Extremely rare case of intravascular solitary fibrous tumour in the inferior vena cava with review of the literature

Solitary fibrous tumour (SFT) is a mesenchymal tumour of the fibroblastic type, typically arising from the pleura [1]. This type of tumour was first described by Klemperer and Rabin in 1931 [2]. For several years, SFTs were considered as mesothelial tumours arising from the pleura. However, such tumours were recently observed in almost every region of the human body. The tumour is predominantly observed in middle-aged individuals, with no gender difference [3]. Most tumours are benign, but approximately 12–22% [4] of cases exhibit aggressive behaviours, such as local recurrence and metastasis [5]. Different treatment methods for such tumours are reported. However, surgical excision is still considered to be the best option for diagnosis and treatment [6]. Moreover, pathological and immunohistochemical examinations are essential for diagnosis, and the fusion of NAB2-STAT6 was identified as the latest molecular hallmark [7]. Although extrapleural solitary fibrous tumours had been well described in previous studies, the incidence of intravascular SFTs is extremely rare. Herein, we present a case of SFT arising from the inferior vena cava (IVC) in a 67- year-old woman who was preoperatively diagnosed with thrombus in the IVC.

Solitary fibrous tumour (SFT) is a rare type of neoplasm of mesenchymal origin, mostly arising from the submesothelial connective tissue beneath the pleura [8]. However, the incidence of extrapleural SFT (ESFT) has been increasing within the last two decades, and approximately more than one-third of literature in English is about ESFTs [9]. Such tumour has been observed at almost every extrapleural anatomic site, including the liver [10], kidney [11], pancreas [12], prostate [13], breast [14], central nervous system [15], reproductive system [16, 17], orbit [18], head and neck [19], pelvis [20], soft tissues in the extremities [21] and retroperitoneum [22]. However, the incidence of intravascular SFT is extremely rare [23]. Previous studies have presented cases of SFT invading or involving the IVC [24, 25]. Thus far, this report first presented about SFT arising from the IVC and conducted an NGS analysis.

Like most SFTs, the initial presentation of intravascular SFT depends on tumour size, location, and adjacent anatomic structures. Based on our review, intravascular SFT can be asymptomatic and incidentally diagnosed on imaging examinations, or it can cause venous obstruction at advanced stage. In addition, some patients with SFTs may present with constitutional symptoms, such as hypoglycaemia [26] due to secretion of insulin-like growth factors and weight loss [27], which has not been reported in intravascular cases.

As the symptoms and imaging results are not typical, the preoperative diagnosis of such disease is extremely challenging. In such location, it can be misdiagnosed as phlebothrombosis or other more common tumours, such as leiomyomas, leiomyosarcoma [28], well-differentiated/dedifferentiated liposarcoma [25], intimal sarcoma [29] and haemangiomas [30]. Clinical and imaging features also overlap. Therefore, the diagnosis of intravascular SFT is hardly achieved until surgical excision and pathological examination are carried out [31].

The patient presented with a well circumscribed spindle cell tumour with a complete capsule. The cellular area was hypervascular, with classical patternless pattern of proliferation. Cellularity ranged from hypercellular to laxis areas surrounding varying amounts of hyalinized collagen bundles [5]. Based on immunohistochemical examination, the tumour cells were positive for CD34, Bcl2, vimentin, and CD99 and negative for desmin and S-100 [7]. Zhanlong, M. et al. have presented compelling results showing that immunohistochemical results might be associated with the origin and site of the tumour [32], which is significant in making a differential diagnosis. However, further studies must be conducted to validate such results. The criteria for classifying malignant SFT are still confusing and conventional. The signs of malignancy include tumour size > 10 cm, high mitotic activity, increased cellularity, and necrosis [33‐35]. In addition, TERT promoter mutation [36] and BCOR mRNA overexpression [37] are correlated to the risk of malignancy in SFT.

However, histologically benign SFT can also have aggressive clinical features. The study of Gold, J. S. et al. have revealed that the rate of recurrence and metastasis of benign SFT were 6.7 and 5.3%, respectively [26]. Regardless of histology, a wide surgical excision is the most essential prognostic feature, both for benign and malignant tumours that behave in a clinically benign way as long as the tumour is completely resected with a clear surgical margin [4, 9]. Moreover, Sepideh Gholami et al. have indicated that tumour location is significantly associated with disease-specific mortality and individuals with tumours in the chest or abdominal/retroperitoneal cavity are at the highest risk [38].

In this report, we presented two tumour-related gene mutations according to the NGS analysis. PMS2 is one of the mismatch repair (MMR) genes [39], which causes genetic instability and is associated with tumour progression [40]. Deletion was believed to be the most frequent mutation of PMS2 [41, 42], which was previously referred to as hereditary nonpolyposis colorectal cancer [43] and other types of malignancy [44, 45]. However, beyond the deletion of PSM2, we did not observe any mutation in other MMR genes (MLH1, MSH2 and MSH6) in this case. In addition, the tumour was microsatellite stable. The correlation between this mutation and tumour invasiveness must be further assessed. ESR1 encodes oestrogen receptor α, which is a significant part of the nuclear hormone receptor family and is expressed in over two-thirds of patients with breast cancer [46]. In addition, it was considered an important tumour suppressor in several types of cancers, such as prostate cancer [47], osteosarcoma [48], non-small cell lung cancer [49] and hepatocellular carcinoma [50]. Interestingly, Hishida M. et al. have indicated that the decreased expression of ESR1 was correlated to pathological invasion of the intrahepatic portal vein (p = 0.0236) [50]. However, the L536P mutation (1607 T > C) was seldom reported [51], and its effects on gene expression and tumour invasion must be further validated.

As for the treatment, there is consensus showing that surgical resection is the most appropriate treatment for SFTs. However, the most intractable problems are recurrence and metastases after surgery [6]. In the study of Nicholas DeVito et al., the outcomes of systemic therapies, including chemotherapy and radiotherapy, were discouraging, which indicate that better systemic therapies are required, particularly in patients with metastatic/unresectable disease [6].

Metastases are usually blood borne and have been observed in sites, such as the liver [52], lung [53] and vertebra [54]. Due to the clinical rarity of intravascular SFT, the risk of metastasis has not been evaluated to date; hence, long-term clinical follow-up, which includes exploration and imaging, is required.

In summary, intravascular SFTs are extremely rare and generally present with luminal defects and changes in haemodynamics [55]. The imaging feature is lack of specificity, which can be missed or misdiagnosed [56]. In addition, several challenges are faced in terms of treatment. Hence, we presented this case involving gene variation as it can be used as reference in future studies.

In this study, we first reported a case of solitary fibrous tumour located in the inferior vena cava. Moreover, NGS analysis was conducted, and two tumour-related mutations were found. We believe that our results might be useful in future studies of such disease.