Pediatric sellar solitary fibrous tumor/ hemangiopericytoma: A rare case report and review of the literature

WHO classification

Extracranial SFT/HPCs have been reclassified as a spectrum of SFTs, whereas the HPC continues to be used among neuropathologists. Both entities share the 12q3 inversion and fusion of the NGFI-A-binding protein 2 (NAB2) and STAT6 genes with the STAT6 nuclear expression visible on immunohistochemistry.[20] This inversion and fusion juxtaposes NAB2 and STAT6 in an initiating event found to be a disease-specific gene fusion.[23] This finding may have contributed to the change to the 2016 WHO classification of central nervous system tumors, assigning three grades to the “SFT/HPC” class, breaking the tradition of assigning names to the classes (e.g., glioblastoma as Grade IV);[8] the specific descriptions of each grade is displayed in [Table 1]. In the prior 2007 WHO classification, “Hemangiopericytoma” was distinct from SFT and anaplastic HPC.[12] For our case, a WHO Grade II SFT/HPC is the same as the prior “hemangiopericytoma” classification, thus the literature search was limited to this term.

Table 1:: Three grades to the “solitary fibrous tumor/ hemangiopericytoma” class, breaking the tradition of assigning names to the classes (e.g., glioblastoma as Grade IV). The specific descriptions of each grade are depicted above.

Pediatric SFT/HPC

HPCs have the potential to occur anywhere in the body as they originate from blood vessels but the most common location is in the lower extremity in the pediatric population.[9] Intracranial SFT/HPC is a rare entity in the pediatric population. Limited cases were identified in the literature as can be found in [Table 2]. Moreover, from the available literature, there are no reports that were of HPC located in the sellar region. The largest case series for pediatric HPC reported nine cases with the cranial convexity and parasagittal region being the most common locations.[10]

Table 2:: Limited cases of intracranial solitary fibrous tumor/ hemangiopericytoma identified in the literature.

Two forms of HPC have been identified during childhood; infantile type which occurs during the first 12 months of life and the adult type which occurs after the age of 12 months old.[4,17] Pediatric HPC consists of both entities and distinction between the two which is essential for treatment strategies. Infantile HPCs are considered congenital and have a favorable prognosis. Similar to adult HPC, infantile HPC has been classified at times in the literature as “infantile myofibromatosis” with studies suggesting both as different stages of the same entity.[16,25] Adult HPCs behave similar in the pediatric population as the adult population. This distinction is made from the clinical standpoint rather than histological.[9]

A recent study[24] from three pediatric hospitals reevaluating prior pathology from the past 30 years found that 18 tumors total were classified as SFTs. However, when immunohistochemistry was performed on the tissue, only three tumors from two patients were found to be STAT6 positive; the remainder tumors required reclassification. This demonstrates that the diagnosis of SFT, and HPC, may be rarer than previously thought. Indeed, in the past, both SFTs and HPCs were referred to histologically as “angioblastic meningiomas” or “hemangiopericytic variant of meningioma,” before the advent of STAT6 immunopositivity studies.[1] Our patient’s tissue was confirmed to be STAT6 positive [Figure 4e]. Furthermore, the implications of this study are vast as much of the prior epidemiological studies may have included false-positive diagnosis.

STAT6 for diagnosis of SFT/HPC

STAT6 immunohistochemistry has been found to be an exclusively nuclear immunostaining signal with a strong ability to verify SFTs and HPCs, with recent studies showing all non-SFT/HPCs unanimously STAT6 negative and 98.7% agreement among observers.[3] In the past, CD34 has been the most characteristic immunohistochemical stain for SFTs, however, it is also nonspecific.[3,20] Very little was known about the molecular genetics of this tumor. Around 2013, immunohistochemical staining for STAT6 was presented in the literature as a more specific marker for SFTs and HPC.[3,11,19] A NAB2-STAT6 gene fusion, results in an inversion at the 12q13 locus, produces a chimeric protein in which a repressor domain of NAB2 (EGR1-binding protein 2) (NAB2) is replaced with a carboxyterminal transactivation domain from signal transducer. The activator of transcription 6 and interleukin-4 induced (STAT6) acts as a transcriptional activator through early growth of the tumor and has been recently believed to be highly sensitive and specific for SFTs. Several journal articles have confirmed the validation of the diagnosis of intracranial and extracranial SFT.[6]

Sellar location SFT/HPC

To date, a total of 15 cases of sellar region SFT/HPC were identified in the English literature, as listed in [Table 3]. However, none have been reported in the pediatric population. The youngest patient in literature was an 18-year-old female who also had similar imaging – homogenously enhancing mass concerning for pituitary adenoma.[2] The surgical approach utilized in these cases was transsphenoidal, transcranial, or the former followed by latter after diagnosis was revealed and significant residual tumor or recurrence occurred. Many of these patients presented with endocrinopathies that would result from pituitary compression, as well as visual change from compression of the optic apparatus. The most common pediatric tumor in this location is a craniopharyngioma (6–9%), followed by hypothalamic glioma (4–8%), germ cell tumors (1–2%), and pituitary adenoma (0.5–2.5%).[10,25]

Table 3:: To date, a total of 15 cases of sellar region solitary fibrous tumor/hemangiopericytoma were identified in the English literature.

Treatment

Given the rarity of HPC, information about management specific to intracranial HPC for pediatric population is scarce. Moreover, the distinction between infantile and adult HPC is paramount to the clinical course. The infantile variant, occurring <12 months of age, is chemoresponsive. There are reports of extracranial infantile HPC exhibiting spontaneous regression.[4,14] Moreover, this variant has a propensity to mature into benign neoplasms, such as hemangioblastoma, and has been shown to be responsive to neoadjuvant chemotherapy.[7] One report of a neonate with intracranial HPC was treated with neoadjuvant anthracycline-based chemotherapeutic agent which was able to decrease tumor size before surgical resection.[5] Another series of two infantile HPCs were treated with surgical resection without adjuvant therapy with no evidence of recurrence at time of report.[9,18,21] Large series specific for intracranial infantile HPC are lacking given limited cases.

On the contrary, adult HPC requires a more aggressive approach. Surgical resection followed by adjuvant radiation therapy has been recommended in the past for treatment from adult literature.[21] In a 29-patient series report for intracranial adult HPC, the 5-, 10-, and 15-year overall survival rates were 85%, 68%, and 43%, respectively, for patients undergoing this treatment route.[15] Another 43-patient series reported 1-, 5-, and 10-year overall survival at 100%, 94.4%, and 72.2%, respectively.[21] Outcome is directly related to the presence of metastatic disease and adequacy of local control; GTR is advocated as the 5-year local disease control rates were 84% when compared to only 38% for subtotal resection (STR).[18]

However, a recent meta-analysis of 563 cases found that GTR alone provided superior survival, with or without adjuvant radiation therapy; patients receiving >50 Gy of radiation had worse survival outcomes.[15] This study included pediatric patients, with age ranging from 1 month to 80 years, however, the distinction between pediatric and adult population was not made in their analysis nor was the number of patients under age 18 reported. A single-institution retrospective review of 43 patients reported adjuvant radiation can hinder tumor progression but appears to have no effect on overall survival.[17] Patients with GTR alone were compared to patients with STR + radiation and the latter group had longer progression-free interval. However, when comparing overall survival for the same groups, GTR alone had better results.

Data specific to pediatric population for intracranial disease is lacking; however, given the similar clinical behavior of extracranial disease,[20] we believe that these results can be extrapolated to the pediatric population with intracranial adult HPC. Surgical intervention with GTR should be the goal with conflicting evidence for adjuvant radiation therapy. Given the benefit of improved recurrence-free interval with radiation therapy, there is likely some benefit to adjuvant radiation therapy if total dose is kept below 50 Gy. This dose limit may need to be decreased in younger population given proximity to optic apparatus, further research is needed in this area.