Myxoid mesenchymal intraventricular brain tumour with EWSR1–CREB1 gene fusion in an adult woman

Intracranial myxoid angiomatoid fibrous histiocytoma with “classic” histology and EWSR1:CREM fusion providing insight for reconciliation with intracranial myxoid mesenchymal tumors

“…To the best of our knowledge, there have been only 10 cases of intracranial AFH in the published literature, including our case (Table 1). [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] As none of the features is pathognomonic, a confident diagnosis of intracranial AFH is based on a constellation of clinical, histological, and immunohistochemical findings, supported by the presence of EWSR1 rearrangement. In view of the morphological variation and rarity of intracranial AFH, there have been cases that were mistaken for cavernous hemangioma or unusual variant of meningioma before a correct diagnosis was made.…”

“…[2][3][4] Notably, a group of tumors, exhibiting intracranial predilection, prominent myxoid change, disparate histological but overlapping immunohistochemical and molecular genetic features with AFH, has been recently reported and referred to as intracranial myxoid mesenchymal tumors (IMMT). [6][7][8][9][10][11][12][13][14] A few of the latter cases demonstrated a fusion between EWSR1 and the cAMP response element modulator gene (CREM), another member of the CREB family that was not previously described in AFHs, sparking debate on whether IMMTs represent a distinct pathological entity. 6,7,9,14 We describe an interesting case of intracranial tumor showing "classic" histological features of myxoid AFH yet harboring the EWSR1:CREM fusion.…”

“…Vice versa, fusions between EWSR1 and CREB1 or ATF1 were identified in several cases of IMMT (Table 1). [6][7][8][10][11][12][13] AFH is generally treated with a wide local excision and followed up regularly and indefinitely, because of its potential to recur, as estimated to be 15%, and the possibility of metastasis, although rare (less than 5%). [2][3][4][5] Unfortunately, no clinicopathological or genetic factors have been established to predict the behavior of the tumor, and complete resection of the lesion with subsequent radiological follow up appears to be the standard of care at present.…”

A case of intracranial myxoid mesenchymal tumor with EWSR1:CREM fusion in an adult female: Extensive immunohistochemical evaluation

“…2 Some fusion genes are not specific to tumor histological types and appear in association with different clinicopathological features. 3,4 As a typical example, the fusion between members of the female-expressed transcript (FET) gene (FET) family, encoding Ewing sarcoma breakpoint region 1 (EWSR1) and fused-in-sarcoma (FUS), and those of the cAMP response element-binding protein (CREB) gene (CREB) family, encoding CREB1, cAMP-dependent transcription 1 (ATF1), and cAMP-responsive element modulator (CREM) is present in several kinds of malignancies, including angiomatoid fibrous histiocytoma (AFH), clear cell sarcoma (CCS), primary pulmonary myxoid sarcoma, and hyalinizing clear cell carcinoma (HCCC) of the salivary gland. [5][6][7][8][9] Tumors with fusions between the FET family genes and the CREB family genes (FET:CREB fusions) occur extremely rarely in intracranial sites.…”

“…They were first described as conventional angiomatoid fibrous histiocytoma (AFH), 10 and more recently as intracranial myxoid mesenchymal tumor (IMMT) and myxoid variants of AFH. 3,4,[11][12][13][14][15][16][17][18] Kao et al suggested that IMMT is a novel tumor entity because the tumor usually lacks histological features of conventional AFH, 11 but thus far it has been controversial whether these intracranial tumors are really a distinct histopathological entity or actually a myxoid variant of AFH. 3,4,17,18 However, Sloan et al indicated that intracranial mesenchymal tumors with FET:CREB fusions displayed a wide variety of histomorphological features that encompassed those previously described in both AFH and IMMT, regardless of the fusion type, and advocated that these tumors represented a single biological entity.…”