Histological spectrum of angiofibroma of soft tissue: histological and genetic analysis of 13 cases

Abstract

Aims: Angiofibroma of soft tissue (AFST) is a rare soft tissue neoplasm characterized by a fibroblastic cytomorphology and a prominent vascular structure. AFSTs possess a novel fusion gene, i.e. NCOA2-AHRR/ AHRR-NCOA2 or GTF2I-NCOA2, providing a useful approach to diagnosing AFST. Morphologically, AFSTs span a wide spectrum, making diagnosis a challenge. The aim of this study was to review AFST cases and to report previously unknown histological features, which we confirmed by genetic analysis. Methods and results: We reviewed 276 cases diagnosed as solitary fibrous tumours/haemangiopericytomas (232 cases), unclassified tumours of fibroblastic differentiation (36 cases), and recently diagnosed AFSTs (eight cases), and retrieved 13 cases compatible with AFST. Immunohistochemical staining was performed for these cases, all 13 of which were analysed by reverse transcription polymerase chain reaction and fluorescence in-situ hybridization. The histological findings were as follows: amianthoid fibres, extravasation of red blood cells, haemosiderin deposition, aggregates of foamy histiocytes, cystic change, necrosis, and haemorrhage. Immunohistochemically, the tumour cells were positive for epithelial membrane antigen (four of 13 cases), desmin (six of 13 cases), CD163 (13 of 13 cases), CD68 (seven of 13 cases), oestrogen receptor (13 of 13 cases), progesterone receptor (three of 13 cases), and STAT6 (one of 13 cases, weak nuclear staining), but they were negative for CD34, a-smooth muscle actin, , S100, pan-cytokeratin, MDM2, and CDK4. The AHRR-NCOA2 fusion gene was detected in eight cases, and NCOA2 gene rearrangement in nine cases. Conclusion: We revealed the previously unreported histological variation and immunohistochemical findings of AFST, and confirmed them by using genetic methods. The results suggested that AFST should be considered in the diagnosis of fibrous or fibrohistiocytic tumours with the above histological features.

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

“…In accordance with the series investigated by Jin et al and Yamada et al, our data suggest that AHRR‐NCOA2 is the most common fusion gene in STAF with in‐frame fusion transcripts of exon 10–14 ( n = 4), exon 10–16 ( n = 2), exon 9–16 ( n = 2), exon 9–14 ( n = 1), and exon 8–11 ( n = 2). The exon combination 8 ‐ 11 was found by RNA sequencing and has not been reported previously.…”

“…Recurrent fusion genes, recognized as driver mutations, are being discovered in a growing number of tumor types, resulting in a specific transcription program of different target genes, which in turn has clinicopathological implications . One example of such a tumor type is the recently delineated benign mesenchymal lesion STAF, which has, in addition to a distinct fibrovascular histological appearance, a AHRR‐ NCOA2 fusion transcript in a large subset of cases …”

Intra‑articular angiofibroma of soft tissue of the knee: A case report

“…Occasional cases may exhibit scattered cells that stain for CD34, SMA and desmin (2). Previous immunohistochemical studies have revealed that CD163 and ER are useful markers in the diagnosis of AFST (3,4), as in the present case. S-100 protein expression is consistently negative (1).…”

“…In addition, Arbajian et al (6) demonstrated a general transcription factor IIi (GTF2I)-NCOA2 fusion gene in a AFST with a three-way t(7;8;14)(q11;q13;q31) translocation, emphasizing the role of NCOA2. Furthermore, a small proportion of NCOA2 gene rearrangement-positive cells have been observed in almost all cases by fluorescence in situ hybridization (3,7). However, it has been noted that a substantial subset of AFSTs were negative for the fusion gene (3,5), as in the current case.…”

Pathophysiology of TFII-I: Old Guard Wearing New Hats

“…First, a novel GTF2I/NCOA2 fusion gene was identified in Soft Tissue Angiofibroma (fibrovascular tumor of unknown cellular origin) (50,51). A fusion product of t(7;8;14)(q11;q13;q31) resulted in two transcripts: one with an in-frame fusion of part of exon 14 of GTF2I with part of exon 15 of NCOA2 whereas the other one consisted of an out of-frame fusion of part of exon 11 of GTF2I with part of exon 14 of NCOA2 (51).…”