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1.
Cells ; 10(6)2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201149

RESUMO

The vast array of metabolic adaptations that cancer cells are capable of assuming, not only support their biosynthetic activity, but also fulfill their bioenergetic demands and keep their intracellular reduction-oxidation (redox) balance. Spotlight has recently been placed on the energy metabolism reprogramming strategies employed by cancer cells to proliferate. Knowledge regarding soft tissue and bone sarcomas metabolome is relatively sparse. Further characterization of sarcoma metabolic landscape may pave the way for diagnostic refinement and new therapeutic target identification, with benefit to sarcoma patients. This review covers the state-of-the-art knowledge on cancer metabolomics and explores in detail the most recent evidence on soft tissue and bone sarcoma metabolomics.


Assuntos
Metaboloma , Metabolômica , Osteossarcoma/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Animais , Linhagem Celular Tumoral , Humanos
2.
Anticancer Res ; 41(5): 2211-2215, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952447

RESUMO

Elastofibroma dorsi is an uncommon benign fibroblastic pseudotumor that typically occurs in the subscapular region of middle-aged or older individuals. The pathogenesis is still unclear and a matter of debate. Magnetic resonance imaging can be used as a first-line investigation of the lesion and reveals a lenticular soft-tissue mass with a signal intensity similar to that of skeletal muscle interlaced with strands of fat. Biopsy is not necessary if all pathognomonic criteria are present. A conservative "wait and see" attitude is reasonable and immediate surgery is no more the standard treatment of elastofibroma dorsi. This review provides an updated overview of the diagnosis, management and pathogenesis of elastofibroma dorsi. We also discuss recent advances in our understanding of genomic alterations in elastofibroma dorsi.


Assuntos
Fibroma/diagnóstico , Fibroma/terapia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/terapia , Antígenos CD34/metabolismo , Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Fibroma/genética , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Muramidase/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Vimentina/metabolismo
3.
Medicine (Baltimore) ; 100(20): e26040, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011115

RESUMO

BACKGROUND: Tumor-specific DNA methylation can potentially be a useful indicator in cancer diagnostics and monitoring. Sarcomas comprise a heterogeneous group of mesenchymal neoplasms which cause life-threatening tumors occurring throughout the body. Therefore, potential molecular detection and prognostic evaluation is very important for early diagnosis and treatment. METHODS: We performed a retrospective study analyzing DNA methylation of 261 patients with sarcoma from The Cancer Genome Atlas (TCGA) database. Cox regression analyses were conducted to identify a signature associated with the overall survival (OS) of patients with sarcoma, which was validated in a validation dataset. RESULTS: Three DNA methylation signatures were identified to be significantly associated with OS. Kaplan-Meier analysis showed that the 3-DNA methylation signature could significantly distinguish the high- and low-risk patients in both training (first two-thirds) and validation datasets (remaining one-third). Receiver operating characteristic (ROC) analysis confirmed that the 3-DNA methylation signature exhibited high sensitivity and specificity in predicting OS of patients. Also, the Kaplan-Meier analysis and the area under curve (AUC) values indicated that the 3-DNA methylation signature was independent of clinical characteristics, including age at diagnosis, sex, anatomic location, tumor residual classification, and histological subtypes. CONCLUSIONS: The current study showed that the 3-DNA methylation model could efficiently function as a novel and independent prognostic biomarker and therapeutic target for patients with sarcoma.


Assuntos
Metilação de DNA/fisiologia , Sarcoma/diagnóstico , Sarcoma/metabolismo , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Adulto Jovem
4.
Pediatr Hematol Oncol ; 38(6): 602-608, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33792506

RESUMO

This study reports a case of superficial CD34-positive fibroblastic tumor (SCPFT) in a child and analyze the major known clinicopathological features of SCPFT and other skin mesenchymal tumors, contributing to an accurate diagnosis of this rare disease. We summarize the clinicopathologic features of an 8-year-old girl who was diagnosed with SCPFT and 46 previously reported SCPFT cases. Post-operative histopathologic examination of the current case showed the tumor lesion was well-circumscribed; tumor cells were spindled-to-polygonal with a fascicular pattern; most nuclei displayed hyperchromasia and low mitotic rate; intranuclear pseudoinclusions could be found; and abundant eosinophilic cytoplasm and partial myxoid stroma were observed. Immunohistochemistry revealed strong and diffuse CD34-positivity, vimentin staining positively but no S-100, SMA, NSE, CD31, desmin, cytokeratin, STAT6, ß-catenin, MDM2, or ERG expression. The Ki-67 and CD68 labeling indexes were approximately 1%. There were no rearrangements of PDGFB or PRDM10 tested by FISH. After surgical resection, the patient had no signs of recurrence or metastasis at a 6-month follow-up. The present case is the first that describes SCPFT in children and has significant clinical implications. SCPFT should be differentiated from other skin mesenchymal tumors. The presented compilation of all so far published SCPFT cases will help in diagnosing successfully SCPFT and increasing awareness of this tumor to guide clinical practice.


Assuntos
Antígenos CD34/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias de Tecidos Moles , Neoplasias Torácicas , Criança , Feminino , Humanos , Imuno-Histoquímica , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias Torácicas/metabolismo , Neoplasias Torácicas/patologia , Neoplasias Torácicas/cirurgia , Parede Torácica
5.
PLoS One ; 16(4): e0250643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33886686

RESUMO

Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS.


Assuntos
Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Tolerância a Radiação , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Adenoviridae/genética , Animais , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Terapia Combinada , Dano ao DNA/efeitos da radiação , Feminino , Humanos , Camundongos , Camundongos Nus , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Terapia Viral Oncolítica , Radiação Ionizante , Sarcoma/metabolismo , Sarcoma/patologia , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/radioterapia , Transplante Heterólogo
6.
Adv Anat Pathol ; 28(3): 139-149, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33559990

RESUMO

Bone and soft tissue tumors of the head and neck are relatively uncommon tumors that often represent a diagnostic challenge because of the wide range of entities that must be considered in the differential diagnosis. Over the past few years, classification of bone and soft tissue tumors has evolved primarily because of substantial contributions from molecular genetics, with the identification of new markers that are increasingly used to complement histopathologic findings in the routine diagnostic workup. This review focuses on the recently described mesenchymal tumors that preferentially involve the head and neck region, with a focus on the most relevant novel immunohistochemical and molecular findings, including gene fusions and mutations, that can help in the diagnosis and in the assessment of clinical behavior.


Assuntos
Neoplasias Ósseas/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia
7.
J Clin Pathol ; 74(3): 137-140, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33441390

RESUMO

TLE 1 is the human homologue belonging to a family of four genes and is located on chromosome 9q21. It consists of 19 exons. Although it does not bind directly to DNA, it acts as a repressor of several signalling pathways via transcription factors. TLE1 protein has several physiological roles in embryogenesis, haematopoiesis, general differentiation, and both neuronal and eye development. Much attention was focused on its expression in the tumour cell nuclei of synovial sarcoma (SS). However, several other soft tissue tumours that do and do not share morphological similarity with SS also display nuclear immunoreactivity for TLE1; hence, caution in interpretation is advocated.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas Correpressoras/genética , Sarcoma Sinovial/genética , Sarcoma Sinovial/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Núcleo Celular/patologia , Proteínas Correpressoras/metabolismo , Humanos , Imuno-Histoquímica , Oncogenes/genética , Neoplasias de Tecidos Moles/patologia
8.
Hum Pathol ; 110: 12-19, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33406387

RESUMO

Although the morphologic diagnosis of hibernoma is usually straightforward, some hibernomas have atypical morphologic features, mimicking atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLs). In addition, the multivacuolated brown fat cells may be mistaken for lipoblasts by pathologists, especially those without significant soft tissue tumor exposure. Thus, we continue to receive in consultation cases of hibernoma sent for MDM2 fluorescence in situ hybridization testing to exclude ALT/WDL. Testing hibernomas for MDM2 amplification, however, adds cost and delays the final diagnosis. Recently, we have noted expression of neprilysin (CD10, CALLA), a zinc-dependent metalloproteinase involved in the inactivation of various peptide hormones, in brown fat cells, and wished to explore the potential utility of this widely available, inexpensive ancillary test in the differential diagnosis of hibernoma. Formalin-fixed, paraffin-embedded tissue sections from well-characterized cases of hibernoma (n = 48), brown fat (n = 21), ALTs/WDLs (n = 17), pleomorphic liposarcomas (PLPSs) (n = 6), lipomas (n = 5), and fat necrosis (n = 5) were immunostained for CD10, using a commercially available antibody and routine laboratory protocols. CD10 expression was evaluated in both adipocytes and in surrounding stromal cells. The hibernomas occurred in 28 men and 20 women, ranging from 11 to 76 years of age and involved the extremities (n = 25), pelvis (n = 7), abdomen/pelvis/retroperitoneum (n = 7), head and neck region (n = 6), back (n = 2), and chest (n = 1). All showed diffuse, strong CD10 expression in multivacuolated brown fat cells and in the majority of adjacent univacuolated fat cells. Brown adipose tissue from various anatomic structures showed an identical pattern of immunoreactivity. In contrast, CD10 expression was present in the adipocytes of only 3 of 17 (18%) ALTs/WDLs and was absent in lipomas and fat necrosis. Lipoblasts expressed CD10 in 3 PLPSs. Expression of CD10 by surrounding fibroblastic stromal cells was more widespread, present in 13 hibernomas, 10 ALTs/WDLs, 1 instance of fat necrosis, 6 PLPSs, and 4 examples of brown fat. We conclude that immunohistochemistry for CD10 may represent a useful, rapid and inexpensive ancillary test in the differential diagnosis of hibernoma from potential morphologic mimics, especially when morphologic features favor hibernoma. CD10 expression in adipocytes, however, should be rigorously distinguished from fibroblastic stromal cell CD10 expression, a nonspecific finding.


Assuntos
Lipoma/metabolismo , Lipoma/patologia , Lipossarcoma/patologia , Neprilisina/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Criança , Diagnóstico Diferencial , Feminino , Humanos , Lipoma/diagnóstico , Lipossarcoma/diagnóstico , Lipossarcoma/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-mdm2/genética , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia , Adulto Jovem
9.
Diagn Pathol ; 16(1): 2, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33419470

RESUMO

BACKGROUND: IL4Rα and IL13Rα1 are constituents of the type II IL4 receptor. Recently, IL4Rα and IL13Rα1 were reported to have roles in cancer progression and suggested as potential prognostic markers. However, studies on IL4Rα and IL13Rα1 in soft-tissue sarcomas have been limited. METHODS: This study investigated the immunohistochemical expression of IL4Rα and IL13Rα1 in 89 soft-tissue sarcomas of the extremities, superficial trunk, and retroperitoneum. Immunohistochemical staining for IL4Rα and IL13Rα1 were scored according to a combination of staining intensity and staining area in tissue microarray samples. Positivity for the immunohistochemical expression of IL4Rα and IL13Rα1 were determined using receiver operating curve analysis. Statistical analysis was performed using regression analysis and a chi-square test. RESULTS: In human soft-tissue sarcomas, immunohistochemical expression of IL4Rα was significantly associated with IL13Rα1 expression. Nuclear and cytoplasmic expression of IL4Rα and IL13Rα1 were significantly associated with shorter survival of soft-tissue sarcoma patients in univariate analysis. Multivariate analysis indicated that nuclear expression of IL4Rα and IL13Rα1 were independent indicators of shorter overall survival (IL4Rα; p = 0.002, IL13Rα1; p = 0.016) and relapse-free survival (IL4Rα; p = 0.022, IL13Rα1; p < 0.001) of soft-tissue sarcoma patients. Moreover, the co-expression pattern of nuclear IL4Rα and IL13Rα1 was an independent indicator of shorter survival of soft-tissue sarcoma patients (overall survival; overall p < 0.001, relapse-free survival; overall p < 0.001). CONCLUSIONS: This study suggests IL4Rα and IL13Rα1 are associated with the progression of soft-tissue sarcoma, and the expression of IL4Rα and IL13Rα1 might be novel prognostic indicators of soft-tissue sarcoma patients.


Assuntos
Subunidade alfa1 de Receptor de Interleucina-13/metabolismo , Subunidade alfa de Receptor de Interleucina-4/metabolismo , Neoplasias Retroperitoneais/diagnóstico , Sarcoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Extremidades/patologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Retroperitoneais/metabolismo , Neoplasias Retroperitoneais/patologia , Espaço Retroperitoneal/patologia , Sarcoma/metabolismo , Sarcoma/patologia , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia , Análise de Sobrevida , Adulto Jovem
10.
J Clin Endocrinol Metab ; 106(5): e2299-e2308, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33462615

RESUMO

CONTEXT: Literature suggests that oncogenic osteomalacia is usually caused by a benign mesenchymal tumor secreting fibroblast growth factor subtype-23 (FGF-23), but the involvement of other phosphatonins has only been scarcely reported. We have previously published a seemingly typical case of oncogenic osteomalacia. Following curative neoplasm resection, we now report unique molecular characteristics and biology of this tumor. CASE DESCRIPTION: A 25-year-old man had been diagnosed with severe oncogenic osteomalacia that gradually crippled him over 6 years. 68Ga-DOTA-TATE positron emission tomography/computed tomography scan localized the culprit tumor to his left sole, which on resection revealed a deep fibrous histiocytoma displaying a proliferation of spindle cells with storiform pattern associated with multinucleated giant cells resembling osteoclasts. Circulating FGF-23, which was elevated more than 2-fold, declined to undetectable levels 24 h after surgery. Microarray analysis revealed increased tumor gene expression of the phosphatonins FGF-23, matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein subtype 4, with elevated levels of all 3 proteins confirmed through immunoblot analysis. Differential expression of genes involved in bone formation and bone mineralization were further identified. The patient made an astonishing recovery from being wheelchair bound to fully self-ambulant 2 months postoperatively. CONCLUSION: This report describes oncogenic osteomalacia due to a deep fibrous histiocytoma, which coincidentally has been found to induce profound muscle weakness via the overexpression of 3 phosphatonins, which resolved fully upon radical resection of the tumor. Additionally, genes involved in bone formation and bone remodeling contribute to the molecular signature of oncogenic osteomalacia.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Histiocitoma Fibroso Benigno/metabolismo , Osteomalacia/etiologia , Síndromes Paraneoplásicas/etiologia , Neoplasias de Tecidos Moles/etiologia , Adulto , Fatores de Crescimento de Fibroblastos/genética , Doenças do Pé/diagnóstico , Doenças do Pé/etiologia , Doenças do Pé/genética , Doenças do Pé/metabolismo , Regulação Neoplásica da Expressão Gênica , Histiocitoma Fibroso Benigno/complicações , Histiocitoma Fibroso Benigno/diagnóstico , Histiocitoma Fibroso Benigno/genética , Humanos , Malásia , Masculino , Osteomalacia/diagnóstico , Osteomalacia/genética , Osteomalacia/metabolismo , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/genética , Síndromes Paraneoplásicas/metabolismo , Singapura , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/metabolismo
11.
Histopathology ; 78(2): 321-326, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32735735

RESUMO

BACKGROUND AND AIMS: Complete loss of histone H3 lysine 27 trimethylation (H3K27me3) has recently emerged as a biomarker for malignant peripheral nerve sheath tumours (MPNST). Loss of H3K27me3 staining has also been reported in post-radiation MPNST; however, it has not been evaluated in a large series of radiation-associated sarcomas of different histological subtypes. The aim of this study was to assess H3K27me3 labelling by immunohistochemistry in radiation-associated sarcomas and to determine the prevalence of H3K27me3 loss in these tumours. METHODS AND RESULTS: Radiation-associated sarcomas (n = 119) from two tertiary care referral centres were evaluated for loss of H3K27me3, defined as complete loss of staining within tumour cells in the presence of a positive internal control. Twenty-three cases (19%) showed H3K27me3 loss, including nine of 10 (90%) MPNST, seven of 77 (9%) undifferentiated spindle cell/pleomorphic sarcomas, five of 25 (20%) angiosarcomas, one of five (20%) leiomyosarcomas and one of two (50%) osteosarcomas. CONCLUSIONS: Complete H3K27me3 loss was present in 19% of radiation-associated sarcomas in our series. Our findings demonstrate that loss of H3K27me3 is not specific for radiation-associated MPNST and may also occur in other histological subtypes of RAS, including radiation-associated undifferentiated spindle cell/pleomorphic sarcoma, angiosarcoma, leiomyosarcoma and osteosarcoma.


Assuntos
Histonas , Metilação , Neoplasias Induzidas por Radiação , Sarcoma , Biomarcadores Tumorais , Diagnóstico Diferencial , Feminino , Histonas/química , Histonas/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias Induzidas por Radiação/metabolismo , Neurilemoma/diagnóstico , Neurilemoma/metabolismo , Neurofibrossarcoma/diagnóstico , Neurofibrossarcoma/metabolismo , Radiação , Sarcoma/diagnóstico , Sarcoma/metabolismo , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/metabolismo
12.
Histopathology ; 78(6): 905-908, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33368602

RESUMO

AIMS: Mucin 4 (MUC4) is a transmembrane glycoprotein normally expressed by several human epithelial surfaces, including those of the colon, vagina, and respiratory tract. Although MUC4 overexpression is seen in various carcinomas, its expression among mesenchymal neoplasms is fairly specific to low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma. Having observed unanticipated anti-MUC4 immunoreactivity in rhabdomyosarcoma, we aimed to further characterise its expression. METHODS AND RESULTS: Expression of MUC4 was assessed by immunohistochemistry in a total of 97 rhabdomyosarcomas using formalin-fixed paraffin-embedded tissue sections. MUC4 was expressed by 21 of 26 PAX3/7-FOXO1 fusion-positive cases, wherein immunoreactivity, varying from weak to strong, was present in 20-100% of neoplastic cells. With the exception of one sclerosing rhabdomyosarcoma showing immunoreactivity in 20% of cells, MUC4 was not expressed by embryonal (n = 28), sclerosing (n = 20), or pleomorphic (n = 23) rhabdomyosarcomas. Analysing published gene expression microarray data from a separate cohort of 33 fusion-positive and 25 fusion-negative rhabdomyosarcomas, we found on average a 11.4-fold increased expression in fusion-positive tumours (P = 0.0004). CONCLUSIONS: MUC4 is expressed to a variable extent in the majority of PAX3/7-FOXO1 fusion-positive (alveolar) rhabdomyosarcomas, while expression in other rhabdomyosarcoma subtypes is rare.


Assuntos
Neoplasias de Cabeça e Pescoço/metabolismo , Mucina-4/metabolismo , Rabdomiossarcoma Alveolar/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Adulto , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Rabdomiossarcoma Alveolar/patologia , Neoplasias de Tecidos Moles/patologia
13.
J Cutan Pathol ; 48(7): 896-901, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33241586

RESUMO

Recently, a novel group of CD34+ and S100+ spindle cell tumors with distinctive stromal and perivascular hyalinization showing recurrent gene fusions involving RAF1, BRAF, NTRK1/2/3, and RET has been identified. ALK rearrangements have been rarely reported in this group of tumors. We report a 24-year-old woman with a 1.5-cm pink mass of the scalp. The tumor was made of spindle cells organized in fascicles or haphazardly arranged in a patternless architecture, with areas of stromal and perivascular hyalinization. The tumor cells diffusely expressed CD34 and S100, without SOX-10 expression. The tumor showed diffuse immunopositivity for ALK. RNA sequencing using next-generation sequencing (NGS) detected an EML4-ALK fusion. This case extends the spectrum of this newly described group of CD34+/S100+ spindle cell tumors at the molecular-genetic level. Dermatopathologists should be aware of this recent entity, as it may fall in the differential diagnosis of many other spindle cell tumors with CD34 expression. NGS-based techniques should be performed when facing spindle cell tumors with similar morphology and immunophenotype. Identification of kinase fusions is essential for the precise classification and better knowledge of these tumors, and for targeted therapy in rare aggressive cases.


Assuntos
Antígenos CD34/metabolismo , Proteínas S100/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Diagnóstico Diferencial , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Hialina/metabolismo , Imuno-Histoquímica/métodos , Proteínas de Fusão Oncogênica , Análise de Sequência de RNA/métodos , Neoplasias de Tecidos Moles/diagnóstico , Células Estromais/metabolismo , Células Estromais/patologia , Recusa do Paciente ao Tratamento , Adulto Jovem
14.
Cytopathology ; 32(1): 20-28, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32853443

RESUMO

OBJECTIVES: To present a comprehensive analysis of cytomorphological features, including clinical scenarios, for 8 cases (4 males, 4 females, aged 17-39 years, average = 28.5) of, retrospectively diagnosed alveolar soft part sarcoma (ASPS), with TFE3 immunostaining in 7 cases. METHODS: Conventional Papanicolaou and May Grunwald-Giemsa (MGG) stained smears and corresponding tissue sections were critically reviewed. Fine needle aspiration cytology was performed for primary diagnosis in 6 cases and for metastatic lesions in 2 cases. TFE3 and other immunohistochemical stains were tested using polymer detection technique. RESULTS: Tumour sites were thigh (n = 6), shoulder (1) and neck (1). Tumour size (n = 6) varied from 5 to 14.5 cm (average = 7.2). Seven out of 8 cases were correctly diagnosed on cytosmears. The smears were mostly hypercellular (5), composed of cohesive clusters (8), including cell balls and pseudopapillae (3) and singly scattered cells (8). Tumour cells were round to oval, containing central to eccentric nuclei (8), abundant granular (8) to finely vacuolated (7) cytoplasm that was ill- to well-defined, intracytoplasmic rod-like or needle-shaped crystals (3) and prominent nucleoli (8), Additionally, there were binucleated cells (7), multinucleation (2), intracytoplasmic inclusions (3), intranuclear inclusions (2), intercellular stroma (5) and bare nuclei (8). Immunohistochemically, 7/8 tumours were positive for TFE3. CONCLUSIONS: This constitutes the largest series describing cytomorphological spectrum of ASPS with TFE3 immunostaining results. Frequently observed features and rod-like/needle-shaped crystals on MGG smears, can help to differentiate ASPS from its mimics. TFE3 immunostaining aids in substantiating diagnoses, in an appropriate clinicoradiological context.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Sarcoma Alveolar de Partes Moles/metabolismo , Sarcoma Alveolar de Partes Moles/patologia , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia , Adolescente , Adulto , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha Fina/métodos , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Estudos Retrospectivos , Sarcoma Alveolar de Partes Moles/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Coloração e Rotulagem/métodos , Adulto Jovem
15.
Histol Histopathol ; 36(1): 3-18, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32885407

RESUMO

Angiosarcomas (AS) represent a heterogenous group of tumors with variable clinical presentation. AS share an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging, especially in poorly-differentiated tumors. Although molecular studies provide significant clues, especially in the differential diagnosis with other vascular neoplasms, a thorough hematoxylin and eosin analysis remains an essential tool in AS diagnosis. In this review, we discuss pathological and molecular insights with emphasis on implications for differential diagnosis in cutaneous, breast, soft tissue and visceral AS.


Assuntos
Hemangiossarcoma/diagnóstico , Hemangiossarcoma/patologia , Imuno-Histoquímica/métodos , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologia , Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Diferenciação Celular , Diagnóstico Diferencial , Feminino , Hemangiossarcoma/metabolismo , Humanos , Sarcoma/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias de Tecidos Moles/metabolismo , Microambiente Tumoral , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/metabolismo , Neoplasias Vasculares/patologia
17.
Pathol Int ; 70(12): 1015-1019, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32940945

RESUMO

Synovial sarcoma is a high-grade soft tissue sarcoma that occurs primarily in the deep soft tissue of extremities, and primary colorectal synovial sarcoma is extremely rare. In this report, we present a synovial sarcoma mostly located within the mucosa of the sigmoid colon. The patient was a man in his forties with a germline deletion in the MSH2 gene. He had experienced undifferentiated pleomorphic sarcoma of the left forearm 7 years before and adenocarcinoma of the transverse colon 6 years before, both of which were successfully treated and exhibited no recurrence to date. A surveillance colonoscopy for Lynch syndrome revealed the tumor which had a submucosal tumor-like appearance with central erosion and endoscopic resection was performed. Histologically, it was composed of monotonous proliferation of spindle cells arranged in cellular fascicles; these findings were compatible with monophasic fibrous synovial sarcoma. In the tumor cells, the presence of the SS18-SSX1 fusion gene was confirmed. Protein expression of mismatch repair genes was intact in the tumor cells, indicating the association between microsatellite instability and synovial sarcoma was weak. The present case highlights a rare primary site of synovial sarcoma in a patient with Lynch syndrome.


Assuntos
Colo Sigmoide/patologia , Proteína 2 Homóloga a MutS , Sarcoma Sinovial , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/metabolismo , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Sarcoma Sinovial/genética , Sarcoma Sinovial/metabolismo , Sarcoma Sinovial/patologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia
18.
Pathol Int ; 70(12): 965-974, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32940946

RESUMO

We demonstrated the clinicopathological findings of 13 myoepitheliomas of soft tissue and bone (MESTBs) and two myoepithelioma-like tumors of the vulvar region (MELTVRs), focusing on the association between nuclear atypia and clinical course, and the utility of immunohistochemistry (IHC) of pleomorphic adenoma gene 1 (PLAG1) for the pathological diagnosis of these tumors. Of the 13 MESTBs, eight, one and four cases exhibited mild, moderate and severe nuclear atypia, respectively. Two cases with venous invasion showed severe nuclear atypia and both died of advanced disease. Two MELTVR cases showed moderate nuclear atypia and had no evidence of disease after surgery. On IHC, 12 of 13 (92.3%) MESTBs showed PLAG1 immunoreactivity and none of the MELTVRs expressed PLAG1. In addition, MELTVRs showed loss of INI1 expression. In contrast, all MESTBs retained INI1 expression. Fluorescence in situ hybridization detected EWSR1, FUS and PLAG1 rearrangement in 5 (38.5%), 0 (0%) and 2 (15.4%) of the 13 MESTBs, respectively. No EWSR1, FUS and PLAG1 rearrangement were observed in the METLVRs. In conclusion, MESTBs with both severe nuclear atypia and venous invasion would be indicative of malignant potential. PLAG1 might be a useful IHC marker in MESTB diagnosis.


Assuntos
Proteínas de Ligação a DNA , Mioepitelioma , Neoplasias Vulvares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Criança , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mioepitelioma/metabolismo , Mioepitelioma/patologia , Prognóstico , Proteína EWS de Ligação a RNA/genética , Proteína EWS de Ligação a RNA/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia , Neoplasias Vulvares/metabolismo , Neoplasias Vulvares/patologia
19.
Ann Diagn Pathol ; 49: 151625, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32932018

RESUMO

To analyze clinicopathological features, including treatment profile of 34 cases of Ewing sarcomas with epithelial differentiation, including 6 cases with adamantinoma-like features. EWSR1 gene rearrangement was tested by fluorescence in-situ hybridization. Thirty-four tumors occurred in 19 males and 15 females (M:F = 1.26:1), with age ranging from 7 to 61 years (average = 24.2); in extremities (17), pelvis (5), paraspinal region (6), head and neck region (3), abdomen (2) and lung (1). Prior to molecular testing, 20/34(58.8%) cases were unequivocally diagnosed as Ewing sarcomas. Histopathologically, the most commonly observed pattern was nesting-type, comprising malignant round cells, including adamantinoma-like features, seen in 6 tumors. Immunohistochemically, tumor cells were diffusely positive (cytoplasmic membranous staining) for CD99/MIC2 (34/34), Fli1 (30/30); focally for synaptophysin (4/16) (25%); variably positive for AE1/AE3(31/32)(96.8%), including diffuse immunoexpression in 4 cases; EMA(6/8) and p40(3/8). All 34 (100%) tumors, tested for EWSR1 rearrangement, displayed positive results. According to the treatment details (available in 24/34 cases, 70.5%), most patients (13/24)(54.1%) were treated with surgical resection and a specific chemotherapy(CT) regimen (neoadjuvant or adjuvant settings), including 7 patients, who received adjuvant radiotherapy. During follow-up (16 cases, 47%), 5 patients developed recurrences and 8 developed metastasis, including a single, who developed recurrence. Finally, 10 patients were alive-with-disease (2-22 months); 6 free-of-disease (5-36 months). This constitutes one of the largest documentation of these rare tumors from our subcontinent, which are diagnostically challenging; require molecular confirmation and associated with treatment implications.


Assuntos
Neoplasias Ósseas/patologia , Sarcoma de Ewing/patologia , Neoplasias de Tecidos Moles/patologia , Adolescente , Adulto , Biomarcadores Tumorais/análise , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Diferenciação Celular , Criança , Feminino , Humanos , Imuno-Histoquímica , Índia , Masculino , Pessoa de Meia-Idade , Proteína EWS de Ligação a RNA/genética , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/metabolismo , Adulto Jovem
20.
Pediatr Dev Pathol ; 23(6): 424-430, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790583

RESUMO

INTRODUCTION: Somatic internal tandem duplication of 3' of BCOR (BCOR ITD) has been found in clear cell sarcomas of the kidney (CCSK), soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and a subgroup of central nervous system high-grade neuroepithelial tumors (CNS-HGNET). BCOR ITD+ tumors share morphologic features. Expression of OLIG2 and epidermal growth factor receptor (EGFR) has been reported in CNS-HGNET with BCOR ITD. Here, we characterize OLIG2 and EGFR expression in URCS/PMMTI with BCOR ITD. METHODS: Paraffin blocks of 9 polymerase chain reaction-confirmed soft tissue BCOR ITD+ tumors (URCS/PMMTI) were immunophenotyped for OLIG2 and EGFR expression and scored semiquantitatively by percentage of positive cells and intensity of staining as negative, 1+, 2+, and 3+. Fluorescence in situ hybridization (FISH) for EGFR amplification was performed (amplification EGFR/CEP7 ratio ≥2.0). RESULTS: All 9 tumors showed membrane/cytoplasmic expression of EGFR, strong and diffuse (3+) in 8 cases; weak (+2) in 1. FISH detected no EGFR amplification. OLIG2 was negative in all. CONCLUSIONS: EGFR is overexpressed in pediatric URCS/PMMTI with BCOR ITD and may be related to transcriptional upregulation of EGFR by BCOR ITD. OLIG2 negative staining differentiates URCS/PMMTI from CNS-HGNET. This finding may further support the possibility that these tumors have a different stem cell of origin.


Assuntos
Biomarcadores Tumorais/metabolismo , Fator de Transcrição 2 de Oligodendrócitos/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Sarcoma/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Sequências de Repetição em Tandem , Biomarcadores Tumorais/genética , Pré-Escolar , Receptores ErbB/metabolismo , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Imunofenotipagem , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Estudos Retrospectivos , Sarcoma/genética , Sarcoma/patologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Regulação para Cima
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