RESUMO
Loss of histone 3 lysine 27 trimethylation (H3K27me3) has been described as a diagnostic marker for malignant peripheral nerve sheath tumor (MPNST), also discriminating MPNST with rhabdomyoblastic differentiation (malignant Triton tumor) from rhabdomyosarcoma (RMS). We studied the immunohistochemical expression of H3K27me3 in embryonal RMSs (ERMSs), performed methylation profiling in order to support the diagnosis and RNA-sequencing for comparison of the transcriptome of H3K27me3-positive and -negative cases. Of the 25 ERMS patients, 17 were males and 8 were females with an age range from 1 to 67 years (median, 6 years). None were known with neurofibromatosis type 1. One patient had Li-Fraumeni syndrome. Tumor localization included paratesticular (n = 9), genitourinary (n = 6), head/neck (n = 5), retroperitoneal (n = 4) and lower arm (n = 1). Five MPNSTs served as reference group. All ERMS had classical features including a variable spindle cell component. Immunohistochemical loss (partial or complete) of H3K27me3 was detected in 18/25 cases (72%). Based on methylation profiling, 22/22 cases were classified as ERMS. Using RNA sequencing, the ERMS group (n = 14) had a distinct gene expression profile in contrast to MPNSTs, confirming that the H3K27me3 negative ERMS cases do not represent malignant Triton tumors. When comparing H3K27me3-negative and -positive ERMSs, gene set enrichment analysis revealed differential expression of genes related to histone acetylation and normal muscle function with H3K27me3 negative ERMSs being associated with acetylation. Conclusion: Loss of H3K27me3 frequently occurs in ERMSs and correlates with H3K27 acetylation. H3K27me3 is not a suitable marker to differentiate ERMS (with spindle cell features) from malignant Triton tumor.
Assuntos
Histonas/genética , Neurofibrossarcoma/patologia , Rabdomiossarcoma Embrionário/genética , Rabdomiossarcoma Embrionário/patologia , Rabdomiossarcoma/patologia , Acetilação , Adolescente , Adulto , Idoso , Diferenciação Celular , Criança , Pré-Escolar , Metilação de DNA , Diagnóstico Diferencial , Feminino , Histonas/metabolismo , Humanos , Imuno-Histoquímica/métodos , Lactente , Masculino , Pessoa de Meia-Idade , Neurofibrossarcoma/diagnóstico , Neurofibrossarcoma/genética , RNA-Seq/métodos , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/genética , Rabdomiossarcoma Embrionário/diagnóstico , Transcriptoma , Adulto JovemRESUMO
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
BACKGROUND: Gallbladder torsion or gallbladder volvulus is a rare condition of the hepatobiliary system, defined as a rotation of the gallbladder along its long axis causing an interruption of the vascular and biliary flow. It clinically mimics acute cholecystitis which makes accurate preoperative diagnosis challenging. CASE DESCRIPTION: We present the case of an 81-year-old woman with a three day history of upper-right quadrant pain, nausea, vomiting and no evidence of cholelithiasis on imaging. Emergency cholecystectomy was performed, intraoperative findings included a necrotic gallbladder with complete torsion. After the secondary diagnosis of gallbladder torsion, the clinical and radiologic findings were reviewed retrospectively. CONCLUSION: The acute onset of abdominal pain without clear progression over time should initially be the trigger for differential diagnostic consideration of gallbladder torsion. This combined with the previously described risk factors and radiological characteristics could result in successful pre-operative diagnosis of gallbladder torsion.
Assuntos
Colelitíase , Doenças da Vesícula Biliar , Feminino , Humanos , Idoso de 80 Anos ou mais , Doenças da Vesícula Biliar/diagnóstico , Doenças da Vesícula Biliar/cirurgia , Doenças da Vesícula Biliar/complicações , Estudos Retrospectivos , Colecistectomia/métodos , Colelitíase/complicações , Dor Abdominal/cirurgia , Anormalidade Torcional/diagnóstico , Anormalidade Torcional/cirurgia , Anormalidade Torcional/complicaçõesRESUMO
Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with variable aggressive clinical behavior. In this retrospective study, we aimed to investigate prognostic factors based on clinicopathologic findings in a molecularly/immunohistochemically confirmed nationwide multicenter cohort of 57 EHE cases. Patients had unifocal disease (n = 29), multifocal disease (n = 5), lymph node metastasis (n = 8) and/or distant metastasis (n = 15) at the time of diagnosis. The overall survival rate was 71.4% at 1 year and 50.7% at 5 years. Survival did not correlate with sex, age or histopathological parameters. No survival differences were observed between multifocal and metastatic disease, suggesting that multifocality represents early metastases and treatment options are limited in comparison to unifocal disease. In unifocal tumors, survival could be predicted using the risk stratification model of Shibayama et al., dividing the cases into low- (n = 4), intermediate- (n = 15) and high- (n = 3) risk groups. No clinical or histopathological parameters were associated with progressive unifocal disease course. Lymph node metastases at the time of diagnosis occurred in 14.0% of the cases and were mainly associated with tumor localization in the head and neck area, proposing lymph node dissection. In conclusion, our results demonstrate the aggressive behavior of EHE, emphasize the prognostic value of a previously described risk stratification model and may provide new insights regarding tumor focality, therapeutic strategies and prognosis.
RESUMO
Nodular fasciitis is usually a benign lesion genetically characterized by ubiquitin-specific protease 6 (USP6) rearrangements. We present a case of a 10-year-old boy with a 1.5-week history of a painless mass on the right chest wall, which was excised. A histomorphologically malignant tumor with pronounced pleomorphism, atypical mitotic figures, and a myoid immunophenotype was observed. The methylation profile was consistent with nodular fasciitis and fluorescence in situ hybridization confirmed USP6 rearrangement. Using Archer Fusion Plex (Sarcoma Panel) and RNA sequencing, a collagen, type VI, alpha 2 (COL6A2)-USP6 gene fusion was subsequently identified. Furthermore, DNA clustering analysis also showed a match with nodular fasciitis. During the follow-up of 22 months, no recurrence or metastasis occurred. In conclusion, we describe a clinically benign, histomorphologically malignant mesenchymal neoplasm with a myoid immunophenotype, and a genetic and epigenetic profile consistent with nodular fasciitis. In such cases, molecular analysis is a useful adjunct to avoid unnecessary overtreatment.