Ultrasonography of Superficial Soft-Tissue Masses: Society of Radiologists in Ultrasound Consensus Conference Statement.

The Society of Radiologists in Ultrasound convened a panel of specialists from radiology, orthopedic surgery, and pathology to arrive at a consensus regarding the management of superficial soft-tissue masses imaged with US. The recommendations in this statement are based on analysis of current literature and common practice strategies. This statement reviews and illustrates the US features of common superficial soft-tissue lesions that may manifest as a soft-tissue mass and suggests guidelines for subsequent management.

PRAME expression in spindle cell melanoma, malignant peripheral nerve sheath tumour, and other cutaneous sarcomatoid neoplasms: a comparative analysis.

Diagnosis of spindle cell/sarcomatoid melanoma may be challenging due to frequent loss of expression of melanocytic marker(s) and histomorphologic resemblance to various mesenchymal tumours, particularly malignant peripheral nerve sheath tumour (MPNST). Overexpression of PReferentially expressed Antigen in MElanoma (PRAME) supports a diagnosis of melanoma when evaluating challenging melanocytic tumours. PRAME expression in MPNST and other cutaneous sarcomatoid neoplasms, however, has not been well characterised. We aimed to determine the utility of PRAME immunostain in distinguishing spindle cell melanoma from MPNST and other sarcomatoid mimics. PRAME expression was scored by extent (0 to 4+) and intensity (0 to 3) of staining. A strong positive correlation was observed between the extent and intensity scores (r = 0.84). An extent score of 4+, defined by staining in 76-100% of tumour cells, was seen in 56% (23/41) of spindle cell melanomas, 18% (7/38) of MPNSTs, 15% (4/27) of cutaneous sarcomatoid squamous cell carcinomas (SCCs), 33% (5/15) of poorly differentiated cutaneous angiosarcomas, 12% (4/33) of atypical fibroxanthomas (AFXs), 4% (1/25) of pleomorphic dermal sarcomas (PDSs), and none (0/16) of the high-grade cutaneous leiomyosarcomas. A significant difference was found between spindle cell melanoma and all other examined sarcomatoid neoplasms except angiosarcoma. While diffuse (and often strong) PRAME expression is more frequently observed in spindle cell melanoma than MPNST, sarcomatoid SCC, AFX, PDS, and high-grade leiomyosarcoma, its limited sensitivity and specificity caution against its use as a standalone diagnostic marker. PRAME may complement other epigenetic or lineage-specific markers and should only be used as part of an immunohistochemical panel when evaluating these sarcomatoid neoplasms.

Imaging Characteristics of the Proximal Lateral Collateral Ligament of the Knee: Findings on Ultrasound and MRI With Histologic Correlation.

OBJECTIVES: Determine prevalence of increased signal intensity of the lateral collateral ligament (LCL) of the knee on MRI and decreased echogenicity on ultrasound, and compare with cadaveric histologic evaluation. METHODS: After IRB approval of this prospective study with informed consent, patients having knee MRI were additionally evaluated with ultrasound. Signal intensities of LCL on MRI (low, intermediate, high), echogenicity at ultrasound (hyperechoic, hypoechoic, anechoic), and extent of findings were assessed. Descriptive statistics, Wilcoxon signed ranked test, and intraclass correlation coefficient (ICC) were calculated. Two cadaveric knees were imaged with MRI and ultrasound, including histologic LCL evaluation. RESULTS: Seventy-three subjects were included (39 males, 34 females; mean age 48 ± 14 years) with 77 knee examinations. On MRI, low, intermediate, and high signals were present in 21% (16/77), 75% (58/77), and 4% (3/77), respectively. On ultrasound, echogenicity was assessed as hyperechoic, hypoechoic, and anechoic in 62% (48/77), 38% (29/77), and 0% (0/77), respectively. Mean length of increased signal was 8.6 mm (±4.9) on MRI, and 6.5 mm (±4.8) on ultrasound. The ICC showed a good to excellent intermodality reliability (0.735-0.899) without statistically significant difference for interreader measurements (P = .163-.795). Histology evaluation showed transition of ligament fibers to fibrocartilage at its insertion with increased connective tissue mucin corresponding to MRI and ultrasound findings. CONCLUSIONS: Increased signal intensity of the proximal LCL on ultrasound and MRI is common and corresponds to normal connective tissue mucin.

Ultrasound of myxofibrosarcoma.

The ultrasound appearance of myxofibrosarcoma is highly variable corresponding to its variable and at times heterogeneous histopathologic appearance. Myxofibrosarcomas may mimic a benign process and the infiltrative tumor margins may be difficult to precisely delineate on ultrasound imaging. These tumor characteristics pose a diagnostic challenge on ultrasound evaluation. The radiologist should be aware of the variable morphologic presentation and infiltrative nature of myxofibrosarcoma and the limitations of ultrasound in the initial diagnosis, biopsy guidance, and post-surgical follow-up of this tumor.

YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases.

YAP1-TFE3-fused hemangioendothelioma is an extremely rare malignant vascular tumor. We present the largest multi-institutional clinicopathologic study of YAP1-TFE3-fused hemangioendothelioma to date. The 24 cases of YAP1-TFE3-fused hemangioendothelioma showed a female predominance (17 female, 7 male) across a wide age range (20-78 years old, median 44). Tumors were most commonly located in soft tissue (50%), followed by bone (29%), lung (13%), and liver (8%), ranging from 3 to 115 mm in size (median 40 mm). About two-thirds presented with multifocal disease, including 7 cases with distant organ metastasis. Histopathologically, we describe three dominant architectural patterns: solid sheets of coalescing nests, pseudoalveolar and (pseudo)vasoformative pattern, and discohesive strands and clusters of cells set in a myxoid to myxohyaline stroma. These patterns were present in variable proportions across different tumors and often coexisted within the same tumor. The dominant cytomorphology (88%) was large epithelioid cells with abundant, glassy eosinophilic to vacuolated cytoplasm, prominent nucleoli and well-demarcated cell borders. Multinucleated or binucleated cells, prominent admixed erythrocytic and lymphocytic infiltrates, and intratumoral fat were frequently present. Immunohistochemically, ERG, CD31, and TFE3 were consistently expressed, while expression of CD34 (83%) and cytokeratin AE1/AE3 (20%) was variable. CAMTA1 was negative in all but one case. All cases were confirmed by molecular testing to harbor YAP1-TFE3 gene fusions: majority with YAP1 exon 1 fused to TFE3 exon 4 (88%), or less commonly, TFE3 exon 6 (12%). Most patients (88%) were treated with primary surgical resection. Over a follow-up period of 4-360 months (median 36 months) in 17 cases, 35% of patients remained alive without disease, and 47% survived many years with stable, albeit multifocal and/or metastatic disease. Five-year progression-free survival probability was 88%. We propose categorizing YAP1-TFE3-fused hemangioendothelioma as a distinct disease entity given its unique clinical and histopathologic characteristics in comparison to conventional epithelioid hemangioendothelioma.

Phase 2 study of dasatinib in patients with alveolar soft part sarcoma, chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor.

BACKGROUND: Alveolar soft part sarcoma (ASPS), chondrosarcoma (CS), chordoma, epithelioid sarcoma, and solitary fibrous tumor (SFT) are malignant tumors that are relatively resistant to chemotherapy and for which more effective drug therapy is needed. METHODS: The 5 listed subtypes were enrolled into a single indolent sarcoma cohort in a phase 2 study of dasatinib using a Bayesian continuous monitoring rule for enrollment. The primary objective was to estimate the 6-month progression-free survival (PFS) rate according to the Choi criteria with a target of ≥50%. Cross-sectional imaging was performed before the start of treatment, every 2 months for 6 months, and then every 3 months during treatment. The 2- and 5-year survival rates were determined. RESULTS: One hundred sixteen patients were enrolled within 45 months, and 109 began treatment with dasatinib. The 6-month PFS rate and the median PFS were 48% and 5.8 months, respectively. The PFS rate at 6 months was highest with ASPS (62%) and lowest with SFT (30%). More than 10% of the patients with ASPS, CS, or chordoma had stable disease for more than 1 year. Collectively, for all 5 subtypes, the 2- and 5-year overall survival rates were 44% and 13%, respectively. An objective response was observed in 18% of the patients with CS or chordoma. CONCLUSIONS: Dasatinib failed to achieve control of sarcoma growth for at least 6 months in more than 50% of the patients in this trial according to the Choi tumor response criteria. An objective tumor response and prolonged stable disease was observed in >10% of patients with CS or chordoma. Cancer 2017;90-97. © 2016 American Cancer Society.

The utility of ETV1, ETV4 and ETV5 RNA in-situ hybridization in the diagnosis of CIC-DUX sarcomas.

AIMS: A recently characterized group of undifferentiated small round cell sarcomas harbours fusions of the genes CIC and DUX4. Studies report a distinctive gene expression profile for these sarcomas, including expression of E26 transformation-specific (ETS) family proto-oncogenic transcription factors ETV1, ETV4 and ETV5. To test the utility of an ancillary diagnostic technique for these tumours, we evaluated chromogenic RNA in-situ hybridization assays for ETV1, ETV4 and ETV5 as diagnostic adjuncts for this emerging group of highly malignant sarcomas. METHODS AND RESULTS: We tested six confirmed CIC-DUX4 sarcomas and 105 lesions in the differential, including 48 Ewing sarcomas for expression of ETV1, ETV4 and ETV5, scoring expression utilizing a previously validated scale. ETV1 and ETV4 were positive in five of six cases, while ETV5 was positive in six of six. No Ewing sarcoma or other sarcoma tested showed coexpression of these transcripts, while one ETV1/ETV4/ETV5 triple positive previously unclassified round cell sarcoma was identified as harbouring a CIC rearrangement by break-apart fluorescence in-situ hybridization (FISH). CONCLUSION: We identified overexpression of ETV1, ETV4 and ETV5 transcripts in situ in CIC-DUX4 sarcomas using a robust assay in routine archival sections. One previously unclassified round cell sarcoma showed ETV1/4/5 positivity, and was proved to harbour a CIC rearrangement by break-apart FISH. The sensitivity and specificity observed with our in-situ hybridization assay implies potential utility as an ancillary diagnostic technique, particularly when faced with limited biopsy samples.

SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma.

BACKGROUND: Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma. METHODS: Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ≥6 months) with a target of ≥25%. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a <1% chance the CBR was ≥25%. RESULTS: A total of 200 patients were enrolled. Accrual was stopped early in 5 cohorts because of low CBR. The leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ≥25% in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36% of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11% of patients. CONCLUSIONS: Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity.

SPARC expression in patients with high-risk localized soft tissue sarcoma treated on a randomized phase II trial of neo/adjuvant chemotherapy.

BACKGROUND: Treatment for localized soft tissue sarcoma includes surgery and radiation, while the role of chemotherapy is controversial. Biomarkers that could predict therapeutic response or prognosticate overall survival (OS) are needed to define patients most likely to benefit from systemic treatment. Serum protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that has been evaluated as a potential biomarker in numerous malignancies given its involvement in cell adhesion, proliferation, migration, and tissue remodeling. METHODS: Using primary biopsy and resection specimens from patients with high-risk localized, soft tissue sarcoma treated on a neo/adjuvant chemotherapy study, SPARC expression was assessed and compared to patient and tumor characteristics, treatment, and outcomes. Survival functions were estimated using the Kaplan-Meier method and compared using the log-rank test. The Cox model was used for multivariate analysis. RESULTS: Fifty patients had primary tumor specimens available. High, low, and no SPARC expression was found in 22, 13, and 15 patients, respectively. There was no significant difference in time to recurrence or OS between patients in these three groups. Comparing lack of SPARC expression with any SPARC expression, there was no significant difference in time to recurrence in patients without SPARC expression (n = 15) compared to patients with SPARC expression (n = 35). Likewise, there was no statistically significant difference in OS in patients without SPARC expression versus patients whose tumors expressed SPARC. CONCLUSIONS: Although we did not find a statistically significant difference in time to recurrence and OS in patients with high-risk soft tissue sarcoma, we did identify a trend toward improved time to recurrence and OS in patients whose tumors lacked SPARC expression. However, SPARC did not demonstrate the ability to discern which high-risk patients may have a worse prognosis or greater benefit from chemotherapy. TRIAL REGISTRATION: The trial was registered on September 13, 2005 with ClinicalTrials.gov, number https://clinicaltrials.gov/ct2/show/NCT00189137?term=sarcoma&id=NCT00189137&state1=NA%3AUS%3AMI&phase=1&rank=1 .

Myxoinflammatory fibroblastic sarcoma: spectrum of disease and imaging presentation.

OBJECTIVES: To describe the imaging findings of a series of myxoinflammatory fibroblastic sarcomas (MFSs) from our institution, including a case of dedifferentiated MFS and two cases with areas of high-grade tumor, in addition to typical cases of low-grade tumor. To correlate the imaging findings with the pathologic features of these tumors. SUBJECTS AND METHODS: IRB approval was obtained. Retrospective search of the pathology database at our institution from 2000 to 2015 identified seven cases of MFS with available imaging. Imaging, pathology, and clinical data were reviewed. RESULTS: Unlike the majority of well-differentiated tumors in our series (four cases), one tumor showed dedifferentiation and two cases had areas of high-grade tumor. The dedifferentiated tumor showed peripheral post-contrast enhancement. One case with a substantial high-grade component showed osseous destruction and peripheral enhancement in the high-grade area, while the low-grade component enhanced diffusely. The second case had a small high-grade area and showed diffuse enhancement. All three of these cases had non-acral locations and lacked association with a tendon. The four cases of low-grade MFS demonstrated diffuse enhancement, were located in the distal extremities, and were associated with a tendon. CONCLUSION: The imaging findings of dedifferentiated and high-grade MFS differ from the more typical low-grade tumors in that they have nonenhancing areas, a non-acral location, lack association with a tendon, and may involve bone. The radiologist should be aware that MFS represents a spectrum that includes low-grade tumors, tumors with high-grade areas, and tumors with dedifferentiation and that this spectrum presents with differing imaging features.

CIC-DUX sarcomas demonstrate frequent MYC amplification and ETS-family transcription factor expression.

Recent molecular advances have identified a novel, clinically aggressive subgroup of undifferentiated round cell sarcomas defined molecularly by oncogenic fusion of the gene, CIC, and either DUX4 or its paralog, DUX4L, herein termed CIC-DUX sarcomas. Morphologically, CIC-DUX sarcomas are round cell sarcomas with high-grade nuclear features, including vesicular chromatin and nucleoli, patchy clear cell foci, myxoid change, and necrosis. Here, we studied a cohort of 10 cases, including 6 newly identified cases, 2 with paired metastases. Given our prior observation of trisomy 8 in these tumors, we assayed for amplification and expression of MYC (c-Myc) and representative downstream targets. Trisomy 8 was detected in 5/7 testable cases, with further amplification of MYC locus in 6/7 testable cases and immunohistochemical expression of MYC in 10/10. The canonical MYC transcriptional target, p21, but not MTDH, was differentially expressed compared with Ewing sarcomas. Given prior observation of induction of ETS-family transcription factors by the fusion oncoprotein, we assayed and identified highly prevalent positivity for ERG (9/10) and FLI1 (8/8). These findings are cautionary regarding use of these immunostains in prospective case workup, whereas the prevalent MYC amplification may represent a therapeutically targetable oncogenic pathway in CIC-DUX sarcomas.

Ewing sarcoma.

Classification of small round cell tumors of bone is often challenging due to overlapping clinicopathologic features. The purpose of this article is to review the clinical, radiological, histologic, and molecular features of Ewing sarcoma and to provide a discussion of the differential diagnosis of small round cell tumors of bone.

Nodular fasciitis: characteristic imaging features on sonography and magnetic resonance imaging.

OBJECTIVES: The purpose of this study was to evaluate the imaging features of nodular fasciitis on sonography and magnetic resonance imaging (MRI). METHODS: A retrospective search of the radiologic and pathologic databases over the past 10 years for the diagnosis of nodular fasciitis was performed. Sonographic and MRI features were described. Pathologic specimens were reviewed. RESULTS: Six pathologically confirmed cases of nodular fasciitis were found. The mean patient age was 19.5 years (range, 8-33 years); 3 patients were male and 3 were female. Four patients had sonography only; 1 patient had both sonography and MRI; and 1 patient had MRI only. Three masses were located in the subcutaneous tissue adjacent to fascia; 2 were at the subcutaneous/muscular border; and 1 was intramuscular; however, all were in contact with fascia and showed a fascial tail on sonography and MRI. On sonography and MRI, masses were oval with poorly defined lobulated borders, averaging 2.6 cm (range, 1.8-3.5 cm). On sonography, all masses were hypoechoic. On MRI, the masses were isointense to muscle on T1-weighted sequences, hyperintense to muscle on fluid-sensitive sequences, and enhanced avidly but heterogeneously. The masses were surrounded by fat. CONCLUSIONS: When a rapidly growing oval mass in contiguity with a fascial plane is recognized, the diagnosis of nodular fasciitis should be entertained. More importantly, the possibility of an inaccurate diagnosis by core biopsy exists, which may warrant gross resection.

A skeleton in a huff: insights in etiologies of osteosclerosis.

A 30-yr-old man developed right lower leg pain and a palpable solid mass. Radiographic imaging revealed a periosteal reaction with an exostotic mass arising from the right distal fibula. Generalized skeletal osteosclerosis with periosteal reaction was discovered on a radiographic skeletal survey. A biopsy of the right fibular mass revealed reactive woven bone. The patient was referred to a metabolic bone disease clinic, where laboratory values were consistent with secondary hyperparathyroidism and increased bone turnover. A DXA bone density scan revealed high bone density, with an L1-4 spine Z-score of +9.3, a left femoral neck Z-score of +8.5, and a total hip Z-score of +6.5. A dental exam revealed generalized gingival inflammation, teeth mobility, generalized horizontal alveolar bone loss and widening of the periodontal ligament space, increased bone density around the teeth, and thickening of the radicular lamina dura. An extensive evaluation was performed, with the result of a single test revealing the diagnosis. The differential diagnoses of osteosclerosis affecting the skeleton, teeth, and oral cavity are discussed.

A 30-yr-old man developed, over a short period, pain in his lower right leg accompanied by a hard mass. He also reported weight loss and night sweats for the past 6 months. After evaluation by his primary physician, an X-ray was ordered that reported a bony mass arising from the right fibula bone. A biopsy was performed of the mass, but no evidence of cancer or any other specific abnormality was found. The patient was then referred to a bone disease specialty clinic. Laboratory tests revealed a large increase in how quickly the patient's skeleton was remodeling, affecting the balance of bone formation and removal involved in maintaining a healthy skeleton. A bone density scan reported that the patient had very dense bones. Other unusual changes were also discovered in a dental exam, suggesting bone thickening. After an extensive evaluation, a single blood test revealed the cause of the fibular bone mass and dense bones.

CD34-positive superficial myxofibrosarcoma: a potential diagnostic pitfall.

BACKGROUND: Myxofibrosarcoma (MFS) arises most commonly in the proximal extremities of the elderly, where it may involve subcutaneous and dermal tissues and masquerade as benign entities in limited biopsy samples. We encountered such a case, in which positivity for CD34 and morphologic features were initially wrongly interpreted as a 'low-fat/fat-free' spindle cell/pleomorphic lipoma. Case series have not assessed prevalence of CD34 reactivity among cutaneous examples of MFS. METHODS: We performed a systematic review of our institution's experience, selecting from among unequivocal MFS resection specimens those superficial cases in which a limited biopsy sample might prove difficult to interpret. These cases were immunostained for CD34 and tabulated for clinicopathologic characteristics. RESULTS: After review of all MFS diagnoses over 5 years (n = 56), we identified a study group of superficial MFS for comparison to the index case (total n = 8). Of these, the index and three additional cases (4 of 8, 50%; 2 low, 2 high grade) demonstrated positive staining for CD34, with diffuse staining of spindled cells including cellular processes. Four additional cases showed no or equivocal/rare staining. CONCLUSIONS: CD34 positivity should be recognized as prevalent among such cases and should not be inappropriately construed as inveighing against a diagnosis of MFS in favor of benign entities.

Clear cell sarcoma of the jaw: a case report and review of the literature.

Clear cell sarcoma (CSS) is a unique malignant soft tissue tumor that mainly occurs from the aponeurotic tissue and tendons of extremities. It is rare in the pediatric population. The tumor does not respond well to chemotherapy or irradiation. Complete surgical resection offers the best chance for a cure. Most studies have demonstrated poor prognosis of this tumor, if it is >5 cm. The literature suggests that local recurrence and distant metastasis are not uncommon even with wide resection and that late recurrence and metastasis commonly occur. This case report discusses CSS in the jaw of a pediatric patient. To our knowledge, this is the only case of CSS of the jaw.

Conventional chondrosarcoma of the rib cage and sternum: clinicopathological and molecular analysis of 27 patients treated at a single institution.

Conventional chondrosarcoma of the chest wall is rare, accounting for 15% of cases. Our purpose was to document clinicopathological, imaging and outcome results from a novel set of chest wall chondrosarcomas, and to analyze for IDH mutations and novel molecular alterations. Gross and microscopic pathology, imaging and clinical charts were reviewed. Targeted next-generation sequencing was performed to identify somatic mutations and copy number alterations. The cohort consisted of 27 patients: 16 men and 11 women (mean age 51 years; range 23-76). Palpable mass was the most common presentation. Five were discovered incidentally. Among 20 tumors with complete imaging, 15 arose from a rib and 5 from the sternum. Seven rib tumors were central/intramedullary, 5 were periosteal, 2 were secondary peripheral chondrosarcomas, and one was indeterminate. Among sternal tumors, 4 were central/intramedullary and one was periosteal. Half the periosteal tumors arose from the costochondral junctional cartilage (CCJ). Periosteal chondrosarcomas were sometimes mistaken for extraskeletal masses on initial clinical or radiological examinations. Fifty-nine percent of all tumors were grade 1 and 41% were grade 2. None were dedifferentiated chondrosarcomas. Heterozygous IDH1 mutation was detected in one tumor and heterozygous RAD50 mutation in another. Local recurrence(s) happened in 41% and metastasis in 41%. Grade had strong association with local recurrence (25% grade 1 vs. 64% grade 2 [P = .0447]), metastatic recurrence (19% grade 1 vs. 73% grade 2 [P = .0058]), and survival. Although chest wall chondrosarcomas share morphologic and molecular features with other chondrosarcomas, there is a much higher incidence of periosteal chondrosarcomas. IDH mutant tumors are uncommon. Early diagnosis and margin-negative resection is treatment of choice since chondrosarcomas are chemo- and radioresistant.

Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials.

Importance: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS). Objective: We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630. Design, Setting, and Participants: RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes. Intervention: Patients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone. Main Outcomes and Measures: Overall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017. Results: Overall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45). Conclusions and Relevance: This ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies. Trial Registration: ClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791).

Extra-abdominal desmoid tumor with osseous involvement.

Deep fibromatoses, or desmoid tumors, arise from connective tissue. Imaging can frequently suggest the diagnosis of these aggressive, benign neoplasms. Cross-sectional imaging commonly demonstrates an enhancing solid mass that resembles scar tissue, typically without osseous involvement. We report a case of an extra-abdominal desmoid tumor involving the teres minor muscle in a symptomatic 42-year-old woman with unusual features of medullary involvement and negative nuclear beta-catenin staining.

Can lymphangiosarcoma be resurrected? A clinicopathological and immunohistochemical study of lymphatic differentiation in 49 angiosarcomas.

AIMS: The term lymphangiosarcoma has largely been abandoned in the current classification of endothelial neoplasms. Recently, a number of lymphatic-associated antibodies have been developed for immunohistochemistry, which frequently stain angiosarcomas, implying lymphatic or mixed lymphatic and blood vascular differentiation is common. The aim was to investigate further lymphatic antigen expression, and to explore the relation of immunohistochemistry to morphological and clinical findings. METHODS AND RESULTS: Forty-nine angiosarcomas in tissue microarrays were analysed with D2-40 and antibodies to Prox-1 and vascular endothelial growth factor receptor (VEGFR)-3. D2-40 was positive in 53%, Prox-1 in 76%, and VEGFR-3 in 57%. Tumours with features attributable to lymphatic differentiation such as hobnail and kaposiform morphologies were more often positive with these markers, including a statistical association between D2-40 and hobnailing. Ten tumours had features suggestive of lymphatic differentiation, namely well-differentiated histology, interanastomosing channels devoid of red cells, prominent hobnailing, lymphoid aggregates, and multi-antigen expression of D2-40 (100%), Prox-1 (100%) and VEGFR-3 (60%), which might be deserving of the appellation lymphangiosarcoma. Nine were cutaneous scalp/facial tumours in elderly patients and one arose within chronic lymphoedema. CONCLUSIONS: Lymphatic differentiation is common in angiosarcoma, certain subsets show greater lymphatic differentiation than others, and lymphangiosarcoma may be defined pathologically, rather than clinically.