Giant cell-rich solitary fibrous tumour of the urinary bladder: case report of an unusual histological variant and literature review

A 56-year-old man presented to Maoming People’s Hospital for routine physical examination with no discomfort symptoms. Pelvic CT with contrast displayed a heterogeneously enhancing oval solid mass measuring 4.5 × 4.3 × 4.0 cm in the left posterior wall of the bladder (Fig. 1). The laboratory examination results showed that the urine occult blood test and urine protein were positive, while the liver function, renal function test and cancer markers were within normal limits. The patient underwent laparoscopic radical tumour resection.

Grossly, the tumour was a 5.0 × 4.0 × 4.0 cm in size with no obvious macroscopic haemorrhage or tumour necrosis on the cut surface. Histopathologically, the tumour was a well-circumscribed, nonencapsulated lesion that was composed of bland spindle-ovoid tumour cells alternating with hypocellular and hypercellular areas, staghorn-like vasculatures and scattered large dark-stained multinucleate giant cells lining pseudovascular spaces (Fig. 2A-B). There was no evidence of necrosis or mitotic activity (0/10HPF). Spindle-ovoid cells and multinucleate giant cells showed strong and diffuse expression of CD34 (Fig. 2C) and nuclear STAT6 (Fig. 2D), while being negative for S-100, Desmin, CD117, DOG-1, SMA, MDM2, P16, Pankeratin and CD68 (the antibody information is detailed in Table 1). The Ki-67 proliferation index of the tumour cells was 3%. In addition, RT‒PCR confirmed the presence of the NAB2ex4-STAT6ex5 fusion gene in the tumour (Fig. 2E). Based on morphology, immunohistochemistry and molecular detection results, it was diagnosed as a GCR-SFT of the urinary bladder.

Based on the 3-tiered model (age at diagnosis, tumour size, mitotic count), the patient was given a score of 2 points (age ≥ 55 years and tumour size = 5 cm, shown in Table 2) and was stratified into low risk of metastasis or recurrence according to the risk assessment criteria of the 2020 WHO classification of soft tissue and bone tumours [17]. The patient underwent regular follow-up for 34 months after surgery, and there was no evidence of local recurrence or metastasis.

GCR-SFT, formerly known as GCA, was first reported in the orbital region by Dei Tos et al. in 1995 [18]. Since then, GCR-SFT has been described in some extraorbital anatomical locations, including the mediastinum, back, retroperitoneum, hip, vulva, and inguinal region [5, 16, 19]. In the most comprehensive review of the English literature to date, approximately 38 reports of GCR-SFT involving 66 cases have been identified between 1995 and 2023 [13, 16, 18‐50]. However, GCR-SFT, as a rare variant, has never been reported to occur in the urinary bladder.

The clinical characteristics of the 66 reported cases of GCR-SFT are detailed in Table 3. Patients (Male38: Female28) ranged in age from 18 to 84 years with a mean age of 48.2 years. GCR-SFT mostly involved the orbit (n = 19, 28.8%) followed by the eyelid (n = 9, 13.6%), conjunctiva (n = 4, 6.1%), buccal mucosa (n = 4, 6.1%) and other head and neck regions (n = 17, 25.8%) including the parotid, occipital scalp, vocal cord, retroauricular region, submandibular, nasolacrimal duct, neck, tongue, parietal region, external auditory, nasopharynx, cheekbone, and sublingual regions. However, rare sites outside the head and neck region were noted in only 13 cases (back, groin, mediastinum, retroperitoneum, vulva, hip, axillary, gallbladder).

The clinical symptoms and signs depend on tumour size and location. The vast majority of bladder SFTs exhibit well-defined and slow-growing masses, with symptoms related to local compression caused by tumour growth, including urinary tract irritation, haematuria, difficulty urinating and lower abdominal discomfort [51‐53]. The maximum diameter of GCR-SFT ranges from 0.5 to 14 cm with a mean size of 3.25 cm. Of note, tumours that occurred in areas such as the orbit and the eyelid often had a smaller diameter than tumours that occurred in subcutaneous soft tissue and deep organs. Although larger tumor diameters are positively correlated with higher risk stratification according to the risk assessment criteria, Feasel et al. demonstrated that 26 cases of SFTs occurring in cutaneous/subcutaneous soft tissue showed no recurrence or metastasis, and 2 cases of histologically malignant SFT were included [8].

Histopathologically, bland spindle-ovoid tumour cells alternating with hypocellular and hypercellular areas, staghorn-like vessels and prominent dark-stained multinucleate giant cells lining pseudovascular spaces are important diagnostic clues for GCR-SFT. For a long time in the past, a combination of CD34, BCL2 and CD99 has been widely used for the diagnosis of SFT. These markers often had good sensitivity and expression intensity in the vast majority of cases. Unfortunately, these markers are not specific and are frequently positively expressed in many spindle cell tumours closely mimicking SFT histologically [54, 55]. STAT6 has emerged as a useful tool for the diagnosis of SFT, and its sensitivity and specificity reached to 90–100% and 95–100%, respectively [13‐15]. Based on the diagnostic needs, the use of CD34 and STAT6, which are better than other markers, is strongly recommended. However, subsequent research found that STAT6 can also be expressed in some other soft tissue neoplasms such as dedifferentiated liposarcoma (12%), desmoid fibromatosis (8%), and neurofibroma (8%) [56].

Given the unique or atypical morphology of cases, NAB2-STAT6 fusion gene detection was performed to ensure accurate diagnosis. SFTs characteristically harbour inv12(q13q13)-derived NAB2-STAT6 fusions with variable breakpoints resulting in diverse fusion variants. According to the literature, only 5 cases of GCR-SFT underwent NAB2-STAT6 fusion gene detection, and fusion variants included NAB2ex6-STAT6ex17 (3 cases), NAB2ex3-STAT6ex18 (1 case) and NAB2ex3-STAT6ex19 (1 case) [13, 50]. In this study, we first confirmed the presence of the NAB2ex4-STAT6ex5 fusion gene in GCR-SFT of the urinary bladder. Nonetheless, the significance of such fusion variants in the GCR-SFT remains unclear. To date, no association has been found between a certain type of mutation variant and poor prognosis in SFT [13].

The differential diagnosis of GCR-SFT includes a number of soft tissue tumours, especially the so-called fibrohistiocytic tumours and fibroblastic/myofibroblastic tumours, such as deep benign fibrous histiocytoma and giant cell fibroblastoma. Deep benign fibrous histiocytoma, occurs mainly in the deep soft tissue or subcutaneous tissue and mostly presents as isolated, slow-growing nodules with branching haemangiopericytoma-like vessels. Furthermore, giant cell fibroblastoma is an intermediate soft tissue tumour that histologically overlaps with dermatofibrosarcoma protuberans.Giant cell fibroblastomas frequently occur in the subcutis and primarily affects children, although some adult cases have been reported. It consists of elongated wavy arrangements of spindle cells distributed in a mucinous-like or collagenous stroma, and multinucleate giant cells often lining larger lacunar or sinusoidal pseudovascular spaces that are irregularly distributed. However, STAT6 nuclear expression is absent in these tumours. A small number of other mesenchymal tumours express STAT6 including dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma, and nodular fasciitis [57]. However, their morphology is quite different from that of GCR-SFT.

In addition, the morphology of GCR-SFT may overlap with other giant cell-rich malignant bladder lesions including osteoclast-type giant cell-rich carcinoma and leiomyosarcoma with osteoclast-like multinucleated giant cells. Histologically, osteoclast-type giant cell-rich carcinoma showed biphasic morphology with polygonal to epithelioid to spindle mononuclear cells and scattered multinucleated osteoclast-like giant cells. Leiomyosarcoma with osteoclast-like multinucleated giant cells is composed of spindle cells and has the presence of numerous multinucleated, osteoclast-like giant cells. Immunohistochemically, in addition to expressing markers of their own intrinsic origin respectively, giant cells in both tumours expressed CD68 positively. However, the giant cells of GCR-SFT were negative for CD68.

Although GCR-SFT exhibits benign histological morphology and slow growth process, incomplete tumour resection may lead to recurrence after many years [29, 58]. Henceforth, complete surgical excision should be performed immediately after detection when eligible for surgery to ensure a positive outcome and minimize the chance of malignant transformation or metastasis [52]. For the management of SFT, extensive and healthy surgical margin resection is currently considered the gold standard.

The clinical course of SFTs can be predicted by establishing a risk stratification model for low, intermediate and high metastatic risk that takes into account age at diagnosis, tumour size, mitotic count, and necrosis [59, 60]. Our case was scored 2 points and classified as low-risk progression. The patient underwent a follow-up of 34 months after complete resection of the tumour and did not experience any local recurrence or metastasis. However, in light of the specific location of the tumour, long-term follow-up is still needed.