Sinonasal Glomangiopericytoma: Case Report With Emphasis on the Differential Diagnosis Open Access

The patient is a 48-year-old woman who presented with epistaxis and symptoms of nasal obstruction and was found to have a polypoid mass in the left nasal cavity. A computed tomography scan revealed a mass filling the left nasal cavity, with bone erosion and extension into the adjacent ethmoid sinus, with associated maxillary sinusitis. A left medial maxillectomy and ethmoidectomy was performed. She has been free of disease after surgical resection, with a follow-up period of 21 years.

The maxillectomy specimen contained a 3.5-cm, circumscribed, smooth-surfaced, and polypoid mass with tan cut surface including foci of hemorrhage. Sections of the mass showed a well-circumscribed, diffuse, subepithelial proliferation (Figure 1, A) of spindled cells growing in sheets and short fascicles (Figure 1, B), with effacement of submucosal structures and an intact overlying surface epithelium. The cells were cytologically bland and evenly spaced with indistinct cell borders, had eosinophilic to vacuolated cytoplasm, and spindled nuclei with smooth nuclear contours and uniform chromatin (Figure 1, C). Some areas had stromal edema yielding relatively hypocellular zones. The cells were intimately associated with a prominent vascular network composed of ectatic, irregularly shaped, staghorn-type vessels with numerous capillary-sized vessels exhibiting perivascular hyalinization (Figure 1, D). An inflammatory infiltrate including eosinophils, mast cells, lymphocytes, and plasma cells was present as well as extravasated red blood cells (Figure 1, C). Immunohistochemical stains demonstrated diffuse and strong staining for muscle-specific actin (Figure 2, A) and smooth muscle actin (Figure 2, B), with negativity for desmin, cytokeratin, and S100 protein. These morphologic and immunophenotypic features were diagnostic of sinonasal glomangiopericytoma.

Glomangiopericytoma falls within the category of borderline and low-malignant-potential soft tissue tumors of the nose and paranasal sinuses. It is defined by the World Health Organization as a sinonasal tumor demonstrating a perivascular myoid phenotype.1 The concept of hemangiopericytoma was first described in 1942 by Stout and Murray2 as a soft tissue tumor with characteristic vascular proliferation including branching vessels and small vessel perivascular hyalinization with otherwise marked morphologic heterogeneity. This lesion was thought to fall in the spectrum between glomus tumors and capillary hemangioma and hence the term hemangiopericytoma was chosen. Although it was believed to be of pericytic derivation, there was no scientific proof to support this.3 From its initial description, significant confusion has surrounded the concept of hemangiopericytoma, as its characteristic features have been found to be nonspecific4 and present in a large group of unrelated neoplasms.5 Currently, the term hemangiopericytoma is used to describe a histologic pattern seen in a wide variety of soft tissue neoplasms and this lesion is no longer regarded as a distinct entity by many authors. Many lesions that previously would have been designated as hemangiopericytoma are now largely better classified as cellular solitary fibrous tumors (SFTs).

As the concept of hemangiopericytoma was evolving, it was noted that when this lesion arose in the nasal cavity, it tended to behave in a more indolent fashion than its soft tissue counterpart, suggesting that sinonasal hemangiopericytomas represented a distinct entity.6 In addition, sinonasal lesions had distinctive morphologic features7 and showed true pericytic differentiation.4 To reflect this, Compagno and Hyams6 termed these lesions hemangiopericytoma-like intranasal tumors.6 Currently it is widely accepted that sinonasal-type hemangiopericytoma, now termed glomangiopericytoma, represents a lesion separate from traditional soft tissue hemangiopericytoma.

Glomangiopericytomas account for fewer than 1% of sinonasal tumors, generally arise in the nasal cavity, and may extend into the paranasal sinuses, although lone paranasal sinus involvement has been reported.1,7,8 Persons across a broad age range may be affected, with a peak incidence in the seventh decade of life and a slight female predominance.7,8 

The gross appearance of these lesions is generally not helpful, as most specimens are fragmented during endoscopic removal. If intact, they may have solid, soft, fleshy, or friable cut surfaces with hemorrhagic and/or edematous areas. They range in size from 1 to 8 cm, with a mean of 3.1 cm.8 

Glomangiopericytoma is a cellular spindle cell neoplasm with characteristic hemangiopericytoma-like vessels and frequent perivascular hyalinization of the capillary-sized vessels, which is often striking at low-power magnification.8–11 In addition to diffuse and fascicular growth, storiform or whorled growth patterns are possible and frequently there is an admixture of different patterns. Squamous metaplasia7 and, rarely, ulceration are noted in the surface epithelium overlying these tumors and frequently a thin, tumor-free zone lies between the basement membrane and the neoplastic cells.10 In addition to spindle cells, occasional tumors have foci with a more round-cell appearance, imparting a resemblance to glomus tumor. Unlike glomus tumors, the eosinophilic cytoplasm of glomangiopericytoma results in a syncytial appearance, as the cells lack prominent cell borders. The nuclei have oval smooth contours with even, pale-staining chromatin and 1 or more small nucleoli. Most tumors have areas with inflammatory cells and extravasated red blood cells. Although not characteristic, mild cytologic atypia and occasional mitotic figures may be present; however, necrosis is not found.10 A small percentage of tumors may demonstrate tumor giant cells, clear cells, or myxoid degeneration.8 

As indicated, glomangiopericytomas are true pericytic tumors that exhibit a myoid phenotype with immunohistochemistry or electron microscopy.12 Most are positive for smooth muscle actin, muscle-specific actin, and vimentin,8,10,12 with staining typically diffuse and strong but sometimes focal. They are also often positive for factor XIIIa.8 Staining for desmin, S100 protein, and CD34 is typically negative, although staining for CD34 and S100 protein can be focally and weakly positive in a small percentage of tumors.8,9,11,12 Additional negative stains include Bcl-2, CD99, CD117, and cytokeratins.8,9 

Glomangiopericytoma is an indolent tumor, associated with 5-year survival greater than 90% after surgical resection.1,8 Local recurrence has been reported in 7% to 40% of cases, in part because of incomplete surgical resection; however, aggressive behavior is rare.7–12 Large tumors (>5 cm) that invade bone have profound nuclear pleomorphism, necrosis, and high mitotic (>4 mitoses/10 high-power fields) to proliferation (>10% Ki-67 proliferation index) rates and are more likely to behave aggressively.1,8 

Glomangiopericytomas may be confused with a variety of spindle cell and vascular neoplasms occurring in the sinonasal tract. The difficulty tends to lie not in distinguishing glomangiopericytoma from sarcomas, as the latter are usually clearly malignant, but rather in differentiating them from other benign/borderline vascular-rich spindle cell lesions, most commonly, lobular capillary hemangioma (pyogenic granuloma), SFT, leiomyoma, and angiofibroma. Here we highlight some of the helpful features that allow distinction of glomangiopericytoma from these commonly confused lesions.

Lobular capillary hemangioma (LCH), also referred to as pyogenic granuloma, is relatively common in the nasal cavity, accounting for nearly one-third of upper aerodigestive tract LCHs.13 Most arise on the septum but any subsite may be involved. They are often smaller (mean size, 1.7 cm; range, 1–8 cm) than glomangiopericytoma but can have a similar clinical presentation; they affect a broad age range, with an overall lower age of peak incidence (mean, 37 years; range, 8–82 years).13 There is a male predominance in patients younger than 18 years (male to female ratio, 4∶1), with a female predominance in patients 18 years and older (male to female ratio, 1∶4).13 Like glomangiopericytoma, LCH typically is a polypoid vascular submucosal mass with intact surface mucosa and effacement of submucosal structures (Figure 3, A). It is a cellular tumor with prominent vasculature, including large irregular ectatic vessels, and it may have stromal hemorrhage. The architecture differs from glomangiopericytoma in that it is lobular, often with an identifiable large, central feeder vessel giving rise to branching, progressively smaller, and ultimately slitlike vascular spaces. The cells tend to be more disorganized, with irregular nuclear contours (Figure 3, B), and these cells actually line the vascular spaces, unlike what is observed in glomangiopericytoma. In contrast to glomangiopericytoma, mitotic figures are frequent in nasal LCH (Figure 3, B). Immunophenotypically the neoplastic cells of LCH show vascular endothelial differentiation with positivity for CD31 and CD34. Actin stains will highlight perivascular myoid cells but not the cells lining the vascular spaces.14 These lesions are cured by surgical excision and rarely recur.13,14 

About 6% of SFTs occur in head and neck sites.15 Among extrapleural SFT, nearly one-third occur in head and neck sites, with 15% in sinonasal locations.16 Sinonasal SFT is uncommon overall, accounting for fewer than 1% of all sinonasal neoplasms,17 with nasal cavity more often affected than paranasal sinuses. They usually affect adults (mean age, 52 years) with roughly equal sex predilection and clinically can present like any obstructive nasal tumor with epistaxis and rhinorrhea.18 Macroscopically, SFT tends to be larger (mean, 5.25 cm; range, 1.7–8 cm)18 than glomangiopericytoma but histologically it may resemble glomangiopericytoma, with its diffuse cellular proliferation of spindled cells effacing submucosal structures with intact surface epithelium (Figure 3, C). Also, like glomangiopericytoma, there may be zones of hypocellularity and hypercellularity with variable vasculature composed of staghorn-type and capillary-sized vessels. Perivascular hyalinization, however, is not typical. The cells are overlapping with irregular nuclear contours and are arranged more haphazardly than in glomangiopericytoma, with no distinct growth pattern. Prominent coarse collagen bundles, not seen in glomangiopericytoma, are present and the neoplastic spindle cells are intimately associated with the stromal collagen (Figure 3, D). Unlike glomangiopericytoma, the neoplastic cells stain positively for CD34, with less consistent actin staining. Sinonasal SFT is less likely to be malignant than its soft tissue counterpart, with a low recurrence rate and only rare metastases.18 

Leiomyomas may occur in the sinonasal tract but are very uncommon, accounting for fewer than 1% of nonepithelial sinonasal neoplasms.19 They affect a broad age range (20–67 years) but middle-aged adults (mean age, 40 years) are most frequently affected, with a slight female predominance (male to female ratio, 1∶1.5).20 Like glomangiopericytoma, these lesions can be vascular, with staghorn-type and capillary-sized vessels and an associated cellular spindle cell proliferation (Figure 3, E). At low-power magnification there are some distinguishing features in that leiomyomas appear more eosinophilic and often exhibit prominent fascicular growth. The low-power features of eosinophilia are due to abundant eosinophilic fibrillary cytoplasm. The nuclei also tend to be more elongated and have coarser chromatin with occasional perinuclear vacuoles (Figure 3, F). Desmin staining is typically strongly positive in these tumors, which helps to separate them from glomangiopericytoma. Clinically, they have a favorable prognosis and rarely recur after complete excision.20 

Angiofibromas (previously juvenile nasopharyngeal angiofibroma) occur almost exclusively in adolescent males but, rarely, can occur in adults.21 These benign vascular mesenchymal neoplasms arise in the posterolateral nasal cavity near the sphenopalatine foramen. They can grow to large sizes, with bone erosion and intracranial extension, and are often difficult to resect. Histologically, they are vascular tumors with large ectatic vessels, which give rise to progressively smaller capillary-sized vessels. Low-power magnification reveals a more eosinophilic appearance than seen in glomangiopericytoma, as there is abundant stromal collagen present (Figure 3, G). The cells of angiofibroma are bland, evenly spaced, stellate cells with vesicular chromatin and are intimately associated with collagen fibrils (Figure 3, H). The clinical scenario, relative paucicellularity, and stromal collagen will allow distinction from glomangiopericytoma. Immunohistochemical stains for androgen receptor22 and β-catenin23 will stain the nuclei of angiofibromas, which can be helpful in separating them from glomangiopericytoma in challenging cases. These tumors are benign, with a 5% to 10% recurrence rate, but can be locally aggressive, with rare patients dying of progressive tumor growth, typically those with intracranial extension.21 

In conclusion, glomangiopericytoma is an uncommon, indolent, unique sinonasal neoplasm of older adults with a perivascular myoid phenotype that differs from traditional soft tissue “hemangiopericytoma” in location, biologic behavior, and morphology. Characteristic histologic features include a diffuse, subepithelial, cellular proliferation of bland, spindled cells and a distinctive vascular network composed of variably sized vascular channels, some with perivascular hyalinization. Entities such as lobular capillary hemangioma, solitary fibrous tumor, sinonasal leiomyoma, and angiofibroma are commonly confused with this lesion. It is important to recognize glomangiopericytomas as they tend to behave in a benign fashion, rarely warranting aggressive treatment beyond local excision.