The utility of FISH analysis in the diagnosis of BCOR-rearranged sarcomas.

BACKGROUND: A BCL6 corepressor (BCOR) gene alteration is a genetic signature of rare subsets of sarcomas. The identification of this alteration has recently contributed to the definition of new entities in the current WHO (2020) classification of soft tissue and bone tumours. We retrospectively examined cases of BCOR-rearranged sarcoma (BRS) to assess the reliability of the BCOR FISH analysis using an IVD (in vitro diagnostic) probe. METHODS: We investigated and compared the molecular diagnostic strategies and features by collecting 17 data from patients with a BCOR gene rearrangement detected using quantitative-Reverse Transcription-Polymerase Chain Reaction (qRTPCR), Next-Generation Sequencing (NGS) and Fluorescence in situ hybridization (FISH). RESULTS: We describe fourteen BCOR::CCNB3 sarcomas, one spindle cell sarcoma with a novel BCOR::MAML1 fusion, one spindle cell sarcoma with a novel BCOR::AHR fusion, and one ossifying fibromyxoid tumour with a BCOR::ZC3H7B fusion. FISH analysis of all, except one, BCOR::CCNB3 sarcoma, showed a FISH break-apart pattern with mild signal separation. The MAML1::BCOR sarcoma showed large-space split signals, while in the two patients with AHR::BCOR and ZC3H7B::BCOR fusions, no BCOR rearrangement was observed using FISH. CONCLUSIONS: Our study indicates that BCOR FISH analysis using an IVD probe, may be useful to detect the presence of a BCOR rearrangement, including both translocations and inversions; however, negative results, in some cases, can occur.

Secondary peripheral chondrosarcoma in multiple osteochondromas: a retrospective single-institution case series.

BACKGROUND: Multiple osteochondromas is genetic disorder characterized by the formation of multiple benign cartilage-capped bone tumors, named osteochondromas, during skeletal development. The most feared complication is the secondary peripheral chondrosarcoma, a malignant cartilaginous neoplasm that arises from the chondroid cap of pre-existent osteochondromas. We conducted a retrospective cohort study on patients diagnosed and followed up from 1960 to 2019 to describe the clinical and pathological features of individuals affected by peripheral chondrosarcoma in multiple osteochondromas, to evaluate follow up information and individual outcome and to compare the results with literature. Data, including age, gender, site, histological grade, cartilage cap thickness, surgical treatments, surgical margins, genotype mutational status as well as treatment details were captured from the hospital electronic health records and from Registry of Multiple Osteochondromas. In addition, a complete histological review of all hematoxylin and eosin (H&E)-stained sections has been performed by expert pathologists. RESULTS: One hundred five of the screened cases were included in the present study. The age at diagnosis of SPC ranges from 13 to 63, with median age at diagnosis of 34 years. The site most frequently affected by malignant degeneration was the pelvis (46 patients, 44%) with higher incidence in male patients (32 males vs.14 females). The second one was lower limbs (including femur, fibula, or tibia), identified in 35 patients. Histological information - available for 103 patients - showed: 59 patients with grade 1; 40 patients had a grade 2 and 4 patients had a grade 3. The most common surgical treatment was the complete resection, followed by debulking, amputation and partial resection. Most of cases did not have recurrence of the disease. Outcome in disease-free survival highlights that a worse course of the disease was associated with histological grade 2 or 3, and partial resection surgery. In most of analyzed cases (94%) a pathogenic variant was identified. CONCLUSIONS: In conclusion, the present study gives an overview of the secondary peripheral chondrosarcomas, confirming that this disease represents an impacting complication for multiple osteochondromas patients and suggests that malignant transformation can occur also in younger patient, in a not irrelevant number of cases.

A Systematic Review of Adjuvant Chemotherapy in Localized Dedifferentiated Chondrosarcoma.

Dedifferentiated chondrosarcoma (DDCS) is a high-grade subtype of chondrosarcoma with the bimorphic histological appearance of a conventional chondrosarcoma component with abrupt transition to a high-grade, non-cartilaginous sarcoma. DDCS can be radiographically divided into central and peripheral types. Wide resection is currently the main therapeutic option for localized DDCS. Moreover, the effectiveness of adjuvant chemotherapy remains controversial. Therefore, we performed a systematic review of available evidence to evaluate the effect of adjuvant chemotherapy on localized DDCS. The purpose was to compare the 5-year survival rate among patients treated with surgery plus adjuvant chemotherapy or surgery alone for localized DDCS. The search was conducted in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Of the 217 studies shortlisted, 11 retrospective non-randomized studies (comprising 556 patients with localized DDCS) were selected. The 5-year survival rates were similar between the two treatment groups (28.2% (51/181) vs. 24.0% (90/375), respectively). The overall pooled odds ratio was 1.25 (95% confidence interval: 0.80-1.94; p = 0.324), and heterogeneity I2 was 2%. However, when limited to peripheral DDCS, adjuvant chemotherapy was associated with prolonged survival (p = 0.03). Due to the paucity of included studies and the absence of prospective comparative studies, no conclusions can be drawn regarding the effectiveness or ineffectiveness of adjuvant chemotherapy for localized DDCS.

Diagnostic challenges in low-grade central osteosarcoma.

Aims: Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes. Methods: We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder's grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome. Results: Based on imaging, 35 of 49 patients (71.4%) exhibited malignant features. Overall, 40 of 49 patients (81.6%) had undergone a biopsy before en-bloc resection: 27 of 40 patients (67.5%) were diagnosed on the first biopsy, which was more accurate when carried out by open rather than needle biopsy (91.3% vs 35.3% diagnostic accuracy, respectively; p < 0.001). Of the 40 patients treated by en-bloc resection, surgical margins were wide in 38 (95.0%) and marginal in two (5.0%). Furthermore, nine of 49 patients (18.4%) underwent curettage (intralesional margin) without previous biopsy. All patients with a positive margin developed local recurrence. Distant metastases occurred in five of 49 patients (10.2%). The mean five-year overall survival (OS) and distant relapse-free survival (D-RFS) were 89.3% (SD 5.1%) and 85.7% (SD 5.5%), respectively. Univariate analysis showed that the occurrence of distant metastasis was a poor prognostic factor for OS (hazard ratio 11.54, 95% confidence interval (CI) 1.92 to 69.17; p < 0.001). Local recurrence was a poor prognostic factor for D-RFS (HR 8.72, 95% CI 1.69 to 45.0; p = 0.002). Conclusion: The diagnosis of LGCOS can be challenging because it may present with non-malignant features and has a low diagnostic accuracy on biopsy. If precisely diagnosed, LGCOS can be successfully treated by surgical excision with wide margins.

Imaging Features of Alveolar Soft Part Sarcoma: Single Institution Experience and Literature Review.

Alveolar soft part sarcoma (ASPS) is an extremely rare and aggressive soft-tissue sarcoma (STS) subtype with poor prognosis and limited response to radiation therapy and chemotherapy. Prompt recognition and referral to sarcoma centers for appropriate management are crucial for patients' survival. The purpose of this study was to report ASPS pre-treatment imaging features and to examine the existing literature on this topic. Twelve patients (7 women, 5 men-mean age 27.1 ± 10.7 years) were included from our single-center experience. Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) available were reviewed according to an analysis grid incorporating features from the latest research on STS. Clinical, histological, and outcome data were collected. MRI was available in 10 patients (83.3%), US in 7 patients (58.3%), and CT in 3 patients (25%). Mean longest tumor diameter was 7.6 ± 2.9 cm, and all tumors were deeply seated. Large peritumoral feeding vessels were systematically found and identified on ultrasonography (7/7), MRI (10/10), and CT (3/3). US revealed a well-defined heterogeneous hypoechoic pattern, with abundant flow signals in all patients (7/7). In all patients, MRI showed mildly high signal intensity (SI) on T1-WI and high SI on T2-WI and peritumoral edema. Moreover, flow-voids (due to arteriosus high-flow) into the peritumoral/intratumoral feeding vessels were detected in the MRI fluid-sensitive sequences of all patients. At baseline, whole-body contrast-enhanced CT revealed metastases in 8/12 (66.7%) patients. A pre-treatment longest diameter > 5 cm was significantly associated with distant metastases at diagnosis (p = 0.01). A maximum diameter > 5 cm represents a risk of metastatic disease at diagnosis (odds ratio = 45.0000 (95% CI: 1.4908-1358.3585), p = 0.0285). In the comprehensive literature review, we found 14 articles (case series or original research) focusing on ASPS imaging, with a total of 151 patients included. Merging our experience with the data from the existing literature, we conclude that the hallmark of ASPS imaging at presentation are the following characteristics: deep location, a slight hyperintense MRI SI on T1-WI and a hyperintense SI on T2-WI, numerous MRI flow voids, high internal vascularization, and large peritumoral feeding vessels.

Myoepithelial carcinoma of soft tissues and bone.

AIM: Myoepithelial carcinoma occurs mainly in salivary glands but rarely can also occur in soft tissues or bone. In this paper, we evaluated the role of surgical margins, radiotherapy, and chemotherapy in myoepithelial carcinoma of soft tissue and bone (MC-SB) treated at our Institute. METHODS: Medical records of 33 patients presenting with MC-SB between 1998 and 2015 at our institution were retrospectively analysed, and diagnosis and treatment were studied. RESULTS: The median follow-up was 58.5 months. Twenty patients had tumours originating in soft tissues and 13 in bone. Eight patients (24.2%) had metastases at diagnosis, the remaining 25 had localised disease. Thirty-two underwent resection of the primary lesion. In 29 surgical margins were evaluated: wide in 28 with 10/28 who recurred (35.7%) and marginal resection in 1 who also recurred. Six patients received adjuvant radiotherapy. Metastases developed in 15/25 patients (60%) with localised disease at onset. Chemotherapy was administered in patients with metastatic advanced disease. Cisplatin+doxorubicin was administered in six patients as first-line chemotherapy with an objective response in 5/6 patients with a median 4-month duration. Five-year overall survival rate was 62.6% in patients with localised tumours and 12.5% in those metastatic at diagnosis. CONCLUSIONS: MC-SB showed a high incidence of local recurrences and metastases. Despite different chemotherapy regimens, the outcome remains poor in patients with metastatic disease. Due to the absence of a standard protocol, we encourage treatment by multidisciplinary teams in referral centres with renowned expertise.

NTRK rearranged sarcoma of the bone. Role for larotrectinib in the neoadjuvant setting of an ultra-rare tumor: a case report.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene-fusion targeted molecules revolutionized the paradigm of treatment of a limited subgroup of cancers of various histologies. Entrectinib and larotrectinib obtained unprecedented response rates in patients with cancer harboring NTRK rearrangements. This evidence recently led to the agnostic approval of these drugs, and evidence (confirmation) of their activity in a broader disease setting is emerging. Here, we report the case of a patient affected by EML4-NTRK3 rearranged undifferentiated spindle cell bone sarcoma treated with larotrectinib, and we argue (discuss about) the incidence and clinical presentation of NTRK gene-fusion positive bone sarcomas, the potential use of upfront treatment with NTRK inhibitors in neoadjuvant setting, and the role of a multidisciplinary tumor board. Despite the rarity of these rearrangements in patients with primitive bone sarcomas, the therapy with NTRK inhibitors represents a highly effective strategy to be pursued in selected cases even in neoadjuvant settings. The management of these very rare cancers should always be discussed in a multidisciplinary board of reference centers.

SMARCB1/INI1 loss in skull base conventional chordomas: a clinicopathological and molecular analysis.

Introduction: The loss of SMARCB1/INI1 protein has been recently described in poorly differentiated chordoma, an aggressive and rare disease variant typically arising from the skull base. Methods: Retrospective study aimed at 1) examining the differential immunohistochemical expression of SMARCB1/INI1 in conventional skull base chordomas, including the chondroid subtype; 2) evaluating SMARCB1 gene deletions/copy number gain; and 3) analyzing the association of SMARCB1/INI1 expression with clinicopathological parameters and patient survival. Results: 65 patients (35 men and 30 women) affected by conventional skull base chordoma, 15 with chondroid subtype, followed for >48 months after surgery were collected. Median age at surgery was 50 years old (range 9-79). Mean tumor size was 3.6 cm (range 2-9.5). At immunohistochemical evaluation, a partial loss of SMARCB1/INI1 (>10% of neoplastic examined cells) was observed in 21 (32.3%) cases; the remaining 43 showed a strong nuclear expression. Fluorescence in situ hybridization (FISH) analysis was performed in 15/21 (71.4%) cases of the chordomas with partial SMARCB1/INI1 loss of expression. Heterozygous deletion of SMARCB1 was identified in 9/15 (60%) cases and was associated to copy number gain in one case; no deletion was found in the other 6 (40%) cases, 3 of which presenting with a copy number gain. No correlations were found between partial loss of SMARCB1/INI1 and the clinicopathological parameters evaluated (i.e., age, tumor size, gender, tumor size and histotype). Overall 5-year survival and 5-year disease-free rates were 82% and 59%, respectively. According to log-rank test analysis the various clinico-pathological parameters and SMARCB1/INI1 expression did not impact on overall and disease free-survival. Discussion: Partial loss of SMARCB1/INI1, secondary to heterozygous deletion and/or copy number gain of SMARCB1, is not peculiar of aggressive forms, but can be identified by immunohistochemistry in a significant portion of conventional skull base chordomas, including the chondroid subtype. The variable protein expression does not appear to correlate with clinicopathological parameters, nor survival outcomes, but still, it could have therapeutic implications.

Fusion transcriptome profiling defines the monoclonal origin of multifocal epithelioid haemangioma of bone.

AIMS: Epithelioid haemangioma (EH) of bone remains a highly controversial entity. Indeed, the WHO classifies EHs of soft tissues as benign tumours, whereas bone EHs are considered intermediate-locally aggressive tumours due to common multifocal presentation and local destructive growth. To gain insights into the clinical behaviour and biology of EH of bone we retrospectively analysed 42 patients treated in a single institution from 1978 to 2021. METHODS AND RESULTS: Multifocal presentation was detected in 17 of 42 patients (40%) primarily as synchronous lesions. Patients were treated with curettage (57%), resection (29%) or biopsy, followed by radiotherapy or embolisation (14%). Follow-up (minimum 24 months) was available for 38 patients, with only five local recurrences (13%) and no death of disease. To clarify whether the synchronous bone lesions in multifocal EH represent multicentric disease or clonal dissemination, four cases were profiled by RNA-sequencing. Separate lesions from the same patient, which showed a similar transcriptional profile, expressed the same fusion transcript (involving FOS or FOSB) with identical gene breakpoints. CONCLUSIONS: These results indicate that, in EH of bone, multifocal lesions are clonally related and therefore represent the spread of a same neoplastic clone rather than simultaneous independent tumours. This finding is in apparent contradiction with the benign clinical course of the disease, and suggests that tumour dissemination in bone EH probably reflects a phenomenon of passive spreading, with tumour cells colonising distal sites while maintaining their benign biological nature.

Indications and Limits of Surgery for Spinal Metastases Derived from Lung Cancer: A Single-Center Experience.

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.

Multicentric Giant Cell Tumor of Bone.

The typical presentation of giant cell tumor of bone is a solitary lesion involving the meta-epiphyseal region of the long bones. The presence of more than one distinct giant cell tumor in the same patient is rare. This study reports on 7 patients with multicentric giant cell tumor of bone. Clinical and radiologic features were reviewed to evaluate the behavior of multicentric giant cell tumor of bone. Immunohistochemistry and genetic analysis for the H3F3A gene were performed to confirm the diagnosis. The knee was most frequently involved, and most of the lesions were in an ipsilateral extremity. All of the patients received surgical management with curettage or resection. The overall median follow-up was 194 months (interquartile range, 41-336 months). Five of 7 patients had local recurrence (71%), but considering the number of surgically treated lesions, the risk of local recurrence was 33% (5 local recurrences among 15 treated lesions). No lung metastases occurred. Multicentric giant cell tumor of bone tends to exhibit the same aggressive clinical behavior as solitary giant cell tumor of bone. Patients should be monitored for the occurrence of other lesions, especially in the ipsilateral extremity. [Orthopedics. 2023;46(6):e376-e380.].

Giant cell tumor of bone with secondary aneurysmal bone cyst does not have a higher risk of local recurrence.

BACKGROUND: Fluid-fluid levels (FFLs) is found in 10%-16% of giant cell tumor of bone (GCTB), and the presence of FFLs raises the suspicion of GCTB with secondary aneurysmal bone cyst (ABC), which can lead to increased intraoperative bleeding and, blurring the operative field, be associated with a risk of local recurrence. The first objective of this study is to determine whether secondary ABC is associated with a higher risk of local recurrence after curettage in patients with GCTB of the extremities. The second objective of this study is to investigate the sensitivity, specificity, positive predictive value, and negative predictive value of the presence of FFLs detected on magnetic resonance imaging (MRI) to diagnose secondary ABC associated with GCTB. METHODS: Two hundred and eighty patients with GCTB of the extremities who underwent curettage at the authors' institutions between 1980 and 2021 were included in this study. RESULTS: Secondary ABC was found in 36 of 280 patients (12.9%) and local recurrence occurred in 66 of 280 patients (23.6%). Multivariate analysis showed no significant correlation between secondary ABC and local recurrence (hazard ratio [HR]: 1.87 (95% confidence interval [CI]: 1.00-3.53]; p = 0.051). Preoperative MRI revealed FFLs in 13 of 82 patients (15.9%). Sensitivity, specificity, positive predictive value, and negative predictive value of FFLs detected on preoperative MRI to diagnose secondary ABC were 36.8%, 90.5%, 53.8%, and 82.6%, respectively. CONCLUSION: The results of this study showed that secondary ABC does not increase the risk of local recurrence after curettage in patients with GCTB of the extremities. Although rare, FFLs were present in patients with GCTB and half of those with FFLs detected on preoperative MRI had secondary ABC.

Sensitivity, Specificity, and Predictive Values of Tru-Cut® Biopsy in Grading Primary Localized Myxoid Liposarcomas of the Extremities.

(1) Background: Histological diagnosis and tumor grading are major prognostic and predictive factors in soft tissue sarcomas (STS), as they dictate the treatment strategies with a direct impact on patient survival. This study aims to investigate the grading accuracy, sensitivity, and specificity of Tru-Cut® biopsy (TCB) in primary localized myxoid liposarcomas (MLs) of the extremities and its impact on patient prognosis. (2) Methods: Patients with ML undergoing TCB and a subsequent tumor resection between 2007 and 2021 were evaluated. Concordance between the preoperative assessment and definitive histology was calculated with a weighted Cohen's kappa coefficient. Sensitivity, specificity, and diagnostic accuracy were calculated. (3) Results: Of 144 biopsies, the histological grade concordance rate was 63% (Kappa 0.2819). Neoadjuvant chemotherapy and/or radiotherapy impacted concordance with a downgrading effect in high-grade tumors. Among forty patients not treated in neoadjuvant settings, the sensitivity of TCB was 57%, the specificity was 100%, and the overall predictive values of positive and negative TCB were 100% and 50%, respectively. Misdiagnosis did not impact overall survival. (4) Conclusions: TCB may underestimate ML grading due to tumor heterogeneity. Neoadjuvant ChT and/or radiotherapy are associated with pathological downgrading; however, discordance in diagnosis does not modify patient prognosis because systemic treatment decision-making also includes other variables.

A global collaboRAtive study of CIC-rearranged, BCOR::CCNB3-rearranged and other ultra-rare unclassified undifferentiated small round cell sarcomas (GRACefUl).

BACKGROUND: Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients. METHODS: URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified. Based on molecular assessment, cases were classified as follows: (1) CIC-rearranged round cell sarcomas, (2) BCOR::CCNB3-rearranged round cell sarcomas, (3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed. RESULTS: In total, 148 patients were identified [88/148 (60%) CIC-rearranged sarcoma (median age 32 years, range 7-78), 33/148 (22%) BCOR::CCNB3-rearranged (median age 17 years, range 5-91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4-70)]. One hundred-one (68.2%) cases presented with localised disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site, and a low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5-98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7-51.3) in CIC-rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1-90.6; p < 0.0001). CONCLUSIONS: This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype.

Imaging presentation of extraskeletal osteosarcomas on CT and MRI and correlation with patients outcome: A two-center retrospective study of 54 patients.

PURPOSE: The purpose of this study was to analyze the imaging features of extraskeletal osteosarcomas (ESOS) on computed tomography (CT) and magnetic resonance imaging (MRI) and to investigate their associations with overall survival (OS) using uni- and multivariable survival analyses. MATERIALS AND METHODS: This two-center retrospective study included all consecutive adult patients between 2008 and 2021 with histopathologically-proven ESOS who underwent pre-treatment CT and/or MRI. Clinical and histological characteristics, ESOS presentation on CT and MRI, treatment and outcomes were reported. Survival analyses were performed using Kaplan-Meier analysis and Cox regressions. Associations between imaging features and OS were searched using uni- and multivariable analyses. RESULTS: Fifty-four patients were included (30/54 [56%] men, median age: 67.5 years). Twenty-four died of ESOS (median OS: 18 months). ESOS were mostly deep-seated (46/54, 85%) in the lower limb (27/54, 50%) with a median size of 95 mm (interquartile range: 64, 142; range: 21-289 mm). Mineralization was seen on 26/42 (62%) patients, mainly gross-amorphous (18/26; 69%). ESOS were generally highly heterogeneous on T2-weighted images (38/48; 79%) and contrast-enhanced (CE) T1-weighted images (29/40; 72%), with necrosis (39/40; 97%), well-defined or focally infiltrative margins (39/47; 83%), with moderate peritumoral edema (39/47; 83%) and rim-like peripheral enhancement (17/40; 42%). Size, location, mineralization on CT, signal intensity heterogeneity on T1-, T2- and CE-T1-weighted images and hemorragic signal on MRI were associated with poorer OS (range of log-rank P = 0.0069-0.0485). At multivariable analysis, hemorragic signal and signal intensity heterogeneity on T2-weighted images remained predictive for poorer OS (hazard ratio [HR] = 2.68, P = 0.0299; HR = 9.85, P = 0.0262, respectively) CONCLUSION: ESOS typically presents as mineralized heterogeneous and necrotic soft tissue tumor with a possible rim-like enhancement and limited peritumoral abnormalities. MRI may help estimate outcome of patients with ESOS.

Osteogenic sarcomas of the hands: A case series with emphasis in its peculiarities and literature review.

AIM: To present our experience on osteosarcomas of the hands and review the existing literature pertaining osteosarcomas in this extremely rare location. METHODS: and results: Seven cases of osteosarcomas of the hands were reviewed, and a literature search of all primary osteosarcomas of the hands was performed. All tumors occurred in adults (mean age, 41 years) and were located mainly around the metacarpophalangeal joints. All patients presented with localized long-lasting pain as main symptom. The mean size at diagnosis was 33 mm. Three tumors were low-grade central osteosarcomas, 1 low-grade central chondroblastoma-like osteosarcoma and 3 high-grade osteosarcomas. All tumors were positive for mouse double-minute 2 homolog (MDM2) immunohistochemistry. Three cases yielded results with fluorescence in-situ amplification for MDM2 (12q15)/CEP12. At last follow-up, one patient with a high-grade osteosarcoma was dead of disease. The literature review revealed similar demographic and site distribution of osteosarcomas within the hands than our series and an unusually high proportion of low-grade central and parosteal osteosarcomas when compared to the proportion of these infrequent neoplasms in the whole skeleton. CONCLUSIONS: osteosarcomas of hands present in older individuals compared to the population affected by conventional osteosarcomas of all sites. Importantly from a diagnostic, therapeutic and prognostic points of view, around 40% of osteosarcomas of the hands are low-grade osteosarcomas of the central or parosteal types.

Primary Soft-Tissue Lymphomas: MRI Features Help Discriminate From Other Soft-Tissue Tumors.

OBJECTIVES: MRI presentation of extra-nodal soft-tissue lymphomas (STLs) is scarcely reported and lacks of comparison with other soft-tissue tumors (STTs) including sarcomas (STS). Yet, suggesting this diagnosis on MRI would considerably reduce diagnostic intervals. Our aim was to investigate if conventional MRI could discriminate STLs from other STTs. METHODS: MRIs of STL patients were compared with those of patients addressed to a sarcoma reference center for the diagnosis of a STT. MRI characteristics depicting the tumor (size, signal, habitats, shape, surrounding tissues) were reported. Uni- and multivariate associations with STL diagnosis were evaluated in the entire cohort, and in the subgroups of benign and malignant STTs patients. Diagnostic performances of MRI features combinations were tested. RESULTS: We included 39 patients with STLs (median age: 69 years) and 368 patients with other STTs (122 benign STTs and 246 STS; median age: 58 years). Six MRI features were independent predictors of STL compared to all other STTs: intermediate SI on T1-WI, homogeneous enhancement (without necrotic areas), no blood signal, no fibrotic signal, no peritumoral enhancement and lack of abnormal intra- and peritumoral vasculature (p-value range: <0.0001-0.0163). Their simultaneous presence had a sensitivity of 0.88 (0.71-0.96) and a specificity of 0.88 (0.84-0.91). Other relevant MRI features were: no fat signal to discriminate against STS (p = 0.0409), the infiltrative growth pattern and the vessel and nerve encasement to discriminate against benign STTs (p = 0.0016 and 0.0011, respectively). CONCLUSION: Our research demonstrates that conventional MRI can help discriminating STLs from other STTs. Indeed, radiologists can help suggesting the possible diagnosis of STL, which could speed-up the subsequent proper histopathological analysis in light of MRI findings.

Pleomorphic Liposarcoma Revisited.

Pleomorphic liposarcoma (PLPS) is the rarest and more aggressive subtype of liposarcomas, accounting for 10% of all liposarcomas. The diagnosis should be considered after the detection of multivacuolated pleomorphic lipoblasts in biopsy specimens. Wide-margin resection is the treatment of choice. Complementary treatment options, such as radiation therapy and chemotherapy, are debatable in terms of their contribution to curing patients with PLPS. This article reviews the clinical, histopathological, and molecular characteristics of PLPS and discusses the latest trends in the management, therapeutic strategies, and novel investigations of the subject. [Orthopedics. 2023;46(2):e72-e80.].

Datasets for the reporting of primary tumour in bone: recommendations from the International Collaboration on Cancer Reporting (ICCR).

BACKGROUND AND OBJECTIVES: Bone tumours are relatively rare and, as a consequence, treatment in a centre with expertise is required. Current treatment guidelines also recommend review by a specialised pathologist. Here we report on international consensus-based datasets for the pathology reporting of biopsy and resection specimens of bone sarcomas. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations. METHODS AND RESULTS: According to the ICCR's process for dataset development, an international expert panel consisting of pathologists, an oncologic orthopaedic surgeon, a medical oncologist, and a radiologist produced a set of core and noncore data items for biopsy and resection specimens based on a critical review and discussion of current evidence. All professionals involved were bone tumour experts affiliated with tertiary referral centres. Commentary was provided for each data item to explain the rationale for selecting it as a core or noncore element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the documents were finalised and ratified, and the datasets, including a synoptic reporting guide, were published on the ICCR website. CONCLUSION: These first international datasets for bone sarcomas are intended to promote high-quality, standardised pathology reporting. Their widespread adoption will improve the consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will help to improve management of bone sarcoma patients.