Original Article
Loss of CD34 and high IGF2 are associated with malignant transformation in solitary fibrous tumors

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Abstract

The aim of this study was to characterize the subgroups of solitary fibrous tumor (SFT) and to investigate the expression of different biomarkers including CD34 and IGF2 in malignant transformation.

Two hundred and ninety-four (294) SFTs from a single German consultation center of soft tissue tumors were categorized into the new proposal of SFT designation. We found the fibrous variant in 223 (75.9%), the cellular variant in 65 (22.1%), the fat forming variant in 4 (1.4%), and the giant cell-rich variant in 2 (0.6%) cases. Anatomical location, size, mitotic index, necrosis, cellularity, collagenous ropes, and growth pattern of the vessels were recorded. Criteria of malignancy were found in 68 (23%) tumors. Expression of IGF2, IGF1R, CD34, BCL2, CD99, SMA, S100, PanCK, and Ki67 was analyzed immunohistochemically. Low expression of CD34 and high expression of IGF2 were significantly associated with malignant transformation and the metastatic rate. Moreover the presence of necrosis showed the most significant p-value (p < 0.004).

Of all SFTs, the fibrous variant is the most common, followed by the cellular variant. The fat-forming and giant cell-rich variants are very rare. Low expression of CD34 and high expression of IGF2 are significantly associated with malignant transformation, and might be an interesting target of individualized therapy.

Introduction

After the first detailed histological description of solitary fibrous tumor (SFT) by Wagner in Leipzig 1870, this tumor group became more popular [21]. Over the years, it appeared that the hemangiopericytoma (HPC)-like growth pattern was a non-specific one, shared by numerous unrelated lesions and that most of these tumors belonged to the SFT family [5], [14]. The SFT was described initially in the pleura and was later recognized to arise in almost any extrapleural site [14], [19]. The constituent tumor cells of this mesenchymal neoplasm show a fibroblastic phenotype and are arranged in a patternless growth of alternating cellularity and a collagenous stroma with a characteristically so called “staghorn pattern” of the blood vessels. The distinctive histopathological morphology is confirmed with consistent CD34 expression [7], [14]. The different morphology of the hypocellular and the hypercellular areas led to the definition of different major subgroups, the fibrous and the cellular variant [5]. The histological features of the fibrous variant included a heterogeneous microscopic appearance, an alternating presence of cellular and fibrous areas, hyalinized thick-walled vessels with opened lumina and keloidal collagen. In contrast, the cellular variant showed a monotonous microscopic appearance, moderate to high cellularity, weakly intervening fibrosis, and thin-walled branching vessels. Furthermore, a fat-forming variant and a giant cell-rich variant were described [5], [12].

While most solitary fibrous tumors follow a benign clinical course [6], approximately 15–20% of SFT present a more aggressive behavior with tumor recurrences and/or distant metastasis [16]. Some morphological features are known to be associated with aggressive clinical behavior, including more than 4 mitoses/10 HPF, nuclear atypia, hypercellularity, and necrosis [14]. Furthermore, positive surgical margins and tumor size ≥10 cm predict poor survival [6], [14]. The treatment of choice for primary tumors is surgical resection with negative margins [2]. However, there are no effective therapies for metastatic or advanced disease. Markers that reliably predict tumor progression and molecular data on the transition from benign to malignant SFTs are needed [7].

The objective of this study was (1) to categorize our cases according to the new proposal of different subgroups, (2) to record the anatomical location, distinct morphological features, and criteria of malignancy in a well characterized tumor collective, and (3) to evaluate the expression level of IGF2, CD34, and other markers on the protein level in malignant transformation of the different subgroups.

Section snippets

Tumor samples

Tissue samples of intra- and extrathoracic solitary fibrous tumors were retrieved from the archives of a German consultation and reference center at the Institute of Pathology at Friedrich-Schiller-University in Jena. All specimens (n = 294) were referred as consultation cases and, in addition to the original pathology report, microscopic findings (cellularity, blood vessels, collagen bundles, necrosis, mitosis and atypia) were reassessed by two authors (B.S. and T.K). The patient cohort was

Clinical and morphological features

The age at presentation of the SFTs ranged from 15 to 86 years (median age 57 years, female n = 153 (52%), male n = 141 (48%)). Tumor size ranged from 1 to 25 cm with a median size of 6 cm. The histological features of the solitary fibrous tumors are shown in Table 2. The most common variant in our study was the fibrous SFT with 223 of 294 cases (75.9%) with thickwalled blood vessels, changes in the amount of cellularity (overall cellularity lower than 90% of the tumor), and a higher degree of

Discussion

The SFT is a rare mesenchymal neoplasm with distinctive histopathological features and a distinctive immunohistochemical expression pattern [4], [7]. The constituent tumor cells show a fibroblastic phenotype, and are arranged in a so called patternless growth of alternating cellularity and a collagenous stroma. Since Guillou et al. proposed different variants of SFTs, the distinction has gained increasing popularity [12]. However, only selected cases of these variants or case reports were

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