245 results on '"Retroperitoneal Neoplasms genetics"'
Search Results
2. Molecular markers of proliferation, DNA repair, and immune infiltration defines high-risk subset of resectable retroperitoneal sarcomas.
- Author
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Seligson ND, Asmann YW, Almerey T, Zayas YC, Edgar MA, Attia S, Knutson KL, and Bagaria SP
- Subjects
- Humans, Male, Female, Middle Aged, Cell Proliferation, Survival Rate, Follow-Up Studies, Prognosis, Adult, Aged, Lymphocytes, Tumor-Infiltrating immunology, Retroperitoneal Neoplasms surgery, Retroperitoneal Neoplasms pathology, Retroperitoneal Neoplasms genetics, Sarcoma surgery, Sarcoma pathology, Sarcoma genetics, DNA Repair, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism
- Abstract
Introduction: For retroperitoneal sarcomas (RPS), aggressive surgical resection offers the only chance for a cure; however, 5-year survival remains below 65%. Therefore, there is a critical need to identify drivers of poor clinical outcomes., Materials and Methods: To identify biomarkers of tumors likely to recur following curative intent resection, we performed genomic and transcriptomic sequencing for 47 and 34 patients, respectively, with non-metastatic RPS at a single, high-volume sarcoma center., Results: At the DNA level, alterations in TERT were associated with poor disease-free survival (DFS) and overall survival (OS). Increased RNA expression of gene sets related to growth signaling and DNA repair were associated with poor DFS and OS. Infiltration of CD8
+ T-Cells and activated dendritic cells were associated with poor DFS and OS., Conclusion: These findings may help to better identify and treat non-metastatic, high-risk RPS., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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3. Clinicopathological and molecular genetic analysis of 13 cases of primary retroperitoneal Ewing sarcoma.
- Author
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Wei X, Cheng M, Wang L, Teng X, Guo D, Xin X, Chen G, Li S, and Li F
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- Humans, Male, Female, Adult, Retrospective Studies, Middle Aged, Young Adult, Adolescent, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, In Situ Hybridization, Fluorescence methods, Gene Rearrangement, Immunohistochemistry methods, Transcription Factors genetics, Transcription Factors metabolism, Oncogene Proteins, Fusion genetics, Child, Nuclear Proteins, Homeodomain Proteins, Zebrafish Proteins, Sarcoma, Ewing genetics, Sarcoma, Ewing pathology, Sarcoma, Ewing diagnosis, Sarcoma, Ewing metabolism, Homeobox Protein Nkx-2.2, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Retroperitoneal Neoplasms diagnosis, RNA-Binding Protein EWS genetics
- Abstract
Retroperitoneal Ewing sarcomas (RES) are very rare and mostly described in case reports. The purpose of this study was to retrospectively analyze the clinicopathology, molecular characteristics, biological behavior, and therapeutic information of 13 cases of primary RES with immunohistochemical staining, fluorescence in situ hybridization, RT-PCR and NGS sequencing detection techniques. The thirteen patients included eight males and five females with a mean age of 34 years. Morphologically, the tumors were comprised of small round or epithelial-like cells with vacuolated cytoplasm (6/13,46 %) arranged in diffuse, nested (8/13,62 %) and perivascular (7/13,54 %) patterns. Unusual morphologic patterns, such as meningioma-like swirling structures and sieve-like structures were relatively novel findings. Immunohistochemical studies showed CD99 (12/13; 92 %), CD56 (11/13; 85 %), NKX2.2 (9/13; 69 %), PAX7 (10/11;91 %) and CD117(6/9;67 %) to be positive.12 cases (92 %) demonstrated EWSR1 rearrangement and 3 cases displayed EWSR1::FLI1 fusion by FISH. ERCC4 splice-site variant, a novel pathogenic variant, was discovered for the first time via RNA sequencing. With a median follow-up duration of 14 months (6 to 79 months), 8/13 (62 %) patients died, while 5/13(38 %) survived. Three cases recurred, and five patients developed metastasis to the liver (2 cases), lung (2 cases) and bone (1 case). RES is an aggressive, high-grade tumor, prone to multiple recurrences and metastases, with distinctive morphologic, immunohistochemical, and molecular genetic features. ERCC4 splicing mutation, which is a novel pathogenic variant discovered for the first time, with possible significance for understanding the disease, as well as the development of targeted drugs., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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4. [TFE3-rearranged perivascular epithelioid cell tumors: a clinicopathological analysis of eight cases].
- Author
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Qin Y, Yang L, Zhang HJ, Wei J, Liu YX, Zhang WH, Wen Z, Wang Z, and Fan LN
- Subjects
- Humans, Female, Male, Middle Aged, Adult, Aged, In Situ Hybridization, Fluorescence, Immunohistochemistry, High-Throughput Nucleotide Sequencing, Prognosis, Neoplasm Recurrence, Local, Liver Neoplasms genetics, Liver Neoplasms pathology, Liver Neoplasms metabolism, MART-1 Antigen metabolism, MART-1 Antigen genetics, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Retroperitoneal Neoplasms metabolism, Uterine Neoplasms genetics, Uterine Neoplasms pathology, Uterine Neoplasms metabolism, Cathepsin K, gp100 Melanoma Antigen, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism, Perivascular Epithelioid Cell Neoplasms genetics, Perivascular Epithelioid Cell Neoplasms pathology, Perivascular Epithelioid Cell Neoplasms metabolism, Gene Rearrangement
- Abstract
Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of TFE3-rearranged perivascular epithelioid cell tumor (PEComa). Methods: Eight cases of PEComa with TFE3 rearrangement diagnosed in the First Affiliated Hospital of Air Force Medical University from January 2014 to July 2022 were collected. Three were consultation cases and 5 were collected from our hospital; 7 cases were resection specimens and 1 case was a needle biopsy specimen. Routine histolopathological analysis, immunohistochemical staining, fluorescence in situ hybridization (FISH) and the next-generation sequencing were performed. Clinical data were collected and the prognosis was assessed. Results: The 8 patients consisted of 5 females and 3 males with a median age of 45 years (ranged from 25 to 65 years). The tumor location included 1 uterus, 1 liver, 1 urachus, 2 kidneys, 1 abdominal cavity, 1 colon, and 1 retroperitoneum (3 subsequent recurrences in the abdominal cavity, pelvis and ovary, and abdominal cavity, respectively). Morphologically, the tumor cells were uniform and epithelioid with translucent or eosinophilic cytoplasm. They were arranged in nests or sheets, most of which were separated by thin-walled blood vessels. There were no papillary structures, and no overt smooth muscle or fat components. Atypical features were seen in 3 cases, with bizarre nuclei and tumor giant cells. Large areas of necrosis were visible, and mitosis was common (up to 28/50 HPF). Melanin deposition was present in 3 cases. Immunohistochemical staining showed diffuse and strong positivity for TFE3 in 8/8 cases and for HMB45 in 6/8 cases; focal positivity for Cathepsin K and Melan-A in 6/8 cases and for SMA in 2/8 of cases. All cases were negative for CKpan, PAX8 and Desmin. TFE3 gene break-apart was detected by FISH in all 8 cases, 4 of which underwent next-generation sequencing, and it revealed that 2 cases presented with SFPQ::TFE3 fusion, 1 case with ASPSCR1::TFE3 fusion, and 1 case with no chimeric fusion. Seven cases were followed up for 4-94 months. All cases were alive; 4 cases were disease-free, 2 cases showed recurrence, and 1 case had metastasis at initial diagnosis. Conclusions: TFE3-rearranged PEComa has unique histomorphological, immunohistochemical and molecular characteristics. The biological behavior is aggressive, which could lead to recurrence and metastasis, and warrants close clinical follow-up.
- Published
- 2024
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5. Paraaortic Extra-Adrenal Paraganglioma: Challenging Robotic Resection.
- Author
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Nikiforchin A, Baron E, Wernberg JA, and Sharma R
- Subjects
- Humans, Female, Adolescent, Retroperitoneal Neoplasms surgery, Retroperitoneal Neoplasms pathology, Retroperitoneal Neoplasms genetics, Prognosis, Pheochromocytoma surgery, Pheochromocytoma genetics, Pheochromocytoma pathology, Paraganglioma, Extra-Adrenal surgery, Paraganglioma, Extra-Adrenal genetics, Paraganglioma, Extra-Adrenal pathology, Robotic Surgical Procedures methods
- Abstract
Background: Up to 41% of intra- and extra-adrenal paragangliomas are linked to germline mutations with autosomal dominant transmission, which necessitates genetic testing for patients and their relatives.
1-4 Certain alterations, such as the succinate dehydrogenase (SDH) subunit B gene mutation, are associated with a significant risk of extra-adrenal, malignant, and metastatic disease forms.4-7 This highlights the need for routine genetic counseling and diligent surveillance, as well as surgeon awareness of hereditary paraganglioma-pheochromocytoma syndrome (HPPS)., Methods: We present a multimedia article featuring a step-by-step video of a complex retroperitoneal resection, enriched with perioperative management insights., Results: A 17-year-old female presented with episodes of hypertension, tachycardia, and diffuse diaphoresis. CT revealed a paraaortic mass adjacent to the left renal hilum later confirmed by a SPECT/CT with iodine-123 meta-iodobenzylguanidine.8 Additional imaging with gallium-68 DOTATATE was not performed then due to unknown mutation status. The patient underwent robotic removal of the tumor and adjacent lymph nodes. Pathology confirmed a poorly differentiated paraganglioma with 0/6 lymph node metastases. Genetic tests revealed SDHB gene mutation, indicative of HPPS.9,10 At 12 months, the patient remained disease-free on CT with normalized metanephrines levels and no detectable circulating tumor DNA. Familial screening detected her mother, maternal uncle, and maternal grandfather to be SDHB mutation carriers, although phenotypically silent., Conclusions: Robotic-assisted resection can be safe and effective for retroperitoneal malignant paragangliomas. However, management extends beyond surgery and requires cascade genetic testing to address familial risks. Because of the high probability of cancer associated with SDHB mutation, lifelong patient surveillance is imperative., (© 2024. Society of Surgical Oncology.)- Published
- 2024
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6. [Advances in the etiology of retroperitoneal liposarcoma].
- Author
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Yuan ZQ and Liu YB
- Subjects
- Humans, Liposarcoma genetics, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology
- Abstract
Retroperitoneal liposarcoma is the most common retroperitoneal soft tissue tumor with insidious onset, difficulty in treatment, and easy recurrence. Different subtypes of retroperitoneal liposarcoma differ significantly in pathogenic mechanism, biological behavior, and prognosis. The characteristic molecular event of well-differentiated and dedifferentiated liposarcoma is the amplification of the long arm segment of chromosome 12. The genome of myxoid liposarcoma is characterized by translocations of chromosomes 12 and 16 to form fusion genes. The genomic changes of pleomorphic and myxoid pleomorphic liposarcoma are complex, with multiple chromosomal structural abnormalities. Several signaling pathways related to adipocyte differentiation or lipid metabolism have been found to be involved in the initiation and progression of retroperitoneal liposarcoma. It is unclear whether retroperitoneal liposarcoma originates from naive preadipocytes or dedifferentiated mature adipocytes, and its metabolic characteristics are also poorly understood. The first-line drug treatment for retroperitoneal liposarcoma is anthracycline-based chemotherapy, but patients receive little benefit. Therefore, it is urgent to strengthen the basic research on retroperitoneal liposarcoma to find effective therapeutic targets.
- Published
- 2024
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7. [A radionomics model for the prediction of grade and histological subtype in retroperitoneal sarcoma].
- Author
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Jakob J and Reissfelder C
- Subjects
- Humans, Radiotherapy, Adjuvant, Sarcoma genetics, Sarcoma pathology, Retroperitoneal Neoplasms diagnostic imaging, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Soft Tissue Neoplasms
- Published
- 2024
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8. Insight of a lipid metabolism prognostic model to identify immune landscape and potential target for retroperitoneal liposarcoma.
- Author
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Wang Z, Tao P, Fan P, Wang J, Rong T, Hou Y, Zhou Y, Lu W, Hong L, Ma L, Zhang Y, and Tong H
- Subjects
- Humans, Ecosystem, Lipid Metabolism, Prognosis, Fatty Acids, Retroperitoneal Neoplasms genetics
- Abstract
Introduction: The exploration of lipid metabolism dysregulation may provide novel perspectives for retroperitoneal liposarcoma (RPLS). In our study, we aimed to investigate potential targets and facilitate further understanding of immune landscape in RPLS, through lipid metabolism-associated genes (LMAGs) based prognostic model., Methods: Gene expression profiles and corresponding clinical information of 234 cases were enrolled from two public databases and the largest retroperitoneal tumor research center of East China, including cohort-TCGA (n=58), cohort-GSE30929 (n=92), cohort-FD (n=50), cohort-scRNA-seq (n=4) and cohort-validation (n=30). Consensus clustering analysis was performed to identify lipid metabolism-associated molecular subtypes (LMSs). A prognostic risk model containing 13 LMAGs was established using LASSO algorithm and multivariate Cox analysis in cohort-TCGA. ESTIMATE, CIBERSORT, XCELL and MCP analyses were performed to visualize the immune landscape. WGCNA was used to identify three hub genes among the 13 model LMAGs, and preliminarily validated in both cohort-GSE30929 and cohort-FD. Moreover, TIMER was used to visualize the correlation between antigen-presenting cells and potential targets. Finally, single-cell RNA-sequencing (scRNA-seq) analysis of four RPLS and multiplexed immunohistochemistry (mIHC) were performed in cohort-validation to validate the discoveries of bioinformatics analysis., Results: LMS1 and LMS2 were characterized as immune-infiltrated and -excluded tumors, with significant differences in molecular features and clinical prognosis, respectively. Elongation of very long chain fatty acids protein 2 (ELOVL2), the enzyme that catalyzed the elongation of long chain fatty acids, involved in the maintenance of lipid metabolism and cellular homeostasis in normal cells, was identified and negatively correlated with antigen-presenting cells and identified as a potential target in RPLS. Furthermore, ELOVL2 was enriched in LMS2 with significantly lower immunoscore and unfavorable prognosis. Finally, a high-resolution dissection through scRNA-seq was performed in four RPLS, revealing the entire tumor ecosystem and validated previous findings., Discussion: The LMS subgroups and risk model based on LMAGs proposed in our study were both promising prognostic classifications for RPLS. ELOVL2 is a potential target linking lipid metabolism to immune regulations against RPLS, specifically for patients with LMS2 tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Tao, Fan, Wang, Rong, Hou, Zhou, Lu, Hong, Ma, Zhang and Tong.)
- Published
- 2023
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9. New developments in the pathology and molecular biology of retroperitoneal sarcomas.
- Author
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Watson S, Gruel N, and Le Loarer F
- Subjects
- Humans, Molecular Biology, Tumor Microenvironment, Sarcoma genetics, Sarcoma therapy, Sarcoma diagnosis, Liposarcoma pathology, Leiomyosarcoma pathology, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms therapy, Retroperitoneal Neoplasms diagnosis, Soft Tissue Neoplasms
- Abstract
Retroperitoneal sarcomas (RPS) refer to a heterogeneous group of malignancies of mesenchymal origin developing from retroperitoneal tissues and vessels. The most frequent RPS are well differentiated/dedifferentiated liposarcomas and leiomyosarcomas, but other rare histological subtypes can be observed. Over the last decade, significant advances have been made in the pathological and molecular characterization of sarcomas. These advances have led to major changes in their diagnostic management as well as in the development of new therapeutic strategies based on tumor biology and microenvironment. This review describes the current knowledge and recent findings in the pathology and molecular biology of the most frequent RPS subtypes., Competing Interests: Declaration of competing interest None to be declared., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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10. Primary retroperitoneal mucinous cystic neoplasm of borderline malignancy with KRAS and GNAS co-mutation: a case report.
- Author
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Son SM, Woo CG, Yun SJ, and Lee OJ
- Subjects
- Adult, Humans, Male, Chromogranins genetics, GTP-Binding Protein alpha Subunits, Gs genetics, Mutation, Neoplasm Recurrence, Local, Proto-Oncogene Proteins p21(ras) genetics, Cystadenoma, Mucinous diagnosis, Cystadenoma, Mucinous pathology, Cystadenoma, Mucinous surgery, Cysts, Neoplasms, Cystic, Mucinous, and Serous, Retroperitoneal Neoplasms diagnostic imaging, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms surgery
- Abstract
Primary retroperitoneal mucinous cystic neoplasms are rare retroperitoneal tumors, which are histologically similar to mucinous cystic neoplasms of the ovaries. Only 31 cases of primary retroperitoneal mucinous cystic neoplasm with borderline malignancy (PRMCN-BM) have been reported (26 in women and five in men). We describe an additional male patient with PRMCN-BM. A 39-year-old man presented to our hospital with back pain. Twelve years earlier, he had undergone an orchiectomy for a germ cell tumor. Computed tomography showed a 6.9- × 4.4-cm cystic mass in the left pararenal space. Laparoscopic mass excision was performed, and a unilocular cystic mass was found in the pararenal space near the lower pole of the left kidney. A histopathological examination showed a cyst lined by atypical mucinous intestinal epithelium without stromal invasion. Targeted next-generation sequencing identified two hotspot mutations, with one each in the KRAS and GNAS genes. Outpatient follow-up 10 months after surgery showed no evidence of tumor recurrence. PRMCNs are extremely rare retroperitoneal neoplasms, especially in men. These neoplasms are rarely considered in the differential diagnosis of retroperitoneal masses, and their preoperative diagnosis is difficult. Evaluation of additional patients is required to better determine the prognosis of PRMCNs and the optimal postoperative follow-up.
- Published
- 2023
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11. Retroperitoneal liposarcoma and craniosynostosis: possible genomic relationship, case report, and literature review.
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Sguinzi RM, Aissaoui S, Genevay-Infante M, Breguet R, Charbonnet P, Francis K, Kini R, and Bühler L
- Subjects
- Male, Humans, Adult, Female, Mutation, Genomics, Liposarcoma genetics, Liposarcoma diagnosis, Liposarcoma pathology, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms diagnosis, Retroperitoneal Neoplasms pathology
- Abstract
Based on a case report, this review explores the genomic landscape for patients with liposarcomas and possible relationships with gene mutations related to craniosynostosis. We describe the case of a 40-year-old man, known for a surgical correction of craniosynostosis before the age of 1 year, who underwent a radical resection of a voluminous retroperitoneal liposarcoma; histopathological analysis revealed a low-grade well-differentiated, mostly sclerosing, liposarcoma. A genetic analysis searching for mutations in blood DNA was performed and did not detect any specific mutation. A literature review was also conducted. Several tumors related to syndromic and non-syndromic craniosynostosis are mentioned in the literature; no specific link with retroperitoneal liposarcoma is established but the FGFR3 mutation is detected in dedifferentiated liposarcomas. To date, no case has been reported in the literature demonstrating a genetic relationship between craniosynostosis and low-grade differentiated retroperitoneal liposarcoma. We conclude that further studies for gene complex mutations should be conducted to show a possible genetic relationship between retroperitoneal liposarcoma and craniosynostosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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12. Expression and function of Siglec-15 in RLPS and its correlation with PD-L1: Bioinformatics Analysis and Clinicopathological Evidence.
- Author
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Cui L, Tian X, Yan L, Guan X, Dong B, Zhao M, Lv A, Liu D, Wu J, and Hao C
- Subjects
- Humans, B7-H1 Antigen genetics, B7-H1 Antigen metabolism, Computational Biology, Sarcoma genetics, Sarcoma metabolism, Liposarcoma genetics, Liposarcoma metabolism, Sialic Acid Binding Immunoglobulin-like Lectins genetics, Sialic Acid Binding Immunoglobulin-like Lectins metabolism, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms metabolism
- Abstract
Purpose : Retroperitoneal liposarcoma (RLPS) is a rare malignancy without effective treatment. Since current treatment for unresectable RLPS is unsatisfactory, immunotherapy and targeted therapy are urgently needed. Siglec-15 is a transmembrane protein highly homologous to PD-L1 and is involved in tumor immune escape. The biological function of Siglec-15 in RLPS, its prognostic relevance and its relationship with PD-L1 need to be further clarified. In this study, we aimed to explore the biological function of Siglec-15 in sarcomas through bioinformatics analysis, and we also evaluated Siglec-15 and PD-L1 expression in RLPS samples. The relationship between the expression of Siglec-15 and PD-L1 and their clinicopathological relevance and prognostic value were also investigated in clinical RLPS patients. Methods: The RNA sequencing data of 259 sarcoma cases and 48 RLPS cases from TCGA were used to analyze the Siglec-15 expression and the differentially expressed genes (DEG) related with Siglec-15 expression. In addition, DEGs were subsequently analyzed through the gene ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network. Tumor specimens were obtained from 91 RLPS patients of our sarcoma center, and Siglec-15 and PD-L1 expression were evaluated using immunohistochemistry. The correlation between the expression level of these two markers as well as their correlation with clinicopathological factors and prognosis of RLPS patients was also assessed. Results: GEPIA analysis showed that the high expression of Siglec-15 was associated with poor sarcoma OS (P=0.034). A total of 682 differential genes were identified between the high and low expression groups of Siglec-15 in RLPS. Enrichment analysis of the KEGG pathway showed that Siglec-15 was related to the Hippo signaling pathway and the neuroactive ligand-receptor interaction. GO annotation analysis showed that the expression of Siglec-15 may thus be able to affect serine hydrolase activity, alongside signal receptor activator activity. The top 5 genes with the largest number of connection points are APOA1, F2, AHSG, AMBP, SERPINC1. In subsequent studies, we used 91 liposarcoma samples from our center for verification. Siglec-15 was expressed in 84.6% of RLPS cases, whereas PD-L1 was expressed in 17.6% of RLPS cases. A negative correlation was observed between Siglec-15 and PD-L1 expression ( P =0.020). In this group of RLPS patients, high Siglec-15 expression was correlated with poorer disease-free survival (DFS) ( P =0.021), and it was an independent predictor of DFS (hazard ratio: 2.298; 95% confidence interval: 1.154-4.576; P =0.018). However, we did not find a correlation between PD-L1 expression and overall survival or DFS in RLPS patients. Conclusion: The DEG and signaling pathways identified in the study could provide a preliminary understanding of the underlying molecular mechanisms of Siglec-15 in the development and progression of RLPS. High expression of Siglec-15 was a negative independent predictive factor for DFS of RLPS. The negative relationship between Siglec-15 and PD-L1 expression suggested that the Siglec-15 pathway might be an important supplement to PD-L1 treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
- Published
- 2022
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13. Retroperitoneal Sclerosing Angiomyolipoma with Long-Term Follow up: A Case Report with Unique Clinicopathologic and Genomic Profile.
- Author
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Jia L, Panwar V, Parmley M, Lucas E, Pedrosa I, and Kapur P
- Subjects
- Angiomyolipoma diagnosis, Angiomyolipoma genetics, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Biomarkers, Tumor genetics, Diagnosis, Differential, Female, Gene Rearrangement, Humans, Middle Aged, Retroperitoneal Neoplasms diagnosis, Retroperitoneal Neoplasms genetics, Angiomyolipoma pathology, Retroperitoneal Neoplasms pathology
- Abstract
Sclerosing angiomyolipoma (sAML) is a rare variant of the perivascular epithelioid tumors exhibiting distinct morphology with extensive stromal hyalinization, which makes it challenging to recognize. It often lacks an adipose tissue component and melanocytic markers may be expressed only focally, further posing a diagnostic challenge. Here, we report a case of sAML of the left pararenal retroperitoneum in a 52-year-old woman with 92 months of clinical follow up and discuss the histologic features, immunoprofile, molecular alterations, and differential diagnoses that can aid in the diagnosis of this unique and rare entity.
- Published
- 2022
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14. A case of retroperitoneal tumor displaying epithelial differentiation, prominent myxoid stroma and loss of INI1/SMARCB1.
- Author
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Rekhi B and Thomas A
- Subjects
- Adult, Biomarkers, Tumor genetics, Cell Differentiation, Humans, Male, SMARCB1 Protein genetics, Retroperitoneal Neoplasms diagnostic imaging, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms surgery, Sarcoma diagnostic imaging, Sarcoma genetics, Sarcoma surgery, Soft Tissue Neoplasms diagnostic imaging, Soft Tissue Neoplasms genetics, Soft Tissue Neoplasms surgery
- Abstract
The clinicopathological spectrum of INI1 deficient tumors is expanding. Epithelioid sarcoma (ES) is a rare sarcoma of uncertain differentiation, more often occurring in the extremities and uncommonly in the deep soft tissues. Histopathologically, it manifests in the form of classical, proximal, or hybrid types, the latter two characterized by rhabdoid cytomorphology. Immunohistochemically, ESs display loss of INI1/SMARCB1 and genetically associated with high percentage of SMARCB1 deletions., We report an extremely uncommon case of a retroperitoneal tumor in a 42-year-old male, who presented with abdominal discomfort. Radiologic imaging disclosed a 12 cm-sized retroperitoneal mass without involvement of any organ parenchyma. The patient underwent tumor excision with left-sided nephrectomy at another hospital. A review of the paraffin-embedded tissue sections revealed a multinodular tumor, composed of dyscohesive epithelioid tumor cells and focally arranged in cords, containing moderate to abundant, eosinophilic cytoplasm, vesicular nuclei, containing prominent nucleoli, including cells with rhabdoid cytomorphology, in a conspicuous myxoid stroma. A focal tumor area resembled proximal-type of ES. Immunohistochemically, tumor cells displayed positivity for pan cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), vimentin and focally for CA125, while these were negative for CD34, S100 protein, CKIT, DOG1, and INI1/SMARCB1., To the best of our knowledge, this constitutes the first case of a malignant tumor with epithelioid morphology, displaying myxoid matrix and loss of INI1/SMARCB1, resembling a myxoid variant of an epithelioid sarcoma and myoepithelioma-like tumor of the vulvar tumor, occurring in the retroperitoneum. A review of similar cases, differential diagnosis and treatment-associated implications are presented., (Copyright © 2021 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)
- Published
- 2021
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15. The molecular landscape of well differentiated retroperitoneal liposarcoma.
- Author
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Tyler R, Dilworth MP, James J, Blakeway D, Stockton JD, Morton DG, Taniere P, Gourevitch D, Desai A, and Beggs AD
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Mutation, Forkhead Transcription Factors genetics, Liposarcoma genetics, Retroperitoneal Neoplasms genetics
- Abstract
Well differentiated liposarcoma (WD-LPS) is a relatively rare tumour, with fewer than 50 cases occurring per year in the UK. These tumours are both chemotherapy- and radiotherapy-resistant and present a significant treatment challenge requiring radical surgery. Little is known of the molecular landscape of these tumours and no current targets for molecular therapy exist. We aimed to carry out a comprehensive molecular characterisation of WD-LPS via whole genome sequencing, RNA sequencing, and methylation array analysis. A recurrent mutation within exon 1 of FOXD4L3 was observed (chr9:70,918,189A>T; c.322A>T; p.Lys108Ter). Recurrent mutations were also observed in Wnt signalling, immunity, DNA repair, and hypoxia-associated genes. Recurrent amplification of HGMA2 was observed, although this was in fact part of a general amplification of the region around this gene. Recurrent gene fusions in HGMA2, SDHA, TSPAN31, and MDM2 were also observed as well as consistent rearrangements between chromosome 6 and chromosome 12. Our study has demonstrated a recurrent mutation within FOXD4L3, which shows evidence of interaction with the PAX pathway to promote tumourigenesis. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland., (© 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.)
- Published
- 2021
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16. Chromosome 10 abnormality predicts prognosis of neuroblastoma patients with bone marrow metastasis.
- Author
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Jiang CY, Xu X, Jian BL, Zhang X, Yue ZX, Guo W, and Ma XL
- Subjects
- Adrenal Gland Neoplasms genetics, Adrenal Gland Neoplasms pathology, Bone Marrow Neoplasms genetics, Child, Preschool, Chromosomes, Human, Pair 1, Female, Humans, Infant, Male, Mediastinal Neoplasms genetics, Mediastinal Neoplasms pathology, N-Myc Proto-Oncogene Protein genetics, Orbital Neoplasms genetics, Orbital Neoplasms secondary, Prognosis, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Bone Marrow Neoplasms secondary, Chromosome Aberrations, Chromosomes, Human, Pair 10, Neuroblastoma genetics, Neuroblastoma pathology
- Abstract
Background: Neuroblastoma (NB) is the most common extracranial solid tumor in children. It is known for high heterogeneity and concealed onset. In recent years, the mechanism of its occurrence and development has been gradually revealed. The purpose of this study is to summarize the clinical characteristics of children with NB and abnormal chromosome 10, and to investigate the relationship between the number and structure of chromosome 10 abnormalities and NB prognosis., Methods: Chromosome G-banding was used at the time of diagnosis to evaluate the genetics of chromosomes in patients with NB and track their clinical characteristics and prognosis. All participants were diagnosed with NB in the Medical Oncology Department of the Beijing Children's Hospital from May 2015 to December 2018 and were followed up with for at least 1 year., Results: Of all 150 patients with bone marrow metastases, 42 were clearly diagnosed with chromosomal abnormalities. Thirteen patients showed abnormalities in chromosome 10, and chromosome 10 was the most commonly missing chromosome. These 13 patients had higher LDH and lower OS and EFS than children with chromosomal abnormalities who did not have an abnormality in chromosome 10. Eight patients had both MYCN amplification and 1p36 deletion. Two patients had optic nerve damage and no vision, and one patient had left supraorbital metastases 5 months after treatment., Conclusions: The results indicated that chromosome 10 might be a new prognostic marker for NB. MYCN amplification and 1p36 deletion may be related to chromosome 10 abnormalities in NB. Additionally, NB patients with abnormal chromosome 10 were prone to orbital metastases.
- Published
- 2021
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17. Modern multimodality management of patients with caval leiomyosarcoma: New treatment paradigms and potential molecular insights.
- Author
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Squires MH, Politano S, Pollock RE, Chen JL, and Grignol V
- Subjects
- Antibodies, Monoclonal administration & dosage, Cohort Studies, Dacarbazine administration & dosage, Doxorubicin administration & dosage, Female, Humans, Ifosfamide administration & dosage, Leiomyosarcoma genetics, Leiomyosarcoma pathology, Male, Middle Aged, Neoadjuvant Therapy, Neoplasm Staging, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Retrospective Studies, Vascular Neoplasms genetics, Vascular Neoplasms pathology, Vena Cava, Inferior surgery, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leiomyosarcoma drug therapy, Leiomyosarcoma surgery, Retroperitoneal Neoplasms drug therapy, Retroperitoneal Neoplasms surgery, Vascular Neoplasms drug therapy, Vascular Neoplasms surgery, Vena Cava, Inferior pathology
- Abstract
Background and Objectives: Caval leiomyosarcomas (cLMS) are rare soft tissue sarcomas historically associated with high recurrence rates and poor prognosis. While radical resection remains the mainstay of therapy for cLMS, new systemic therapies have presented opportunities for multimodality treatment. We examined the clinical outcomes of patients with cLMS treated with modern, multimodality approaches, and compared their outcomes to those of patients with noncaval retroperitoneal LMS (ncLMS)., Methods: A retrospective, single-institution review identified all patients diagnosed with primary retroperitoneal LMS from 2012 to 2018. Radiographic and pathologic review distinguished patients with cLMS and ncLMS. Standard clinicopathologic variables and response to chemotherapy (when applicable) were analyzed. Primary endpoints were overall (OS) and progression-free survival (PFS)., Results: Eleven patients with cLMS were identified. Median tumor size was 7.5 cm (IQR, 5.0-14.3 cm); all patients had Stage II/III disease. Seven patients received neoadjuvant chemotherapy. Nine cLMS patients underwent R0/R1 resection; two did not complete resection. Six patients received adjuvant systemic therapy. Twenty patients with ncLMS were treated during the same period. No statistical intergroup differences were noted in tumor size, pathologic grade, stage, or resection margin status. Patients with ncLMS were less likely to receive neoadjuvant (10% vs. 64%) and adjuvant chemotherapy (30% vs. 55%). Two-year OS (81% vs. 78%; p = NS) and PFS (55% vs. 46%; p = NS) were comparable between cLMS and ncLMS patients., Conclusions: Multimodality treatment with systemic therapy and aggressive surgical resection may achieve equivalent survival outcomes for patients with cLMS versus similar ncLMS. We recommend that all patients with cLMS be evaluated for multidisciplinary treatment. Genomic and proteomic expression profiling may identify novel or targetable mutations., (© 2021 Wiley Periodicals LLC.)
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- 2021
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18. [Giant lipomas or retroperitoneal liposarcomas? Controversies in their diagnosis and treatment].
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Fernández Hernández JÁ, Navarro-Barrios Á, Gil Vázquez PJ, Gil JE, Varona Garcíal L, López Motos D, Fernández Selles C, Nieto G, Frutos Bernal MD, Torres Salmerón G, and Soria Cogollos T
- Subjects
- Adult, Aged, Buttocks, Cyclin-Dependent Kinase 4 genetics, Female, Humans, Incidental Findings, Inguinal Canal, Lipoma genetics, Lipoma surgery, Liposarcoma surgery, Male, Proto-Oncogene Proteins c-mdm2 genetics, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms surgery, Retrospective Studies, Lipoma pathology, Liposarcoma pathology, Retroperitoneal Neoplasms pathology
- Abstract
Background: Retroperitoneal lipomas are extremely rare tumors that must be differentiated from well-differentiated liposarcomas (WD-LPS)., Objectives: To summarize the evidence about giant retroperitoneal lipomas or liposarcomas; and to elaborate recommendations for their management., Data Sources: A systematic literature search from January 1985 to December 2019 and a review of our own cases was performed., Results: Our series comprises four patients, two females and two males. The diagnosis was incidental in two cases. The medium size was 26 cm, being two cases located exclusively in the retroperitoneum, one in the inguinal region and one in the buttock via pelvic space. All cases were surgically removed being confirmed the initial diagnosis of retroperitoneal lipomas in two cases, as the rest two cases were classified as WD_LPS after MDM2/CDK4 genetic analysis. The review of the available literature plus our own cases revealed 30 cases, of which 58% were woman. Only two cases were asymptomatic. The main symptom was abdominal mass (53%) followed by abdominal pain (40,6%). The median size of the lesions was 24,9 cm with a median weight of 4.576,3 g. All cases were surgically removed, being necessary to remove contiguous organs in only four cases (12,5%)., Conclusions: Retroperitoneal lipoma is a rare tumor which must be differentiated from WD-LPS. This is a very difficult task, being necessary to determinate MDM2 status (by FISH or MLPA), present in liposarcoma but not in lipomas, for its correct diagnosis. The treatment must be based on a complete surgical resection with negative margins., (Copyright © 2020 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)
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- 2021
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19. Renal metastases from esophageal cancer and retroperitoneal lymphoma detected via chromosome duplications identified by fluorescence in situ hybridization in urine exfoliated cells: First 2 case reports.
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Hu Z, Ke C, Shen Y, Zeng X, and Yang C
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- Chromosome Duplication, Esophageal Neoplasms diagnosis, Esophageal Neoplasms genetics, Esophageal Neoplasms urine, Esophagus diagnostic imaging, Humans, In Situ Hybridization, Fluorescence, Kidney diagnostic imaging, Kidney pathology, Kidney surgery, Kidney Neoplasms genetics, Kidney Neoplasms secondary, Kidney Neoplasms urine, Liquid Biopsy methods, Lymph Nodes diagnostic imaging, Lymphoma genetics, Lymphoma urine, Magnetic Resonance Imaging, Male, Middle Aged, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms urine, Retroperitoneal Space diagnostic imaging, Tomography, X-Ray Computed, Urinalysis methods, Esophageal Neoplasms pathology, Kidney Neoplasms diagnosis, Lymphoma pathology, Retroperitoneal Neoplasms pathology
- Abstract
Rationale: Renal-occupying lesions positive for urine fluorescence in situ hybridization (FISH) are usually considered urothelial carcinomas. Here, we describe 2 cases of renal metastases with chromosome duplications in urine exfoliated cells., Patient Symptoms: Patient 1, a 56-year-old male with a history of esophageal cancer, was admitted to our hospital on May 2017 after presenting with right back pain with microscopic hematuria for 1 month. Magnetic resonance imaging (MRI) showed right renal space-occupying lesions (5.4 cm × 4.6 cm) and multiple enlarged lymph nodes in the right renal hilum and retroperitoneum. The cystoscopy results were negative, and FISH analysis of urine exfoliated cells was positive, indicative of chromosome 3, 7, and 17 amplifications. Patient 2 was a 50-year-old male who was admitted to our hospital on May 2019 with no obvious cause of abdominal pain and abdominal distension (lasting for 7 days), with a serum creatinine level of 844 μmol/L. Patient 2 had no hematuria or fever, and MRI showed left renal inferior and medial space-occupying lesions, and multiple mesenteric nodules at the junction of the left adrenal gland, retroperitoneum, abdomen, and pelvis, which were partially fused. The tumor lesions were approximately 3.1 cm × 2.3 cm in size. The urine FISH results were positive, indicating chromosome 3, 7, and 17 amplifications., Diagnoses: Both patients were diagnosed with renal tumors with unknown pathology., Interventions: Patient 1 underwent laparoscopic resection of the kidney and ureter, and sleeve cystectomy. The postoperative pathological diagnosis was metastatic keratinized squamous cell carcinoma, with squamous cell carcinoma in the right hilar lymph node. Histological FISH of the primary esophageal cancer and renal metastases were consistent with the urine FISH test results. Patient 2 underwent a biopsy of the left renal inferior and retroperitoneal areas, and was diagnosed with diffuse large B-cell lymphoma., Outcomes: Patient 1 survived 6 months after urological surgery. After treating patient 2 with the R-CHOP regimen and kinase inhibitors, his renal function recovered significantly and the mass become undetectable., Lessons: Our results imply that FISH-positive renal occupying lesions should be considered as potential renal metastases with chromosome aberrations when making a differential diagnosis., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2021
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20. Acute megakaryoblastic leukaemia with t(1;22)(p13·3;q13·1)/RBM15-MKL1 in an adult patient following a non-mediastinal germ cell tumour.
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Saito Y, Makita S, Chinen S, Kito M, Fujino T, Ida H, Hosoba R, Tanaka T, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Miyagi-Maeshima A, Matsushita H, and Izutsu K
- Subjects
- Adult, Humans, Male, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 1 metabolism, Chromosomes, Human, Pair 22 genetics, Chromosomes, Human, Pair 22 metabolism, Leukemia, Megakaryoblastic, Acute genetics, Leukemia, Megakaryoblastic, Acute metabolism, Leukemia, Megakaryoblastic, Acute pathology, Neoplasms, Germ Cell and Embryonal genetics, Neoplasms, Germ Cell and Embryonal metabolism, Neoplasms, Germ Cell and Embryonal pathology, Neoplasms, Second Primary genetics, Neoplasms, Second Primary metabolism, Neoplasms, Second Primary pathology, Oncogene Proteins, Fusion genetics, Oncogene Proteins, Fusion metabolism, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms metabolism, Retroperitoneal Neoplasms pathology, Translocation, Genetic
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- 2020
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21. Identification of TYMS as a promoting factor of retroperitoneal liposarcoma progression: Bioinformatics analysis and biological evidence.
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Zhang S, Yan L, Cui C, Wang Z, Wu J, Zhao M, Dong B, Guan X, Tian X, and Hao C
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- Adult, Aged, Apoptosis genetics, Cell Line, Tumor, Cell Movement genetics, Cell Proliferation genetics, Computational Biology, Datasets as Topic, Disease Progression, Disease-Free Survival, Female, G1 Phase Cell Cycle Checkpoints genetics, Gene Expression Profiling, Gene Knockdown Techniques, Humans, Liposarcoma mortality, Liposarcoma pathology, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Retroperitoneal Neoplasms mortality, Retroperitoneal Neoplasms pathology, Thymidylate Synthase genetics, Up-Regulation, Gene Expression Regulation, Neoplastic, Liposarcoma genetics, Retroperitoneal Neoplasms genetics, Thymidylate Synthase metabolism
- Abstract
Retroperitoneal liposarcoma (RLPS) is one of the most common types of retroperitoneal sarcomas, and has a high recurrence rate. There is an urgent need to further explore its pathogenesis and develop more effective treatment strategies. The aim of the present study was to identify potential driver genes of RLPS through bioinformatics analysis and molecular biology to elucidate potential targets that are suitable for further analysis for the treatment of RLPS. Differentially expressed genes (DEGs) between liposarcoma and normal fatty (NF) tissues were identified based on microarray data through bioinformatics analysis, and thymidylate synthase (TYMS) was selected from the DEGs, based on high content screening (HCS). TYMS expression was evaluated in RLPS tumor tissues and cell lines. A total of 21 RLPS tissues and 10 NF frozen tissues were used for reverse transcription‑quantitative PCR, and 47 RLPS formalin‑fixed specimens were used for immunohistochemical analysis. The effect of TYMS downregulation on cell proliferation, apoptosis, cell cycle progression, and cell migration and invasion were evaluated using lentivirus‑mediated short hairpin RNA. The underlying mechanisms of TYMS in RLPS were examined by protein microarray and verified by western blotting. A total of 855 DEGs were identified. TYMS knockdown had the most notable effect on the proliferative capacity of RLPS cells according to the HCS results. TYMS mRNA expression levels were higher in RLPS tissues compared with NF tissues (P<0.001). TYMS expression was higher in high‑grade RLPS tissues compared with low‑grade RLPS tissues (P=0.003). The patients with positive TYMS expression had a worse overall survival (OS) and disease‑free survival (DFS) compared with the patients with negative TYMS expression (OS, P=0.024; DFS, P=0.030). The knockdown of TYMS reduced proliferation, promoted apoptosis, facilitated cell cycle progression from G1 to S phase, and reduced cell migration and invasion of RLPS cells. Protein microarray analysis and western blotting showed that the Janus Kinase/Signal transducers and activators of transcription pathway was downregulated following TYMS knockdown. In conclusion, TYMS expression is upregulated in RLPS tissues, and downregulation of TYMS reduces RLPS progression.
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- 2020
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22. Molecular Characterization of a Rare Dedifferentiated Liposarcoma With Rhabdomyosarcomatous Differentiation in a 24 Year Old.
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Olson N, Gularte-Mérida R, Selenica P, Da Cruz Paula A, Alemar B, Weigelt B, Lefferts J, and Linos K
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- Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Biopsy, Chemoradiotherapy, Adjuvant, Diagnosis, Differential, Fatal Outcome, Female, Gene Amplification, Humans, In Situ Hybridization, Fluorescence, Liposarcoma genetics, Liposarcoma pathology, Liposarcoma therapy, Proto-Oncogene Proteins c-mdm2 genetics, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Retroperitoneal Neoplasms therapy, Retroperitoneal Space surgery, Rhabdomyosarcoma, Embryonal genetics, Rhabdomyosarcoma, Embryonal pathology, Exome Sequencing, Young Adult, Cell Dedifferentiation genetics, Liposarcoma diagnosis, Retroperitoneal Neoplasms diagnosis, Retroperitoneal Space pathology, Rhabdomyosarcoma, Embryonal diagnosis
- Abstract
Aims . The aim of this study was to identify potential driver genetic alterations in a dedifferentiated liposarcoma (DDLPS) with rhabdomyosarcomatous differentiation. Methods and Results . A 24-year-old female underwent resection of an abdominal mass, which on a previous biopsy demonstrated rhabdomyosarcomatous differentiation concerning for embryonal rhabdomyosarcoma. Histologically the resected tumor displayed a high-grade sarcoma with rhabdomyosarcomatous differentiation in the background of well-differentiated liposarcoma consistent with DDLPS. Fluorescence in situ hybridization confirmed MDM2 amplification, as did array-based copy number profiling. Whole-exome sequencing revealed a somatic FGFR1 hotspot mutation and RNA sequencing an LMNB2-MAP2K6 fusion only within the dedifferentiated component. Conclusions . This study represents an in-depth examination of a rare DDLPS with rhabdomyosarcomatous differentiation in a young individual. Additionally, it is also instructive of a potential pitfall when assessing for MDM2 amplification in small biopsies. Despite exhaustive analysis, mutation and gene copy number analysis did not identify any molecular events that would underlie the rhabdomyoblastic differentiation. Our understanding of what causes some tumors to dedifferentiate as well as undergo divergent differentiation is limited, and larger studies are needed.
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- 2020
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23. A review of retroperitoneal liposarcoma genomics.
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Tyler R, Wanigasooriya K, Taniere P, Almond M, Ford S, Desai A, and Beggs A
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- Animals, Antineoplastic Agents, Alkylating therapeutic use, Chromosome Aberrations, Genomics methods, Humans, Liposarcoma drug therapy, Liposarcoma metabolism, Oncogene Proteins, Fusion genetics, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases metabolism, Retroperitoneal Neoplasms drug therapy, Retroperitoneal Neoplasms metabolism, Trabectedin therapeutic use, Liposarcoma genetics, Retroperitoneal Neoplasms genetics
- Abstract
Retroperitoneal liposarcomas are rare tumours that carry a poorer prognosis than their extremity counterparts. Within their subtypes - well differentiated (WDL), dedifferentiated (DDL), myxoid (MLS) and pleomorphic (PLS) - they exhibit a diverse genomic landscape. With recent advances in next generation sequencing, the number of studies exploring this have greatly increased. The recent literature has deepened our understanding of the hallmark MDM2/CDK4 amplification in WDL/DDL and addressed concerns about toxicity and resistance when targeting this. The FUS-DDIT3 fusion gene remains the primary focus of interest in MLS with additional potential targets described. Whole genome sequencing has driven identification of novel genes and pathways implicated in WDL/DDL outside of the classic 12q13-15 amplicon. Due to their rarity; anatomical location and histologic subtype are infrequently mentioned when reporting the results of these studies. Reports can include non-adipogenic or extremity tumours, making it difficult to draw specific retroperitoneal conclusions. This narrative review aims to provide a summary of retroperitoneal liposarcoma genomics and the implications for therapeutic targeting., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2020
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24. MDM2-positive papillary sarcomatoid renal cell carcinoma: a potential diagnostic pitfall.
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Jeruc J, Čugura T, Tomažič A, and Boštjančič E
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- Aged, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell pathology, Humans, Immunohistochemistry, Liposarcoma genetics, Liposarcoma pathology, Male, Proto-Oncogene Proteins c-mdm2 metabolism, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Sarcoma genetics, Sarcoma pathology, Carcinoma, Renal Cell diagnosis, Liposarcoma diagnosis, Proto-Oncogene Proteins c-mdm2 genetics, Retroperitoneal Neoplasms diagnosis, Sarcoma diagnosis
- Abstract
Sarcomatoid renal cell carcinoma is a highly aggressive form of carcinoma, histologically showing both carcinomatous and mesenchymal component in different proportions. We present a case of advanced type 1 papillary sarcomatoid renal cell carcinoma infiltrating adjacent organs and showing positivity for MDM2 by immunohistochemistry and MDM2 amplification by fluorescence in situ hybridization. This finding, together with sarcomatoid morphology, poses a potential pitfall for diagnosis with dedifferentiated liposarcoma. MDM2 is known to be altered in various human sarcomas. Only recently, MDM2 alterations have been reported in carcinomas. The presented case illustrates the need of thorough sampling with clinic-pathological correlation before making a final diagnosis in sarcomatoid retroperitoneal tumours. Additionally, the potential clinical implications of MDM2 amplification in renal cell carcinoma are discussed.
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- 2020
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25. Uncommon Localization of Extrarenal Xp11.2 Translocation-associated Renal Cell Carcinoma (RCC): Case Report.
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Al-Maghrabi JA and Khabaz MN
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- Adult, Humans, In Situ Hybridization, Fluorescence, Male, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell metabolism, Carcinoma, Renal Cell pathology, Chromosomes, Human, X genetics, Kidney Neoplasms genetics, Kidney Neoplasms metabolism, Kidney Neoplasms pathology, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms metabolism, Retroperitoneal Neoplasms pathology, Translocation, Genetic
- Abstract
The World Health Organization has recognized Xp11.2 translocation-associated renal cell carcinoma (RCC) as a distinct neoplasm that arises within the kidney. Although many reports of extrarenal carcinoma may be found in the literature, to the best of our knowledge, Xp11 translocation-associated RCC with intact kidneys has not been documented. This report describes a multilobulated right retroperitoneal soft tissue mass (7.9×5.3×12.6 cm) of a 37-year-old man complaining of abdominal pain in the right side. The patient underwent a computed tomography-guided biopsy. Microscopic evaluation reveals a tumor with papillary and sheaths architectures with cells revealing clear to eosinophilic cytoplasm. Immunohistochemical evaluation on the biopsy reveals that the tumor is positive for PAX-8, CD10, and TFE3. It is negative for CK7, EMA, Vimentin, RCC, CK8/18, D20, CD3, PLAP, OCT4, CD30, MART-1, Inhibin, S-100, HMB-45, Desmin, SMA, and DOG-1. The diagnosis was malignant epithelioid neoplasm and the diagnosis of translocation RCC was suggested. Excision was recommended. The patient underwent right radical nephrectomy with removal of this large mass. Pathologic examination showed a large cystic and solid, nonhomogenous mass with some necrotic areas, originating from the perirenal fat between the adrenal gland and the kidney. Microscopic features showed a tumor with papillary, rhabdoid, and clear cell features. Immunohistochemical stains showed that the tumor cells positively expressed AMACR, PAX-8, CD10, RCC, and TFE3, but were negative for cytokeratins, vimentin, HMB-45, desmin, SMA, EMA, and MSA. Cytogenetic studies confirmed the diagnosis of Xp11.2 translocation-associated RCC with positive TFE3 gene rearrangement. To the best of our knowledge, this type of extrarenal tumor has never been reported.
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- 2020
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26. Generalised mosaicism for TSC2 mutation in isolated lymphangioleiomyomatosis.
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Ogórek B, Hamieh L, Lasseter K, Bagwe S, Machado T, Herranz-Ors C, Thorner AR, Nag A, Gulleman P, Giannikou K, Young LR, Pujana MÀ, Darling TN, El-Chemaly S, Moss J, Henske EP, and Kwiatkowski DJ
- Subjects
- Adult, Aged, Cell-Free Nucleic Acids genetics, Female, Humans, Lymphangioleiomyomatosis blood, Middle Aged, Pneumothorax, Vascular Endothelial Growth Factor D blood, Young Adult, Angiomyolipoma genetics, Kidney Neoplasms genetics, Lung Neoplasms genetics, Lymphangioleiomyomatosis genetics, Mosaicism, Neoplasms, Multiple Primary genetics, Retroperitoneal Neoplasms genetics, Tuberous Sclerosis Complex 2 Protein genetics
- Abstract
Competing Interests: Conflict of interest: B. Ogórek has nothing to disclose. Conflict of interest: L Hamieh has nothing to disclose. Conflict of interest: K. Lasseter has nothing to disclose. Conflict of interest: S. Bagwe has nothing to disclose. Conflict of interest: T. Machado has nothing to disclose. Conflict of interest: C. Herranz-Ors has nothing to disclose. Conflict of interest: A.R. Thorner has nothing to disclose. Conflict of interest: A. Nag has nothing to disclose. Conflict of interest: P. Gulleman has nothing to disclose. Conflict of interest: K. Giannikou has nothing to disclose. Conflict of interest: L.R. Young reports grants from The LAM Foundation during the conduct of the study. She has served a paediatric advisory board member for Boehringer Ingelheim and has received payment for authorship from UpToDate, outside the submitted work. In addition, she has a patent “VEGF-D in diagnosis of LAM” licensed to Cincinnati Children's (no personal royalties). Conflict of interest: M.À. Pujana reports grants from Roche Pharma outside the submitted work. Conflict of interest: T.N. Darling has nothing to disclose. Conflict of interest: S. El-Chemaly has nothing to disclose. Conflict of interest: J. Moss has nothing to disclose. Conflict of interest: E.P. Henske has nothing to disclose. Conflict of interest: D.J. Kwiatkowski has nothing to disclose.
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- 2019
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27. Comprehensive immune characterization and T-cell receptor repertoire heterogeneity of retroperitoneal liposarcoma.
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Yan L, Wang Z, Cui C, Guan X, Dong B, Zhao M, Wu J, Tian X, and Hao C
- Subjects
- Adult, Aged, B-Lymphocytes immunology, Disease-Free Survival, Down-Regulation, Female, Gene Expression Regulation, Neoplastic, Humans, Liposarcoma genetics, Liposarcoma mortality, Male, Middle Aged, Prognosis, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms mortality, Sequence Analysis, DNA, T-Lymphocytes immunology, Up-Regulation, B7-H1 Antigen metabolism, High-Throughput Nucleotide Sequencing methods, Liposarcoma immunology, Lymphocytes, Tumor-Infiltrating immunology, Programmed Cell Death 1 Receptor metabolism, Receptors, Antigen, T-Cell, alpha-beta genetics, Retroperitoneal Neoplasms immunology
- Abstract
Retroperitoneal liposarcoma (RLPS) is one of the most common subtypes of retroperitoneal soft tissue sarcomas and lacks effective treatment. This study aimed to provide a thorough profile of immune characteristics of RLPS. This study included 56 RLPS patients. Multisite tumor tissues were collected from 16 patients. Immunohistochemistry was carried out to identify CD4
+ , CD8+ , FoxP3+ , CD20+ , or programmed cell death-1 (PD-1)+ tumor infiltrating lymphocytes (TILs) and Programmed cell death ligand-1 (PD-L1) expression in tumor tissues. Ultradeep sequencing of T-cell receptor (TCR) β-chain gene was carried out in 42 tumor samples as well as peripheral blood samples collected from 6 patients. In RLPS, TILs were distributed in 3 patterns and T cells were more prevalent than B cells. Generally, the proportion of TILs decreased and PD-L1 expression increased with tumor progression. Patients with higher PD-1/PD-L1 expression tended to have poorer prognosis, whereas patients with tertiary lymphoid structure tended to have a favorable disease-free survival. Although T-cell clones in tumors were quite different from those in peripheral blood, TCR sequencing showed low TCR repertoire reads as well as polyclonal status within tumors, which indicated limited T cell response in the tumors. Both TILs distribution and TCR repertoires suggested spatial immune heterogeneity in RLPS. Our research described the immune landscape of RLPS, and suggested RLPS might be a kind of tumor with low T cell infiltration as well as great immune heterogeneity. Therefore, strategies that can facilitate lymphocytic infiltration and immune reactivity need to be developed in the future to improve the efficacy of immunotherapy., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)- Published
- 2019
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28. Multiple primary malignancies associated with a germline SMARCB1 pathogenic variant.
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Eelloo JA, Smith MJ, Bowers NL, Ealing J, Hulse P, Wylie JP, Shenjere P, Clarke NW, Soh C, Whitehouse RW, Jones M, Duff C, Freemont A, and Gareth Evans D
- Subjects
- Female, Hemangioma therapy, Horner Syndrome diagnostic imaging, Humans, Middle Aged, Neoplasms, Multiple Primary complications, Neoplasms, Multiple Primary pathology, Neoplasms, Multiple Primary therapy, Neurilemmoma complications, Neurilemmoma pathology, Neurilemmoma therapy, Neurofibromatoses complications, Neurofibromatoses therapy, Neurofibrosarcoma pathology, Neurofibrosarcoma therapy, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms therapy, Skin Neoplasms complications, Skin Neoplasms therapy, Hemangioma genetics, Neoplasms, Multiple Primary genetics, Neurilemmoma genetics, Neurofibromatoses genetics, Neurofibrosarcoma genetics, SMARCB1 Protein genetics, Skin Neoplasms genetics
- Abstract
A 51-year old presented with a 6-month history of increasing pelvic/lower back pain with nocturnal waking and episodes of anorexia and vomiting. Examination revealed right torticollis and Horner's syndrome, and a large abdominal mass arising from the pelvis. Magnetic resonance and positron emission tomography imaging revealed (A) a 14 cm heterogeneous enhancing mass, abutting the left kidney with standardised uptake value max = 2.9, (B) a large heterogeneous enhancing pelvic mass (C) mesenteric adenopathy standardised uptake value max = 10.3 and (D) 6 cm right lung apex mass standardised uptake value max = 4.3. Computerised tomography-guided biopsy of lesion A was reported as neurofibroma with occasional atypia, lesion B a benign uterine leiomyoma and lesion C follicular lymphoma world health organisation Grade 2. Although she had been given the diagnosis of Neurofibromatosis Type-1 (NF1) 25-years previously following removal of an intradural extramedullary schwannoma she had no cutaneous stigmata of NF1. Genetic analysis of blood lymphocyte DNA identified a pathogenic variant in SMARCB1 confirming a diagnosis of schwannomatosis. Following 6-months chemotherapy for lymphoma, surgery was performed to remove lesion A. Histology revealed a malignant peripheral nerve sheath tumour with areas of low and high-grade change. An incidental, well-differentiated small bowel neuroendocrine carcinoma was also excised. Close surveillance continues with no recurrence after 6 years. This case study describes a novel finding of three separate synchronous primary malignancies in a patient with schwannomatosis and a proven SMARCB1 pathogenic variant.
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- 2019
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29. miR-34b/c rs4938723 T>C Decreases Neuroblastoma Risk: A Replication Study in the Hunan Children.
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Li Y, Zhuo ZJ, Zhou H, Liu J, Xiao Z, Xiao Y, He J, and Liu Z
- Subjects
- Adrenal Gland Neoplasms diagnosis, Adrenal Gland Neoplasms ethnology, Adrenal Gland Neoplasms pathology, Alleles, Asian People, Case-Control Studies, Child, Preschool, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Infant, Infant, Newborn, Logistic Models, Male, Mediastinal Neoplasms diagnosis, Mediastinal Neoplasms ethnology, Mediastinal Neoplasms pathology, Mutation, Neuroblastoma diagnosis, Neuroblastoma ethnology, Neuroblastoma pathology, Odds Ratio, Retroperitoneal Neoplasms diagnosis, Retroperitoneal Neoplasms ethnology, Retroperitoneal Neoplasms pathology, Risk, Adrenal Gland Neoplasms genetics, Gene Expression Regulation, Neoplastic, Mediastinal Neoplasms genetics, MicroRNAs genetics, Neuroblastoma genetics, Retroperitoneal Neoplasms genetics
- Abstract
Neuroblastoma is the most common seen solid neural tumor in children less than age one. As mutation in the miR-34b/c gene is observed in several types of human malignancies, there likely to be similar events that contribute to the pathogenesis of neuroblastoma. We hypothesize that polymorphism in the miR-34b/c gene might predispose to neuroblastoma. Here, we conducted this replication study by genotyping rs4938723 T>C from miR-34b/c in Hunan children (162 subjects with neuroblastoma and 270 control subjects) and examined its effect on the risk of neuroblastoma. We determined such association using logistic regression, adjusted for age and gender. Relative to those with TT genotype, subjects with C allele had reduced neuroblastoma risk (TC vs. TT: adjusted OR = 0.46, 95%CI = 0.30-0.71; additive model: adjusted OR = 0.64, 95%CI = 0.47-0.88; TC/CC vs. TT: adjusted OR = 0.49, 95%CI = 0.33-0.73). Stratified analysis revealed that rs4938723 TC/CC carriers were less likely to develop neuroblastoma for patients in the subgroups of age ≤ 18 months, age > 18 months, females, males, tumors in retroperitoneal, tumors in other sites, and clinical stages II, III, IV, and III+IV. Our findings verified miR-34b/c rs4938723 C variant allele as a protective factor for the risk of neuroblastoma. Further investigation of how miR-34b/c rs4938723 T>C might modify neuroblastoma risk is warranted., Competing Interests: The authors declared that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2019 Yong Li et al.)
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- 2019
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30. Linc00423 as a tumor suppressor in retroperitoneal liposarcoma via activing MAPK signaling pathway through destabilizing of NFATC3.
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Zhang Y, Tong H, He J, Shao Y, Guo X, Zhuang R, Yang J, Liu J, Ding Y, Liu W, Lu W, and Zhou Y
- Subjects
- Animals, Cell Proliferation genetics, Female, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Liposarcoma genetics, MAP Kinase Signaling System genetics, Mice, Mice, Inbred BALB C, Mice, Nude, NFATC Transcription Factors genetics, Protein Binding, RNA, Long Noncoding genetics, RNA-Seq, Retroperitoneal Neoplasms genetics, Transplantation, Heterologous, Up-Regulation genetics, Genes, Tumor Suppressor, Liposarcoma metabolism, NFATC Transcription Factors metabolism, RNA, Long Noncoding metabolism, Retroperitoneal Neoplasms metabolism
- Abstract
Unraveling the noncoding RNA expression networks governing cancer initiation and development is essential while remains largely uncompleted in retroperitoneal liposarcoma (RLS). Through RNA-seq technologies and computational biology, deregulated long noncoding RNAs (lncRNAs) are being identified and reveal that lncRNAs are implicated in serial steps of RLS development. High-throughput sequencing with computational methods for assembling the transcriptome of five paired RLS patient's tissues. We found that long intergenic noncoding RNA 423 (linc00423) was downregulated in RLS tissues. Gain-of-function assays revealed that overexpressed linc00423 obviously inhibited RLS cell growth in vitro and in vivo. Additionally, RNA sequence, RNA-pulldown and RIP assays evidenced that linc00423 involved in MAPK signaling pathway via destabilizing of nuclear factor of activated T-cells 3 (NFATC3). Summing up, our findings demonstrated that linc00423 acted as the tumor suppressor in RLS cells through regulating the protein level of NFATC3 at a post-transcriptional level and negatively regulated the MAPK signaling pathway at a transcriptional level. Linc00423 might serve as a candidate prognostic biomarker and a target for novel therapies of RLS patients.
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- 2019
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31. [Dedifferentiated liposarcoma with inflammatory myofibroblastic tumor-like features: a clinicopathological analysis of five cases].
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Si HP, Wang Z, Fan QH, Zhang YF, Yang DQ, Zhang ZH, and Gong QX
- Subjects
- Aged, Cyclin-Dependent Kinase Inhibitor p16 analysis, Cyclin-Dependent Kinase Inhibitor p16 genetics, Diagnosis, Differential, Duodenal Neoplasms genetics, Fibrosarcoma genetics, Gene Amplification, Genital Neoplasms, Male genetics, Humans, Immunophenotyping, In Situ Hybridization, Fluorescence, Intestinal Neoplasms genetics, Liposarcoma genetics, Male, Middle Aged, Neoplasm Recurrence, Local, Proto-Oncogene Mas, Proto-Oncogene Proteins c-mdm2 genetics, Retroperitoneal Neoplasms genetics, Tumor Burden, Duodenal Neoplasms pathology, Fibrosarcoma pathology, Genital Neoplasms, Male pathology, Intestinal Neoplasms pathology, Liposarcoma pathology, Retroperitoneal Neoplasms pathology
- Abstract
Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of dedifferentiated liposarcoma (DDLPS) with inflammatory myofibroblastic tumor (IMT)-like features. Methods: Five cases of DDLPS with IMT-like features were collected from the First Affiliated Hospital of Nanjing Medical University, the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine and the First People's Hospital of Qinzhou between 2013 and 2018. EnVision method and fluorescence in situ hybridization (FISH) were used to detect the immunophenotype of the tumor cells and the profile of MDM2 gene amplification respectively. Results: All five cases were male and the median age was 61 (range 53 to 65) years. The clinical symptoms were mainly related to the space-occupying lesions. The tumors were located in duodenal mesentery (two cases), intestinal wall (one case), retroperitoneum (one case), and spermatic cord (one case). Grossly, the tumors were not well encapsulated, ranging from 3 to 13 cm (median 6.7 cm) in diameter, with tan to gray and firm cut surface. Histologically, the dedifferentiated component closely resembled inflammatory myofibroblastic tumor (IMT), with spindle/polygonal/stellate-shaped cells arranged in storiform, sheet-like, or random pattern, with varying degrees of chronic inflammation and fibrosis. All three major patterns seen in IMT (myxoid, cellular and hypocellular fibrous) were observed, the hypocellular fibrous pattern was the most common. Well-differentiated liposarcomatous component was found in the peripheral areas of all the tumors. One case had high grade dedifferentiated component. Four cases were strongly positive for MDM2 and p16. Two cases were positive for SMA, and one case was focally positive for desmin and one for CD34. None of the cases stained for ALK-1. FISH demonstrated MDM2 gene amplification in all five cases. Clinical follow-ups were available in all five cases and the interval ranged from 3 to 66 months (median 23 months). Two patients developed recurrences and one patient had metastasis. The remaining two patients were alive with no evidence of tumor recurrence at 3 and 14 months after surgery respectively. Conclusions: DDLPS with IMT-like features is a more aggressive neoplasm than its histological mimic (IMT), and should not be misdiagnosed as other intermediate or low-grade malignant tumors, such as IMT, sclerosing liposarcoma, inflammatory liposarcoma, aggressive fibromatosis, solitary fibrous tumors, low-grade myofibroblastic sarcoma, and low-grade fibrosarcoma.
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- 2019
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32. Concurrent isolated retroperitoneal HGSC and STIC defined by somatic mutation analysis: a case report.
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Suda K, Nakaoka H, Hata C, Yahata N, Isobe M, Kameyama H, Wakai T, Motoyama T, Inoue I, Yoshihara K, and Enomoto T
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- BRCA2 Protein genetics, Carcinoma in Situ genetics, Cystadenocarcinoma, Serous genetics, Cystadenocarcinoma, Serous secondary, DNA Mutational Analysis, Fallopian Tube Neoplasms genetics, Female, Humans, Middle Aged, Mutation, Neoplasms, Second Primary genetics, Retroperitoneal Neoplasms genetics, Tumor Suppressor Protein p53 genetics, Carcinoma in Situ pathology, Fallopian Tube Neoplasms pathology, Neoplasms, Second Primary pathology, Retroperitoneal Neoplasms secondary
- Abstract
Background: Retroperitoneal high-grade serous carcinoma (HGSC) is extremely rare and the origin remains unclear. We present a case of retroperitoneal HGSC and coexisting serous tubal intraepithelial carcinoma (STIC), which is considered as the main origin of ovarian HGSC. We reviewed the available literature and discussed about the origin of this rare disease., Case Presentation: A 58-year-old female with a 93 × 65 × 62 mm-solid tumor with a cystic part was located immediately dorsal to the rectum underwent bilateral salpingo-oophorectomy, total abdominal hysterectomy, and en bloc resection of the retroperitoneal tumor together with lower anterior resection of the rectum. Histological diagnosis was retroperitoneal HGSC and STIC at the right fallopian tube. Two deleterious somatic mutations in TP53 and BRCA2 genes were shared between retroperitoneal HGSC and STIC., Conclusions: In addition to clinical features in the previous reports, our genetic findings suggest the origin of retroperitoneal HGSC might be STIC.
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- 2019
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33. Sarcoma in neurofibromatosis 2: case report and review of the literature.
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Linder C, Smith MJ, Bulman M, Wallace A, Freemont AJ, Mangham DC, and Evans DGR
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- Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Delayed Diagnosis, Diagnosis, Differential, Doxorubicin therapeutic use, Fatal Outcome, Humans, Male, Neoplasm Grading, Neurofibromatosis 2 genetics, Neurofibromin 2 genetics, Palliative Care methods, Retroperitoneal Neoplasms drug therapy, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, SMARCB1 Protein genetics, Sarcoma drug therapy, Sarcoma genetics, Sarcoma pathology, Sorafenib therapeutic use, Spinal Neoplasms drug therapy, Spinal Neoplasms genetics, Spinal Neoplasms pathology, Young Adult, Neurofibromatosis 2 complications, Retroperitoneal Neoplasms diagnosis, Sarcoma diagnosis, Spinal Neoplasms diagnosis
- Abstract
Neurofibromatosis type 2 (NF2) is associated with the development of several types of benign nervous system tumours, while malignancies are rare. We report a 22-year-old man who presented with retroperitoneal and spinal high-grade sarcomas with epithelial features. Samples showed a mixed epithelioid and spindled cell content with little associated matrix and inconclusive immunochemistry. Genetic analysis of a schwannoma and matched blood samples demonstrated a constitutional de novo substitution at the splice donor site of intron 8 of the NF2 gene and aa acquired large deletion of the entire NF2 gene as a second hit, with some loss of SMARCB1. The sarcoma also showed evidence of loss of SMARCB1 and NF2 with loss of INI1 staining. Unfortunately the mass was unresectable and the patient died 6 months after diagnosis. This malignancy was most consistent with SMARCB1-deficient epithelioid malignant peripheral nerve sheath tumour, although a significant differential was proximal-type epithelial sarcoma. Each differential has previously been reported only once with NF2. This demonstrates an extremely rare potential complication of the condition.
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- 2019
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34. Retroperitoneal Paraganglioma Involving the Renal Hilum: A Case Report and Literature Review.
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Cai PY, Golan R, and Yanke B
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- Adult, Age Factors, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Diagnosis, Differential, Female, Genetic Testing standards, Humans, Kidney diagnostic imaging, Kidney pathology, Kidney surgery, Nephrectomy, Paraganglioma genetics, Paraganglioma pathology, Paraganglioma therapy, Practice Guidelines as Topic, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Retroperitoneal Neoplasms therapy, Tomography, X-Ray Computed, Treatment Outcome, Urological Agents therapeutic use, Paraganglioma diagnosis, Retroperitoneal Neoplasms diagnosis
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- 2018
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35. Extraneuraxial hemangioblastoma: A clinicopathologic study of 10 cases with molecular analysis of the VHL gene.
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Muscarella LA, Bisceglia M, Galliani CA, Zidar N, Ben-Dor DJ, Pasquinelli G, la Torre A, Sparaneo A, Fanburg-Smith JC, Lamovec J, Michal M, and Bacchi CE
- Subjects
- Adult, Aged, Female, Humans, Kidney Neoplasms genetics, Male, Middle Aged, Mutation, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Soft Tissue Neoplasms genetics, Young Adult, Hemangioblastoma genetics, Hemangioblastoma pathology, Kidney Neoplasms pathology, Soft Tissue Neoplasms pathology, Spinal Nerve Roots pathology, Von Hippel-Lindau Tumor Suppressor Protein genetics
- Abstract
Less than 250 extraneuraxial hemangioblastomas occurring in paraneuraxial or peripheral sites have been reported to date, sporadically or in the setting of von Hippel-Lindau disease. Seventeen such cases underwent molecular genetic analysis, using either the patient's peripheral blood in 9 cases or paraffin embedded tumor tissue in the rest. VHL gene mutations were documented in 3/9 cases in which DNA from peripheral blood lymphocytes was used, all with clinically manifest von Hippel-Lindau disease; instead, no VHL gene alterations were found in all of the 8 cases with sporadic extraneuraxial hemangioblastoma in which DNA from tumor tissue was analyzed. Our aim is to investigate the molecular genetic profile of the VHL gene in extraneuraxial hemangioblastoma using paraffin embedded tumor tissues. The clinical features, histopathology, and molecular investigations of 10 extraneuraxial hemangioblastomas (7 females, 3 males; median age: 47 years) are presented herein. The histopathologic diagnosis was supported by immunohistochemistry (10/10) and electron microscopy (4/10). Molecular genetic analysis was conducted (10/10) for VHL gene mutations, LOH, and gene promoter methylation. Two of the present cases were already published with only limited or no molecular investigations. Four tumors of the present series were paraneuraxial, and 6 peripheral (2 involved soft tissues, and 4 the kidney). One tumor was von Hippel-Lindau disease-associated, 1 was classified as "hemangioblastoma-only VHLD", 7 were sporadic, and one was unknown. All were histopathologically analogous to their counterpart located inside the central nervous system. Immunophenotypically, all tumors expressed vimentin, S-100, NSE, and alpha-inhibin (10/10). Ultrastructurally, unbound lipid droplets filled the cytoplasms of the stromal cells. Molecular analysis revealed 3 inactivating mutations (1 germline, two somatic) in the coding sequence of the VHL gene in 2 different extraneuraxial hemangioblastomas, and LOH in 4 (two as a double hit), all non-renal extraneuraxial hemangioblastomas. Methylation analysis failed to disclose promoter methylation in any case. In conclusion, we report eight new cases from the wide category of extraneuraxial hemangioblastomas (4 paraneuraxial, and 4 renal), one of which was von Hippel-Lindau disease-associated and 7 sporadic. VHL gene alterations were found not only in the von Hippel-Lindau disease-associated tumor, but - for the first time - also in 3 sporadic ones, two of which with novel mutations., (Copyright © 2018 Elsevier GmbH. All rights reserved.)
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- 2018
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36. Ectopic, retroperitoneal adrenocortical carcinoma in the setting of Lynch syndrome.
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Wright JP, Montgomery KW, Tierney J, Gilbert J, Solórzano CC, and Idrees K
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- Adrenocortical Carcinoma genetics, Aged, Choristoma genetics, Choristoma pathology, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Colorectal Neoplasms, Hereditary Nonpolyposis pathology, Humans, Male, MutS Homolog 2 Protein genetics, Mutation, Retroperitoneal Neoplasms genetics, Adrenocortical Carcinoma complications, Adrenocortical Carcinoma pathology, Colorectal Neoplasms, Hereditary Nonpolyposis complications, Retroperitoneal Neoplasms complications, Retroperitoneal Neoplasms pathology
- Abstract
Adrenocortical carcinoma (ACC) is rare within the adult population. Ectopic ACC proves even rarer. This variant is formed by cortical fragments arrested during embryologic migration. ACC is also known to be associated with several genetic syndromes and has recently been linked to Lynch syndrome in 3% of cases. We present the case of a 68-year-old male with a confirmed diagnosis of Lynch syndrome secondary to a germline MSH2 mismatch-repair gene-mutation who presented with 2 months history of non-specific abdominal pain. After imaging work-up, the patient was found to have a right upper quadrant, retroperitoneal mass. Biochemical tests were without any evidence of a hormonally active process. Fine needle aspiration of the mass revealed a poorly differentiated carcinoma of unknown etiology. The lesion was resected and found to be consistent with ectopic ACC with an associated MSH2 mutation.
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- 2018
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37. HOTAIR gene polymorphisms contribute to increased neuroblastoma susceptibility in Chinese children.
- Author
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Yang X, He J, Chang Y, Luo A, Luo A, Zhang J, Zhang R, Xia H, and Xu L
- Subjects
- Case-Control Studies, Child, Child, Preschool, Female, Genetic Predisposition to Disease, Humans, Infant, Male, Mediastinal Neoplasms pathology, Neuroblastoma pathology, Polymorphism, Single Nucleotide, Retroperitoneal Neoplasms pathology, Asian People genetics, Mediastinal Neoplasms genetics, Neuroblastoma genetics, RNA, Long Noncoding genetics, Retroperitoneal Neoplasms genetics
- Abstract
Background: Neuroblastoma is the most frequently diagnosed extracranial solid tumor in children. Previous studies have shown that single-nucleotide polymorphisms in some genes are associated with the risk of multiple cancers, including neuroblastoma. Although Hox transcript antisense intergenic RNA (HOTAIR) gene polymorphisms have been investigated in a variety of cancers, to the authors' knowledge the relationships between HOTAIR gene polymorphisms and neuroblastoma susceptibility have not been reported to date. The objective of the current study was to evaluate the correlation between HOTAIR gene polymorphisms and neuroblastoma risk in Chinese children., Methods: The authors genotyped 6 polymorphisms (rs920778 A>G, rs12826786 C>T, rs4759314 A>G, rs7958904 G>C, rs874945 C>T, and rs1899663 C>A) of the HOTAIR gene in 2 Chinese populations including 393 neuroblastoma cases and 812 healthy controls. The strength of the associations was evaluated using odds ratios and 95% confidence intervals. Further stratification analyses were conducted to explore the association between the HOTAIR gene polymorphisms rs12826786 C>T, rs874945 C>T, and rs1899663 C>A with neuroblastoma susceptibility in terms of age, sex, clinical stage of disease, and sites of origin., Results: The authors found that the rs12826786 C>T (P =.013), rs874945 C>T (P =.020), and rs1899663 C>A (P =.029) polymorphisms were significantly associated with increased neuroblastoma risk. In stratification analyses, these associations were more predominant in females and among patients with tumor in the retroperitoneal region or mediastinum. The remaining 3 polymorphisms were not found to be related to neuroblastoma susceptibility., Conclusions: The results of the current study verified that HOTAIR gene polymorphisms are associated with increased neuroblastoma risk and suggest that HOTAIR gene polymorphisms might be a potential biomarker for neuroblastoma susceptibility. Cancer 2018;124:2599-606. © 2018 American Cancer Society., (© 2018 American Cancer Society.)
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- 2018
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38. Retroperitoneal Angiomatoid Fibrous Histiocytoma Presenting as a Recurrent Spontaneous Retroperitoneal Hemorrhage in a 9-Year-Old Boy.
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Slack JC, Sanchez-Glanville C, Steele M, Wong AL, and Bründler MA
- Subjects
- Child, Humans, Male, Gene Rearrangement, Hemorrhage genetics, Hemorrhage pathology, Hemorrhage surgery, Histiocytoma, Benign Fibrous genetics, Histiocytoma, Benign Fibrous pathology, Histiocytoma, Benign Fibrous surgery, RNA-Binding Protein EWS genetics, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Retroperitoneal Neoplasms surgery
- Abstract
Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that typically presents in children and young adults. Occurrence outside of the extremities and the head and neck region is exceedingly rare. We report the case of a 9-year-old boy who presented with recurrent retroperitoneal hemorrhage initially thought to be a manifestation of an underlying bleeding disorder. After comprehensive diagnostic work-up, including multiple negative biopsies, the patient underwent surgical resection of an extensively hemorrhagic intramuscular mass and to date remains well. Pathologic examination confirmed AFH with EWSR1 gene rearrangement. This first documented report of an AFH in a retroperitoneal location in a child highlights the diagnostic difficulties and clinical challenges of AFH arising in an atypical location.
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- 2018
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39. Clinicopathological and Molecular Factors, Risk Factors, Treatment Outcomes and Risk of Recurrence in Mesenteric and Retroperitoneal Extragastrointestinal Stromal Tumors.
- Author
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Apostolou KG, Schizas D, Vavouraki E, Michalinos A, Tsilimigras DI, Garmpis N, Damaskos C, Papalampros A, and Liakakos T
- Subjects
- Humans, Immunohistochemistry, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local metabolism, Neoplasms, Connective Tissue genetics, Neoplasms, Connective Tissue metabolism, Neoplasms, Connective Tissue surgery, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms metabolism, Retroperitoneal Neoplasms surgery, Risk Factors, Treatment Outcome, Mesentery pathology, Neoplasm Recurrence, Local pathology, Neoplasms, Connective Tissue pathology, Retroperitoneal Neoplasms pathology, Stromal Cells pathology
- Abstract
Background/aim: The objective of the present study was to determine the clinicopathological factors and treatment outcomes of patients suffering from mesenteric or retroperitoneal extragastrointestinal stromal tumors (EGISTs)., Materials and Methods: A detailed search in PubMed, using the key words "extragastrointestinal stromal tumors" and "EGIST", found eight studies fulfilling the criteria of this study., Results: Thirty-six patients with a mesenteric and 24 patients with a retroperitoneal EGIST were analyzed, with a follow-up period ranging from 2 to 192 months. Retroperitoneal tumors presented as larger tumors than mesenteric ones, with 95% and 93% immunohistochemical positivity for CD117 antigen, respectively. Surgical resection was performed in 91% of cases, with 57% of patients with mesenteric and 70% of patients with retroperitoneal EGISTs being alive at the last follow-up., Conclusion: EGISTs most commonly are of considerable size and usually with a high mitotic count, rendering them high-risk tumors. Tumor necrosis, nuclear atypia, tumor histology, and mutations in the tyrosine kinase KIT or platelet-derived growth factor receptor A (PDGFRA) gene, seem to influence tumor behavior., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2018
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40. Histiocytic sarcoma: New insights into FNA cytomorphology and molecular characteristics.
- Author
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Hung YP, Lovitch SB, and Qian X
- Subjects
- Aged, Aged, 80 and over, Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic metabolism, Bone Neoplasms genetics, Bone Neoplasms metabolism, Bone Neoplasms surgery, DNA-Binding Proteins genetics, Epigenesis, Genetic, Female, High-Throughput Nucleotide Sequencing, Histiocytic Sarcoma genetics, Histiocytic Sarcoma metabolism, Histiocytic Sarcoma surgery, Humans, Immunohistochemistry, Liver Neoplasms metabolism, Liver Neoplasms secondary, Liver Neoplasms surgery, Lung Neoplasms genetics, Lung Neoplasms metabolism, Lung Neoplasms surgery, Male, Middle Aged, Neck, Neoplasm Proteins genetics, Proto-Oncogene Proteins metabolism, Receptors, Cell Surface metabolism, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms metabolism, Retroperitoneal Neoplasms surgery, Scapula metabolism, Scapula surgery, Sequence Analysis, DNA, Soft Tissue Neoplasms metabolism, Soft Tissue Neoplasms secondary, Soft Tissue Neoplasms surgery, Trans-Activators metabolism, Uterine Neoplasms genetics, Uterine Neoplasms metabolism, Uterine Neoplasms surgery, Bone Neoplasms pathology, Histiocytic Sarcoma pathology, Liver Neoplasms pathology, Lung Neoplasms pathology, Retroperitoneal Neoplasms pathology, Scapula pathology, Soft Tissue Neoplasms pathology, Uterine Neoplasms pathology
- Abstract
Background: Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphologic and immunophenotypic features of histiocytes. Molecular characteristics of HS and fine-needle aspiration (FNA) criteria for its diagnosis have not been established., Methods: A case series of HS in 8 FNA samples from 6 patients was reviewed along with histopathologic and clinical data. Immunohistochemistry was performed on cell blocks (3 cases), core biopsies (5 cases), and surgical specimens (4 cases). Targeted-exome next-generation sequencing (NGS) was performed on surgical resection specimens in 4 cases., Results: Four patients had a known history of hematolymphoid malignancy. Cytomorphologic features included variably cellular smears composed of large epithelioid cells with reniform nuclei and abundant vacuolated cytoplasm, in an inflammatory background, with occasional cytophagocytosis and lymphoglandular bodies. Marked pleomorphism, multinucleated monster cells, and binucleated histiocytoid cells with partially overlapping, eccentrically placed nuclei resembling Pac-Man were common. Most cases expressed histiocytic markers CD68 (6 of 7 cases), CD163 (5 of 5 cases), and PU.1 (3 of 4 cases). In 3 cases, NGS analysis revealed alterations in lysine methyltransferase 2D (KMT2D)/mixed-lineage leukemia 2 (MLL2), a gene involved in chromatin regulation and previously implicated in the pathogenesis of follicular lymphoma., Conclusions: Although diagnosing HS with FNA alone is extremely challenging, the presence of pleomorphic and epithelioid large cells with binucleation and/or multinucleation in an inflammatory background should prompt the diagnosis of HS with judicious use of confirmatory histiocytic lineage markers. The detection of recurrent KMT2D/MLL2 alterations implicates epigenetic regulation in the pathogenesis of HS and supports the notion of transdifferentiation from a genetically similar but phenotypically distinct tumor of a different lineage. Cancer Cytopathol 2017;125:604-14. © 2017 American Cancer Society., (© 2017 American Cancer Society.)
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- 2017
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41. GIST Manifesting as a Retroperitoneal Tumor: Clinicopathologic Immunohistochemical, and Molecular Genetic Study of 112 Cases.
- Author
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Miettinen M, Felisiak-Golabek A, Wang Z, Inaguma S, and Lasota J
- Subjects
- Adult, Aged, Aged, 80 and over, Anoctamin-1, Biopsy, Chloride Channels analysis, Female, Gastrointestinal Stromal Tumors chemistry, Gastrointestinal Stromal Tumors genetics, Gastrointestinal Stromal Tumors pathology, Genetic Predisposition to Disease, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mitotic Index, Multivariate Analysis, Mutation, Neoplasm Proteins analysis, Phenotype, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Proto-Oncogene Proteins c-kit analysis, Proto-Oncogene Proteins c-kit genetics, Receptor, Platelet-Derived Growth Factor alpha genetics, Retroperitoneal Neoplasms chemistry, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Risk Factors, Succinate Dehydrogenase analysis, Survival Rate, Time Factors, Tumor Burden, Young Adult, Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, DNA Mutational Analysis, Gastrointestinal Stromal Tumors diagnosis, Immunohistochemistry, Molecular Diagnostic Techniques, Retroperitoneal Neoplasms diagnosis
- Abstract
Most gastrointestinal stromal tumors (GISTs) occur in the tubular gastrointestinal (GI) tract, but some present apparently outside the GI tract. In this study, we analyzed 112 GISTs located in the retroperitoneum. These tumors occurred in 55 women and 57 men with a median age of 65 years (range: 21 to 89 y). On the basis of clinically or histologically detected connections to GI tract, 15 tumors were considered likely of gastric, 9 duodenal, and 13 of small intestinal origin. The remaining cases were categorized by location as peripancreatic (n=25), pelvic (n=11), mesenteric (n=4), and of unspecified/miscellaneous sites (n=35). The tumors varied in size 3 to 35 cm (median, 15 cm) and by mitotic rate per 5 mm, 0 to >100 (median, 10). Histologically the tumors apparently arising outside the GI tract had features of intestinal (n=41) and gastric GISTs (n=25); 9 cases had indeterminate histology. The histologic variants included spindled, epithelioid, vacuolated, nested, and myxoid potentially simulating other tumors such as liposarcoma and solitary fibrous tumor. Most GISTs were KIT-positive (106/112 cases), and the remaining 6 tumors were DOG1/Ano1-positive. Five cases showed focal nuclear positivity for MDM2. KIT mutations were detected in 42/59 cases, and PDGFRA mutations in 4/16 KIT wild-type and 3/5 of the KIT-negative tumors analyzed. One pelvic retroperitoneal GIST was succinate dehydrogenase deficient. All 79 patients were dead at last follow-up with a median survival of 14 months, with few survivals >5 years. Only operable versus inoperable tumor was a statistically favorable factor in univariate analysis (P<0.01). In multivariate analysis, mitotic rate >50/5 mm was significant for a shorter survival (hazard ratio, 5.25; 95% confidence interval, 1.65-16.8; P<0.01). Histologic and clinicopathologic similarity of extragastrointestinal retroperitoneal GISTs with GISTs of GI tract suggests their GI tract origin. Potentially overlapping features between GIST and other retroperitoneal tumors necessitate use of multiple diagnostic markers and molecular genetic studies.
- Published
- 2017
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42. Detection of mosaic 15q11.1-q11.2 deletion encompassing NBEAP1 and POTEB in a fetus with diffuse lymphangiomatosis.
- Author
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Chen CP, Wang KG, Huang HK, Peng CR, Chern SR, Wu PS, Chen YN, Chen SW, Lee CC, and Wang W
- Subjects
- Abortion, Eugenic, Amniocentesis, Cytogenetic Analysis, Female, Humans, Karyotype, Lymphangioma, Cystic diagnostic imaging, Pregnancy, Retroperitoneal Neoplasms diagnostic imaging, Ultrasonography, Prenatal, Apoptosis Regulatory Proteins genetics, Chromosomes, Human, Pair 15, Lymphangioma, Cystic genetics, Mosaicism, Neoplasm Proteins genetics, Retroperitoneal Neoplasms genetics
- Abstract
Objective: We present cytogenetic and molecular cytogenetic diagnoses of mosaic deletion of chromosome 15q11.1-q11.2 in a fetus with diffuse lymphangiomatosis., Case Report: A 33-year-old woman underwent amniocentesis at 22 weeks of gestation because of fetal diffuse lymphangiomatosis involving left-side chest, abdominal cavity, thigh and vulva, and intrauterine growth restriction. Amniocentesis revealed a karyotype of 46,XX,del(15) (q11.1q11.2)[9]/46,XX[26]. The mother had a karyotype of 46,XX. The father had a karyotype of 46,XY. The parents elected to terminate the pregnancy. A 610-g female fetus was delivered at 23 weeks of gestation with large cystic lymphangioma over the left abdomen, thigh, and vulva. The umbilical cord had a karyotype of 46,XX,del(15)(q11.1q11.2)[24]/ 46,XX[16]. The placental tissue had a karyotype of 46,XX,del(15)(q11.1q11.2)[23]/ 46,XX[17]. Array comparative genomic hybridization analysis of the umbilical cord and placenta revealed a 2.42-Mb deletion of 15q11.1-q11.2 encompassing the genes of NBEAP1 and POTEB., Conclusion: Deletion of 15q11.1-q11.2 encompassing NBEAP1 and POTEB may be associated with diffuse lymphangiomatosis., (Copyright © 2017. Published by Elsevier B.V.)
- Published
- 2017
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43. A novel long noncoding RNA PILRLS promote proliferation through TCL1A by activing MDM2 in Retroperitoneal liposarcoma.
- Author
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Shao Y, Zhang Y, Hou Y, Tong H, Zhuang R, Ji Z, Wang B, Zhou Y, and Lu W
- Subjects
- Animals, Blotting, Northern, Blotting, Western, Cell Proliferation, Female, Heterografts, Humans, Liposarcoma genetics, Liposarcoma metabolism, Mice, Mice, Inbred BALB C, Mice, Nude, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins c-mdm2 genetics, Real-Time Polymerase Chain Reaction, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms metabolism, Gene Expression Regulation, Neoplastic genetics, Liposarcoma pathology, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-mdm2 metabolism, RNA, Long Noncoding, Retroperitoneal Neoplasms pathology
- Abstract
It is becoming evident that lncRNAs may be an important class of pervasive genes involved in carcinogenesis and metastasis. However, the biological and molecular mechanisms of lncRNAs in retroperitoneal liposarcoma have never been reported. In our study, we found a novel lncRNA PILRLS (Proliferation Interacting LncRNA in Retroperitoneal Liposarcoma), which as an oncogene significantly overexpressed in retroperitoneal liposarcoma. Functions of PILRLS on tumor progression both in vitro and in vivo have verified in this study which PILRLS knockdown significantly inhibited cell proliferation and colony formation. RNA pull-down assay found PILRLS can specific binding with TCL1A which also regulate the expression level of TCL1A. Our work for the first time demonstrated PILRLS can activating the MDM2 by binding with TCL1A which suppress the P53 pathway to promote the unlimited growth of retroperitoneal Liposarcoma cells. It suggests that PILRLS may be an important targets for retroperitoneal liposarcoma therapy.
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- 2017
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44. A subset of fat-predominant angiomyolipomas label for MDM2: a potential diagnostic pitfall.
- Author
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Asch-Kendrick RJ, Shetty S, Goldblum JR, Sharma R, Epstein JI, Argani P, and Cimino-Mathews A
- Subjects
- Actins analysis, Adipose Tissue pathology, Adult, Aged, Angiomyolipoma genetics, Angiomyolipoma pathology, Biomarkers, Tumor genetics, Calcium-Binding Proteins analysis, Diagnosis, Differential, Diagnostic Errors, Female, Gene Amplification, Humans, In Situ Hybridization, Fluorescence, Liposarcoma genetics, Liposarcoma pathology, Male, Melanoma-Specific Antigens analysis, Microfilament Proteins analysis, Middle Aged, Predictive Value of Tests, Proto-Oncogene Proteins c-mdm2 genetics, Reproducibility of Results, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms pathology, Retrospective Studies, gp100 Melanoma Antigen, Calponins, Adipose Tissue chemistry, Angiomyolipoma chemistry, Biomarkers, Tumor analysis, Immunohistochemistry, Liposarcoma chemistry, Proto-Oncogene Proteins c-mdm2 analysis, Retroperitoneal Neoplasms chemistry
- Abstract
Angiomyolipomas (AMLs) are typically benign mesenchymal tumors with variable histologic composition. Fat-predominant AMLs can mimic well-differentiated liposarcomas (WDLSs) both radiographically and histologically because of the abundance of fat with admixed atypical cells resembling lipoblasts. However, the treatment and prognosis of AMLs and WDLSs are vastly different. Immunohistochemistry for murine double minute 2 (MDM2) has been used to support a diagnosis of WDLS; however, MDM2 labeling has not been specifically evaluated in fat-predominant AMLs. Here, we evaluated MDM2 immunohistochemistry in 36 AMLs (including 14 conventional AMLs, 13 fat-predominant AMLs, 6 fat-rich AMLs, 3 epithelioid AMLs) and 10 WDLSs. In addition, we labeled cases for HMB45, calponin, or actin, which are immunostains traditionally used to label AML. We performed fluorescence in situ hybridization (FISH) for MDM2 amplification on selected cases. By immunohistochemistry, 14% (5/36) of AMLs were MDM2+, including 23% (3/13) of fat-predominant AMLs. All MDM2+ AMLs evaluated by FISH (n=4) were negative for MDM2 amplification. By immunohistochemistry, 90% of WDLSs were MDM2+, and both MDM2+ WDLSs evaluated by FISH (n=2) were MDM2 amplified. All 36 AMLs labeled with HMB45 and calponin or actin. No WDLS labeled with HMB45; however, 80% of WDLSs labeled with calponin or actin. Although uncommon, MDM2 labeling is seen in a subset of fat-predominant AMLs and is a potential diagnostic pitfall in the evaluation of fatty tumors of the retroperitoneum. HMB45 is more sensitive and specific for AML than calponin or actin, and an immunopanel containing both HMB45 and MDM2 may be warranted to distinguish between fat-predominant AML and WDLS in histologically ambiguous cases., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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45. Gene expression profiling identifies distinct molecular subgroups of leiomyosarcoma with clinical relevance.
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Lee YF, Roe T, Mangham DC, Fisher C, Grimer RJ, and Judson I
- Subjects
- Abdominal Neoplasms genetics, Aged, Datasets as Topic, Extremities, Female, Humans, Leiomyosarcoma genetics, Male, Middle Aged, Neoplasm Grading, Neoplasm Proteins biosynthesis, Neoplasm Proteins genetics, Retroperitoneal Neoplasms genetics, Thoracic Neoplasms genetics, Tissue Array Analysis, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Leiomyosarcoma classification
- Abstract
Background: Soft tissue sarcomas are heterogeneous and a major complication in their management is that the existing classification scheme is not definitive and is still evolving. Leiomyosarcomas, a major histologic category of soft tissue sarcomas, are malignant tumours displaying smooth muscle differentiation. Although defined as a single group, they exhibit a wide range of clinical behaviour. We aimed to carry out molecular classification to identify new molecular subgroups with clinical relevance., Methods: We used gene expression profiling on 20 extra-uterine leiomyosarcomas and cross-study analyses for molecular classification of leiomyosarcomas. Clinical significance of the subgroupings was investigated., Results: We have identified two distinct molecular subgroups of leiomyosarcomas. One group was characterised by high expression of 26 genes that included many genes from the sub-classification gene cluster proposed by Nielsen et al. These sub-classification genes include genes that have importance structurally, as well as in cell signalling. Notably, we found a statistically significant association of the subgroupings with tumour grade. Further refinement led to a group of 15 genes that could recapitulate the tumour subgroupings in our data set and in a second independent sarcoma set. Remarkably, cross-study analyses suggested that these molecular subgroups could be found in four independent data sets, providing strong support for their existence., Conclusions: Our study strongly supported the existence of distinct leiomyosarcoma molecular subgroups, which have clinical association with tumour grade. Our findings will aid in advancing the classification of leiomyosarcomas and lead to more individualised and better management of the disease.
- Published
- 2016
- Full Text
- View/download PDF
46. Annulate Lamellae in a Desmoplastic Small Round Cell Tumor.
- Author
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Alfaro-Cervelló C, Soriano-Navarro M, Cebrián-Silla A, and Forteza-Vila J
- Subjects
- Adult, Biomarkers, Tumor analysis, Desmoplastic Small Round Cell Tumor genetics, Female, Humans, Immunohistochemistry, Microscopy, Electron, Transmission, Neoplasm Recurrence, Local pathology, Oncogene Proteins, Fusion genetics, Retroperitoneal Neoplasms genetics, Reverse Transcriptase Polymerase Chain Reaction, Desmoplastic Small Round Cell Tumor pathology, Desmoplastic Small Round Cell Tumor ultrastructure, Retroperitoneal Neoplasms pathology, Retroperitoneal Neoplasms ultrastructure
- Published
- 2016
- Full Text
- View/download PDF
47. Primary Retroperitoneal Myxoid Liposarcomas.
- Author
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Setsu N, Miyake M, Wakai S, Nakatani F, Kobayashi E, Chuman H, Hiraoka N, Kawai A, and Yoshida A
- Subjects
- Adult, Aged, Female, Gene Rearrangement, Humans, In Situ Hybridization, Fluorescence, Liposarcoma genetics, Liposarcoma, Myxoid genetics, Male, Retroperitoneal Neoplasms genetics, Retrospective Studies, Transcription Factor CHOP genetics, Liposarcoma pathology, Liposarcoma, Myxoid pathology, Retroperitoneal Neoplasms pathology
- Abstract
Myxoid liposarcomas (MLSs) are genetically defined by the presence of DDIT3 gene fusions and most commonly arise in the extremities of young adults. Whether MLSs develop primarily in the retroperitoneum is controversial, and a recent retrospective study found no molecularly confirmed examples. Because MLSs tend to metastasize to deep soft tissues, purported examples of primary retroperitoneal lesions might represent distant metastasis, most commonly from extremities. In addition, well-differentiated or dedifferentiated liposarcomas, which are characterized by MDM2 amplifications, may exhibit prominent myxoid changes and mimic MLSs. Here, we document 5 cases of MLSs that originated in the retroperitoneum that were identified through critical clinicopathologic reevaluation. These cases accounted for 2.3% of 214 primary retroperitoneal liposarcomas and 3.2% of 156 MLSs in our database. They occurred in 3 men and 2 women with a median age of 32 years. All tumors were localized to the retroperitoneum at presentation, and no patient developed extra-abdominal recurrences during the clinical course (median, 50 mo). All 5 cases exhibited at least focal classic histologic findings. All harbored DDIT3 gene rearrangements, and none harbored MDM2 amplifications according to fluorescence in situ hybridization. This study demonstrates that primary MLSs can occur in the retroperitoneum, albeit rarely, and can be accurately diagnosed through combined clinicopathologic and molecular analysis., Competing Interests: and Source of Funding: Supported in part by the National Cancer Center Research and Development Fund (26-A-9 and 26-A-21) and the Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (AMED, 15ck0106089h0002). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
- Published
- 2016
- Full Text
- View/download PDF
48. Giant intra-abdominal mature cystic teratoma (dermoid cyst) in an adult man, with male genitourinary tissue including prostatic and penile elements.
- Author
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Thway K, Berney D, Hayes AJ, and Fisher C
- Subjects
- Adult, Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Biopsy, Cell Plasticity, Dermoid Cyst chemistry, Dermoid Cyst genetics, Dermoid Cyst surgery, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Male, Retroperitoneal Neoplasms chemistry, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms surgery, Teratoma chemistry, Teratoma genetics, Teratoma surgery, Cell Differentiation, Dermoid Cyst pathology, Penis pathology, Prostate pathology, Retroperitoneal Neoplasms pathology, Teratoma pathology, Tumor Burden
- Abstract
We describe a case of a giant intra-abdominal mature cystic teratoma in a 36-year-old man, which comprised typical features of differentiated teratoma/dermoid cyst but which contained a macroscopic rudimentary penis, with vasoformative erectile tissue-like structures consistent with corpora cavernosa, as well as scrotal-type skin and prostatic tissue. The genitourinary structures were well formed both grossly and microscopically and sharply demarcated from the rest of the neoplasm, which comprised typical differentiated teratoma, without any other macroscopic foci of organoid differentiation or of other histologic differentiation. The plasticity of the cells of differentiated teratoma, which enables it to undergo multidirectional differentiation, is well recognized, but the factors determining this distinct path of differentiation remain to be established., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
49. Congenital Retroperitoneal Teratoma in Neurofibromatosis Type 1.
- Author
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Yap P, Super L, Qin J, Burgess T, Prodanovic Z, Edwards C, Thomas R, Carpenter K, and Tan TY
- Subjects
- Genes, Neurofibromatosis 1, Humans, Infant, Newborn, Male, Multiplex Polymerase Chain Reaction, Mutation, Neurofibromatosis 1 genetics, Retroperitoneal Neoplasms pathology, Teratoma pathology, Neurofibromatosis 1 complications, Retroperitoneal Neoplasms congenital, Retroperitoneal Neoplasms genetics, Teratoma congenital, Teratoma genetics
- Abstract
Neurofibromatosis type 1 (NF1) is caused by mutations in the tumor suppressor gene NF1. The increased tumor risk in affected individuals is well established, caused by somatic biallelic inactivation of NF1 due to loss of heterozygosity. Pediatric teratoma has not been reported in individuals with NF1 previously. We report a case of congenital teratoma in an infant with a heterozygous maternally inherited pathogenic NF1 mutation (c.[1756_1759delACTA] and p.[Thr586Valfs*18]). We detected a "second hit" in the form of mosaic whole NF1 deletion in the tumor tissue using multiplex ligation-dependent probe amplification, as a proof to support the hypothesis of NF1 involvement in the pathogenesis of teratoma., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2016
- Full Text
- View/download PDF
50. Retroperitoneal catecholamine-producing ganglioneuroma with a birth history of monozygotic twins who both suffered from neuroblastoma during their childhoods: a case report with genome analysis.
- Author
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Ishihara H, Kikuno N, Hayakawa N, Ryoji O, and Tanabe K
- Subjects
- Child, Preschool, Diseases in Twins genetics, Female, Ganglioneuroma genetics, Ganglioneuroma metabolism, Humans, Infant, Male, Middle Aged, Neuroblastoma genetics, Reproductive History, Retroperitoneal Neoplasms genetics, Retroperitoneal Neoplasms metabolism, Catecholamines metabolism, Diseases in Twins diagnosis, Ganglioneuroma diagnosis, Neuroblastoma diagnosis, Retroperitoneal Neoplasms diagnosis, Twins, Monozygotic genetics
- Published
- 2015
- Full Text
- View/download PDF
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