Costantino Errani

A novel WWTR1‐CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites

The classification of epithelioid vascular tumors remains challenging, as there is considerable morphological overlap between tumor subtypes, across the spectrum from benign to malignant categories. A t(1;3)(p36.3;q25) translocation was reported in two cases of epithelioid hemangioendothelioma (EHE), however, no follow‐up studies have been performed to identify the gene fusion or to assess its prevalence in a larger cohort of patients. We undertook a systematic molecular analysis of 17 EHE, characterized by classic morphological and immunophenotypic features, from various anatomical locations and with different malignant potential. For comparison, we analyzed 13 epithelioid hemangiomas, five epithelioid angiosarcomas, and four epithelioid sarcoma‐like EHE. A fluorescence in situ hybridization (FISH) positional cloning strategy, spanning the cytogenetically defined regions on chromosomes 1p36.3 and 3q25, confirmed rearrangements in two candidate genes from these loci in all EHE cases tested. None of the other benign or malignant epithelioid vascular tumors examined demonstrated these abnormalities. Subsequent reverse transcription‐polymerase chain reaction (RT‐PCR) confirmed in three EHE the WWTR1‐CAMTA1 fusion product. CAMTA1 and WWTR1 have been previously shown to play important roles in oncogenesis. Our results demonstrate the presence of a WWTR1‐CAMTA1 fusion in all EHE tested from bone, soft tissue, and visceral location (liver, lung) in keeping with a unique and specific pathological entity. Thus, FISH or RT‐PCR analysis for the presence of WWTR1‐CAMTA1 fusion may serve as a useful molecular diagnostic tool in challenging diagnoses.

Percutaneous CT-guided biopsy of the spine: results of 430 biopsies

Biopsies of lesions in the spine are often challenging procedures with significant risk of complications. CT-guided needle biopsies could lower these risks but uncertainties still exist about the diagnostic accuracy. Aim of this retrospective study was to evaluate the diagnostic accuracy of CT-guided needle biopsies for bone lesions of the spine. We retrieved the results of 430 core needle biopsies carried out over the past fifteen years at the authors’ institute and examined the results obtained. Of the 430 biopsies performed, in 401 cases the right diagnosis was made with the first CT-guided needle biopsy (93.3% accuracy rate). Highest accuracy rates were obtained in primary and secondary malignant lesions. Most false negative results were found in cervical lesions and in benign, pseudotumoral, inflammatory, and systemic pathologies. There were only 9 complications (5 transient paresis, 4 haematomas that resolved spontaneously) that had no influence on the treatment strategy, nor on the patient’s outcome. In conclusion we can assert that this technique is reliable and safe and should be considered the gold standard in biopsies of the spine.

68Ga-Citrate PET/CT for Evaluating Patients with Infections of the Bone: Preliminary Results

The aim of this work was to preliminarily evaluate the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of 68Ga-citrate PET/CT in a population of patients with suspected bone infections. Methods: We enrolled 31 patients with suspected osteomyelitis or diskitis who underwent a total of forty 68Ga-citrate PET/CT scans. The results were compared with different combinations of diagnostic procedures (MRI, radiography, CT, or white blood cell scintigraphy), biopsy (when diagnostic), and follow-up data (at least 1 y) to determine the performance of 68Ga-citrate PET/CT. Results: We found a sensitivity of 100%, a specificity of 76%, a positive predictive value of 85%, a negative predictive value of 100%, and an overall accuracy of 90%. Conclusion: Although preliminary, these data confirm a possible role for 68Ga-citrate in the diagnosis of bone infections, especially in consideration of its favorable characteristics.

Osteosarcoma in Patients Older Than 65 Years

PURPOSE We reviewed the outcome of osteosarcoma patients older than 65 years, an age group usually excluded from protocols, to determine the different clinical features and prognostic factors in this age group compared with younger patients. PATIENTS AND METHODS Patients treated at our institute who had high-grade osteosarcoma and were older than 65 years were observed. RESULTS Forty-three patients were eligible to be enrolled onto this study; of these, 22 were male and 21 were female. The median age of this group was 69 years (range, 65 to 80 years). Of the 43 patients, 29 patients had localized disease, and 14 patients had metastatic disease. Localizations were appendicular in 33 patients, and axial in 10 patients. Twenty-nine patients had a primary osteosarcoma, 13 patients (30%) had a sarcoma in Pagets disease, and one patient had postradiotherapy (RT) osteosarcoma. The median interval from onset of symptoms to diagnosis was 4 months (range, 0 to 73 months).Thirty-two of 43 patients received surgery for a primary tumor. Of these, 18 patients had limb salvage, 13 patients had an amputation, and one patient had palliative surgery; the remaining 11 patients received palliative RT. Fourteen patients received chemotherapy; two deaths related to chemotherapy were observed. Median overall survival (OS) for all 43 patients was 19 months (range, 3 to 229 months); 5-year OS was 22% (SE = 3%) for the whole group, and 45% OS for those patients with localized primary osteosarcoma. Multivariate analysis demonstrated that stage, volume, and surgery were significant prognostic factors. Insignificant prognostic factors were sex, type of surgery, chemotherapy, and Pagets disease. CONCLUSION Patients older than 65 years with osteosarcoma have a worse prognosis compared with younger patients. This older age group is characterized by a longer time lapse from the onset of symptoms to diagnosis, more metastatic cases at diagnosis, less use of limb salvage, fewer patients receiving chemotherapy, and more patients excluded from clinical trials than a younger age group.

Palliative therapy for osteosarcoma.

Despite advances in diagnostic imaging, the evolution of neoadjuvant chemotherapy and the refinements in limb-salvage surgery, the progression-free survival rate remains poor for patients with metastatic, recurrent or unresectable osteosaroma. Different therapeutic strategies for these subgroups of patients have been employed to control disease and prolong survival. Treatment options are limited and controversial, including systemic and localized therapies. Surgical resection, whenever feasible, is still the standard treatment in advanced osteosarcoma. The role of chemotherapy is unclear while the use of radiotherapy, embolization and thermal ablation is increasing. New therapeutic experimental approaches and novel target therapies are needed to improve the outcome of these subgroups of patients.

Current concepts in the biopsy of musculoskeletal tumors: AAOS exhibit selection.

BACKGROUND A musculoskeletal tumor biopsy can involve fine needle aspiration, core needle biopsy, or incisional biopsy. Controversy regarding the diagnostic yield of these biopsy techniques continues. The purpose of this article is to summarize the current concepts in the biopsy of musculoskeletal tumors. METHODS We performed a literature review of clinical articles reporting on the biopsy of bone and soft-tissue primary tumors. Clinical articles were excluded on the basis on abstract content if they represented case reports, review or opinion articles, or technique descriptions. Eighteen of the thirty-nine articles that remained were excluded because the results did not indicate the diagnostic accuracy of the various biopsy techniques. Thus, twenty-one articles with diagnostic data on the biopsy of bone and soft-tissue tumors were included in this review. RESULTS Core needle biopsy appeared to be more accurate than fine needle aspiration, and incisional biopsy appeared to be more accurate than both of these techniques, but the differences did not reach significance. Incisional biopsy was more expensive than the percutaneous biopsy methods. In deep musculoskeletal tumors, incorporation of ultrasonography or computed tomography for guidance is easy and safe and can be useful for increasing the accuracy of the biopsy. Advantages of a percutaneous technique compared with an incisional one are the low risk of contamination and the minimally invasive nature. Certain anatomic locations and histologic types were associated with diagnostic difficulty. Vertebral tumors had the lowest diagnostic accuracy regardless of the biopsy technique. Myxoid, infection, and round cell histologies were associated with the lowest diagnostic accuracy. CONCLUSIONS The current literature has not clarified the optimal biopsy technique for the diagnosis of bone and soft-tissue tumors. However, core needle biopsy is usually preferable to incisional biopsy because of the low risk of contamination and the low cost. In addition, the use of imaging guidance increases the diagnostic accuracy of musculoskeletal biopsies and reduces the risk of complications. If the result of a percutaneous biopsy is nondiagnostic, a small incisional biopsy should be performed. LEVEL OF EVIDENCE Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Protocol of surgical treatment of long bone pathological fractures

Long bone pathological fractures in patients with primary and metastatic bone tumours are difficult to treat and their management may alter the prognosis of the disease and jeopardize survival. The aim of this article was to review the relevant studies reporting on the management of tumour patients with pathological fractures of the long bones, to discuss the most suitable approach in these patients, to highlight specific treatment recommendations, and finally based on this analysis and our clinical practice, to propose a treatment algorithm for decision making and treatment.

Epithelioid Hemangioma of Bone and Soft Tissue: A Reappraisal of a Controversial Entity

BackgroundThe controversy surrounding diagnosis of an epithelioid hemangioma (EH), particularly when arising in skeletal locations, stems not only from its overlapping features with other malignant vascular neoplasms, but also from its somewhat aggressive clinical characteristics, including multifocal presentation and occasional lymph node involvement. Specifically, the distinction from epithelioid hemangioendothelioma (EHE) has been controversial. The recurrent t(1;3)(p36;q25) chromosomal translocation, resulting in WWTR1-CAMTA1 fusion, recently identified in EHE of various anatomic sites, but not in EH or other epithelioid vascular neoplasms, suggests distinct pathogeneses.Question/purposesWe investigated the clinicopathologic and radiologic characteristics of bone and soft tissue EHs in patients treated at our institution with available tissue for molecular testing.Patients and MethodsSeventeen patients were selected after confirming the pathologic diagnosis and fluorescence in situ hybridization analysis for the WWTR1 and/or CAMTA1 rearrangements. Four patients had multifocal presentation. Most patients with EH of bone were treated by intralesional curettage. None of the patients died of disease and only four patients had a local recurrence.ResultsOur results, using molecular testing to support the pathologic diagnosis of EH, reinforce prior data that EH is a benign lesion characterized by an indolent clinical course with an occasional multifocal presentation and rare metastatic potential to locoregional lymph nodes.ConclusionThese findings highlight the importance of distinguishing EH from other malignant epithelioid vascular tumors as a result of differences in their management and clinical outcome.Level of Evidence Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Post traumatic myositis ossificans: Sonographic findings

The aim of this paper is to describe the sonographic (US) features of post traumatic myositis ossificans (PTMO).

Current Concepts in the Biopsy of Musculoskeletal Tumors

In the management of bone and soft tissue tumors, accurate diagnosis, using a combination of clinical, radiographic, and histological data, is critical to optimize outcome. On occasion, diagnosis can be made by careful history, physical examination, and images alone. However, the ultimate diagnosis usually depends on histologic analysis by an experienced pathologist. Biopsy is a very important and complex surgery in the staging process. It must be done carefully, so as not to adversely affect the outcome. Technical considerations include proper location and orientation of the biopsy incision and meticulous hemostasis. It is necessary to obtain tissue for a histological diagnosis without spreading the tumor and so compromise the treatment. Furthermore, the surgeon does not open compartmental barriers, anatomic planes, joint space, and tissue area around neurovascular bundles. Nevertheless, avoid producing a hematoma. Biopsy should be carefully planned according to the site and definitive surgery and should be performed by an orthopedic surgeon with an experience in musculoskeletal oncology who will perform the definitive surgery. Improperly done, it can complicate patient care and sometimes even eliminate treatment options. Different biopsy techniques are suitable: fine-needle aspiration, core-needle biopsy, and incisional biopsy. The choice of biopsy depends on the size, the location of the lesion, and the experience of the pathologist.