Pancreatic Solitary Fibrous Tumor: A Common Tumor Occurring in a Rare Location

Introduction

Solitary fibrous tumor (SFT) of the pancreas is a rare fibroblastic neoplasm [1]. To date, fewer than 50 cases have been documented globally [2–36]. Clinically, SFTs often present nonspecific symptoms and imaging features, complicating preoperative diagnosis and increasing the risk of misdiagnosis. Although most pancreatic SFTs exhibit benign behavior, a subset demonstrates aggressive potential with recurrence or metastasis [1]. Pathologically, SFT overlaps morphologically with other pancreatic spindle cell neoplasms, posing diagnostic challenges. This study retrospectively analyzed the clinicopathological and molecular characteristics of 2 primary pancreatic SFTs, aiming to provide insights into their diagnosis, treatment, and prognosis.

Case Reports

CLINICAL AND IMAGING MANIFESTATIONS:

Case 1 involved a 53-year-old woman who presented with an asymptomatic pancreatic head mass (2.4×2.5 cm) incidentally detected a decade prior but left untreated. Over the past decade, the patient remained asymptomatic and did not undergo any relevant examinations. It was not until the recent physical examination, when the patient underwent an abdominal computed tomography (CT) scan again, that an enlargement of the pancreatic mass was detected, showing a well-circumscribed, hyperenhancing lesion with delayed enhancement relative to pancreatic parenchyma during arterial and venous phases (Figure 1). Radiologically misdiagnosed as a pancreatic neuroendocrine tumor (PNET), the patient underwent pancreaticoduodenectomy. The patient in Case 2 was a 69-year-old woman with a 1.9×2.6-cm mass at the pancreatic body-tail junction, detected during routine screening 1 month prior. Magnetic resonance imaging (MRI) demonstrated a hypointense lesion on T1-weighted imaging and hyperintensity on T2-weighted sequences, with mild contrast enhancement. Similarly misclassified as a PNET, the patient received distal pancreatectomy. Preoperative workup for both cases showed normal serum CA19-9, carcinoembryonic antigen (CEA), and hormone levels. Pathological examination of resected specimens confirmed solitary fibrous tumor (SFT) with negative margins. Both patients remained recurrence-free at their 24-month follow-up examinations.

PATHOLOGICAL CHARACTERISTICS:

In Case 1, gross examination revealed a well-circumscribed oval mass in the pancreatic head. In Case 2, the tumor was located in the body and tail of the pancreas. Both tumors exhibited grayish-white cut surfaces with a firm-to-rubbery texture. Microscopically, the 2 cases demonstrated similar morphological features, including expansile growth with indistinct borders and local encapsulation of normal pancreatic tissue (Figure 2A). The tumor cells displayed fascicular arrangement with alternating cellular and hypocellular zones (Figure 2B, 2C). Branched, antler-shaped capillaries were prominent in the tumor stroma (Figure 2D). High-power microscopy confirmed the absence of cytologic atypia, mitotic activity, and necrosis (Figure 2E). Case 2 was distinguished by marked intercellular collagen proliferation (Figure 2F). Immunohistochemistry showed uniform expression of BCL-2, CD99, vimentin, and CD34 in both tumors, with strong nuclear STAT6 positivity (Figure 2G, 2H). Dog1, CD117, smooth muscle antibody (SMA), and S100 were immunonegative. Both cases had KI67 proliferation indices <5%. Neither patient received molecular diagnostic testing.

Discussion

Pancreatic SFT is exceptionally rare. Since the initial report by Lüttges et al [2] in 1999, 47 cases (including the 2 cases in our series) have been reported [2–36] (Table 1). Based on a comprehensive analysis of all previously reported cases, we found that pancreatic SFT predominantly occurs in middle-aged to elderly individuals, with an age range of 1 to 82 years (median age: 55 years) and no sex difference (M: F=23: 24) (Table 1). Most patients are asymptomatic and are only diagnosed incidentally during imaging examinations, while a minority may present with abdominal pain or jaundice (Table 1). On imaging, pancreatic SFTs often appear as well-defined nodules with mixed density and delayed, heterogeneous enhancement. These features are similar to those of PNETs [37]. Therefore, preoperative imaging examinations often lead to misdiagnosis as PNETS (30/47) (Table 1). Both patients in the present report were elderly women who presented without any clinical symptoms. Pancreatic space-occupying lesions were detected during imaging examinations for routine health check-ups, and both were initially misdiagnosed as neuroendocrine tumors. Therefore, it is clear that pathological examination is still required for the definitive diagnosis of SFT of the pancreas.

Histologically, SFT typically exhibits well-defined borders and is composed of alternating hypercellular and hypocellular regions. The tumor cells are primarily composed of spindle cells that exhibit no atypia and grow in a disorganized manner (referred to as “patternless growth pattern”). In a minority of cases, they may also demonstrate fascicular, herringbone-like, or hemangiopericytoma-like patterns [1]. In the tumor stroma, collagen fibers of varying shapes or branched “antler-like” blood vessels can be observed [35]. Necrosis and pathological mitotic figures are typically rare. In rare cases, SFT can present with 2 variants: lipomatous type and giant cell type [1]. Immunophenotypically, SFT tumor cells show positivity for CD34, BCL-2, and CD99, as well as nuclear expression of STAT6 in the tumor cells. STAT6 has emerged as a highly sensitive (98–100%) and specific (95–100%) diagnostic marker for SFT, validated by multiple studies [38–40]. Both cases in this series exhibited typical morphological and immunohistochemical features of SFT.

In terms of molecular genetics, NAB2:: STAT6 fusion is a characteristic molecular alteration in SFT, caused by an inversion of chromosome 12q13. This fusion gene was initially discovered in cases of malignant SFT of the meninges [40–42]. The NAB2:: STAT6 fusion protein localizes to the nucleus and activates EGR1, resulting in a significant increase in the expression of its downstream targets, including IGF2 and FGFR1, which leads to cell proliferation and tumorigenesis [43]. Unfortunately, due to limited laboratory resources, molecular testing related to SFT was not performed for either of the 2 patients.

In terms of biological behavior, SFT is a borderline tumor with an overall good prognosis, but there is a 10–30% risk of recurrence or metastasis [1]. Among 47 documented cases of pancreatic SFT, distant metastasis occurred in 1 patient (2.1%), local recurrence in 1 patient (2.1%), and disease-specific mortality was observed in 4 patients (8.5%) (Table 1). According to other previous research, older patient age, larger tumor size, increased cellularity, increased mitotic activity (≥4/10 high-power fields or >2 mitoses/2 mm2), nuclear pleomorphism, tumor necrosis, and infiltrative borders are considered poor prognostic factors [1,44–49]. Additionally, Yamada et al [50] found that, morphologically, the occurrence of dedifferentiation/sarcomatoid change in SFT is a poor prognostic factor. Recent studies have also indicated that mutations in the TERT promoter or TP53 in SFT may be associated with malignant behavior [51,52]. Although there is still uncertainty regarding effective methods for predicting the biological behavior of an SFT, a prognostic risk scoring system that incorporates patient age, tumor size and necrosis, and mitotic count is currently widely used [53]. Based on this risk assessment method, we analyzed 41 cases of pancreatic SFT (excluding 6 cases due to incomplete information) and found that the low-risk group accounted for 80.5% (33/41), the intermediate-risk group for 17.1% (7/41), and the high-risk group for 2.4% (1/41) of the tumors. Both SFT cases reported herein belong to the low-risk group. For both, after a follow-up of 24 months, there was no evidence of recurrence or metastasis in either case.

The differential diagnosis of SFTs in the pancreas is often challenging due to the nonspecific clinical manifestations and radiological features as well as the diversity of histomorphological characteristics. Differential diagnosis requires distinguishing them from gastrointestinal stromal tumors (GISTs), desmoid-like fibromatosis, inflammatory myofibroblastic tumors (IMTs), and the recently proposed sclerosing epithelioid mesenchymal tumor of the pancreas. The typical characteristics of GISTs is the presence of spindle-shaped cells with various arrangements, and diffuse positivity for CD34, DOG1, and CD117 on immunophenotyping; together these can assist in differentiating GIST from SFT. Furthermore, genetically, GISTs often exhibit mutations in KIT (80%) or PDGFR (5–10%) [54], rather than exhibiting NAB2:: STAT6 fusion. The typical characteristic of desmoid-like fibromatosis is fascicular arrangement of spindle-shaped or stellate cells, often with infiltrative borders. Due to mutations in CTNNB1, the tumor cells in desmoid-like fibromatosis exhibit nuclear expression of β-catenin [1], which facilitates differential diagnosis. IMTs consist of dense or loose cellular bundles of spindle-shaped fibroblasts and myofibroblasts. In addition to varying degrees of collagenization, inflammatory cell infiltration – mainly composed of lymphocytes and plasma cells – is frequently observed between the tumor cells. These features are rarely observed in SFTs. Furthermore, IMTs typically harbor ALK or ROS1 fusion genes, with corresponding expression of ALK or ROS1 on immunophenotyping [55], which can be helpful in differential diagnosis. Pancreatic sclerosing epithelioid mesenchymal tumor is a newly described pancreatic-specific entity [56]. Similar to SFTs, the tumor cells demonstrate variable morphologies. Morphologically, pancreatic sclerosing epithelioid mesenchymal tumors do not exhibit antler-like blood vessels. Immunohistochemically, these tumors are only positive for vimentin, CD99, and CK18, and do not express CD34 or STAT6. These characteristics can effectively differentiate them from SFTs [56,57].

Surgical resection is the cornerstone of pancreatic SFT treatment [58]. Complete tumor resection can significantly improve the prognosis of patients with SFTs, and no additional postoperative treatment is required [43,59]. However, for cases with positive surgical margins, high mitotic count, or metastasis, postoperative adjuvant radiation therapy can yield better therapeutic outcomes [58,60]. Research has shown that chemotherapy is effective for patients with advanced or metastatic SFTs [43]. However, antiangiogenic therapy has demonstrated better efficacy than chemotherapy for undifferentiated SFTs [51]. Furthermore, new therapeutic approaches such as RNA-targeted therapy specifically inhibiting the NAB2:: STAT6 fusion and immunotherapy targeting PD-1 and PD-L1 through tumor-infiltrating lymphocytes have opened new doors for the treatment of SFT [61,62]. Although these treatments are still in the research phase, their efficacy has been partially confirmed. Both patients we reported underwent complete resection of pancreatic tumors. Given their favorable clinical presentations and the absence of adverse morphological features in the postoperative pathological findings, neither patient received additional adjuvant therapy after surgery, and no tumor recurrence or metastasis was observed during the follow-up period.

Conclusions

In summary, owing to the extreme rarity of pancreatic SFTs and their lack of specific clinical and radiological features, this disease is almost always misdiagnosed in clinical practice. Therefore, an accurate diagnosis of pancreatic SFT through pathological examination is of paramount importance for the treatment and management of patients. The “patternless growth pattern”, antler-like small blood vessels, and strong nuclear expression of STAT6 are key and practical pathological features for diagnosing SFTs. Due to limitations in terms of cost-effectiveness and convenience, molecular testing is generally not employed as a routine examination but can serve as an adjunctive tool only when immunohistochemistry results are inconclusive. Our cases further enrich the clinicopathological features of pancreatic SFT, thereby enhancing understanding for clinicians and pathologists, which can help to avoid misdiagnosis and provide a basis for clinical diagnosis, treatment, and prognosis assessment. Continued in-depth exploration of the molecular mechanisms underlying SFTs and improvements in therapeutic approaches in the future will provide valuable assistance for the precise treatment of patients.