Alveolar solitary fibrous tumor: an uncommon morphological form

Abstract

Solitary fibrous tumor (SFT) is a fibroblastic tumor characterized by a prominent staghorn vasculature and collagen deposition. However, little is known about SFTs with alveolar structures. Herein, we present a case of an alveolar pattern SFT in a 55-year-old woman. The tumor was present in the lumbosacral spinal canal and showed an alveolar architecture composed of ovoid to spindle-shaped cells. Immunohistochemical examination showed that the tumor cells were positive for STAT6 (nuclear expression), CD34, CD99, and Bcl-2, but negative for cytokeratins (CK-pan and AE1/AE3), EMA, GFAP, CD31, progesterone receptor, S-100 protein, and smooth muscle actin. Furthermore, NAB2::STAT6 fusion was detected using DNA-based next-generation sequencing, which established the diagnosis of SFT at a molecular level. The present case expands the morphological categories of SFT.

Introduction

Solitary fibrous tumor (SFT) is a unique mesenchymal neoplasm that may occur anywhere in the body. SFT is typically characterized by the proliferation of oval to spindle-shaped cells, deposition of varying amounts of collagen, and staghorn or hemangiopericytomatous vasculature. Of note, previous research has revealed a wide spectrum of histopathological variants of SFTs, including giant cell-rich, fat-forming (lipomatous), myxoid, and pseudopapillary [1–7]. Immunohistochemical studies have shown that SFTs essentially express CD34 and/or STAT6. NAB2::STAT6 gene fusions are pathognomonic for SFTs. Furthermore, SFTs expanded to include what were previously called hemangiopericytomas (HPCs) in other body regions that had similar immunohistochemical and morphological characteristics as SFTs [8].

Materials and methods

Case report

A 55-year-old female patient with a complaint of lumbago and difficulty in emptying the bowels was admitted to Shandong Provincial Hospital Affiliated to Shandong First Medical University. The magnetic resonance imaging (MRI) revealed a 6 × 7 cm lesion within the intraspinal canal at the L5-S3 level (as shown by an arrow in Fig. 1 A-C). Based on clinical and radiological features, the lesion was identified as a tumor of vascular or neural origin. Subsequently, the patient underwent intraspinal tumor resection.

Fig. 1.

Radiological features of the tumor. MRI T1-weighted image (A) and T2-weighted image (B) showing a heterogeneous lesion of 6 × 7 cm at the L5-S3 level, with inhomogeneous enhancement (C)

Immunohistochemistry

Biopsy specimens were obtained from representative areas of the tumor. The obtained tissue specimens were fixed in formalin and embedded in paraffin. Then, an automated immunohistochemistry (IHC) system was used to perform staining on formalin-fixed and paraffin-embedded (FFPE) tissue specimens using the following primary antibodies: CK-pan (AE1/AE3; ZSGB-BIO, Peking, China), S-100 protein (15E2E2 + 4C4.9; ZSGB-BIO), EMA (GP1.4; ZSGB-BIO), CD34 (10C9; ZSGB-BIO), STAT6 (EP325; ZSGB-BIO), CD31 (EP78; ZSGB-BIO), GFAP (UMAB129; ZSGB-BIO), BCL-2 (OTIR1H2; ZSGB-BIO), CD99 (PCB1; ZSGB-BIO), synaptophysin (EP158; ZSGB-BIO), smooth muscle actin (SMA) (UMAB237l; ZSGB-BIO), progesterone receptor (PR) (1E2; Roche, Basel, Switzerland), and Ki-67 (MIB1; Dako Cytomation, Glostrup, Denmark).

RNA-based next-generation sequencing

Total RNA was extracted from FFPE tissue specimens using an RNeasy FFPE Kit (Qiagen GmbH, Hilden, Germany) according to the manufacturer’s instructions. The RNA Exome Fusion Panel v2.0 assay was used to analyze 600 cancer-related genes generated with the TruSeq RNA exome kit (Illumina, Inc., San Diego, CA, USA).

Results

Pathological findings

Grossly, the mass showed a nodular appearance with dimensions of 4.8 × 3.7 × 2 cm. The tumor was well circumscribed, with a gray-white to reddish-brown, fleshy cut surface. Microscopic examination at low magnification revealed that the tumor had a pushing border and a fibrous capsule (Fig. 2A). The tumor cells were arranged in a nested pattern separated by fibrovascular septa, which frequently exhibited loss of cellular cohesion in the center and showed a predominantly cystic architecture (Fig. 2B). Some tumor areas featured alveolar architecture composed of a single layer of oval-shaped tumor cells and contained light pink material, while some featured alveolar architecture composed of multiple layers of tumor cells (Fig. 2B). The tumor cells were small, oval to spindle-shaped, and had round or oval nuclei, inconspicuous nucleoli, and little cytoplasm (Fig. 2B). These cells showed low-grade nuclear features, and there was one mitotic figure per 10 high-power fields. Thin-walled, “staghorn” vessels were only seen at the margin of the tumor cells. The tumor lacked some typical SFT features, such as variable cellularity or alternating hypocellular and hypercellular regions, patternless architecture or abundant keloid-type collagen; furthermore, tumor necrosis was absent. According to the fifth edition of the WHO Classification of Central Nervous System Tumors, the above findings fit the diagnostic criteria for WHO grade I SFT.

Fig. 2.

Histopathological features. (A) Microscopic examination at low magnification revealed that the tumor had a pushing border and a fibrous capsule. (B) The tumor showed two growth patterns: alveolar patterns. Some tumor areas featured alveolar architectures composed of multiple layers of tumor cells. The tumor cells were positive for CD34 (C) and STAT6 (D)

Immunohistochemical examination showed that all tumor cells were positive for CD34 (Fig. 2C), CD99, and Bcl-2. The tumor cells exhibited diffuse and strong nuclear staining for STAT6 (Fig. 2D). Furthermore, the tumor cells were negative for CK-pan, EMA, GFAP, CD31, S-100 protein, PR, and SMA; 10% of the tumor cells were positive for Ki-67.

Next-generation sequencing

RNA sequencing analysis of the tumor revealed two major fusion points in chromosome 12 q13.3. The first fusion point was at breakpoint 1: chr12:57486973 and breakpoint 2: chr12:57503742, and the second fusion point was at breakpoint 1: chr12:57486751 and breakpoint 2: chr12:57502082; both these fusion points contributed to NAB2::STAT6 gene fusion (Fig. 3).

Fig. 3.

Identification of NAB2-STAT6 fusion using next-generation sequencing. (A) The first fusion point was at breakpoint 1: chr12:57486973 and breakpoint 2: chr12:57503742; (B) the second fusion point was at breakpoint 1: chr12:57486751 and breakpoint 2: chr12:57502082

Discussion

SFTs/HPCs are mesenchymal tumors that may occur anywhere in the body. HPCs are phenotypically similar to SFTs. Eventually, SFT became the preferred term, and it included both pleural SFT and most tumors previously labeled as HPC [9]. SFTs/HPCs arising in the central nervous system (CNS) are rare, accounting for less than 1% of primary CNS tumors [9]. The majority of CNS SFTs occur in the supratentorial dura mater, with only approximately 10% located within the spinal canal [9]. Spinal SFTs most commonly occur in the thoracic spine, and occurrences in the lumbar-sacral spine are extremely rare [10]. Here, we report a case of primary lumbosacral spinal canal SFT.

Previous studies have revealed some distinct variants of SFTs: giant cell-rich, fat-forming (lipomatous), myxoid, papillary (or pseudopapillary), and dedifferentiated variants [11–13]. Recently, microcystic structures have been described as a part of SFT morphology but have not been proposed as an independent subtype of SFTs [13]. In our case, the tumor showed a predominantly alveolar architecture with hypercellularity. And thin-walled, “staghorn” blood vessels were seen at the margin of the tumor. Although the tumor lacked some typical SFT features, STAT6 positivity supported the diagnosis, which was further confirmed by molecular testing. Therefore, alveolar-type SFT may be proposed as a novel histological variant.

The genetic hallmark of SFT is a paracentric inversion involving chromosome 12q, resulting in the fusion of the NAB2 and STAT6 genes [14, 15]. Recently, some studies have shown a correlation between fusion types and histological features [16–18]. In our case, NAB2::STAT6 fusion was confirmed by next-generation sequencing, which established the diagnosis of SFT at a molecular level.

This study highlights that it is challenging to diagnose SFTs with alveolar patterns based on histopathological findings alone. In our case, numerous alveolar components with varying sizes resembled the morphology of microcystic meningioma/spinal meningioma, ependymoma, and metastatic acinar adenocarcinoma. The differential diagnosis of SFT from microcystic meningioma/spinal meningioma was performed using the following criteria: oval to spindle-shaped cells rather than stellate cells with long interconnecting cytoplasmic projections, and CD34 and STAT6 immunoreactivity, with immunohistochemical negativity for EMA and PR. Ependymomas may occur either in the brain or in the spinal cord [19]. The following diagnostic criteria were used to distinguish SFT from ependymoma: the positive expression of STAT6 in tumor cells, and immunohistochemical negativity for GFAP, EMA, and S-100 protein. In addition, ependymoma is characterized by perivascular pseudorosettes, which were not detected in our case; therefore, the differential diagnosis of ependymoma was excluded. Metastatic acinar adenocarcinoma is mainly composed of adenoid-like structures and exhibits high-grade nuclear features. Immunohistochemistry can help distinguish SFT from metastatic acinar adenocarcinoma: CK-pan is negatively expressed in SFT, while it shows diffuse expression in metastatic acinar adenocarcinoma.

In summary, we present a case of lumbosacral spinal canal alveolar SFT that was composed of alveolar structures of varying sizes. It is challenging to diagnose SFT when it lacks some characteristic features such as variable cellularity or alternating hypocellular and hypercellular regions, patternless patterns or abundant keloid-type collagen and so on; furthermore, its unusual histological patterns add to the complexity. NAB2::STAT6 fusion is the decisive criterion for the diagnosis of SFT.

Author contributions

Z YY and SL: Conceptualization and Writing-original draft. WZ and ZZF: Formal analysis. LDL: Investigation. All authors read and approved the final version of the manuscript.

Funding

This study was funded by the National Natural Science Foundation of China (NSFC) under Grant No. 82303421 and the Shandong Provincial Natural Science Foundation under Grant No. ZR2023QH031.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. The procedures followed were in accordance with the ethical standards of Shandong Provincial Hospital Affiliated to Shandong First Medical University.

Competing interests

The authors declare no competing interests.