Malignant solitary fibrous tumor in the extremity: Cytopathologic findings.

Malignant solitary fibrous tumor (SFT) is an extremely rare neoplasm. There are only rare published accounts of the cytopathologic features of this tumor. We report a case of a 59-year-old woman presented with a 10-year history of a right thigh mass. A preoperative fine needle aspiration (FNA) was performed. Smears were hypercellular, with cohesive and crowded tissue fragments, haphazard cell arrangements and many single cells. The tumor cells were polymorphous, plump spindled or round with often indented or bare nuclei. A differential diagnosis of low grade sarcoma was favored. The diagnosis of malignant SFT is extremely difficult on FNA and must be included in the differential diagnosis of spindle cell neoplasms.

Introduction

Malignant solitary fibrous tumors (SFT) are extremely rare mesenchymal tumors.[1] Originally thought to occur exclusively in intrathoracic sites, they are now known to be quite ubiquitous.[2] There is very little literature regarding the cytologic findings in this tumor. In the current study we describe the cytologic features of malignant SFT arising in the right thigh.

Case Report

A 59-year-old woman presented with a 10-year history of a right thigh mass. An ultrasound examination showed a solid mass of 10 × 10 cm with heterogeneous echotexture and rich vascularity. Magnetic resonance imaging scan (MRI) showed inhomogeneous low intensity signal on T1-weighted image and intermediate intensity signal on T2-weighted image of 6 cm in the anterior thigh. A preoperative FNA aspiration was performed using 22- and 25-gauge needles and air-dried and alcohol-fixed smears were made. The air dried-smears were stained by May-Grünwald-Giemsa (MGG) stain and alcohol-fixed smears were stained with Papanicolaou stain.

Cytologic findings

Smears were hypercellular, with cohesive and crowded tissue fragments, haphazard cell arrangements, and many single cells in a background of dense collagen bands and capillary blood vessels [Figure 1a]. The tumor cells were polymorphous, plump spindled or round with often indented or bare nuclei [Figure 1b]. A diagnosis of low-grade sarcoma was favored. The patient underwent a complete resection of the tumor.

Figure 1

FNA of malignant SFT (a) A large hypercellular, haphazard cell arrangements and many single cells. The tumor cells are polymorphous, plump spindled or round with often indented or bare nuclei (MGG, ×400) (b) Single oval to spindle cells within a background of dense collagenous bands (Pap stain, ×400)

Pathologic findings

At gross examination, the tumor was 10×5, 5×3 cm in size. It was firm and well circumscribed. The cut surface was reddish and whorled [Figure 2a].

Figure 2

(a) Gross appearance of malignant SFT (b) Histologic section: patternless growth and hemangiopericytoma-like vessels (H and E, ×200) juxtaposed with (c) areas displaying malignant features such as hypercellularity, pleomorphism and mitosis (H and E, ×400) (d) Immunohistochemical studies: The tumor cells are diffusely positive for CD34 (IHC, ×250)

Pathological examination showed a highly cellular neoplasm. The tumor showed a patternless architecture with branching hemangiopericytoma-like vessels [Figure 2b]. The tumor cells were relatively monomorphic ovoid or sometimes spindle cells showing a moderate nuclear pleomorphism. Mitotic rate was 8 mitoses per 10 high-power fields [Figure 2c].

Immunohistochemical studies revealed a heterogeneous cytoplasmic positivity for CD34 [Figure 2d] and a strong cytoplasmic positivity for vimentin, bcl-2 and CD99.

On the basis of the cytological, histological and immunohistochemical findings this case was classified as malignant SFT.

Discussion

The increasingly wide spread use of FNA for soft tissue lesions necessitate the recognition of even rare neoplasms.[3] SFTs are uncommon mesenchymal tumors with usually benign behavior. Nevertheless 10% to 15% of SFTs will recur and/or metastasize.[4] The soft tissues of the extremities are among the rarest sites of occurrence of this entity. In this location SFT is likely to have a malignant potential.[5]

Cytologic features of SFT are relatively non specific, comprising of hypocellular clusters of cohesive, bland spindled cells with inconspicuous nucleoli in a collagenic and hemorrhagic background with staghorn vessels. These features are better seen in cell block preparations.[3] In the few series describing cytologic features of malignant SFT the clue of malignancy are hypercellularity, pleomorphism and epithelioid or round cell features, as well as necrosis and mitoses.[3] However, hypercellularity and even necrosis have also been described in rare cases of benign SFT.[4] Some authors suggested that a predominance of single cells as features would favor malignancy.[4] In our case cytologic features of malignancy were hypercellularity, pleomorphism and many single cells. There were neither mitoses nor necrosis.

Grossly, malignant SFTs are large with an average of 13.4 cm, (the tumor in our case sized 10 cm), consistent with the notion that malignant SFTs are generally larger than benign SFTs.[1] Hemorrhage and/or necrosis, common gross features of malignant neoplasms, were not seen in our case.[3]

Microscopically, the typical benign SFTs, display zones of both hypercellular and hypocellular collagenized stroma in a so called patternless architecture.[1] It is characterized by a branching hemangiopericytoma-like (staghorn) vasculature.[1] Criteria of malignancy are not standardized, but malignant SFT is described by the World Health Organization classification of soft tissue tumors as having features including hypercellularity, at least focal moderate to marked cellular atypia, tumor necrosis, ≥ 4 mitoses/10 high-power fields, and infiltrative margins.[2]

The differential diagnosis of malignant SFT in the extremity, include a spectrum of benign or low-grade malignant spindle cell lesions such as hemangiopericytoma, benign and malignant neurogenic tumors, fibrosarcoma, synovial sarcoma (SS) and dermatofibrosarcoma protuberans (DFSP). The CD34 may prove a useful positive marker in cytology. However, it is not necessarily specific.[6]

Probably the most difficult diagnosis to distinguish from malignant SFT is benign SFT. Flint and Weiss[7] reported CD34 positivity in 77% of benign solitary fibrous tumors and 100% of malignant SFT. However, Ali et al[6] described a loss of CD34 expression in malignant SFTs. Our case showed an heterogeneous expression of this antigen. Bcl-2, which has been reported to be more consistently positive than CD34 in malignant SFT, was positive in our case.[7]

SFTs are usually negative for S-100 protein, actins, desmin and cytokeratins. However, focal immunoreactivity for cytokeratins, actins, S-100 protein, epithelial membrane antigen may be seen.[1]

Hemangiopericytoma shows a monotonous pattern with a staghorn configuration. A feature of “patternless pattern” is a characteristic of solitary fibrous tumors and cannot be detected in hemangiopericytoma. It is diffusely positive for CD 34. Peripheral nerve sheath tumors are characterized by a pain during aspiration biopsy procedure.[8] They show focally positive immunoreactivity to CD34 antibody in dendritic cells.[9] Benign peripheral nerve sheath tumors diffusely express S100 protein. This expression may be lost in 30-50% of malignant peripheral nerve sheath tumors.[10] The appearance of a monotonous population with spindled and/or round cells may be reminiscent of SS. If present, glandular structures of a biphasic SS exclude the possibility of malignant SFT. Immunohistochemically, both malignant SFT and SS share bcl-2 positivity, but any significant positivity for CD34 effectively excludes the diagnosis of SS.[3] Fibrosarcoma present the pattern of a uniform population of spindle cells, both dispersed and arranged in clusters of fascicular structures.[8] They do not show positive immunoreactivity to CD34 antibody.[8] Smears from a malignant SFT show cytologic and immunohistochemical patterns similar to dermatofibrosarcoma protuberans (DFSP). Compared with SFT, DFSP is less deeply located and involves the dermis.

In conclusion, malignant SFT in the extremity is rare. It is crucial to correlate the cytomorphologic features of FNA with the clinical presentation and the radiologic findings. It shares some features with benign SFT, and malignancy is usually difficult to assess in the absence of mitoses and necrosis. Because of its non specific appearance, it is most often not possible to accurately diagnose malignant SFT on FNA material.