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Competing Interests: Les auteurs déclarent n’avoir aucun lien d’intérêts.

There is growing concern over the effects of medical diagnostic procedures on cancer risk. Although numerous studies have demonstrated that low doses of ionizing radiation can have protective effects including reduced cancer risk and increasing lifespan, the hypothesis that any radiation exposure increases cancer risk still predominates. In this study, we investigated cancer development and longevity of cancer-prone Trp53 +/- mice exposed at 7-8 weeks of age to a single 10 mGy dose from either a diagnostic CT scan or gamma radiation. Mice were monitored daily for adverse health conditions until they reached end point. Although the median lifespan of irradiated mice was extended compared to control animals, only CT scanned mice lived significantly longer than control mice (P < 0.004). There were no differences in the frequency of malignant cancers between the irradiated and control groups. Exposure to a single CT scan caused a significant increase in the latency of sarcoma and carcinoma (P < 0.05), accounting for the increased lifespan. This study demonstrates that low-dose exposure, specifically a single 10 mGy CT scan, can prolong lifespan by increasing cancer latency in cancer-prone Trp53 +/- mice. The data from this investigation add to the large body of evidence, which shows that risk does not increase linearly with radiation dose in the low-dose range.

The popliteal fossa is the site of several diseases that may be similar in the clinical setting but very different in etiology, treatment, and prognosis. The contemporary presentation of more than one of these conditions is a rare though potentially fatal combination that may lead to a delay in the diagnosis and therapeutic approach. In this report, we describe the case of a patient who presented at our Vascular Department for persistent pain and severe swelling of the right popliteal fossa 8 months after the surgical treatment of a symptomatic popliteal aneurysm by mean of a Dacron prosthetic graft. With the suspect of the graft infection, as defined by angio-computer tomography and fluorodeoxyglucose positron emission tomography, the patient underwent graft removal and revascularization with a biologic conduit. Subsequent surgical revisions for unjustified recurrent hematic collections were necessary without any significative clinical improvement. The histologic analysis of the removed tissue was consistent with a high-grade sarcoma, and the patient underwent above-the-knee amputation of the right limb., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Opinion Statement: Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) tumors share many clinical, etiologic, and histologic features and likely represent components of a tumor spectrum. In dermatologic oncology, differentiating between AFX and PDS is pivotal as tumors with histological features consistent with PDS are more likely to behave in a clinically aggressive manner. Importantly, the term "pleomorphic dermal sarcoma" (PDS) is a more appropriate designation than "undifferentiated pleomorphic sarcoma" (UPS) for describing deeper, more aggressive, histologically high-grade cutaneous tumors that otherwise resemble AFX. Surgery remains the gold standard for treatment. In the setting of AFX, excision with the Mohs micrographic technique appears to offer superior tumor control rates while maintaining greater tissue preservation over wide local excision and should be considered first line. In the setting of PDS, optimal management is less clear given the paucity of available data. However, due to its greater propensity to recur and metastasize, extirpation with complete tumor margin control appears paramount. The roles of imaging and SLNB in management and clinical outcomes of AFX and PDS are unclear given the lack of available data. In reality, these tools are unlikely to be helpful in most cases of AFX. However, in the setting of PDS, emerging literature indicates that these tumors are inherently higher risk, and thus, imaging and SLNB may be helpful in select cases. Additionally, radiation therapy may be of adjuvant benefit for these tumors when clear surgical margins cannot be obtained. While traditional chemotherapy has been largely ineffectual, the recent discovery of key oncogenetic mutations has allowed for the identification of several potential molecular drug targets that may have a therapeutic role with future study. In the unfortunate setting of metastatic disease, a multidisciplinary approach is optimal. Further studies are needed to establish definitive conclusions regarding risk stratification and best management practices.

Background: An increasing number and proportion of cancer patients with apparently localised disease are treated with chemotherapy and radiation therapy in contemporary oncology practice. In a pilot study of radiation-induced sarcoma (RIS) patients, we demonstrated that chemotherapy was associated with a reduced time to development of RIS. We now present a multi-centre collaborative study to validate this association., Methods: This was a retrospective cohort study of RIS cases across five large international sarcoma centres between 1 January 2000 to 31 December 2014. The primary endpoint was time to development of RIS., Results: We identified 419 patients with RIS. Chemotherapy for the first malignancy was associated with a shorter time to RIS development (HR 1.37; 95% CI: 1.08-1.72; P=0.009). In the multi-variable model, older age (HR 2.11; 95% CI 1.83-2.43; P<0.001) and chemotherapy for the first malignancy (HR 1.61; 95% CI 1.26-2.05; P<0·001) were independently associated with a shorter time to RIS. Anthracyclines and alkylating agents significantly contribute to the effect., Conclusions: This study confirms an association between chemotherapy given for the first malignancy and a shorter time to development of RIS.

Because of their locally invasive growth and high recurrence rate despite of aggressive local therapy, treatment of feline sarcomas is challenging. The tyrosine kinase inhibitor (TKI) toceranib is currently licensed for the treatment of canine mast cell tumours. There are only few reports about TKI usage in cats. Previous studies indicated promising potential of TKI for the treatment of feline injection site sarcoma (FISS). In this prospective clinical trial, 18 cats with unresectable FISS were treated at a target dosage of 3.25 mg kg -1 every other day to evaluate the clinical efficacy and toxicity of toceranib. There was no clinical response measurable. Adverse events were generally mild and temporary. Grade 3 or 4 adverse events developed infrequently and all resolved with drug holidays and dose reductions., (© 2016 John Wiley & Sons Ltd.)

Feline injection-site sarcoma (FISS) is commonly treated with surgery and radiation therapy. Despite aggressive therapy, FISS has a high recurrence rate. The true benefit of adjuvant chemotherapy is not known. DNA damage response mechanisms help protect against genomic instability but can also promote chemoresistance. In order to determine whether DNA damage is a feature of FISS, we evaluated tumour tissues with γH2AX immunohistochemistry. H2AX is phosphorylated to form γH2AX following DNA double strand breaks. Seventeen FISS specimens were evaluated prospectively. DNA damage ranged from 2.18 to33.7%, with a median of 16.2%. Significant differences were noted between cats (P < 0.0001). Mitotic index ranged from 0 to 57 with a median of 13 and did not correlate with γH2AX positivity (P = 0.2). Further studies are needed to determine if γH2AX expression may predict chemosensitivity and have independent value as a prognostic factor., (© 2016 John Wiley & Sons Ltd.)

Radiation to the chest wall is common before resection of tumors. Osteoradionecrosis can occur after radiation treatment. Radical resection and reconstruction can be lifesaving. Soft tissue coverage using myocutaneous or omental flaps is determined by the quality of soft tissue available and the status of the vascular pedicle supplying available myocutaneous flaps. Radiation-induced sarcomas of the chest wall occur most commonly after radiation therapy for breast cancer. Although angiosarcomas are the most common radiation-induced sarcomas, osteosarcoma, myosarcomas, rhabdomyosarcoma, and undifferentiated sarcomas also occur. The most effective treatment is surgical resection. Inoperable tumors are treated with chemotherapy, with low response rates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Low-grade sinonasal sarcoma with neural and myogenic features is an entity recently described in the literature. Little is known about its etiopathogenesis, natural history, or optimal treatment. In fact, it has relatively unique findings: it has a distinctive cytogenetic signature, and it expresses both smooth muscle actin and S100 protein. However, its diagnosis is challenging on biopsies showing negative staining for these 2 markers. The differential diagnoses include fibrosarcoma, malignant peripheral nerve sheath tumors, and other benign and malignant lesions. A complete resection, with or without radiotherapy, is required because this lesion appears to be locally aggressive. However, the clinical outcome seems to be good. Low-grade sinonasal sarcoma with neural and myogenic features merits classification as an independent tumor in the next World Health Organization classification of head and neck tumors. Reports of additional cases are required to support its unique classification.

Opinion Statement: Desmoid-type fibromatosis is a sarcoma subtype that gathers some singular characteristics, making it a difficult challenge to face in clinical practice. Despite its excellent survival prognosis, these tumors may be unpredictable, ranging from an asymptomatic indolent course to persistent, local, and extended recurrences that significantly impair quality of life. Although surgery was initially considered the first elective treatment, collected published data during the past few years are now pointing to the "wait and see" approach as a reasonable initial strategy because many patients can live a long life with the disease without having symptoms. When symptoms appear or there is a risk of functional impairment, a wide spectrum of therapies (local and systemic) can be useful in improving symptoms and controlling the disease. Because of the low incidence of desmoid-type fibromatosis, there is scarce scientific evidence supporting any specific treatment. Nonetheless, if volumetric responses are needed, chemotherapy may be a reasonable early option. However, if long-term control of disease is desirable, hormonal therapy, NSAIDs, and TKIs are the likely treatments of choice. Recent new findings in the biologic development of these tumors, such as the role of Wnt/β-catenin dependent pathway, have shown that the prognostic information provided by specific CTNNB1 gene mutations and other genetic profiles can lead to better methods of selecting patients as candidates for other approaches. Based on recent research, the Notch pathway inhibition in DF is one of the most promising potential targets to explore. As an orphan disease, it is mandatory that as many patients as possible be included in clinical trials.

The zebrafish ( Danio rerio) provides a powerful model for analyzing genetic contributors to cancer. Multiple zebrafish lines with cancer-associated genetic mutations develop soft tissue sarcomas that are histologically consistent with malignant peripheral nerve sheath tumor (MPNST). The goal of this study was to determine the phenotype of soft tissue sarcomas in a brca2-mutant/ tp53-mutant zebrafish line using immunohistochemical markers that are commonly expressed in mammalian MPNST. We classified 70 soft tissue sarcomas from a brca2-mutant/ tp53-mutant zebrafish cohort as MPNST, undifferentiated sarcoma, or other tumor based on histologic features. The expression of S100, CD57, and glial fibrillary acidic protein (GFAP) was analyzed in nonneoplastic neural tissues and tumor specimens by immunohistochemistry. Each marker was expressed in nonneoplastic neural tissues. In MPNST, S100 and CD57 were widely expressed in neoplastic cells, with greater consistency observed for CD57 expression. In undifferentiated sarcomas, results were variable and correlated to anatomic location. Coelomic undifferentiated sarcomas often exhibited widespread CD57 expression but limited S100 expression. In comparison, ocular undifferentiated sarcomas exhibited limited expression of both CD57 and S100. Overall, CD57 and S100 expression was significantly higher in MPNST than in undifferentiated sarcomas. GFAP was not expressed in any of the tumors. This study identified commercially available antibodies that are useful for analyzing S100, CD57, and GFAP expression in zebrafish. This study further shows a correlation between degree of histologic differentiation and expression of these markers in soft tissue sarcomas from brca2-mutant/ tp53-mutant zebrafish and suggests that these cancers are derived from the neural crest with differentiation toward myelinating Schwann cells.

Feline injection-site sarcoma (FISS) is an aggressive tumor believed to arise from the proliferation of fibroblasts and myofibroblasts in areas of chronic inflammation, particularly at sites of injection. Local recurrence is frequent after surgical excision. Gelatinases (MMP-2 and MMP-9) and their inhibitor (TIMP-2) are endopeptidases pivotal in extracellular matrix remodeling and therefore in tumor invasiveness. The aim of this study was to investigate the immunohistochemical expression of MMP-2, MMP-9, and TIMP-2 in FISS to assess their usefulness as prognostic factors. Size, soft tissue sarcoma (STS) grading system, depth of infiltration, surgical margins, and Ki-67 index were evaluated as additional prognostic markers. Twenty-four cases of primary FISS were classified according to clinical follow-up as nonrecurrent (NR, n = 14; 58.3%) and recurrent (R, n = 10; 41.7%). MMP-2, MMP-9, and TIMP-2 were variably expressed in the FISS examined, confirming their role in tumor invasiveness, yet they did not show significant differences between the R and NR groups. These results could be due to different tumor stages or to the multiple activities of these enzymes, not limited to ECM remodeling. The immunohistochemical expression of these enzymes considered alone does not seem to be useful as a prognostic marker. STS grading system, depth of infiltration, surgical margins, and Ki-67 index did not relate to recurrence. Instead, the size of the tumor, measured after formalin fixation, with an optimal cutoff of 3.75 cm (accuracy = 86%; P < .05), and the mitotic count, with an optimal cutoff of 20 mitoses/10 HPF (accuracy = 80%; P < .05), could be evaluated as useful prognostic markers.

Objective: Radiation-induced sarcomas (RISs) of the central nervous system are an uncommon late risk of irradiation. We conducted a systematic review of individual patient data to characterize RISs., Methods: We conducted a systemic search of the PubMed databases and compiled a comprehensive literature review. Student t tests were used to evaluate differences between variables. Kaplan-Meier analysis was used to estimate survival. Statistical significance was assessed using a log-rank test., Results: We analyzed 180 cases of RISs, including 59 osteosarcomas, 50 fibrosarcomas, and 16 malignant fibrous histiocytomas. The average age of onset for primary lesions was 28.8 ± 17.9 years, and the average dose of radiation delivered to the primary lesion was 51.4 ± 18.6 Gy. The latency period between radiotherapy and the onset of sarcomas was 12.4 ± 8.6 years. The median overall survival time for all sarcoma patients was 11 months, with a 5-year survival rate of 14.3%. The median survival in patients who received chemotherapy was 18 months, with a 2-year survival rate of 39.4%, whereas patients who did not receive chemotherapy had a median survival of 5 months and a 2-year survival rate of 13.7% (P < 0.0001)., Conclusions: The risk of secondary sarcomas in patients treated with cranial radiotherapy warrants longer follow-up periods beyond the standard time frame typically designated for determining the risk of primary tumor relapse. Moreover, chemotherapy should be considered a potential treatment option for RISs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To estimate the long-term risk of second malignancies after breast cancer treatment in a large homogeneous cohort from a single institution., Patients and Methods: All patients in this study were treated for non-metastatic breast cancer at the Curie institute, Paris, between 1981 and 2000. We calculated the cumulative incidence of second malignancies and the risk of developing each type of second malignancies over a period of 10 to 15 years. The observed crude incidence rates in the entire patient population were then compared to the expected incidence in the general population of French women, as provided by age-standardized data. A standardized incidence ratio (SIR) was calculated for all second malignancies. We also calculated second malignancies standardized incidence ratios for patients who underwent adjuvant therapy for breast cancer., Results: The study cohort included a total of 17,745 women. The median follow-up since diagnosis was 13.4 years (range: 2-29 years). The 15-year cumulative incidence of second malignancies was 1.807 per 100,000 (CI 1.729-1.884). A total of 2370 second malignancies were observed during follow-up, 2010 in the radiotherapy arm and 360 in the no radiotherapy arm (relative risk [RR] 1.15 [1.03-1.28], P=0.0134). Crude incidence rates were significantly higher in our cohort than in the general population for contralateral breast cancer (SIR 2.96 [confidence interval (CI) 2.82-3.12], P<0.0001), sarcomas (SIR 8.48 [CI 6.41-11.22], P<0.0001), leukaemia (SIR 2.37 [CI 1.85-3.04], P<0.0001), lung cancer (SIR 1.39 [CI 1.13-1.72], P<0.0022) and gynaecological cancer (SIR 1.31 [CI 1.15-1.50], P=0.0001). Among patients treated for breast cancer, those who received radiotherapy was associated with an excess risk of sarcoma as compared to those have not had (RR 5.59 [CI 1.35-23.17], P<0.001)., Conclusions: Women treated for breast cancer had a significantly increased risk of several kinds of second malignancies compared to the general population., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

While surgical resection (±radiotherapy) is standard treatment for localized soft tissue sarcomas (STS), chemotherapy is the mainstay for managing locally advanced and metastatic disease. Expanding knowledge of the biologies and sensitivities of STS histotypes, in conjunction with results from a growing collection of retrospective reviews and prospective randomized studies, point to the importance of treating in consideration of histological subtype. Doxorubicin ± ifosfamide continues to be standard first-line therapy for most STS subtypes. Main options for second- or later-line therapy include trabectedin, dacarbazine, gemcitabine combinations, pazopanib and, most recently, eribulin. Using illustrative case studies, treatment options are reviewed for three of the more common STS subtypes - uterine leiomyosarcoma, liposarcoma and synovial sarcoma - with a focus on use of trabectedin.

Background: In several studies, dioxin exposure has been associated with increased risk from several causes of death., Aims: To compare the mortality experience of workers exposed to dioxins during trichlorophenol (TCP) and pentachlorophenol (PCP) production to that of the general population and to examine mortality risk by estimated exposure levels., Methods: A retrospective cohort study which followed up workers' vital status from 1940 to 2011, with serum surveys to support estimation of historical dioxin exposure levels., Results: Among the 2192 study subjects, there were nine deaths in TCP workers from acute non-lymphatic leukaemia [standardized mortality ratio (SMR) = 2.88, 95% confidence interval (CI) 1.32-5.47], four mesothelioma deaths (SMR = 5.12, 95% CI 1.39-13.10) and four soft tissue sarcoma (STS) deaths (SMR = 3.08, 95% CI 0.84-7.87). In PCP workers, there were eight deaths from non-Hodgkin's lymphoma (SMR = 1.92, 95% CI 0.83-3.79), 150 from ischaemic heart disease (SMR = 1.20, 95% CI 1.01-7.89) and five from stomach ulcers (SMR = 3.38, 95% CI 1.10-7.89). There were no trends of increased mortality with increased dioxin exposure except for STS and 2,3,7,8-tetrachlorodibenzo-p-dioxin levels. This finding for STS should be interpreted with caution due to the small number of deaths and the uncertainty in diagnosis and nosology., Conclusions: While some causes of death were greater than expected, this study provides little evidence of increased risk when dioxin exposures are considered., (© The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Gemcitabine is an antimetabolite chemotherapy agent with schedule-dependent metabolism and efficacy. The purpose of this study was to identify the fixed-dose-rate (FDR) of gemcitabine administration in cancer-bearing cats that achieved a target plasma concentration (TPC) of 10 to 20 μM. Fifteen client-owned cats received gemcitabine infusions administered at various FDR for 1 to 6 hours. Plasma gemcitabine and dFdU (2',2'-difluorodeoxyuridine), the major gemcitabine metabolite, were quantitated by high performance liquid chromatography. Cats treated with an FDR less than 2.5 mg/m 2 per minute failed to achieve TPC, whereas cats treated with an FDR of 10 mg/m 2 per minute quickly exceeded the target range. An FDR of 5 mg/m 2 per minute provided the longest duration of exposure without exceeding the upper limit of the TPC. Plasma dFdU concentration mirrored plasma gemcitabine concentrations. These data suggest that in order to maintain TPC of gemcitabine in cats the FDR lies between 2.5 and 5 mg/m 2 per minute. A Phase II study to evaluate efficacy and toxicity of this approach is underway.

Background: The aims of this study were to evaluate the impact of initial uterus-preserving surgery, such as myomectomy or subtotal hysterectomy, on the recurrence rates of patients with uterine sarcoma found incidentally and to investigate the role of surgical re-exploration in this disease subset., Methods: We performed a retrospective chart review for patients who had previously undergone either total hysterectomy or subtotal hysterectomy or myomectomy at the time of initial surgery for presumed benign uterine leiomyoma and were found to have uterine sarcoma on final pathology. Survival analysis was performed comparing patients according to the type of initial surgery., Results: Between 2006 and 2014, 45 patients with uterine sarcoma were identified. Myomectomy or subtotal hysterectomy was performed in 15 patients, and 30 patients underwent total hysterectomy as the initial surgery. Of the patients who underwent myomectomy or subtotal hysterectomy as the initial surgery (n = 15), 14 were re-explored to complete staging. Of the patients who underwent re-exploration (n = 14), five (35.8 %) had remnant sarcoma on the remaining uterus and no patients had disseminated disease. A Kaplan-Meier curve and log-rank test showed no difference in progression-free survival (P = 0.941) between the two groups., Conclusion: Initial uterus-preserving surgery does not appear to be associated with an adverse impact on survival outcomes for unexpected uterine sarcoma when surgical re-exploration was performed immediately. As such, surgical re-exploration may be useful for removing any remnant sarcoma.

Radiation-induced sarcoma (RIS) is a rare complication following therapeutic external irradiation for lung cancer patients. Patients with RIS may develop recurrence or metastasis of the previous disease and also at high risk for early chest wall complications following operation, which requires close follow-up and multidisciplinary approach. We present a challenging case of RIS with a multidisciplinary teamwork in the decision-making and successful management., Competing Interests: Dr. D’Amico is a consultant for Scanlan International. All the other authors have declared no competing interest.

Background: Angiosarcoma is an uncommon, malignant neoplasm often found in skin and soft tissue. Epithelioid angiosarcoma (EA) is a rarer, more aggressive form of angiosarcoma most common in men in their seventh decade. Dacron ® , a polymer comprised of polyethylene terephthalate used in endografts for abdominal aortic aneurysm repairs, has been a suspected carcinogen associated with EA. Currently, three case reports exist in the literature purporting Dacron ® -associated epithelioid angiosarcoma. Herein we report a case of Dacron ® -associated EA.
, Case: A 64-year-old male with a recent history of a repaired type 2 endoleak and Dacron ® endograft for his AAA presented with a painful skin eruption, fever, and weight loss. On exam, erythematous and violaceous papules and nodules were present on the patient's lower back. Biopsy revealed atypical, epithelioid cells forming vascular channels in a sheet-like and infiltrative pattern. These results and subsequent immunostaining were consistent with the diagnosis of EA. A bone marrow biopsy confirmed metastatic angiosarcoma.
, Conclusion: This case further highlights Dacron ® as a rare, but, potential carcinogen associated with EA. , , J Drugs Dermatol. 2016;15(7):897-899.

This study assesses the outcome of two combined treatment strategies for the treatment of feline injection-site sarcoma (FISS). Twenty-one cats with primary or recurrent FISS received 3 cycles of neoadjuvant chemotherapy with epirubicin (25 mg m(-2) ), then an anatomical resection of the entire muscle compartment containing the tumour was performed based on the findings of co-axial imaging. Cats then received a further 3 cycles of adjuvant chemotherapy. Follow-up was performed by telephone contact with a median follow-up time of 1072 days. Three cats (14%) developed local tumour recurrence at days 264, 664 and 1573 after surgery. A median survival time could not be calculated as over 80% of the study population remained alive or were censored due to death from other causes. When compared to historical controls, the results of this study demonstrate superior rates of tumour-free survival and disease-free interval., (© 2014 John Wiley & Sons Ltd.)

OBJECTIVE To evaluate changes in the dimension and volume of feline injection-site sarcomas (FISSs) before (in vivo) and after surgical excision and formalin fixation (ex vivo) as determined by measurements obtained from 2-D and 3-D CT images. SAMPLE 10 excised FISSs. PROCEDURES The maximum length, width, and depth of each FISS were measured on contrast-enhanced 2-D CT images of the tumor obtained in vivo and ex vivo. Those measurements were used to estimate tumor volume with the standard ellipsoid formula. Tumor volume was also calculated from 3-D CT images with software that used a volume-rendering algorithm. Student paired t tests were used for comparisons between the in vivo and ex vivo assessments. RESULTS Small decreases were detected in maximum tumor length, width, and depth between the in vivo and ex vivo assessments; however, tumor length was the only dimension that decreased significantly between the 2 assessments. Median tumor volume decreased significantly between the in vivo and ex vivo assessments regardless of the method used to estimate it. Tumor volume estimated by the ellipsoid formula was significantly lower than that estimated by the 3-D CT software at both assessments. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that shrinkage of FISSs following excision and formalin fixation was small and may be less than that of grossly normal tissue. Tumor volume estimated by the ellipsoid formula was consistently less than that estimated by 3-D CT software and should not be used when accuracy of tumor volume is of particular concern and advanced CT imaging is available.

Radiation-induced sarcoma of the head and neck (RISHN) is a rare and long-term complication of radiation therapy (RT). This report describes a case of RISHN characterized by early and insidious onset. An 80-year-old man was surgically treated for advanced oral squamous cell carcinoma of the left retromolar trigone (pT4aN0). Sixteen months after completion of adjuvant RT, an exophytic sessile lesion arose in the left border of the soft palate. Histologic assessment showed a malignant neoplasm with spindle-shaped cells and areas of bone matrix without perivascular or perineural invasion; such features in addition to immunohistochemical assessment (negative for pan-cytokeratin; positive for vimentin; negative for epithelial membrane antigen; negative for p63; Ki-67, 30%) are consistent with poorly differentiated sarcoma (cT1aN0M0). Fifteen months after a wide surgical resection, the patient was free of disease. RISHN is usually an aggressive neoplasm with insidious onset. Nevertheless, early diagnosis followed by complete surgical excision could make the prognosis comparable to that of spontaneous sarcoma., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To identify the prevalence of unexpected uterine sarcoma after total laparoscopic or abdominal hysterectomy for presumed leiomyoma and compare clinical consequences after hysterectomy with and without transvaginal scalpel morcellation (TVSM)., Methods: In this retrospective study, the medical records of patients who had unexpected uterine sarcoma after total laparoscopic or abdominal hysterectomy for presumed leiomyoma between 2009 and 2013 were reviewed., Results: Among 3021 patients who underwent total hysterectomy for presumed leiomyoma, 18 (1/168, 0.60%) had unexpected uterine sarcoma (5 [1/604, 0.17%] had leiomyosarcoma and 13 [1/232, 0.43%] had low-grade endometrial stromal sarcoma). The risk of unexpected leiomyosarcoma increased steadily in ages from the 40s to the 50s, whereas the risk of unexpected endometrial stromal sarcoma (ESS) decreased steadily in the same period. The unexpected sarcoma was identified in 7 (1/158, 0.63%) of 1104 patients treated by laparoscopy and 11 (1/174, 0.57%) of 1917 patients by laparotomy. Transvaginal scalpel morcellation was performed to extract the uterus in majority (78.53%) of the patients with total laparoscopic hysterectomy. Sixteen (88.89%) cases were low grade, and 2 (11.11%) were high grade: 17 at stage I and 1 at stage II. Nine patients underwent a secondary operation, and 11 patients received adjuvant therapy postoperatively. Except for 1 patient with additional power morcellation, all patients with unexpected ESS survived without recurrence after total hysterectomy with and without TVSM, with mean follow-ups of 25.20 (16-36) months and 32.57 (21-50) months, respectively., Conclusions: The overall incidence of unexpected uterine sarcoma after total hysterectomy for presumed leiomyoma was low. Low-grade endometrial stromal sarcoma was the dominant subtype of unexpected uterine sarcoma in the present study. Currently, incidental TVSM of unexpected ESS during total laparoscopic hysterectomy seemed to cause no additional increase in sarcoma dissemination in the short-term.

The definition of soft tissue and bone sarcomas include a large group of several heterogeneous subtypes of mesenchymal origin that may occur at any age. Among the different sarcomas, rhabdomyosarcoma, synovial sarcoma, Ewing sarcoma and osteosarcoma are aggressive high-grade malignancies that often arise in adolescents and young adults. Managing these malignancies in patients in this age bracket poses various clinical problems, also because different therapeutic approaches are sometimes adopted by pediatric and adult oncologists, even though they are dealing with the same condition. Cooperation between pediatric oncologists and adult medical oncologists is a key step in order to assure the best treatment to these patients, preferably through their inclusion into international clinical trials., (© 2016 S. Karger AG, Basel.)

There are more than 100 sarcoma subtypes, each uncommon and diagnostically challenging. Conventional chemotherapy has little benefit for most soft-tissue sarcomas; new treatment strategies are needed. Multiple recent genomic studies have provided detailed insights into sarcoma biology, including more accurate classification by molecular subtype, identification of recurrent mutations in oncogenic pathways, and evidence of epigenetic dysregulation. Advances in immunotherapy (adoptive immune cell transfer, tumor vaccine strategies, and immune checkpoint inhibition) have also provided a better understanding of how immuno-oncology might best be applied to sarcoma treatment, including connections to oncogenic pathways that may support combination strategies with conventional and targeted therapies. In this article, we review the latest sarcoma genomic studies and immuno-oncology developments and discuss how the findings suggest potential strategies to improve diagnosis and treatment across multiple sarcoma subtypes., (©2015 American Association for Cancer Research.)

The NCCN Guidelines for Uterine Neoplasms provide interdisciplinary recommendations for treating endometrial carcinoma and uterine sarcomas. These NCCN Guidelines Insights summarize the NCCN Uterine Neoplasms Panel's 2016 discussions and major guideline updates for treating uterine sarcomas. During this most recent update, the panel updated the mesenchymal tumor classification to correspond with recent updates to the WHO tumor classification system. Additionally, the panel revised its systemic therapy recommendations to reflect new data and collective clinical experience. These NCCN Guidelines Insights elaborate on the rationale behind these recent changes., (Copyright © 2015 by the National Comprehensive Cancer Network.)

Radiation associated sarcoma is a significant consequence of cancer therapy. Incidence of radiation associated sarcoma correlates with overall radiotherapy exposure. Prognosis is generally poor with 5 year survival rates lower than that for spontaneously occurring sarcomas. Surgical management presents many challenges including having to work in irradiated tissue planes while trying to achieve negative margins. We present a patient with a rare radiation associated pelvic sarcoma whose course illustrates the complexity of this problem., (© 2015 Wiley Periodicals, Inc.)

We report a case of sarcomatoid carcinoma of the skin in a 63-year-old man who was treated with the carbon dioxide snow freezing method for a huge congenital pigmented nevus that extended from the right upper extremity to the right trunk during childhood. He had an exophytic red tumor on the nevus in the right upper extremity that grew slowly for 4 years and rapidly recently. Histological and immunohistochemical studies revealed both epithelial and mesenchymal malignancy in the same tumor. The epithelial component was composed of basaloid cells forming multiple nests with peripheral palisading, positive for keratins and BerEP4, implying basal cell carcinoma. The mesenchymal component was composed of spindle-shaped cells negative for keratins and positive for vimentin, suggesting sarcoma. This is, to our knowledge, the first report of sarcomatoid carcinoma arising in the primary pigmented nevus that had been treated by the carbon dioxide snow freezing method., (© 2015 Japanese Dermatological Association.)

Objective: The objective of our study was to characterize infarct-associated bone sarcoma and its imaging features., Materials and Methods: Our databases were searched for instances of sarcoma arising in association with osteonecrosis. Demographic and imaging data were recorded. The imaging studies of 258 patients with sarcomas were reviewed to determine whether underlying osteonecrosis was present. Radiographic and MRI studies of patients with bone infarction were reviewed to categorize the various appearances of infarction and to determine if sarcomas tended to arise in a particular pattern. A literature review was performed., Results: Nine infarct-associated bone sarcomas were found in eight patients: seven malignant fibrous histiocytomas (MFHs) and two osteosarcomas. All occurred in the femur or tibia; multifocal infarction was documented in all patients except one. Sarcomas were commonly associated with a so-called "mature"-type pattern of osteonecrosis-that is, with well-defined calcified margins. Osteolysis of infarct-associated MFHs was often overlooked at initial presentation and was often detected only after pathologic fracture. CT and MRI revealed cortical penetration in all cases; infarct margin disruption was evident, but preservation of fat within the infarct was typical. Increased radiotracer activity with relative central photopenia was characteristic of large infarct-associated bone sarcomas on scintigraphy. All lesions, including those treated at our institution and those found in the literature, were metaphyseal or diaphyseal, and although epiphyseal extension of sarcoma from a metadiaphyseal infarct was common, no purely epiphyseal lesions were encountered., Conclusion: Radiologists must remain vigilant for this rare occurrence, especially in patients with new pain in an area of known bone infarction.

Purpose: To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single-dose or clinically relevant, fractioned-dose γ-ray radiation., Methods and Materials: C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gy or fractionated doses totaling 40 to 80 Gy delivered at 2-Gy/d fractions, 5 d/wk, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days after irradiation, and all tumors were characterized histologically., Results: A total of 210 tumors were induced within the radiation field in 788 mice. An overall decrease in tumor incidence was observed after fractionated irradiation (16.4%) in comparison with single-dose irradiation (36.1%). Sarcomas were the predominant postirradiation tumor observed (n=201), with carcinomas occurring less frequently (n=9). The proportion of mice developing tumors increased significantly with total dose for both single-dose and fractionated schedules, and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice after single-dose irradiation; however, significant differences in tumor susceptibilities after fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common after fractionated irradiation, whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common after single-dose irradiation., Conclusions: This study investigated the tumorigenic effect of acute large doses in comparison with fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiation therapy. Differences in tumor histotype after single-dose or fractionated radiation exposures provide novel in vivo evidence for differences in tumor susceptibility among stromal cell populations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Overview: In cats, the most serious of adverse effects following vaccination is the occurrence of invasive sarcomas (mostly fibrosarcomas): so-called 'feline injection-site sarcomas' (FISSs). These develop at sites of previous vaccination or injection. They have characteristics that are distinct from those of fibrosarcomas in other areas and behave more aggressively. The rate of metastasis ranges from 10-28%., Pathogenesis: The pathogenesis of these sarcomas is not yet definitively explained. However, chronic inflammatory reactions are considered the trigger for subsequent malignant transformation. Injections of long-acting drugs (such as glucocorticoids, and others) have been associated with sarcoma formation. Adjuvanted vaccines induce intense local inflammation and seem therefore to be particularly linked to the development of FISS. The risk is lower for modified-live and recombinant vaccines, but no vaccine is risk-free., Treatment and Prevention: Aggressive, radical excision is required to avoid tumour recurrence. The prognosis improves if additional radiotherapy and/or immunotherapy (such as recombinant feline IL-2) are used. For prevention, administration of any irritating substance should be avoided. Vaccination should be performed as often as necessary, but as infrequently as possible. Non-adjuvanted, modified-live or recombinant vaccines should be selected in preference to adjuvanted vaccines. Injections should be given at sites at which surgery would likely lead to a complete cure; the interscapular region should generally be avoided. Post-vaccination monitoring should be performed., (© Published by SAGE on behalf of ISFM and AAFP 2015.)

Paget's sarcoma is a rare complication of Paget's disease and isolated Paget's disease of the patella is extremely rare. We describe a unique case of Paget's sarcoma of the patella in a 69-year-old male farmer who had a remote history of a fracture in the same patella 40 years previously. In this case, imaging and pathogenesis of Paget's disease of bone is described and factors implicated in the development of Paget's disease in this patient are evaluated.

Reactive oxygen species (ROS) produced by the inducible NADPH oxidase type 2 (NOX2) complex are essential for clearing certain infectious organisms but may also have a role in regulating inflammation and immune response. For example, ROS is involved in myeloid derived suppressor cell (MDSC)- and regulatory T cell (T(reg)) mediated T- and NK-cell suppression. However, abundant ROS produced within the tumor microenvironment, or by the tumor itself may also yield oxidative stress, which can blunt anti-tumor immune responses as well as eventually leading to tumor toxicity. In this study we aimed to decipher the role of NOX2-derived ROS in a chemically (by methylcholanthrene (MCA)) induced sarcoma model. Superoxide production by NOX2 requires the p47(phox) (NCF1) subunit to organize the formation of the NOX2 complex on the cell membrane. Homozygous mutant mice (NCF1*/*) have a functional loss of their super oxide burst while heterozygous mice (NCF1*/+) retain this key function. Mice harboring either a homo- or a heterozygous mutation were injected intramuscularly with MCA to induce sarcoma formation. We found that NOX2 functionality does not determine tumor incidence in the tested MCA model. Comprehensive immune monitoring in tumor bearing mice showed that infiltrating immune cells experienced an increase in their oxidative state regardless of the NOX2 functionality. While MCA-induced sarcomas where characterized by a T(reg) and MDSC accumulation, no significant differences could be found between NCF1*/* and NCF1*/+ mice. Furthermore, infiltrating T cells showed an increase in effector-memory cell phenotype markers in both NCF1*/* and NCF1*/+ mice. Tumors established from both NCF1*/* and NCF1*/+ mice were tested for their in vitro proliferative capacity as well as their resistance to cisplatin and radiation therapy, with no differences being recorded. Overall our findings indicate that NOX2 activity does not play a key role in tumor development or immune cell infiltration in the chemically induced MCA sarcoma model.

Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson's tumor, is a rare nonneoplastic vascular lesion caused by the abnormal proliferation of endothelial cells. Clinically and radiologically, IPEH presents as a soft tissue mass that may simulate and be mistaken for a sarcomatous tumor. There have been reports of this entity involving the skin or subcutaneous tissues in normal blood vessels and vascular malformations. Herein, we present the first reported case of Masson's tumor arising from an arteriovenous hemodialysis fistula. We emphasize the imaging features of this lesion and briefly discuss its pathophysiology.

Sarcomas are a rare group of mesenchymal tumors affecting a younger population. The etiology remains unknown in most cases. Environmental factors that increase sarcoma risk include radiation exposure and chemical carcinogens. Several familial cancer syndromes confer sarcoma predisposition, such as the Li-Fraumeni Syndrome (LFS). In this increasingly genomic focussed era of medicine, it will be clinically important to understand the genetic basis of sarcoma risk., (© 2014 Wiley Periodicals, Inc.)

One of the important questions in understanding the mechanisms of carcinogenesis induced with foreign body (or plastic carcinogenesis), is a question about normal progenitor cells in sarcomas (FB sarcomas) appearing in close proximity to the plastic plate implanted under the skin of an experimental animal. There is an assumption in literature that progenitor cells in FB sarcomas originate from vascular endothelium cells feeding a connective tissue capsule that forms around foreign body. In our research, we studied mRNA expression of one of the endothelial cell markers--receptor VEGFR2/FIk1--and growth factor VEGF-A, which interacts with it, in precancerous cells of FB sarcomas in mice. In examined cells, mRNA expression of VEGF-A was found while mRNA expression of VEGFR2/FIk1 was absent. In light of this and formerly established properties of progenitor cells in FB sarcomas, possibilities of the origin of these sarcomas from endothelial cells, pericytes, and pluripotent mesenchymal stem cells are being discussed.

Feline injection site sarcomas (FISS) are malignant neoplasms of mesenchymal origin which arise in sites of injections in cats. The prevalence is estimated between 1 in 1000 and 1 in 10 000 vaccinations in the United Kingdom. The aim of this study was to estimate the incidence of FISS in Poland and to analyse clinical aspects and histological and cytological features of injection site sarcomas. In our study the prevalence of FISS was 0.16% (16 FISS on 10.000 of cats) in feline patients in one of a veterinary surgery which conducts the general practice and 85 on 10.000 cats in a practice focused on veterinary oncology. The most typical microscopic features of FISS found in the present analysis were: the presence of perilesional scarring and inflammation, aggregates of lymphocytes at the tumour periphery, moderate but usually marked cellular pleomorphism and intralesional necrosis. The most typical cytologic features of FISS found in present study were: the presence of neutrophils, marked cellular pleomorphism, the presence of lymphocytes and macrophages, the presence of extremely large nuclei in the neoplastic cells, and high sample cellularity.

Purpose: To compare mean heart and left anterior descending coronary artery (LAD) doses (NTDmean) and positional reproducibility in larger-breasted women receiving left breast radiotherapy using supine voluntary deep-inspiratory breath-hold (VBH) and free-breathing prone techniques., Materials and Methods: Following surgery for early breast cancer, patients with estimated breast volumes >750 cm(3) underwent planning-CT scans in supine VBH and free-breathing prone positions. Radiotherapy treatment plans were prepared, and mean heart and LAD doses were calculated. Patients were randomised to receive one technique for fractions 1-7, before switching techniques for fractions 8-15 (40 Gy/15 fractions total). Daily electronic portal imaging and alternate-day cone-beam CT (CBCT) imaging were performed. The primary endpoint was the difference in mean LAD NTDmean between techniques. Population systematic (Σ) and random errors (σ) were estimated. Within-patient comparisons between techniques used Wilcoxon signed-rank tests., Results: 34 patients were recruited, with complete dosimetric data available for 28. Mean heart and LAD NTDmean doses for VBH and prone treatments respectively were 0.4 and 0.7 (p<0.001) and 2.9 and 7.8 (p<0.001). Clip-based CBCT errors for VBH and prone respectively were ⩽3.0 mm and ⩽6.5 mm (Σ) and ⩽3.5 mm and ⩽5.4 mm (σ)., Conclusions: In larger-breasted women, supine VBH provided superior cardiac sparing and reproducibility than a free-breathing prone position., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The aim of the present study was to investigate the possible association between occurrence of soft tissue sarcomas (STS) and residence in an Italian area affected by illegal practices of dumping and setting fire to both hazardous and solid urban wastes. Standardized incidence ratios (SIRs) were computed separately for STS and some specific STS subtypes. The analysis was performed for the total population and for specific age groups, namely, children, adolescents, and adults. In adults, no significant increase in STS was found other than for gastrointestinal stromal tumors in males. A nonsignificant increase in incidence of STS was observed for male children and female adolescents. The results of the present study do not allow conclusions for a causal association. In the absence of previous epidemiological studies on this issue, further investigations are needed.

Sarcomas are a heterogeneous group of rare malignancies arising from mesenchymal tissue. Although several occupational exposures have been evaluated in association with sarcoma, little is known about the role of socioeconomic indicators such as education. Socioeconomic status has been found to be associated with risk of development of several types of cancers, primarily lung, gastric, and cervical cancers. We conducted a hospital-based case-control study to evaluate the association of socioeconomic level with the risk for sarcoma. A total of 371 incident cases of sarcoma were matched in terms of age, sex, and year of enrollment in the study with 742 cancer-free controls. Education and income levels were evaluated as the indicators of socioeconomic status. Higher education (college level) was associated with a significantly lower risk for sarcoma [odds ratio (OR)=0.48, 95% confidence interval (CI)=0.29-0.80], even after adjusting for important confounders. After stratifying by sex, significantly lower risk for sarcoma was observed among men who had college level education compared with men with a level of education of eighth grade or lower (OR=0.38, 95% CI=0.19-0.74). A significant association between education and the risk for sarcoma remained after stratifying by income (OR=0.49, 95% CI=0.28-0.86, among the low income group). When analyzed as a composite exposure, individuals with high education and high income status had significantly lower risk for sarcoma compared with those with low income and low education status (OR=0.41, 95% CI=0.23-0.71). Thus, socioeconomic factors may play a significant role in determining the risk for sarcoma and should be explored further to elucidate the underlying factors that may explain these sociodemographic inequalities related to sarcoma.

This review focuses on epidemiology, aetiology, clinical presentation, diagnosis, management, prognosis and follow-up of soft tissue sarcomas (STS) involving limbs and trunk. Any patient with a suspected STS should be referred to a specialized sarcoma centre and managed by a multidisciplinary group. The standard treatment is surgical excision followed by adjuvant radiotherapy (RT). Radiotherapy is recommended in patients with intermediate-or high-grade tumors, >5 cm of diameter or <5 cm. RT may be indicated in low grade, deep and large-size STS and/or in absence of adequate margins, after discussion within a multidisciplinary group. Neoadjuvant radiotherapy and chemotherapy should be taken into consideration for patients with borderline resectable tumors. In selected cases, amputation may be the only curative option. Isolated limb perfusion is a pre-operative treatment that may allow for amputation to be avoided. Adjuvant chemotherapy should be considered only in selected cases. Regular follow-up with clinical examination, ultrasound (US) or magnetic resonance imaging (MRI) to exclude local recurrences and chest-X-ray or chest computed tomography (CT) to exclude metastatic disease is recommended. For metastatic disease, doxorubicin is the first-line standard therapy. Second-line agents include trabectedin, ifosfamide, dacarbazine and the combination of gemcitabine-plus-docetaxel. Surgical resection of local recurrences or lung metastases should be evaluated in selected cases., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Opinion Statement: Sarcomas are rare malignant tumors that develop from mesenchymal tissue. Most sarcomas are idiopathic, however, a significant minority develops as a consequence of prior radiation exposure. Although the absolute risk of developing a radiation-associated sarcoma is small, these tumors represent significant clinical challenges. For recurrent, unresectable or metastatic disease, the standard treatment is systemic chemotherapy. Radiation-associated sarcomas tend to be undifferentiated sarcomas, angiosarcomas, or leiomyosarcomas, which are variably sensitive to chemotherapy. The best general approach is to treat each radiation-associated sarcoma as one would its sporadic histologic counterpart. There are limited data to guide the best treatment for radiation-associated sarcoma, therefore, the standard chemotherapy options are reasonable choices. These include doxorubicin, ifosfamide, gemcitabine, docetaxel, and pazopanib. Patients with radiation-associated sarcomas may have received prior anthracyclines to treat antecedent malignancies such as breast cancer or lymphoma. Thus, if additional doxorubicin cannot be used, liposomal doxorubicin is a reasonable substitute. More prospective research is needed on how radiation-associated sarcomas respond to systemic therapy. Future clinical trials of new agents in sarcoma should identify and include patients with radiation-associated sarcoma.

Opinion Statement: Primary sarcomas of the spine are rare diseases and include osteosarcoma, chondrosarcoma, chordoma, and Ewing's sarcoma. Surgery for these lesions remains an important part of their treatment. Strong evidence exists for the en bloc resection of chondrosarcoma and chordoma since these lesions respond poorly to both chemotherapy and radiation. Weaker but important evidence suggests that osteosarcoma and Ewing's sarcoma may also benefit from wide excisions, but after the application of neoadjuvant therapy, which may significantly aid the surgical process as well as independently prolong the survival. The unacceptable morbidity associated with damage to the neural elements makes resection with wide margins difficult in the spine. Nevertheless, this can be achieved in many circumstances and can, on occasion, lead to long term disease-free survival and even cure. There are numerous techniques described for en bloc resections in the mobile spine and pelvis and these vary widely for the region of the spine involved and the preferences of the surgeon. There are constant principles that do apply to all cases. We think of these surgeries as consisting of 2 stages which can be done in 1 or multiple operations. In the first phase, a corridor free of tumor is removed from the bone and the neural elements to be protected are dissected free from surrounding tissues. In the second phase, the tumor and a margin of normal tissue is circumferentially dissected and delivered while sparing the neural structures. Patient selection, in terms of age, overall disease burden, personal preferences, and comorbidities need to be carefully taken into account to optimize the risk benefit ratio. Sarcomas of the spine are a challenging group of lesions to treat but they can also be the most rewarding. Our newly acquired insight into the pathogenesis of these lesions, as well as improved surgical techniques combined with better neoadjuvant and adjuvant therapies are leading to longer survival times as well as long term disease free survivors.

Purpose: The study was designed to investigate the influence of surrogate factors associated with sex (SH) and growth hormones (GH) on the risk of developing soft tissue sarcomas (STS)., Background and Methods: The etiology of soft tissue sarcoma is largely unknown. We have studied the effect of hormone related factors on STS in the Swedish population between 1988 and 2009 using a population-based matched case-control design., Results: Our study is the largest on this topic to date, including 634 cases in a primary matched analysis and 855 cases in an unmatched sensitivity analysis. We identified protective effects connected to constitutional characteristics, hormonal and reproductive factors. Being shorter than your peers at age 11 was associated with an odds ratio (OR) of 0.51 (0.36-0.74). Having used oral contraceptives (OC), OR 0.75 (0.49-1.15), and high parity, OR 0.16 (0.04-0.63), comparing three or more children to two or less, also appeared to reduce the risk of STS. The risk was further reduced with the duration of OC use (p = 0.01), comparing use for 11 years or more to use for 3 years or less yielded an OR of 0.10 (0.02-0.41). No effect was observed for ever having had perimenopausal hormone therapy OR 1.02 (0.70-1.47). The effect of BMI varied significantly with subtype (p = 0.03) and tumor location (p < 0.001)., Conclusions: We observed surrogates of SH, GH, and insulin-like growth factor 1 to be associated with STS development. These findings are important as they may connect STSs to the group of hormone-dependent tumors, potentially revealing common treatment and prevention targets.