Solitary fibrous tumor (SFT) of the pleura is a rare mesenchymal neoplasm arising from mesenchymal cells in the areolar tissue subjacent to the mesothelial-lined pleura and accounting for less than 5% of primary pleural tumors. SFTs are generally benign and asymptomatic, with 10-year survival rates of up to 98%. Unfortunately, approximately 10% have malignant potential, leading to local recurrence after radical surgery and/or metastatic spread. Of note, giant pleural SFT, which consists of a tumor occupying at least 40% of the affected hemithorax, is even less common with only anecdotal cases reported in the medical literature.
We describe a unique case of giant SFT of the pleura that metastasized to the thyroid gland 1 year after complete resection, focusing on its clinical and pathological features of presentation.
En bloc resection remains the mainstay of therapy with curative intent. Patients with large tumors may undergo preoperative angiography with percutaneous embolization of the tumor, which allows to reduce perioperative bleeding. In case of local recurrence, surgery still remains the best treatment option. However, surgery can also be considered in patients with isolated metastatic spread.
Every suspected and proven SFT of the pleura should undergo surgical resection, as clinical and radiological criteria cannot accurately distinguish benign from malignant forms. Moreover, the peculiar histological features of SFT should not be neglected when planning clinicoradiological follow-up. Additionally, suspicious clinical findings during follow-up should always be thoroughly investigated in order to exclude or confirm the diagnosis of recurrent disease.
Tumori 2016; 102(Suppl. 2): e16 - e21
Article Type: CASE REPORT
AuthorsBiagio Ricciuti, Giulio Metro, Giulia Costanza Leonardi, Rachele del Sordo, Renato Colella, Francesco Puma, Silvia Ceccarelli, Rossella Potenza, Alberto Rebonato, Daniele Maiettini, Lucio Crinò, Rita Chiari
- • Accepted on 30/03/2016
- • Available online on 23/04/2016
- • Published online on 11/11/2016
This article is available as full text PDF.
First described in 1931 by Klemperer and Rabin (1), solitary fibrous tumors (SFTs) of the pleura represent a rare and heterogeneous subgroup of spindle-cell tumors that include benign and malignant forms. These tumors arise from non-committed mesenchymatous cells in the submesothelial pleural tissue. SFTs typically consist of variably pleomorphic spindle cells blended with collagen and randomly arranged, whereas tumors previously included within the hemangiopericytoma spectrum are more frequently made up of monomorphic and ovoid cells with typical thin-walled anastomosing vessels (1). Usually, pleural SFTs exhibit positive staining for CD34 and Bcl-2, and negative staining for cytoplasmic keratin. Although initially reported as being pleura-based lesions, these malignancies have also been recorded in extrathoracic areas including the subcutaneous soft tissue (which accounts for roughly 40% of all extrapleural SFTs), head and neck, liver, skin, thyroid, and gastrointestinal tract. SFTs have an indolent natural history and a low risk of metastatic spread (1, 2). Nevertheless, SFTs are classified into “typical” and “malignant” forms, the latter being based on the number of mitotic figures (≥4 per 10 high-power fields [HPFs]), nuclear polymorphism, intratumoral hemorrhage or necrosis, presence of anaplastic or poorly differentiated foci, and infiltrative margins (2). However, because of their rarity, the relationship between tumor morphology and clinical behavior is uncertain, and no definitive prognostic factors have been established to date. Pleural SFTs occupying at least 40% of the affected hemithorax are referred to as giant SFTs, and are even less common, with only anecdotal cases reported in the medical literature.
Here we report a unique case of a giant pleural SFT that metastasized to the thyroid gland shortly after being treated with radical surgery.
A 71-year-old woman presented to the emergency department of the Hospital of Perugia with severe dyspnea (grade 4 on the Modified Medical Research Council Dyspnea Scale). Shortness of breath had first occurred roughly 1 month before. She was a never smoker with no history of asbestos exposure and her medical history was unremarkable. Physical examination revealed a decrease in breath sounds on the left hemithorax with consensual hypophonia. Laboratory tests showed no clinically significant abnormalities. A chest x-ray documented a large opacity in the lower field of the left lung (
Preoperative imaging findings. Plain PA and LL chest x-rays showing the mass taking up more than half of the left lung (
Intraoperative findings. Tumor pedicle to the left upper lobe (
Pathological findings. The pleural lesion was composed of spindle cells with a perivascular distribution (hematoxylin and eosin, ×200) (
The postoperative course was uneventful and the patient was discharged in good clinical condition. Unfortunately, 1 year later she returned to our attention because of a progressive increase in size of the thyroid gland. Clinical examination revealed a retrosternal goiter. Following preoperative clinical and radiological assessment, the patient underwent a complete thyroidectomy. On gross examination the thyroid showed marked symmetric enlargement (right lobe 6.4 × 3.3 × 2.6 cm, left lobe 9.5 × 5 × 5.3 cm, isthmus 3.2 cm, and pyramidal lobe 1.3 cm). The sectioned surface had a nodular, heterogeneous appearance with a semitranslucent aspect. Foci of hemorrhage and calcification were also present. In the upper portion of the left lobe there was a confined minute gray area measuring 5 mm. This small lesion was microscopically found to be a mesenchymal tumor characterized by spindled and pleomorphic cells with marked nuclear atypia that invaded the adjacent thyroid gland parenchyma (
Currently the patient is following a clinical and radiological follow-up program with CT scan at 6-month intervals, and has no signs of disease recurrence.
To our knowledge this is the first report of thyroid metastasis from SFT of the pleura. Pleural SFT is a rare mesenchymal tumor, accounting for <5% of primary pleural tumors. Its size has been reported to vary between 1 cm and 36 cm in diameter (2-3). Many large tumors are pedunculated on pleura-based pedicles with a hypertrophic vasculature. Giant pleural SFT is even less common, with only anecdotal cases reported (3). In contrast to mesothelioma, 87% of SFTs are benign and asymptomatic, with 10-year survival rates up to 98% (1, 4). Most cases occur in the sixth decade of life, affecting both genders equally and not displaying any association with exposure to tobacco or asbestos. Although generally benign, a minority of cases are diagnosed as malignant, with most deaths occurring within 24 months. Lung, bone and liver are the most common sites of metastasis, and metastases may appear after a long interval, usually 5-8 years, but sometimes more than 20 years (1, 2, 5). Compared to benign pleural SFTs, malignant tumors are characterized by larger size and aggressive biological behavior with a greater likelihood of PET positivity and symptomatic presentation (1, 4, 5). The diagnosis of malignant pleural SFT is based on several histological features including a mitotic count of ≥4 per 10 HPFs, nuclear atypia and polymorphism, intratumoral hemorrhage or necrosis, and the presence of anaplastic or poorly differentiated foci. Pleural effusion, large tumor size (>10 cm), an atypical location, invasion of adjacent structures and gain of a supernumerary chromosome 8 are additional criteria for malignancy in pleural SFTs (4-5-6-7-8).
Tumors larger than 10 cm compressing intrathoracic structures can cause symptoms such as dyspnea, chest pain and cough. Intriguingly, patients affected by SFTs may occasionally present paraneoplastic syndromes, such as Pierre Marie-Bamberger syndrome (pulmonary hypertrophic osteoarthropathy) and Doege-Potter syndrome (also known as refractory hypoglycemia), which are caused by abnormal secretion of hyaluronic acid or hepatocyte growth factor and insulin-like growth factor 2 (8). However, no paraneoplastic syndrome was present in our patient. Complete resection of the lesion is the mainstay of treatment in all cases. Video-assisted thoracoscopic surgery (VATS) may be considered the treatment of choice for lesions less than 5 cm, although conversion to open surgery should be employed if margin clearance cannot be obtained through VATS. Even though there have been reports of adjuvant therapy for malignant and recurrent tumors, its role remains unclear because of the rarity of these tumors. Similarly, also in the metastatic setting there is no established role for conventional chemotherapy or radiotherapy, although recent data from genetic profiling of SFTs suggests that they may respond to tyrosine kinase inhibitors (1). Data on the efficacy of cytotoxic chemotherapy are extremely limited and derive from small retrospective series. In this regard, Stacchiotti et al (9) conducted a retrospective study including 30 European patients with advanced SFT who received traditional chemotherapy (single-agent anthracyclines or a combination of anthracyclines plus ifosfamide). Six of these patients (20%) achieved a partial response and 8 (27%) had stable disease. Nevertheless, the median progression-free survival (PFS) was 4 months (9). Consistent with these data, 2 retrospective studies reported a median PFS of 4.6 and 5.2, respectively, for patients with advanced SFT treated with cytotoxic chemotherapy (doxorubicin-based and gemcitabine-based regimens, paclitaxel, dacarbazine and vinorelbine) (10, 11).
As in our case, patients with large tumors may undergo preoperative angiography with percutaneous embolization of the tumor, which allows to reduce perioperative bleeding (12). In this way, our patient did not experience any clinically significant blood loss after surgery. In case of local recurrence, surgery still remains the best treatment option. However, surgery can also be considered in patients with isolated metastatic spread, as in our case of metachronous metastasis to the thyroid. Importantly, we did not observed disease recurrence after approximately 1 year of follow-up post thyroidectomy. Nevertheless, follow-up is planned for a long period in our patient, as disease recurrence has been reported to occur even years after initial surgery (4, 5).
Interestingly, some pathological features may help identify which patients should undergo follow-up and for how long. In our case, similarly to other reports, the presence of anaplastic foci, necrosis, a high Ki-67 index, and a high mitotic count were suggestive of increased tumor aggressiveness (4-5-6-7). Consistently, our patient experienced distant disease recurrence, which occurred in a very unusual site such as the thyroid gland. Therefore, we conclude that the peculiar histological features of SFT of the pleura should not be neglected when planning clinicoradiological follow-up for these patients. In addition, suspicious clinical findings during follow-up should always be thoroughly investigated, which is crucial in order to exclude or confirm the diagnosis of recurrent disease.
- Ricciuti, Biagio [PubMed] [Google Scholar] 1, * Corresponding Author (firstname.lastname@example.org)
- Metro, Giulio [PubMed] [Google Scholar] 1
- Leonardi, Giulia Costanza [PubMed] [Google Scholar] 1
- Sordo, Rachele del [PubMed] [Google Scholar] 2
- Colella, Renato [PubMed] [Google Scholar] 2
- Puma, Francesco [PubMed] [Google Scholar] 3
- Ceccarelli, Silvia [PubMed] [Google Scholar] 3
- Potenza, Rossella [PubMed] [Google Scholar] 3
- Rebonato, Alberto [PubMed] [Google Scholar] 4
- Maiettini, Daniele [PubMed] [Google Scholar] 4
- Crinò, Lucio [PubMed] [Google Scholar] 1
- Chiari, Rita [PubMed] [Google Scholar] 1
Department of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia - Italy
Department of Experimental Medicine and Biochemical Sciences, Section of Anatomic Pathology and Histology, University of Perugia, Perugia - Italy
Department of Thoracic Surgery, Santa Maria della Misericordia Hospital, University of Perugia, Perugia - Italy
Department of Diagnostic Imaging, Santa Maria della Misericordia Hospital, University of Perugia, Perugia - Italy