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Review Article

Solitary Fibrous Tumor of The Larynx: Report of Two Cases With Literature Review

Stacey K Mardekian MD1*, Jill N D’Souza, MD2, Madalina Tuluc MD1

1Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, PA
2Department of Otolaryngology, Thomas Jefferson University Hospital, Philadelphia, PA

*Corresponding author: Dr. Stacey K Mardekian, Department of Pathology, Thomas Jefferson University Hospital, 132. 10th St., 285 Main Building, PA 19107, Philadelphia, Tel: 908-304-4881; Fax: 215-923-1969; Email: Stacey.Mardekian@jefferson.edu

Submitted: 11-05-2015 Accepted: 11-20-2015 Published: 01-06-2016

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Article


Solitary fibrous tumor (SFT) is an anatomically ubiquitous neoplasm with intermediate biologic potential. SFT occurring in the larynx is exceedingly rare, with only 18 cases reported in the English literature. Here we report two additional cases of laryngeal SFT. A 31-year-old male presented with hoarseness and dyspnea and was found to have a mass involving the right true vocal cord. A 73-year-old female presented with throat fullness and abnormal swallowing sensation and was found to have a mass involving the left aryepiglottic fold. Both patients underwent microdirect laryngoscopy with carbon dioxide (CO2) laser excision, and pathologic examination established the diagnosis of SFT. Here we aim to summarize the clinicopathologic features, diagnostic approach and treatment options for laryngeal SFT.

Keywords: Solitary fibrous tumor; hemangiopericytoma; larynx; CD34; CO2 laser surgery

Introduction

Originally described in 1931 in a pleural location, solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that is now known to occur in virtually any anatomic site [1]. The clinical and radiologic findings are nonspecific, so the diagnosis of SFT relies on its characteristic histologic appearance and immunohistochemical profile [2]. The tumor is composed of CD34-positive spindle cells, branching hyalinized vessels, and a collagenous stroma [3]. Atypical features such as high mitotic activity increase the risk of clinically aggressive behavior, but generally SFTs follow an indolent course and are curable with adequate surgical excision [3,4].

The first report of SFT within the head and neck came in 1991, with a series of six cases involving the nasal cavity, nasopharynx, and nasal septum [5]. In this region, these tumors are discovered when the mass causes local compressive symptoms, and they are difficult to clinically distinguish from other soft tissue tumors [6]. In a comprehensive review of SFT occurring in the head and neck, Cox et al. found that the most frequently involved sites are the buccal mucosa, nasal cavity, pharyngeal area, tongue and orbit [7]. The larynx is an exceptionally rare site, with only 18 cases reported in the English literature thus far [8-25]. Here we report two new cases of SFT occurring in the larynx. We also provide a comprehensive review of the literature of this rare entity.

Case 1

A 31-year-old male presented to the emergency department complaining of progressive hoarseness and shortness of breath. He had previously been treated for laryngitis without relief. Laryngoscopic examination revealed a bulky exophytic mass arising from the right true vocal fold and causing substantial narrowing of the laryngeal airway. A computed tomography (CT) scan revealed a 1.5 cm exophytic focus at the level of the right vocal fold, extending to the anterior commissure (Figure 1). The patient was taken to the operating room for fiberoptic intubation and microdirect laryngoscopy with carbon dioxide (CO2) laser excision of the mass (Figure 2).

Figure 1. Axial (A) and sagittal (B) views of CT neck with IV contrast show a soft tissue density (arrows) at the level of the larynx.

Otolaryn fig 24.1

Figure 2. Intraoperative direct laryngoscopy shows the vascular fibers of the tumor capsule (arrow) and its extension to the right vocal fold, which has lost the sharp edge on its medial aspect.

 Otolaryn fig 24.2

Intraoperatively, the laser was set to 5-7 Watt power, and the attachments between the mass and the undersurface of the right true vocal fold and the anterior subglottic larynx were divided. A biopsy of the mass was sent for frozen section analysis, which was negative for neoplasm. Given the bulky and infiltrative nature of the tumor, serial excision was deemed necessary, so the remainder of the specimen was sent for routine sections. Histologic examination established the diagnosis of SFT (Figure 3).

Figure 3. Histologic sections (A and B, hematoxylin and eosin stain, original magnification x40 and x200, respectively) reveal haphazardly arranged spindle cells and gaping staghorn vessels with a dense collagenous background. CD34 stain (C) highlights tumor cells and the lining of vascular spaces.

 Otolaryn fig 24.3

The tumor was serially excised with 2 additional operative procedures over the next 8 months. During the next procedure, margins were sent for routine processing and were positive for SFT. The final procedure utilized intraoperative frozen sections for margin evaluation, and all margins were negative for tumor. There has been no evidence of recurrence at one year following the last procedure.

Case 2

A 73-year-old female presented to ENT clinic for evaluation of left ear pain, sensation of left throat fullness and abnormal swallowing sensation. On neck exam, fullness was palpated over the left lateral thyrohyoid membrane. Flexible laryngoscopy with strobovideolaryngoscopy and dynamic voice analysis revealed an expansile submucosal mass involving the left aryepiglottic fold. Vocal fold motion was normal and the lesion did not affect normal glottic closure. Magnetic resonance imaging (MRI) showed a 2.5 cm homogeneously enhancing solid mass at the level of the thyrohyoid membrane on T1-weighted image, with intermediate enhancement throughout on T2-weighted image (Figure 4). Radiologic differential diagnosis for the mass included benign and malignant neoplasm, as well as low-flow vascular malformation.

Figure 4. Coronal (A) and axial (B) views of T1-weighted post-contrast fat-saturated MRI neck show a homogeneously enhancing mass (arrows) at the level of the thyrohyoid membrane.

Otolaryn fig 24.4

The patient was taken to the operating room for microdirect laryngoscopy with CO2 laser excision of the mass. Intraoperatively, laser was set to 5-8 Watt power, and a linear incision was made parallel to the aryepiglottic fold. Submucosal dissection revealed a mass with a vascular fibrous capsule. Dissection was carried out circumferentially until fibrous attachments were divided and the mass was removed in its entirety.

Otolaryn fig 24.5

Figure 5. Gross specimen consists of a 2.5 cm well-circumscribed ovoid mass with vascular fibrous capsule.

The fibrous capsule provided adequate delineation of the mass from the surrounding tissues, so intraoperative frozen section analysis was not performed. Pathologic examination of the gross surgical specimen revealed a well-circumscribed fibrous mass (Figure 5), and histologic sections confirmed the diagnosis of SFT. The patient is free of disease at one postoperative year.

Discussion

With the addition of these two cases, there are a total of 20 cases of laryngeal SFT reported in the English literature (Table). The mean patient age is 49.9 (range 13-75) years. Twelve of the 20 patients are male and eight are female (male:female ratio = 1.5:1). This is comparable to the epidemiology of SFT overall, which typically presents in middle-aged adults and less commonly in adolescents and elderly patients, with an equal gender predilection [26]. Laryngeal SFTs are located most commonly in the supraglottis (80% of cases), with the glottis and subglottis less commonly involved. Patients experience hoarseness, dyspnea, abnormal sensation in the throat, or a combination of these symptoms due to compressive effects of the mass on airway structures. Mean tumor size of laryngeal SFT is 3.4 cm (range 2.2-6.3 cm). This is similar to the average size reported at other head and neck sites, and smaller than reported for SFTs overall, which can reach much larger dimensions before causing symptoms [3,7]. Larger tumors may also be the source of paraneoplastic syndromes such as hypoglycemia, due to tumor production of insulin-like growth factor 2 (IGF-2); however, this phenomenon has not been reported in SFT of the head and neck region [2,7]. Laryngoscopic findings typically show a smooth, non-mucosal based polypoid mass bulging into the laryngeal lumen, causing partial or complete occlusion and sometimes vocal fold immobility [20].

Cases diagnosed as hemangiopericytoma (HPC) of the larynx were included in the literature review, as these tumors would be designated as SFT under the current classification system. The term HPC was first used in 1942 to describe a neoplasm thought to be derived from pericytes, which are modified smooth muscle cells present in the walls of small blood vessels [27]. However, pathologists gradually discovered that pericytic differentiation could be established, via ultrastructural or immunohistochemical analysis, only in a minority of cases [28]. As the term HPC gradually fell out of favor, SFT was gaining popularity as a diagnostic entity, especially after its identification at extrapleural sites [27]. Later, with the recognition that HPC and SFT share overlapping morphologic and immunohistochemical features, many pathologists embraced the concept that the two tumors encompassed a spectrum of the same neoplastic process, arising from fibroblasts or myofibroblasts [29]. The fact that HPC was a diagnosis of exclusion, along with the fact that up to 15% of soft tissue neoplasms show focal HPC-like features, has led to the general acceptance of HPC as a growth pattern rather than as a specific entity [27].

Otolaryn table 24.1

The most recent WHO classification abandons the entity HPC and categorizes extrapleural SFT within the group of fibroblastic/ myofibroblastic tumors of intermediate biologic potential [26]. The entity formerly known as HPC of the soft tissues is now believed to represent a cellular form of SFT, and HPC is a term now exclusively used to describe distinct tumors arising in the meninges and sinonasal region [27]. Therefore, most lesions formerly classified as HPC involving the soft tissues would today be classified as SFT.

The radiological appearance of SFT of the larynx is nonspecific, and it can closely resemble other more common lesions in this location, such as hemangioma or schwannoma [30]. The classic appearance is that of a solitary well-defined ovoid, often pedunculated mass arising from the submucosal tissue, without evidence of destructive growth or penetration into the deeper
soft tissues of the larynx [20]. The mass will characteristically show isodensity on noncontrast CT scan, isointensity on magnetic resonance (MR) T1-weighted image, and variable signal intensity on MR T2-weighted image [6,21,30]. The presence
of hypointense linear/curvilinear septae within the mass has been described on T2-weighted images and is thought to reflect the hypocellular areas of densely sclerotic stroma [21,30]. Perhaps the most common distinctive radiologic feature of SFT is strong post-contrast enhancement, which is more commonly homogeneous than heterogeneous, and is consistent with the richly vascularized nature of the neoplasm [20,31]. Time-intensity curves with rapid enhancement and slow washout pattern should prompt inclusion of SFT into the radiologic differential diagnosis [30].

Gross macroscopic findings of SFT include a well-circumscribed, sometimes partially encapsulated solitary mass, with a pale, firm, whorled cut surface [26]. The histologic appearance varies depending on the relative proportion of the cellular and stromal components. At low power, the random alternating areas of hypercellularity and hypocellularity are apparent [31]. In the cellular areas, the cells are arranged haphazardly in ill-defined fascicles or a vague storiform pattern, thus accounting for the description as a “patternless” architec ture [28].The cell morphology is round to spindled with vesicular nuclear chromatin and ill-defined syncytial cytoplasmic borders. The cells are intermixed with abundant vascular spaces, which range from small capillaries to large dilated and angulated (so-called “staghorn”) vessels [20]. The final major histologic component of SFT is the background collagenous stroma, which can contain prominent hyalinization, dense “keloid-like” areas, and/or myxoid change. Mitoses are generally rare; if greater than four mitotic figures per high power field are found, this indicates a malignant SFT. Other features of malignancy include high cellularity, cytologic atypia, tumor necrosis, and/or infiltrate margins [26].

The differential diagnosis of laryngeal SFT includes many benign (soft tissue perineurioma, spindle cell lipoma, cellular angiofibroma) and malignant (malignant peripheral nerve sheath tumor, monophasic synovial sarcoma) mesenchymal lesions which may focally show histologic features similar to SFT, especially the HPC-like branching vascular pattern [27,32]. Diagnosis on a small biopsy sample may prove especially challenging. A panel of select immunohistochemical markers should be used to support the histologic impression. Expression of CD34 antigen in neoplastic cells is the most reliable and consistently positive marker of SFT at any site [7]. In our series, every case for which CD34 was tested (n = 12) was positive for this marker. An estimated 80-90% of SFTs show CD34 staining, which varies in strength and distribution. While classic SFTs will usually demonstrate strong and diffuse CD34 staining, cellular forms of SFT tend to show less frequent, weaker, and more focal CD34 staining [27]. SFT may also variably express CD99 (70%), nuclear beta-catenin (40%), bcl-2 (30%), epithelial membrane antigen (30%), and smooth muscle actin (20%) [28,32]. However, these markers are not specific for SFT and can be observed in other tumors on the differential diagnosis, so it is important to also stain for select pertinent negative markers in order to reach a conclusive diagnosis [7]. Desmin, cytokeratin and S-100 protein are usually negative in SFT [27,28].

Although in most cases the histological diagnosis of SFT is straightforward, some tumors may closely mimic other neoplasms, and a subset of SFT lack expression of CD34. Very recently, a characteristic NAB2-STAT6 gene fusion has been found to occur in nearly all SFTs, at both pleural and extrapleural sites. Interestingly, this fusion gene has also been identified in meningeal HPCs, providing further evidence of the equivalence of these lesions [32]. Detection of this fusion gene can be performed by reverse transcriptase polymerase chain reaction. Alternatively, immunohistochemistry for STAT6 is a reliable and more practical surrogate for detection of the fusion oncoprotein, which is highly expressed and localizes to the nucleus, resulting in a strong and diffuse nuclear expression of STAT6 [32,33]. Furthermore, it is present in very few (less than 3%) non-SFT tumors, including low-grade fibromyxoid sarcoma, myxoid/round-cell liposarcoma, and dedifferentiated liposarcoma [34,35]. Therefore, this unique genetic aberration can be another helpful tool in distinguishing SFT from its histologic mimics.

Extrapleural SFT is classified as having intermediate biological potential. Approximately 10% exhibit aggressive behavior, including local recurrence or distant metastasis, which can occur many years after primary resection [26]. The general trend is that most histologically benign SFTS are non-recurring and non-metastasizing, while most histologically malignant SFTs behave aggressively. Indeed, malignant histology, in particular high mitotic counts, is the best indicator of poor outcome [4]. SFTs located in the mediastinum, retroperitoneum, abdomen and pelvis also tend to be more aggressive [26]. Because of its rarity in the larynx, the clinical behavior of SFT in this location is not well characterized [18]. Other predictors of poorer prognosis of SFT in general include tumor size greater than 10 cm and positive surgical margins [4]. In the confined space of the larynx, a mass becomes clinically apparent much earlier than in other sites, thus limiting the extent of disease; however, the complicated anatomy of this region may render complete surgical resection more difficult [6]. In this series, 3 out of 20 cases (15%) showed atypical or malignant histologic features. Of the patients who received surgical treatment with reported follow-up (n = 14, mean = 15 months, range = 1-42 months), none experienced disease recurrence or metastasis. Two patients died of other causes before their treatment for SFT was completed, and one patient died of metastatic adenocarcinoma of unknown origin.

Overall, SFTs have a favorable clinical course, and complete local surgical excision is the treatment of choice for laryngeal SFT [7]. In our series, the majority of patients underwent surgical resection. Exceptions were a patient who had multifocal disease at presentation and received two cycles of radiation therapy before passing away, and a patient who died from other causes before undergoing surgery [8,9]. The specific location of the tumor within the larynx and its extension should dictate the extent of the resection area. Function-preserving, limited excision seems to yield the same outcome as a more radical procedure [20]. In subglottic SFT, a transcervical approach with preservation of the larynx is considered the most effective surgical choice. In supraglottic SFT, an endoscopic resection by means of a CO2 laser or partial laryngectomy is usually performed [22]. CO2 laser surgery has gained popularity, especially given that the rich vascular nature of SFT demands careful cauterization and hemostatic control during surgery [19]. CO2 laser surgery was the method of choice in 3 previously reported cases and the 2 new cases presented here. One disadvantage of CO2 laser surgery is that extensive cautery of the lesion may hinder evaluation of surgical margins [19]. Additionally, patients may require more than one procedure to remove the mass in its entirety. In one case of laryngeal SFT, the patient experienced clinical remission for several months following CO2 laser surgery before subsequently developing clinical symptoms concerning for recurrence, which was confirmed on imaging and endoscopic examination. This patient then underwent a modified left vertical laryngectomy for complete resection of the recurrent mass [15]. In another case (Case 1 reported here), multiple operative procedures were necessary before complete macroscopic and microscopic removal of his tumor was ensured.

Even in cases with atypical or malignant microscopic features, complete resection with negative surgical margins appears to be curative, with no additional treatment required [25]. The ability for complete excision may be affected by the anatomic complexity of the larynx. Patients with positive surgical margins or whose tumors have a malignant component may benefit from adjuvant postoperative radiation therapy, but there is limited data available to make any accurate conclusions on its effect on preventing local recurrence [31]. Additionally, SFT is a chemoresistant tumor, so neither radiotherapy nor  chemotherapy are considered standard of care in the treatment of SFT of the head and neck [2,4,20].

Conclusion

Although infrequently diagnosed 25 years ago, extrapleural SFTs have been increasingly reported and are now more prevalent than their pleural counterpart, although they remain very rare within the larynx [6,27]. The appropriate nomenclature for this lesion has historically been the source of much confusion and controversy, but with better understanding and a more consistent classification, there will be improvements in the recognition and prognostic assessment of such tumors. The high sensitivity of CD34 for SFT has resulted in a more accurate and consistent diagnosis of the entity, undoubtedly accounting for the increasing number of SFTs now diagnosed at extrathoracic sites. New information about STAT6 as a highly sensitive and specific immunohistochemical marker provides another opportunity to simplify the diagnosis. Generally, SFTs have a favorable clinical course and are adequately treated with complete surgical resection, but the importance of preserving vital structures within the head and neck may pose a challenge. Local recurrence and metastasis have been correlated with tumors possessing malignant features on histology as well as those with gross or microscopic residual disease after resection. Patients meeting these criteria clearly require close follow-up and may benefit from consideration for postoperative radiation treatment; however, because of the unpredictable behavior of SFT, even histologically benign cases necessitate careful long-term monitoring. Improved understanding of the molecular pathogenesis of SFT will be instrumental for the development of targeted therapy in patients with advanced disease.

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Cite this article: Mardekian. Solitary Fibrous Tumor of The Larynx: Report of Two Cases With Literature Review. J J Otolaryn. 2015, 1(5): 024.

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