Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue and 90% of cases are due to dominant mutations in COL1A1 and COL1A2 genes. To increase OI disease knowledge and contribute to patient follow-up management, a homogeneous Italian cohort of 364 subjects affected by OI types I–IV was evaluated. The study population was composed of 262 OI type I, 24 type II, 39 type III, and 39 type IV patients. Three hundred and nine subjects had a type I collagen affecting function mutations (230 in α1(I) and 79 in α2(I)); no disease-causing changes were noticed in 55 patients. Compared with previous genotype–phenotype OI correlation studies, additional observations arose: a new effect for α1- and α2-serine substitutions has been pointed out and heart defects, never considered before, resulted associated to quantitative mutations (P = 0.043). Moreover, some different findings emerged if compared with previous literature; especially, focusing the attention on the lethal form, no association with specific collagen regions was found and most of variants localized in the previously reported “lethal clusters” were causative of OI types I–IV. Some discrepancies have been highlighted also considering the “50–55 nucleotides rule,” as well as the relationship between specific collagen I mutated region and the presence of dentinogenesis imperfecta and/or blue sclera. Despite difficulties still present in defining clear rules to predict the clinical outcome in OI patients, this study provides new pieces for completing the puzzle, also thanks to the inclusion of clinical signs never considered before and to the large number of OI Italian patients.

Myxofibrosarcoma (MFS) is a malignant soft tissue sarcoma (STS) that originates in the body’s connective tissues. It is characterized by the presence of myxoid (gel-like) and fibrous components and typically affects patients after the fifth decade of life. Considering the ongoing trend of increasing lifespans across many nations, MFS is likely to become the most common musculoskeletal sarcoma in the future. Although MFS patients have a lower risk of developing distant metastases compared with other STS cases, MFS is characterized by a high frequency of local recurrence. Notably, in 40–60% of the patients where the tumor recurs, it does so multiple times. Consequently, patients may undergo multiple local surgeries, removing the risk of potential amputation. Furthermore, because the tumor relapses generally have a higher grade, they exhibit a decreased response to radio and chemotherapy and an increased tendency to form metastases. Thus, a better understanding of MFS is required, and improved therapeutic options must be developed. Historically, preclinical models for other types of tumors have been instrumental in obtaining a better understanding of tumor development and in testing new therapeutic approaches. However, few MFS models are currently available. In this review, we will describe the MFS models available and will provide insights into the advantages and constraints of each model.

The partial loss of SMARCB1/INI1 expression has recently been reported in skull base conventional chordomas, with possible therapeutic implications. We retrospectively analyzed 89 patients with conventional spinal chordomas to investigate the differences in the immunohistochemical expression of SMARCB1/INI1 and the underlying genetic alterations in the SMARCB1 gene. Moreover, we assessed the correlation of clinicopathological features (age, gender, tumor size, tumor location, surgical margins, Ki67 labelling index, SMARCB1/INI1 pattern, previous surgery, previous treatment, type of surgery, and the Charlson Comorbidity Index) with patient survival. Our cohort included 51 males and 38 females, with a median age at diagnosis of 61 years. The median tumor size at presentation was 5.9 cm. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates were 90.8% and 54.9%, respectively. Partial SMARCB1/INI1 loss was identified in 37 (41.6%) patients with conventional spinal chordomas (27 mosaic and 10 clonal). The most frequent genetic alteration detected was the monoallelic deletion of a portion of the long arm of chromosome 22, which includes the SMARCB1 gene. Partial loss of SMARCB1/INI1 was correlated with cervical–thoracic–lumbar tumor location (p = 0.033) and inadequate surgical margins (p = 0.007), possibly due to the high degree of tumor invasiveness in this site. Among all the considered clinicopathological features related to patient survival, only tumor location in the sacrococcygeal region and adequate surgical margins positively impacted DFS. In conclusion, partial SMARCB1/INI1 loss, mostly due to 22q deletion, was detected in a significant number of patients with conventional spinal chordomas and was correlated with mobile spine location and inadequate surgical margins.

Lung cancer is the second most frequently diagnosed cancer in the world, and surgery is an integral part of the treatment for spinal metastases. The aims of this retrospective study were to assess the overall survival of surgically treated patients affected by lung cancer spinal metastases and identify any factors related to a better survival rate. We recruited 56 consecutive patients (34 male and 22 female) surgically treated for metastatic lung cancer in the spine from 2009 to 2019. Surgical indications were based on a previously published and validated flow chart following a multidisciplinary evaluation. We assessed the localization of vertebral metastases, the presence of other bone or visceral metastases, neurological status according to the Frankel score, ambulatory autonomy, and general status, measured with the Karnofsky performance scale. The expected prognosis was retrospectively assessed according to the revised Tokuhashi score. The median survival was 8.1 months, with over a third of patients surviving more than 1 year. We observed a global improvement in all clinical parameters after surgical treatment. The Tokuhashi predictive score did not correlate with survival after surgery. The results of this study suggest that the surgical treatment of symptomatic spinal metastases from lung cancer can improve quality of life, even in patients with a shorter life expectancy, by controlling pain and improving autonomy.

Bone metastases from osteosarcoma occur in only 10% of patients, and related preclinical models are lacking. A patient diagnosed with pelvic osteosarcoma developed a metachronous scapular metastasis and was treated with multi-agent chemotherapy and surgery. Patient-derived tissue fragments (PDTFs) were obtained from leftover material after diagnosis and biobanking. PDTFs were grown on chick chorioallantoic membrane, establishing an in vivo-like predictive model. Additionally, we obtained a patient-derived cell culture, OS-MET-R-092, which has been maintained in vitro for nearly one year. OS-MET-R-092 cells were authenticated based on short tandem repeats and on their morphology when grown on commercial 3D scaffolds. Using U-2 OS and SaOS-2 as controls, we characterized growth, clonogenic potential, ability to form spheroids, migration, osteogenic differentiation, and expression of related genes. OS-MET-R-092 cells showed a low proliferation rate, impaired differentiation potential, and migratory abilities comparable to SaOS-2, while expressing higher levels of some MMPs and CD44. Functionally, OS-MET-R-092 cells demonstrated a resistant phenotype to doxorubicin, cisplatin, gemcitabine, and docetaxel, corroborated by higher expression of chemo-resistance-related genes. Collectively, OS-MET-R-092 represents a valuable tool for studying bone metastasis from osteosarcoma across various experimental settings and serves as the foundational building block for composite and translatable 3D models.