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1.
Cytopathology ; 35(1): 149-152, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37688410

RESUMO

Mesenchymal chondrosarcoma (MC) is a rare but extremely aggressive type of chondrosarcoma distinguished by the presence of both primitive mesenchymal cells and fully developed chondroid tissue. The identification of a biphasic morphology in pleural effusion, along with detection of the HEY1::NCOA2 fusion using next-generation sequencing, serve as vital indicators for an accurate diagnosis.


Assuntos
Neoplasias Ósseas , Condrossarcoma Mesenquimal , Derrame Pleural , Humanos , Condrossarcoma Mesenquimal/diagnóstico , Condrossarcoma Mesenquimal/genética , Condrossarcoma Mesenquimal/metabolismo , Imuno-Histoquímica , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Ciclo Celular , Sequenciamento de Nucleotídeos em Larga Escala , Coativador 2 de Receptor Nuclear/metabolismo
2.
Asian J Endosc Surg ; 16(4): 795-799, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37574440

RESUMO

Mesenchymal chondrosarcoma is a rare subset of sarcomas accounting for 3%-10% of all cases of chondrosarcomas. Radical resection is the only curative strategy, even in patients with metastatic tumors. However, data regarding treatment strategies remain limited owing to the small number of cases. Herein, we report a patient who underwent repeated robotic pancreatectomy for recurrent pancreatic metastasis originating from extraskeletal mesenchymal chondrosarcoma of the pelvis. First, robotic pancreaticoduodenectomy with a reconstruction of pancreaticogastrostomy was performed for synchronous pancreatic metastasis 5 months after the primary resection of mesenchymal chondrosarcoma. Ten months after robotic pancreaticoduodenectomy, tumor recurrence was observed at the tail end of the pancreas, which was removed by reperforming robotic distal pancreatectomy. Given the precise tissue manipulation that can be achieved with robotic articulated forceps, the peripheral splenic artery and pancreas were easily isolated and divided in close proximity to the tumor. The central part of the pancreas was preserved. Robotic surgery allowed safe and effective resection of the reconstructed remnant pancreas. The patient survived for 28 months after primary tumor resection. Repeated pancreatectomy with minimally invasive techniques is a feasible and curative treatment for metastatic mesenchymal chondrosarcoma.


Assuntos
Condrossarcoma Mesenquimal , Segunda Neoplasia Primária , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Condrossarcoma Mesenquimal/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/métodos , Segunda Neoplasia Primária/cirurgia
3.
Cancer Rep (Hoboken) ; 6(10): e1883, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37559178

RESUMO

BACKGROUND: Chondrosarcomas are an exceedingly rare form of cancer, impacting only a few individuals per million. Among chondrosarcomas, a small fraction belongs to the mesenchymal sub-type. Furthermore, only one-third of mesenchymal chondrosarcomas manifest in extraskeletal locations. CASE: A 38-year-old woman was referred by a midwife after experiencing pain in the right upper quadrant of her right breast for 2 months. The mass had been palpable for 1 week before the initial assessment. According to radiological evaluations, the tumor is outside breast tissue and not connected to the bones. Hence, a biopsy of the mass is done. The biphasic morphology of the tumor during pathological evaluation, in addition to immunohistochemistry testing, confirms the diagnosis of extraskeletal mesenchymal chondrosarcoma (EMCS). Finally, the mass was surgically removed, and 6 months of chemotherapy were administered to the patient. CONCLUSION: Given the tumor's rarity and the lack of established guidelines, diagnosing EMCS can be challenging and prone to errors. As such, meticulous sampling, along with precise pathological and imaging investigations, is imperative to accurately establish the diagnosis of these tumors.


Assuntos
Neoplasias Ósseas , Condrossarcoma Mesenquimal , Condrossarcoma , Feminino , Humanos , Adulto , Condrossarcoma Mesenquimal/diagnóstico , Condrossarcoma Mesenquimal/cirurgia , Condrossarcoma Mesenquimal/patologia , Condrossarcoma/diagnóstico , Imuno-Histoquímica , Diagnóstico por Imagem , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/tratamento farmacológico
4.
JCI Insight ; 8(10)2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37212282

RESUMO

Mesenchymal chondrosarcoma affects adolescents and young adults, and most cases usually have the HEY1::NCOA2 fusion gene. However, the functional role of HEY1-NCOA2 in the development and progression of mesenchymal chondrosarcoma remains largely unknown. This study aimed to clarify the functional role of HEY1-NCOA2 in transformation of the cell of origin and induction of typical biphasic morphology of mesenchymal chondrosarcoma. We generated a mouse model for mesenchymal chondrosarcoma by introducing HEY1-NCOA2 into mouse embryonic superficial zone (eSZ) followed by subcutaneous transplantation into nude mice. HEY1-NCOA2 expression in eSZ cells successfully induced subcutaneous tumors in 68.9% of recipients, showing biphasic morphologies and expression of Sox9, a master regulator of chondrogenic differentiation. ChIP sequencing analyses indicated frequent interaction between HEY1-NCOA2 binding peaks and active enhancers. Runx2, which is important for differentiation and proliferation of the chondrocytic lineage, is invariably expressed in mouse mesenchymal chondrosarcoma, and interaction between HEY1-NCOA2 and Runx2 is observed using NCOA2 C-terminal domains. Although Runx2 knockout resulted in significant delay in tumor onset, it also induced aggressive growth of immature small round cells. Runx3, which is also expressed in mesenchymal chondrosarcoma and interacts with HEY1-NCOA2, replaced the DNA-binding property of Runx2 only in part. Treatment with the HDAC inhibitor panobinostat suppressed tumor growth both in vitro and in vivo, abrogating expression of genes downstream of HEY1-NCOA2 and Runx2. In conclusion, HEY1::NCOA2 expression modulates the transcriptional program in chondrogenic differentiation, affecting cartilage-specific transcription factor functions.


Assuntos
Neoplasias Ósseas , Condrossarcoma Mesenquimal , Proteínas de Fusão Oncogênica , Animais , Camundongos , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Diferenciação Celular , Condrossarcoma Mesenquimal/genética , Condrossarcoma Mesenquimal/metabolismo , Condrossarcoma Mesenquimal/patologia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Camundongos Nus , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo
5.
Pathology ; 55(5): 621-628, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37225644

RESUMO

Mesenchymal chondrosarcoma (MCS) is a rare and highly aggressive tumour of soft tissue and bone that is defined by an underlying and highly specific fusion transcript involving HEY1 and NCOA2. Histologically, the tumours show a biphasic appearance consisting of an undifferentiated blue and round cell component as well as islands of highly differentiated cartilage. Particularly in core needle biopsies, the chondromatous component can be missed and the non-specific morphology and immunophenotype of the round cell component can cause diagnostic challenges. We applied NKX3.1 immunohistochemistry which was recently reported as a highly specific marker as well as methylome and copy number profiling to a set of 45 well characterised MCS cases to evaluate their potential diagnostic value. Methylome profiling revealed a highly distinct cluster for MCS. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. NKX3.1 immunohistochemistry showed positivity in 36% of tumours, the majority of which was rather focal and weak. Taken together, NKX3.1 expression showed a low sensitivity but a high specificity in our analysis. Methylome profiling on the other hand represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. Furthermore, it can aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available.


Assuntos
Neoplasias Ósseas , Condrossarcoma Mesenquimal , Humanos , Condrossarcoma Mesenquimal/diagnóstico , Condrossarcoma Mesenquimal/genética , Condrossarcoma Mesenquimal/patologia , Imuno-Histoquímica , Epigenoma , Osso e Ossos/patologia , Diferenciação Celular , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia
8.
Indian J Pathol Microbiol ; 66(1): 58-62, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36656211

RESUMO

Context: Ewing sarcoma (ES) are malignant small round cell tumors (MSRCT) characterized by rearrangements of EWSR1 gene. Although gold standard for diagnosis is detection of specific fusion genes by molecular testing, these ancillary tests are costly and only available in limited number of settings. There is a persuasive evidence for reliability of NKX2.2 immunohistochemistry (IHC) as a surrogate marker for EWSR1 gene rearrangement in ES. Aims: The aim of this study is to correlate the NKX2.2 immuno-expression with genetically confirmed ES cases and also to assess the reliability and accuracy of NKX2.2 along with combined positivity of NXX2.2 and CD99 in diagnosing ES and differentiating it from other relevant histological mimics. Settings and Design: The present study is a retrospective study conducted over a period of 6-year duration in a tertiary cancer care center. Methods and Material: We evaluated NKX2.2 immunoexpression in 35 genetically confirmed cases of ES and also in pertaining differential entities (n = 58) of ES including rhabdomyosarcoma (n = 20), lymphoblastic lymphoma (n = 14), Wilms tumor (n = 10), poorly differentiated synovial sarcoma (n = 4), small-cell osteosarcoma (n = 4), neuroblastoma (n = 5), and mesenchymal chondrosarcoma (n = 1). CD99 was performed in the category of MSRCTs showing NKX2.2 positivity to evaluate combined specificity for the diagnosis of ES. Results: Of the 35 genetically confirmed cases of ES, 29 cases (83%) showed NKX2.2-positive expression (83% sensitivity). Compared to ES, NKX2.2 was positive in only 05% cases (3/58 cases) of non-ES MSRCT. Only two of five cases of neuroblastomas and one case of mesenchymal chondrosarcoma showed NKX2.2 positivity. CD99 positivity was seen in 100% of ES and in the single case of mesenchymal chondrosarcoma. All five cases (100%) of neuroblastoma were negative for CD99. Conclusions: The presented study, which is the first from an Indian oncology center, showed NKX2.2 IHC is quite reliable in diagnosis of ES in the right clinicopathological context. With remarkable sensitivity and specificity of NKX2.2 IHC for diagnosis of ES, we propose that combined positivity of CD99 and NKX2.2 IHC can obviate or minimize the need of EWSR1 gene rearrangement molecular testing for diagnosis of ES.


Assuntos
Condrossarcoma Mesenquimal , Neuroblastoma , Tumores Neuroectodérmicos Primitivos Periféricos , Sarcoma de Ewing , Sarcoma , Humanos , Antígeno 12E7/metabolismo , Biomarcadores Tumorais/genética , Imuno-Histoquímica , Reprodutibilidade dos Testes , Estudos Retrospectivos , Proteína EWS de Ligação a RNA , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Homeobox Nkx-2.2
9.
Cancer Med ; 12(1): 368-378, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35603739

RESUMO

BACKGROUND: Mesenchymal chondrosarcoma (MCS) is an ultra-rare sarcoma that follows a more aggressive course than conventional chondrosarcoma. This study evaluates prognostic factors, treatments (surgery, chemotherapy, and radiation), and outcomes in an Australian setting. METHODS: We collected demographics, clinicopathological variables, treatment characteristics, and survival status from patients with MCS registered on the national ACCORD sarcoma database. Outcomes include overall survival (OS) and progression-free survival (PFS). RESULTS: We identified 22 patients with MCS between 2001-2022. Median age was 28 (range 10-59) years, 19 (86%) had localised disease at diagnosis of whom 16 had surgery (84%), 11 received radiation (58%), and 10 chemotherapy (53%). Ten (52%) developed recurrence and/or metastases on follow-up and three patients with initial metastatic disease received surgery, radiation, and chemotherapy. At a median follow-up of 50.9  (range 0.4-210) months nine patients had died. The median OS was 104.1 months (95% CI 25.8-182.3). There was improved OS for patients with localised disease who had surgical resection of the primary (p = 0.003) and those with ECOG 0-1 compared to 2-3 (p = 0.023) on univariate analysis. CONCLUSIONS: This study demonstrates contemporary Australian treatment patterns of MCS. The role of chemotherapy for localised disease remains uncertain. Understanding treatment patterns and outcomes help support treatment decisions and design of trials for novel therapeutic strategies.


Assuntos
Neoplasias Ósseas , Condrossarcoma Mesenquimal , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Condrossarcoma Mesenquimal/cirurgia , Neoplasias Ósseas/patologia , Austrália/epidemiologia , Estudos de Coortes , Estudos Retrospectivos
10.
Genes Chromosomes Cancer ; 62(3): 171-175, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36416671

RESUMO

HEY1-NCOA2 fusion is most described in mesenchymal chondrosarcoma. This is the first case report of a primary renal spindle cell neoplasm of uncertain malignant potential with a HEY1::NCOA2 fusion identified by Fusionplex RNA-sequencing that is histologically distinct from mesenchymal chondrosarcoma. The neoplasm was identified in a 33-year-old woman without significant past medical history who underwent partial nephrectomy for an incidentally discovered renal mass. The histologic features of the mass included spindle cells with variable cellularity and monotonous bland cytology forming vague fascicles and storiform architecture within a myxoedematous and collagenous stroma with areas of calcification. The morphologic and immunophenotypic features were not specific for any entity but were most similar to low-grade fibromyxoid sarcoma. To date, the patient has not had recurrence, and the malignant potential of the neoplasm is uncertain.


Assuntos
Neoplasias Ósseas , Condrossarcoma Mesenquimal , Feminino , Humanos , Adulto , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Condrossarcoma Mesenquimal/genética , Condrossarcoma Mesenquimal/cirurgia , Condrossarcoma Mesenquimal/patologia , Nefrectomia , Coativador 2 de Receptor Nuclear/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
12.
Genes Chromosomes Cancer ; 61(11): 670-677, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35672279

RESUMO

BACKGROUND: Mesenchymal chondrosarcoma (MCS) is a rare translocation-associated sarcoma, driven by a canonical HEY1::NCOA2 fusion. The tumors typically have a biphasic phenotype of primitive small blue round cells intermixed with hyaline cartilage. The head and neck (HN) region is a common site for MCS, accounting for 12-45% of all cases reported. AIMS: We assembled a relatively large cohort of 13 molecularly confirmed HN MCS for a detailed clinicopathologic analysis. The underlying fusion events were determined using fluorescence in situ hybridization and/or targeted RNA sequencing. RESULTS: The median age of presentation was 19 years. Five MCSs (39%) had an intraosseous presentation (skull, maxilla, palate, and mandible), while the remaining eight cases occurred in the brain/meninges, orbit, and nasal cavity. Microscopically, HN MCSs were characterized by primitive round cells arranged in a distinctive nested architecture and a rich staghorn vasculature. A cartilaginous component of hyaline cartilage islands and/or single chondrocytes were present in 69% cases. A combined immunoprofile of CD99(+)/SATB2(+)/CD34(-)/STAT6(-) was typically noted. As this immunoprofile is non-specific, the referral diagnoses in cases lacking a cartilaginous component included Ewing sarcoma family and osteosarcoma. Among the seven patients with follow-up data, three developed distant metastasis and one died of disease. CONCLUSION: HN MCS may arise at intra- or extra-osseous sites. The HN MCS appears to have a more prolonged survival compared other MCS sites. Testing for HEY1::NCOA2 fusion is recommended in HN tumors with nested round cell morphology and staghorn vasculature that lack a distinctive cartilaginous component.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Condrossarcoma Mesenquimal , Fusão Gênica , Neoplasias de Cabeça e Pescoço , Coativador 2 de Receptor Nuclear , Adulto , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Ciclo Celular/genética , Criança , Condrossarcoma Mesenquimal/genética , Condrossarcoma Mesenquimal/patologia , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hibridização in Situ Fluorescente , Masculino , Coativador 2 de Receptor Nuclear/genética , Adulto Jovem
13.
Medicina (Kaunas) ; 58(5)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35630056

RESUMO

Background: Mesenchymal chondrosarcoma is a rare but aggressive subtype of sarcoma. The majority of involvement locates in the axial skeleton. Treatment modalities include radical surgery, local radiotherapy, and systemic chemotherapy. However, the long-term survival outcome remains poor. Case presentation: We present the case of a 33-year-old male with a palpable chest wall mass for one year, diagnosed with mesenchymal chondrosarcoma with surgical removal. Later, he had an unusual pancreatic tail tumor as the first presentation of disease metastasis which was proven by surgical resection one year later. Conclusion: Although mesenchymal chondrosarcoma locates mainly in the axial skeletal system, extra-skeletal soft tissue or organ involvement might be seen occasionally. Active surveillance with multidisciplinary team management could significantly prolong survival outcomes.


Assuntos
Condrossarcoma Mesenquimal , Neoplasias Pancreáticas , Sarcoma , Adulto , Condrossarcoma Mesenquimal/patologia , Condrossarcoma Mesenquimal/cirurgia , Humanos , Masculino
14.
BMC Neurol ; 22(1): 112, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35321663

RESUMO

BACKGROUND: Mesenchymal chondrosarcoma (MCS) is an ultra-rare, high-grade subtype of chondrosarcoma affecting both bone and soft tissues. Extra-skeletal MCS rarely occurs in intra- and extradural regions. CASE PRESENTATION: We presented a case of intraspinal dumbbell-shaped MCS at the T12-L2 level with isolated punctate calcification in a 19-year-old male complaining of progressive lower back pain. Surgical treatment for removal of the tumor was performed. The postoperative pathological result confirmed MCS. The patient showed symptomatic improvement and follow-up MRI showed no evidence of recurrence or metastasis for nearly 1 year after surgery. CONCLUSIONS: CT and MRI play an important role in differential diagnosis for intraspinal MCS. MCS should be added to the differential diagnosis of intraspinal dumbbell-shaped tumors, especially when radiological examinations reveal punctate calcification in a homogeneous enhanced tumor without dural tail sign. However, the final diagnosis depends on histopathological results. Despite the good prognosis of intraspinal MCS, close follow-up after operation is still necessary.


Assuntos
Calcinose , Condrossarcoma Mesenquimal , Neoplasias da Coluna Vertebral , Adulto , Calcinose/complicações , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Condrossarcoma Mesenquimal/diagnóstico , Condrossarcoma Mesenquimal/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Adulto Jovem
15.
Neurol India ; 70(1): 285-288, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35263897

RESUMO

Background: Extraskeletal mesenchymal chondrosarcoma (MCS) of the central nervous system (CNS) is extremely rare. Herein, we present the clinicopathological features of five CNS extraskeletal MCS. Material and Methods: Over the past 10 years, five cases of CNS MCS have been retrieved from in the archives of histopathology department. All biopsies were stained with vimentin, S-100, CD99, desmin, GFAP, INI1, WT1, STAT6, and EMA. Results: There were four males and one female patient in the age group of 1.5-35 years. The clinical and radiological impression was meningioma in three cases, glomus jugulare and primitive neuroectodermal tumor in one case each. All showed classic biphasic morphology, areas of undifferentiated small blue round cells sharply demarcated from the island of cartilage. Three patients experienced multiple recurrences and died subsequently. Conclusion: Extraskeletal MCS of CNS is rare and favors children and young adults. They show aggressive behavior and tend to recur despite surgery and radiotherapy.


Assuntos
Neoplasias Ósseas , Condrossarcoma Mesenquimal , Neoplasias Meníngeas , Adulto , Neoplasias Ósseas/patologia , Sistema Nervoso Central/patologia , Condrossarcoma Mesenquimal/diagnóstico , Condrossarcoma Mesenquimal/patologia , Condrossarcoma Mesenquimal/cirurgia , Feminino , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia
16.
J Pathol ; 257(5): 579-592, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35342947

RESUMO

Mesenchymal chondrosarcoma is a rare, high-grade, primitive mesenchymal tumor. It accounts for around 2-10% of all chondrosarcomas and mainly affects adolescents and young adults. We previously described the HEY1-NCOA2 as a recurrent gene fusion in mesenchymal chondrosarcoma, an important breakthrough for characterizing this disease; however, little study had been done to characterize the fusion protein functionally, in large part due to a lack of suitable models for evaluating the impact of HEY1-NCOA2 expression in the appropriate cellular context. We used iPSC-derived mesenchymal stem cells (iPSC-MSCs), which can differentiate into chondrocytes, and generated stable transduced iPSC-MSCs with inducible expression of HEY1-NCOA2 fusion protein, wildtype HEY1 or wildtype NCOA2. We next comprehensively analyzed both the DNA binding properties and transcriptional impact of HEY1-NCOA2 expression by integrating genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) and expression profiling (RNA-seq). We demonstrated that HEY1-NCOA2 fusion protein preferentially binds to promoter regions of canonical HEY1 targets, resulting in transactivation of HEY1 targets, and significantly enhances cell proliferation. Intriguingly, we identified that both PDGFB and PDGFRA were directly targeted and upregulated by HEY1-NCOA2; and the fusion protein, but not wildtype HEY1 or NCOA2, dramatically increased the level of phospho-AKT (Ser473). Our findings provide a rationale for exploring PDGF/PI3K/AKT inhibition in treating mesenchymal chondrosarcoma. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Neoplasias Ósseas , Condrossarcoma Mesenquimal , Adolescente , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Carcinogênese , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Transformação Celular Neoplásica , Condrossarcoma Mesenquimal/genética , Condrossarcoma Mesenquimal/metabolismo , Condrossarcoma Mesenquimal/patologia , Fusão Gênica , Genômica , Humanos , Coativador 2 de Receptor Nuclear/genética , Coativador 2 de Receptor Nuclear/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adulto Jovem
17.
Zhonghua Bing Li Xue Za Zhi ; 51(2): 114-119, 2022 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-35152629

RESUMO

Objective: To investigate the immunohistochemical expression of NKX3.1 and NKX2.2 in mesenchymal chondrosarcoma (MC), and to explore the differential diagnostic value of NKX3.1 and NKX2.2 in MC and other types of small round cell malignant tumors. Methods: A total of 12 cases of MC and 97 other small round cell malignant tumors diagnosed in Jinling Hospital, Nanjing University School of Medicine from 2001 to 2020 were collected for NKX3.1 and NKX2.2 immunohistochemical detection. Among them, two kinds of NKX3.1 antibodies [rabbit polyclonal antibody and rabbit monoclonal antibody (EP356)] were used for detection in 12 cases of MC, and one NKX3.1 antibody (rabbit polyclonal antibody) was detected in 97 cases of other small round cell malignant tumors, and the relevant literature was reviewed. Results: The 12 MC patients included 7 females and 5 males, with a mean age of 33 years (14-54 years). Nine cases were from bone and three from soft tissue. Among the 12 MC patients, 8 patients had postoperative recurrence or metastasis, and 3 of them died of tumor recurrence or metastasis. Histologically, 12 cases of MC showed typical bidirectional differentiation.The positive rate of both NKX3.1 antibodies in MC was 12/12, NKX3.1 was focal weakly positive in only one of 12 chondrosarcomas (grade 3), 5 alveolar rhabdomyosarcomas, 5 embryonal rhabdomyosarcomas, and 5 solitary fibrous tumors, respectively. The remaining 70 cases of other small round cell malignant tumors were negative. The positive rates of NKX2.2 in MC, Ewing sarcoma and olfactory neuroblastoma were 12/12, 15/15 and 4/5, respectively. In 12 cases of chondrosarcoma (grade 3), 5 cases of poorly differentiated synovial sarcoma, 5 cases of alveolar rhabdomyosarcoma, and 5 cases of solitary fibrous tumor, NKX2.2 was focally and weakly positive in only one case, respectively, and all the remaining 50 cases of other small round cell malignant tumors were negative. Conclusions: The expression of NKX3.1 and NKX2.2 proteins are significant indicators in the diagnosis of MC, and the combined detection of NKX3.1 and NKX2.2 can help distinguish MC from most other small round cell malignant tumors.


Assuntos
Condrossarcoma Mesenquimal , Biomarcadores Tumorais , Condrossarcoma Mesenquimal/diagnóstico , Diagnóstico Diferencial , Feminino , Proteínas de Homeodomínio , Humanos , Imuno-Histoquímica , Masculino , Proteínas Nucleares
18.
Pathol Res Pract ; 232: 153803, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35217266

RESUMO

STAT6 is usually considered to be a very sensitive and specific immunomarker for diagnosis of solitary fibrous tumor (SFT), being a surrogate of the NAB2-STAT6 fusion gene identified in most cases of this tumor. STAT6 expression has also been reported in rare cases of other soft tissue tumors, such as low-grade fibromyxoid sarcoma, myxoid/round cell liposarcoma, dedifferentiated liposarcoma and deep fibrous histiocytoma. The aim of this study was to report, for the first time, a case of mesenchymal chondrosarcoma showing diffuse aberrant immunohistochemical expression of STAT6. Molecular biology, showing the HEY1-NCOA2 fusion gene, was crucial to rule out SFT.


Assuntos
Condrossarcoma Mesenquimal , Tumores Fibrosos Solitários , Biomarcadores Tumorais/metabolismo , Condrossarcoma Mesenquimal/diagnóstico , Condrossarcoma Mesenquimal/genética , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Fator de Transcrição STAT6/metabolismo , Tumores Fibrosos Solitários/patologia
19.
BMJ Case Rep ; 15(1)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996769

RESUMO

Mesenchymal chondrosarcoma (MC) is a rare cartilaginous tumour that occurs in the extraskeletal locations in about one-third of cases. It is aggressive in behaviour and may involve the lower extremities, central nervous system or spine. Mesenchymal tumours are known for distant metastasis; however, metastasis to bilateral kidneys after treatment has not been reported earlier. We present a case of a soft-tissue intramuscular MC of the thigh in a 38-year-old patient which had been surgically excised after neoadjuvant chemotherapy. The patient presented with bilateral dense calcified renal masses after 6 years, which were cytologically proven as MC metastases. In the evaluation of bilateral calcified renal masses in patients with a history of MC, metastasis should be considered.


Assuntos
Condrossarcoma Mesenquimal , Condrossarcoma , Neoplasias de Tecido Conjuntivo , Adulto , Condrossarcoma Mesenquimal/diagnóstico por imagem , Condrossarcoma Mesenquimal/cirurgia , Humanos , Coxa da Perna
20.
Lab Invest ; 102(9): 1038-1049, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34837064

RESUMO

Mesenchymal chondrosarcoma (MCS) is a high-grade malignancy that represents 2-9% of chondrosarcomas and mostly affects children and young adults. HEY1-NCoA2 gene fusion is considered to be a driver of tumorigenesis and it has been identified in 80% of MCS tumors. The shortage of MCS samples and biological models creates a challenge for the development of effective therapeutic strategies to improve the low survival rate of MCS patients. Previous molecular studies using immunohistochemical staining of patient samples suggest that activation of PDGFR signaling could be involved in MCS tumorigenesis. This work presents the development of two independent in vitro and in vivo models of HEY1-NCoA2-driven MCS and their application in a drug repurposing strategy. The in vitro model was characterized by RNA sequencing at the single-cell level and successfully recapitulated relevant MCS features. Imatinib, as well as specific inhibitors of ABL and PDGFR, demonstrated a highly selective cytotoxic effect targeting the HEY1-NCoA2 fusion-driven cellular model. In addition, patient-derived xenograft (PDX) models of MCS harboring the HEY1-NCoA2 fusion were developed from a primary tumor and its distant metastasis. In concordance with in vitro observations, imatinib was able to significantly reduce tumor growth in MCS-PDX models. The conclusions of this study serve as preclinical results to revisit the clinical efficacy of imatinib in the treatment of HEY1-NCoA2-driven MCS.


Assuntos
Neoplasias Ósseas , Condrossarcoma Mesenquimal , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Carcinogênese , Proteínas de Ciclo Celular , Reposicionamento de Medicamentos , Xenoenxertos , Humanos , Mesilato de Imatinib , Coativador 2 de Receptor Nuclear
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