RESUMO
We report the largest series to date (N = 6) of EWSR1-SMAD3 rearranged fibroblastic tumor. Initially described in 2018, the tumor features a marked female predominance (F:M, 5:1, mean age 44-years, median age 45.5 years; range 27-57), with most cases (5/6, 83%) arising in acral locations (4 on foot/toe, 1 on hand). One case presented on the lower extremity. The lesions presented as nodules and were composed of short, variably cellular, intersecting fascicles of uniform spindled cells in a collagenous to myxoid stroma. In four cases, the tumor abutted the epidermis without a grenz zone. In one case, there was an abrupt transition to a central, acellular hyalinized area. Two other cases had admixed smaller collagenous areas, reminiscent of collagen rosettes. One had a concentric arrangement of tumor cells around blood vessels. Mitotic activity was low (<1/10 HPFs). All were positive for ERG by immunohistochemistry and negative for CD34 (6/6). An EWSR1-SMAD3 fusion was identified in three cases tested by next-generation sequencing (3/3). Rearrangement of EWSR1 by fluorescence in situ hybridization was showed in 1/1 case. Our series reaffirms prior findings and expands the known histopathologic spectrum of this emerging entity.
Assuntos
Rearranjo Gênico , Neoplasias de Tecido Fibroso , Proteínas de Fusão Oncogênica , Proteína EWS de Ligação a RNA , Neoplasias Cutâneas , Proteína Smad3 , Adulto , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Fibroso/genética , Neoplasias de Tecido Fibroso/metabolismo , Neoplasias de Tecido Fibroso/patologia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteína EWS de Ligação a RNA/genética , Proteína EWS de Ligação a RNA/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteína Smad3/genética , Proteína Smad3/metabolismoRESUMO
Atypical fibroxanthoma is a rare mesenchymal skin tumor of intermediate malignancy that typically occurs on sun-damaged skin of elderly patients. Histologically, it is composed of pleomorphic cells with hyperchromatic nuclei and abundant cytoplasm, commonly arranged in a spindle cell pattern. Different histologic variants have been described during the past years. We present a case of atypical fibroxanthoma containing a dense inflammatory infiltrate, which in conjunction with the existence of immunoblast-like and Reed-Sternberg-like neoplastic cells could be misinterpreted as a lymphoid neoplasm. Immunohistochemical studies revealed strong positivity of tumor cells for CD10 and negativity for cytokeratins, p63, p40, S100, SOX10, ERG, actin, desmin, B and T-cell markers, BCL6, CD15, and CD30. The inflammatory infiltrate contained a mixed reactive T- and B-cell population with negative T-cell receptor and immunoglobulin heavy rearrangements. We discuss the differential diagnosis of this entity in which clinical, immunohistochemical, and molecular features are essential to avoid the diagnosis of a lymphoproliferative disease.
Assuntos
Neoplasias de Tecido Fibroso/patologia , Pseudolinfoma/patologia , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Diagnóstico Diferencial , Rearranjo Gênico do Linfócito T , Genes de Cadeia Pesada de Imunoglobulina , Genes Codificadores dos Receptores de Linfócitos T , Humanos , Imuno-Histoquímica , Masculino , Neoplasias de Tecido Fibroso/genética , Neoplasias de Tecido Fibroso/imunologia , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Pseudolinfoma/genética , Pseudolinfoma/imunologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologiaRESUMO
Uterine inflammatory myofibroblastic tumors (IMTs) have been reported in association with pregnancy and, in some instances, secondarily involve the placenta. The clinicopathological spectrum of these tumors in the setting of pregnancy is not well defined. We investigated the clinical, morphologic, immunohistochemical, molecular cytogenetic, and genetic features of 6 uterine IMTs occurring in pregnant women. Each tumor was discovered at parturition, and none was identified by prenatal ultrasound. Patient age ranged from 25 to 41â¯years (mean 31.5). Tumor size ranged from 1.5 to 9â¯cm (mean 4.7). Four of 6 had usual IMT features, with at least focal deciduoid change in 3. Necrosis was identified in 3 tumors; and multinucleated cells, in 3 tumors. Sex hormone receptor expression was consistent with estrogen receptor negative or focally weakly positive and progesterone receptor diffusely moderately or moderately to strongly positive in all 6 tumors. ALK immunohistochemistry was strongly positive in 5 tumors, and all of these had an ALK rearrangement detected by break-apart fluorescence in situ hybridization. Subsequent RNA sequencing of these 5 tumors identified a TIMP3-ALK fusion in 4 and a THBS1-ALK in 1. In the ALK-negative tumor, RNA sequencing detected a novel TIMP3-RET fusion that was confirmed by RET break-apart fluorescence in situ hybridization. Follow-up was available for 2 of 6 patients 5 and 19â¯months after diagnosis. Neither patient developed recurrence. ALK immunohistochemistry will distinguish most uterine IMTs, but if ALK expression and gene studies are negative, in the appropriate morphologic context, evaluation of other tyrosine kinase genes known to be more commonly altered in extrauterine IMTs such as ROS1, NTRK3, PDGFRß, and RET may be necessary for diagnostic confirmation.
Assuntos
Biomarcadores Tumorais/genética , Fusão Gênica , Miofibroblastos/patologia , Neoplasias de Tecido Fibroso/genética , Placenta/patologia , Complicações Neoplásicas na Gravidez/genética , Proteínas Proto-Oncogênicas c-ret/genética , Inibidor Tecidual de Metaloproteinase-3/genética , Neoplasias Uterinas/genética , Adulto , Quinase do Linfoma Anaplásico/genética , Feminino , Rearranjo Gênico , Predisposição Genética para Doença , Humanos , Necrose , Neoplasias de Tecido Fibroso/patologia , Neoplasias de Tecido Fibroso/terapia , Fenótipo , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/terapia , Resultado do Tratamento , Carga Tumoral , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapiaRESUMO
Over the last 10 years, a number of advances have been made in our understanding of fibroblastic and myofibroblastic tumors. The rapidly evolving field of molecular diagnostics has resulted in the recognition of new entities and better understanding of tumor pathogenesis, while careful clinicopathologic correlative analyses have led to improvements in modeling tumor behavior. This review will discuss new and emerging entities in fibroblastic neoplasia and provide updates on the pathogenesis, diagnosis, and prognostication of these diverse and challenging tumors.
Assuntos
Fibroblastos/patologia , Neoplasias de Tecido Fibroso/patologia , Antígenos CD34/análise , Rearranjo Gênico , Humanos , Neoplasias de Tecido Fibroso/etiologia , Neoplasias de Tecido Fibroso/genética , Prognóstico , Proteína EWS de Ligação a RNA/genética , Sarcoma/patologia , Proteína Smad3/genética , Neoplasias de Tecidos Moles/etiologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologiaRESUMO
Based on histological findings, calcifying fibrous tumor (CFT) may be a late (burned out) stage of inflammatory myofibroblastic tumor (IMT). This concept, however, has not been proven by molecular means. Five CFTs were analyzed for IMT-related rearrangements in ALK, ROS1 and RET using fluorescence in situ hybridization (FISH). Additionally, genome-wide methylation patterns were investigated and compared with IMT (nâ¯=â¯7), leiomyoma (nâ¯=â¯7), angioleiomyoma (nâ¯=â¯9), myopericytoma (nâ¯=â¯7) and reactive soft tissue lesions (nâ¯=â¯10) using unsupervised hierarchical cluster analysis and t distributed stochastic neighbor embedding. CFT patients, 4 females and 1 male, had a median age of 20â¯years ranging from 7 to 43â¯years. Two patients were younger than 18â¯years old. The tumors originated in the abdomen (nâ¯=â¯4) and axilla (nâ¯=â¯1). Histologically, all lesions were (multi) nodular and hypocellular consisting of bland looking (myo)fibroblasts embedded in a collagenous matrix with calcifications. FISH analysis brought up negative results for ALK, RET and ROS1 rearrangements. However, genome-wide methylation analysis revealed overlapping methylation patterns of CFT and IMT forming a distinct homogeneous methylation cluster with exception of one case clustering with myopericytoma/angioleiomyoma. In conclusion, DNA methylation profiling supports the concept that CFT and IMT represent both ends of a spectrum of one entity with CFT being the burn out stage of IMT.
Assuntos
Granuloma de Células Plasmáticas/genética , Neoplasias de Tecido Fibroso/genética , Neoplasias Abdominais/genética , Neoplasias Abdominais/patologia , Adolescente , Adulto , Axila/patologia , Calcinose/genética , Calcinose/patologia , Criança , Metilação de DNA , Epigênese Genética , Feminino , Estudo de Associação Genômica Ampla , Granuloma de Células Plasmáticas/patologia , Humanos , Masculino , Neoplasias de Tecido Fibroso/patologia , Adulto JovemRESUMO
We report a case of a 20-month-old male presenting with seizures who was found to have a hyperintense lesion on T2-weighted images of magnetic resonance imaging in the left medial temporal lobe that was initially clinically and radiologically thought to be either low-grade glioma or focal cortical dysplasia. Histologic, immunohistochemical and molecular evaluation (array comparative genomic hybridization, Archer fusion panel) of the resection specimen demonstrated a highly infiltrative fibroblastic spindle cell neoplasm with mild nuclear atypia and an RBPMS-NTRK3 fusion. NTRK-fused mesenchymal tumors are known to involve extracranial sites but, to our knowledge, have not been described within the central nervous system. Accurate and timely diagnosis of this entity has important prognostic and therapeutic implications, as NTRK-fused tumors may recur locally and may respond to selective kinase inhibitor therapies.
Assuntos
Neoplasias Encefálicas/genética , Receptor com Domínio Discoidina 2/genética , Neoplasias de Tecido Fibroso/genética , Proteínas de Ligação a RNA/genética , Neoplasias Encefálicas/patologia , Humanos , Lactente , Masculino , Neoplasias de Tecido Fibroso/patologia , Fusão Oncogênica/genéticaRESUMO
Calcifying fibrous tumor of the pleura (CFTP) is a rare mesenchymal tumor of unknown pathogenesis. The diagnosis often requires exclusion of other common entities. Our aim was to determine if genomic changes were associated with CFTP that could contribute to mechanisms underlying tumorigenesis. Three cases of CFTP with their corresponding uninvolved control lung tissue were identified. Two patients were male, and 1 was female (age range, 21-32 years). Tumors were multifocal in 2 cases and solitary in 1. Immunohistochemistry for STAT6, BCL-2, CD34, cytokeratin AE1/AE3, calretinin, desmin, S100, ALK, and ß-catenin was used. All immunohistochemistries were negative in CFTPs. DNA was isolated from all 3 pairs of CFTPs and matching normal lungs for whole-exome sequencing. Damaging, tumor-specific, coding variants were identified in 3 genes including multiple heterozygotic, de novo mutations in the Zinc Finger Protein 717 (ZNF717), fascioscapulohumeral muscular dystrophy-1 (FRG1) and cell division cycle 27 (CDC27) genes. Whole-exome sequencing revealed statistically significant, focal, tumor-specific copy number losses among all CFTPs including a large (302 kb) loss at 6p22.2 comprising 32 genes of the histone cluster 1 family and the hemochromatosis (HFE) gene. This is the first study to evaluate the molecular pathogenesis of CFTP and to identify novel deleterious mutations in ZN717, FRG1, and CDC27 genes as well as significant copy number losses on 8 chromosomes with a large loss common to all samples on chromosome 6. These mutations deleteriously altered coding domains in a manner predicted to be damaging to protein function and may contribute to CFTP tumorigenesis.
Assuntos
Variações do Número de Cópias de DNA/genética , Mutação/genética , Neoplasias de Tecido Fibroso/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Feminino , Humanos , Masculino , Neoplasias de Tecido Fibroso/diagnóstico , Análise de Sequência de DNA/métodos , Sequenciamento do Exoma/métodosRESUMO
Benign/low-grade fibroblastic tumors encompass a broad spectrum of tumors with different morphologies and molecular genetic abnormalities. However, despite significant progress in recent genomic characterization, there are still tumors in this histologic spectrum that are difficult to classify, lacking known molecular characteristics. Triggered by a challenging congenital spindle cell neoplasm arising in the heel of a 1-year-old boy, we applied RNA sequencing for genetic discovery and identified a novel EWSR1-SMAD3 gene fusion. On the basis of the index case superficial acral location and fibroblastic appearance with a nonspecific immunophenotype, we searched our files for similar cases and screened them by fluorescence in situ hybridization for these abnormalities. Thus an identical EWSR1-SMAD3 fusion was identified in 2 additional spindle cell tumors with similar clinicopathologic features. Both cases occurred in the feet of adult women (58 and 61 y old) and were characterized by distinctive nodular growth with zonation pattern of peripheral hypercellular areas arranged in short fascicles, transitioning to hypocellular central areas of hyalinization and infarction. Focal stippled calcification in the collagenous area was present in 1 case. All 3 tumors had similar immunoprofiles, being negative for SMA, CD34, CD31, and S100, but showing consistent ERG positivity of uncertain significance. Follow-up information was available in 2 patients who developed local recurrences after incomplete initial excisions, at 5 and 14 months, respectively. None developed metastatic disease. In summary, we report a group of locally recurrent superficial acral tumors, characterized by bland spindle cell fascicular growth, occasional zonation pattern, ERG positivity, and recurrent EWSR1-SMAD3 gene fusions.
Assuntos
Biomarcadores Tumorais/genética , Fusão Gênica , Neoplasias de Tecido Fibroso/genética , Proteína EWS de Ligação a RNA/genética , Neoplasias Cutâneas/genética , Proteína Smad3/genética , Biomarcadores Tumorais/análise , Feminino , Fibroblastos/química , Fibroblastos/patologia , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lactente , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Fibroso/química , Neoplasias de Tecido Fibroso/patologia , Neoplasias de Tecido Fibroso/cirurgia , Fenótipo , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Regulador Transcricional ERG/análiseRESUMO
Here, we report an inflammatory myofibroblastic tumor (IMT) of the urinary bladder with a novel HNRNPA1-ALK fusion. To the best of our knowledge, this is the first case of a tumor with HNRNPA1-ALK fusion. A 42-year-old Japanese man underwent total cystectomy because of an invasive urinary bladder tumor. Grossly, the tumor had invaded the peribladder fat tissue. Histologically, it comprised spindle neoplastic cells with intermingled inflammatory cells. Immunohistochemically, it was positive for ALK, SMA, desmin, cytokeratin, and vimentin, consistent with the immunohistochemical characteristics of IMTs. Fluorescence in situ hybridization demonstrated an ALK split, and the presence of HNRNPA1-ALK was revealed by RNA sequencing. We identified a novel transcript fusion of exon 2 of HNRNPA1 and exon 18 of ALK, resulting in ALK protein overexpression. These findings provide useful information on the biology and tumorigenesis of IMTs, thus facilitating the development of molecular-targeted therapeutics.
Assuntos
Biomarcadores Tumorais/genética , Fusão Gênica , Ribonucleoproteína Nuclear Heterogênea A1/genética , Miofibroblastos , Neoplasias de Tecido Fibroso/genética , Receptores Proteína Tirosina Quinases/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Quinase do Linfoma Anaplásico , Biomarcadores Tumorais/análise , Cistectomia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Imageamento por Ressonância Magnética , Masculino , Miofibroblastos/enzimologia , Miofibroblastos/patologia , Neoplasias de Tecido Fibroso/enzimologia , Neoplasias de Tecido Fibroso/patologia , Neoplasias de Tecido Fibroso/cirurgia , Receptores Proteína Tirosina Quinases/análise , Neoplasias da Bexiga Urinária/enzimologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
HT1080 - a human fibrosarcoma-derived cell line - forms aggressive angiogenic tumours in immuno-compromised mice. In spite of its extensive use as a model of tumour angiogenesis, the molecular event(s) initiating the angiogenic program in these cells are not known. Since hypoxia stimulates tumour angiogenesis, we examined the hypoxia-induced events evoked in these cells. In contrast to cells grown under normoxic conditions, hypoxia-primed (1% O(2)) HT1080 cells formed robust tubules on growth factor-reduced matrigel and formed significantly larger tumours in xenograft models in a chetomin-sensitive manner, indicating the role of HIF-1α-mediated transcription in these processes. Immuno-histochemical analyses of tumours formed by GFP-expressing HT1080 cells clearly showed that the tumour cells themselves expressed various angiogenic markers including Neuropilin-1 (NRP-1) and formed functional vessels containing red blood cells, thereby unambiguously demonstrating the vasculogenic mimicry of HT1080 cells in vivo. Experiments performed with the HT1080 cells stably transfected with plasmid constructs expressing shNRP-1 or full-length NRP-1 clearly established that the HIF1α-mediated up-regulation of NRP-1 played a deterministic role in the process. Hypoxia-exposure resulted in an up-regulation of c-Myc and OCT3/4 and a down-regulation of KLF4 mRNAs, suggesting their involvement in the tumour formation and angiogenesis. However, silencing of NRP-1 alone, though not affecting proliferation in culture, was sufficient to abrogate the tumour formation completely; clearly establishing that the hypoxia-mediated HIF-1α-dependent up-regulation of NRP-1 is a critical molecular event involved in the vasculogenic mimicry and tumor formation by HT1080 cells in vivo.
Assuntos
Fibrossarcoma/irrigação sanguínea , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias de Tecido Fibroso/irrigação sanguínea , Neuropilina-1/genética , Oxigênio/farmacologia , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Dissulfetos/farmacologia , Fibrossarcoma/genética , Fibrossarcoma/metabolismo , Inativação Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Alcaloides Indólicos/farmacologia , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Camundongos , Neoplasias de Tecido Fibroso/genética , Neoplasias de Tecido Fibroso/metabolismo , Neovascularização Patológica , Neuropilina-1/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Plasmídeos , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transfecção , Ensaios Antitumorais Modelo de XenoenxertoAssuntos
Tumores do Estroma Gastrointestinal/diagnóstico , Neoplasias do Íleo/diagnóstico , Mutação/genética , Neoplasias de Tecido Fibroso/diagnóstico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Idoso de 80 Anos ou mais , Benzamidas , Análise Mutacional de DNA , Éxons/genética , Evolução Fatal , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Neoplasias do Íleo/genética , Neoplasias do Íleo/metabolismo , Neoplasias do Íleo/patologia , Neoplasias do Íleo/cirurgia , Mesilato de Imatinib , Masculino , Neoplasias de Tecido Fibroso/genética , Neoplasias de Tecido Fibroso/metabolismo , Neoplasias de Tecido Fibroso/patologia , Neoplasias de Tecido Fibroso/cirurgia , Piperazinas , Pirimidinas , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismoRESUMO
Calcifying fibrous tumor (CFT) is a rare benign mesenchymal tumor composed of hyalinized fibrous tissue with interspersed bland fibroblastic spindled cells, scattered psammomatous, and/or dystrophic calcifications and variably prominent mononuclear inflammatory infiltrate. CFTs show a predilection for the abdominal cavity and soft tissue. To date, 6 gastric and 3 intestinal CFTs have been reported. We analyzed 7 gastric CFTs including 6 new cases. Patients were 4 men and 3 women with a mean age of 53 years (range, 40 to 77). Mean tumor size was 2.2 cm. Most tumors originated in the gastric body (6/7). Six were incidental findings at autopsy or during surgery for other diseases. One ulcerated tumor caused iron deficiency anemia and ulcer symptoms. Six tumors involved the muscularis propria with variable submucosal and subserosal extension and 1 arose within thickened muscularis mucosae adjacent to a mucosal invagination. Histology was typical with uniformly hypocellular vaguely storiform collagen, lymphoplasmacytic infiltrates, lymphoid aggregates and psammomatous, and dystrophic calcifications. Peritumoral lymphoid aggregates were seen in 3 cases. Adjacent muscle coat contained lymphoid aggregates with fiber degeneration (2), minute CFT-like foci (1), and calcifications (1). In none of the cases were there remnants of burnt-out GIST, inflammatory fibroid polyp, inflammatory myofibroblastic tumor, leiomyoma, schwannoma, or other specific lesion. All tumors were negative for CD117, S100, smooth muscle actin, desmin, ALK1, h-caldesmon, and PDGFRA. Two stained focally with CD34. Scattered IgG4-positive plasma cells were seen in 4 of 6 cases stained with this marker. All 5 tumors with available tissue for molecular analysis were wild-type for KIT and PDGFRA. Three patients had follow-up (range, 12 to 24 mo); none developed recurrence. Gastric CFTs are distinct from sclerosing GIST and other mesenchymal gut lesions and may represent a localized inflammatory fibrosclerosis in response to immune-mediated or other-type tissue injury affecting the muscularis propria. They differ from soft tissue CFTs by smaller size, older age at presentation and lack of recurrence, and from peritoneal CFTs by equal gender distribution, older age, and absent multifocal occurrence.
Assuntos
Calcinose/patologia , Neoplasias de Tecido Fibroso/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Análise Mutacional de DNA , Feminino , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Fibroso/genética , Neoplasias de Tecido Fibroso/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMO
We report on a case of a solitary fibrous tumor that developed in the thigh of an 82-year-old woman. The tumor was composed of areas of high-grade sarcoma and typical solitary fibrous tumor. Its karyotype was: 70,XXX,+X[4],+1[2],add(1)(p36)[4],add(1)[2],+2[4],-3[4],+6[4],add(6)(p11)x2[4],+7[4],+9[3],-11[4],-12[4],-13[4],add(13)(p11)x2[4],-14[4],+15[4],-16[3],-17[4],-19[4],+20,[4],+21[4],+22[2],+mar1x2[4][cp4].
Assuntos
Neoplasias de Tecido Fibroso/patologia , Neoplasias de Tecidos Moles/patologia , Idoso , Idoso de 80 Anos ou mais , Análise Citogenética , Feminino , Humanos , Neoplasias de Tecido Fibroso/genética , Neoplasias de Tecidos Moles/genética , Coxa da PernaRESUMO
Lipomatous hemangiopericytoma is a rare mesenchymal tumor showing areas of lipid-containing cells admixed with a spindle-cell component. Like other hemangiopericytomas, it shows a similar vascular pattern to solitary fibrous tumor and, partly for this reason, it and other hemangiopericytomas have been subsumed into solitary fibrous tumor. The present study provides a comprehensive documentation of a single case of pulmonary lipomatous hemangiopericytoma of the lung, the first to be described at this site, and compares it with solitary fibrous tumor, in terms of clinical, histological, immunohistochemical, ultrastructural, and cytogenetic findings. Apart from the lipid-laden-cell component, pulmonary lipomatous hemangiopericytoma and solitary fibrous tumor were similar histologically. Bcl-2 was positive in both. CD34 was minimally expressed in pulmonary lipomatous hemangiopericytoma, which possessed some non-descriptive intercellular junctions, a feature shared by solitary fibrous tumor, which was CD34 positive. However, one of the latter was rich in gap junctions, a feature consistent with strong connexin (Cx) 43 staining and the existence, hitherto unappreciated, of a CD34/Cx43-positive tumor cell network. In pulmonary lipomatous hemangiopericytoma, chromosomal deletions of 43-44, X, -Y were found. In solitary fibrous tumor, 46, XY, del(13)(q?) abnormalities and abnormalities involving chromosome 10 were frequently observed. These similarities and differences are discussed in the context of the currently favored diagnostic fusion of hemangiopericytoma and solitary fibrous tumor.
Assuntos
Hemangiopericitoma/ultraestrutura , Lipoma/ultraestrutura , Neoplasias Pulmonares/ultraestrutura , Neoplasias de Tecido Fibroso/ultraestrutura , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/análise , Aberrações Cromossômicas , Conexina 43/análise , Análise Citogenética , Diagnóstico Diferencial , Feminino , Hemangiopericitoma/química , Hemangiopericitoma/diagnóstico , Hemangiopericitoma/genética , Humanos , Imuno-Histoquímica , Lipoma/química , Lipoma/diagnóstico , Lipoma/genética , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Neoplasias de Tecido Fibroso/química , Neoplasias de Tecido Fibroso/diagnóstico , Neoplasias de Tecido Fibroso/genética , Proteínas Proto-Oncogênicas c-bcl-2/análiseRESUMO
A case of solitary fibrous tumor of the pleura with the karyotype 46,XY,t(8;12)(p11.2;q24.3) is reported. Although rearrangement of 12q15 approximately 24 is a recurring abnormality in solitary fibrous tumors, rearrangement of chromosome 8 was previously unreported in these tumors.
Assuntos
Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 8/genética , Neoplasias de Tecido Fibroso/genética , Neoplasias Pleurais/genética , Translocação Genética/genética , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Neoplasias de Tecido Fibroso/patologiaRESUMO
A 3-month-old African American female infant had a rapidly growing lipoblastoma with a prominent fibrous component in the soft tissue of the left lateral knee, which recurred at 10 months. Cytogenetic analysis revealed deletion of 8(q11.2q13) with a 19(q12q13.3) insertion at that site, confirming that this is closely related to the conventional lipoblastoma. The presence of multivacuolated lipoblasts and the staining characteristics (no staining for CD99, CD34, or smooth muscle actin) distinguish this from the recently described lipofibromatosis.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 8 , Neoplasias Lipomatosas/genética , Neoplasias Lipomatosas/patologia , Neoplasias de Tecido Fibroso/genética , Neoplasias de Tecido Fibroso/patologia , Deleção Cromossômica , Cromossomos Humanos Par 19 , Feminino , Humanos , Lactente , Joelho , Recidiva Local de Neoplasia/genética , Translocação GenéticaRESUMO
We report the case of an 18-month-old girl who came to medical attention with a left cervical mass. Surgical excision was performed 16 months later. Histology revealed a fibrous hamartoma of infancy. Follow-up has been uneventful, and no recurrence of the mass has been observed. Cytogenetic analysis showed a complex translocation involving chromosomes 6, 8, and 12, namely, t(6;12;8)(q25;q24.3;q13). This case represents the second cytogenetic analysis reported to date in fibrous hamartoma of infancy and reveals a different translocation than the reciprocal translocation t(2;3)(q31;q21) previously reported.
Assuntos
Cromossomos Humanos Par 12 , Cromossomos Humanos Par 6 , Cromossomos Humanos Par 8 , Hamartoma/genética , Translocação Genética , Pré-Escolar , Feminino , Hamartoma/patologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Lactente , Neoplasias de Tecido Fibroso/genética , Neoplasias de Tecido Fibroso/patologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologiaRESUMO
Pleural malignant solitary fibrous tumors (SFTs) are uncommon, and little is known about their histogenesis and molecular features. We report a case of pleural SFT with sarcomatous overgrowth that showed expression for PDGFRbeta and a missense mutation on exon 18 of the PDGFRbeta gene. The involvement of the PDGFRbeta gene in SFT is compatible with a pericytic derivation, also supporting a possible role of this tyrosine kinase in malignant transformation and in the adoption of novel molecular therapies.
Assuntos
DNA de Neoplasias/genética , Mutação , Neoplasias de Tecido Fibroso/complicações , Neoplasias Pleurais/complicações , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Sarcoma/complicações , Idoso , Biópsia , Broncoscopia , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Neoplasias de Tecido Fibroso/diagnóstico , Neoplasias de Tecido Fibroso/genética , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/genética , Sarcoma/diagnóstico , Sarcoma/genética , Tomografia Computadorizada por Raios XRESUMO
Using comparative genomic hybridization (CGH), array CGH, fluorescence in situ hybridization, and loss of heterozygosity analysis, we examined a recurrent solitary fibrous tumor of the orbit for chromosomal imbalances. In the primary tumor, loss of chromosomal material was observed at 9p, 9q, and 16q. In the first recurrent tumor, cells with these abnormalities were detected, but in some parts of the tumor, cells with losses at 13q (homozygous deletion at 13qter) and 20p were dominant. In the second recurrence, only cells with losses at 13q and 20p were seen. Although morphologically similar, the second recurrent tumor invaded the anterior cranial fossa and demonstrated considerably faster growth than the first recurrent tumor. Thus, the clone of tumor cells that dominated the second recurrent tumor was shown by cytogenetic analysis to be different from that present in the primary tumor, and was associated with a more aggressive nature of the tumor.
Assuntos
Aberrações Cromossômicas , Neoplasias de Tecido Fibroso/genética , Neoplasias Orbitárias/genética , Adulto , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 9 , Fossa Craniana Anterior , Feminino , Humanos , Hibridização in Situ Fluorescente , Perda de Heterozigosidade , Recidiva Local de Neoplasia , Neoplasias da Base do Crânio/genética , Neoplasias da Base do Crânio/secundárioRESUMO
This report describes the occurrence of solitary fibrous tumors of the pleura in a mother and her daughter. No other occurrence of this rare tumor in members of the same family has ever been reported.