Soft Tissues: Angiomatoid fibrous histiocytoma with t(2;22)(q34;q12) EWSR1/CREB1

2009-12-01   Jean-Loup Huret  

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Epidemiology

Twenty two cases of angiomatoid fibrous histiocytoma with a (2;22)(q34;q12) have so far been described; there were 13 male and 9 female patients, aged 16 years (median, range 3-38) (Antonescu et al., 2007; Rossi et al., 2007; Shao et al., 2009).

Pathology

Cases presented either a spindle or a mixed spindle and small cell morphology; there was no case of pure small cell morphology; one case showed pleomorphism; however, the prognosis in this later case has been as good as that of other cases.

Cytogenetics

Cytogenetics morphological

The t(2;22)(q34;q12) appears to be the most frequent anomaly in angiomatoid fibrous histiocytoma, while the t(12;22)(q13;q12) (5 EWSR1 - 3 ATF1), and the t(12;16)(q13;p11) (5 FUS- 3 ATF1) are rarer.

Genes Involved and Proteins

Gene name

CREB1 (cAMP responsive element binding protein 1)

Location

2q33.3

Protein description

Contains a KID domain (kinase inductible domain), a basic motif (DNA binding) and a leucine-zipper for dimerization, like ATF1. Stimulates transcription by binding the cAMP response element TGACGTCA (CRE). Transcription factor.

Gene name

EWSR1 (Ewing sarcoma breakpoint region 1)

Location

22q12.2

Protein description

From N-term to C-term: a transactivation domain (TAD) containing multiple degenerate hexapeptide repeats, 3 arginine/glycine rich domains (RGG regions), a RNA recognition motif, and a RanBP2 type Zinc finger. Role in transcriptional regulation for specific genes and in mRNA splicing.

Result of the chromosomal anomaly

Description

5 EWSR1 - 3 CREB1. EWSR1 exon 7 is fused in frame to CREB1 exon 7 in all cases so far studied.

Description

Fusion of the N terminal transactivation domain of EWSR1 to the DNA binding domain of CREB1.

Highly cited references

Pubmed IDYearTitleCitations
195615682009Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts).49
183008042008Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases.44
225107622012Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status.43
177247452007EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma.42
180944132007EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma.37
280096022017EWSR1 Fusions With CREB Family Transcription Factors Define a Novel Myxoid Mesenchymal Tumor With Predilection for Intracranial Location.36
259271512015Angiomatoid fibrous histiocytoma: the current status of pathology and genetics.28
219976932011Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a new tumor entity.27
282813182018Intracranial myxoid mesenchymal tumors with EWSR1-CREB family gene fusions: myxoid variant of angiomatoid fibrous histiocytoma or novel entity?20
224063602012Identification of biomarkers to distinguish clear cell sarcoma from malignant melanoma.19
200871592010Cutaneous clear cell sarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of 12 cases emphasizing its distinction from dermal melanoma.19
257240382015Clear cell sarcoma-like tumor of the gastrointestinal tract: an evolving entity.17
240437182014Angiomatoid fibrous histiocytoma: clinicopathological and molecular characterisation with emphasis on variant histomorphology.15
313052682019Expanding the Phenotypic Spectrum of Mesenchymal Tumors Harboring the EWSR1-CREM Fusion.14
225880662012Endobronchial pulmonary angiomatoid fibrous histiocytoma: two cases with EWSR1-CREB1 and EWSR1-ATF1 fusions.14
243783902014Promiscuous genes involved in recurrent chromosomal translocations in soft tissue tumours.13
299702522018Clear cell sarcoma of the gastrointestinal tract and malignant gastrointestinal neuroectodermal tumour: distinct or related entities? A review.12
331414882021Intracranial mesenchymal tumor with FET-CREB fusion-A unifying diagnosis for the spectrum of intracranial myxoid mesenchymal tumors and angiomatoid fibrous histiocytoma-like neoplasms.11
277648302016Activity of c-Met/ALK Inhibitor Crizotinib and Multi-Kinase VEGF Inhibitor Pazopanib in Metastatic Gastrointestinal Neuroectodermal Tumor Harboring EWSR1-CREB1 Fusion.11
329978532021The spectrum of rare central nervous system (CNS) tumors with EWSR1-non-ETS fusions: experience from three pediatric institutions with review of the literature.10
247159282014Clear cell sarcoma-like tumor of the gastrointestinal tract, presenting as a second malignancy after childhood hepatoblastoma.10
322158042020Intracranial myxoid mesenchymal tumor with EWSR1-CREB1 gene fusion: a case report and literature review.9
300470652019Clear Cell Odontogenic Carcinoma: Occurrence of EWSR1-CREB1 as Alternative Fusion Gene to EWSR1-ATF1.9
261631852015An unusual association of malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like) and Ewing sarcoma.9
251345182014Primary pulmonary myxoid sarcomas with EWSR1-CREB1 translocation might originate from primitive peribronchial mesenchymal cells undergoing (myo)fibroblastic differentiation.8
302190842018Detection of specific gene rearrangements by fluorescence in situ hybridization in 16 cases of clear cell sarcoma of soft tissue and 6 cases of clear cell sarcoma-like gastrointestinal tumor.7
295334642018Genetic analyses of undifferentiated small round cell sarcoma identifies a novel sarcoma subtype with a recurrent CRTC1-SS18 gene fusion.7
232528712012Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion, resembling extraskeletal myxoid chondrosarcoma: Case report with a review of Literature.7
326324732021Myxoid mesenchymal intraventricular brain tumour with EWSR1-CREB1 gene fusion in an adult woman.6
294910752018Clear Cell Sarcoma-like Tumor of the Gastrointestinal Tract: Clinical Outcome and Pathologic Features of a Molecularly Characterized Tertiary Center Case Series.6
258042552015Angiomatoid fibrous histiocytoma: comparison of fluorescence in situ hybridization and reverse transcription polymerase chain reaction as adjunct diagnostic modalities.6
214111192011Reticular angiomatoid "malignant" fibrous histiocytoma--a case report with cytogenetics and molecular genetic analyses.6
198019662010Utility of FISH in the diagnosis of angiomatoid fibrous histiocytoma: a series of 18 cases.6
299322832018Therapeutic response of metastatic angiomatoid fibrous histiocytoma carrying EWSR1-CREB1 fusion to the interleukin-6 receptor antibody tocilizumab.5
299243412018Molecular and Clinicopathologic Heterogeneity of Intracranial Tumors Mimicking Extraskeletal Myxoid Chondrosarcoma.5
261654032015Paraneoplastic Syndrome of Angiomatoid Fibrous Histiocytoma May Be Caused by EWSR1-CREB1 Fusion-induced Excessive Interleukin-6 Production.5
330805632020Intracranial myxoid mesenchymal tumor with EWSR1-CREB1 fusion.4
327735302020Primary Pulmonary Myxoid Sarcoma and Myxoid Angiomatoid Fibrous Histiocytoma: A Unifying Continuum With Shared and Distinct Features.4
320397362020Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a case report and review of the literature.4
286956862017Imprint cytology of clear cell sarcoma-like tumor of the gastrointestinal tract in the small intestine: A case report.4
287222162017Primary pulmonary myxoid sarcoma located in interlobar fissure without parenchymal invasion.4
284496082017Primary Pulmonary Myxoid Sarcoma: A Newly Described Entity-Report of a Case and Review of the Literature.4
271660302016Angiomatoid fibrous histiocytoma: Clinicopathological spectrum of five cases, including EWSR1-CREB1 positive result in a single case.4
239535912013A rare case of clear cell sarcoma with 4 types of EWSR1-ATF1 fusions detected not in primary site but in metastatic site.4
205981472010Small blue round cell tumor of the interosseous membrane bearing a t(2;22)(q34;q12)/EWS-CREB1 translocation: a case report.4
330059822021Clear cell sarcoma-like/malignant gastrointestinal neuroectodermal tumor of the tongue: a clinicopathologic and molecular case report.3
231995252013Metastatic angiomatoid fibrous histiocytoma of the scalp, with EWSR1-CREB1 gene fusions in primary tumor and nodal metastasis.3
220385022012Angiomatoid fibrous histiocytoma: pleomorphic variant associated with multiplication of EWSR1-CREB1 fusion gene.3
233202322012Subcutaneous angiomatoid fibrous histiocytoma mimicking metastatic melanoma.3
340493182022Cytokeratin-positive Malignant Tumor in the Abdomen With EWSR1/FUS-CREB Fusion: A Clinicopathologic Study of 8 Cases.2
341939432021Generation of human embryonic stem cell models to exploit the EWSR1-CREB fusion promiscuity as a common pathway of transformation in human tumors.2
334627432021Clear cell tumor with melanocytic differentiation and MITF-CREM translocation: a novel entity similar to clear cell sarcoma.2
333357312021Malignant gastrointestinal neuroectodermal tumor with BRAF mutation and a history of malignant melanoma: A case report.2
315651802019Difficult diagnosis of Angiomatoid Fibrous Histiocytoma of the leg mimicking a benign condition.2
303261502019Intraluminal EWSR1-CREB1 gene rearranged, low-grade myxoid sarcoma of the pulmonary artery resembling extraskeletal myxoid chondrosarcoma (EMC).2
307750242019Mesenchymal tumors of the lung: diagnostic pathology, molecular pathogenesis, and identified biomarkers.2
276371572016'Pure' spindle cell variant of angiomatoid fibrous histiocytoma, lacking classic histologic features.2
354667252022Primary Pulmonary Myxoid Sarcoma with EWSR1::ATF1 Fusion: A Case Report.1
336168522021Clear Cell Odontogenic Carcinoma: First Report of Novel EWSR1-CREM Fusion Gene in Case of Long-Term Misdiagnosis.1
348214262022Intracranial mesenchymal tumors with FET-CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas.1
345136652021Synchronous Malignant Gastrointestinal Neuroectodermal Tumor and SMARCA4-Deficient Undifferentiated Carcinoma With Independent Origins in the Small Intestine: A Case Report.1
341569762021The clear cell sarcoma functional genomic landscape.1
337135762021Angiomatoid fibrosis histiocytoma in the pulmonary artery: A case report.1
323108592020Angiomatoid Fibrous Histiocytoma With ALK Expression in an Unusual Location and Age Group.1
315672752020SOX9 Immunohistochemistry in the Distinction of Angiomatoid Fibrous Histiocytoma From Histologic Mimics: Diagnostic Utility and Pitfalls.1
308195302019Paraneoplastic disorders associated with miscellaneous neoplasms with focus on selected soft tissue and Undifferentiated/ rhabdoid malignancies.1
305548332019[Clear cell sarcoma or gastrointestinal neuroectodermal tumor (GNET) of the tongue? Case report and review of the literature of an extremely rare tumor localization].1
228864382012Clear cell sarcoma expressing a novel chimerical transcript EWSR1 exon 7/ATF1 exon 6.1
355682792022Durable response to crizotinib in metastatic angiomatoid fibrous histiocytoma with EWSR1-CREB1 fusion and ALK overexpression.0
356931892022Clinicopathological and Genomic Features of Pediatric Intracranial Myxoid Mesenchymal Tumor with both of EWSR1-CREM Gene Fusion and MAP3K13 Mutation: A Case Report and Comparison with Adult Cases in the Literature.0
351526362022[Intracranial myxoid mesenchymal tumors with EWSR1-CREB1 fusion: report of a case].0
347927842022Clinical, pathological, and genetic profile of clear cell sarcoma-like tumour of jejunum: report of a rare aggressive tumour of small bowel.0
340573772022CRTC1-SS18 Fusion Sarcoma With Aberrant Anaplastic Lymphoma Kinase Expression.0
347716002021Clinical Value of NGS Genomic Studies for Clinical Management of Pediatric and Young Adult Bone Sarcomas.0
340553462021Intracranial non-myxoid angiomatoid fibrous histiocytoma with EWSR1-CREB1 transcript fusion treated with doxorubicin: A case report.0
352006082022A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases.0
349296032022Myoepithelial and oral intracranial myxoid mesenchymal tumor-like neoplasms as diagnostic considerations of the ever-expanding extracranial myxocollagenous tumors harboring FET-CREB fusions.0
333146852021Distinct clinicopathological features of pulmonary primary angiomatoid fibrous histiocytoma: A report of four new cases and review of the literature.0
346311872021Scapular Angiomatoid Fibrous Histiocytoma with EWSR1-CREB1 Fusion in an Adult Patient.0
334556942021[Primary pulmonary myxoid sarcoma associated with translocation EWSR1-CREB1 and locorregional micrometastases].0
333919502020Superficial Clear Cell Sarcoma (Melanoma of Soft Parts) of the Large toe in an 80-Year-Old Female With a Rare Cytogenetic Translocation.0
303177422018[Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: report of a case].0

Article Bibliography

Pubmed IDLast YearTitleAuthors
177247452007EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma.Antonescu CR et al
180944132007EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma.Rossi S et al
186668232009Angiomatoid fibrous histiocytoma with t(2;22)(q33;q12.2) and EWSR1 gene rearrangement.Shao L et al

Citation

Jean-Loup Huret

Soft Tissues: Angiomatoid fibrous histiocytoma with t(2;22)(q34;q12) EWSR1/CREB1

Atlas Genet Cytogenet Oncol Haematol. 2009-12-01

Online version: http://atlasgeneticsoncology.org/solid-tumor/5670/soft-tissues-angiomatoid-fibrous-histiocytoma-with-t(2;22)(q34;q12)-ewsr1-creb1