Hemangiopericytoma

* Two cases of nasal tumors with pericytic myoid differentiation are reported. The tumors occurred in a 77-yearold woman and a 60-year-old man as polypoid lesions covered by normal mucosa. Histologically, the tumors were composed of uniform short spindle or stellate cells with indistinct cell borders arranged in narrow and short fascicles. Numerous blood vessels of various sizes were common in both cases. The tumor cells of both cases stained intensely with anti-vimentin and anti-actin antibodies, but not with anti-desmin, CD34, or anti-high-molecularweight caldesmon antibodies. Ultrastructural examination revealed well-developed actin thin filaments with dense bodies, subplasmalemmal plaques, intercellular junctions, and irregular discontinuous basement membranes. These histopathologic features suggest true pericytic differentiation of the tumors (true hemangiopericytoma), unlike soft tissue-type hemangiopericytoma. Generally, sinonasal hemangiopericytomas are subdivided into soft tissue-type hemangiopericytomas and true hemangiopericytomas identical to the cases presented here. Soft tissue-type hemangiopericytomas are frequently highly aggressive, whereas true hemangiopericytomas show localized benign behavior. Sinonasal true hemangiopericytomas should be strictly differentiated from soft tissue-type hemangiopericytomas.

(Arch Pathol Lab Med. 2001;125:686-690)

Since first reported by Stout and Murray,1 hemangiopericytomas have been accepted as soft tissue tumors with distinct clinicopathologic features. They are characterized as benign or malignant, round to spindle cell tumors with numerous "staghorn" branching vascular channels? Another characteristic is the difficulty encountered in predicting their clinical behavior.1-4 The cellular differentiation of hemangiopericytomas has been questioned recently, because they commonly lack the immunohistochemical and electron microscopic differentiation properties of pericytes.5-8 Indeed, the hemangiopericytoma-like pattern is a nonspecific feature observed in various soft tissue tumors.9 Thus, hemangiopericytoma has become a nonspecific diagnosis rather than a specific concept indicating cellular differentiation.

Sinonasal hemangiopericytomas, which were also described by Stout,3 are thought to be distinct from hemangiopericytomas of the soft tissues because of their excellent prognosis and uniform cellular features.10 Compagno et al 10 described this entity as "hemangiopericytomalike tumor" as early as 1976, and Fletcher8 recently pointed out that sinonasal hemangiopericytomas are tumors with true pericytic myoid differentiation distinct from soft tissue hemangiopericytomas.

In this article, we present 2 cases of nasal hemangiopericytoma with conspicuous pericytic myoid differentiation, which seem to be intimately related to perivascular myoma. We also review cases reported previously as sinonasal hemangiopericytoma, hemangiopericytoma-like tumor, and glomus tumor and attempt to classify these cases into distinct clinicopathologic entities.

MATERIALS AND METHODS

Tissue specimens from 2 patients were fixed in formalin, embedded in paraffin, and stained with hematoxylin-eosin and silver impregnation stain. The streptavidin-biotin-peroxidase complex method (SABC kit, Dako, Kyoto, Japan) was used for immunohistochemistry. The primary antibodies and their final dilutions were anti-desmin (1333, Dako, 1:50), anti-smooth muscle actin (Dako, 1:200), anti-muscle actin (HHF-35, Enzo Diagnostics, New York, NY, 1:8000), CD34 (NU-4A1, Nichirei, Tokyo, Japan, 1:100), and anti-high-molecular-weight caldesmon (Dako, 1:50). Microwave pretreatment was performed for desmin and high-molecular-weight caldesmon analyses. The nuclei were counterstained with hematoxylin. Fresh tissue from case 1 was fixed in 2% glutaraldehyde and then embedded in epoxy resin. Ultrathin sections were stained with uranyl acetate and lead citrate and were observed using a JEM 1200EX transmission electron microscope (JEOL Ltd, Tokyo, Japan).

REPORT OF CASES

Case 1

A 78-year-old woman was admitted to the hospital complaining of right nasal obstruction and hemorrhage. Rhinoscopic examination disclosed a slightly red polypoid tumor covered by mucosa. The tumor grew slowly, and 3 months after her first admission a polypectomy was performed. The tumor arose from the right nasal septum and was extirpated together with neighboring normal mucosa. The tumor was approximately 25 mm in its maximum length. This was a recent case, and as of 4 months' follow-up there had been no recurrence.

Case 2

A 60-year-old man was admitted to the hospital with a complaint of nasal hemorrhage. A right nasal polyp arising from the septum was observed under the rhinoscope. The polyp was extirpated piece by piece. The tumor recurred 1 year later and was re-extirpated with neighboring normal mucosa. The histology of the recurrent tumor was unchanged from that of the primary tumor. The patients postoperative course has been uneventful for 8 years.

PATHOLOGIC FINDINGS

Microscopic Findings

Both tumors exhibited polypoid growth covered by normal respiratory epithelium (Figure 1). The tumors were composed of uniform, rather eosinophilic short spindle or small stellate cells with indistinct cytoplasmic borders (Figures 2 and 3). The round to oval, uniform nuclei did not show atypia. The spindle cells tended to be arranged in short narrow fascicles. In case 1, concentric cellular configurations were occasionally seen (Figure 1). The tumors were rich in thin or dilated venule-like vessels, but staghorn-like vessels were rarely seen. There was sparse infiltration of a few lymphocytes and mast cells. Mitoses were rare and were seen only in case 1. Although silver impregnation stain disclosed numerous reticulum fibers between the tumor cells, they were thin and delicate and did not surround the individual cells clearly.

Immunohistochemistry

Both tumors were diffusely positive for vimentin. ax-Smooth muscle actin and muscle actin (HHF-35) were also diffusely immunolabeled in both tumors, except for the concentric cellular area seen in case 1 (Figure 4). Neither tumor was positive for desmin, CD34, or high-molecular-weight caldesmon.

Electron Microscopy

Ultrastructurally, there were 2 cell types: spindleshaped cells and stellate cells. Cells surrounding the blood vessels were clearly separated by basement membrane from nonneoplastic endothelial cells. Occasionally, stellate cells formed a concentric configuration, as seen by light microscopy. The spindle tumor cells had many mitochondria, free ribosomes, and rough endoplasmic reticulum and were surrounded by discontinuous, irregularly thickened basement membrane. Characteristically, they contained a bundle of microfilaments with fusiform dense bodies and subplasmalemmal plaques (Figure 5). In contrast, the stellate tumor cells in the circular concentric structure had numerous cytoplasmic processes and mitochondria, and scattered Golgi apparatus. Although microfilaments were inconspicuous in these cells, perinuclear bundles of intermediate filaments were evident. Well-developed intercellular junctions were observed in both cell types. Pinocytotic vesicles were not observed.

COMMENT

Recently, Granter et al 11 described distinctive tumors showing perivascular proliferations of small spindle and round cells with myoid differentiation as "perivascular myomas." They subdivided the tumors into myofibromatosis, glomangiopericytoma, and myopericytoma types, but these forms are interrelated and frequently indistinguishable. Perivascular myomas exhibit a broad histologic spectrum, from hemangiopericytoma-like or glomus tumor-like to angioleiomyoma-like, and it is speculated that they differentiate along the lines of smooth muscle, pericytic, and glomus cells. Immunohistochemically, perivascular myomas are stained frequently with anti-actin antibodies and rarely with anti-desmin antibodies, according to their degree of cellular differentiation.11

The tumors presented here, one of which was examined by electron microscopy, are thought to belong to a lineage above perivascular myoid cells, based on their features such as small spindle or stellate cells, abundance of various-sized blood vessels, intense immunoreactivity for cxsmooth muscle actin, and well-developed bundles of microfilaments with dense bodies. Furthermore, these tumors are distinctive in the sense that under light microscopy they are composed of more uniform tumor cells, lacking glomus tumor or myofibroblastic-like differentiation. These characteristics suggest that such tumors may be a pure form of hemangiopericytoma, which is thought to be situated at one end of the broad spectrum of perivascular myomas.

Stout, together with Murray,1,3 first reported hemangiopericytomas and noticed their great variety of cellular and structural features. This variety was explained by the hypothesis that pericytes are related to smooth muscle cells, and therefore hemangiopericytomas can consist of cells that are incomplete smooth muscle-like to epithelioid glomus tumor-like.3 However, it has become clear that hemangiopericytoma-like features are encountered in various soft tissue tumors and that soft tissue hemangiopericytomas generally lack pericytic differentiation, both ultrastructurally and immunohistochemically.5-7 Thus, hemangiopericytomas now tend to be recognized as heterogeneous tumors with various cellular differentiation.

Although hemangiopericytomas arising from sites other than soft tissues are rare,1,3,4 more than 60 cases of sinonasal hemangiopericytoma have been described in the literature since the first report by Stout.3,9,10,12-26 Because sinonasal hemangiopericytomas are frequently composed of more uniform, smaller cells and show excellent prognosis compared with the soft tissue types, it has been suggested that they may be distinct from soft tissue hemangiopericytoma. Compagno et a11 used the designation hemangiopericytoma-like tumor as early as 1976. In contrast, based on ultrastructural and immunohistochemical findings, Eichhorn et a126 suggested that nasal hemangiopericytoma does not differ from similar tumors in other locations. However, they observed focal smooth muscle actin immunoreactivity in nasal tumors, suggesting myoid differentiation, which is exceptional in soft tissue hemangiopericytomas.26 Recently, Fletcher- concluded that sinonasal hemangiopericytoma is the only tumor showing convincing pericytic differentiation among the hemangiopericytomas that arise in adulthood.

We reviewed the cases of sinonasal hemangiopericytomas reported previously in the literature 3,9,10,12-26 and found at least 3 histologic subtypes. The first subtype consists of tumors that are identical to soft tissue hemangiopericytomas composed of rather plump spindle cells with various degrees of nuclear atypia. At least 6 cases reported by Stout,3 Murashima,12 Lenczyk et al,15 Benveniste et al,19 Gudrun,22 and Tsuneyoshi et al,9 and some of the 11 cases reported by Eichhorn et al,26 appear to be of this type (Table). Myoid differentiation was not confirmed in this type as well as in the soft tissue-type hemangiopericytomas. As expected, the tumors in these cases were frequently aggressive, and fatal cases were not uncommon.3,9,12,15,19,22 Very recently, intimate relationships between hemangiopericytoma and solitary fibrous tumor have been reported. It is important to differentiate these tumors, because most solitary fibrous tumors of the soft tissue are benign. CD34 is an extremely useful marker for this purpose.27,28

The second subtype includes true hemangiopericytoma tumors, similar or almost identical to the present cases, which are composed of uniform spindle or stellate cells and which exhibit various degrees of myoid differentiation mimicking normal pericytes.7,29 Previously reported cases that seem to be of the true hemangiopericytoma type, based on the histologic descriptions and microphotographs, are summarized in the Table.10,24,26 Compagno et al10 analyzed the largest series, which included 23 cases. Although immunohistochemical and electron microscopic examinations were not included in their study, we believe most of these cases are of the true hemangiopericytoma type, based on their distinctive uniform histologic features. We think that at least 1 (case 8) of the 11 cases described by Eichhorn et al 26 also is of true hemangiopericytoma type, because of its histologic features and actin immunopositivity. Although some of 10 cases reported by Gorenstein et al also seem to be perivascular myomas, unfortunately the clinical details are unclear. One case reported by Batsakis et al 24 is a convincing case of true hemangiopericytoma from the clearly depicted light and electron microscopic features showing well-developed myofilaments with dense bodies, as pointed out by Fletcher.8 These tumors occasionally recur locally, but no case with an adverse outcome has been reported.

The third subtype consists of tumors intimately related to glomus tumors. Sinonasal glomus tumors are extremely rare, and only 6 cases have been reported in the English literature to date, excluding the paragangliomas reported as glomus tumors in an old series.18,30-M The histology ranges from a typical glomus tumor composed of compact epithelioid cells to tumors indistinguishable from perivascular myoma.31,32,34 In contrast, some tumors reported as sinonasal hemangiopericytoma seem to closely resemble glomus tumor.20 Glomus and glomuslike tumors and true hemangiopericytomas, if not identical with respect to degree of myoid differentiation as judged by electron microscopy,7 are likely to belong to one cellular spectrum. In their biological behavior, these tumors seem to be almost benign, like true hemangiopericytoma. Recently, glomus tumors of the soft tissue were demonstrated to constantly express high-molecular-weight caldesmon, which does not exist in normal pericytes.35,36 It may be useful to analyze the differences between glomus tumors and pericytic tumors in the future.

In summary, the immunohistochemical and ultrastructural features of 2 cases of nasal hemangiopericytoma are described. They are identical to tumors formerly reported as hemangiopericytoma-like tumors and are thought to be true hemangiopericytomas. So-called sinonasal hemangiopericytomas reported in the past include different histologic types, and sinonasal true hemangiopericytoma should be differentiated from soft tissue-type hemangiopericytoma because of its far better prognosis.

References

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35. Watanabe K, Kusakabe T, Hoshi N, Saito A, Suzuki T. h-Caldesmon in leiomyosarcoma and tumors with smooth muscle cell-like differentiation: its specific expression in the smooth muscle cell tumor. Hum Pathol. 1999;30:392-396.

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Kazuo Watanabe, MD; Atsuko Saito, MD; Masahiro Suzuki, MD; Shu Yamanobe, MD; Toshimitsu Suzuki, MD

Accepted for publication October 19, 2000.

From the Pathology Division, Fukushima Medical University School of Medicine Hospital, Fukushima, Japan (Drs Watanabe and T. Suzuki); and the Divisions of Pathology (Dr Saito) and Otolaryngology (Drs M. Suzuki and Yamanobe), Jusendo General Hospital, Koriyama, Japan.

Reprints: Kazuo Watanabe, MD, Pathology Division, Fukushima Medical University School of Medicine Hospital, 1 Hikariga-oka, Fukushima City, 960-1295, Japan (e-mail: w-kazuo@fmu.ac.jp).

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