HEMANGIOPERICYTOMA

An electron microscopic study was made of a nasal hemangiopericytoma. Previous ultrastructural studies of hemangiopericytomas established no uniform description of these tumor cells. The ultrastructure of this tumor revealed the presence of several cellular morphological variations. The majority of tumor cells resembled pericytes. Less frequently occurring tumor cells showed features compatible with smooth muscle cells, the cytoplasm being filled by bundles of fibrillar material and dense bodies. Numerous cells of transitional morphology between pericytes and smooth muscle cells were also present. The concept that pericytes are a transitional form from mesenchymal cell to smooth muscle cell is discussed.

January 1970, with a 3-week history of nasal obstruction and epistaxis. A dark red, smooth-surfaced mass extended from the left choanae to the vestibule and occluded the internal nares. T h e left nasal cavity was distended, and the septum was deviated to the right. Roentgenograms showed increased density in the left nares with normal paranasal sinuses.
In February 1970, a snare was employed to remove the poIypoid mass which arose above the left middle turbinate area. Most of the tumor was removed as a large, 6 x 2 x 1 cni, soft, rubbery, red mass along with several smaller fragments. Blood loss was estimated to be 85 nil. T h e tissue diagnosis was hemangiopericytoma.
Postoperative tomographs and thermographs a t 1 month and 4 months were unremarkable.
In August 1970, a small polypoid mass located 1 cm anterior to the choanal orifice and attached above the left middle turbinate by a base about 0.5 cm in diameter was noted. TIie 2.5 x 1.5 cm, soft, rubbery, pink-gray tumor mass was removed with a snare. T h e tissue diagnosis was hemangiopericytoma, and the tumor was considered to represent local recurrence.

MATERIAI s A N D METHODS
T h e nasal polyp was fixed in neutral-buffered 10% formaldehyde solution, and paraffin-embedded sections were stained with hematoxylin and eosin, reticulin stain, aldeliyde fuchsin, PAS, and Masson's trichrome.
Forty-eight hours after the polyp had been 256 CANCER January 1973 Tumor cell borders were prominent, and each cell had the same uniform round-to-oval shape. T h e cytoplasm stained lightly eosinophilic. T h e cellular density of the tumor varied from very denoe in most areas to loosely packed tumor tells separated by reticulumpositive amorphouq homogeneous material. Rare mitotic figures were seen. Several necrotic hemorrhagic areas were present.
Electron microscopy revealed the vascular spaces to be lined by a single layer of endothelial cells which was surrounded by basement membrane on the side opposite the lumen ( Fig. 3, 4). These appeared to be normal enclothelial cells with fine fibrils, sparse endoplasmic reticulum, numerous free ribosomes, and a few large oval mitochondria. T h e cytoplasmic border opposite the vascular lumen showed prominent pinocytosis.
T h e intercellular material of the tumor was granular and slightly osmiophilic and contained random collagen fibrils paralleling the long axis of the tumor cells (Fig. 3).
Tliroughout the tumor, cells appeared which were intermediate in both size and cytoplasmic complexity to the pericyte-like cells and smooth muscle cells.
T h e more numerous form of tumor cells was large, oblong or oval, with smooth cytoplasmic borders, and was quite comparable to normal pericytes (Fig. 5). T h e nucleus was oblong or oval, arranged longitudinally in the cell, and had even, regular borders and only a rare indentation or irregularity. Numerous round-to-oval mitochondria were present, many of which showed only the double outer membrane with some glycogen in tlie vacant central portions. Abundant free ribosomes antl granular entloplasmic reticulum were noted. Golgi apparatus was present but not prominent. Many cells contained numerous randomly dispersed fine filaments which were smaller antl more delicate than those seen in tlie entlotlielial cells. Each cell was wholly separated from neighboring tumor cells by an investing basement membrane and in more loosely packed areas by intercellular matrix as well. T h e intercellular matrix was most prominent about vessels separating the sheets of tumor cells from endothelium, except for rare areas where tumor cells and endothelial cells were separated only by their basement membranes.
A minority of tumor cells were comparable to smooth muscle cells. These cells were characterized by more darkly staining cytoplasmic matrix antl more angulated indented nuclei than tlie more numerous tumor cell type. T h e cytoplasmic borders showed more irregularities and indentations. In some cells, prominent cytoplasmic vacuoles contained glycogen-like material. Bundles of fibrillar material in the cytoplasm were associated with structures resembling the dense bodies found in smooth muscle cells. This fibrillar material accounted for darkly staining cytoplasm. T h e nucleus showed scattered clumps and peripheral condensation of chromatin.
Cells appeared throughout the tumor which were intermetliatc in both size and cyto-,.plasmic complexity to the pericyte-like cell and smooth muscle cells. These transitional forms contained varying amounts of fibrillar bundles which were concentrated in the periphery of the cell. T h e perinuclear area was filled with mitochondria, abundant free ribosomes, antl granular endoplasmic reticulum. T h e nuclei tended to have greater peripheral clumping and condensation of chromatin than the pericytes. All cells were invested by a basement membrane.
Numerous mast cells were observed near capillaries and did not possess a basement membrane. No neural elements were noted.
T h e tumor recurrence was histologically similar to the original. T h e intercellular matrix of the recurrence contained increased amounts of collagen. Basement membranes enveloped the tumor and endothelial cells but were absent from the mast cells and fibroblasts (Figs. 3, 4).

DISCUSSION
T h e diagnosis of hemangiopericytoma depends upon its histologic differentiation among tumors of vascular origin and from highly vascular soft tissue tumors. Tumors exhibiting histologic similarity, and thus confusion, include glomangioma, hemangioendothelial sarcoma, undifferentiated or metastatic carcinoma, vascular leiomyoma, leiomyoblastoma, treated malignant melanoma, and vascular portions of fibrosarcoma.
A specific diagnosis of hemangiopericytoma is important because the tumor is locally aggressive and infiltrative.' Five of the 25 cases reported by Stout recurred one or more times because of incomplete excision.13 Malignant hemangiopericytomas exist, and hematogenous dissemination predilects involvement of lungs and skeletal system.l~J~9.*:l However, no firm histologic criteria can distinguish these malignant tumors.13 When Stout and Murray first proposed the pathologic entity hemangiopericytoma, they emphasized the following two prerequisites for the diagnosis: 1. Endothelial cells must retain their normal appearance and be separated from pericytes by a fibrous sheath, and 2. the proliferating tumor cell milst be a pericyte.14 While the first criteria may be met convincingly with a reticulin stain, the second is more difficult to establish. T h e nature and function of the pericyte was largely unknown then, and identification by morphology is difficult indeed because the cell has few morphological features to distinguish it from endothelial cells, fibroblasts, or so-called primitive mesenchymal cells. Ultrastructural studies of normal pericytes3,5-7.** show them to be completely surrounded by basement membrane except for occasional small areas of contact either with other pericytes or endothelial cells.
There are frequent small densities along the cytoplasmic aspect of the plasma membrane which are associated with bundles of fine fibrils.7.12 T h e cytoplasmic components have been described as indistinguishable from those of endothelial cells,G and similar to those of fibroblasts,l2 while others have clearly distinguished them from these and other cell All agree that there is a clear cytoplasmic matrix, that the few mitochondria are large and oval to elongate, that there is an abundant supply of free ribosomes, that the Golgi complexes are prominent, that fine filaments occiir singly or in small bundles widely scattered throughout the cytoplasm, and that pinocytotic vessels may be observed along the cell membrane.
From these studies, then, the pericyte emerges as a somewhat bland cell distinguished by the presence of an enveloping basement membrane, the small fibrils in the cytoplasm, and the pinocytotic vesicles along the plasma membrane.
T h e origin and function of these cells is unclear. It has been proposed that the pericyte takes its origin from primitive mesenchymal cells.l2 Numerous speculations concerning the role of the pericyte exist.ZJ2 Rhodin speculates that the pericyte synthesizes both its own basement membrane and nearby collagen fibers, that it provides mechanical support for capillaries, and that it serves as the precursor cell that may transform into smooth muscle cells.'* Recently, Crocker has proposed that pericytes also act as a regulatory mechanism for capillary proliferation via "contact inhibition."* Previous ultrastructural studies of hemangiopericytoma have not established uniform criteria for tumor recognition.8f10q11 Tumor cells have been alternately described by some as being uniform in sliapell and by others as showing extreme variation in size and shape.8 Basement membrane around tumor cells was not identified in some instances.s~IOJ1 N o cytoplasmic fibrils or pinocytotic vesicles were present, but all tumor cells were separated from a normal endothelium by intercellular matrix containing collagen fibrils.
This study, however, shows that most of the cells of this tumor are quite comparable to pericytes, and supports the concept of hemangiopericytoma as a valid histologic tumor type. However, in this tumor, there exists a gradation of cytoplasmic differentiation from rather bland organelle-poor pericyte type to those cells with increasing numbers of fine cytoplasmic fibrils. This seems to support Rhodin's proposition of a "primitive smooth muscle cell" which represents a transitional form be- tween pericytes and smooth muscle cells. The pericytes are located along venous capillaries antl post-capillary venules and gradually give way to these primitive smooth muscle cells which are likewise replaced by smooth muscle cells as the vessels become larger and larger.I2 This concept, we feel, may explain the presence in this case of many tumor cells which are morphologically identical to pericytes and the presence of some cells which show increasing numbers of cytoplasmic fibrils mimicking the first step of differentiation from pericytes to smooth muscle cells. This very hypothesis was used by Stout as an explanation for the "marked and confusing variations" in this tumor entity he first described in 1942. 14