Q1. B
Q2. D
Q3. D
Q4. A

Metastatic cellular solitary fibrous tumor / hemangiopericytoma

Additional case history: The prior orbital exenteration was for a cellular solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) (anaplastic variant) which had an elevated mitotic activity (30 mitoses per 10 HPF) and high Ki-67 proliferation index (>65%) that was diagnosed three years previously. The prior tumor was negative for CD34 but showed nuclear labeling of tumor cells for STAT6 and was found to be positive for a NAB2-STAT6 gene fusion.

Solitary fibrous tumor constitutes a heterogeneous group of spindle-cell neoplasms initially described in the pleura. These neoplasms can arise in a wide range of anatomical locations including the subcutaneous/deep soft tissue, mediastinum, abdomen/retroperitoneum, and central nervous system (CNS), among others(1-2). The cellular form of SFT is histologically and immunohistochemically identical to hemangiopericytoma, leading to the 2016 WHO classification of tumors of the central nervous system introducing the combined entity of solitary fibrous tumor/hemangiopericytoma (SFT/HPC)(3).

Histologically, these tumors are characterized by uniform collagen-forming plump or spindle-shaped tumor cells together with numerous thin-walled hyalinized vessels of "staghorn" appearance (Figures 1-3). Myxoid change, fibrosis, hyalinization, necrosis, or rarely calcifications may be seen in some cases. Most SFT are benign (80%). Criteria for malignancy include increased cellularity, cellular pleomorphism, necrosis, and increased mitotic activity (≥4 mitotic figures per 10 HPF). Cytology shows a spindle cell neoplasm with cells embedded in a collagenous matrix or singly dispersed, with elongated bland nuclei and finely granular chromatin (Figure 4). Immunohistochemically, the tumor cells are negative for cytokeratin and epithelial membrane antigen, but usually positive for CD34, STAT6 (Figure 5), Bcl2, and vimentin. Cellular SFT/HPC tends to be less frequently and less strongly positive for CD34 (50% of cases) (Figure 6). A NAB2-STAT6 gene fusion, resulting in a chimeric protein has been recently identified as a consistent finding in SFT/HPC(4-5).

Surgery is the recommended treatment for both benign and malignant SFT. For SFT displaying criteria for malignancy, adjuvant radiotherapy, when feasible, is recommended similar to that of other soft tissue sarcomas. Local and distant relapse can occur more than 20 years after initial treatment.

Take home message for trainees: SFT and HPC are two ends of a spectrum of neoplasms characterized by NAB2-STAT6 gene fusions and positivity for the immunohistochemical marker STAT6. Increasing cellularity, mitotic activity, large size, and other atypical features are associated with a greater risk of recurrence and metastasis.

Chmielecki J, Crago AM, Rosenberg M, et al. Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors. Nat Genet 2013;45:131-2.

Doyle LA, Vivero M, Fletcher CD, et al. Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol 2014;27:390-5.

Klemperer P, Rabin CB. Primary neoplasms of the pleura: a report of five cases. Arch Pathol 1931;11:385–412.

Louis DN, Ohgaki H, Wiestler OD, et al (2016) World Health Organization Histological Classification of Tumours of the Central Nervous System. International Agency for Research on Cancer, France.

Robinson DR, Wu YM, Kalyana-Sundaram S, et al. Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nat Genet 2013;45:180-5.

Sinchita Roy-Chowdhuri M.D., Ph.D.
Associate Professor
Department of Pathology
The University of Texas MD Anderson Cancer Center, Houston, TX
USA