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1.
Cell Prolif ; 54(8): e13090, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34197016

RESUMO

OBJECTIVES: Derivation and maintenance of pluripotent stem cells (PSCs) generally require optimized and complex culture media, which hinders the derivation of PSCs from various species. Expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) can reprogram somatic cells into induced PSCs (iPSCs), even for species possessing no optimal culture condition. Herein, we explored whether expression of OSKM could induce and maintain pluripotency without PSC-specific growth factors and signaling inhibitors. METHODS: The culture medium of Tet-On-OSKM/Oct4-GFP mouse embryonic stem cells (ESCs) was switched from N2B27 with MEK inhibitor, GSK3ß inhibitor, and leukemia inhibitory factor (LIF) (2iL) to N2B27 with doxycycline. Tet-On-OSKM mouse embryonic fibroblast (MEF) cells were reprogrammed in N2B27 with doxycycline. Cell proliferation was traced. Pluripotency was assessed by expression of ESC marker genes, teratoma, and chimera formation. RNA-Seq was conducted to analyze gene expression. RESULTS: Via continuous expression of OSKM, mouse ESCs (OSKM-ESCs) and the resulting iPSCs (OSKM-iPSCs) reprogrammed from MEF cells propagated stably, expressed pluripotency marker genes, and formed three germ layers in teratomas. Transcriptional landscapes of OSKM-iPSCs resembled those of ESCs cultured in 2iL and were more similar to those of ESCs cultured in serum/LIF. Furthermore, OSKM-iPSCs contributed to germline transmission. CONCLUSIONS: Expression of OSKM could induce and maintain mouse pluripotency without specific culturing factors. Importantly, OSKM-iPSCs could produce gene-modified animals through germline transmission, with potential applications in other species.


Assuntos
Autorrenovação Celular , Reprogramação Celular , Fatores de Transcrição/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Autorrenovação Celular/efeitos dos fármacos , Doxiciclina/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Edição de Genes , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator Inibidor de Leucemia/farmacologia , Camundongos , Camundongos Transgênicos , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Teratoma/metabolismo , Teratoma/patologia , Fatores de Transcrição/genética , Transcriptoma/efeitos dos fármacos
2.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205983

RESUMO

In the human embryo, the genetic program that orchestrates germ cell specification involves the activation of epigenetic and transcriptional mechanisms that make the germline a unique cell population continuously poised between germness and pluripotency. Germ cell tumors, neoplasias originating from fetal or neonatal germ cells, maintain such dichotomy and can adopt either pluripotent features (embryonal carcinomas) or germness features (seminomas) with a wide range of phenotypes in between these histotypes. Here, we review the basic concepts of cell specification, migration and gonadal colonization of human primordial germ cells (hPGCs) highlighting the analogies of transcriptional/epigenetic programs between these two cell types.


Assuntos
Neoplasias Embrionárias de Células Germinativas/genética , Teratoma/genética , Neoplasias Testiculares/genética , Transcrição Genética , Diferenciação Celular/genética , Epigenômica , Células Germinativas/crescimento & desenvolvimento , Células Germinativas/patologia , Gônadas/crescimento & desenvolvimento , Gônadas/patologia , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Células-Tronco Pluripotentes/citologia , Teratoma/patologia , Neoplasias Testiculares/patologia
4.
Cancer Sci ; 112(7): 2921-2927, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33934450

RESUMO

Mature teratomas are usually benign tumors that rarely undergo malignant transformation. We report an advanced neuroblastoma arising in a mature teratoma of the ovary. Whole-exome sequencing identified extensive copy-neutral loss of heterozygosity (LOH) in both neuroblastoma and teratoma elements, suggesting that the neuroblastoma evolved from the teratoma. In addition, several truncating germline heterozygous variants in tumor suppressor genes, including RBL2 and FBXW12, became homozygous as a result of LOH. Collectively, we speculate that extensive LOH in teratoma cells may force heterozygous germline variants to become homozygous, which, in turn, may contribute to the development of neuroblastoma with the acquisition of additional chromosomal changes.


Assuntos
Mutação em Linhagem Germinativa , Perda de Heterozigosidade , Neoplasias Primárias Múltiplas/genética , Neuroblastoma/genética , Neoplasias Ovarianas/genética , Teratoma/genética , Adolescente , Proteínas F-Box/genética , Feminino , Homozigoto , Humanos , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/patologia , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Proteína p130 Retinoblastoma-Like/genética , Teratoma/tratamento farmacológico , Teratoma/patologia , Sequenciamento Completo do Exoma
5.
Int J Mol Sci ; 22(9)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922276

RESUMO

Sialidosis, caused by a genetic deficiency of the lysosomal sialidase gene (NEU1), is a systemic disease involving various tissues and organs, including the nervous system. Understanding the neurological dysfunction and pathology associated with sialidosis remains a challenge, partially due to the lack of a human model system. In this study, we have generated two types of induced pluripotent stem cells (iPSCs) with sialidosis-specific NEU1G227R and NEU1V275A/R347Q mutations (sialidosis-iPSCs), and further differentiated them into neural precursor cells (iNPCs). Characterization of NEU1G227R- and NEU1V275A/R347Q- mutated iNPCs derived from sialidosis-iPSCs (sialidosis-iNPCs) validated that sialidosis-iNPCs faithfully recapitulate key disease-specific phenotypes, including reduced NEU1 activity and impaired lysosomal and autophagic function. In particular, these cells showed defective differentiation into oligodendrocytes and astrocytes, while their neuronal differentiation was not notably affected. Importantly, we found that the phenotypic defects of sialidosis-iNPCs, such as impaired differentiation capacity, could be effectively rescued by the induction of autophagy with rapamycin. Our results demonstrate the first use of a sialidosis-iNPC model with NEU1G227R- and NEU1V275A/R347Q- mutation(s) to study the neurological defects of sialidosis, particularly those related to a defective autophagy-lysosome pathway, and may help accelerate the development of new drugs and therapeutics to combat sialidosis and other LSDs.


Assuntos
Astrócitos/patologia , Células-Tronco Pluripotentes Induzidas/patologia , Mucolipidoses/patologia , Células-Tronco Neurais/patologia , Neuraminidase/metabolismo , Oligodendroglia/patologia , Teratoma/patologia , Astrócitos/metabolismo , Autofagia , Diferenciação Celular , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Lisossomos , Mucolipidoses/genética , Mucolipidoses/metabolismo , Mutação , Células-Tronco Neurais/metabolismo , Neuraminidase/genética , Oligodendroglia/metabolismo , Fenótipo , Teratoma/genética , Teratoma/metabolismo
6.
Nat Commun ; 12(1): 2382, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888706

RESUMO

Conventional approaches to identify secreted factors that regulate homeostasis are limited in their abilities to identify the tissues/cells of origin and destination. We established a platform to identify secreted protein trafficking between organs using an engineered biotin ligase (BirA*G3) that biotinylates, promiscuously, proteins in a subcellular compartment of one tissue. Subsequently, biotinylated proteins are affinity-enriched and identified from distal organs using quantitative mass spectrometry. Applying this approach in Drosophila, we identify 51 muscle-secreted proteins from heads and 269 fat body-secreted proteins from legs/muscles, including CG2145 (human ortholog ENDOU) that binds directly to muscles and promotes activity. In addition, in mice, we identify 291 serum proteins secreted from conditional BirA*G3 embryo stem cell-derived teratomas, including low-abundance proteins with hormonal properties. Our findings indicate that the communication network of secreted proteins is vast. This approach has broad potential across different model systems to identify cell-specific secretomes and mediators of interorgan communication in health or disease.


Assuntos
Carbono-Nitrogênio Ligases/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteômica/métodos , Proteínas Repressoras/metabolismo , Coloração e Rotulagem/métodos , Animais , Animais Geneticamente Modificados , Biotina/metabolismo , Biotinilação , Carbono-Nitrogênio Ligases/genética , Linhagem Celular , Modelos Animais de Doenças , Drosophila , Células-Tronco Embrionárias , Proteínas de Escherichia coli/genética , Feminino , Humanos , Masculino , Camundongos , Engenharia de Proteínas , Transporte Proteico , Proteínas Repressoras/genética , Espectrometria de Massas em Tandem/métodos , Teratoma/diagnóstico , Teratoma/patologia
7.
Indian J Pathol Microbiol ; 64(2): 385-389, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33851642

RESUMO

Mature cystic teratoma of the ovary (MCT) is rare in pre and postmenopausal age patients. Among various types of malignant transformation in MCT, adenocarcinoma is a rare subtype. Dual type tumors arising from ovarian MCT have been described in the literature very rarely. A 47-year-old postmenopausal female patient presented with abdominal mass for ten years. The radiological opinion was a dermoid cyst. Grossly, a 22 × 20 × 10 cm, unilocular cystic left ovarian mass with intact capsular surface and focal thickened wall measured 3.0 cm. Microscopically, it showed components of all three germ cell layers. In addition, features of colonic type adenocarcinoma and well-differentiated neuroendocrine tumor (carcinoid) were noted and confirmed by immunohistochemistry (IHC). We report this rare case of synchronous malignancy arising from an ovarian MCT with a clinicopathological review.


Assuntos
Adenocarcinoma/patologia , Tumor Carcinoide/patologia , Neoplasias do Colo/patologia , Neoplasias Ovarianas/patologia , Teratoma/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Adulto , Idoso , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/cirurgia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Ovário/patologia , Pós-Menopausa , Teratoma/diagnóstico , Teratoma/cirurgia
8.
Adv Anat Pathol ; 28(4): 258-275, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33871428

RESUMO

Testicular tumors are incredibly diverse and one of the most challenging areas in surgical pathology. Because of the rarity and overlapping features with numerous entities occurring in the testis and paratestis, these tumors pose a diagnostic challenge even to the most experienced general pathologists. In 2016, the latest "World Health Organization (WHO) classification of testicular tumors" was released, which incorporated several updates to the previous 2004 classification system. These updates involved several entities, including germ cell tumors, sex cord-stromal tumors, tumors containing both germ cells and sex-cord stromal cells, a miscellaneous group of testicular tumors and paratesticular tumors. In addition, significant changes were also introduced in the 2018 AJCC TNM staging (8th edition) regarding testicular tumors. The germ cell tumors are divided into 2 major groups; tumors derived from germ cell neoplasia in situ (GCNIS) and those unrelated to GCNIS. The GCNIS associated tumors include seminomatous and nonseminomatous germ cell tumors, which constitute a heterogeneous group of tumors. Non-GCNIS-associated tumors include prepubertal-type teratoma, prepubertal yolk sac tumor, mixed prepubertal-type teratoma and yolk sac tumor and spermatocytic seminoma. In the sex cord-stromal category, the tumors are classified based on their cells of origin. Most are Leydig cell tumors and Sertoli cell tumors; however, several mixed and diverse entities based on cell types are included in this group. Gonadoblastoma is the only tumor in the mixed germ cell and sex cord-stromal tumor category. Because of recent advances in molecular techniques, abundant new genetic information has emerged which helped classify the tumors based on the molecular alterations and provided insights into the tumor pathogenesis. This review focused on the updates related to testicular germ cell tumors and sex cord-stromal tumors and described the morphologic, immunohistochemical and molecular characteristics with an aim to provide a practical diagnostic approach and an update on relevant recent molecular advances.


Assuntos
Tumor do Seio Endodérmico/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Seminoma/patologia , Teratoma/patologia , Neoplasias Testiculares/patologia , Tumor do Seio Endodérmico/genética , Tumor do Seio Endodérmico/metabolismo , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/metabolismo , Seminoma/genética , Seminoma/metabolismo , Teratoma/genética , Teratoma/metabolismo , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo
9.
Cells ; 10(4)2021 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-33800535

RESUMO

Regenerative medicine in ophthalmology that uses induced pluripotent stem cells (iPS) cells has been described, but those studies used iPS cells derived from fibroblasts. Here, we generated iPS cells derived from iris cells that develop from the same inner layer of the optic cup as the retina, to regenerate retinal nerves. We first identified cells positive for p75NTR, a marker of retinal tissue stem and progenitor cells, in human iris tissue. We then reprogrammed the cultured p75NTR-positive iris tissue stem/progenitor (H-iris stem/progenitor) cells to create iris-derived iPS (H-iris iPS) cells for the first time. These cells were positive for iPS cell markers and showed pluripotency to differentiate into three germ layers. When H-iris iPS cells were pre-differentiated into neural stem/progenitor cells, not all cells became positive for neural stem/progenitor and nerve cell markers. When these cells were pre-differentiated into neural stem/progenitor cells, sorted with p75NTR, and used as a medium for differentiating into retinal nerve cells, the cells differentiated into Recoverin-positive cells with electrophysiological functions. In a different medium, H-iris iPS cells differentiated into retinal ganglion cell marker-positive cells with electrophysiological functions. This is the first demonstration of H-iris iPS cells differentiating into retinal neurons that function physiologically as neurons.


Assuntos
Fenômenos Eletrofisiológicos , Células-Tronco Pluripotentes Induzidas/fisiologia , Iris/citologia , Regeneração Nervosa/fisiologia , Neurônios Retinianos/fisiologia , Diferenciação Celular , Células Cultivadas , Reprogramação Celular , Corpos Embrioides/metabolismo , Células-Tronco Embrionárias/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Proteínas do Tecido Nervoso/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Recoverina/metabolismo , Reprodutibilidade dos Testes , Células Ganglionares da Retina/metabolismo , Neurônios Retinianos/citologia , Teratoma/patologia
10.
J Biochem Mol Toxicol ; 35(6): 1-9, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33759321

RESUMO

Among the various gynaecological cancers, ovarian cancer (OC) is the third most severe cancer worldwide affecting women. Syringic acid (SRA) exhibits several hypoglycaemia, antioxidant, and anti-inflammatory properties. The study aimed to examine the proapoptotic activities of SRA on OC in PA-1 cells. SRA has been shown to decrease cell viability, increase the rate of cell apoptosis, and cause mitochondrial membrane potential to dissipate and induce over-accumulation of intracellular reactive oxygen species in PA-1 cells after 24 h of exposure. We examined the anticancer efficacy of SRA with its responsible molecular mechanism in the PA-1 cell lines of human OC. In a dose-dependent manner, SRA substantially suppressed cell proliferation and migration. SRA exhibited significant downregulation of cyclins including CDK2, CDK4, and Cyclin D1 responsible for cell-cycle regulation. The apoptosis-mediated anticancer activity was mainly mediated through caspase-3, caspase-8, caspase-9 and Bax upregulation, and Bcl-2 downregulation. We report that SRA significantly inhibits the expression of signal transducer and activator of transcription 3 (STAT3), c-Jun N-terminal kinase (JNK), P65, and protein kinase B (AKT) pathways. These findings depict the effective inhibition of STAT3, p38, and AKT expression by SRA, making it a potential therapeutic candidate for human OC.


Assuntos
Proliferação de Células/efeitos dos fármacos , Ácido Gálico/análogos & derivados , MAP Quinase Quinase 4/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Teratoma/metabolismo , Linhagem Celular Tumoral , Feminino , Ácido Gálico/farmacologia , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Teratoma/tratamento farmacológico , Teratoma/patologia
11.
Ann Surg Oncol ; 28(7): 3648-3655, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33689081

RESUMO

PURPOSE: Following radical orchiectomy, surveillance and primary retroperitoneal lymph node dissection (RPLND) are acceptable options for the management of early stage pure testicular teratoma in adult patients; however, there is no uniform consensus. The aim of this study was to investigate survival outcomes of adults with early stage pure testicular teratoma based on management strategy. METHODS: Data was extracted from the National Cancer Database (NCDB) from testicular cancer patients diagnosed with clinical stage (CS) I pure teratoma (pT1-4N0M0S0) between 2004 and 2014. Kaplan-Meier and Cox regression analyses were used to assess clinical outcomes based on management strategy. RESULTS: Of the 61,167 patients diagnosed with testicular cancer, 692 (1.1%) had pure teratoma. Only individuals with CS I disease were considered (n = 237). The median age was 28 (23-35) years. Overall, 43 (18%) patients underwent RPLND and 194 (82%) patients were managed with surveillance. There was an increase in surveillance for CS I teratoma during the study period. Increasing distance from residence to treatment facility was an unadjusted predictor for undergoing primary RPLND (p < 0.001). Median follow-up was 54 months and there was no significant difference in overall survival between CS I teratoma patients managed with RPLND and those managed with surveillance (p = 0.13). CONCLUSIONS: There has been a trend toward increasing adoption of surveillance for the management of early stage pure testicular teratoma in adults. Our findings suggest that surveillance provides comparable survival outcomes to primary retroperitoneal lymph node dissection in this setting.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Teratoma , Neoplasias Testiculares , Adulto , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Espaço Retroperitoneal/patologia , Espaço Retroperitoneal/cirurgia , Teratoma/patologia , Teratoma/cirurgia , Neoplasias Testiculares/cirurgia
12.
Afr J Paediatr Surg ; 18(2): 99-103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642408

RESUMO

Facial teratomas are uncommon tumours in children that distort the face and may be associated with functional problems. They are less common than cervical teratomas though they are often grouped together and considered an emergency due to their tendency to cause respiratory compromise. They tend to be large and cause cosmetic issues; hence usually noticed early and medical help sought promptly by parents. The close proximity of facial teratomas to structures like eyes, parotid gland, facial nerve, vessels and brain makes them challenging and requires a patient and meticulous exploration during surgery. We present a case of an 11 month old girl with left sided temporal teratoma. Well planning of the incision and complete excision of the tumour with careful sparing of the facial nerves and parotid gland yielded good result.


Assuntos
Neoplasias Faciais/patologia , Neoplasias Faciais/cirurgia , Teratoma/patologia , Teratoma/cirurgia , Neoplasias Faciais/diagnóstico por imagem , Feminino , Humanos , Lactente , Teratoma/diagnóstico por imagem
13.
Medicine (Baltimore) ; 100(13): e24726, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787574

RESUMO

ABSTRACT: Malignant transformation arising in mature cystic teratoma (MT-MCT) is a rare neoplasm of the ovary. Herein, we aimed to evaluate the clinicopathological features and treatment outcome of the Han Chinese women with MT-MCT.In this retrospective study, the clinical data of patients who had been surgically treated from January 2000 to November 2019 and in whom the diagnosis of MCT was confirmed based on the pathology were included. Fourteen patients with MT-MCT from a total of 569 cases (2.46% incidence) of MCT were reviewed.The mean age of patients with MT-MCT was 51.3 (range, 31-71) years, while the mean age of patients with MCT was 45.3 (range, 17-62) years. Upon gross examination, the mean size of MT-MCT was 14.0 (range, 11-25) cm, whereas the mean size of MCT was 7.5 (range, 4-10) cm. Primary surgical staging was performed in all cases. Complete cytoreduction and suboptimal surgical resection were performed in 12 (85.7%) and 2 (14.3%) cases, respectively. Thirteen patients with malignant transformation of squamous cell carcinoma (SCC) whose Federation International of Gynecology and Obstetrics stage was >1 received chemotherapy, comprising carboplatin and paclitaxel. Response to the chemotherapy regimen was complete in 12 patients; 1/12 patients died within the median follow-up period of 16.5 months. The 5-year overall survival rate and disease-free survival rates were 31.2% and 31.6%, respectively.From the data generated, we conclude that the rate of MT-MCT increases with age. The MT-MCT was much higher in women of postmenopausal age than in younger women. We described our experience of successfully treating patients with malignant transformation of SCC with primary surgical staging and adjuvant chemotherapy (cisplatin, paclitaxel, bleomycin, and etoposide) that might improve survival in patients with advanced-stage disease.


Assuntos
Antineoplásicos/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/métodos , Cistos Ovarianos/patologia , Neoplasias Ovarianas/patologia , Ovário/cirurgia , Teratoma/patologia , Adolescente , Adulto , Idoso , Quimioterapia Adjuvante , China , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cistos Ovarianos/terapia , Neoplasias Ovarianas/terapia , Estudos Retrospectivos , Teratoma/terapia , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
14.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670958

RESUMO

Ovarian mature cystic teratomas comprise tissues derived from all three germ layers. In rare cases, malignant tumors arise from ovarian mature cystic teratoma. A variety of tumors can arise from mature cystic teratoma, among which primary malignant melanoma (MM), for which no molecular analyses such as genomic sequencing have been reported to date, is exceedingly rare, thereby limiting possible therapeutic options using precision medicine. We used targeted gene sequencing to analyze the status of 160 cancer-related genes in a patient with MM arising from an ovarian mature cystic teratoma (MM-MCT). KRAS amplification and homozygous deletion in PTEN and RB1 were detected in tumor samples collected from the patient. No KRAS amplification has been previously reported in cutaneous MM, indicating that the carcinogenesis of MM-MCT differs from that of primary cutaneous melanomas. A better understanding of the underlying genetic mechanisms will help clarify the carcinogenesis of MM-MCT. In turn, this will enable treatment with novel targeting agents as well as the initial exploration of gene-based precision oncological therapies, which aim to improve treatment outcomes for patients with this disease.


Assuntos
Genes Neoplásicos , Melanoma/genética , Mutação , Neoplasias Ovarianas/complicações , Teratoma/complicações , Variações do Número de Cópias de DNA , Feminino , Genoma Humano , Humanos , Melanoma/etiologia , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas de Ligação a Retinoblastoma/genética , Análise de Sequência de DNA , Teratoma/patologia , Ubiquitina-Proteína Ligases/genética
15.
Hum Pathol ; 112: 1-8, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33741347

RESUMO

Loss of SMARCB1 protein expression has recently been identified in a variety of tumor types such as poorly differentiated chordoma (PCh) and malignant rhabdoid tumor (MRT) including atypical teratoid/rhabdoid tumor (AT/RT). PCh is characterized by poorly differentiated epithelioid tumor cells, sheet arrangement, and coexpression of nonepithelial and epithelial markers. Rhabdoid cells are sometimes present. Therefore, the differentiation of these tumors is often difficult. Brachyury is a transcription factor within the T-box family typically expressed in notochord tissue and chordomas. Some studies have reported high specificity and sensitivity of brachyury expression in chordomas. In the present study, we analyzed immunohistochemical brachyury expression in SMARCB1-deficient tumors and discuss important clinicopathological and diagnostic points, especially in cases of intracranial SMARCB1-deficient tumors with brachyury expression. Brachyury and cytokeratin immunoexpression status was examined in 42 formalin-fixed paraffin-embedded SMARCB1-deficient tumor specimens (PCh, 6 cases; extra-central nervous system [CNS] MRT, 26 cases; AT/RT, 10 cases) and 25 cases of conventional chordoma (CCh). All cases of PCh and CCh showed diffuse immunopositivities for cytokeratin 8, pan-cytokeratin, and brachyury. Brachyury immunoexpression was present in 2 extra-CNS MRT (8%) and 5 AT/RT (50%) cases, but immunopositivity was focal not diffuse. Indeed, in almost all cases of AT/RT (cytokeratin 8, 7/10 cases; pan-cytokeratin, 7/10 cases) and extra-CNS MRT (cytokeratin 8, 23/26 cases; pan-cytokeratin, 25/26 cases), fewer than 50% of cells showed immunoreactivity. Although the histological and clinical features of PCh resemble those of AT/RT, semiquantitative evaluations of the degree of brachyury and cytokeratin immunoexpressivity may help to distinguish PCh from AT/RT.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/diagnóstico , Cordoma/diagnóstico , Proteínas Fetais/biossíntese , Tumor Rabdoide/diagnóstico , Proteínas com Domínio T/biossíntese , Teratoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Cordoma/metabolismo , Cordoma/patologia , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Tumor Rabdoide/metabolismo , Tumor Rabdoide/patologia , Proteína SMARCB1/deficiência , Teratoma/metabolismo , Teratoma/patologia
16.
Head Neck Pathol ; 15(1): 25-40, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33723758

RESUMO

The spectrum of "developmental" lesions that occur in the head and neck predominantly congenital in origin and arising at birth and/or discovered in childhood is broad and fascinating. These have been grouped into categories such as "ectopias", "heterotopias", "hamartomas", and "choristomas". On a philosophical and consequently systematic level, these lesions, mostly benign tumors seem to lack a true understanding of the pathogenetic foundation on which to base a more unified taxonomic designation. In this review, we will consider some of these select tumors as they represent syndromic associations (nasal chondromesenchymal hamartoma and DICER1 syndrome), the lingual choristoma from the perspective of its nomenclature and classification, lesions with ectopic meningothelial elements, and teratomas and the enigmatic "hairy polyp" in reference to a broader discussion of pathogenesis and pluripotent cells in the head and neck. A consistent thread will be how these lesions are designated with some final thoughts on future directions regarding the investigation of their pathogenesis and taxonomic nomenclature.


Assuntos
Cabeça/anormalidades , Cabeça/patologia , Pescoço/anormalidades , Pescoço/patologia , Otorrinolaringopatias/patologia , Criança , Coristoma/congênito , Coristoma/patologia , Feminino , Hamartoma/congênito , Hamartoma/patologia , Humanos , Masculino , Otorrinolaringopatias/congênito , Teratoma/congênito , Teratoma/patologia
17.
Medicine (Baltimore) ; 100(4): e24323, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530223

RESUMO

ABSTRACT: Although the incidence of malignant sacrococcygeal germ cell tumors (MSGCTs) is high in the East Asian countries, information about MSGCTs from this region is limited. This report aimed to analyze the data of children with MSGCTs in a single medical center in Taiwan.Patients aged 18 years or younger with primary MSGCTs or malignant recurrence of a sacrococcygeal teratoma who underwent surgery during the neonatal period between January 1999 and December 2016 were identified from the Linkou Chang Gung Cancer Center registry. The clinical features, laboratory data, and treatment outcomes were reviewed.Fifteen children (1 man and 15 women) with MSGCTs were identified. Sacrococcygeal tumors were present at birth in 7 patients. All patients presented with a bulging mass at the buttock region and they had normal alpha-fetoprotein levels at the time of diagnosis. They underwent primary excision of the tumor. Immature teratoma was histologically diagnosed in 5 neonates, and mature teratoma in 2. Only 1 patient with grade 3 immature teratoma received adjuvant chemotherapy. Two patients with mature teratoma developed malignant recurrence 1.6 and 2.1 years later, respectively. Eight patients were diagnosed with MSGCTs after the neonatal period. The common presenting symptoms included buttock asymmetry (37.5%), abdominal distension (25%), and constipation (12.5%). Seven patients had elevated alpha-fetoprotein levels for their age. They were administered neoadjuvant chemotherapy followed by tumor excision if a residual tumor was present. The histology of the excised tumor included mature teratoma (66.7%) and necrosis (33.3%). One patient with a normal alpha-fetoprotein level underwent primary tumor excision followed by adjuvant chemotherapy. Grade 2 immature teratoma with embryonal carcinoma was diagnosed histologically. Among the 15 patients with MSGCTs, 3 had a recurrence (at age of 2.1, 0.5, and 2.4 years, respectively) and 1 died (at age of 6.1 years) of disease progression. The 5-year overall and event-free survival rates were 90% and 80%, respectively.Children with MSGCTs had good overall prognoses in this case series. For those with sacrococcygeal mature teratoma or low-grade immature teratoma in the neonatal period, we recommend close follow-up for at least 3 years after surgery to detect malignant recurrence.


Assuntos
Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias da Coluna Vertebral/patologia , Teratoma/patologia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/terapia , Estudos Retrospectivos , Região Sacrococcígea/patologia , Neoplasias da Coluna Vertebral/epidemiologia , Neoplasias da Coluna Vertebral/terapia , Taiwan/epidemiologia , Teratoma/epidemiologia , Teratoma/terapia , Resultado do Tratamento
18.
Int J Gynecol Pathol ; 40(4): 383-390, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33560745

RESUMO

Primary ovarian melanoma arising from ovarian teratomas are rarely reported and difficult to accurately diagnose. Cases in the literature rely on a diagnosis of exclusion, and cases of primary ovarian melanoma with pathologic evidence of melanoma in situ are exceedingly rare. We report a case of a 66-yr-old female who presented to emergency department with abdominal pain and bloating. Computed tomography scan showed a 21 cm complex pelvic mass. An urgent laparoscopic bilateral salpingo-oophorectomy was performed. Pathologically the mass was identified as a mature teratoma. Within the cystic teratoma, there was an area showing a sheet arrangement of atypical cells. Those atypical cells were positive for Melan A, Sox10, HMB45, and c-KIT, and negative for PD-L1. Melanoma in situ was present in both the squamous and ciliated columnar epithelium. The melanoma was negative for PD-L1, and no BRAF (codon 600, exons 11, 14, and 15) or c-KIT (exons 2, 9, 10, 11, 13, 14, 15, 17, 18) mutations were identified, thus supporting the so-called triple negative malignant melanoma. A thorough dermatologic exam was conducted and only a 3 mm skin basal cell carcinoma was confirmed on biopsy. At 11 mo of follow-up, the patient is disease free and doing well and no metastatic melanoma has been identified. To the best of our knowledge, this is the first documented case of a primary ovarian melanoma arising in a mature teratoma with evidence of melanoma in situ present in both ciliated columnar and squamous epithelium in a patient with synchronous skin basal cell carcinoma. Our case is positive for c-KIT protein (CD117) by immunohistochemistry, but negative for KIT mutation. More case reports are needed to further characterize the disease.


Assuntos
Carcinoma Basocelular/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Melanoma/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Proteínas Proto-Oncogênicas c-kit/metabolismo , Teratoma/diagnóstico por imagem , Idoso , Carcinoma Basocelular/patologia , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Células Epiteliais , Epitélio/diagnóstico por imagem , Epitélio/patologia , Epitélio/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Melanoma/patologia , Melanoma/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovário/diagnóstico por imagem , Ovário/patologia , Ovário/cirurgia , Prognóstico , Salpingo-Ooforectomia , Teratoma/patologia , Teratoma/cirurgia , Tomografia Computadorizada por Raios X
19.
Sci Rep ; 11(1): 3483, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568756

RESUMO

Teratomas in mice, composed of different tissue types, are derived from primordial germ cells (PGCs) in the foetal gonads. The strongest candidate gene in the testicular teratoma locus (Ter) responsible for testicular teratoma formation was identified as mutation in Dnd1, Dnd1R178*. However, the phenotype of mice with a mutated Dnd1 gene was germ cell loss. This suggests that other genes are involved in teratoma formation. Testicular teratomas can also be induced experimentally (experimentally testicular teratomas: ETTs) in 129/Sv mice by transplanting E12.5 foetal testes into adult testes. Previously, we mapped the ett1 locus, which is the locus responsible for ETT formation on chromosome 18. By exome sequence analysis of the 129 and LTXBJ (LT) strains, we identified a missense mutation in the melanocortin 4 receptor (MC4R) gene among 8 genes in the ett1 region. The missense mutation causes a substitution of glycine 25 by serine. Thus, this gene is a candidate for ETT formation. We established the LT-ett1 congenic strain, which introduced the locus responsible for ETT formation genetically into the genomes of a testicular teratoma non-susceptible strain. In this study, we crossed LT-ett1 and a previously established LT-Ter strain to establish the double congenic strain LT-Ter-ett1. Also, we established a strain with a point mutation in the MC4R gene of the LT strain by genome editing, LT-MC4RG25S. Furthermore, double genetically modified strain LT-Ter-MC4RG25S was established to address the relation between Ter and MC4R. Surprisingly, highly developed ovarian teratomas (OTs), instead of testicular teratomas, appeared not only in the LT-Ter-MC4RG25S and LT-MC4RG25S strains but also in the LT-ett1 and LT-Ter-ett1 strains. The incidence of OT formation was high in double genetically modified strains. The results demonstrated that MC4R is one of the genes responsible for OT formation. It was suggested that the effect of the missense mutation in MC4R on teratoma formation was promoted by abnormal germ cell formation by the mutation in DND1.


Assuntos
Neoplasias Ovarianas/genética , Receptor Tipo 4 de Melanocortina/genética , Teratoma/genética , Substituição de Aminoácidos , Animais , Sistemas CRISPR-Cas , Feminino , Edição de Genes , Masculino , Camundongos , Mutação , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Oócitos/metabolismo , Neoplasias Ovarianas/patologia , Mutação Puntual , Receptor Tipo 4 de Melanocortina/metabolismo , Teratoma/patologia , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia
20.
Indian J Pathol Microbiol ; 64(1): 171-173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33433434

RESUMO

Collision tumor consists of two tumors occurring in the same organ without intermixture of the two cell types. The most common type of collision tumor in ovary is between teratoma and surface epithelial tumor. A 38-year-old woman presented with complained of lower abdominal pain and tightness, and a solid partially cystic left ovarian mass with minimal ascites was detected. Left salpingo-oophorectomy was performed. The ovarian mass measured 15 × 12 × 7 cm with a pedunculated mass on its surface which measured 6 × 2.5 × 2.5 cm. Histologically, it was a collision tumor of fibroma and mature cystic teratoma. Fibroma becomes more edematous as their size increases, which is frequently accompanied by the escape of increasing quantities of fluid from the tumor surfaces. Ascites is often detected when the fibroma is more than a diameter of 10 cm. It is important to identify the different components of a collision tumor for proper management.


Assuntos
Fibroma/diagnóstico , Cistos Ovarianos/complicações , Neoplasias Ovarianas/diagnóstico , Teratoma/diagnóstico , Teratoma/patologia , Adulto , Feminino , Fibroma/patologia , Fibroma/cirurgia , Humanos , Cistos Ovarianos/diagnóstico por imagem , Cistos Ovarianos/cirurgia , Neoplasias Ovarianas/cirurgia , Ovário/patologia , Ultrassonografia
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