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Diagnosis and Discussion: Case 1141

Final Diagnosis

Dedifferentiated solitary fibrous tumor, high-grade

Discussion

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm of fibroblastic differentiation, often with indolent clinical behavior though with the ability to dedifferentiate, portending more aggressive behavior [1]. Dedifferentiation of SFT is extremely rare, most often seen in middle-aged adults in the retroperitoneum and deep soft tissues, with metastasis most commonly in the lung but also reported in the brain, liver, and bone [1].

Dedifferentiated SFT grossly appears tan-white, fleshy, and firm often with hemorrhage and necrosis with possible invasion into surrounding structures [1]. Microscopically, conventional areas often show spindle cells in a “patternless pattern” with interspersed collagen and branching “staghorn” vessels. There is often an abrupt transition between the conventional portion and the dedifferentiated portion, which shows round-oval cells with pleomorphic nuclei, increased mitotic activity, and frequent cystic degeneration and necrosis [1]. The high-grade component may also contain areas of heterologous differentiation including rhabdomyosarcomatous, osteosarcomatous, and chrondrosarcomatous components [2-4].

Immunohistochemically, SFTs are CD34 and CD99 positive, sometimes with BCL-2, EMA, and SMA staining, while this staining pattern is often lost in the dedifferentiated component [1]. Specifically, about half of reported cases showed CD34 loss in the high-grade component [1]. STAT6 is also often positive due to the NAB2::STAT6 fusion driver mutation pathognomonic for SFTs which converts a transcriptional repressor of mitogenic pathways (NAB2) into a transcriptional activator [1,5]. Nuclear STAT6 staining and cytoplasmic ALDH1 staining are highly sensitive and specific markers for SFTs [6] although STAT6 staining is sometimes lost in the dedifferentiated component of SFTs [7,8]. Similarly to our case, Kurisaki-Arakawa et al. report a case in which the dedifferentiated component of the SFT showed loss of CD34 with retained STAT6 staining [2].

Molecularly, our case showed the NAB2::STAT6 gene fusion along with TERT and TP53 gene mutations and multiple copy number alterations. The NAB2::STAT6 fusion is seen in nearly all SFTs including dedifferentiated SFTs, while the genomes of dedifferentiated SFTs are reportedly more complex and unstable than those of usual and malignant SFT types [8]. TP53 mutations are also common in dedifferentiated SFTs while not identified in usual SFTs [8]. TERT activating mutations have been linked to adverse outcomes in SFTs and appear to be common in dedifferentiated SFTs [1,9]. Overall, dedifferentiated SFTs appear to display more aggressive clinical behavior conferring a worse prognosis than conventional or malignant SFTs [1].

We demonstrate a clinically aggressive case of dedifferentiated SFT, a rare presentation of a relatively rare tumor.

References

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  2. Kurisaki-Arakawa A, Akaike K, Hara K, Arakawa A, Takahashi M, Mitani K, Yao T, Saito T. A case of dedifferentiated solitary fibrous tumor in the pelvis with TP53 mutation. Virchows Arch. 2014 Nov;465(5):615-21. doi: 10.1007/s00428-014-1625-3. PMID: 25015562.
  3. Magro G, Emmanuele C, Lopes M, Vallone G, Greco P. Solitary fibrous tumour of the kidney with sarcomatous overgrowth. Case report and review of the literature. APMIS. 2008 Nov;116(11):1020-5. doi: 10.1111/j.1600-0463.2008.01012.x. PMID: 19133003.
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  6. Ouladan S, Trautmann M, Orouji E, Hartmann W, Huss S, Büttner R, Wardelmann E. Differential diagnosis of solitary fibrous tumors: A study of 454 soft tissue tumors indicating the diagnostic value of nuclear STAT6 relocation and ALDH1 expression combined with in situ proximity ligation assay. Int J Oncol. 2015;46(6):2595-605. doi: 10.3892/ijo.2015.2975. Epub 2015 Apr 20. PMID: 25901508.
  7. Schneider N, Hallin M, Thway K. STAT6 Loss in Dedifferentiated Solitary Fibrous Tumor. Int J Surg Pathol. 2017 Feb;25(1):58-60. doi: 10.1177/1066896916650257. Epub 2016 Jul 28. PMID: 27189111.
  8. Dagrada GP, Spagnuolo RD, Mauro V, Tamborini E, Cesana L, Gronchi A, Stacchiotti S, Pierotti MA, Negri T, Pilotti S. Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation. Mod Pathol. 2015 Aug;28(8):1074-83. doi: 10.1038/modpathol.2015.70. Epub 2015 May 29. PMID: 26022454.
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