 cases with potential central nervous system involvement are demonstrated. The scanning parameters and the advantages of secondary image reconstructions (multiplanar reconstruction, maximum intensity projection, three-dimensional volume rendering technique) are presented with the cases., Results: The authors demonstrate a case with destructive skull lesions due to syphilis from the 15th century AD, a condition rarely seen or even unknown nowadays in the modern world. With the CT images of the skull base fracture from the Iron Age, signs of healing could be verified. Using the CT images a non-invasive approach is presented in the case of the craniofacial osteosarcoma in order to visualize the local status and the direct intracranial propagation. Advantages of the 3D VRT reconstructions are shown in the case of unilateral coronal suture synostosis., Conclusion: Paleoradiological CT examinations serve as a non-invasive, non-destructive tool for studying archaeological remains and artifacts. The special applications provided by the imaging modality contribute to the conventional paleopathological investigations.

Osteosarcoma is the bone tumor that most commonly affects children, adolescents, and young adults. Before 1970, treatment primarily included surgical resection. However, the introduction of chemotherapy led to a dramatic improvement in prognosis for patients with localized osteosarcoma; long-term survival rates of less than 20% improved to 65% to 70% after the advent of multiagent chemotherapy regimens. Controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. However, large cooperative group studies and international collaboration have demonstrated that the most effective regimens include the combination of high-dose methotrexate, doxorubicin, and cisplatin (MAP). The introduction of biologic agents such as muramyl tripeptide and the use of additional cytotoxic chemotherapy such as ifosfamide have not definitively improved the survival of patients with osteosarcoma. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel agents will be critical to identify the path toward improving outcomes for patients. Once promising agents are identified, an international infrastructure exists for clinical trials. Herein, biologic, preclinical, and clinical trial efforts will be described along with future international collaborative strategies to improve outcomes for patients who develop this challenging tumor., (© 2015 by American Society of Clinical Oncology.)

Osteosarcoma is the most common primary malignant tumor of bone usually occurring in young adolescent and children. This disease has a poor prognosis, because of the metastases in the period of tumor progression, which are usually developed previous to the clinical diagnosis. In this paper, a 2000-year-old ancient bone remain with osteogenic sarcoma was analyzed searching for tumor biomarkers which are closely related to this disease. After a specific extraction SDS-PAGE gel electrophoresis followed by tryptic digestion was performed. After the digestion the samples were measured using MALDI TOF/TOF MS. Healthy bone samples from same archaeological site were used as control samples. Our results show that in the pathological skeletal remain several well known tumor biomarkers are detected such as annexin A10, BCL-2-like protein, calgizzarin, rho GTPase-activating protein 7, HSP beta-6 protein, transferrin and vimentin compared to the control samples. The identified protein biomarkers can be useful in the discovery of malignant bone lesions such as osteosarcoma in the very early stage of the disease from paleoanthropological remains.

As the American Society of Clinical Oncology celebrates its 50th anniversary, physicians can appreciate the significant advances made in the treatment of patients with sarcoma. Historically, these rare tumors have garnered great interest in the medical profession, due to their ability to reach extraordinary size, resulting in substantial deformities and disabilities. Fortunately, advances in surgical management, which have occurred concurrently with advances in imaging, diagnostic techniques, and both local and systemic adjuvant treatments, offer patients diagnosed with sarcoma significant hope for successful treatment and the expectation of a meaningful quality of life.

Much of the progress in systemic therapy for sarcomas was accomplished in the first half of the last 5 decades. Various chemotherapeutic agents were tested in the 70s through the 80s and became part of the standard of care for this patient population. During the decade of the 90s, dose intensification became feasible as a result of improved supportive care and the availability of growth factors, thus maximizing the therapeutic potential of this class of agents. However, response rates and survival plateaued and it became obvious that newer and mechanistically different agents were needed to improve the therapeutic index and gain further enhancement of outcomes. Since early 2000, primarily inspired by the experience with imatinib in gastrointestinal stromal tumors (GISTs), several targeted therapies have been tested in sarcomas with modest success. The major limitations encountered include the lack of drivers and actionable targets for bone and soft tissue sarcomas with complex genomic profiles. Continued investigations and sequencing of larger numbers of these rare and heterogeneous malignancies could shed some light on a path toward improved outcomes.

Cancer is a devastating diagnosis for anyone, but none more so than for children and their parents--so many questions to be asked, so much information to sift through and absorb, and so many difficult decisions to be made. It is no wonder that a diagnosis of childhood cancer is often met with fear, anger, guilt, and feelings of being overwhelmed, yet also a determined resilience on the part of families to do whatever it takes to help their child get well again (Rishel, 2010).

The ability of parathyroid glandular extracts to stimulate bone acquisition in rodents was established in the 1920s, but interest in this action lay dormant for almost 50 years until application of contemporary laboratory methods permitted the large-scale production of an amino-terminal fragment of PTH, (1-34) hPTH (teriparatide), which was capable of carrying out all known actions of the full-length (1-84) PTH molecule. In the 1970s, largely stimulated by the efforts of a British pharmacologist, Dr. John Parsons, the scientific community began to revisit these anabolic actions and showed that single daily injections of teriparatide dramatically increased bone mass in several mammalian species and restored bone in oöphorectomized rats. Shortly thereafter, human studies confirmed a striking increase in trabecular bone mass and showed also that an important part of teriparatide's action is to increase cortical bone. Eli Lilly and Company conducted a formal registration trial in postmenopausal women with osteoporosis. The unexpected occurrence of osteosarcomas in Fisher 344 rats treated long-term with teriparatide provoked an abrupt cessation of that trial, but ambiguity concerning the relevance of this rat finding to human disease, combined with significant anti-fracture efficacy, led to FDA approval of teriparatide for men and postmenopausal women with osteoporosis "at high risk for fracture" in 2002. Subsequently, teriparatide has been approved also for treatment of patients with glucocorticoid-associated osteoporosis, and papers indicating utility of this agent for dental and orthopedic applications have begun to appear.

This biographical sketch on Ernest Amory Codman corresponds to the historic text, The Classic: The Registry of Bone Sarcomas as an Example of the End-Result Idea in Hospital Organization, available at DOI 10.1007/s11999-009-1048-7 and The Classic: Registry of Bone Sarcoma: Part I.-Twenty-Five Criteria for Establishing the Diagnosis of Osteogenic Sarcoma. Part II.-Thirteen Registered Cases of "Five Year Cures" Analyzed According to These Criteria, available at DOI 10.1007/s11999-009-1049-6 .

Micro-computed tomography (muCT) is of great interest for palaeopathological examination because it is less invasive than histology. This study evaluates the diagnostic value of muCT for postcranial macerated bones. We investigated five specimens (osteomyelitis, tuberculosis, trauma, osteosarcoma and hypertrophic osteoarthropathy) of a pathology reference series by muCT and polarised light microscopy. The 3D muCT images allow an easy orientation within the specimen. Surface structures, thickness, continuity of the cortex and number, thickness and orientation of the trabeculae can be evaluated. The high number of muCT slices helps to choose the most interesting areas for further investigations. Grey value images display the degree of mineralisation. Yet, the differentiation between woven and lamellar bone is only possible using polarised light microscopy. muCT is a tool of high value for the examination of postcranial bone disorders. It cannot replace histological examinations completely because it cannot assess the bone quality (woven or lamellar). For the choice of the optimal location where slices for the microscopic investigation are later cut in heterogeneous samples, muCT is very useful. Therefore, we suggest performing the muCT examination first, followed by histology if necessary.

One of the most remarkable operations carried out in the Royal Infirmary of Edinburgh during the early decades of the 19th century was the surgical excision of an enormous tumour, believed to be an osteosarcoma, of the lower jaw of Robert Penman, that produced severe disfigurement of his face. James Syme, then in his late twenties, was invited to see the patient by Professor Ballingall and Dr John Abercrombie and, in July 1828, he operated, without the benefit of an anaesthetic, to completely remove the tumour. The patient not only survived the operation, but also remained in excellent health for many years afterwards. He emigrated to the United States, but occasionally returned home to Scotland. In 1855, Lord Lister, who noted that his "deformity" had been wonderfully masked by a bushy beard, saw him. This case is re-evaluated in the light of information from the archives in the Royal College of Surgeons of Edinburgh and from the contemporary and more recent literature.

A survey of the tumors found in the remains of the Ancient Egyptians shows the occurrence of all the kinds of tumors which would be expected to be preserved in the osteological evidence. On the other hand, findings of tumors in the soft tissues of mummies are only exceptional. The frequency of tumors seems to be lower than in recent years, probably because of the shorter mean duration of life. The pathological lesions preserved in bony sturcture reveal not only osseous tumors, but also the presence of some tumors of soft tissues eroding the bone. To the survey of cases described in the literature, original findings of a calcified myoma uteri and of a probably epipharyngeal carcinoma are added. Because our knowledge on the history of tumors is not yet comprehensive, much more attention should be devoted to the search for them, starting from the moment of excavation of any cemetary.

This report concerns a probable case of osteosarcoma found in a precontact Hawaiian skeleton from the east coast of Oahu Island, Hawaii. A young adult female showed a tumorous bone proliferation with a coarse, corallike appearance at the distal metaphyseal area of the left femur. In gross observation, a profusion of coalescing bone was extended to the surrounding space and also invaded the marrow space. X-ray films revealed spotted and ringed shadows in the shaft and a "sunburst appearance" in the lesion. Histological examination of the tumor bone fragment showed a great deal of primitive bone tissue formation without any systemic Haversian structure. The diagnosis of osteogenic osteosarcoma is much more compatible than other primary malignant bone tumors such as Ewing's sarcoma, fibrosarcoma, and chondrosarcoma or osteoplastic metastatic carcinoma of the bone when the location and morphology of the tumor are considered along with the age of the decedent.