The Effect of Neoadjuvant Systemic Therapy on Surgical Outcomes After Lymph Node Dissections for Stage III Melanoma; An Australian Cohort.

BACKGROUND: Neoadjuvant systemic therapy (NAST) for patients with stage III melanoma achieves high major pathologic response rates and high recurrence-free survival rates. This study aimed to determine how NAST with targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) influences surgical outcomes after lymph node dissection in terms of complications, morbidity, and textbook outcomes. METHODS: Patients who underwent a lymph node dissection after either NAST in a clinical trial or upfront surgery for stage III melanoma between 2014 and 2022 were identified from an institutional research database. RESULTS: The study included 89 NAST-treated patients and 79 upfront surgery-treated patients. The rate of postoperative complications did not differ between the NAST- and upfront surgery-treated patients (55% vs. 51%; p = 0.643), and steroid treatment for drug toxicity did not influence the complication rate (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.4-3; p = 0.826). No significant differences in postoperative morbidity were observed in terms of seroma (23% vs. 11%; p = 0.570) or lymphedema (36% vs. 51%; p = 0.550). The rate of achieving a textbook outcome was comparable for the two groups (61% vs. 57%; p = 0.641). CONCLUSIONS: The surgical outcomes after lymph node dissections were comparable between the patients who received NAST and those who had upfront surgery, indicating that surgery can be safely performed after NAST with TT or ICI for stage III melanoma.

Comprehensive mutational profiling identifies new driver events in cutaneous leiomyosarcoma.

BACKGROUND: Cutaneous leiomyosarcoma (cLMS) is a rare soft tissue neoplasm, showing smooth muscle differentiation, that arises from the mesenchymal cells of the dermis. To-date, genetic investigation of these tumours has involved studies with small sample sizes and limited analyses that identified recurrent somatic mutations in RB1 and TP53, copy number gain of MYCOD and IGF1R, and copy number loss of PTEN. OBJECTIVES: To better understand the molecular pathogenesis of cLMS, we comprehensively explored the mutational landscape of these rare tumours to identify candidate driver events. METHODS: In this retrospective, multi-institutional study, we performed whole-exome sequencing and RNA sequencing on 38 cases of cLMS. RESULTS: TP53 and RB1 were identified as significantly mutated, thus, represent validated driver genes of cLMS. COSMIC mutational signatures SBS7a/b and DBS1 were recurrent, thus, ultraviolet light exposure may be an aetiological factor driving cLMS. Analysis of significantly recurrent somatic copy number alterations, which represent candidate driver events, found focal (<10Mb) deletions encompassing TP53 and KDM6B, and amplifications encompassing ZMYM2, MYOCD, MAP2K4 and NCOR1. A larger (24 Mb) recurrent deletion encompassing CYLD was also identified as significant. Significantly recurrent broad copy number alterations, involving at least half of a chromosome arm, included deletions of 6p/q, 10p/q, 11q, 12q, 13q and 16p/q, and amplification of 15q. Notably PTEN is located on 10q, RB1 on 13q and IGFR1 on 15q. Fusion gene analysis identified recurrent CRTC1/3::MAML2 fusions, as well as many novel fusions in individual samples. CONCLUSIONS: Our analysis of the largest number of cLMS cases to-date highlights the importance of large cohort sizes and the exploration beyond small targeted gene panels when performing molecular analyses, as it allowed a comprehensive exploration of the mutational landscape of these tumours and identification of novel candidate driver events. It also uniquely afforded the opportunity to compare the molecular phenotype of cLMS with LMS of other tissue types, such as uterine and soft tissue LMS. Given that molecular profiling has resulted in the development of novel targeted treatment approaches for uterine and soft tissue LMS, our study now allows the same opportunities to become available for patients with cLMS.

Tranexamic acid use in sarcoma surgery patients: A systematic review and meta-analysis.

INTRODUCTION: Perioperative bleeding increases morbidity and mortality in sarcoma patients. Tranexamic acid (TXA), an antifibrinolytic, is widely utilized in non-sarcoma orthopaedic surgeries, but its adoption in sarcoma surgery is hindered by concerns about thrombotic events. METHODS: Searches in Ovid MEDLINE, EMBASE, and CENTRAL were performed without date restrictions. Inclusion criteria encompassed sarcoma patients undergoing surgery with TXA intervention. Two authors independently screened studies, resolved conflicts, and assessed biases. RESULTS: Eight studies met inclusion criteria, comprising 2142 patients. TXA administration varied in dose and timing across studies. Meta-analysis revealed significantly reduced mean blood loss with TXA of -462.5 mL ([95% confidence interval [CI: -596.7, -328.31], p < 0.001) but no difference in transfusion rates (odds ratio [OR] = 0.51 [95% CI: 0.14-1.89]) or venous thromboembolism events (OR = 0.93 [95% CI: 0.40, 2.16]). Study biases were predominantly moderate to high due to retrospective designs and lack of control for confounders. Quality of reporting varied, with limitations identified in outcome reporting and effect size estimation. CONCLUSIONS: Despite evidence of reduced blood loss, the absence of prospective studies limits conclusive recommendations on TXA use in sarcoma surgery. Further research is warranted to determine optimal TXA regimens and assess safety concerns regarding thrombotic events in this patient population.

The utility of intraoperative marrow margin frozen section in extremity bone sarcoma resection.

BACKGROUND AND OBJECTIVES: Intraoperative frozen section analysis is commonly used to evaluate marrow margins during extremity bone sarcoma resections, but its efficacy in the era of magnetic resonance imaging is debated. This study aimed to compare the accuracy of intraoperative frozen section assessment with final pathology, assess its correlation with gross intraoperative margin assessment, and evaluate its impact on surgical decision making. METHODS: Consecutive patients undergoing extremity bone sarcoma resections from 2010 to 2022 at a single sarcoma center were included. Intraoperative frozen section and gross margin assessments were compared to final pathology using positive predictive values (PPV) and negative predictive values (NPV). Changes in surgical decisions due to positive intraoperative margins were recorded. RESULTS: Of 166 intraoperative frozen section marrow margins, four were indeterminant/positive, with two false positive/indeterminant findings and two false negatives compared to final pathology. Gross intraoperative assessment had no false positives and two false negatives. Frozen section analysis yielded a PPV of 50% (95% confidence interval [CI]: 16%-84%) and NPV of 98.8% (95% CI: 97%-100%), while gross assessment had a PPV of 100% (95% CI: 16%-100%) and NPV of 98.8% (95% CI: 97%-100%). Positive frozen section margins led to additional resections in three of four cases. CONCLUSIONS: Intraoperative frozen section analysis did not offer added clinical value beyond gross margin assessment in extremity bone sarcoma resections. It exhibited a low PPV and led to unnecessary additional resections. Gross intraoperative assessment proved adequate for margin evaluation, potentially saving time and resources.

Obesity increases the risk of major wound complications following pelvic resection for bone sarcoma.

BACKGROUND: Given the paucity of data, the objective of this study is to evaluate the association between obesity and major wound complications following pelvic bone sarcoma surgery specifically. METHODS: Patients who underwent pelvic resection for bone sarcoma from 2005 to 2021 with a minimum 6-month follow-up were reviewed. Patients with benign tumors, primary soft tissue sarcomas, local recurrence at presentation, pelvic metastatic disease, and underweight patients were excluded. A major wound complication was defined as the need for a secondary debridement procedure. Differences in baseline demographics, surgical factors, postoperative complications, and functional outcomes were compared between obese and nonobese patients. A multivariate logistic regression was performed to identify independent risk factors for major wound complications, and a Kaplan-Meier analysis to estimate overall survival between both groups. RESULTS: Of the 93 included patients, 21 were obese (body mass index ≥ 30 kg/m2). The obesity group had a significantly higher rate of major wound complication (52% vs. 26%, p = 0.034) and a lower Toronto Extremity Salvage Score at 1-year postoperatively (47.5 vs. 71.4, p = 0.025). Obesity was the only independent risk factor in the multivariate analysis. No differences in overall survival were demonstrated between groups. CONCLUSIONS: Obesity is a significant risk factor for major wound complications in pelvic bone sarcoma treatment. This highlights the importance of careful perioperative optimization and wound management.

Remote cutaneous confocal microscopy: A multicentric prospective study evaluating diagnostic accuracy for melanoma and keratinocyte carcinoma in tertiary settings.

BACKGROUND: Cutaneous confocal microscopy (CCCM) facilitates in vivo visualisation of skin at a cellular level. Use of a "store and forward" approach for remote CCM interpretation (Remote-CCM) across multiple sites has not been tested and may increase access to non-invasive diagnosis. OBJECTIVE: To test the diagnostic accuracy and safety of Remote-CCM. METHODS: We prospectively recruited lesions selected for biopsy for skin malignancy across five Australian tertiary dermatology centres. CCM, clinical and dermoscopy images were acquired pre-biopsy and accessed by a cloud-based platform for interpretation by CCM readers. CCM diagnosis was compared to histopathology results. RESULTS: Amongst the 201 lesions included, melanoma was the most common malignancy (34/72, 47.2%). Of the 89 lesions (44.8%) potentially 'saved' from biopsy, 80 (90%) were truly benign lesions and 9 (10.1%) were missed malignant lesions of MIS (n=7) and SCC (n=2). No invasive melanomas were missed. Sensitivity of remote-CCM for detection of malignancy was 89% (95%CI 79-95%) and specificity was 64% (95%CI 55-73%). LIMITATIONS: The study recruited from high-risk populations and excluded lesions that were not biopsied. CONCLUSION: Remote-CCM has comparable accuracy to bedside-CCM and safely reduces unnecessary biopsies. Potential SCCs are not appropriate for remote-CCM. Follow-up of borderline melanocytic lesions is recommended.

The Prognostic Significance of Tumoral Melanosis.

BACKGROUND: Tumoral melanosis (TM) is a histological term to describe a nodular aggregation of macrophages containing melanin pigment (melanophages) that is devoid of viable melanocytes. It is most often identified in skin, where it may be appreciated clinically as a pigmented lesion; however, it can also be found in other organs such as lymph nodes. The presence of TM is usually thought to signify the presence of a regressed melanoma or other pigmented tumor. Until recently, it was a relatively uncommon finding; however, with the use of effective systemic therapies against melanoma, its occurrence in histological specimens is more frequent. METHODS: We identified and reviewed all histopathological diagnoses of TM at any organ site reported at a single institution from 2006 to 2018. TM cases were paired with non-TM cases of cutaneous melanoma through propensity score matching at a 1:2 ratio, and their survival outcomes were compared. The clinical outcomes examined included recurrence-free survival (RFS), distant disease-free survival (DDFS), melanoma-specific survival (MSS), and overall survival (OS). RESULTS: TM was reported in 79 patients. Their median age was 65 years (range 22-88), with a 2:1 male predominance (51 out of 79, 65%). The most common organ involved was the skin (67%), with a third of all cases localized to a lower limb (36%). TM had a strong association with the presence of melanoma (91%) and regression at other sites of melanoma (54%), suggesting that it is part of a systemic immune response against melanoma. Most patients with TM either previously or subsequently developed histologically confirmed melanoma in the same anatomical region as the TM (89%). Thirty-five TM patients were matched with 70 non-TM cases. Patients with melanoma who developed TM without prior regional or systemic therapy showed improved MSS (p = 0.03), whereas no statistically significant differences were observed in terms of RFS, DDFS, and OS. CONCLUSIONS: TM usually occurs in the context of a previous or subsequent cutaneous melanoma and is associated with improved MSS. It is important that TM is recognized by pathologists and documented in pathology reports.

Does Freehand, Patient-specific Instrumentation or Surgical Navigation Perform Better for Allograft Reconstruction After Tumor Resection? A Preclinical Synthetic Bone Study.

BACKGROUND: Joint-sparing resection of periarticular bone tumors can be challenging because of complex geometry. Successful reconstruction of periarticular bone defects after tumor resection is often performed with structural allografts to allow for joint preservation. However, achieving a size-matched allograft to fill the defect can be challenging because allograft sizes vary, they do not always match a patient's anatomy, and cutting the allograft to perfectly fit the defect is demanding. QUESTIONS/PURPOSES: (1) Is there a difference in mental workload among the freehand, patient-specific instrumentation, and surgical navigation approaches? (2) Is there a difference in conformance (quantitative measure of deviation from the ideal bone graft), elapsed time during reconstruction, and qualitative assessment of goodness-of-fit of the allograft reconstruction among the approaches? METHODS: Seven surgeons used three modalities in the same order (freehand, patient-specific instrumentation, and surgical navigation) to fashion synthetic bone to reconstruct a standardized bone defect. National Aeronautics and Space Administration (NASA) mental task load index questionnaires and procedure time were captured. Cone-beam CT images of the shaped allografts were used to measure conformance (quantitative measure of deviation from the ideal bone graft) to a computer-generated ideal bone graft model. Six additional (senior) surgeons blinded to modality scored the quality of fit of the allografts into the standardized tumor defect using a 10-point Likert scale. We measured conformance using the root-mean-square metric in mm and used ANOVA for multipaired comparisons (p < 0.05 was significant). RESULTS: There was no difference in mental NASA total task load scores among the freehand, patient-specific instrumentation, and surgical navigation techniques. We found no difference in conformance root-mean-square values (mean ± SD) between surgical navigation (2 ± 0 mm; mean values have been rounded to whole numbers) and patient-specific instrumentation (2 ± 1 mm), but both showed a small improvement compared with the freehand approach (3 ± 1 mm). For freehand versus surgical navigation, the mean difference was 1 mm (95% confidence interval [CI] 0.5 to 1.1; p = 0.01). For freehand versus patient-specific instrumentation, the mean difference was 1 mm (95% CI -0.1 to 0.9; p = 0.02). For patient-specific instrumentation versus surgical navigation, the mean difference was 0 mm (95% CI -0.5 to 0.2; p = 0.82). In evaluating the goodness of fit of the shaped grafts, we found no clinically important difference between surgical navigation (median [IQR] 7 [6 to 8]) and patient-specific instrumentation (median 6 [5 to 7.8]), although both techniques had higher scores than the freehand technique did (median 3 [2 to 4]). For freehand versus surgical navigation, the difference of medians was 4 (p < 0.001). For freehand versus patient-specific instrumentation, the difference of medians was 3 (p < 0.001). For patient-specific instrumentation versus surgical navigation, the difference of medians was 1 (p = 0.03). The mean ± procedural times for freehand was 16 ± 10 minutes, patient-specific instrumentation was 14 ± 9 minutes, and surgical navigation techniques was 24 ± 8 minutes. We found no differences in procedure times across three shaping modalities (freehand versus patient-specific instrumentation: mean difference 2 minutes [95% CI 0 to 7]; p = 0.92; freehand versus surgical navigation: mean difference 8 minutes [95% CI 0 to 20]; p = 0.23; patient-specific instrumentation versus surgical navigation: mean difference 10 minutes [95% CI 1 to 19]; p = 0.12). CONCLUSION: Based on surgical simulation to reconstruct a standardized periarticular bone defect after tumor resection, we found a possible small advantage to surgical navigation over patient-specific instrumentation based on qualitative fit, but both techniques provided slightly better conformance of the shaped graft for fit into the standardized post-tumor resection bone defect than the freehand technique did. To determine whether these differences are clinically meaningful requires further study. The surgical navigation system presented here is a product of laboratory research development, and although not ready to be widely deployed for clinical practice, it is currently being used in a research operating room setting for patient care. This new technology is associated with a learning curve, capital costs, and potential risk. The reported preliminary results are based on a preclinical synthetic bone tumor study, which is not as realistic as actual surgical scenarios. CLINICAL RELEVANCE: Surgical navigation systems are an emerging technology in orthopaedic and reconstruction surgery, and understanding their capabilities and limitations is paramount for clinical practice. Given our preliminary findings in a small cohort study with one scenario of standardized synthetic periarticular bone tumor defects, future investigations should include different surgical scenarios using allograft and cadaveric specimens in a more realistic surgical setting.

DOxy: A Dissolved Oxygen Monitoring System.

Dissolved Oxygen (DO) in water enables marine life. Measuring the prevalence of DO in a body of water is an important part of sustainability efforts because low oxygen levels are a primary indicator of contamination and distress in bodies of water. Therefore, aquariums and aquaculture of all types are in need of near real-time dissolved oxygen monitoring and spend a lot of money on purchasing and maintaining DO meters that are either expensive, inefficient, or manually operated-in which case they also need to ensure that manual readings are taken frequently which is time consuming. Hence a cost-effective and sustainable automated Internet of Things (IoT) system for this task is necessary and long overdue. DOxy, is such an IoT system under research and development at Santa Clara University's Ethical, Pragmatic, and Intelligent Computing (EPIC) Laboratory which utilizes cost-effective, accessible, and sustainable Sensing Units (SUs) for measuring the dissolved oxygen levels present in bodies of water which send their readings to a web based cloud infrastructure for storage, analysis, and visualization. DOxy's SUs are equipped with a High-sensitivity Pulse Oximeter meant for measuring dissolved oxygen levels in human blood, not water. Hence a number of parallel readings of water samples were gathered by both the High-sensitivity Pulse Oximeter and a standard dissolved oxygen meter. Then, two approaches for relating the readings were investigated. In the first, various machine learning models were trained and tested to produce a dynamic mapping of sensor readings to actual DO values. In the second, curve-fitting models were used to produce a successful conversion formula usable in the DOxy SUs offline. Both proved successful in producing accurate results.

Outcome After Surgical Treatment of Dermatofibrosarcoma Protuberans (DFSP): Does it Require Extensive Follow-up and What is an Adequate Resection Margin?

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumour of indeterminate malignant potential. The mainstay treatment for DFSP is surgical resection. Given the reported high local recurrence rate, the ideal resection margin for DFSP is unclear. The purpose of this study was to ascertain the local recurrence and metastatic rate of DFSP and DFSP with fibrosarcomatous degeneration (FS-DFSP), with specific attention to margin status in an attempt to address the issue of margin adequacy. METHODS: Patients treated for DFSP at a single sarcoma centre were identified from a prospective database. DFSP and FS-DFSP patients with and without prior surgery were included. Patients were followed after surgery to monitor complications, local recurrence and metastasis. RESULTS: The study included 200 patients: 166 patients with DFSP and 34 patients with FS-DFSP. In the DFSP group, nine patients (5.4%) had positive margins, one case (0.6%) developed local recurrence (LR) and no patients developed distant metastases. In the FS-DFSP group, seven patients (20.6%) had positive margins, six patients (17.6%) developed local recurrence (LR) and eight patients (23.5%) developed distant metastases, of which three (37.5%) were in the lungs, one (12.5%) in bone and four (50%) in other soft tissue sites. DISCUSSION AND CONCLUSION: Local recurrence and metastases are extremely rare in patients with DFSP. Achieving a negative as opposed to a wide surgical margin may be sufficient to avoid local recurrence of most DFSP. We suggest that no ongoing surveillance for local or systemic relapse is required for DFSP patients after negative margin resection. For FS-DFSP, we recommend the same surveillance schedule, based on tumour grade, as other soft tissue sarcoma.

A Size-Based Criteria for Flap Reconstruction After Thigh-Adductor, Soft-Tissue Sarcoma Resection.

BACKGROUND: Resection of soft-tissue sarcomas from the adductor compartment is associated with significant complications. Free/pedicled flaps often are used for wound closure, but their effect on healing is unclear. We compared wound complications, oncologic, and functional outcomes for patients undergoing flap reconstruction or primary closure following resection of adductor sarcomas. METHODS: A total of 177 patients underwent resection of an adductor sarcoma with primary closure (PrC) or free/pedicled flap reconstruction (FR). Patient, tumor, and treatment characteristics were compared, as well as wound complications, oncologic, and functional outcomes (TESS/MSTS87/MSTS93). To examine the relative benefit of flap reconstruction, number needed to treat (NNT) was calculated. RESULTS: In total, 143 patients underwent PrC and 34 had FR, 68% of which were pedicled. There were few differences in demographic, tumor, or treatment characteristics. No significant difference was found in the rate of wound complications. Length of stay was significantly longer in FR (18 days vs. PrC 8 days; p < 0.01). Oncologic and functional outcomes were similar over 5 years follow-up. Uncomplicated wound healing occurred more often in FR compared with PrC for tumors with ≥15 cm (NNT = 8.4) or volumes ≥ 800 ml (NNT = 8.4). Tumors ≤ 336 ml do not benefit from a flap, whereas those > 600 ml are 1.5 times more likely to heal uneventfully after flap closure. CONCLUSIONS: Although flap use prolonged hospitalization, it decreased wound healing complications for larger tumors, and in all sized tumors, it demonstrated similar functional and oncologic outcomes to primary closure. Our size-based treatment criteria can help to identify patients with large adductor sarcomas who could benefit from flap reconstruction. LEVEL OF EVIDENCE III: (Retrospective cohort study).

LUMiC® endoprosthesis for pelvic reconstruction: A Canadian experience.

BACKGROUND AND OBJECTIVES: The LUMiC® prosthesis was introduced to reduce the mechanical complications encountered with periacetabular reconstruction after pelvic tumor resection. Few have evaluated the outcomes associated with its use. METHODS: A retrospective study from five Orthopedic Oncology Canadian centers was conducted. All patients with a LUMiC® endoprosthesis were included. Their charts were reviewed for surgical and functional outcomes. RESULTS: A total of 16 patients were followed for 28 months (3-60). A total of 12 patients (75%) had a LUMiC® after a resection of a primary sarcoma. Mean surgical time was 555 min. Four patients (25%) had a two-stages procedure. MSTS score was 60.3 preoperatively and 54.3 postoperatively. Patients got a dual mobility bearing and the silver coated implant was used in 7 patients (43.7%). Five patients (31.3%) underwent capsular reconstruction using a fabric. Silver-coating was not found to reduce infection risk (p = 0.61) and capsuloplasty did not prevent dislocation (p = 0.6). Five patients had peroperative complications (31.3%). Eight patients (50%) had an infection including all four with two-stages surgery. Dislocation occurred in five patients (31.3%) whereas no cases of aseptic loosening were reported. A total of 10 patients (62.5%) needed a reoperation. CONCLUSION: LUMiC® endoprosthesis provides low rates of aseptic loosening on medium-term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and silver-coated implants.

In vivo reflectance confocal microscopy can detect the invasive component of lentigo maligna melanoma: Prospective analysis and case-control study.

BACKGROUND: Lentigo maligna (LM), a form of melanoma in situ, has no risk of causing metastasis unless dermal invasive melanoma (LMM) supervenes. Furthermore, the detection of invasion impacts prognosis and management. OBJECTIVE: To assess the accuracy of RCM for the detection of invasion component on LM/LMM lesions. METHODS: In the initial case-control study, the performance of one expert in detecting LMM at the time of initial RCM assessment of LM/LMM lesions was recorded prospectively (n = 229). The cases were assessed on RCM-histopathology correlation sessions and a panel with nine RCM features was proposed to identify LMM, which was subsequently tested in a subset of initial cohort (n = 93) in the matched case-control study by two blinded observers. Univariable and multivariable logistic regression models were performed to evaluate RCM features predictive of LMM. Reproducibility of assessment of the nine RCM features was also evaluated. RESULTS: A total of 229 LM/LMM cases evaluated by histopathology were assessed blindly and prospectively by an expert confocalist. On histopathology, 210 were LM and 19 were LMM cases. Correct identification of an invasive component was achieved for 17 of 19 LMM cases (89%) and the absence of a dermal component was correctly diagnosed in 190 of 210 LM cases (90%). In the matched case-control (LMM n = 35, LM n = 58), epidermal and junctional disarray, large size of melanocytes and nests of melanocytes were independent predictors of LMM on multivariate analysis. The interobserver analysis demonstrated that these three features had a fair reproducibility between the two investigators (K = 0.4). The multivariable model including those three features showed a high predictive performance AUC = 74% (CI 95% 64-85%), with sensitivity of 63% (95% CI 52-78%) and specificity of 79% (CI 95% 74-88%), and likelihood ratio of 18 (p-value 0.0026). CONCLUSION: Three RCM features were predictive for identifying invasive melanoma in the background of LM.

T2-weighted MRI radiomics in high-grade intramedullary osteosarcoma: predictive accuracy in assessing histologic response to chemotherapy, overall survival, and disease-free survival.

OBJECTIVE: To analyze radiomic features obtained from pre-treatment T2-weighted MRI acquisitions in patients with histologically proven intramedullary high-grade osteosarcomas and assess the accuracy of radiomic modelling as predictive biomarker of tumor necrosis following neoadjuvant chemotherapy (NAC), overall survival (OS), and disease-free survival (DFS). MATERIALS AND METHODS: Pre-treatment MRI exams in 105 consecutive patients who underwent NAC and resection of high-grade intramedullary osteosarcoma were evaluated. Histologic necrosis following NAC, and clinical outcome-survival data was collected for each case. Radiomic features were extracted from segmentations performed by two readers, with poorly reproducible features excluded from further analysis. Cox proportional hazard model and Spearman correlation with multivariable modelling were used for assessing relationships of radiomics features with OS, DFS, and histologic tumor necrosis. RESULTS: Study included 74 males, 31 females (mean 32.5yrs, range 15-77 years). Histologic assessment of tumor necrosis following NAC was available in 104 cases, with good response (≥ 90% necrosis) in 41, and poor response in 63. Fifty-three of 105 patients were alive at follow-up (median 40 months, range: 2-213 months). Median OS was 89 months. Excluding 14 patients with metastases at presentation, median DFS was 19 months. Eleven radiomics features were employed in final radiomics model predicting histologic tumor necrosis (mean AUC 0.708 ± 0.046). Thirteen radiomic features were used in model predicting OS (mean concordance index 0.741 ± 0.011), and 12 features retained in predicting DFS (mean concordance index 0.745 ± 0.010). CONCLUSIONS: T2-weighted MRI radiomic models demonstrate promising results as potential prognostic biomarkers of prospective tumor response to neoadjuvant chemotherapy and prediction of clinical outcomes in conventional osteosarcoma.

ZFP64::NCOA3 gene fusion defines a novel subset of spindle cell rhabdomyosarcoma.

Spindle cell rhabdomyosarcoma represents a rare neoplasm characterized by monomorphic spindle cells with a fascicular architecture and variable skeletal muscle differentiation. Following incidental identification of a ZFP64::NCOA3 gene fusion in an unclassified spindle cell sarcoma resembling adult-type fibrosarcoma, we performed a retrospective archival review and identified four additional cases with a similar histology and identical gene fusion. All tumors arose in adult males (28-71 years). The neoplasms were found in the deep soft tissues, two were gluteal, and one each arose in the thigh, abdominal wall, and chest wall. Morphologically, the tumors were characterized by spindle cells with a distinctive herringbone pattern and variable collagenous to myxoid stroma. The nuclei were relatively monomorphic with variable mitotic activity. Three tumors had immunoreactivity for MyoD1, and four contained variable expression of desmin and smooth muscle actin. All cases tested for myogenin, CD34, S100, pankeratin, and epithelial membrane antigen were negative. Targeted RNA sequencing revealed a ZFP64::NCOA3 fusion product in all five tumors. Three patients developed distant metastases, and two ultimately succumbed to their disease within 2 years of initial diagnosis. This study suggests ZFP64::NCOA3 fusions define a novel subtype of rhabdomyosarcoma with a spindle cell morphology and aggressive clinical behavior. The potential for morphologic and immunohistochemical overlap with several other sarcoma types underscores the value of molecular testing as a diagnostic adjunct to ensure accurate classification and management of these neoplasms.

Expanding the spectrum of mesenchymal neoplasms with NR1D1-rearrangement.

Undifferentiated mesenchymal neoplasms can be morphologically subclassified based on cell shape; epithelioid tumors may be diagnostically challenging, particularly since they can show morphologic and immunohistochemical overlap with epithelial neoplasms. Following the recent report of an NR1D1::MAML1 gene fusion in an undifferentiated pediatric neoplasm, we performed a retrospective archival review and identified four additional cases of undifferentiated mesenchymal neoplasms with NR1D1-rearrangement. All four tumors occurred in adult women. The tumors involved superficial and/or deep soft tissues of the extremities or abdomen. Morphologically, they showed a spectrum of overlapping features. In addition to epithelioid cells, two cases also had a prominent spindle cell component. Two cases also had admixed polygonal cells containing prominent cytoplasmic vacuoles with amorphous debris. The immunophenotype was nonspecific but all cases had at least focal keratin expression; this was extensive in two tumors. Targeted RNA-sequencing revealed two cases each with NR1D1::MAML1 and NR1D1::MAML2 gene fusions. One patient developed lung and liver metastases, and one patient required amputation due to multifocal disease and underlying bone involvement. This study confirms undifferentiated NR1D1-rearranged sarcoma represents a distinct mesenchymal neoplasm with an epithelioid morphology and potential for aggressive behavior. Further, we offer new insight into the spectrum of clinical, morphologic, immunohistochemical, and molecular findings possible in these rare neoplasms. An awareness of this entity is especially important given the potential for misclassification as a carcinoma.

Management of giant cell tumors of the distal radius: a systematic review and meta-analysis.

PURPOSE: The treatment of giant cell tumors (GCT) of the distal radius remains challenging, with no consensus on the optimal surgical management. Surgical management remains the mainstay of treatment with options including intralesional curettage and en-bloc resection with reconstruction. The objective of this systematic review and meta-analysis was to evaluate and compare the outcomes of these two procedures. METHODS: Using OVID-Medline and Embase databases, a systematic literature search was performed. Comparative studies, assessing intralesional curettage and en-bloc resection in patients with GCTs of the distal radius, were included. Data regarding rates of local recurrence, metastasis, overall complications, and functional outcomes, were collected and analyzed. The ROBINS-I tool was utilized for risk of bias appraisal within each study outcome. RESULTS: Thirteen studies (n = 373 patients) reporting on 191 intralesional curettage procedures and 182 en-bloc resections were included in the analysis. The average age of participants was 31.9 (SD ± 2.4) years and average follow-up was 7.1 (SD ± 3.6) years. Patients that underwent intralesional curettage were more likely to develop local recurrence (Risk Ratio (RR) 3.3, 95% CI, [2.1, 5.4], p < 0.00001) when compared to patients that underwent en-bloc resection. In Campanacci grade 3 lesions, the risk for local recurrence was 5.9 (95% CI, [2.2, 16.3], p = 0.0006) times higher in patients that received intralesional curettage. Patients that underwent intralesional curettage showed an 84% reduction in the relative risk of developing overall complications compared to en-bloc resection (95% CI, [0.1, 0.4], p < 0.00001), and a larger decrease in Visual Analog Scale and lower Disabilities of the Arm, Shoulder, and Hand (DASH) scores (p < 0.00001). Risk ratio for developing a local recurrence, with PMMA versus bone graft following an intralesional procedure was not significant (RR 1.2, 95% CI, [0.6, 2.6], p = 0.62). CONCLUSIONS: In the surgical management of GCT of the distal radius, intralesional curettage increased local recurrence compared to en-bloc resection with reconstruction, particularly in grade 3 tumors. However, it led to significantly fewer operative complications, lower pain scores, and improved functional outcomes compared to en-bloc resection. Both treatment options remain relevant in the contemporary management of GCTs of the distal radius. Surgical decision making should include both patient and tumor factors when determining the optimal treatment strategy for these patients. LEVEL 3 EVIDENCE: Meta-analysis of Level 3 studies.

Surgical Outcomes of Primary Dermatofibrosarcoma Protuberans: A Retrospective, Multicenter Study.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumor with a low rate of metastatic disease. Previous series have shown a superiority of Mohs micrographic surgery (MMS) compared with wide local excision (WLE). Likewise, there is paucity of data examining the long-term follow-up of patients. OBJECTIVE: The purpose of the current study was to examine the outcome of surgical treatment of primary DFSP of the trunk and extremities. METHODS: We reviewed 236 patients (115 females, 121 males, mean age 41 ± 15 years) undergoing MMS (n = 81, 34%) or WLE (n = 155, 66%) to treat a primary DFSP. Mean tumor size and follow-up was 4 ± 2 cm and 7 years, respectively. Final margins were negative in 230 (97%) patients. RESULTS: There was no difference (p > 0.05) in patient age, sex, tumor size, negative margin excision, or history of a previous inadvertent excision between patients who underwent WLE and those undergoing MMS. There were two cases of local recurrence and two cases of metastasis, with no difference in the 5-year local recurrence-free survival (98% vs. 99%, p = 0.69) or metastatic-free survival (98% vs. 100%, p= 0.27) between WLE and MMS. CONCLUSION: There was no difference in oncologic outcome comparing MMS with WLE for DFSP outside the head and neck. The goal of treatment for DFSP is to achieve a negative margin, regardless of surgical treatment modalities. A 'less is more' approach to follow-up can likely be taken for patients with completely resected DFSP in easy-to-examine anatomical areas. In these patients, no formal follow-up should be required.

Dermoscopic features and screening strategies for the detection of small-diameter melanomas.

BACKGROUND: Around 70% of cutaneous malignant melanomas (MMs) develop de novo, and small-diameter or 'tiny' lesions are expected to represent the earliest manifestation of most MMs. AIM: To describe the clinical, histopathological and dermoscopic features of tiny MMs, and to investigate the impact of imaging tools, including total body photography (TBP) and sequential digital dermoscopy imaging (SDDI) in their detection. METHODS: Consecutive MMs diagnosed over 2 years in a referral centre were retrospectively included. Tiny MMs were defined as MMs with a diameter of ≤ 5 mm on dermoscopy. Dermoscopic features and the performance of four imaging methods were evaluated. RESULTS: Of the 312 MMs included, 86 (27.6%) measured ≤ 5 mm, and 44.2% of these were invasive. Tiny MMs were more frequently excised for being new and/or changing compared with nontiny MMs (77.9% vs. 50.9%; P < 0.001). Half of the tiny MMs would have been missed by the dermoscopic seven-point checklist (48.2%) or the three-point checklist (49.4%), while Menzies' method and the revised pattern analysis correctly identified respectively 65.9% and 63.5% of the tiny MMs. The most frequent positive features for tiny MMs were asymmetry in structure or colour (77.6%), brown dots (65.9%), irregular dots and globules (76.5%) and atypical pigment network (44.7%). Dermoscopic features predictive of invasion in tiny MMs were atypical vascular pattern (OR = 26.5, 95% CI 1.5-475.5, P < 0.01), shiny white lines (OR = 12.4, 95% CI 0.7-237.8, P = 0.04) and grey/blue structures (OR = 3.7, 95% CI 1.3-10.5, P = 0.01). CONCLUSION: Tiny MMs are frequently invasive and represent a clinical, dermoscopic and histopathological challenge. Dermoscopy alone has suboptimal diagnostic accuracy. Early diagnosis relies on the detection of new or changing lesions aided by TBP and SDDI.

Lumbopelvic shortening and local host bone-to-host bone reconstruction: a surgical method for lumbopelvic fusion following total sacrectomy.

PURPOSE: Primary sacral tumors are rare, representing fewer than 7% of spinal neoplasms. Following total sacrectomy, lumbopelvic instrumentation and fusion carries a high risk of non-union with no current consensus on fixation techniques to augment bony defects. We aim to describe the outcome of a reconstruction technique following total sacrectomy whereby lumbopelvic shortening is performed and the posterior pelvic ring is compressed to enable contact with the native L5 vertebra. METHODS: Retrospective chart review of 2 patients with 2 and 7 years post-operative follow-up. A review of hospital records including clinical assessments, complications, pathology and imaging reports. RESULTS: Patient 1 was a 17-years-old male with recurrent sacral chondrosarcoma, who presented with lumbosacral neuropathic pain and radiculopathy after failed intralesional surgery. Patient 2 was a 51-years-old male with chronic low back pain caused by a large low-grade chondroid sacral chordoma. Reconstruction technique involved mobilizing the L5 vertebra into the pelvis and pelvic ring closure to obtain host-bone-to-bone contact, eliminating the need for alternative grafts. Post-operative complications included superficial abdominal wound drainage, lower limb DVT, pulmonary emboli and deep pelvic infection. Serial CT scans demonstrated bony fusion in both patients. Neither patients had evidence of tumor recurrence and were able to ambulate at recent follow-up. Imaging demonstrated changed acetabular version of - 4.6/- 8.1 and - 14.4/- 14.8 (patient 1/2, R/L, respectively). CONCLUSION: Primary lumbopelvic shortening represents an alternative local autograft reconstructive technique for management of large sacral defects following total sacrectomy. This technique obviates the additional morbidity and surgical cost associated with the use of previously described techniques.