Multifocal cytokeratin expression in pleural and abdominal malignant solitary fibrous tumors: an unusual diagnostic pitfall

Abstract

Dear Editor, Solitary fibrous tumor (SFT) is an uncommon mesenchymal fibroblastic neoplasm usually arising in the pleura, but it can virtually affect any extrapleural site. Conventional SFTs are characterized by short, cytologically bland spindle cells arranged in a patternless architecture, a fibro-collagenous stroma, and a prominent hemangiopericytomatous branching vascular network [1]. The vast majority of SFTs are morphologically and clinically benign. However, 5 to 10 % of SFTs will recur and/or metastasize. Proposed prognostic clinical and morphological criteria for SFT include age at presentation, tumor size, cellularity, mitotic activity (>4 mitoses per 10 high-power fields), the presence of necrosis, and the presence of sharply demarcated anaplastic areas. The vast majority of aggressive SFTs demonstrate these clinical and morphological features of malignancy; however, also morphologically benign-appearing SFTs can metastasize, and therefore, the biological behavior of this tumor type still remains largely unpredictable [1, 2]. Immunohistochemistry is commonly used as a valuable adjunct to diagnosis of SFT, alongside convincing histology. Bcl-2, CD99, and CD34 are often positive in SFT (in nearly 100, 75, and 81–95 % of cases, respectively), but positivity for these markers can also be seen at a high frequency in other soft tissue tumors that can mimic SFT, and they are therefore non-specific [1]. Recent studies have discovered that almost all SFTs harbor a NAB2-STAT6 fusion gene [3]. This fusion gene is considered a driving mutation in the initiation of SFTs through EGR1 activation and transcriptional deregulation of EGR1-dependent target genes. The resulting overexpression of STAT6 protein has recently been shown to be a highly sensitive and specific marker for these tumors. Hence, STAT6 immunochemistry should lead to a more accurate diagnosis [4, 5]. We describe three cases of a morphological malignant SFT with unexpected strong cytokeratin expression, and we discuss the diagnostic implications thereof. All tumors were primary. The patientswerewomen aged between 42 and 84 years. In two cases, the tumor was located in the pleura, and in one case, the tumor was situated in the abdomen. Histologically, all three cases showed, at least focally, typical histological features of SFTwith branching hemangiopericytoma-like vessels and a variable fibro-collagenous background. They all met the proposed criteria of morphologically malignant SFTs, with increased mitotic activity, cytonuclear atypia, and tumoral necrosis (Figs. 1 and 2). Immunohistochemically, the atypical spindle cells in all three cases showed strong and patchy to diffuse expression for CD99 and Bcl-2. However, CD34 expression was heterogenous and loss of CD34 expression was observed in the malignant areas of both pleural tumors (Fig. 3). Staining for cytokeratin AE1/AE3 showed strong multifocal positivity (Fig. 4), but none of the cases was positive for cytokeratin 5, calretinin, and Wilms’ tumor protein 1 (WT1). The unforeseen strong positivity for cytokeratin AE1/AE3 together with the clinical setting of a large pleural or abdominal tumor point to sarcomatoid carcinoma or sarcomatoid mesothelioma as major differential diagnoses. The loss of CD34 reactivity contributes further to this diagnostic dilemma. Nevertheless, a histopathological diagnosis of SFT was made for three reasons. First, characteristic CD34 reactivity can be absent or only focally present in SFT cases [1]. Secondly, a few anecdotal single case reports of cytokeratin * Evelyne Lecoutere evelyne.lecoutere@ugent.be