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Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumor of intermediate biologic potential and uncertain differentiation that most frequently occurs in the superficial extremities of children and young adults. It is histologically typified by nodules of ovoid to spindle cells with pseudoangiomatoid spaces and a surrounding dense lymphoplasmacytic infiltrate, desmin expression in about 50%, and association with EWSR1-CREB1, EWSR1-ATF1 or FUS-ATF1 gene fusions. The diagnosis still poses a challenge because AFH may not display all classic features, can show a variety of unusual histologic findings and lacks a specific immunoprofile. We describe a case of 'pure' spindle cell AFH arising in the forearm musculature of a 19 year-old female, which harbored EWSR1-CREB1 fusion transcripts by reverse transcription-polymerase chain reaction. The neoplasm was composed entirely of highly cellular fascicles of spindled cells architecturally resembling spindle cell sarcoma, and lacked obvious pseudoangiomatoid spaces or a lymphoid cuff. This purely spindle cell variant adds to the significant morphologic spectrum of AFH, and emphasizes that even when occuring at a typical site, AFH may be difficult to recognize when showing non-classical morphology. This is of clinical relevance, as AFH with this morphology could be potentially misdiagnosed as a high-grade sarcoma, with the patient subject to more radical therapeutic approaches., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Well-differentiated liposarcoma (WDL) can show a morphologic spectrum, including lipoma-like, sclerosing and inflammatory subtypes. It does not metastasize but can dedifferentiate, acquiring metastatic potential. Hibernomas are benign neoplasms that show variable differentiation toward brown fat, and can sometimes occur in the abdomen or retroperitoneum. We illustrate a case of retroperitoneal WDL that showed extensive hibernoma-like morphology, with sheets of multivacuolated adipocytes of varying sizes, with abundant cytoplasm and numerous lipid vacuoles or granular eosinophilic cytoplasm. However, very focally there were fibrous septa containing spindle cells with enlarged, hyperchromatic, mildly pleomorphic nuclei. Further sampling showed areas of typical WDL, with lobules of mature fat intersected by fibrous septa containing atypical, enlarged spindle cells, as well as small foci of dedifferentiation. Immunohistochemistry for CDK4 and p16 showed strong and diffuse nuclear expression in the hibernoma-like areas, and fluorescence in situ hybridization showed MDM2 gene amplification, all in keeping with WDL. We highlight hibernoma-like morphology as part of the histologic spectrum of WDL, and recognition of this variant is important for correct treatment and prognostication., (© The Author(s) 2016.)

Aims: Soft tissue tumours are a heterogeneous group of neoplasms that can arise at almost every anatomical site. As they often show similar clinical and radiological findings, histology is the definitive diagnostic method and it is crucial that the surgical pathology report contains accurate, useful information for management and prognostication. The soft tissue sarcoma minimum dataset produced by the Royal College of Pathologists in the UK outlines a structure for handling and reporting soft tissue tumours, including the core data required, and aiding pathologists in forming a consistent reporting approach., Methods: We assessed the information in surgical pathology reports for soft tissue lesions at a tertiary soft tissue centre, in 1 year prior to the development of this dataset, and 1 year after its release, to audit the comparative adequacy of macroscopic and microscopic information provided, and to assess for differences in reporting since the advent of routine ancillary molecular diagnostic testing., Results and Conclusions: We found that while essential information was always included in reports, more specific details contributing to better quality reports such as more detailed macroscopic descriptions and a higher proportion of clinical summaries with radiological correlation were included in 2011 than 2006, despite increasing workload. Specimen handling, particularly of core biopsies, was also improved, reflecting the increasing need to conserve the maximum amount of patient material for molecular investigations., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Synovial sarcoma is a malignant mesenchymal tumor with variable epithelial differentiation, which is defined by the presence of a specific t(X;18)(p11.2;q11.2) chromosomal translocation that generates SS18-SSX fusion oncogenes. Synovial sarcoma typically arises within extremity deep soft tissue (particularly around large joints) of young adults, but has been shown to occur at almost any location. When it arises in more unusual sites, such as the abdomen, it can present a significant diagnostic challenge. We describe a case of intraabdominal monophasic synovial sarcoma that immunohistochemically showed strong expression of smooth muscle actin and calponin but only very scanty cytokeratin, and which showed morphologic and immunohistochemical overlap with other spindle cell neoplasms that can arise at this site, such as gastrointestinal stromal tumor and myofibrosarcoma. As correct diagnosis is of clinical and prognostic importance, surgical pathologists should be aware of the potential for synovial sarcoma to occur at a variety of anatomic sites and of its spectrum of immunoreactivity. Synovial sarcoma should be in the differential diagnosis of spindle cell neoplasms with myoid differentiation that do not fall into any definite tumor category, for which there should be a relatively low threshold for performing fluorescence in situ hybridization or reverse transcription-polymerase chain reaction to assess for the specific SS18 gene rearrangement or SS18-SSX fusion transcripts, which remain the diagnostic gold standard., (© The Author(s) 2016.)

While endometriosis, defined as the presence of endometrial tissue in extrauterine sites, is most frequently encountered within the peritoneal cavity, a small but significant proportion of cases occur at extra-abdominal soft tissue sites, particularly in relation to previous abdominal surgery. We reviewed the cases of endometriosis of soft tissue sites seen at a tertiary soft tissue center. All cases of extra-abdominal soft tissue endometriosis diagnosed at this institution over a 13-year period were reviewed, and clinical and pathologic findings were recorded. Forty-five patients had diagnoses of soft tissue endometriosis and there were 34 diagnostic biopsies and 26 surgical excision specimens. All but 1 case were abdominal wall lesions, with 1 located in the upper arm. A total of 33 patients presented with lesions in scars of previous operations (31 in Pfannenstiel incisions for Caesarean sections, presenting with a median interval of 6 years (range 1-16 years) following surgery). The lesions ranged in size from 1 to 8 cm (median 3.5 cm). One case showed decidualized stroma with trophoblast cells, while 2 had secondary adenocarcinoma arising from endometriosis. Eighteen cases were tested for β-catenin expression immunohistochemically, of which 5 showed at least focal nuclear positivity in the surrounding fibrous tissue (although not within glands or stroma). Soft tissue endometriosis is seen most commonly in surgical scars, particularly following Caesarean sections. Spontaneous endometriosis also most commonly occurs in the abdominal wall, although can occur exceptionally at unusual sites, such as extremities. Secondary changes, including carcinomas, can arise from endometriosis. The differential diagnosis of these lesions includes fibromatosis, which may be erroneously diagnosed on small, nonrepresentative core biopsy specimens., (© The Author(s) 2016.)

Background: Soft tissue sarcomas are a group of neoplasms with differentiation towards mesenchymal tissue, many of which are aggressive and chemotherapy resistant. Histology and immunoprofiles often overlap with neoplasms of other lineages, and establishing an accurate histopathological diagnosis is crucial for correct management, and therapeutic stratification. The endosialin cell surface glycoprotein is predominantly expressed by stromal fibroblasts and pericytes in epithelial neoplasms; however, tumour cell expression has been reported in small series of sarcomas., Methods: We assessed endosialin expression by immunohistochemistry in a large set of 514 human soft tissue sarcomas., Results: Tumour cell endosialin expression was seen in 89% of undifferentiated pleomorphic sarcomas (104/117), 77% adult fibrosarcomas/spindle cell sarcomas (20/26), 62% synovial sarcomas (37/60), 51% leiomyosarcomas (94/185) and 31% rhabdomyosarcomas (39/126)., Conclusions: Endosialin immunohistochemistry has potential to distinguish undifferentiated and poorly differentiated sarcomas from other poorly differentiated, non-mesenchymal neoplasms. A Phase II trial randomising patients with advanced sarcomas to receive chemotherapy with/without an endosialin therapeutic antibody has recently completed enrolment. Endosialin expression could be used to select patients for such clinical trials. Based on our results, patients with undifferentiated pleomorphic sarcoma may be particularly suitable for such a therapeutic approach.

Adenoid cystic carcinoma (ACC) is a malignant neoplasm that mainly affects the salivary glands but has been described in many other anatomical sites. It is composed of basaloid cells with myoepithelial/basal cell differentiation and ductal epithelial cells that proliferate in a fibrous stroma, with variable amounts of myxohyaline material. Three patterns (cribriform, tubular, and solid) occur, and the solid variant is characterized by a predominant compact sheet-like and nested pattern of rounded basaloid cells lacking obvious cribriform or tubular architecture. The solid variant has significant morphological and immunohistochemical overlap with a large range of neoplasms of different lineages, including other carcinomas and sarcomas. We describe a case of solid variant ACC of the paranasal sinuses, which showed an almost entirely solid pattern of growth (in >95% of cells) and which on initial biopsy showed no features of classical ACC. This highlights the potential for diagnostic misinterpretation with a variety of other neoplasms, which is particularly important because of the significant difference in treatment for ACC and tumors in its differential diagnosis., (© The Author(s) 2016.)

We describe a case of a giant intra-abdominal mature cystic teratoma in a 36-year-old man, which comprised typical features of differentiated teratoma/dermoid cyst but which contained a macroscopic rudimentary penis, with vasoformative erectile tissue-like structures consistent with corpora cavernosa, as well as scrotal-type skin and prostatic tissue. The genitourinary structures were well formed both grossly and microscopically and sharply demarcated from the rest of the neoplasm, which comprised typical differentiated teratoma, without any other macroscopic foci of organoid differentiation or of other histologic differentiation. The plasticity of the cells of differentiated teratoma, which enables it to undergo multidirectional differentiation, is well recognized, but the factors determining this distinct path of differentiation remain to be established., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Inflammatory myofibroblastic tumor arose as a defined neoplasm from the disparate group of tumors (both neoplastic and inflammatory) originally described as inflammatory pseudotumors. The morphologic features are well described, and 50-60% of cases are associated with fusions of the anaplastic lymphoma kinase (ALK) gene. We describe an inflammatory myofibroblastic tumor in the lower abdominal wall of an adult male, which occurred 88days after he received an allogeneic stem cell transplant for T-lymphoblastic lymphoma, and which was positive for ALK immunohistochemistry and showed ALK gene rearrangement by fluorescence in situ hybridization. Two other cases are reported in the post-stem cell transplant setting, but both occurred in children and did not have molecular analysis performed. The etiology remains unclear, but may be due to immune dysregulation caused by any combination of prior chemotherapy, radiotherapy and immune suppression. These neoplasms should be considered as a rare consequence of allogeneic stem cell transplantation and referral to a specialist sarcoma center for further management may be required., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Despite recent advances in the field, treatment options for metastatic soft tissue sarcoma patients are limited. Eribulin, an antimitotic derived from the natural marine sponge product halichondrin B, is currently approved for the treatment of metastatic breast cancer. Following the promising activity of eribulin in sarcoma in a Phase II trial, the drug was recently compared to dacarbazine in pretreated advanced leiomyosarcoma (LMS) and liposarcoma (LPS) patients in a Phase III trial. Eribulin was associated with a significant 2-month improvement in median overall survival compared to dacarbazine (13.5 vs. 11.5 months, heart rate: 0.768) despite no documented significant difference in progression-free survival. In a subgroup analysis, the survival advantage associated with eribulin was evident in the LPS subgroup but not in the LMS subgroup. Following these encouraging results, the Food and Drug Administration has approved eribulin for the treatment of advanced LPS for patients who received prior anthracycline chemotherapy. In this short review, we will evaluate the evidence for eribulin in soft tissue sarcoma, highlight its mechanisms of action, and summarize the results of the major preclinical and clinical studies with a particular focus on the results of the Phase III trial.

Aims: The histological diagnosis of soft tissue tumours (STTs) can be difficult, sometimes requiring a combination of morphology, immunophenotype and ancillary molecular tests. Many STTs are associated with characteristic genetic aberrations that can be assessed using fluorescence in situ hybridisation (FISH), reverse transcription-PCR (RT-PCR) or mutational analysis. We have previously assessed the practicality and sensitivity of using these modalities as part of the routine diagnosis of STT in paraffin-embedded material and now revisit the subject in light of further experience in this field., Methods: 200 consecutive cases from 2013 that had undergone FISH, RT-PCR or mutational analysis were assessed to evaluate their diagnostic utility compared with preliminary histological assessment., Results: 218 FISH, 91 RT-PCR and 43 mutational analysis tests were performed. Compared with the previous study, FISH for MDM2 amplification in possible well-differentiated/dedifferentiated liposarcomas, and mutational analysis for assessing KIT, PDGFR and BRAF mutations made up a large proportion of the workload (107 and 43 tests, respectively). As in the previous study, alveolar rhabdomyosarcoma showed the best FISH:RT-PCR concordance. Unlike previously, RT-PCR showed marginally higher sensitivity than FISH (78.9% and 76.9%), while continuing to demonstrate higher specificity (90.9% and 84.3%). RT-PCR again showed an increased failure rate (5.5%; 1% for FISH)., Conclusions: We demonstrate the continuing utility of RT-PCR and FISH for STT diagnosis, and that each has advantages in specific contexts. These ancillary molecular tests are important tools in both defining and excluding diagnoses of STT, which is crucial in determining prognosis and guiding appropriate management., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Solitary fibrous tumor (SFT) is a fibroblastic mesenchymal tumor originally described in the pleura but now shown at almost every anatomic site. Histopathologically, SFT is characteristically a circumscribed neoplasm composed of variably cellular and patternless distributions of bland spindle and ovoid cells within prominent collagenous stroma and shows diffuse expression of CD34, but it has a broad spectrum of both morphology and of biologic behavior. Many different names (particularly hemangiopericytoma) were previously used in the course of our understanding of this neoplasm but are now subsumed under the term "SFT," and the putative cell of origin was debated. However, it is now recognized that SFT is a translocation-associated neoplasm, consistently associated with NAB2-STAT6 gene fusions arising from recurrent intrachromosomal rearrangements on chromosome 12q, and this translocation is a likely major contributor to its pathogenesis. While most SFT with classical morphologic features behave in an indolent manner and those with overtly malignant histologic features tend to be aggressive neoplasms that behave as high-grade sarcomas, the behavior of SFT is unpredictable, and it is important to be aware of the propensity for aggressive behavior in a minority of histologically classical SFT and to ensure adequate clinical follow-up. Surgical excision remains the treatment gold standard; while radiotherapy and conventional chemotherapeutic agents have only shown limited efficacy, further understanding of the molecular events underlying tumorigenesis may allow the development of novel targeted treatments. We review SFT, discussing the morphologic spectrum and variants, including malignant and dedifferentiated subtypes, clinicopathological aspects, recent molecular genetic findings, and the differential diagnosis., (© The Author(s) 2016.)

Exon 11 KIT mutations are found in a majority of gastrointestinal stromal tumors (GIST) and are usually predictive of response to imatinib, a KIT, PDGFRA and ABL inhibitor. Exon 11 mutations with poor sensitivity to imatinib and poor outcome can be observed on rare occasions, including p.(L576P). In silico and in vitro studies suggested a decreased binding affinity for imatinib in p.(L576P) KIT mutations, thereby offering an explanation for their poor outcome and poor response to standard therapy. These observations were further corroborated with anecdotal case reports of refractoriness or non-durable response to imatinib therapy. However, we describe the favorable response to imatinib and outcome in 5 p.(L576P)-KIT mutant GIST patients treated at a tertiary sarcoma referral center. The sensitivity of p.(L576P)-KIT mutations to imatinib, and the prognostic impact of this mutation need to be further evaluated in a larger cohort. Based on our observations, p.(L576P) mutated GISTs should be treated with standard first line imatinib therapy.

We describe a case of intra-abdominal fibromatosis, which occurred in a 44-year-old woman who had a previous history of gastrointestinal stromal tumor (GIST) of the sigmoid mesocolon, which was treated with imatinib and resection. A mass was detected at the site of ileocolic anastomosis of the previous small bowel resection and sigmoid colectomy, nearly 3 years later. Clinically, this was suspected to represent recurrent GIST and was excised, but histology and mutational analysis showed desmoid-type fibromatosis with a mutation in codon 41 of exon 3 of the CTNNB1 (β-catenin) gene. The occurrence of fibromatosis at the site of excision of GIST is very rare, but its recognition is important as the treatment of the two neoplasms differs significantly. As imaging cannot reliably distinguish between these 2 entities, histological diagnosis is crucial for correct clinical management., (© The Author(s) 2015.)

A fit and active amateur cyclist was referred by his general practitioner to a surgical oncology outpatient clinic with a slowly-growing perineal mass. Following clinical examination, the patient underwent imaging and biopsy at a tertiary soft tissue tumour centre, which diagnosed perineal nodular induration: a rare, benign tumour caused by repetitive trauma associated with 'saddle sports' such as cycling or horse riding. It is important to consider soft tissue tumours in patients who present with 'lumps and bumps'; they can occur anywhere in the body including the groin or perineum, where it is sometimes referred to as a 'third' or 'accessory' testicle in men. Although unusual, the case emphasises the importance of rapid specialist referral from primary care, and consideration of a patient's occupation and hobbies when formulating diagnoses., (2016 BMJ Publishing Group Ltd.)

Purpose: Up to 50% of patients diagnosed with stage I nonseminomatous germ cell tumors (NSGCTs) harbor occult metastases. Patients are managed by surveillance with chemotherapy at relapse or adjuvant treatment up front. Late toxicities from chemotherapy are increasingly recognized. Based on a potential biologic role in germ cells/tumors and pilot data, our aim was to evaluate tumor expression of the chemokine CXCL12 alongside previously proposed markers as clinically useful biomarkers of relapse., Experimental Design: Immunohistochemistry for tumor expression of CXCL12 was assessed as a biomarker of relapse alongside vascular invasion, histology (percentage embryonal carcinoma), and MIB1 staining for proliferation in formalin-fixed paraffin-embedded orchidectomy samples from patients enrolled in the Medical Research Council's TE08/22 prospective trials of surveillance in stage I NSGCTs., Results: TE08/TE22 trial patients had a 76.4% 2-year relapse-free rate, and both CXCL12 expression and percentage embryonal carcinoma provided prognostic value independently of vascular invasion (stratified log rank test P = 0.006 for both). There was no additional prognostic value for MIB1 staining. A model using CXCL12, percentage embryonal carcinoma, and VI defines three prognostic groups that were independently validated., Conclusions: CXCL12 and percentage embryonal carcinoma both stratify patients' relapse risk over and above vascular invasion alone. This is anticipated to improve the stratification of patients and identify high-risk cases to be considered for adjuvant therapy., (©2015 American Association for Cancer Research.)

Ossifying fibromyxoid tumor (OFMT) is a soft tissue neoplasm of uncertain differentiation and intermediate (rarely metastasizing) biologic potential, with typical morphologic features, of an encapsulated, lobulated tumor comprising uniform polygonal cells within fibromyxoid stroma, which is surrounded by or contains metaplastic bone, classically as a peripheral rim of lamellar bone. Ossifying fibromyxoid tumor can arise at almost any site, although most frequently occurs within the extremities and trunk. Although most behave in a benign fashion, tumors can rarely show atypical or malignant features. It is now established that OFMTs represent translocation-associated tumors, with up to 85% associated with recurrent gene rearrangements, mostly involving the PHF1 gene (including in typical, atypical, and malignant neoplasms), with EP400-PHF1 in approximately 40% of tumors, and ZC3H7B-BCOR, MEAF6-PHF1, and EPC1-PHF1 fusions also described. Correct diagnosis is clinically important to ensure correct treatment and prognostication, both to avoid overdiagnosing OFMT as a malignant neoplasm such as osteosarcoma and also because of the propensity for aggressive behavior in a small number of OFMT. We review OFMT, with emphasis on the morphologic spectrum, recent molecular genetic findings, and the differential diagnosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Soft tissue tumors (STTs) are rare mesenchymal neoplasms accounting for less than 1% of adult cancers. More than 50 different subtypes of STTs have been identified, with this number expected to grow as our understanding of the complex genetic landscape of these diseases improves. As the classification of soft tissue neoplasms continues to diversify, so does the approach to therapy. Accurate histopathologic diagnosis, utilizing the appropriate ancillary immunohistochemical and molecular diagnostic platforms, underpins the oncologic management of soft tissue sarcomas. As increasing numbers of reproducible genetic abnormalities in soft tissue neoplasms are defined, molecular genetic and molecular cytogenetic investigations have become a standard part of the ancillary diagnostic repertoire. However, other soft tissue neoplasms lack reproducible genetic abnormalities, and for these, traditional histology and immunohistochemistry remain the cornerstones for diagnosis. Here, we give an overview of histology-driven therapy in STTs, highlighting the critical role of accurate surgical pathology in guiding the systemic treatment of patients with these neoplasms, and the importance of close collaboration between the surgical pathologist and the oncologist. We also summarize what is considered standard practice in nonhistology- and histology-driven therapy., (© The Author(s) 2015.)

Well-differentiated liposarcoma (WDL) and dedifferentiated liposarcoma (DDL) form the largest subgroup of liposarcomas, and represent a morphologic and behavioral spectrum of 1 disease entity, which arises typically in middle to late adult life, most frequently within the retroperitoneum or extremities. DDL is defined as nonlipogenic sarcoma that is juxtaposed to WDL, occurs as a recurrence of WDL or which can arise de novo, and typically has the appearance of undifferentiated pleomorphic or spindle cell sarcoma. DDL have a propensity for local recurrence, whereas distant metastasis is rarer, and behavior is related to anatomic site, with retroperitoneal neoplasms showing a significantly worse prognosis. Surgical resection remains the mainstay of treatment, and medical options for patients with aggressive recurrent or metastatic disease are limited. DDL share similar genetic abnormalities to WDL, with high-level amplifications of chromosome 12q14-15, including the MDM2 and CDK4 cell cycle oncogenes, and DDL harbor additional genetic changes, particularly coamplifications of 6q23 and 1p32. Novel therapies targeted at the gene products of chromosome 12 are being tested in clinical trials. We review the pathology and genetics of DDL, discussing morphologic patterns, immunohistochemical and genetic findings, the differential diagnosis, and future therapeutic strategies.

Epithelioid sarcoma (ES) is a rare, aggressive soft-tissue neoplasm of uncertain differentiation, characterized by nodular aggregates of epithelioid cells, which are immunoreactive to cytokeratins (CKs) and epithelial membrane antigen, and often for CD34. It has a propensity for multifocal disease at presentation, local recurrence, and regional metastasis. These are aggressive neoplasms with particularly poor prognosis after regional or distant metastatic disease, for which surgical resection is still the mainstay of treatment, and options for patients with metastatic disease remain undefined. There are 2 distinct variants: classic ES, which typically presents as a subcutaneous or deep dermal mass in the distal extremities of young adults and comprises nodular distributions of relatively uniform epithelioid cells with central necrosis, and the proximal variant, which has a predilection for proximal limbs and limb girdles and the midline of the trunk, which is composed of sheets of larger, more atypical cells with variable rhabdoid morphology. Both classic and proximal-type ESs are associated with the loss of SMARCB1/INI1 protein expression, but appear otherwise molecularly relatively heterogeneous. We review classic and proximal-type ES, discussing morphology, immunohistochemical and genetic findings, the differential diagnosis, and the future potential for targeted therapies.

Composite hemangioendothelioma (HE) is a rare vascular neoplasm of intermediate malignant potential that predominantly occurs within the dermis or subcutis of the extremities, and occurs in a wide age range. It is locally aggressive with a high rate of local recurrence, and more rarely regional lymph node or distant metastasis. Histologically, it is composed of a complex admixture of benign, intermediate and malignant vascular components. Although composite HE may contain angiosarcoma-like areas, its prognosis is better than that of pure angiosarcoma. We describe a case of composite HE presenting as a submandibular mass in a 43 year-old male, which included areas of prominent 'high grade' epithelioid angiosarcoma. This adds to the range of anatomic sites of these neoplasms, highlights the importance of recognition of the head and neck as a potential site, and emphasizes the importance of accurate diagnosis for correct management (including of long term follow up) and prognostication.

The accurate diagnosis of soft tissue neoplasms has crucial therapeutic and prognostic importance. There is frequent morphologic overlap between entities, and ancillary modalities are used in the vast majority of diagnoses. Immunohistochemistry is rapid and inexpensive, and in addition to the older markers that mainly detected cytoplasmic proteins, antibodies can indirectly detect tumor-specific genetic and molecular abnormalities. The use of molecular diagnostic techniques is now widespread, with molecular services often integrated into routine histopathology laboratories; as their cost and turnaround times begin to parallel those for immunohistochemistry, we compared the usefulness of ancillary immunohistochemistry, molecular genetic, and molecular cytogenetic techniques in the diagnosis of soft tissue lesions. We evaluated the number and contribution of immunohistochemical tests and panels and of ancillary molecular techniques in the primary histopathologic diagnosis of 150 soft tissue lesions. Ninety of 150 cases required either only one immunohistochemical panel or minimal immunohistochemistry for diagnosis, while 39/150 required 2 to 4 panels. In 5/150, ancillary molecular tests alone (without immunohistochemistry) were diagnostically sufficient. The majority of cases required one immunohistochemical panel for diagnosis, with a smaller proportion requiring a second, and a minority requiring a third or fourth (which mainly comprised neoplasms for which the final diagnosis was uncertain). Certain neoplasms required both extensive immunohistochemistry and ancillary molecular testing, despite which the final diagnosis was inconclusive. Ancillary molecular techniques now make a significant contribution to soft tissue tumor diagnosis, being required in over one third (52/150) of cases, and were useful in confirming or excluding tumors that were not possible to conclusively diagnose with histology and immunohistochemistry. Only a small proportion of soft tissue neoplasms (16/150; all benign) did not require immunohistochemistry or ancillary molecular methods, with morphology alone being sufficient for diagnosis., (© The Author(s) 2015.)

Dermatofibrosarcoma protuberans (DFSP), the most common dermal sarcoma, is a low-grade, slow growing fibroblastic malignant neoplasm that most frequently affects middle aged adults and is characterized by a high local recurrence rate and a low propensity for metastasis. Wide surgical resection or Mohs micrographic surgery (MMS) are the preferred approaches for localized disease, while radiation therapy is warranted for inoperable disease or for cases with positive margins where re-excision is not possible. DFSP is generally regarded as refractory to conventional chemotherapy. Treatment options for systemic disease were limited until the discovery of a unique translocation, t(17;22)(q22;q13) (COL1A1;PDGFB) found in a majority of cases. In recent years, imatinib, a PDGFβR, ABL and KIT inhibitor, has revolutionized systemic therapy in DFSP. In this review, we summarize the epidemiological, clinical, histological and genetic characteristics of DFSP and update the readers on its current management.

Primary intrathoracic sarcomas constitute a rare, heterogeneous group of neoplasms that occur in the lung parenchyma, pleura, and mediastinum. Although pathologically diverse, they frequently show similar clinical and radiological features, and accurate histopathological diagnosis is therefore crucial for correct management and prognostication. The characterization of sarcomas can be difficult, as there is frequent overlap between the histological patterns of benign and malignant lesions, and between different malignant tumours and with non-mesenchymal neoplasms. This is particularly critical within the thorax, where many spindle cell neoplasms represent tumours of epithelial origin or metastatic disease. Immunohistochemistry and molecular genetic techniques are important ancillary contributors to histological interpretation, but several groups of tumours still lack reliable immunohistochemical markers or reproducible genetic changes. We review the pathology of the major types of intrathoracic sarcoma with reference to clinical factors, morphology, immunohistochemistry, and molecular genetics., (© 2015 John Wiley & Sons Ltd.)

Intraneural extension of soft tissue sarcomas is uncommon; it is most frequently seen in malignant peripheral nerve sheath tumor, but its occurrence is exceptional in synovial sarcoma. We describe a case arising extraneurally within the deep soft tissues of the forearm, which recurred and resulted in above-elbow amputation, revealing an unexpected finding of diffuse intraneural extension of tumor within a macroscopically normal major nerve. Despite macroscopic and microscopically clear soft tissue margins, the neoplasm had "traveled" a significant distance intraneurally to involve the neural resection margin. This feature does not appear to have been described before; it highlights the issue of whether intraneural spread of synovial sarcoma might have been previously underrecognized, and we discuss briefly some practical implications., (© The Author(s) 2015.)

Ameloblastic fibro-odontosarcoma (AFOS) is an extremely rare malignant odontogenic tumor. Complete surgical excision is the treatment of choice. Deaths due to disease recurrence and/or progression are documented. Here, we report the case of a 15-year-old female with multiple recurrent AFOS. She responded to chemotherapy with ifosfamide and doxorubicin consolidated by stereotactic reirradiation using cyberknife and remained in complete remission 14 months from the end of reirradiation therapy. Chemotherapy with ifosfamide and doxorubicin should be considered in advanced cases of AFOS., (© 2015 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.)

Background: Pleomorphic rhabdomyosarcoma (RMS) is a rare sub-type of RMS. Optimal treatment remains undefined., Patients and Methods: Between 1995 and 2014, 45 patients were diagnosed and treated in three tertiary sarcoma Centers (United Kingdom, Switzerland and Germany). Treatment characteristics and outcomes were analyzed., Results: The median age at diagnosis was 71.5 years (range=28.4-92.8 years). Median survival for those with localised (n=32, 71.1%) and metastatic disease (n=13, 28.9%) were 12.8 months (95% confidence interval=8.2-34.4) and 7.1 months (95% confidence interval=3.8-11.3) respectively. The relapse rate was 53.8% (four local and 10 distant relapses). In total, 14 (31.1%) patients received first line palliative chemotherapy including multi-agent paediatric chemotherapy schedules (n=3), ifosfamide-doxorubicin (n=4) and single-agent doxorubicin (n=7). Response to chemotherapy was poor (one partial remission with vincristine-actinomycin D-cyclophosphamide and six cases with stable disease). Median progression-free survival was 2.3 (range=1.2-7.3) months., Conclusion: Pleomorphic RMS is an aggressive neoplasm mainly affecting older patients, associated with a high relapse rate, a poor and short-lived response to standard chemotherapy and an overall poor prognosis for both localised and metastatic disease., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Distinguishing well-differentiated liposarcoma (WDL) from lipoma is of clinical and prognostic importance, but can be difficult on imaging and histology alone. WDL characteristically harbor amplifications of the MDM2 and CDK4 cell cycle oncogenes and overexpress the cell cycle regulator p16. Fluorescence in situ hybridization (FISH) to assess for MDM2 and CDK4 gene amplification is the diagnostic gold standard, and immunohistochemistry for the overexpressed MDM2 and CDK4 proteins is also useful but may not be routinely offered by pathology laboratories. p16 immunohistochemistry is a sensitive marker for WDL and is in the repertoire of most laboratories, and it has been suggested as a useful method of distinguishing WDL from lipomas when other ancillary modalities are not readily available. We describe a case of a large retroperitoneal adipocytic mass occurring in a 27-year-old male, which was clinically and radiologically in keeping with WDL. Histologically this was a differentiated adipocytic neoplasm with prominent fibrous septa and fat necrosis, more suggestive of retroperitoneal lipoma. Immunohistochemistry showed diffuse, strong nuclear expression of p16 in the areas of fat necrosis. However, CDK4 was negative and the lesion lacked evidence of MDM2 amplification with FISH. Diffuse expression of p16 in areas of fat necrosis in large or deep lipomas highlights the potential for diagnostic misinterpretation as well differentiated liposarcoma, and we therefore emphasize that p16 immunohistochemistry should always be interpreted as part of a panel with CDK4 +/- MDM2 in the differential diagnosis of WDL and lipoma., (© The Author(s) 2015.)

Perivascular epithelioid cell tumors, or PEComas, are mesenchymal neoplasms composed of histologically and immunohistochemically distinctive epithelioid or spindle cells, which are immunoreactive for both smooth muscle and melanocytic markers. The cells in PEComas are typically arranged around blood vessels and appear to form the vessel wall, often infiltrating the smooth muscle of small- to medium-sized vessels. Periluminal cells are usually epithelioid and the more peripheral cells are spindle shaped. The cells have small, round to oval nuclei, sometimes with focal nuclear atypia, and clear to eosinophilic cytoplasm, and no counterpart normal cell has been identified. The PEComa "family" now includes angiomyolipoma, pulmonary clear cell "sugar" tumor and lymphangioleiomyomatosis, primary extrapulmonary sugar tumor, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, abdominopelvic sarcoma of perivascular epithelioid cells, and other tumors with similar features at various sites that are simply termed PEComa. Some PEComas occur in patients with tuberous sclerosis complex and share the genetic abnormalities. There is a behavioral spectrum from benign to frankly malignant, and histologic criteria have been proposed for assessing malignant potential. The differential diagnosis can include carcinomas, smooth muscle tumors, other clear cell neoplasms, and adipocytic tumors. PEComas constitute a genetically diverse group that includes neoplasms harboring TFE3 gene rearrangements and those with TSC2 mutations, indicating alternative tumorigenic pathways. Recent advances in therapy of malignant PEComas relate to increased knowledge of specific genetic changes and their effects on metabolic pathways that are susceptible to specific interventions. We review PEComas, emphasizing the diagnostic spectrum and recent immunohistochemical and genetic findings., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Desmoid-type fibromatosis is a rare, locally infiltrative, mesenchymal neoplasm that is associated with high rates of local recurrence but lacks the potential to metastasise. The disease affects younger individuals, with a peak age of 30 years, and is the most common cause of an anterior abdominal wall mass in young women of childbearing age. It may, however, involve nearly every body part, including the extremities, head and neck, trunk, and abdominal cavity; as such, desmoid-type fibromatosis may present to a range of general and subspecialty radiologists. These rare tumours have a widely variable clinical presentation and unpredictable natural history, hence input from a soft-tissue tumour centre is recommended, although much of the imaging may be performed at the patient's local hospital. The consensus for treatment has changed over the past decade, with most centres moving away from primary radical surgery towards a front-line 'watch-and-wait' policy. Therefore, imaging has an increasingly important role to play in both the diagnosis and follow-up of these patients. This review will discuss the typical imaging characteristics of these lesions and suggest diagnostic and follow-up magnetic resonance imaging protocols, with details of suitable sequences and scanning intervals., (Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

DOG1 is a highly sensitive marker for gastrointestinal stromal tumor (GIST) and is in the routine diagnostic antibody repertoire of many surgical pathology laboratories. Moreover, GIST is well recognized by both pathologists and clinicians in the differential diagnosis of intra-abdominal and pelvic neoplasms. Low-grade fibromyxoid sarcoma (LGFMS) is, however, much less frequently anticipated, particularly when occurring at unusual sites, because of its rarity and bland histology, particularly on core biopsy. We describe a case of a 53-year-old male with a large pelvic and pararectal mass, which on biopsy showed a moderately cellular spindle cell neoplasm within fibrous stroma. Immunohistochemistry at the referring center showed diffuse and strong expression of DOG1 with negativity for other markers. After referral to a tertiary center, repeat DOG1 immunohistochemistry again showed diffuse expression, but MUC4 was also positive, and this was confirmed to be LGFMS, harboring FUS-CREB3L2 fusion transcripts by reverse transcription-polymerase chain reaction and FUS rearrangement with fluorescence in situ hybridization. In view of this we assessed DOG1 expression in 10 other LGFMS (all MUC4 positive, and 9 molecularly confirmed to harbor FUS-CREB3L2 fusion transcripts and/or FUS or EWSR1 gene rearrangement), of which 5 showed DOG1 expression in up to 75% of tumor cells, varying in intensity from weak to strong. While LGFMS and GIST are generally morphologically dissimilar, less typical variants of each exist, and both can contain bland spindled cells within fibrous stroma. As the morphologic spectrum of LGFMS is wide, and as it can occur in unusual sites and may not be well recognized by general pathologists and non-soft tissue pathologists, we highlight the potential for diagnostic confusion with GIST owing to aberrant DOG1 expression. This is clinically pertinent, as the management and prognosis of these 2 neoplasms differs significantly., (© The Author(s) 2015.)

Epithelioid sarcoma (ES) is a soft tissue sarcoma of children and young adults for which the preferred treatment for localized disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review, we will summarize clinically relevant biomarkers (e.g., SMARCB1, CA125, dysadherin, and others) with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR, and polykinase inhibitors (e.g., sunitinib) in the management of local and disseminated disease. Toward building a consortium of pharmaceutical, academic, and non-profit collaborators, we will discuss the state of resources for investigating ES with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed toward effective biology-driven therapies.

Fluorescence in situ hybridization (FISH) for FOXO1 gene rearrangement and reverse transcription-polymerase chain reaction (PCR) for PAX3/7-FOXO1 fusion transcripts have become routine ancillary tools for the diagnosis of alveolar rhabdomyosarcomas (ARMS). Here we summarize our experience of these adjunct diagnostic modalities at a tertiary center, presenting the largest comparative series of FISH and PCR for suspected or possible ARMS to date. All suspected or possible ARMS tested by FISH or PCR for FOXO1 rearrangement or PAX3/7-FOXO1 fusion transcripts over a 7-year period were included. FISH and PCR results were correlated with clinical and histologic findings. One hundred samples from 95 patients had FISH and/or PCR performed. FISH had higher rates of technical success (96.8 %) compared with PCR (88 %). Where both tests were utilized successfully, there was high concordance rate between them (94.9 %). In 24 histologic ARMS tested for FISH or PCR, 83.3 % were translocation-positive (all for PAX3-FOXO1 by PCR) and included 3 histologic solid variants. In 76 cases where ARMS was excluded, there were 3 potential false-positive cases with FISH but none with PCR. PCR had similar sensitivity (85.7 %) and better specificity (100 %) in aiding the diagnosis of ARMS, compared with FISH (85 and 95.8 %, respectively). All solid variant ARMS harbored FOXO1 gene rearrangements and PAX3-FOXO1 ARMS were detected to the exclusion of PAX7-FOXO1. In comparative analysis, both FISH and PCR are useful in aiding the diagnosis of ARMS and excluding its sarcomatous mimics. FISH is more reliable technically but has less specificity than PCR. In cases where ARMS is in the differential diagnosis, it is optimal to perform both PCR and FISH: both have similar sensitivities for detecting ARMS, but FISH may confirm or exclude cases that are technically unsuccessful with PCR, while PCR can detect specific fusion transcripts that may be useful prognostically.

Divergent differentiation occurs in a subset of malignant peripheral nerve sheath tumors (MPNST), but differentiation toward epithelial elements is unusual. MPNST with both heterologous rhabdomyosarcomatous differentiation (malignant Triton tumor), and glandular epithelial differentiation is exceedingly rare, with only 11 cases reported since 1973, and only 1 with histologically proven metastasis. We describe a case occurring in the mediastinum (between the ascending aorta and the main pulmonary artery) of a 40-year-old man with neurofibromatosis type-1. Despite treatment, the tumor metastasized to the right frontal lobe 16 months after diagnosis. Histologically, the primary neoplasm comprised cellular fascicles of atypical spindle cells, with discrete foci of well-formed or more primitive glandular epithelial structures, while the metastases comprised spindle cell sarcoma, including rhabdomyosarcoma, without epithelial elements. We review and discuss the literature on these little characterized neoplasms, including histology and clinical features, adding to the spectrum of documented cases of divergent epithelial differentiation in Triton tumor., (© The Author(s) 2015.)

Composite hemangioendotheliomas are rare vascular neoplasms of intermediate biological potential, characterized by a complex admixture of benign, low-grade malignant, and malignant vascular components. They can affect both adults and children, and occur predominantly as long-standing lesions in the dermis and subcutis of the extremities, but have also been increasingly reported at other sites, including the oral cavity and in viscera such as kidney and spleen. These usually behave in a low-grade manner, with a relatively high rate of local recurrence and rarely lymph node and distant metastases, but no tumor-related deaths have been reported. Microscopically these are heterogenous neoplasms with merging of different vascular patterns, which immunohistochemically variably express vascular endothelial markers. Because of the wide morphologic spectrum, they can be difficult to recognize, but accurate diagnosis is crucial for correct treatment and prognostication. We review the literature, discussing clinical and histopathologic features, and the differential diagnosis of these rare tumors.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade malignant soft tissue neoplasm, which usually presents on the distal extremities of adults and sometimes children. It has a characteristic appearance, of a lobulated or multinodular neoplasm of moderately atypical epithelioid or spindled cells, vacuolated cells, and enlarged or bizarre cells with macronuclei, with prominent mixed inflammatory infiltrate, and variably myxoid stroma. However, the proportions of each component vary, making diagnosis difficult, particularly when tumors arise at unusual nonextremity sites. We describe a case of MIFS occurring as a primary neoplasm on the scalp of an 80-year-old male, which recurred locally after 2 years and developed extensive bilateral cervical lymph node metastases. MIFS is exceptionally rare in the head and neck, and it has been described only once on the scalp. This case showed classical histologic features, and additionally a high mitotic index and atypical mitoses, which may be suggestive of a poorer prognosis. This case highlights the need to consider MIFS in the differential diagnoses of pleomorphic tumors of the head and neck, and it adds to the small number of MIFS showing highly aggressive behavior., (© The Author(s) 2015.)

Myoepithelial and mixed tumors represent a heterogeneous group of neoplasms for which classification is incomplete and continues to evolve. Those arising in the soft tissues appear to represent subgroups that are genetically distinct from those that occur within salivary glands. We describe a case of soft tissue myoepithelial carcinoma with rhabdoid morphology, which presented as an enlarging neck mass in a 40 year old male, and in which EWSR1 rearrangement was demonstrated by fluorescence in situ hybridization. This neoplasm showed diffuse INI1 loss, making distinction from other INI1-negative rhabdoid tumors difficult. This expands the range of reported histologic features of EWSR1-rearranged myoepithelial neoplasms, and highlights the significant morphologic and immunohistochemical overlap between this and other INI1-negative malignant rhabdoid neoplasms.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of intermediate biologic potential and uncertain differentiation, most often arising in the extremities of children and young adults. Although it has characteristic histologic features of a lymphoid cuff surrounding nodules of ovoid cells with blood-filled cystic cavities, diagnosis is often difficult due to its morphologic heterogeneity and lack of specific immunoprofile. Angiomatoid fibrous histiocytoma is associated with recurrent chromosomal translocations, leading to characteristic EWSR1-CREB1, EWSR1-ATF1, and, rarely, FUS-ATF1 gene fusions; fluorescence in situ hybridization (FISH), detecting EWSR1 or FUS rearrangements, and reverse transcription-polymerase chain reaction (RT-PCR) for EWSR1-CREB1 and EWSR1-ATF1 fusion transcripts have become routine ancillary tools. We present a large comparative series of FISH and RT-PCR for AFH. Seventeen neoplasms (from 16 patients) histologically diagnosed as AFH were assessed for EWSR1 rearrangements or EWSR1-CREB1 and EWSR1-ATF1 fusion transcripts. All 17 were positive for either FISH or RT-PCR or both. Of 16, 14 (87.5%) had detectable EWSR1-CREB1 or EWSR1-ATF1 fusion transcripts by RT-PCR, whereas 13 (76.5%) of 17 had positive EWSR1 rearrangement with FISH. All 13 of 13 non-AFH control neoplasms failed to show EWSR1-CREB1 or EWSR1-ATF1 fusion transcripts, whereas EWSR1 rearrangement was present in 2 of these 13 cases (which were histopathologically myoepithelial neoplasms). This study shows that EWSR1-CREB1 or EWSR1-ATF1 fusions predominate in AFH (supporting previous reports that FUS rearrangement is rare in AFH) and that RT-PCR has a comparable detection rate to FISH for AFH. Importantly, cases of AFH can be missed if RT-PCR is not performed in conjunction with FISH, and RT-PCR has the added advantage of specificity, which is crucial, as EWSR1 rearrangements are present in a variety of neoplasms in the histologic differential diagnosis of AFH, that differ in behavior and treatment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Context: Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of intermediate biologic potential and uncertain differentiation, most often arising in the superficial extremities of children and young adults. While it has characteristic histologic features of nodular distributions of ovoid and spindle cells with blood-filled cystic cavities and a surrounding dense lymphoplasmacytic infiltrate, there is a significant morphologic spectrum, which coupled with its rarity and lack of specific immunoprofile can make diagnosis challenging. Angiomatoid fibrous histiocytoma is associated with 3 characteristic gene fusions, EWSR1-CREB1 and EWSR1-ATF1, which are also described in other neoplasms, and rarely FUS-ATF1. Angiomatoid fibrous histiocytoma is now recognized at an increasing number of sites and is known to display a variety of unusual histologic features., Objective: To review the current status of AFH, discussing putative etiology, histopathology with variant morphology and differential diagnosis, and current genetics, including overlap with other tumors harboring EWSR1-CREB1 and EWSR1-ATF1 fusions., Data Sources: Review of published literature, including case series, case reports, and review articles, in online medical databases., Conclusions: The occurrence of AFH at several unusual anatomic sites and its spectrum of morphologic patterns can result in significant diagnostic difficulty, and correct diagnosis is particularly important because of its small risk of metastasis and death. This highlights the importance of diagnostic recognition, ancillary molecular genetic confirmation, and close clinical follow-up of patients with AFH. Further insight into the genetic and epigenetic changes arising secondary to the characteristic gene fusions of AFH will be integral to understanding its tumorigenic mechanisms.

Background: Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) occurs frequently in prostate cancers. Preclinical evidence suggests that activation of PI3K/AKT signaling through loss of PTEN can result in resistance to hormonal treatment in prostate cancer., Objective: To explore the antitumor activity of abiraterone acetate (abiraterone) in castration-resistant prostate cancer (CRPC) patients with and without loss of PTEN protein expression., Design, Setting, and Participants: We retrospectively identified patients who had received abiraterone and had hormone-sensitive prostate cancer (HSPC) and/or CRPC tissue available for PTEN immunohistochemical analysis., Outcome Measurements and Statistical Analysis: The primary end point was overall survival from initiation of abiraterone treatment. Relationship with outcome was analyzed using multivariate Cox regression and log-rank analyses., Results and Limitations: A total of 144 patients were identified who had received abiraterone post-docetaxel and had available tumor tissue. Overall, loss of PTEN expression was observed in 40% of patients. Matched HSPC and CRPC tumor biopsies were available for 41 patients. PTEN status in CRPC correlated with HSPC in 86% of cases. Loss of PTEN expression was associated with shorter median overall survival (14 vs 21 mo; hazard ratio [HR]: 1.75; 95% confidence interval [CI], 1.19-2.55; p=0.004) and shorter median duration of abiraterone treatment (24 vs 28 wk; HR: 1.6; 95% CI, 1.12-2.28; p=0.009). PTEN protein loss, high lactate dehydrogenase, and the presence of visceral metastases were identified as independent prognostic factors in multivariate analysis., Conclusions: Our results indicate that loss of PTEN expression was associated with worse survival and shorter time on abiraterone treatment. Further studies in larger and prospective cohorts are warranted., Patient Summary: PTEN is a protein often lost in prostate cancer cells. In this study we evaluated if prostate cancers that lack this protein respond differently to treatment with abiraterone acetate. We demonstrated that the survival of patients with loss of PTEN is shorter than patients with normal PTEN expression., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Hormonal manipulation is sometimes recommended in the treatment of metastatic endometrial stromal sarcoma, but there are few data assessing the efficacy of endocrine therapies in this subtype of uterine sarcomas., Methods: We performed a retrospective electronic medical record review of patients with metastatic ESS treated with a hormonal agent at Royal Marsden Hospital between 1999 and 2011. We assessed progression-free survival (PFS), objective response and toxicity profile among patients with measurable disease., Results: Thirteen patients with metastatic ESS were treated with hormonal therapies. Hormone receptor status (estrogen and progesterone receptors) was assessed in 9 out of 13 patients and in all of them it was moderately to strongly positive. Aromatase inhibitors (AIs) were prescribed as first endocrine line in 11/13 patients and progestins in the remainder, while in 2(nd) line treatment AIs were prescribed in 7/10 patients, followed by progestins and GnRH analogues. Median PFS for 1(st)line was 4.0 years (95% CI: 2.4 - 5.5 years) with 5-year progression-free rate of 30.8% (95% CI: 5.7 - 55.9%), both of which reflect the indolent natural history of ESS. Best objective response was partial response (PR) in 6/13 patients (46.2%; 95% CI: 19.2 - 74.9) and clinical benefit rate (defined as complete response + PR + stable disease ≥6 months) was 92.4% (95% CI: 64.0 - 99.8%; 12/13 patients). Median PFS for 2(nd) line was 3.0 years (95% CI: 2.0 - 4.1 years) with 2-year progression-free rate of 88.9% (95% CI: 68.3 - 100.0)., Conclusions: In this cohort of metastatic ESS patients, 1st line endocrine treatment achieved objective response in 46.2% of them and clinical benefit in 92.4%. Tamoxifen and hormone replacement therapy should not be prescribed in patients with ESS due to their detrimental effects. Until more solid data are available, a reasonable recommendation would be that 1(st) line treatment with an endocrine treatment, preferably with an AI. Moreover, in view of the positive outcomes of our patients that received 2(nd)/3(rd)line endocrine treatments, all available hormonal options should be used in sequence in the management of ESS.

We describe a case of superficial low-grade fibromyxoid sarcoma (LGFMS) in a 12-year-old boy, confirmed by the detection of FUS-CREB3L2 fusion transcripts by reverse-transcription polymerase chain reaction and FUS rearrangement with fluorescence in situ hybridization, which had morphological features similar to ossifying fibromyxoid tumor (OFMT), including an almost complete rim of mature, metaplastic bone. LGFMS and OFMT can appear morphologically similar, with bland ovoid cells within a fibrous to myxoid matrix. Both can occur superficially; and whereas MUC4 immunoreactivity is characteristic of LGFMS, this can also be seen in some OFMTs. As the morphological spectrum of LGFMS is wide, we highlight the potential for diagnostic confusion with OFMT, which is clinically pertinent as most OFMTs behave in a benign manner whereas LGFMS is a malignant neoplasm with a propensity for local recurrence and a significant metastatic rate., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is a rare malignant neoplasm that occurs in the wall of the small bowel, stomach, or large bowel, predominantly in young adults. It is an aggressive neoplasm that frequently presents with metastatic disease and has a high mortality rate. Histologically, it is usually composed of medium-sized primitive ovoid or epithelioid cells with pale or clear cytoplasm that are arranged in sheets or in papillary or alveolar architectures. Clear cell sarcoma-like tumor of the gastrointestinal tract is positive for S100 protein, invariably negative for melanocyte-specific markers and is often also positive for neuroendocrine markers. The etiology of CCSLGT is unknown, but many studies have shown associations with EWSR1-CREB1 gene fusions and, less frequently, with EWSR1-ATF1 fusions. Here, we discuss the current status of CCSLGT, including histologic, immunophenotypic, and molecular findings.

Background: Solitary Fibrous Tumour (SFT) is a rare soft tissue neoplasm, described in several locations in the body. It is classified as intermediate malignant potential with low risk of metastasis and has a low tendency to recur after primary surgery., Methods: We performed a prospective data collection of the patients with SFT presented to the Royal Marsden Hospital from January to December 2013, and treated with pazopanib in first line. Demographics, anatomic primary sites, treatment and survival outcomes were collected from patients' electronic records., Results: 13 patients (54% females) were identified with a median age of 51 years (range 37-77). Most of the patients (77%) were diagnosed with extra-thoracic SFT. All the patients received first line treatment with pazopanib for metastatic disease. Median overall survival (OS) was 13.3 months. Median progression free survival (PFS) was 4.7 months. No statistically significant difference was found in OS and PFS between primary thoracic SFT and primary extra-thoracic SFT. According to RECIST, one partial response (9%) and eight disease stabilizations (73%) were found as best responses. Using Choi criteria, there were 5 partial responses (46%) and 4 stabilizations (36%)., Conclusion: Our prospective data confirm that anti-angiogenic drugs are active in SFT. PFS and overall response do not appear significantly lower than other reported series on the same disease. Furthermore, pazopanib is a drug already licensed in soft tissue sarcomas and these data suggest its activity also in this particular subtype of sarcomas.