Soft tissue angiofibroma: Clinicopathologic, immunohistochemical and molecular analysis of 14 cases

Bekers, Elise M.; Groenen, Patricia J.T.A.; Verdijk, Marian A. J.; Geloof, Winny L Raaijmakers-van; Roepman, Paul; Vink, Robert; Gilhuijs, Nathalie D B; Gorp, Joost M. van; Bovée, Judith V.M.G.; Creytens, David; Flanagan, Adrienne M.; Suurmeijer, Albert; Mentzel, Thomas; Arbajian, Elsa; Flucke, Uta

doi:10.1002/gcc.22478

Cited by 36 publications

(62 citation statements)

References 28 publications

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“…The genetic hallmark of solitary fibrous tumor is the presence of a recurrent NAB2‐STAT6 gene fusion . Soft tissue angiofibroma—which tends to occur in middle age adults—has a broad anatomic distribution . The lower limbs are a common site of involvement, and tumors may be superficial or deep.…”

Section: Discussionmentioning

confidence: 99%

“…Tumors have a characteristic vasculature composed of innumerable branching vessels of variable caliber; the smaller vessels have been likened to those seen in myxoid liposarcoma, but more numerous, while the larger vessels may resemble the vasculature of solitary fibrous tumor . Immunohistochemistry frequently demonstrates staining for epithelial membrane antigen, and a subset of cases may show staining for CD34, desmin, smooth muscle actin, and/or hormone receptors . Molecular testing has revealed most cases of soft tissue angiofibroma are characterized by balanced fusions involving the NCOA2 gene; the most common fusion pair is AHRR‐NCOA2 , with isolated reports of GTF2I‐NCOA2 , and GAB1‐ABL1 10 fusion products.…”

Section: Discussionmentioning

confidence: 99%

“…Our groups recently independently encountered a distinctive soft tissue neoplasm characterized by fusions involving PRRX1 and NCOA1 . The presence of NCOA ‐rearrangement initially raised the possibility of soft tissue angiofibroma, as a majority of these tumors appear to contain NCOA2 ‐rearangement . However, as the NCOA1 rearranged tumors appeared to be morphologically distinct from soft tissue angiofibroma, we undertook an investigation to further characterize the histology and genetics of these neoplasms.…”

Section: Introductionmentioning

confidence: 99%

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PRRX‐NCOA1/2 rearrangement characterizes a distinctive fibroblastic neoplasm

Lacambra

Weinreb

Demicco

et al. 2019

Genes Chromosomes & Cancer

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Fibroblastic/myofibroblastic neoplasms represent a broad, and occasionally diagnostically challenging, category of soft tissue neoplasms. A subset of these tumors defy conventional classification. However, with the advent of next‐generation sequencing, the identification of disease‐defining molecular alterations is gradually improving their subclassification. Following identification of two index cases of a distinctive fibroblastic neoplasm with a fusion gene involving PRRX1 and NCOA1, we performed a retrospective review to further characterize this entity. We identified two additional cases, including one with a fusion between PRRX1 and NCOA2. The average patient age was 38 years, and three patients were female. Two tumors occurred on the neck, and the others involved the groin and thigh. Tumors were centered in the subcutis and ranged from 2.3 to 14.0 cm (average 5.8 cm). Morphologically, they were predominantly hypocellular, with focal hypercellularity. They were composed of monomorphic spindle‐stellate cells with a vague fascicular pattern. The nuclei were bland with only rare mitotic activity, and occasional multinucleation. The intervening stroma was typically abundant and ranged from myxoid to collagenous, with frequent rope‐like collagen bundles. Three of the cases had a prominent vasculature ranging from numerous small curvilinear vessels to ectatic and branching staghorn‐like vessels. Immunohistochemistry was negative for desmin, smooth muscle actin, S100, CD34, keratin, and epithelial membrane antigen. Each of the patients was treated by simple excision and none of the tumors were associated with local recurrence or metastasis. Based on their unique morphological and molecular attributes, we believe this represents a novel fibroblastic tumor for which we have tentatively proposed the name “PRRX‐NCOAx‐rearranged fibroblastic tumor.”

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PRRX‐NCOA1/2 rearrangement characterizes a distinctive fibroblastic neoplasm

Lacambra

Weinreb

Demicco

et al. 2019

Genes Chromosomes & Cancer

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“…We considered the possibility that an ABL1-fusion might be located on the der(4), and therefore searched the relevant literature for ABL1 fusions in mesenchymal tumors. This gave information on a third tumor which was located in the foot of a 7-year-old boy, diagnosed as a soft tissue angiofibroma and carrying a GAB1-ABL1 fusion gene (46) (Table I, case 12). However, soft tissue angiofibromas are characterized by the pathognomonic t(5;8)(p15;q13) chromosome translocation or variants thereof resulting in an AHHR-NCOA2 fusion gene (46)(47)(48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

Recurrent Fusion of the GRB2 Associated Binding Protein 1 (GAB1) Gene With ABL Proto-oncogene 1 (ABL1) in Benign Pediatric Soft Tissue Tumors

Panagopoulos

Gorunova

Andersen

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: Fusions of the ABL protooncogene 1 gene (ABL1 in 9q34) are common in leukemias but rare in solid tumors. The most notable is the t(9;22)(q34;q11)/BCR-ABL1 coding for a chimeric tyrosine kinase. We herein report an ABL1-fusion in a pediatric tumor. Materials and Methods: G-banding, fluorescence in situ hybridization, reverse transcription polymerase chain reaction and Sanger sequencing were performed on a soft tissue perineurioma found in the left musculus erector spinae of a child. Results: A der(4)t(4;9)(q31;q34) and a fusion of the GRB2 associated binding protein 1 (GAB1 in 4q31) gene with ABL1 were found. A literature search revealed 3 more cases with similar genetic and clinicopathological characteristics: a soft tissue perineurioma with t(2;9;4)(p23;q34;q31) and ABL1 rearrangement, a soft tissue angiofibroma with a GAB1-ABL1 chimeric gene, and a solitary fibrous tumor carrying a der(4)t(4;9)(q31.1;q34). Conclusion: GAB1-ABL1 is a recurrent fusion gene in benign pediatric tumors. The ABL proto-oncogene 1 gene (ABL1, previous symbol ABL) in chromosome band 9q34 is ubiquitously expressed and codes for a non-receptor tyrosine kinase which is localized at many subcellular sites including the nucleus, cytoplasm, mitochondria, and endoplasmic reticulum. It is involved in a variety of cellular processes such as cell division, adhesion, differentiation, and response to stress (1-3). ABL1 together with ABL2 (the proto-oncogene 2 gene which encodes a non-receptor tyrosine kinase and maps to chromosome band 1q25) constitute the ABL family of kinase genes (2, 4-6). Both ABL1 and ABL2 fuse with a variety of translocation partner genes in various hematological malignancies (7-10). The most notable fusion is between ABL1 and the 5' end of the breakpoint cluster region gene (BCR), located in 22q11, through the t(9;22)(q34;q11) chromosome translocation that gives rise to the Philadelphia chromosome in chronic myeloid leukemia (CML) (11, 12). The BCR-ABL1 fusion gene codes for a leukemogenic, constitutively active tyrosine kinase (11, 12). The discovery that 2-phenylaminopyrimidines inhibit the ABL protein kinase both in vitro and in vivo, led to the development of imatinib mesylate that now constitutes the first-line treatment of CML, as well as to introduction of other protein kinase inhibitors into cancer therapy (13-19). Rearrangements of the ABL1 and ABL2 genes in solid tumors have also been documented (3-6, 20). Phosphorylation and activation of ABL kinases were reported in various tumors such as breast and lung adenocarcinomas, melanomas, and cancers of the brain (3-6, 20). The mechanisms for activation of ABL1 and ABL2 kinases are in these settings not chromosome translocations/fusion genes but rather genomic amplification, increased expression of mRNA, enhanced protein expression, and increased catalytic activity (3-6, 20). Perineurioma is a tumor composed entirely of neoplastic perineurial cells with ultrastructural and immunohistochemical features similar to those of their normal counterparts (21). A...

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“…2 A characteristic AHRR-NCOA2 fusion gene secondary to t(5;8)(p15;q13) is present in approximately two thirds of cases. 3 Aims: We present three cases of AFST encountered at RPAH Tissue Pathology in order to outline and explore the clinical, macroscopic, histopathologic, immunohistochemical, and cytogenetic features of this tumour. Methods: Three cases underwent histopathological and immunohistochemical analysis, as well as presentation at a multidisciplinary soft tissue meeting.…”

Section: Epstein-barr Virus Associated Smooth Muscle Tumour; Rare Sofmentioning

confidence: 99%