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Myositis ossificans, a benign tumor composed of spindle cells and osteoblasts, can clinically and radiologically mimic osteosarcoma. While recognition and accurate diagnosis of myositis ossificans can be a challenge, this is critical as it may allow a conservative surgical approach to maximize functional outcomes. Herein, we present a patient with surface myositis ossificans confirmed genetically by the presence of COL1A1::USP6 gene fusion, along with a literature review. Due to the enhanced visualization of the bone matrix, computed tomography (CT) imaging may be a superior imaging modality to magnetic resonance (MR) imaging. Staged biopsies with samples obtained from the periphery and center of the lesions may allow pathologists to discern the zonal distribution histologically. Furthermore, immunohistochemistry fluorescence in situ hybridization and molecular testing can aid in the distinction of myositis ossificans from mimics. Because of their resemblance to other bone tumors, these cases of myositis ossificans highlight the importance of a multidisciplinary approach integrating clinical, radiologic, and pathologic analysis and involving serial imaging, sampling, and judicious use of ancillary immunohistochemical and molecular testing. [ABSTRACT FROM AUTHOR]

Aims: Anastomosing haemangiomas are benign tumours with anastomosing vascular channels that may mimic angiosarcoma. While anastomosing haemangiomas have been described in diverse locations, particularly the abdominal/paraspinal region, data on anastomosing haemangiomas in the mediastinum remain limited. We report the clinicopathological, radiological and molecular characteristics of the largest single‐institutional series of mediastinal anastomosing haemangiomas. Methods and results: In our pathology archives in 2011–23, we reviewed all vascular lesions involving the mediastinum and identified seven anastomosing haemangiomas. Clinical information was abstracted from medical charts; available radiological imaging was reviewed. Targeted DNA‐based next‐generation sequencing (447 genes, including GNAQ and GNA11) was performed on five cases. The seven patients included five women and two men, with an age range of 55–77 (median = 72) years. Of the six tumours with available radiology, two each were in the prevascular, visceral and paravertebral mediastinum, with lobulated peripheral enhancement in all tumours examined with contrast enhancement. Six patients underwent tumour resection; one patient received proton radiotherapy. Microscopically, each tumour was solitary and characterised by anastomosing capillary‐sized vessels lined by hobnail endothelial cells. Fibrin microthrombi, hyaline globules and extramedullary haematopoiesis were common. In the five tumours analysed by next‐generation sequencing, GNAQ p.Q209P was identified in one tumour; no additional reportable alterations were identified in the remaining cases. No recurrence was noted in the four patients with available follow‐up of 3–58 (median = 9.5) months after resection. Conclusion: While mediastinal anastomosing haemangiomas can microscopically mimic angiosarcoma, awareness of this entity and radiological correlation may help to circumvent this diagnostic pitfall. [ABSTRACT FROM AUTHOR]

Primary bone tumours can pose diagnostic problems due to their overlapping radiologic and histologic features. Given the recent advancement in our understanding of the biology of bone tumours, multiple immunohistochemical and molecular markers have been devised to aid in their diagnosis. This review provides brief updates on select bone tumours, including chondrosarcomas, benign chondrogenic tumours, osteosarcomas, benign osteogenic tumours, fibroosseous lesions, vascular tumours, osteoclastic giant cell‐rich or cystic tumours, chordoma, adamantinoma, small round blue cell sarcomas, and others. We discuss their salient molecular features and novel immunohistochemical correlates, along with some tips to avoid common diagnostic pitfalls. [ABSTRACT FROM AUTHOR]

Background and objectives: Bone tumours are relatively rare and, as a consequence, treatment in a centre with expertise is required. Current treatment guidelines also recommend review by a specialised pathologist. Here we report on international consensus‐based datasets for the pathology reporting of biopsy and resection specimens of bone sarcomas. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter‐)national pathology and cancer organisations. Methods and results: According to the ICCR's process for dataset development, an international expert panel consisting of pathologists, an oncologic orthopaedic surgeon, a medical oncologist, and a radiologist produced a set of core and noncore data items for biopsy and resection specimens based on a critical review and discussion of current evidence. All professionals involved were bone tumour experts affiliated with tertiary referral centres. Commentary was provided for each data item to explain the rationale for selecting it as a core or noncore element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the documents were finalised and ratified, and the datasets, including a synoptic reporting guide, were published on the ICCR website. Conclusion: These first international datasets for bone sarcomas are intended to promote high‐quality, standardised pathology reporting. Their widespread adoption will improve the consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will help to improve management of bone sarcoma patients. [ABSTRACT FROM AUTHOR]

Angiomyofibroblastoma (AMF), a rare benign vulvovaginal mesenchymal tumour, poses a diagnostic challenge due to histologic and immunohistochemical overlap with other vulvar mesenchymal tumours. Recently, MTG1‐CYP2E1 fusion transcripts were reported in 5/5 AMFs; no other genetic alterations have been described to date. Herein, we sought to investigate the frequency of the MTG1‐CYP2E1 fusion and the presence of other potential genetic alterations in a cohort of AMFs (n = 7, patient age range: 28–49 years). Tumours demonstrated classic morphologic features including alternating hypo/hypercellular areas, capillary channels surrounded by epithelioid/spindled tumour cells, and variable amounts of mature adipose tissue. reverse transcription‐polymerase chain reaction (RT‐PCR) for MTG1‐CYP2E1 fusion, performed in all seven cases, showed the fusion transcript in five of six cases (one case with technical failure). Two tumours, including the one lacking the fusion, were subjected to targeted next‐generation sequencing (104 genes) and a sarcoma fusion assay (28 genes); the fusion negative AMF also underwent RNA sequencing. No additional mutations, copy number alterations, or fusion genes were identified with the assays employed. We conclude that the majority of AMFs harbour recurrent MTG1‐CYP2E1 fusion transcripts and identification of this fusion may aid in the diagnosis. [ABSTRACT FROM AUTHOR]

The use of denosumab to treat giant cell tumors of bone (GCT) and other giant cell‐containing bone tumors has become more common. While the clinicopathologic features of denosumab‐treated giant cell tumors of bone have been well‐illustrated, descriptions of other denosumab‐treated bone tumors are very limited. Surgical pathology files of two institutions and consultation files from two authors were searched for denosumab‐treated aneurysmal bone cysts and denosumab‐treated osteoblastomas. Clinicopathologic features were reviewed and analyzed. We identified four patients with denosumab‐treated bone tumors other than GCT from our surgical pathology and consultation files, including two aneurysmal bone cysts and two osteoblastomas. All were treated with denosumab for 0.5‐7.0 (median 4.5) months. Radiologically, denosumab‐treated tumors showed decreased size with increased ossification and mineralization on CT and heterogeneous intermediate to hypointense signal on MRI. Histologically, denosumab‐treated aneurysmal bone cyst contained thin, elongated, curvilinear, and anastomosing strands of bone with empty lacunae, while denosumab‐treated osteoblastoma showed circumscribed nodules of woven bone lined by small osteoblasts. Denosumab‐treated aneurysmal bone cyst and osteoblastoma showed treatment‐related morphologic changes that can mimic other bone neoplasms. Their recognition requires correlation with the clinical history of denosumab use and radiologic findings. [ABSTRACT FROM AUTHOR]

Aims: Simple bone cysts are benign intramedullary tumours primarily involving the long bones in skeletally immature individuals. Several mechanisms have been proposed for their pathogenesis. Although the diagnosis is typically straightforward, the interpretation can be problematic, because of superimposed fracture causing them to resemble aneurysmal bone cysts and other tumours. EWSR1–NFATC2 or FUS–NFATC2 fusions, which are characteristic of a subset of aggressive round cell sarcomas, have been recently detected in simple bone cysts. The aim of this study was to examine the clinicopathological and molecular features in a series of simple bone cysts. Methods and results: Using RNA‐based next‐generation sequencing and/or fluorescence in‐situ hybridisation, we investigated the presence of EWSR1 or FUS rearrangements in nine simple bone cysts. The patients were five females and four males, aged 3–23 years (median, 14 years); the tumours ranged from 19 mm to 160 mm (median, 46 mm) in size, and involved the femur (n = 3), humerus (n = 2), fibula (n = 2), tibia (n = 1), and iliac wing (n =1). We identified three cases with EWSR1–NFATC2 fusion (showing identical breakpoints to those in EWSR1–NFATC2 sarcomas) and one additional case with FUS rearrangement. Unlike in EWSR1–NFATC2 sarcomas, immunohistochemical expression of NKX3.1 and NKX2.2 was absent in two simple bone cysts tested. Conclusions: More than 40% of simple bone cysts harbour genetic alterations confirming that they are neoplastic, investigation of EWSR1 and/or FUS rearrangement may help to distinguish simple bone cysts from mimics, and NFATC2 rearrangement is not pathognomonic of malignancy. [ABSTRACT FROM AUTHOR]

Aims: Nuclear protein in testis (NUT) carcinoma, an aggressive tumour driven by NUTM1 rearrangements, often involves the lung/mediastinum and shows squamous differentiation. We encountered an index patient with a thoracic NUT carcinoma diagnosed by molecular testing, showing extensive pleural involvement and diffuse thyroid transcription factor‐1 (TTF‐1) expression, initially suggestive of lung adenocarcinoma with pseudomesotheliomatous growth. We thus gathered an institutional series of thoracic NUT carcinomas to examine their pathological spectrum. Methods and results: We searched for thoracic NUT carcinomas in our surgical pathology files and in 2289 consecutive patients with primary thoracic tumours investigated with RNA‐based assays. We performed NUT immunohistochemistry on 425 additional lung adenocarcinomas. Collectively, we identified six patients (five men and one woman; age 31–80 years; four never‐smokers) with thoracic NUT carcinomas confirmed by molecular testing (including five with positive NUT immunohistochemistry). They died at 2.3–12.9 months (median, 2.8 months) after presentation. Two patients were diagnosed by histopathological assessment, and the remaining four (including the index patient) were diagnosed by molecular testing. Analysis of the index case revealed expression of multiple neuroendocrine markers and TTF‐1; no ultrastructural evidence of neuroendocrine differentiation was noted. No additional NUT‐positive cases were found by immunohistochemical screening. Conclusions: Although NUT carcinoma classically shows squamous differentiation, it can rarely express TTF‐1 (even diffusely) and/or multiple neuroendocrine markers. This immunophenotypic spectrum may lead to diagnostic confusion with pulmonary adenocarcinoma, neuroendocrine tumour, and others. To circumvent this pitfall, NUT immunohistochemistry and/or NUTM1 molecular testing should be considered in primitive‐appearing tumours, regardless of their immunophenotypic features. [ABSTRACT FROM AUTHOR]

Chemical cross‐linking of ultrahigh molecular weight polyethylene (UHMWPE) using an organic peroxide followed by high temperature melting results in a large increase in toughness accompanied by a decrease in cross‐link density, which, surprisingly does not compromise the wear resistance. We compared the mechanical properties and wear behavior of a vitamin E blended, chemically cross‐linked and high temperature melted UHMWPE produced by ram extrusion (PRX HTM) to those measured with the clinically available 100‐kGy irradiated and melted UHMWPE (CISM 100). We also assessed the local biocompatibility of PRX‐HTM in rabbit subcutaneous pouch and osteochondral defect models. The ultimate tensile strength and pin‐on‐disc wear rate were similar to CISM 100; whereas the elongation‐at‐break and impact toughness were much higher with PRX‐HTM. The stress intensity factor range at crack inception was also higher with PRX‐HTM. Accelerated aging did not result in any measurable oxidation or changes in mechanical properties. Hip simulator wear rate of acetabular liners made with PRX‐HTM was 0.3 ± 0.4 mg/million‐cycle, similar to that reported for CISM 100 liners. The wear particles were largely spherical with a number‐averaged particle size of 0.95 μm with ~75% of particles below 1 μm. The subcutaneous and osteochondral rabbit implantations showed no histological differences between PRX‐HTM and the control CISM 100. Pre‐clinical wear, mechanical, and biocompatibility testing of PRX HTM showed feasibility for the use of this material as a total joint arthroplasty implant bearing surface. This process has the potential of eliminating the additional step of radiation cross‐linking by combining consolidation and cross‐linking while improving toughness. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1945–1952, 2019. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diagnosing giant cell‐rich bone tumors can be challenging on limited biopsies. H3 histone family member 3A (H3F3A) (G34W/V/R/L) mutations are present in the majority of giant cell tumors (GCTs) of bone and H3 histone family member 3B (H3F3B) (K36M) mutations are present in nearly all chondroblastomas, but are absent in histologic mimics. Mutation‐specific immunohistochemistry (IHC) is highly specific for GCT and chondroblastoma in surgical excisions. The objective of the current study was to validate H3G34W and H3K36M IHC in the diagnosis of giant cell‐rich bone tumors on fine‐needle aspiration and core needle biopsy specimens. METHODS: IHC was performed using monoclonal antibodies against histone H3.3 G34W and K36M in GCTs of bone (26 cases, including 2 malignant cases), GCT of Paget disease (1 case), chondroblastoma (8 cases), aneurysmal bone cyst (7 cases), and osteosarcoma (13 cases) with available fine‐needle aspiration and/or core needle biopsy specimens from 2 institutions. H3F3A and H3F3B Sanger sequencing was performed on all 4 H3G34W IHC‐negative GCTs. RESULTS: IHC for H3G34W was positive in 22 of 26 GCTs (85%) and negative in all histologic mimics. IHC for H3K36M was positive in all 8 chondroblastomas and negative in all histologic mimics. IHC results were concordant between biopsy and surgical specimens in 152 of 158 samples (96%). Sequencing identified alternate H3F3A G34L and G34V mutations in 1 IHC‐negative GCT each, but no mutation was found in the remaining 2 cases. CONCLUSIONS: H3G34W and H3K36M IHC is highly specific for GCT and chondroblastoma, respectively, among giant cell‐rich bone tumors, and is useful for confirming the diagnosis in limited biopsies. The presence of alternate H3F3A mutations accounts for the H3G34W IHC negativity in a subset of GCT of bone cases. Cancer Cytopathol 2018. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Aims: Cystic lesions derived from the synovial and ligamentous structures of the spine have varied histological appearances. Not uncommonly, there is discrepancy between the clinicoradiological diagnosis and histology. Therefore, we sought to characterise the histological features of tissue submitted as ‘synovial cysts’ of the spine. Methods and results: Resected specimens of the spine labelled ‘synovial cysts’ and ‘lumbar cysts’ were histologically evaluated and classified on the basis of histopathological features. Seventy‐five histological samples of spinal cysts were identified. Thirty‐one were classified as synovial cysts (definite synovial lining), 28 showed pseudocystic degeneration of the ligamentum flavum, seven showed pseudocyst formation without evidence of a synovial lining or degeneration of the ligamentum flavum, and eight showed cyst contents only or no histological evidence of cyst wall for evaluation. Twenty‐five cases (33%), especially those showing pseudocystic degeneration of the ligamentum flavum, were associated with very characteristic tumour calcinosis‐like calcium deposition with a surrounding foreign‐body giant‐cell reaction. Conclusion: Histology of ‘synovial cysts’ of the spine shows varied types of cyst; a large proportion are not synovial‐lined cysts, but rather show pseudocystic degenerative changes of the ligamentum flavum, often associated with very characteristic finely granular calcifications and a foreign‐body giant‐cell reaction. This may have implications not only for understanding the pathogenesis of these lesions, but also for their varied responses to non‐surgical interventions. [ABSTRACT FROM AUTHOR]

Aims To assess the clinical and histopathological spectrum of primary intra-articular sarcomas. Methods and results Fifteen patients were identified as having primary intra-articular sarcomas and the clinical and pathological features were evaluated. There were nine males and six females who ranged in age from 16 to 84 (mean 44) years. All tumours originated in the knee joint. The pathological diagnoses included: five synovial sarcoma, three extraskeletal myxoid chondrosarcomas, two high-grade myxofibrosarcoma (one conventional, one epithelioid), two undifferentiated pleomorphic sarcoma (one with giant cells) and one each myxoinflammatory fibroblastic sarcoma, conventional hyaline chondrosarcoma, and high-grade myofibroblastic sarcoma. All tumours were treated by segmental resection or amputation. Adjuvant therapy was given in selected cases. Follow-up ranged from 11 to 150 months. Of patients with follow-up, two died of disease; one developed pulmonary metastases after 6 years and was then lost to follow-up. Nine patients were alive and free of disease 12-150 months after diagnosis. Conclusions Primary sarcomas of the joints are very rare and most frequently affect the knee. Our experience indicates that synovial sarcoma and extraskeletal myxoid chondrosarcoma are the most common intra-articular sarcomas. [ABSTRACT FROM AUTHOR]

A case study of a 62-year-old female with swelling of the left knee and pain, is presented. It mentions the case demonstrated the presence of primary extra-axial, para-articular chordoma of the knee. it also mentions extraskeletal myxoid chondrosarcoma in the patient demonstrated a cord-like growth pattern and is embedded in abundant extracellular myxoid matrix.

BACKGROUND Fine-needle aspiration biopsy of spindled mesenchymal lesions, including schwannomas, are challenging because of overlapping cytomorphological features. The objective of the current study was to identify key diagnostic cytological criteria for the diagnosis of schwannoma and to distinguish it from its common mimics. METHODS A total of 58 schwannomas were evaluated and compared with 98 benign and low-grade spindle cell lesions, including 17 gastrointestinal stromal tumors and 20 fibromatosis cases. Biopsy confirmation was available for all cases. The authors semiquantitatively evaluated cellularity, quality of stroma (fibrous and fibrillar), the presence of single cells with bipolar cytoplasmic processes, and marked nuclear pleomorphism (in the absence of other features of malignancy). Nuclear features evaluated included fishhook-type nuclei, intranuclear inclusions, chromatin pattern, and nucleoli. RESULTS Schwannomas demonstrated cohesive tissue fragments with fibrillary and occasionally fibrous stroma. The presence of intranuclear inclusions and marked nuclear pleomorphism and the absence of single cells with bipolar cytoplasmic processes emerged as statistically significant differences between the schwannoma and the nonschwannoma groups. When 5 criteria were present (high numbers of clusters, few to no single cells, fibrillary stroma, nuclei with pointed tips, and anisonucleosis) the sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of schwannoma were 22%, 97%, 81%, and 68%, respectively. CONCLUSIONS Cohesive tissue fragments with fibrillary/fibrous stroma, intranuclear inclusions, marked nuclear pleomorphism, and the absence of spindled cells with bipolar cytoplasmic processes are strongly suggestive of schwannoma and assist in excluding potential mimics. Cancer (Cancer Cytopathol) 2015. © 2015 American Cancer Society. Cancer (Cancer Cytopathol) 2015;123:171-179. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Histologic response to chemotherapy has been shown to be an independent prognostic factor in patients with osteosarcoma and Ewing sarcoma. However, in patients with soft tissue sarcoma (STS), the prognostic impact of histologic response to chemotherapy is less clear. In the current study, the authors sought to determine the prognostic significance of treatment-induced pathologic necrosis in patients receiving neoadjuvant chemoradiotherapy for STS. METHODS Between 1989 and 2011, a total of 113 patients with grade 2 or 3 (graded according to the National Cancer Institute grading system using 3 tiers) extremity or truncal STS were identified who received neoadjuvant interdigitated chemoradiotherapy according to protocol followed by surgery. The extent of tumor necrosis in the resected specimens was quantified and correlated with outcome. RESULTS The median tumor necrosis rate was 90%, and 103 patients (91%) received all 3 cycles of planned neoadjuvant chemotherapy. The likelihood of achieving ≥95% necrosis was not related to the number of preoperative cycles of chemotherapy received but was found to be related to tumor histology (62% for malignant fibrous histiocytoma vs 0% for synovial sarcoma [ P<.001]; 56% for myxoid liposarcoma vs 0% for synovial sarcoma [ P = .002]). At a median follow-up of 6 years, there were no statistically significant differences noted in the 5-year local control, disease-specific survival, and overall survival rates for patients with ≥95% necrosis (50 patients; 44%) and <95% necrosis (63 patients; 56%), even when stratifying by histology. CONCLUSIONS In a homogeneous population of patients with high-grade extremity and truncal STS who were treated with neoadjuvant chemoradiotherapy, the extent of pathologic tumor necrosis did not correlate with outcome. Cancer 2014;120:3676-3682. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

ABSTRACT Reliable prognostic biomarkers for chordoma have not yet been established. Recent studies revealed that expression of miRNA-1 (miR-1) is frequently downregulated in several cancer types including chordoma. The goal of this follow-up study is to investigate the expression of miR-1 as a prognostic biomarker and further confirm the functional role of miR-1 in chordoma cell growth and proliferation. We determined the relative expression levels of miR-1 and Met in chordoma tissue samples and correlated those to clinical variables. The results showed that miR-1 was downregulated in 93.7% of chordoma tissues and expression was inversely correlated with Met expression. miR-1 expression levels also correlated with clinical prognosis. To characterize and confirm the functional role of miR-1 in the growth and proliferation of chordoma cells, miR-1 precursors were stably transfected into chordoma cell lines UCH-1 and CH-22. Cell Proliferation Assay and MTT were used to evaluate cell growth and proliferation. Restoring expression of miR-1 precursor decreased cell growth and proliferation in UCH-1 and CH-22 cells. These results indicate that suppressed miR-1 expression in chordoma may in part be a driver for tumor growth, and that miR-1 has potential to serve as prognostic biomarker and therapeutic target for chordoma patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:695-701, 2014. [ABSTRACT FROM AUTHOR]

Background and Objectives. Atypical lipomas are uncommon, slow-growing benign tumors. While surgery has been the primary treatment modality, we have managed some patients with radiation (RT) as a component of the treatment and have reported their outcomes in this study. Methods. A retrospective review of all cases of extremity and trunk atypical lipomas in The Sarcoma Database at the study institution was conducted. Results. Thirteen patients were identified. All patients underwent surgical resection at initial presentation and received pre- or postoperative radiation for subtotal resection (2 = 2), local recurrence (n = 8), or progressive disease (n = 3). The median total radiation dose was 50 Gy. Median followup was 65.1 months. All patients treated with RT remained free of disease at the last followup. No grade 3 or higher late toxicity from radiation was observed. No cases of tumor dedifferentiation occurred. Conclusion. For recurrent or residual atypical lipomas, a combination of reexcision and RT can provide long-term local control with acceptable morbidity. For recurrent tumors, pre-op RT of 50 Gy appears to be an effective and well-tolerated management approach. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that microRNA (miRNA) expression signatures in cancer may have important diagnostic, prognostic, and therapeutic value, but there is no data on miRNA expression in chordoma. The purpose of this study was to identify the role of miRNAs in human chordoma. We analyzed miRNA expression in chordoma-derived cell lines and chordoma tissue by using miRNA microarray technology with unsupervised hierarchical clustering analysis. The relative expression levels of these miRNAs were confirmed by real-time quantitative RT-PCR and Northern blot analysis. To characterize the potential role of miRNA-1, miRNA-1 was stably transfected into a chordoma cell line, UCH1. The expression of miRNA-1 targeted gene Met in chordoma tissues was also studied. We observe that human chordoma tissues and cell lines can be distinguished from normal muscle tissue by comparing miRNA expression profiles. Several miRNAs were differentially expressed in chordoma cell lines compared to controls, and similar expression patterns were found in primary chordoma tissues. Importantly, we were able to show for the first time, to our knowledge, that expression of miRNA-1 and miRNA-206, two miRNAs implicated in a number of other cancer types, were markedly decreased in both chordoma tissues and cell lines. When chordoma cell lines were transfected with miRNA-1, downregulation of known miRNA-1 targets was observed. These targets included Met and HDAC4-two genes that were observed to be overexpressed in chordoma. Our results demonstrate that some miRNAs are differentially expressed in chordoma and, in particular, miRNA-1 may have a functional effect on chordoma tumor pathogenesis. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:746-752, 2010 [ABSTRACT FROM AUTHOR]

Spindle cell lipoma is a benign lipomatous tumor, which usually arises on the back of the neck, shoulder or upper back of males in the third to seventh decade of life. We report herein an unusual infiltrating intramuscular spindle cell lipoma arising in the nose of a 53-year-old man. The patient presented with a 0.5-cm ‘cyst’ of the nose, just above the right alar crease, which was removed. Four years later, the lesion recurred and was re-excised. Histologically, a proliferation of mature adipocytes, ropey collagen fibers and spindle cells within a myxoid stroma was present in the subcutaneous tissue and infiltrated between skeletal muscle fibers. Nine cases of intramuscular spindle cell lipoma with histological examination have previously been reported and have involved the oral cavity and muscles of the extremities. To our knowledge, this is the first report of an infiltrating intramuscular spindle cell lipoma arising on the face. [ABSTRACT FROM AUTHOR]

Understanding the biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour biomarkers, prognostic factors and therapeutics. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells ( n = 10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) ( n = 22), malignant peripheral nerve sheath tumour (MPNST) cell lines ( n = 13), benign neurofibromas (NF) ( n = 26) and MPNST ( n = 6). Dermal and plexiform NFs were indistinguishable. A prominent theme in the analysis was aberrant differentiation. NFs repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes up-regulated in sarcomas were significantly enriched for genes activated in neural crest cells. We validated the differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in NF and MPSNT tissue sections and targeting SOX9 - strongly expressed in NF1-related tumours - caused MPNST cell death. SOX9 is a biomarker of NF and MPNST, and possibly a therapeutic target in NF1. [ABSTRACT FROM AUTHOR]