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Myxoma is a rare tumor that can be challenging to diagnose, with imaging findings that can be nonspecific. We present a case of a 21-year-old man who presented with a subacute history of right visual deterioration and proptosis. Imaging showed a large right superomedial orbital mass of 43 × 31 × 24 mm, which enhanced heterogeneously and was eroding the adjacent orbital roof and medial wall. An excisional biopsy was performed via a lid crease approach under transorbital endoscopic guidance. We review the clinical, radiological, and histological characteristics of myxoma. In addition, we highlight important associations with genetic syndromes including Carney complex and Mazabraud syndrome.
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AIMS: Amplification of the murine double minute-2 (MDM2) gene, which is usually detected with fluorescence in-situ hybridisation (FISH), is the key driving event for atypical lipomatous tumours (ALTs)/well-differentiated liposarcomas (WDLs). We sought to determine the concordance between the histopathological findings and MDM2 FISH in the diagnosis of ALT/WDL, and to identify the histological features of MDM2-amplified tumours lacking classic atypia. METHODS AND RESULTS: We performed a retrospective analysis of all mature lipomatous lesions subjected to MDM2 FISH analysis at our institution. MDM2 FISH analysis was performed on 439 mature lipomatous lesions: 364 (82.9%) were negative and 75 (17%) were positive. In 17 of 75 (22.6%) ALTs/WDLs, cytological atypia was not identified on initial histological assessment, thus favouring lipoma. On review, these cases shared common histological features, consisting of a very low number of relatively small stromal cells within the tumour lobules, with mildly coarse chromatin and oval nuclei, admixed with unremarkable adipocytes in a tumour background devoid of fibroconnective septa, areas of fibrosis, or blood vessels. These cells matched the cells in which FISH showed MDM2 amplification. In contrast, 13 cases (3.5%) regarded as suspicious for ALT/WDL on the basis of histology lacked MDM2 amplification and were reclassified following the FISH findings. CONCLUSIONS: We conclude that a subset of lipoma-like ALTs/WDLs are not associated with any of the features typically described in ALT/WDL. Our study also showed that tumours >100 mm are more likely to be ALT/WDL; however, a history of recurrence or concerning clinical/radiological features was not significantly associated with classification as ALT/WDL.
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Lipoma/metabolismo , Lipossarcoma/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Adulto , Idoso , Humanos , Hibridização in Situ Fluorescente , Lipoma/genética , Lipoma/patologia , Lipossarcoma/genética , Lipossarcoma/patologia , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-mdm2/genética , Estudos Retrospectivos , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologiaRESUMO
Multiple myeloma and its precursor and variant types represent some of the most common hematologic malignancies in adults. These plasma cell dyscrasias are well-known in modern medicine. There are well-established clinical, laboratory, and pathologic criteria for diagnosis and staging. There is debate about the diagnosis of some of the earliest cases of myeloma described in the literature. We present a critical review of one such case.
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Mieloma Múltiplo , Osteíte Fibrosa Cística , Adulto , Humanos , Mieloma Múltiplo/diagnósticoRESUMO
AIMS: Myxoid liposarcoma (MLPS) is characterised by DNA damage-inducible transcript 3 (DDIT3) gene rearrangements, confirmation of which is commonly used diagnostically. Recently, DDIT3 immunohistochemistry (IHC) has been reported to be highly sensitive and, when strict criteria are employed, specific for the diagnosis of MLPS. The aim of this study was to independently investigate DDIT3 IHC as a diagnostic marker for MLPS. METHODS AND RESULTS: DDIT3 IHC was performed on 52 MLPS and on 152 mimics on whole sections, and on 515 non-MLPS sarcomas in tissue microarray format. Only one MLPS (which had undergone acid-based decalcification) was completely negative. With inclusion of this case if any nuclear expression is considered to indicate positivity, the overall sensitivity of DDIT3 is 98% (51 of 52 cases) and the specificity is 94% (633 of 667 non-MLPS cases are negative). If a cut-off of >10% of neoplastic cells is required for positivity, then the sensitivity remains 98% (51/52) and the specificity is 98.5% (657 of 667 non-MLPS cases are negative). If a cut-off of >50% of cells is required for positivity, then the sensitivity is 96% (50 of 52 cases) but the specificity improves to 100%. CONCLUSIONS: Diffuse nuclear DDIT3 expression occurs in the overwhelming majority of MLPSs, and can be used to confirm the diagnosis in most cases without the need for molecular testing. A complete absence of expression argues strongly against MLPS, and almost completely excludes this diagnosis, particularly if there is consideration of technical factors such as decalcification. The significance of focal DDIT3 expression should be interpreted in the morphological and clinical context, although most tumours showing only focal expression are not MLPS.
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Biomarcadores Tumorais/metabolismo , Lipossarcoma Mixoide/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Fator de Transcrição CHOP/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Lipossarcoma Mixoide/patologia , Masculino , Pessoa de Meia-Idade , Sarcoma/diagnóstico , Sensibilidade e Especificidade , Neoplasias de Tecidos Moles/patologia , Fator de Transcrição CHOP/análiseRESUMO
Members of the International Skeletal Society compiled a glossary of terms for musculoskeletal radiology. The authors also represent national radiology or pathology societies in Asia, Australia, Europe, and the USA. We provide brief descriptions of musculoskeletal structures, disease processes, and syndromes and address their imaging features. Given the abundance of musculoskeletal disorders and derangements, we chose to omit most terms relating to neoplasm, spine, intervention, and pediatrics. Consensus agreement was obtained from 19 musculoskeletal radiology societies worldwide.
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Diagnóstico por Imagem/métodos , Doenças Musculoesqueléticas/diagnóstico por imagem , Terminologia como Assunto , Humanos , Internacionalidade , Sistema Musculoesquelético/diagnóstico por imagem , Sociedades MédicasRESUMO
PURPOSE: To examine the histologic properties of supercritical carbon dioxide (sCO2)-sterilized bone allograft for tunnel grafting and determine in vivo graft quality, as well as graft incorporation and remodeling, in 2-stage revision anterior cruciate ligament (ACL) surgery. METHODS: Histologic evaluation was performed in 12 subjects undergoing 2-stage revision ACL reconstruction. In the first stage, the femoral and tibial tunnels were debrided, tunnel dimensions were measured, and tunnels were grafted with sCO2-sterilized bone allograft. In the second stage, revision ACL reconstruction was performed and bone biopsy specimens were taken from the tibia. Tissue, bone, and graft volumes were measured, and histomorphometric analysis was performed. RESULTS: The mean time between the 2 stages was 8.8 months (range, 5.6-21.3 months). In the second stage, bone graft material was easily identified by its necrotic appearance comprising mature lamellar bone devoid of osteocyte nuclei within osteocyte lacunae. In all tissue samples, host-bone apposition of predominantly mature lamellar bone was noted on the surface of graft fragments in keeping with "creeping substitution." In several regions in 3 cases, osteoblastic and osteoclastic activity was evident in keeping with ongoing creeping substitution and remodeling. The mean bone volume over tissue volume was 68% (range, 33%-92%), and the mean graft volume over bone volume was 41% (range, 19%-70%). The mean graft volume (8 cases) harvested at less than 7 months (44%; 95% confidence interval, 31.4%-56.8%) was not significantly different than the mean graft volume (4 cases) harvested at greater than 10 months (34%; 95% confidence interval, 14.3%-54.2%; P = .214). CONCLUSIONS: The sCO2-sterilized bone allograft showed graft incorporation and remodeling through creeping substitution. CLINICAL RELEVANCE: The initial bone apposition and graft fragment bridging appear to provide a strong environment for ACL graft fixation resulting in technically successful 2-stage revision ACL reconstruction.
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Reconstrução do Ligamento Cruzado Anterior , Osso Esponjoso/patologia , Osso Esponjoso/transplante , Dióxido de Carbono , Esterilização/métodos , Aloenxertos , Artroscopia , Remodelação Óssea , Temperatura Alta , Humanos , ReoperaçãoRESUMO
AIMS: We recently identified the presence of Rosai-Dorfman-type histiocytes (RDH) in sinonasal tissue removed from individuals with eosinophilic chronic rhinosinusitis (ECR). We sought to determine their clinical significance. METHODS AND RESULTS: Sinonasal biopsies from 10 individuals (index cases) with classical features of ECR and the additional finding of RDH were collected during a two-and-a-half-year period. Twenty-one sinonasal biopsies with a diagnosis of ECR accrued during a 6-month period were reviewed at one institution to assess the presence of this phenomenon in archived material. Five of the 10 index cases were recurrent; in four of these in which archival material was available, three had RDH on review. Of the 21 review cases, 52% contained RDH. Six of the review cases represented recurrent disease and in five of these RDH were demonstrable. Archival material was available from five cases that recurred, RDH being demonstrable in three. RDH were seen to persist across multiple recurrences. CONCLUSIONS: The presence of RDH within ECR samples is associated highly with recurrence. RDH have properties of antigen-presenting cells and may play a hitherto unrecognized role in the initiation and persistence of ECR.
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Histiócitos/patologia , Rinite/patologia , Sinusite/patologia , Adulto , Idoso , Doença Crônica , Eosinofilia/patologia , Feminino , Histiocitose Sinusal , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The pathophysiologic mechanisms behind proliferation of fibroblasts and deposition of dense collagen matrix in idiopathic frozen shoulder remain unclear. Accumulation of advanced glycation end products (AGEs) with cross-linking and stabilization of collagen has been hypothesized to contribute to this pathophysiologic process. This study investigated whether the immunoreactivity of AGEs is higher in patients with idiopathic frozen shoulder than in the control groups. METHODS: Shoulder capsule samples were collected from 8 patients with idiopathic frozen shoulder, 6 with unstable shoulders (control 1), and 8 with rotator cuff tears (control 2). The samples were hematoxylin and eosin stained and analyzed by immunohistochemistry using antibodies against AGEs. Immunoreactivities were rated in a blinded fashion from none (0) to strong (3). Immunohistochemical distribution within the capsule was noted. RESULTS: Frozen shoulder patients had greater frequency and severity of self-reported pain (P = .02) than rotator cuff tear patients and more restricted range of motion in all planes (P < .05) than patients of the instability and rotator cuff tear groups. Hematoxylin and eosin-stained capsular tissue from frozen shoulder showed fibroblastic proliferation, increased numbers of adipocytes, and increased subsynovial vascularity. Immunoreactivity of AGEs was stronger in frozen shoulder capsules (2.8) than in instability (0.3; P = .0001) and rotator cuff tear (1.1; P = .016) capsules. CONCLUSION: This study highlights a potential role for AGEs in the pathogenesis of frozen shoulder. The overexpression of AGEs may explain the fibroblastic proliferation and deposition of collagen matrix in idiopathic frozen shoulder. LEVEL OF EVIDENCE: Basic Science Study; Histology.
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Bursite/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Instabilidade Articular/metabolismo , Lesões do Manguito Rotador/metabolismo , Articulação do Ombro/metabolismo , Adipócitos , Adolescente , Adulto , Idoso , Bursite/patologia , Bursite/fisiopatologia , Estudos de Casos e Controles , Contagem de Células , Proliferação de Células , Feminino , Fibroblastos/fisiologia , Produtos Finais de Glicação Avançada/imunologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Amplitude de Movimento Articular , Lesões do Manguito Rotador/fisiopatologia , Articulação do Ombro/fisiopatologia , Dor de Ombro/etiologia , Adulto JovemRESUMO
Paget's sarcoma is a rare complication of Paget's disease and isolated Paget's disease of the patella is extremely rare. We describe a unique case of Paget's sarcoma of the patella in a 69-year-old male farmer who had a remote history of a fracture in the same patella 40 years previously. In this case, imaging and pathogenesis of Paget's disease of bone is described and factors implicated in the development of Paget's disease in this patient are evaluated.
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Neoplasias Ósseas/diagnóstico , Osteíte Deformante/diagnóstico , Patela/patologia , Sarcoma/diagnóstico , Idoso , Neoplasias Ósseas/etiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Osteíte Deformante/complicações , Patela/diagnóstico por imagem , Sarcoma/etiologia , Tomografia Computadorizada por Raios X/métodosRESUMO
Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumour of intermediate (rarely metastasising) malignant potential, which harbours EWSR1/FUS gene fusions. These tumours can express anaplastic lymphoma kinase (ALK) in the absence of gene rearrangement or copy number alteration and can also coexpresses Pan-TRK immunohistochemistry (IHC). All EWSR1/FUS-rearranged AFH were retrieved from the files of three institutions and Pan-TRK (EPR17341), ALK and BRAF V600E IHC were performed. Fourteen AFH cases were identified, which included three cases of intracranial mesenchymal tumours with FET-CREB fusions. PanTRK and ALK positive immunostaining was identified in 9 (64.2%) and 12 (85.7%) cases, respectively. No NTRK or ALK translocations or increased copy number/amplification were identified in all eight cases which had fluorescence in situ hybridisation and/or next generation sequencing for NTRK1-3 and ALK available for assessment. None of the cases expressed BRAF-V600E.Although our study is limited, our report is the first to document PanTRK expression in AFH in the absence of identifiable NTRK1-3 gene alterations.
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Neoplasias Encefálicas , Histiocitoma Fibroso Benigno , Histiocitoma Fibroso Maligno , Humanos , Histiocitoma Fibroso Benigno/genética , Proteínas Proto-Oncogênicas B-raf/genética , Histiocitoma Fibroso Maligno/genética , Histiocitoma Fibroso Maligno/patologia , Neoplasias Encefálicas/patologia , Rearranjo Gênico , Receptores Proteína Tirosina Quinases/genéticaRESUMO
Introduction. Epithelioid hemangioma is a benign vascular neoplasm associated with FOS and/or FOSB protein overexpression detected by immunohistochemistry (IHC). Methods. The aim of our study was to determine the co-expression or independent IHC expression of FOS and FOSB in a cohort of epithelioid hemangiomas. We also included two cohorts of other vascular lesions: papillary endothelial hyperplasia and lobular capillary hemangioma / pyogenic granuloma. Results. We identified 50 cases of epithelioid hemangioma, 84% of which were cutaneous and the remaining involved other anatomic locations. Over two thirds of all cases expressed FOSB (68%; 34/50) while FOS immunoreactivity was identified in 46% of all cases. Co-expression of FOSB and FOS occurred in 37% of cases while 76% of all cases stained for at least one of the antibodies. Fifty-eight percent (n = 14/24) and 33% (8/24) of all cases of papillary endothelial hyperplasia expressed FOS and FOSB, respectively. Thirty-two per cent of lobular capillary hemangiomas (n = 8/25) were positive for either FOS or FOSB. Conclusion. In summary, we present the largest cohort of epithelioid hemangiomas assessed with both FOS and FOSB and demonstrated that the use of both antibodies increases the detection rate of these proliferations by 10%. Nonetheless, the use of thresholds may not be appropriate, as only a subset of lesional endothelial cells label with FOS/FOSB. Over half of all cases of papillary endothelial hyperplasia and a third of lobular capillary hemangiomas also displayed immunoreactivity with FOS and/or FOSB.
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Granuloma Piogênico , Hemangioma Capilar , Hemangioma , Neoplasias Vasculares , Humanos , Imuno-Histoquímica , Hiperplasia/patologia , Células Endoteliais/patologia , Hemangioma/diagnóstico , Granuloma Piogênico/patologia , Neoplasias Vasculares/patologia , Hemangioma Capilar/patologia , Proteínas Proto-Oncogênicas c-fosRESUMO
Our aim was to utilise a 241-gene RNA hybridisation capture sequencing (CaptureSeq) gene panel to identify unexpected fusions in undifferentiated, unclassified or partly classified sarcomas of young individuals (<40 years). The purpose was to determine the utility and yield of a large, targeted fusion panel as a tool for classifying tumours that do not fit typical diagnostic entities at the time of the original diagnosis. RNA hybridisation capture sequencing was performed on 21 archival resection specimens. Successful sequencing was obtained in 12 of 21 samples (57%), two of which (16.6%) harboured translocations. A novel NEAT1::GLI1 fusion, not previously reported in the literature, presented in a young patient with a tumour in the retroperitoneum, which displayed low grade epithelioid cells. The second case, a localised lung metastasis in a young male, demonstrated a EWSR1::NFATC2 translocation. No targeted fusions were identified in the remaining 83.4% (n=10) of cases. Forty-three per cent of the samples failed sequencing as a result of RNA degradation. RNA-based sequencing is an important tool, which helps to redefine the classification of unclassified or partly classified sarcomas of young adults by identifying pathogenic gene fusions in up to 16.6% of the cases. Unfortunately, 43% of the samples underwent significant RNA degradation, falling below the sequencing threshold. As CaptureSeq is not yet available in routine pathology practice, increasing awareness of the yield, failure rate and possible aetiological factors for RNA degradation is fundamental to maximise laboratory procedures to improve RNA integrity, allowing the potential identification of significant gene alterations in solid tumours.
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Sarcoma , Neoplasias de Tecidos Moles , Adulto Jovem , Humanos , Masculino , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologia , Fusão Gênica , Fatores de Transcrição/genética , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Rearranjo Gênico , Proteínas de Fusão Oncogênica/genéticaRESUMO
A 71-year-old man was referred for evaluation of incidental generalized osteosclerosis. He was found to have a high bone mass (HBM) with an elevated lumbar spine bone mineral density (BMD) Z-score of +5.3. Over an 18-month period, his lumbar spine BMD measured by dual energy X-ray absorptiometry (DXA) had increased by +64% from 1.09 to 1.79 g/cm2 and femoral neck by +21% from 0.83 to 1.01 g/cm2. Biochemical markers of bone turnover were markedly increased (serum propeptide of type 1 collagen and urine telopeptides greater than 10-times normal). The high bone formation and increased skeletal calcium acquisition resulted in profound hypocalcemia (low serum calcium 1.88 mmol/L) and hypocalciuria (low urinary calcium <0.2 mmol/day). Positron emission tomography (PET) with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (FDG) confirmed diffuse osteosclerosis without focal areas of abnormal FDG uptake in the skeleton or elsewhere to suggest either an underlying primary malignancy or metastatic disease. Bone biopsy showed markedly sclerotic woven and lamellar bone. The marrow space was devoid of typical bone cells and adipocytes and instead was filled by fibromyxoid stroma, infiltrated by small clusters of tumor cells. Bone histomorphometry and micro-computed tomography demonstrated an elevated trabecular bone volume and trabecular plate thickness. The bone disorder in this case is unique and raises the possibility of a new yet undefined novel anabolic paracrine factor (or factors) secreted by an adenocarcinoma of unknown primary that resulted in dramatic increases in BMD, HBM, and radiological osteosclerosis. The differential diagnosis and potential mechanisms responsible for the HBM are discussed. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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PURPOSE: The phase III, open-label, prospective, multicenter, randomized Ewing 2008R1 trial (EudraCT2008-003658-13) was conducted in 12 countries to evaluate the effect of zoledronic acid (ZOL) maintenance therapy compared with no add-on regarding event-free survival (EFS, primary endpoint) and overall survival (OS) in standard-risk Ewing sarcoma (EWS). PATIENTS AND METHODS: Eligible patients had localized EWS with either good histologic response to induction chemotherapy and/or small tumors (<200 mL). Patients received six cycles of VIDE induction and eight cycles of VAI (male) or eight cycles of VAC (female) consolidation. ZOL treatment started parallel to the sixth consolidation cycle. Randomization was stratified by tumor site (pelvis/other). The two-sided adaptive inverse-normal four-stage design (planned sample size 448 patients, significance level 5%, power 80%) was changed after the first interim analysis using the Müller-Schäfer method. RESULTS: Between April 2010 and November 2018, 284 patients were randomized (142 ZOL/142 no add-on). With a median follow-up of 3.9 years, EFS was not significantly different between ZOL and no add-on group in the adaptive design (HR, 0.74; 95% CI, 0.43-1.28, P = 0.27, intention-to-treat). Three-year EFS rates were 84.0% (95% CI, 77.7%-90.8%) for ZOL vs. 81.7% (95% CI, 75.2%-88.8%) for no add-on. Results were similar in the per-protocol collective. OS was not different between groups. The 3-year OS was 92.8% (95% CI, 88.4%-97.5%) for ZOL and 94.6% (95% CI, 90.9%-98.6%) for no add-on. Noticeable more renal, neurologic, and gastrointestinal toxicities were observed for ZOL (P < 0.05). Severe renal toxicities occurred more often in the ZOL arm (P = 0.003). CONCLUSIONS: In patients with standard-risk localized EWS, there is no additional benefit from maintenance treatment with ZOL.
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Neoplasias Ósseas , Sarcoma de Ewing , Humanos , Masculino , Feminino , Sarcoma de Ewing/patologia , Ácido Zoledrônico/uso terapêutico , Estudos Prospectivos , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/patologiaRESUMO
BACKGROUND: Our understanding of the pathogenesis of frozen shoulder and why it is so painful is undetermined. This study investigated the expression of neuronal proteins in the capsular tissue of frozen shoulder. METHODS: Shoulder capsular samples were collected from 8 patients with idiopathic adhesive capsulitis and 10 patients with a rotator cuff tear but no stiffness (controls). Samples were analyzed by immunohistochemistry using antibodies against protein gene product 9.5 (PGP9.5), a general nerve marker; growth associated protein 43 (GAP43), a nerve growth marker; nerve growth factor receptor p75; and CD34, an endothelial cell marker. RESULTS: Samples from frozen shoulders showed subsynovial hypercellularity and fibroblastic proliferation, with increased expression of nerve growth factor receptor p75 and CD34 compared with controls. Nerves positive for PGP9.5 and GAP43 were more abundant in samples of frozen shoulder (2.8 ± 0.2 and 2.4 ± 0.4 per field; P < .01) compared with controls (1.6 ± 0.3 and 1.3 ± 0.3 per field; P < .05). Expression of neuronal proteins followed that of CD34. CONCLUSION: Increased expression of nerve growth factor receptor and new nerve fibers were found in the shoulder capsular tissue of patients with frozen shoulder compared with those without a frozen shoulder. These data suggest that neoinnervation and neoangiogenesis in the shoulder capsule are important events in the pathogenesis of frozen shoulder and may help explain the often-severe pain of patients with frozen shoulder.
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Antígenos CD34/biossíntese , Bursite/metabolismo , Proteína GAP-43/biossíntese , Fator de Crescimento Neural/biossíntese , Receptor de Fator de Crescimento Neural/biossíntese , Articulação do Ombro/metabolismo , Ubiquitina Tiolesterase/biossíntese , Adulto , Idoso , Anticorpos/análise , Antígenos CD34/imunologia , Bursite/patologia , Feminino , Proteína GAP-43/imunologia , Humanos , Imuno-Histoquímica , Cápsula Articular/metabolismo , Cápsula Articular/patologia , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Neural/imunologia , Prognóstico , Receptor de Fator de Crescimento Neural/imunologia , Articulação do Ombro/patologia , Ubiquitina Tiolesterase/imunologiaRESUMO
MYC over-expression by immunohistochemistry (IHC) is utilised in routine pathology practice as a surrogate marker for MYC amplification, which plays a key oncogenic role in post-irradiation and chronic lymphedema-associated angiosarcoma. We present the case of a 32-year old male, who presented with high-grade angiosarcoma arising in a background of metastatic testicular teratoma. IHC for MYC showed strong nuclear expression in the angiosarcoma cells prompting the consideration of post-irradiation-induced angiosarcoma but our patient did not undergo radiotherapy. Fluorescence in-situ hybridization (FISH) excluded MYC amplification and instead showed Chromosome 8 polysomy, which accounted for the strong MYC IHC expression present, not previously described in the context of germ cell tumours. The occurrence of MYC over-expression due to polysomy illustrates a novel clinical scenario (angiosarcoma arising as somatic malignancy) where strong MYC IHC expression can be found in the absence of underlying amplification or prior radiotherapy exposure.
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Hemangiossarcoma , Segunda Neoplasia Primária , Teratoma , Cromossomos Humanos Par 8/genética , Cromossomos Humanos Par 8/metabolismo , Amplificação de Genes , Hemangiossarcoma/genética , Hemangiossarcoma/patologia , Humanos , Masculino , Segunda Neoplasia Primária/genética , Proteínas Proto-Oncogênicas c-myc/genética , Teratoma/genéticaRESUMO
CIC-rearranged sarcoma is a recently established, ultra-rare, molecularly defined sarcoma subtype. We aimed to further characterise clinical features of CIC-rearranged sarcomas and explore clinical management including systemic treatments and outcomes. METHODS: A multi-centre retrospective cohort study of patients diagnosed between 2014-2019. RESULTS: Eighteen patients were identified. The median age was 27 years (range 13-56), 10 patients were male (56%), 11 patients (61%) had localised disease and 7 patients had advanced (metastatic or unresectable) disease at diagnosis. Of 11 patients with localised disease at diagnosis, median overall survival (OS) was 40.6 months and the 1-, 2- and 5-year OS estimates were 82%, 64% and 34% respectively. Nine patients (82%) underwent surgery (all had R0 resections), 8 (73%) patients received radiotherapy to the primary site (median dose 57Gy in 28 fractions), and 8 (73%) patients received chemotherapy (predominantly Ewing-based regimens). Metastases developed in 55% with a median time to recurrence of 10.5 months. In patients with advanced disease at diagnosis, median OS was 12.6 months (95% CI 5.1-20.1), 1-year OS was 57%. Median progression-free survival was 5.8 months (95% CI 4.5-7.2). Durable systemic therapy responses occurred infrequently with a median duration of systemic treatment response of 2.1 months. One durable complete response of metastatic disease to VDC/IE chemotherapy was seen. Responses to pazopanib (n = 1) and pembrolizumab (n = 1) were not seen. CONCLUSION: In this series, CIC-rearranged sarcomas affected young adults and had a high incidence of presenting with, or developing, metastatic disease. The prognosis overall was poor. In advanced disease, durable systemic therapy responses were infrequent.
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Sarcoma de Células Pequenas , Sarcoma , Neoplasias de Tecidos Moles , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcoma/genética , Sarcoma/patologia , Sarcoma/terapia , Sarcoma de Células Pequenas/patologia , Adulto JovemRESUMO
PURPOSE: Ewing 2008R3 was conducted in 12 countries and evaluated the effect of treosulfan and melphalan high-dose chemotherapy (TreoMel-HDT) followed by reinfusion of autologous hematopoietic stem cells on event-free survival (EFS) and overall survival in high-risk Ewing sarcoma (EWS). METHODS: Phase III, open-label, prospective, multicenter, randomized controlled clinical trial. Eligible patients had disseminated EWS with metastases to bone and/or other sites, excluding patients with only pulmonary metastases. Patients received six cycles of vincristine, ifosfamide, doxorubicin, and etoposide induction and eight cycles of vincristine, actinomycin D, and cyclophosphamide consolidation therapy. Patients were randomly assigned to receive additional TreoMel-HDT or no further treatment (control). The random assignment was stratified by number of bone metastases (1, 2-5, and > 5). The one-sided adaptive-inverse-normal-4-stage-design was changed after the first interim analysis via Müller-Schäfer method. RESULTS: Between 2009 and 2018, 109 patients were randomly assigned, and 55 received TreoMel-HDT. With a median follow-up of 3.3 years, there was no significant difference in EFS between TreoMel-HDT and control in the adaptive design (hazard ratio [HR] 0.85; 95% CI, 0.55 to 1.32, intention-to-treat). Three-year EFS was 20.9% (95% CI, 11.5 to 37.9) in TreoMel-HDT and 19.2% (95% CI, 10.8 to 34.4) in control patients. The results were similar in the per-protocol collective. Males treated with TreoMel-HDT had better EFS compared with controls: median 1.0 years (95% CI, 0.8 to 2.2) versus 0.6 years (95% CI, 0.5 to 0.9); P = .035; HR 0.52 (0.28 to 0.97). Patients age < 14 years benefited from TreoMel-HDT with a 3-years EFS of 39.3% (95% CI, 20.4 to 75.8%) versus 9% (95% CI, 2.4 to 34); P = .016; HR 0.40 (0.19 to 0.87). These effects were similar in the per-protocol collective. This observation is supported by comparable results from the nonrandomized trial EE99R3. CONCLUSION: In patients with very high-risk EWS, additional TreoMel-HDT was of no benefit for the entire cohort of patients. TreoMel-HDT may be of benefit for children age < 14 years.