Hemangiopericytoma

* Hemangiopericytoma of soft tissue is a controversial pathologic entity. The relative nonspecificity of the characteristic branching capillary pattern and cytologic features of the constituent cells, in addition to the lack of a distinct immunohistochemical staining profile, has resulted in uncertainty and a lack of consensus regarding this subgroup of tumors. Notwithstanding the doubt surrounding this entity, a morphologically unique variant, designated lipomatous hemangiopericytoma, was reported in 1995. To our knowledge, there have been no further reports of these tumors since the original description. We describe a lipomatous hemangiopericytoma that arose within the thigh of a 41-year-old woman. The tumor presented as a slowly enlarging, minimally tender, pulsatile mass. The tumor was completely excised and was found to be composed of an admixture of typical hemangiopericytoma and predominantly mature adipose tissue. Unlike previous descriptions of this entity, the current example exhibited a full range of adipocyte differentiation, including many multivacuolated adipocytes of variable size with characteristic nuclear scalloping (lipoblast-like cells). The mitotic count was less than 2 per 10 high-power fields examined. The clinical course has been benign during the short follow-up period. We discuss the pathologic features, including the immunohistochemical staining profile and ultrastructural appearance of this distinctive tumor, and briefly discuss the relationship between hemangiopericytoma and solitary fibrous tumor of soft tissue, a neoplasm with many clinical and pathologic similarities.

(Arch Pathol Lab Med 1999;123:941-945)

The concept of hemangiopericytoma as a diagnostic enti has been controversial since its original description by Stout and Murray in 1942.1 In recent years, criticism of hemangiopericytoma has been based on the recognition that a branching capillary vascular network supporting a cellular spindle cell proliferation is a rather nonspecific finding present in a variety of mesenchymal neoplasms.2,3 Additionally, there is incomplete ultrastructural and poor immunohistochemical concordance between normal pericytes and the neoplastic cells of hemangiopericytoma, further calling into question the validity of this diagnostic terminology.2-6 Notwithstanding the controversy concerning nomenclature, many pathologists acknowledge the existence of soft tissue tumors characterized by cytologically uniform spindle cells arranged in a consistent architectural pattern around a branching capillary vasculature. Although these tumors demonstrate a spectrum of ultrastructural features and a consistent, but nonspecific immunohistochemical staining profile (positive for vimentin and CD34), they are considered to represent a distinct clinicopathologic entity and are classified as hemangiopericytomas.3,7

In 1995, Nielsen et al8 reported a series of 3 previously undescribed soft tissue tumors composed of an admixture of hemangiopericytoma and mature adipose tissue. They coined the term lipomatous hemangiopericytoma for these singular neoplasms. Fletcher2 alluded to the existence of tumors with a similar appearance in a monograph in 1994, and Nielsen et al5 referenced an additional case from the German language literature in their original paper. To the best of our knowledge, however, no other reports of this morphologically unique tumor have been published. In this report, we describe a soft tissue tumor with the features of lipomatous hemangiopericytoma, as described by Nielsen et al, that was removed from the thigh of a 41-- year-old woman.

REPORT OF A CASE

A 41-year-old woman presented with a 4-month history of a slowly enlarging, minimally tender left groin mass. Past medical and family history was noncontributory. Physical examination revealed a 10-cm, warm, pulsatile, painless mass within the deep soft tissue of the proximal thigh adjacent to the left femoral neurovascular bundle. Motor and sensory examination of the limb was normal. There was no lymphadenopathy, and the remainder of the physical examination was unremarkable.

RADIOLOGIC FINDINGS

Intravenous, contrast-enhanced computerized tomography of the thigh revealed an inhomogeneous, moderately enhancing mass anterior to the femur. Scattered areas of low attenuation consistent with fat were present within the mass, as were focal regions of calcification. Selective femoral angiography showed an intensely vascular spherical mass with a blood supply arising from the profunda femoris artery (Figure 1). Slow washout of contrast was observed on the delay films. A computerized tomography-- guided biopsy was performed, followed by a wide excision of the mass.

PATHOLOGIC FINDINGS

The tumor measured 9.0 x 6.0 x 8.5 cm and was contained within the skeletal muscle of the proximal thigh adjacent to the profunda femoris artery. It was grossly well delineated, and the muscle retracted from the surface of the tumor. On cut section, the tumor was tan-white and rubbery, and had admixed, soft, grossly fatty regions (Figure 2). Microscopically, the tumor exhibited a lobular growth pattern and was composed of cellular nodules with the classic appearance of hemangiopericytoma admixed with adipocyte-rich lobules (Figures 3 and 4). In the pure hemangiopericytoma regions, the tumor cells were spindled and arranged in the typical fashion around branching capillaries. Nuclei were uniform and spindled, and the cells had scant cytoplasm. Mitotic figures were infrequent (fewer than 2 per 10 high-power fields examined). In some of the lobules, the spindle cells were more widely separated by myxoid ground substance and the supporting vasculature was less prominent. Most of the tumor lobules contained an admixture of fat and spindle cells. These regions varied from lobules composed almost entirely of mature adipose tissue to foci that exhibited scattered fat cells within otherwise typical hemangiopericytoma. In general, the greater the amount of fat within a tumor lobule, the less distinct the branching vascular pattern. The majority of the adipocytes were uniform, round, univacuolar cells with peripherally located, compressed nuclei having the appearance of mature fat cells. However, a subtle variation in adipocyte size was apparent within most of the tumor lobules, and multivacuolated small cells with nuclear scalloping were evident focally (Figure 5). We classified these cells as lipoblast-like cells. The nuclear chromatin in this population of cells was uniform, and no mitotic figures were identified in any of the fat-- containing cells. Focal areas of metaplastic bone formation were also evident (Figure 6).

Immunohistochemical stains performed on formalin-- fixed, paraffin-embedded tissue sections demonstrated positive staining for vimentin (BioGenex, San Ramon, Calif) and CD34 (Novocastra, Newcastle upon Tyne, United Kingdom) within the spindle cell nonadipocyte cells. Stains for muscle actin (Dakopatts, Glostrup, Denmark), smooth muscle actin (Dakopatts), S100 (Banting and Best Department of Medical Research, Toronto, Ontario), and desmin (Dakopatts) were negative in this population. The fat-containing cells exhibited positive staining for S100, but were negative for all the remaining antibodies.

The examined adipocytes were unremarkable on ultra-- structural examination. The multivacuolated adipocytes were not included in the sample of glutaraldehyde-fixed tissue. The spindle cells had elongated cell processes that were surrounded focally by basement membrane material. Primitive cell junctions were present between tumor cells. Occasional pinocytotic vesicles were identified. A diagnosis of lipomatous hemangiopericytoma was made. The patient has been observed for 13 months, and there is no evidence of tumor recurrence or metastasis.

COMMENT

Hemangiopericytoma originally was described by Stout and Murray in 1942. However, the diagnosis has been controversial since its inception because of the relative non-- specificity of the so-called hemangiopericytoma vascular pattern and the poor ultrastructural and immunohistochemical resemblance between the constituent tumor cells and their normal counterparts.2-6

It is well recognized that hemangiopericytoma-like vascular patterns occur in many soft tissue tumors, including synovial sarcoma, mesenchymal chondrosarcoma, and fibrous histiocytoma. Following the appreciation that solitary fibrous tumor (formerly thought to be a mesothelial neoplasm) occurs in a wide variety of anatomic sites, including the somatic soft tissues, some authors have proposed that virtually all hemangiopericytomas are in fact other neoplasms exhibiting nothing more than a characteristic growth pattern.2 These authors propose that the majority of hemangiopericytomas may in fact be solitary fibrous tumors of somatic soft tissue or deep benign fibrous histiocytomas.2 Other groups acknowledge the lack of specificity of the light microscopic appearance, ultra-- structural characteristics, and immunohistochemical staining profile of hemangiopericytoma, but they reserve the use of the term for pathologically uniform soft tissue tumors that lack evidence of alternative lines of differentiation.3,7 In essence, these investigators recognize hemangiopericytoma as a diagnosis of exclusion. We subscribe to this second approach, acknowledging that strictly speaking the appellation hemangiopericytoma may be incorrect, since there is incomplete evidence that neoplastic cells are derived from, or exhibit differentiation toward, normal pericytes.

The immunohistochemical staining profile of hemangiopericytoma and solitary fibrous tumor is remarkably similar, and it is undeniable that in selected microscopic fields the histologic appearance of these 2 entities may be identical.6 There are, however, differences between the 2 lesions. Although architectural variability is the hallmark of solitary fibrous tumor regardless of its location,9-11 the converse is true of hemangiopericytoma.12,13 The relative cellularity and proportion of extracellular myxoid ground substance in hemangiopericytoma may result in variable vascular prominence; however, capillary vessels should always form a prominent component of the architecture as viewed under low power.12,13 This characteristic is in stark contrast to solitary fibrous tumor, in which architectural variability is typical.9 Recently, Miettinen et al6 examined the genetic composition of a series of solitary fibrous tumors of the pleura and soft tissue hemangiopericytomas by comparative genomic hybridization and demonstrated that solitary fibrous tumors exhibit frequent DNA copy number changes in contrast to hemangiopericytoma. Their data suggest fundamental differences between these 2 entities. The existence of lipomatous tumors (as in our case) further supports the concept that soft tissue hemangiopericytoma is distinct from solitary fibrous tumor, since to the best of our knowledge adipose tissue has never been reported as a component of solitary fibrous tumor of the pleura or any other location.

In the original description of lipomatous hemangiopericytoma, Nielsen et al hypothesized that immature pericytes within the tumor may undergo adipocytic differentiation following a pathway that occurs in normal embryologic development and that has been observed in primitive cells in liposarcoma.8,14-16 These authors, however, cited the lack of "intermediate or transitional cells with features of both pericytes and adipocytes by light or electron microscopy" within their original tumors. We fully agree with the proposal of Nielsen et al and think that the presence of adipocyte cells exhibiting a spectrum from immature-appearing multivacuolated forms to mature univacuolar cells in our case supports their theory. We also think that the adipocyte component of lipomatous hemangiopericytoma most likely arises from the population of "pericyte" cells. The recognition that multivacuolated (lipoblast-like) fat-containing cells may be present within this distinctive variant of hemangiopericytoma is important because the potential for diagnostic confusion with liposarcoma exists with these neoplasms. In this regard, it is useful to review Weiss's criteria for the identification of diagnostic lipoblasts in the setting of liposarcoma. She emphasizes that, in the context of liposarcoma, a lipoblast must demonstrate "a hyperchromatic indented or scalloped nucleus, lipid-rich [neutral fat] droplets in the cytoplasm, [and an] appropriate histologic background."17 Chondroid lipoma and pleomorphic lipoma, both benign adipose tissue tumors that may demonstrate multivacuolated lipoblast-like cells, exemplify the importance of the third of these criteria.18,19 We believe that lipomatous hemangiopericytoma should be added to the list of benign fat-containing neoplasms that may exhibit multivacuolated lipoblast-like cells.

In our opinion, myxoid/round cell liposarcoma and dedifferentiated liposarcoma are the neoplasms that pose the greatest potential for diagnostic confusion with lipomatous hemangiopericytoma. The vasculature of hemangiopericytoma is usually more compact and branching than that of myxoid and round cell liposarcoma, and the nuclei of cells in hemangiopericytomas are typically more spindled and irregular in outline than the more uniform oval hyperchromatic nuclei that occur in the liposarcomas. Finally, immunohistochemistry should prove useful in the distinction of these lesions since hemangiopericytomas exhibit at least focal CD34 positivity within the spindle cells in contrast to the cells of myxoid and round cell liposarcoma.20

Lipomatous hemangiopericytoma should be readily distinguishable from the usual type of histologically high-grade dedifferentiated liposarcomas by the lack of high-grade nuclear atypia within the nonadipose tissue component. Distinguishing these tumors from the more recently described low-grade dedifferentiated tumors21 requires careful evaluation of the fat-containing regions of the tumor. In all subtypes of dedifferentiated liposarcoma, the low-grade liposarcoma component exhibits enlarged atypical hyperchromatic stromal cells that lack intracellular lipid, in addition to the multivacuolated lipoblasts.

Lipomatous hemangiopericytoma lacks such atypical stromal cells. Finally, although experience with low-grade dedifferentiated liposarcoma is still somewhat limited, in most examples of this tumor the dedifferentiated component of the mass has resembled fibromatosis or low-grade fibrosarcoma.21

References

1. Stout AP, Murray MR. Hemangiopericytoma: a vascular tumor featuring Zimmerman's pericytes. Ann Surg. 1942;116:26-33.

2. Fletcher CDM. Haemangiopericytoma: a dying breed? Reappraisal of an "entity" and its variants: a hypothesis. Curr Diagn Pathol. 1994;1:19-23. 3. Nappi 0, Ritter JH, Pettinato G, Wick MR. Hemangiopericytoma: histopathological pattern or clinicopathologic entity? Semin Diagn Pathol. 1995;12:

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4. Dardick I, Hammar P, Scheithauer BW. Ultrastructural spectrum of heman5. Erlandson RA. Hemangiopericytoma: a comparative study of fetal, adult and ned. Diagnostic pericytes. UlTransmission Electron Microscopy of Tumors With Pathological, Immu-154.

5. Erlandson RA. Hemangiopericytoma. In: Erlandson RA, ed. Diagnostic Correlations. New York, NY: Raven Press; 1994: Transmission Electron Microscopy of Tumors With Clinicopathological, /mmunohistochemical and Cytogenetic Correlations. New York, NY: Raven Press;1994: 413-416.

6. Miettinen MM, EI-Rifai W, Sarlomo-Rikala M, Andersson LC, Knuutila S. Tumor size-related DNA copy number changes occur in solitary fibrous tumors but not in hemangiopericytomas. Mod Pathol.1997;10:1194-1200. 7. Enzinger FM, Weiss SW. Perivascular tumors. In: Enzinger FM, Weiss SW, eds. Soft Tissue Tumors. 3rd ed. St Louis, Mo: Mosby; 1995:701-734. 8. Nielsen GP, Dickersin GR, Provenzal JM, Rosenberg AE. Lipomatous hemangiopericytoma: a histologic, ultrastructural and immunohistochemical study of a unique variant of hemangiopericytoma. Am/Surg Pathol.1995;19:748-756.

9. Chan JKC. Solitary fibrous tumor: everywhere and a diagnosis in vogue. Histopathology. 1997;31:568-576.

10. Hasegawa T, Hirose T, Seki K, Yang P, Sano T. Solitary fibrous tumor of the soft tissue: an immunohistochemical study and ultrastructural study. Am , Clin Pathol. 1996;106:325-331.

11. Suster S, Nascimento AG, Miettinen M, Sickel JZ, Moran CA. Solitary fibrous tumors of soft tissue: a clinicopathologic and immunohistologic study of 12 cases. Am I Surg Pathol.1995;19:1257-1266.

12. Angervall L, Kindblom L, Nielsen LM, Stener B, Svendsen P. Hemangiopericytoma: a clinicopathologic, angiographic and microangiographic study. Cancer. 1978;42:2412-2427.

13. Enzinger FM, Smith BH. Hemangiopericytoma: an analysis of 106 cases. Hum Pathol.1976;7:61-82.

14. Cinti S, Cigolini M, Bosello O, Bjorntorp P. A morphological study of the adipocyte precursor. Submicrosc Cytol.1984;16:243-251.

15. lyama K, Ohzono K, Usuku G. Electron microscopical studies on the genesis of white adipocytes: differentiation of immature pericytes into adipocytes in transplanted preadipose tissue. Virchows Arch B Cell Pathol. 1979;31:143-155. 16. Rossouw DJ, Cinti S, Dickersin GR. Liposarcoma: an ultrastructural study of 15 cases. Am J Clin Pathol.1986;85:649-667.

17. Weiss SW. Lipomatous tumors. In: Weiss SW, Brooks JSJ, eds. Soft Tissue Tumors. Baltimore, Md: Williams & Wilkins;1996:207-239.

18. Nielsen GP, O'Connell JX, Dickersin GR, Rosenberg AE. Chondroid lipoma, a tumor of white fat cells: a brief report of two cases with ultrastructural analysis. Am J Surg Pathol. 1995;19:1272-1276.

19. Shmookler BM, Enzinger FM. Pleomorphic lipoma: a benign tumor simulating liposarcoma: a clinicopathologic analysis of 48 cases. Cancer. 1981;47: 126-133.

20. Suster S, Fisher C. Immunoreactivity for the human hematopoietic progenitor cell antigen (CD34) in lipomatous tumors. Am I Surg Pathol. 1997;21:195200.

21. Hendricks WH, Chu YC, Goldblum JR, Weiss SW. Dedifferentiated liposarcoma: a clinicopathologic analysis of 155 cases with a proposal for an expanded definition of dedifferentiation. Am J Surg Pathol.1997;21:271-281.

Katherine M. Ceballos, MD; Peter L. Munk, MD, FRCPC; Bassam A. Masri, MD, FRCSC; John X. O'Connell, MB, FRCPC

Accepted for publication March 10, 1999.

From the Departments of Pathology (Drs Ceballos and O'Connell), Radiology (Dr Munk), and Orthopedic Surgery (Dr Masri), Vancouver General Hospital, Vancouver, British Columbia, Canada.

Reprints: John X. O'Connell, MB, FRCPC, Department of Pathology, Vancouver General Hospital, 855 W 12th Ave, Vancouver, British Columbia, Canada V5Z 1M9.

Copyright College of American Pathologists Oct 1999
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