Dedifferentiation and progression of an intracranial solitary fibrous tumor: Autopsy case of a Japanese woman with a history of radiation therapy of the head during infancy

Abstract

Solitary fibrous tumor (SFT) is usually an indolent neoplasm with a low rate of local recurrence and metastasis. Although dedifferentiation of low-grade sarcoma is well documented, the concept of dedifferentiated SFT was not recognized until recently. A case of intracranial SFT with seven recurrences within 5 years, showing progression and dedifferentiation during the course of disease, is reported here. A 51-year-old woman with a history of irradiation during infancy presented with a SFT in the right posterior fossa. Because of the close proximity to the brain stem, the tumor could not be removed completely. The tumor recurred 12, 16, and 28 months after the initial operation. With the repeated recurrences, cellularity, mitotic count, and Ki-67 (MIB-1) index increased gradually. The histology suddenly changed at the fourth recurrence, which occurred 16 months after postoperative radiation therapy for the third recurrence. The tumor revealed a fibrosarcoma-like appearance with necrosis and markedly increased mitotic activity. The tumor further recurred 50, 52, and 55 months after the initial operation with the same fibrosarcoma-like histology. The patient died of uncontrolled tumor 58 months after the initial operation. In this case radiation may have played some role in the tumorigenesis, progression, and dedifferentiation of the SFT.

Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation

“…TP53 mutations/overexpression have been reported in high-grade/dedifferentiated solitary fibrous tumors, 12,13,[33][34][35] and both deletion 13 and TP53 mutations have been observed to appear during disease progression in longitudinal studies of solitary fibrous tumors. 19,20 Cumulatively, the main features of dedifferentiated solitary fibrous tumors are the complete or partial loss of NAB2/STAT6 chimeric protein expression (despite the retention of chimeric RNA expression), and the acquisition of genome instability. It can therefore be hypothesized that a dysregulated post-translational mechanism (responsible for the chimeric protein downregulation) is involved in the acquisition of the dedifferentiated phenotype.…”

“…[7][8][9][10][11][12][13][14], and 10 as having dedifferentiated solitary fibrous tumors (nos. [15][16][17][18][19][20][21][22][23][24].…”

“…Despite their generally 'simple' genomic and cytogenetic profiles, [16][17][18] it has been reported that solitary fibrous tumors undergo genetic alterations during their progression to malignancy 19,20 and dedifferentiation. 2 Given the availability of suitable representative samples of all types of solitary fibrous tumors (including two cases progressing to dedifferentiated), we used array comparative genomic hybridization analysis in order to define the genetic events associated with their morphophenotypical evolution.…”

“…All of the usual tumors had a normal profile, and only two of the malignant solitary fibrous tumors showed abnormalities: no. 8 had copy-number abnormalities involving entire chromosomes (gains for chromosomes 5,8,18,19, and 21 and the loss of chromosome 13), and no. 22a had two (13q and 17p) interstitial deletions (Figures 3c and f; Supplementary Fig.…”

Solitary Fibrous Tumor of the Central Nervous System

“…70 In addition, a patient had synchronous occurrence of an occipital SFT with 2 parasagittal frontal tumors, 1 of which was a histologically proven meningioma, 96 another patient had cafe´-au-lait spots not associated with neurofibromatosis type 1. 125 Finally, in 2 cases, 70,173 SFT was suspected to be radiation induced.…”