The development of musculoskeletal radiology for 100 years as presented in the pages of Acta Radiologica.

During the last 100 years, musculoskeletal radiology has developed from bone-only radiography performed by everyone to a dedicated subspecialty, still secure in its origins in radiography but having expanded into all modalities of imaging. Like other subspecialties in radiology, it has become heavily dependent on cross-sectional and functional imaging, and musculoskeletal interventions play an important role in tumor diagnosis and treatment and in joint diseases. All these developments are reflected in the pages in Acta Radiologica, as shown in this review.

Paleopathological study of a podal osteochondroma from the prehistoric Hypogeum of Calaforno (Sicily).

In this article, we report a case of isolated podal osteochondroma from the prehistoric Hypogeum of Calaforno (Giarratana, Ragusa, Sicily). Although the phalanx exhibiting the benign tumoral mass comes from a context featuring several commingled remains, the very good state of preservation of this bone allowed us to perform a comprehensive study of the neoplasm by applying a multidisciplinary approach encompassing archeology, morphology, stereomicroscopy, and radiology. The results from this very ancient specimen have been assessed in the light of the available paleopathological literature and clinical implications currently encountered in modern patients.

Osseous mass in a maxillary sinus of an adult male from the 16th-17th-century Spain: Differential diagnosis.

OBJECTIVE: To undertake a differential diagnosis of a large mass found in the left maxillary sinus of a cranium dated to the 16th-17th-century, and to expand knowledge of the diagnosis of osseous tissue formation in osteoarchaeological studies. MATERIAL: A cranium recovered from the cemetery of San Salvador de Palat de Rey church, León (Spain). METHODS: Macroscopic analysis, CT scanning. RESULTS: Macroscopic analysis indicated that the individual was probably a male over 30 years old with an ossified mass in the left maxillary sinus, measuring 24 × 19 × 24 mm, occupying approximately 27 % of the maxillary antrum. Computed tomography revealed a well-demarcated radiolucent unilocular mass with some radiopaque areas, with no communication with the alveoli of the premolars or molars. No erosive lesions or signs of inflammation were found. CONCLUSIONS: Neither the macroscopic, nor the radiological characteristics are compatible with inflammatory or malignant pathology, favoring a diagnosis of ossifying fibroma. SIGNIFICANCE: This case adds to the few reported cases in the osteoarchaeological literature, especially since there is limited relevant reference data to assist diagnosis. The CT scans and 3D reconstruction presented here facilitate differential diagnosis in future paleopathological studies. LIMITATIONS: Destructive methods were not authorized. SUGGESTIONS FOR FURTHER RESEARCH: In the future, micro-CT analysis, which was not performed in the current study, may add new and valuable information.

Multiple osteomata from medieval Tuscany, Italy (ca. 10th-12th AD).

OBJECTIVE: To explore the possible etiology of multiple osteomata on a skull and long bones from an individual from a medieval site in Tuscany, Italy. MATERIALS: Human skeletal remains dating to the 10th-12th century AD from the parish church of S. Pietro in Pava, in the province of Siena (Tuscany, Central Italy). METHODS: Macroscopic and imaging analyses (Cone Beam Computed Tomography). RESULTS: Nine round-shaped new bone formations are observed on a female individual aged 40-50 years. The lesions have a smooth surface and range from 2.2-6 mm in diameter. CONCLUSIONS: Cone Beam Computed Tomography confirmed that the lesions were composed of compact bone. Macroscopic and radiological features suggest the presence of nonsyndromic multiple osteomata. SIGNIFICANCE: Single cranial osteomata are commonly observed in osteoarchaeological remains, but multiple osteomata are rare and might assist in our understanding of neoplastic conditions in the past. LIMITATIONS: The lack of soft tissues prevents the diagnosis of complex disorders, such as the Gardner syndrome, which is characterised by multiple osteomata and polyposis of the colon. SUGGESTIONS FOR FURTHER RESEARCH: Careful investigation and reporting of all neoplastic lesions in ancient human remains in order to increase our knowledge about the etiology in past human populations.

The overlooked primary: bladder cancer metastases on dry bone. A study of the 20th century CAL Milano Cemetery Skeletal Collection.

OBJECTIVE: The aim of this article is to provide additional documentation of bone metastases to help anthropologists recognize the condition and potentially suggest the diagnosis of bladder carcinoma in differential diagnosis. MATERIALS AND METHODS: Thirteen individuals clinically diagnosed with bladder carcinoma from the 20th century Milano Cemetery Skeletal Collection were macroscopically studied to document bone metastases in bladder cancer. RESULTS: Bone metastases were found through macroscopic observation in three individuals or 23% of the study sample. Metastases were mostly of a mixed nature (45%), although both osteoblastic (13%) and osteolytic (9%) also occurred. In particular, mixed and osteoblastic metastases exhibited different distribution patterns, even when affecting the same bones. The vertebrae (24.7%), skull (12.9%), ribs (11.7%), proximal humeri (7.8%), pelvis (5.2%), proximal femora (2.6%), sacrum (1.3%) and sternum (1.3%) were the most commonly affected. Osteolytic lesions included coalescing superficial pits or lesions perforating the bone cortex. Proliferative lesions manifested as spongiosclerosis or periosteal new bone. Mixed metastases were osteolytic lesions exposing a thickened trabecular bone or coalescent porosity with reactive new bone. CONCLUSIONS: Bladder carcinoma metastases were mostly mixed, exhibiting periosteal reactions, perforations of bone cortex, spongiosclerosis and coalescing porosity. SIGNIFICANCE: Bladder carcinoma is rarely considered in the differential diagnosis of the primary organ. This study reports the macroscopic aspect of bone metastases in bladder carcinoma and may help anthropologists diagnose the condition in skeletons. LIMITATIONS: Absence of evidence is not evidence of absence; some lesions may have been hidden from macroscopic observation and therefore missed. FURTHER RESEARCH: Radiographic analysis and comparison with other neoplasms should provide additional details for the diagnosis of bladder cancer bone metastases.

The Intriguing History of Cancer Immunotherapy.

Immunotherapy is often perceived as a relatively recent advance. In reality, however, one should be looking for the beginnings of cancer immunotherapy under different names as far as in the Antiquity. The first scientific attempts to modulate patients' immune systems to cure cancer can be attributed to two German physicians, Fehleisen and Busch, who independently noticed significant tumor regression after erysipelas infection. The next significant advances came from William Bradley Coley who is known today as the Father of Immunotherapy. It was Coley who first attempted to harness the immune system for treating bone cancer in 1891. His achievements were largely unnoticed for over fifty years, and several seminal discoveries in the field of Immunology, such as the existence of T cells and their crucial role in immunity in 1967, stepped up the research toward cancer immunotherapy known today. The following paper tracks cancer immunotherapy from its known beginnings up until recent events, including the 2018 Nobel Prize award to James Allison and Tasuku Honjo for their meticulous work on checkpoint molecules as potential therapeutic targets. That work has led to the successful development of new checkpoint inhibitors, CAR T-cells and oncolytic viruses and the pace of such advances brings the highest hope for the future of cancer treatment.

Increased survival of patients aged 0-29 years with osteosarcoma: A period analysis, 1984-2013.

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.

Frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from gastric cancer: A SEER-based study.

The hematogenous metastatic pattern of gastric cancer (GC) was not fully explored. Here we analyzed the frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from GC patients. Data queried for this analysis included GC patients from the Surveillance, Epidemiology, and End Results Program database from 2010 to 2014. All of statistical analyses were performed using the Intercooled Stata 13.0 (Stata Corporation, College Station, TX). All statistical tests were two-sided. Totally, there were 19 022 eligible patients for analysis. At the time of diagnosis, there were 7792 patients at stage IV, including 3218 (41.30%) patients with liver metastasis, 1126 (14.45%) with lung metastasis, 966 (12.40%) with bone metastasis and 151 (1.94%) with brain metastasis. GC patients with lung or liver metastasis have a higher risk of bone and brain metastasis than those without lung nor liver metastasis. Intestinal subtype had significantly higher rate of liver and lung metastasis, while diffuse type was more likely to have bone metastasis. Proximal stomach had significantly higher risk to develop metastasis than distal stomach. African-Americans had the highest risk of liver metastasis and Caucasian had the highest prone to develop lung and brain metastasis. The median survival for patients with liver, lung, bone, and brain metastasis was 4 months, 3 months, 4 months and 3 months, respectively. It is important to evaluate the status of bone and brain metastasis in GC patients with lung or liver metastasis. Knowledge of metastatic patterns is helpful for clinicians to design personalized pretreatment imaging evaluation for GC patients.

Ewing Sarcoma and the History of Similar and Possibly Related Small Round Cell Tumors: From Whence Have We Come and Where are We Going?

The diagnosis of small round cell tumors always has been extremely difficult, and our current classification systems continue to evolve. Since its initial discovery by Dr James Ewing, the historical context of what is acceptably included under the designation "Ewing sarcoma" has changed. Although Ewing sarcoma and primitive neuroectodermal tumor were both initially described in the early 20th century, these tumors were considered likely distinct entities until the end of that same century, almost 75 years later. With modern immunohistochemistry and more recent advances in molecular techniques, the understanding of Ewing sarcoma and Ewing-like tumors has improved dramatically but also raises new questions and challenges. We now know that this category of tumors is remarkably more heterogenous than initially thought, especially in regards to its cytogenetics and molecular properties, and some of these differences likely have prognostic relevance. Whether we are now expanding the spectrum of Ewing sarcoma or simply recognizing new entities is controversial. Therapeutic approaches to address these new categories and/or entities need further focus and attention. Herein, we provide a comprehensive historical perspective on Ewing sarcoma, Ewing-like tumors (CIC and BCOR-rearranged sarcomas), and related and/or similar small round cell tumors, often included in the differential diagnosis, including mesenchymal chondrosarcoma, desmoplastic small round cell tumor, and small cell osteosarcoma. We also seek to provide updates and insights into the evolving classification and clinical relevance of the Ewing family of tumors.

A probable case of metastatic carcinoma in the medieval Netherlands.

Despite recent considerable gains, our knowledge of cancer in antiquity is still limited. This paper discusses an adult individual from a Dutch medieval hospital site who demonstrates osteoblastic and osteolytic lesions on the ribs, scapula, clavicle, and vertebrae. The morphology, radiographic appearance, and distribution of the skeletal lesions suggest that this individual was affected by metastatic carcinoma. This case increases the number of publications that present an osteoblastic and osteolytic response to cancer and contributes to the body of evidence for archaeological neoplastic disease. For the Netherlands, this individual presents the first published case of probable metastatic carcinoma with mixed skeletal lesions.

A probable primary malignant bone tumor in a pre-Columbian human humerus from Cerro Brujo, Bocas del Toro, Panamá.

We present a rare case of primary bone cancer principally affecting the right humerus of a skeleton from the pre-Columbian site of Cerro Brujo (1265-1380 CE) in Bocas del Toro, on the Caribbean coast of Panamá, excavated in the early 1970s. The humerus contains a dense, calcified sclerotic mass with associated lytic lesions localized around the midshaft of the diaphysis. Evidence of systemic inflammation and anemia, likely caused by the cancer, are visible in the form of severe porotic hyperostosis of the cranial vault and bilateral periosteal reactions in the tibiae. Differential diagnosis and future probes of the tumor are discussed. A tooth from the individual yielded a radiocarbon date 150 years later than those of the domestic occupation at the site. Given that it was the only formal burial recovered from the site, and as the individual had such a visible, painful, and rare pathology, this likely constitutes a ritual burial.

Extensive periosteal new bone formation in a skeleton from post-Medieval Chichester, England: A probable case of metastatic prostatic carcinoma.

An elderly male skeleton from a site in Chichester, UK, was found with a widespread periosteal reaction, principally affecting the axial skeleton and the pelvis. Radiography showed the presence of sclerosing infiltrates, mainly involving the lumbar vertebrae and pelvis. The differential diagnosis is discussed, reaching the conclusion that hypertrophic osteo-arthopathy (HOA) is the only reasonable alternative condition likely to produce such a widespread periosteal reaction as found here. HOA does not produce secondary deposits in the skeleton, however, and we conclude that his is most likely a case of prostatic carcinoma.

Differential diagnosis of a neoplastic condition in a prehistoric juvenile individual from La Falda site, Northwest Argentina.

Bone neoplasms or tumors are of great interest for paleopathological studies due to their close relationship with health and survivorship as well as for their epidemiologic and demographic relevance. However, the identification of these lesions in archaeological specimens is very uncommon. The aim of this paper is to report the case of skeleton R5 E#1 from the prehistoric cemetery La Falda, in the Northwest region of Argentina. During the osteopathological analysis of the skeletal series, proliferative lesions in several bones of the skeleton of a 7-10-year-old juvenile were observed (i.e., both scapulae; left clavicle, humerus, and ulna, both os coxae, femora, and fibulae, and right foot bones). Age-at-death estimation, location and distribution pattern, and morphological appearances of the lesions indicated that this juvenile suffered from a neoplastic condition. A comprehensive differential diagnosis was carried out, suggesting that these lesions were compatible with hereditary multiple osteochondromas. However, Ewing's sarcoma was not definitively ruled out as a probable diagnosis. Thus, this work adds new evidence to the existence of neoplastic conditions in the prehistoric populations of the Americas, and it contributes original data to perform a differential diagnosis for multiple proliferative lesions.

Possible prostate cancer in northern Peru: Differential diagnosis, vascular anatomy, and molecular signaling in the paleopathology of metastatic bone disease.

This paper describes four possible cases of metastasized prostate cancer in archaeological human skeletons from the north coast of Peru spanning the Middle Sicán to Colonial eras (roughly A.D. 900-1600). Varying combinations of exuberant abnormal new bone formation and some abnormal bone loss affecting lumbar vertebrae and the bony sacrum were observed in these individuals. Detailed lesion descriptions are followed by a differential diagnosis that systematically eliminates pseudopathology, infectious diseases, sclerosing bone disorders, and most metastatic processes. However, metastasized prostate cancer cannot be rejected and is highly consistent with the observed lesions. Metastasized pancreatic, bladder, or carcinoid tumors represent additional, though far less likely, diagnostic options. Anatomical and molecular signaling factors further validate this differential diagnosis. The paravertebral venous plexus of Baston plays an anatomical role in the metastatic seeding of lumbar vertebra from prostate cancer. Further, abundant molecular signaling mechanisms upregulate multiple bone-forming mechanisms in prostate metastases, though initially such lesions may originate as lytic phenomena. These multiple lines of evidence help demonstrate a multi-level framework for explanation in paleopathology and especially to help better elucidate the complexities of ancient neoplastic diseases.

On the importance of considering disease subtypes: Earliest detection of a parosteal osteosarcoma? Differential diagnosis of an osteosarcoma in an Anglo-Saxon female.

A case of potentially dedifferentiated parosteal osteosarcoma was found in the proximal humerus of an adult female buried in the late Anglo-Saxon cemetery of Cherry Hinton, Cambridgeshire, UK. Key features include a large, dense, lobulated mass attached to the medial metaphysis of the proximal humerus by a broad-based attachment, accompanied by cortical destruction and widespread spiculated periosteal reaction. Radiographic images confirm medullary involvement, lack of continuity between the cortex and external mass, a radiolucent cleavage plane and possible radiolucent zones within the bony masses. Differential diagnoses considered include osteochondroma, myositis ossificans, fracture callus, as well as the primary malignancies of osteosarcoma and chondrosarcoma, and their various subtypes. The macroscopic and radiographic analysis of the tumor is described and discussed within clinical and paleopathological contexts. One of only 19 uncontested examples of osteosarcoma from past human populations, most of which remain unconfirmed, this case represents what we believe to be the earliest, and probably singular, bioarcheological example of parosteal osteosarcoma in human history.

Neoplasm or not? General principles of morphologic analysis of dry bone specimens.

Unlike modern diagnosticians, a paleopathologist will likely have only skeletonized human remains without medical records, radiologic studies over time, microbiologic culture results, etc. Macroscopic and radiologic analyses are usually the most accessible diagnostic methods for the study of ancient skeletal remains. This paper recommends an organized approach to the study of dry bone specimens with reference to specimen radiographs. For circumscribed lesions, the distribution (solitary vs. multifocal), character of margins, details of periosteal reactions, and remnants of mineralized matrix should point to the mechanism(s) producing the bony changes. In turn, this allows selecting a likely category of disease (e.g. neoplastic) within which a differential diagnosis can be elaborated and from which a favored specific diagnosis can be chosen.

Romuald Weglowski (1876-1935) - Orthopaedic Surgeon, Forgotten Pioneer of Limb Saving Tumour Surgery.

On May 16, 1914, The Lancet Journal published a paper by Romuald Weglowski, a Polish-born professor of Moscow University, entitled "Malignant tumours of bones: a new method in conservative operative treatment." The idea of biological resection presented in the paper consisted in thermocoagulation of the apparently cancerous part of a bone with a jet of steam. According to the author, dead bone rid of live malignant cells reconstructed itself quickly, which helped to preserve the functionality of the organ without considerable limitations. The events of the First World War, political changes in tsarist Russia and the recovery of independence by Poland greatly complicated Weglowski's professional career. We thought it would be interesting to present the life story of the great Polish surgeon in the context of his own method of bone cancer treatment, which without doubt marked the beginning of Polish orthopaedic oncology aimed at limb-saving surgery.

A rare probable chondroblastoma of the calcaneus in a pre-Columbian subadult from Illinois.

Discrete cystic or tumorous intraosseous lesions can arise from a variety of benign and malignant conditions as well as trauma and infection. They are clinically rarely observed in the calcaneus. A fourteen-to-seventeen-year-old subadult recovered from a Late Woodland (∼AD 800-1100) period mortuary context in the Mississippi River Valley of central Illinois presents with a single lytic intraosseous lesion on the posterior right calcaneus that bilaterally perforates the cortex. The lesion, although primarily anterior to the epiphyseal plate, does breach it. There is also a small perforation of the outer cortex of the epiphysis above the insertion of the Achilles' tendon. The lesion is well-defined with a primarily spongy cancellous interior margin. On the body of the calcaneus, there is periostosis and a slightly expansive endosteal reaction. Comparative radiographic assessments undertaken to differentially diagnose the lesion indicate that it was likely not malignant. Based on the posterior location, the radiographic signature, the bilateral cortical perforation and the breach of the epiphysis, the lesion is best interpreted as a chondroblastoma.