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Clinical outcome data in the United Kingdom, Europe, and the United States have yet to facilitate appropriately specific surveillance for liposarcoma histological subtypes, despite being one of the most common soft tissue sarcomas. Therefore, this study aims to demonstrate histologic-specific differences in liposarcoma recurrence, disease progression, and survival and discuss the implications.This cohort study involves patients from a regional sarcoma service in the UK who have had a primary surgical excision of liposarcoma between October 2002 and September 2019. The median follow-up is five years. Confirmed histopathological diagnoses of liposarcoma (n = 193) are organised according to the World Health Organisation recognised subtypes: atypical lipomatous tumours (ALT), myxoid, pleomorphic, and dedifferentiated liposarcomas. In addition, retroperitoneal variants (n = 34) are included to illustrate the broader spectrum of phenotypes. The primary outcomes were local recurrence, distant disease progression, and disease-specific death, and compared using Kaplan-Meier analyses and tumour variables using Cox proportional hazard analyses. All three primary outcomes significantly differed (P0.0001, n = 193). There were no metastases or disease-specific death in patients with ALT (n = 92) and no metastases of their retroperitoneal counterparts (n = 17). Amongst the metastasising cases of rarer subtypes, there were pulmonary spread of pleomorphic (8/9, n = 20), dedifferentiated (4/5, n = 18), and myxoid (2/3, n = 29) liposarcomas.An absence of metastases of ALT should be considered alongside global evidence. Surveillance protocols could better differentiate between these subtypes and, in doing so, save patients a considerable amount of irradiation, time, fear, and anxiety.

Spindle cell lipoma, cellular angiofibroma and mammary myofibroblastoma are mesenchymal tumours that have overlapping morphological and immunophenotypic features. Aberrations in chromosome 13q14 have been identified as a recurrent feature. We report a unique case of a 69-year-old woman who metachronously developed all three tumours. She developed a peri-urethral and a recurrent peri-vaginal cellular angiofibroma at age 54 and 57, respectively, a spindle cell lipoma at age 62 and a mammary myofibroblastoma at age 69. Dual-colour interphase fluorescent in situ hybridisation (FISH) revealed losses of RB1 and FOXO1 (13q14LOH [loss of heterozygosity]) within neoplastic cells. There was also loss of retinoblastoma (Rb) protein expression. To our knowledge, this is the first report of these three tumours arising in the same patient. The genetic link between these tumours supports the hypothesis that they may arise from the same progenitor cells. However, further research is required to elucidate the precise pathogenetic link.

Paediatric dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue malignant tumour which displays aggressive local behaviour and has low metastatic potential. The diagnosis is often delayed as DFSP is usually mistaken for other skin conditions, particularly in the early stages of disease. DFSP tends to follow an indolent course after the initial presentation with what is often described as a "rubbery lump". As the disease progresses, the lump tends to enlarge, change colour, and exhibit a more nodular consistency. In rare cases, DFSP can present as an ulcerated exophytic lesion or a depressed area of skin, making diagnosis even more challenging. A high index of suspicion is warranted for early diagnosis, and referral to a specialist unit with expertise in both oncologic resection and reconstruction. DFSP tumours arise from the dermis and grow with finger-like projections. Therefore, in cosmetically sensitive or functionally important locations, an excision and analysis technique that assesses all excision margins is the gold standard of care. Slow Mohs technique performed with en bloc excision is a well-tolerated option for oncologic resection of the tumour. Mohs technique can also be considered but can be challenging in children for reasons explained below. As an alternative, depending on the anatomical location, tumours can be excised with a wide local excision. While an excision technique that incorporates the deep fascia with a 3-cm peripheral margin is acceptable in adults, planning of the excision margin in children should involve consideration of preoperative imaging with MRI, site of the tumour, age, and physical built of the child. Patients should be offered all treatment options considering the local outcomes, available expertise, and cost. A multidisciplinary approach and good communication between team members is crucial. Close collaboration with a pathologist who is familiar with sectioning technique that allows margin control is of paramount importance. Soft tissue reconstruction should be performed immediately after oncologic clearance, although a staged approach may be required. Adjuvant radiotherapy should be avoided in children due to the long-term risk of secondary malignancies and potential for growth disruption.

OBJECTIVE: Glomus coccygeum is a glomus body which is found in the pericoccygeal soft tissue. This specialised arteriovenous anastomosis is a non-pathological vestigial structure usually larger than its equivalent in the distal extremities. Its prevalence is uncertain. Glomus coccygeum has been associated with coccygodynia and can cause diagnostic problems to pathologists unfamiliar with this entity. MATERIALS AND METHODS: The presence of a glomus coccygeum was sought in 40 coccygectomy specimens and correlated with clinical, radiological and histological findings. RESULTS: A glomus coccygeum was identified in 13 samples (35%). Glomus cells expressed smooth muscle actin (SMA) and were negative for desmin, S100, cytokeratin and a wide range of vascular markers. Proliferative activity was low. Pre-operative MRI did not identify these tiny lesions, and most patients with coccygodynia did not have a glomus coccygeum. CONCLUSION: Glomus coccygeum is a common microanatomical structure which can be distinguished from glomus and other tumours by its small size, SMA expression and low proliferative activity.

Somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 occur in gliomas and acute myeloid leukaemia (AML). Since patients with multiple enchondromas have occasionally been reported to have these conditions, we hypothesized that the same mutations would occur in cartilaginous neoplasms. Approximately 1200 mesenchymal tumours, including 220 cartilaginous tumours, 222 osteosarcomas and another ∼750 bone and soft tissue tumours, were screened for IDH1 R132 mutations, using Sequenom(®) mass spectrometry. Cartilaginous tumours and chondroblastic osteosarcomas, wild-type for IDH1 R132, were analysed for IDH2 (R172, R140) mutations. Validation was performed by capillary sequencing and restriction enzyme digestion. Heterozygous somatic IDH1/IDH2 mutations, which result in the production of a potential oncometabolite, 2-hydroxyglutarate, were only detected in central and periosteal cartilaginous tumours, and were found in at least 56% of these, ∼40% of which were represented by R132C. IDH1 R132H mutations were confirmed by immunoreactivity for this mutant allele. The ratio of IDH1:IDH2 mutation was 10.6 : 1. No IDH2 R140 mutations were detected. Mutations were detected in enchondromas through to conventional central and dedifferentiated chondrosarcomas, in patients with both solitary and multiple neoplasms. No germline mutations were detected. No mutations were detected in peripheral chondrosarcomas and osteochondromas. In conclusion, IDH1 and IDH2 mutations represent the first common genetic abnormalities to be identified in conventional central and periosteal cartilaginous tumours. As in gliomas and AML, the mutations appear to occur early in tumourigenesis. We speculate that a mosaic pattern of IDH-mutation-bearing cells explains the reports of diverse tumours (gliomas, AML, multiple cartilaginous neoplasms, haemangiomas) occurring in the same patient.

Extramammary-type myofibroblastoma is a rare, benign spindle cell lesion, strictly resembling the breast counterpart, but occurring in extramammary sites, mainly in the inguinal/groin area. In this paper, we describe an extramammary-type myofibroblastoma in the groin of a 37-year-old male patient. The tumor showed a typical morphological and immunophenotypical profile, including staining for both CD34 and desmin. Dual-color interphase florescent in situ hybridization analysis revealed losses of RB/13q14 and FKHR/13q14 loci within tumor cells. The chromosome 13 rearrangements associated with the loss of the 13q14 chromosomal region are typically seen in spindle cell lipoma, and have been previously recognized in mammary myofibroblastoma, providing strong evidence for a pathogenetic link between these lesions.

Background: Tissue necrosis and a macrophage and perivascular lymphocytic infiltrate are commonly seen in periprosthetic tissues around metal-on-metal hip resurfacing implants, including pseudotumors associated with these implants. The purpose of the present study was to correlate pathological changes in periprosthetic tissues with clinical findings and the amount of implant-derived metal wear. Methods: We analyzed morphological changes in the periprosthetic soft tissues around fifty-six failed metal-on-metal hip resurfacing implants. The most common reason for failure was the presence of a symptomatic pseudotumor (n = 45). The extent of necrosis and the nature of the inflammatory cell infiltrate, including aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL), was evaluated semiquantitatively. Bearing surface wear was determined for all patients. Prostheses were considered to be highly worn if the total linear wear rate was ≥4 μm/yr. Results: Substantial necrosis and a heavy macrophage infiltrate were noted in most periprosthetic tissues, including all pseudotumors, many of which contained a prominent ALVAL infiltrate. Most pseudotumors (80%) were associated with highly worn prostheses. It was noted that the extent of necrosis and macrophage infiltration correlated with the volume of generated metal wear. Although increased wear volume moderately correlated with a high ALVAL response, all pseudotumors associated with low wear had a strong ALVAL response. Conclusions: The majority of pseudotumors are associated with increased implant wear. This increased wear is associated with soft-tissue necrosis and a heavy nonspecific foreign-body macrophage response coupled with a variable adaptive or specific immune response (ALVAL). A minority of pseudotumors are associated with low wear and a prominent immune response. These findings confirm that minimizing wear from metal-on-metal hip resurfacing arthroplasty prostheses would lead to a reduction in the incidence of pseudotumor. However, a small number of pseudotumors are still likely to occur, which may be due to an exacerbated adaptive immune response. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2013 by The Journal of Bone and Joint Surgery, Incorporated.

Aim Osteoclasts are multinucleated cells which are specialised to carry out lacunar bone resorption. Osteoclasts form part of the mononuclear phagocyte system, and immunophenotypic criteria for distinction from macrophage polykaryons include expression of CD51 (vitronectin receptor) and absence of HLA-DR and CD14. Methods The expression of CD14, CD163, HLA-DR and CD51 in formalin-fixed paraffin-embedded sections of normal bone and neoplastic and non-neoplastic lesions of bone and soft tissue known to contain osteoclasts and macrophage polykaryons respectively was assessed immunohistochemically; the immunophenotype of osteoclast-like giant cells in a wide range of giant cell-containing bone lesions was similarly assessed. Results Both osteoclasts and macrophage polykaryons were found to express CD51. Macrophage polykaryons, but not osteoclasts, expressed CD14 and HLA-DR. CD51+/CD14−/HLA-DR-/CD163– giant cells were noted in all giant-cell lesions of bone, including giant cell tumour of bone, aneurysmal bone cyst, non-ossifying fibroma, chondroblastoma, telangiectatic osteosarcoma, chondromyxoid fibroma, Langerhans cell histiocytosis and brown tumour. Conclusion Our findings indicate that CD51 expression alone is not sufficient for immunocytochemical identification of osteoclasts, which do not express the macrophage-associated antigens CD14 and HLA-DR. Giant cells in most giant cell-rich lesions of bone have an osteoclast phenotype, suggesting that they are formed from mononuclear phagocyte osteoclast precursors.

Background Chordomas are rare neoplasms, arising from notochordal remnants in the midline skeletal axis, for which the current treatment is limited to surgery and radiotherapy. Recent reports suggest that receptor tyrosine kinases (RTK) might be essential for the survival or proliferation of chordoma cells, providing a rationale for RTK targeted therapy. Nevertheless, the reported data are conflicting, most likely due to the assorted tumor specimens used for the studies and the heterogeneous methodological approaches. In the present study, we performed a comprehensive characterization of this rare entity using a wide range of assays in search for relevant therapeutic targets. Methods Histopathological features of 42 chordoma specimens, 21 primary and 21 advanced, were assessed by immunohistochemistry and fluorescent in situ hybridization (FISH) using PDGFRB, CSF1R, and EGFR probes. Twenty-two of these cases, for which frozen material was available (nine primary and 13 advanced tumors), were selectively analyzed using the whole-genome 4.3 K TK-CGH-array, phospho-kinase antibody array or Western immunoblotting. The study was supplemented by direct sequencing of KIT, PDGFRB, CSF1R and EGFR. Results We demonstrated that EGFR is frequently and the most significantly activated RTK in chordomas. Furthermore, concurrent to EGFR activation, the tumors commonly reveal co-activation of alternative RTK. The consistent activation of AKT, the frequent loss of the tumor suppressor PTEN allele, the recurrent activation of upstream RTK and of downstream effectors like p70S6K and mTOR, all indicate the PI3K/AKT pathway as an important mediator of transformation in chordomas. Conclusions Given the complexity of the signaling in chordomas, combined treatment regimens targeting multiple RTK and downstream effectors are likely to be the most effective in these tumors. Personalized therapy with careful selection of the patients, based on the molecular profile of the specific tumor, is anticipated.

Somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 occur in gliomas and acute myeloid leukaemia (AML). Since patients with multiple enchondromas have occasionally been reported to have these conditions, we hypothesized that the same mutations would occur in cartilaginous neoplasms. Approximately 1200 mesenchymal tumours, including 220 cartilaginous tumours, 222 osteosarcomas and another ∼750 bone and soft tissue tumours, were screened for IDH1 R132 mutations, using Sequenom(®) mass spectrometry. Cartilaginous tumours and chondroblastic osteosarcomas, wild-type for IDH1 R132, were analysed for IDH2 (R172, R140) mutations. Validation was performed by capillary sequencing and restriction enzyme digestion. Heterozygous somatic IDH1/IDH2 mutations, which result in the production of a potential oncometabolite, 2-hydroxyglutarate, were only detected in central and periosteal cartilaginous tumours, and were found in at least 56% of these, ∼40% of which were represented by R132C. IDH1 R132H mutations were confirmed by immunoreactivity for this mutant allele. The ratio of IDH1:IDH2 mutation was 10.6 : 1. No IDH2 R140 mutations were detected. Mutations were detected in enchondromas through to conventional central and dedifferentiated chondrosarcomas, in patients with both solitary and multiple neoplasms. No germline mutations were detected. No mutations were detected in peripheral chondrosarcomas and osteochondromas. In conclusion, IDH1 and IDH2 mutations represent the first common genetic abnormalities to be identified in conventional central and periosteal cartilaginous tumours. As in gliomas and AML, the mutations appear to occur early in tumourigenesis. We speculate that a mosaic pattern of IDH-mutation-bearing cells explains the reports of diverse tumours (gliomas, AML, multiple cartilaginous neoplasms, haemangiomas) occurring in the same patient.

The Authors report on two cases of small bowel stromal tumours and underline more recent findings regard to histogenesis, etiopathogenesis and classification as well examine the problems related to diagnosis, surgical management and prognosis of these pathology.At present, surgical treatment is the best therapy even in patients with local relapse and/or metastasis. Whereas in unresectable patients a new therapeutic possibility is given to the use of Imatinib mesylate, nevertheless is still to prove its effectiveness in regard to survival or as adyuvant treatment in resectable patients with high risk of relapse.

In 1996, 10 years after Chernobyl accident, a cytogenetic analysis was carried out to assess whether chromosome aberrant cells (CA) were still detectable in the lymphocytes and clastogenic factors (CFs) were present in the plasma of children coming from Gomel (Belarus), one of the most heavily contaminated regions. Furthermore, the possible contribution of plasmatic CFs to the amount of CA was investigated. The presence of CA was examined in the lymphocytes from 29 thyroid tumour-affected children and 41 healthy children (local controls). Thirty healthy children living in Pisa (Italy) were enrolled in the study as additional controls from an uncontaminated area. No significant difference was observed between the two control groups, whereas a significantly increased frequency of CA was found in the tumour-affected children, as compared with Gomel and Pisa controls (chi 2-test, p0.001). However, when soil contamination level was taken into account, the chromosome type CA frequency observed in tumour-affected children coming from the more contaminated areas (4 Ci/km2) resulted significantly higher than that in other children, either affected or not (p = 0.003). The presence of CFs was analyzed on the plasma ultrafiltrate from 41 children. 7/10 (70%) plasma samples from tumour-affected children and 17/23 (74%) Gomel controls resulted to possess clastogenic activity irrespective of soil contamination levels. No activity was detected in the plasma of eight Pisa controls (0%). The difference between both Gomel groups and Pisa controls was highly significant (p = 0.002). A borderline, but not statistically significant correlation (p = 0.08) was observed between basal CA frequency and CF potency, which became significant (p = 0.03) when only chromosome type of aberrations was considered. We conclude that, although the presence of CFs in the plasma of these children might be partly responsible of the cytogenetic effects observed, the main source of damage has considered to be do to the previous and/or continuous exposure to environmental radiocontaminants. Tumour-affected children may represent a subset of the population either more sensitive to clastogenic damage or exposed to higher levels of contaminants.