Cemented and Press-fit Femoral Stems for the Management of Oncologic Femoral Tumors.

BACKGROUND: Stem fixation in reconstruction after resection of femoral tumors is debated. Cemented stems offer immediate stability but risk aseptic loosening, while press-fit stems allow bone ingrowth but risk stress shielding and subsidence. Our retrospective review aimed to determine implant failure rates and their associated factors, as well as the rates of infection, debridement, and mortality for both fixation groups (cemented or press-fit stems) used in patients undergoing resection of femoral tumor disease and subsequent arthroplasty. METHODS: We retrospectively studied 252 patients who underwent resection of femoral tumors and subsequent arthroplasty using cemented (n = 173; 69%) or press-fit (noncemented) (n = 79; 31%) stems between 1999 and 2020. Implant failure was the primary outcome, with secondary outcomes including rates of implant infection, debridement, and mortality. Multivariable regression was done to assess risk factors for implant failures. RESULTS: The study found implant failure rates of 11% and 18% for cemented stems and press-fit stems, respectively. Lower stem to diaphyseal ratios (P = 0.024) and younger patients (P = 0.008) were associated with a higher risk of implant failure in cemented stems. The infection rates were 14% and 10% for cemented and press-fit stems, respectively. Debridement rates were 16% and 13% for cemented and press-fit stems, respectively, while the 1-year mortality rate was 16% for cemented stems and 1.5% for press-fit stems. CONCLUSIONS: This study is the largest of its kind, providing patient characteristics and outcomes in both cemented and press-fit stems in the setting of reconstruction for femoral tumors. Both methods can be effective, with outcomes dependent on patient-specific factors, such as life expectancy, activity level, and body habitus, as well as proper implant fit. Additional studies of both implants and longer follow-up are required to elucidate the optimal fixation method for each individual patient. LEVEL OF EVIDENCE: Level III, retrospective noncomparative study.

Dual Mobility for Oncological Hip Reconstruction: Significantly Reduced Dislocation Rates at 5 years.

BACKGROUND: Although dual mobility total hip arthroplasty has become increasingly common in recent years, limited remains known on dual mobility in surgical oncology. This university-based investigation compared dislocation and revision rates of DMs, conventional total hip arthroplasty (THA), and hemiarthroplasties (HAs) for oncological hip reconstruction. METHODS: An institutional tumor registry was used to identify 221 patients undergoing 45 DMs, 67 conventional THAs, and 109 HAs, performed for 17 primary hip tumors and 204 hip metastases between 2010 and 2020. The median age at surgery was 65 years, and 52% were female. The mean follow-up was 2.5 years. Kaplan-Meier survivorship curves and log-rank tests were done to compare dislocation and revision rates among all 221 patients, after a one-to-one propensity match, based on age, sex, tumor type (metastasis, primary tumor), and tumor localization (femur, acetabulum). RESULTS: The 5-year survivorship free of dislocation was 98% in DMs, 66% in conventional THAs ( P = 0.03; all P values compared with DMs), and 97% among HAs ( P = 0.48). The 5-year survivorship free of revision was 69% in DMs, 62% in conventional THAs ( P = 0.68), and 92% in HAs ( P = 0.06). After propensity matching, the 5-year survivorship free of dislocation was 42% in 45 conventional THAs ( P = 0.027; compared with all 45 DMs) and 89% in 16 matched HAs ( P = 0.19; compared with 16 DMs with femoral involvement only). The 5-year survivorship free of revision was 40% in matched conventional THAs ( P = 0.91) and 100% in matched HAs ( P = 0.19). CONCLUSIONS: DMs showed markedly lower rates of dislocation than conventional THAs, with overall revision rates remaining comparable among different designs. DMs should be considered the option of choice for oncological hip reconstruction if compared with conventional THAs. HAs are a feasible alternative when encountering femoral disease involvement only. LEVEL OF EVIDENCE: III.

Management of limb length discrepancy after bone sarcoma resection about the knee in the skeletally immature.

Patients with bone sarcomas increasingly choose limb salvage. This can lead to issues with limb length discrepancy (LLD) for the skeletally immature. We synthesize management options into an algorithm and report our results. Patients with bone sarcomas involving any location from the femoral diaphysis to the tibial diaphysis 12 years or younger were reviewed. Our clinical pathway prescribed patients with metadiaphyseal lesions to intercalary allograft reconstruction, epiphyseal lesions and less than 5 cm expected LLD to osteoarticular allograft and patients with more than 5 cm expected LLD to extendable prosthesis. Twenty patients met inclusion criteria: 11 with osteoarticular allografts, 5 with extendable prostheses and 4 with intercalary allografts; median age 11.5 years; median follow-up 8.2 years; and final median LLD 1.6 cm. Five patients had contralateral epiphysiodesis, two patients underwent contralateral femoral shortening and a median of 6 (range 4-8) lengthenings were performed for extendable prostheses. Four patients had residual LLD over 3 cm. There were 13 revisions in 8 patients and 2 amputations. Limb-salvage in paediatric bone sarcoma of the knee can be managed with multiple techniques producing satisfactory results in regards to LLD. Careful pre-operative planning and shared decision making is a requisite given the high rate of secondary procedures for both LLD and reconstructive failures. Level of evidence: Level III Retrospective Comparative Study.

Giant cell-rich osteosarcoma: A match pair analysis of 11 new cases and literature review of 56 patients.

BACKGROUND: Limited remains known on giant cell-rich osteosarcoma (GCRO) with current studies being case reports or smaller series. This investigation compared GCRO and conventional osteoblastic osteosarcoma (OOS) with regard to demographics and survival. METHODS: An institutional tumor registry was used to identify 11 patients (six males) treated for GCRO. Mean age was 43 years. Staging showed American Joint Committee on Cancer (AJCC) stages IIA in four and IIB in seven patients. Mean follow-up was 14 years. Study initiatives were: (1) Comparison of demographics between GCRO and 167 OOS from our institutional registry, (2) Differences in survival between GCRO and 33 OOS case controls (based on sex and AJCC stage), as well as 10 OOS using an age-based propensity match, and (3) Summary of all GCRO cases reported in the literature. RESULTS: (1) Sex (p = 0.53), grading (p = 0.56), AJCC stage (p = 0.42), and chemotherapeutic response rate (p = 0.67) did not differ between groups. Age was significantly increased in GCRO (p = 0.001). (2) Case-control and propensity-matched groups revealed no difference in disease-free survival, local recurrence, and distant disease-free survival at 2 years (p > 0.05). (3) Mean age of 56 patients (50% males) reported in the literature was 26 years. After merging with our 11 cases, the 2-year disease-free survival was 66%. CONCLUSIONS: GCRO remains a rare disease with high short-term mortality. Although affecting older patients more than conventional osteosarcoma, GCRO should not be viewed as a predictor of survival compared to OOS.

What is the Value of Radiology Input During a Multidisciplinary Orthopaedic Oncology Conference?

BACKGROUND: Multidisciplinary orthopaedic oncology conferences are important in developing the treatment plan for patients with suspected orthopaedic bone and soft tissue tumors, involving physicians from several services. Past studies have shown the clinical value of these conferences; however, the impact of radiology input on the management plan and time cost for radiology to staff these conferences has not been fully studied. QUESTIONS/PURPOSES: (1) Does radiology input at multidisciplinary conference help guide clinical management and improve clinician confidence? (2) What is the time cost of radiology input for a multidisciplinary conference? METHODS: This prospective study was conducted from October 2020 to March 2022 at a tertiary academic center with a sarcoma center. A single data questionnaire for each patient was sent to one of three treating orthopaedic oncologists with 41, 19, and 5 years of experience after radiology discussion at a weekly multidisciplinary conference. A data questionnaire was completed by the treating orthopaedic oncologist for 48% (322 of 672) of patients, which refers to the proportion of those three oncologists' patients for which survey data were captured. A musculoskeletal radiology fellow and musculoskeletal fellowship-trained radiology attending physician provided radiology input at each multidisciplinary conference. The clinical plan (leave alone, follow-up imaging, follow-up clinically, recommend different imaging test, core needle biopsy, surgical excision or biopsy or fixation, or other) and change in clinical confidence before and after radiology input were documented. A second weekly data questionnaire was sent to the radiology fellow to estimate the time cost of radiology input for the multidisciplinary conference. RESULTS: In 29% (93 of 322) of patients, there was a change in the clinical plan after radiology input. Biopsy was canceled in 30% (24 of 80) of patients for whom biopsy was initially planned, and surgical excision was canceled in 24% (17 of 72) of patients in whom surgical excision was initially planned. In 21% (68 of 322) of patients, there were unreported imaging findings that affected clinical management; 13% (43 of 322) of patients had a missed finding, and 8% (25 of 322) of patients had imaging findings that were interpreted incorrectly. For confidence in the final treatment plan, 78% (251 of 322) of patients had an increase in clinical confidence by their treating orthopaedic oncologist after the multidisciplinary conference. Radiology fellows and attendings spent a mean of 4.2 and 1.5 hours, respectively, reviewing and presenting at a multidisciplinary conference each week. The annual combined prorated time cost for the radiology attending and fellow was estimated at USD 24,310 based on national median salary data for attendings and internal salary data for fellows. CONCLUSION: In a study taken at one tertiary-care oncology program, input from radiology attendings and fellows in the setting of a multidisciplinary conference helped to guide the final treatment plan, reduce procedures, and improve clinician confidence in the final treatment plan, at an annual time cost of USD 24,310. CLINICAL RELEVANCE: Multidisciplinary orthopaedic oncology conferences can lead to changes in management plans, and the time cost to the radiologists should be budgeted for by the radiology department or parent institution.

Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma.

BACKGROUND: Survival in patients who have Ewing sarcoma is correlated with postchemotherapy response (tumor necrosis). This treatment response has been categorized as the response rate, similar to what has been used in osteosarcoma. There is controversy regarding whether this is appropriate or whether it should be a dichotomy of complete versus incomplete response, given how important a complete response is for in overall survival of patients with Ewing sarcoma. The purpose of this study was to evaluate the impact that the amount of chemotherapy-induced necrosis has on (1) overall survival, (2) local recurrence-free survival, (3) metastasis-free survival, and (4) event-free survival in patients with Ewing sarcoma. METHODS: In total, 427 patients who had Ewing sarcoma or tumors in the Ewing sarcoma family and received treatment with preoperative chemotherapy and surgery at 10 international institutions were included. Multivariate Cox proportional-hazards analyses were used to assess the associations between tumor necrosis and all four outcomes while controlling for clinical factors identified in bivariate analysis, including age, tumor volume, location, surgical margins, metastatic disease at presentation, and preoperative radiotherapy. RESULTS: Patients who had a complete (100%) tumor response to chemotherapy had increased overall survival (hazard ratio [HR], 0.26; 95% CI, 0.14-0.48; p < .01), recurrence-free survival (HR, 0.40; 95% CI, 0.20-0.82; p = .01), metastasis-free survival (HR, 0.27; 95% CI, 0.15-0.46; p ≤ .01), and event-free survival (HR, 0.26; 95% CI, 0.16-0.41; p ≤ .01) compared with patients who had a partial (0%-99%) response. CONCLUSIONS: Complete tumor necrosis should be the index parameter to grade response to treatment as satisfactory in patients with Ewing sarcoma. Any viable tumor in these patients after neoadjuvant treatment should be of oncologic concern. These findings can affect the design of new clinical trials and the risk-stratified application of conventional or novel treatments.

Primary Undifferentiated Neoplasm of the Left Arm with Characteristics of Extragonadal Germ Cell Tumor and High-Grade Sarcoma.

A previously healthy man in his late 20s was diagnosed with a primary undifferentiated non- metastatic tumor of the left arm. After a biopsy, a clear pathological diagnosis could not be established. The tumor had positive immunohistological markers for both an extragonadal germ cell tumor and a high-grade sarcoma. Given the presumed germ cell etiology, he was started on empiric chemotherapy with etoposide and cisplatin. After a few cycles, the tumor showed dramatic response. However, due to poor patient follow- up, it progressed to massive size with severe compromise of the joint and critical neurovascular structures, which led to the decision for limb amputation. Post-surgical checkups showed no recurrence of the primary tumor or metastasis. This is the first report in the literature showing a tumor with these histological characteristics that responded to platinum-based therapy. It provides evidence for the need of more specific markers for the pathological evaluation of undifferentiated neoplasms.

Rare FGFR Oncogenic Alterations in Sequenced Pediatric Solid and Brain Tumors Suggest FGFR Is a Relevant Molecular Target in Childhood Cancer.

PURPOSE: Multiple FGFR inhibitors are currently in clinical trials enrolling adults with different solid tumors, while very few enroll pediatric patients. We determined the types and frequency of FGFR alterations (FGFR1-4) in pediatric cancers to inform future clinical trial design. METHODS: Tumors with FGFR alterations were identified from two large cohorts of pediatric solid tumors subjected to targeted DNA sequencing: The Dana-Farber/Boston Children's Profile Study (n = 888) and the multi-institution GAIN/iCAT2 (Genomic Assessment Improves Novel Therapy) Study (n = 571). Data from the combined patient population of 1,395 cases (64 patients were enrolled in both studies) were reviewed and cases in which an FGFR alteration was identified by OncoPanel sequencing were further assessed. RESULTS: We identified 41 patients with tumors harboring an oncogenic FGFR alteration. Median age at diagnosis was 8 years (range, 6 months-26 years). Diagnoses included 11 rhabdomyosarcomas, nine low-grade gliomas, and 17 other tumor types. Alterations included gain-of-function sequence variants (n = 19), amplifications (n = 10), oncogenic fusions (FGFR3::TACC3 [n = 3], FGFR1::TACC1 [n = 1], FGFR1::EBF2 [n = 1], FGFR1::CLIP2 [n = 1], and FGFR2::CTNNA3 [n = 1]), pathogenic-leaning variants of uncertain significance (n = 4), and amplification in combination with a pathogenic-leaning variant of uncertain significance (n = 1). Two novel FGFR1 fusions in two different patients were identified in this cohort, one of whom showed a response to an FGFR inhibitor. CONCLUSION: In summary, activating FGFR alterations were found in approximately 3% (41/1,395) of pediatric solid tumors, identifying a population of children with cancer who may be eligible and good candidates for trials evaluating FGFR-targeted therapy. Importantly, the genomic and clinical data from this study can help inform drug development in accordance with the Research to Accelerate Cures and Equity for Children Act.

Surgical Hip Dislocation for a Diagnostic Dilemma: Differentiating Synovial Chondromatosis and Pigmented Villonodular Synovitis.

Pigmented villonodular synovitis (PVNS) and synovial chondromatosis (SC) of the hip are rare synovial diseases that can induce joint destruction without early diagnosis and treatment. The extent of surgical excision is critical given the high rates of recurrence. In the presented case, a 19-year-old female was referred to our institution with progressive left hip pain and radiologic evidence of an intra-articular mass that was consistent with PVNS versus SC. Her medical history was notable for a prior excision of a fibrous lesion at an outside hospital at age 13 with persistent pain. The patient underwent a surgical hip dislocation approach to obtain near-complete visualization of the femoroacetabular joint, ensuring complete evaluation and excision. The tumor was intraoperatively diagnosed as SC and excised accordingly, during an uneventful operation. Pathology confirmed the diagnosis. The essential diagnostic and surgical steps for the management of this pelvic tumor diagnostic dilemma are described. Level of Evidence: V.

Distant migration of gluteal augmentation fat presenting as a soft tissue knee mass.

Gluteal augmentation with autologous fat grafting is an increasingly popular procedure. While complication rates are low, the clinical and imaging evaluation of the various complications can be challenging. We report a case of distal migration of a failed gluteal fat graft in a young female patient presenting as a soft tissue mass in the knee, mimicking a soft tissue sarcoma. Surgical resection of the migrated fat graft confirmed the diagnosis. The diagnosis was challenging as the patient was initially reluctant to disclose her surgical history due to perceived negative social stigmas related to cosmetic contouring procedures. This case highlights the imaging findings of a rare complication following autologous fat grafting for gluteal augmentation and the importance of obtaining a thorough medical history.

Epithelioid Sarcoma Presenting in the Thumb of a Child.

Epithelioid sarcoma (ES) is a high-grade, soft tissue tumor of mesenchymal origin that rarely occurs in children and is often misdiagnosed as a benign entity. We present the case of a 12-year-old girl with a delayed diagnosis of ES of the left thumb. Radiological examination showed possible calcinosis from inflammation or traumatic injury. However, histopathological and immunohistochemistry studies showed findings consistent with a diagnosis of ES. She was treated with amputation of the interphalangeal joint of the left thumb. This case highlights the clinical and pathologic correlation required for the appropriate diagnosis and treatment of patients with soft tissue masses.

Characteristics and oncologic outcomes of patients with Ewing sarcoma of the scapula.

BACKGROUND AND OBJECTIVES: Ewing sarcoma is the second most common bone sarcoma of childhood. Ewing sarcomas of the scapula are rare, with little known about their characteristics and outcomes. In this study, we describe the demographic characteristics, tumor characteristics, and oncologic outcomes of patients with Ewing sarcoma of the scapula. METHODS: This is a retrospective case series of thirty-four patients treated at three urban hospitals between 1993 and 2014 for Ewing sarcomas affecting the scapula. Their demographic data, tumor characteristics, and oncologic outcomes are reported and contrasted with data on Ewing sarcoma described in the literature. RESULTS: Patients in our case series were 59% male. The average age at diagnosis was 16 years. 44% of patients had metastatic disease at presentation. 26% of patients had a tumor size >8 cm in largest dimension at diagnosis. 9 patients in our series had the t (11; 22) translocation present. Patients had a survival rate of 68% at five years. No patients had local recurrence of disease. Compared with findings reported in the literature concerning Ewing sarcoma affecting other locations, patients with Ewing sarcoma of the scapula were slightly older at time of diagnosis, had a lower percentage of tumors with size > 8 cm in largest dimension at presentation, and more commonly had metastatic disease at presentation. Patients in our cohort had a 5-year survival rate of 68%, which is higher than the rate of approximately 55% as reported in the general literature. CONCLUSIONS: In this study, we describe a retrospective case series of thirty-four patients with Ewing sarcomas of the scapula. This is the largest case series to date of Ewing sarcoma affecting this location to our knowledge. These results will contribute to the understanding of the clinical profile and oncologic behavior of Ewing sarcomas affecting the scapula.

Oncological and Functional Outcomes in Joint-sparing Resections of the Proximal Femur for Malignant Primary Bone Tumors.

BACKGROUND: Joint-sparing resections (JSR) of the proximal femur allow for preservation of the proximal femoral growth plate and native hip joint, but whether this offers fewer complications or better function and longevity of the reconstruction remains unknown. In this study, we compared the functional outcomes of pediatric patients with bone sarcomas undergoing JSR of the proximal femur with intercalary allograft (ICA) reconstruction to those undergoing proximal femoral resections (PFR) with allograft-prosthetic composite (APC) reconstructions. METHODS: We retrospectively reviewed all patients undergoing JSR with ICA reconstruction and PFR with APC reconstructions between 1995 and 2013 at a tertiary pediatric referral center. Primary outcomes included major and minor complications and secondary outcomes included the need for a secondary procedure, presence of local or distant relapse, survival status, and the presence of pain and ambulatory status (limp, assistive device, highest level of function). We assessed differences in outcomes using the Fisher exact and Wilcoxon rank-sum tests. RESULTS: Eight patients underwent a JSR and ICA reconstruction, while 7 patients underwent a PFR with APC reconstruction. Median patient follow-up was 60.4 months (interquartile range: 36.8 to 112.9) Patients undergoing JSR and ICA reconstruction were younger than patients undergoing PFR with APC reconstruction (7.7 vs. 11.7 y, P=0.043); however, we found no other statistically significant differences in patient demographics. There were no statistically significant differences in primary or secondary outcomes between the study groups; however, patients who underwent JSR with ICA had more major complications (62.5% vs. 42.9%, P=0.29) and a lower rate of minor complications (25% vs. 28.6%, P=0.22). CONCLUSION: Treatment of proximal femoral bone sarcomas in pediatric and adolescent patients remains a challenging enterprise. JSR with ICA reconstruction in the proximal femur, when feasible, may provide a similar function and risk of intermediate-term major and minor complications when compared with PFR with APC reconstruction. Further long-term studies are required to determine the impact of the native femoral head retention with respect to revision rates. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Sclerotherapy for Aneurysmal Bone Cysts: Scale for Response.

BACKGROUND: The objective of this study was to develop a response scale for aneurysmal bone cysts (ABCs) treated with sclerotherapy and determine its inter-rater reproducibility. METHODS: Patients treated with sclerotherapy for an ABC between 1993 and 2014 were identified. An attending orthopaedic surgeon and an attending interventional radiologist independently reviewed the radiographic series for each patient and determined response to treatment using a novel grading system. Pain scores were collected from each visit. Inter-rater reliability was assessed using the intraclass correlation coefficient (ICC). General estimating equations analysis was used to evaluate the relationship between radiographic and pain scores and outcome, to develop an algorithm for the study patient population. A receiver operating characteristic curve was constructed to evaluate the diagnostic performance of the radiographic and pain scores in identifying the necessity of further treatment. To quantify the diagnostic utility, the area under the receiver operating characteristic curve was estimated along with a 95% confidence interval (CI). RESULTS: The inter-rater reliability was excellent for magnetic resonance imaging (ICC=0.83; 95% CI=0.74-0.89) and good for computed tomography/x-ray (ICC=0.69; 95% CI=0.51-0.81). The radiographic and pain scores proved to be independent predictors of treatment (P<0.001 and 0.004, respectively). An algorithm to determine the predictive probability for treatment versus observation in the study population was developed and tested based on these assessments. The area under the receiver operating characteristic curve of 0.85 (95% CI=0.79-0.92) indicated the good diagnostic performance of the algorithm. CONCLUSIONS: This novel grading system for radiographic response to sclerotherapy treatment demonstrates excellent to good inter-rater reliability giving providers a platform for discussion among themselves and with patients/parents. When incorporated with an assessment of pain, a predictive algorithm shows how this information could be used to determine the next steps after sclerotherapy treatment. LEVEL OF EVIDENCE: Level IV-case series.

Surgical Treatment of Solitary Periarticular Osteochondromas About the Knee in Pediatric and Adolescent Patients: Complications and Functional Outcomes.

BACKGROUND: Solitary osteochondromas, or osteocartilaginous exostoses (OCEs), represent the most common benign bone tumor. Despite frequently causing symptoms about the knee in younger populations, there is minimal previous literature investigating surgical treatment. METHODS: We retrospectively reviewed the records of patients <20 years old who had undergone surgical treatment of symptomatic, pathologically confirmed, solitary periarticular knee OCE at a single pediatric center between 2003 and 2016. The clinical course, radiographic and pathological features, and complications were assessed. Prospective outreach was performed to investigate patient-reported functional outcomes. RESULTS: Two hundred and sixty-four patients (58% male, 81% athletes) underwent excision of a solitary OCE about the knee at a mean age (and standard deviation) of 14.3 ± 2.24 years. Fifty-five percent of the procedures were performed by orthopaedic oncologists, 25% were performed by pediatric orthopaedic surgeons, and 20% were performed by pediatric orthopaedic sports medicine surgeons, with no difference in outcomes or complications based on training. Of the 264 lesions, 171 (65%) were pedunculated (versus sessile), 157 (59%) were in the distal part of the femur (versus the proximal part of the tibia or proximal part of the fibula), and 182 (69%) were medial (versus lateral). Postoperatively, 96% of the patients returned to sports at a median of 2.5 months (interquartile range, 1.9 to 4.0 months). Forty-two patients (16%) experienced minor complications not requiring operative intervention. Six patients (2%) experienced major complications (symptoms or disability at >6 months or requiring reoperation), which were more common in patients with sessile osteochondromas (p = 0.01), younger age (p = 0.01), and distal femoral lesions as compared with proximal tibial lesions (p = 0.003). Lesion recurrence was identified in 3 patients (1.1%). Overall, the median Pediatric International Knee Documentation Committee (Pedi-IKDC) and mean Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS) scores were 97 (interquartile range, 93 to 99) and 16.7 ± 8.15, respectively, at a median duration of follow-up of 5.8 years. CONCLUSIONS: In our large cohort of pediatric patients who underwent excision of solitary knee osteochondromas, most patients were male adolescent athletes. Most commonly, the lesions were pedunculated, were located in the distal part of the femur, and arose from the medial aspect of the knee. Regardless of surgeon training or lesion location, patients demonstrated excellent functional outcomes, with minimal clinically important postoperative complications and recurrences, although patients with sessile lesions and younger age may be at higher risk for complications. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Verrucous Venous Malformation-Subcutaneous Variant.

BACKGROUND: Verrucous venous malformation (VVM), previously called "verrucous hemangioma," typically involves the dermis and the subcutaneous fat. We have encountered patients with VVM confined to the hypodermis. MATERIALS AND METHODS: During a nearly 20-year period, 13 patients, aged 2-17 years, presented with a subcutaneous mass in the limb without clinically obvious epidermal alterations. Consequently, operative excisions did not include the skin. RESULTS: Histopathologically, the specimens were composed of blood-filled channels with morphologic characteristics of capillaries and veins that infiltrated adipose tissue. Aggregates often formed nodules with variable fibrosis and a component of large and radially oriented vessels. A diagnosis of VVM was supported by endothelial immunopositivity for GLUT-1 (25%-75% immunopositive channels in 16/16 specimens); D2-40 (1%-25% channels in 14/15 specimens); and Prox-1 (1%-50% of channels in 14/16 specimens). A MAP3K3 mutation was identified by droplet digital PCR in 3 of the 6 specimens. CONCLUSIONS: Diagnosis of VVM in this uncommon location is challenging because of absence of epidermal changes and lack of dermal involvement. Imaging is not pathognomonic, and mimickers are many. Appropriate immunohistochemical stains and molecular analysis contribute to the correct diagnosis.

Image-Guided Core Needle Biopsy of Adipocytic Tumors: Diagnostic Accuracy and Concordance With Final Surgical Pathology.

OBJECTIVE. Diagnostic accuracy of core needle biopsy (CNB) for adipocytic tumors can be low because of sampling error from these often large, heterogeneous lesions. The purpose of this study was to evaluate the diagnostic accuracy of image-guided CNB for various adipocytic tumors in comparison with excisional pathology. MATERIALS AND METHODS. Adipocytic tumors (n = 77) of all adult patients undergoing image-guided CNB and subsequent surgical excision of an adipocytic tumor at a tertiary referral center between 2005 and 2019 were studied. To determine concordance, we compared pathologic diagnoses based on CNB to the reference standard of pathologic diagnoses after surgical excision. Tumors were divided into three categories (benign lipomatous tumors [lipoma, lipoma variants, hibernomas], atypical lipomatous tumors [ALTs] or well-differentiated liposarcomas [WDLs], and higher grade liposarcomas [myxoid, dedifferentiated, pleomorphic]), and diagnostic accuracy was calculated for each category. RESULTS. In 73 of 77 adipocytic tumors (95%), diagnosis at CNB and diagnosis after excision were concordant. Accuracy of diagnosis was poorer for ALTs and WDLs than for the other two categories, and the difference was statistically significant (p < .002). For the 29 benign lipomatous tumors and the 27 higher-grade liposarcomas, diagnoses at CNB and after excision were concordant in all cases (100%). Seventeen of the 21 tumors (81%) diagnosed as ALTs or WDLs at CNB had a concordant diagnosis after excision; four of the 21 were upgraded (dedifferentiated liposarcoma, n = 3; myxoid liposarcoma, n = 1). CONCLUSION. CNB provides high diagnostic accuracy for adipocytic tumors, particularly for benign lipomatous tumors and higher grade liposarcomas. However, though still high at 81%, diagnostic accuracy of CNB is not as high for tumors diagnosed as ALTs or WDLs. Awareness of this limitation is important when determining management, particularly of cases of ALT or WDL for which surgery is not planned.

Quantification of Osteosarcoma Mineralization on Plain Radiographs - Novel Software Applications to Assess Response to Chemotherapy.

Osteosarcoma is the most common primary malignant bone tumor in children. Patient survival with osteosarcoma is heavily influenced by the response to chemotherapy, measured by tumor necrosis upon histological analysis. Unfortunately, response is not measurable until the time of surgery and therefore modifications to chemotherapy protocol are only made after several weeks of treatment and surgery. Osteosarcoma tumors often demonstrate increased mineralization following the onset of chemotherapy. Furthermore, it has been hypothesized that this mineralization-apparent on radiographs-may correlate with chemotherapy response, however, this has not been demonstrated with qualitative visual evaluation. The ability to non-invasively measure a patient's response to chemotherapy using plain radiographs, which is currently included in the normal clinical workflow, would guide the medical oncologists to tailor treatment for patients with osteosarcoma. After obtaining appropriate multi-center institutional review board approvals, we identified 31patients that possess a pair of pre-and post-chemotherapy radiograph along with the necrosis measure. The images were digitized scans of physical radiographs between 1999 and 2013. Software was designed to measure the signal intensities in the tumor, a region of the soft tissue, air, and healthy bone. The tumor signals were normalized based on the random combination of air, soft tissue or bone, by subtraction or division. The differences in tumor signal between pre-and post-image were plotted against the percent necrosis determined by histological analysis. Different combinations of the normalization methods were compared 2based on the slope, coefficient of determination (R2) and Pearson correlation coefficient (ρ).

Osteosarcoma mineralization changes on radiographs have moderate correlation to chemotherapy response using bone subtraction methodology.

Background: Survival following a diagnosis of osteosarcoma is correlated strongly with response to chemotherapy. Mineralization changes seen on radiographs have been hypothesized to correlate with chemotherapy response, however, this has never been analyzed using modern techniques. Methods: Retrospective review of radiographs obtained before and after neoadjuvant chemotherapy was performed for 31 patients with high-grade, conventional osteosarcoma. Pre-chemotherapy (PreC) images and post-chemotherapy (PostC) images were co-registered. Tumor luminance measurements were normalized based on the non-tumor bone and then the relative change in tumor mineralization were measured. Results: Mean luminance values for pre-chemotherapy non-tumor-affected bone and tumor were 0.63±0.12 and 0.65±0.12, respectively. Mean values for PostC non-tumor-affected bone were 0.59±0.14 and 0.64±0.10, respectively. Once normalized, osteosarcoma mineralization change showed a statistically significant moderate correlation-Pearson correlation coefficient (ρ) of 0.36 (P=0.038)-with the tumor necrosis value. Conclusions: Moderate, positive correlation was found between osteosarcoma mineralization change during chemotherapy and chemotherapy response. Further work is required to determine if these findings are prognostic by identifying best practice for image analysis and repeating this work with prospectively acquired digital radiographs using uniform technique and phantom normalization.