Case 4 -

Anaplastic Hemangiopericytoma, WHO Grade III Eyas M. Hattab, Indiana University, Indianapolis, IN

Click on slide thumbnail images for an enlarged view.

If you have any difficulties viewing these slides, email the webmaster.

Introduction: A 75-year-old man with a past medical history of metastatic "deltoid sarcoma" status post resection, who presented with a 2-month history of right-sided upper extremity weakness. He also complained of pain and swelling over the midline of his head while combing his hair. MRI, with and without contract, was performed and demonstrated a 6.4 x 2.5 x 4.5 cm extra-axial, avidly enhancing lesion centered at the left parafalcine frontoparietal region extending across the midline posteriorly. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: H&E sections demonstrate a hypercellular spindle cell neoplasm penetrated by a rich network of branching, dilated, and congested "staghorn" blood vessels. The tumor cells are arranged in short bundles, small sheets or poorly formed storiform pattern. The spindle cells are characterized by large, pleomorphic, hyperchromatic round to oval nuclei, many with prominent nucleoli and moderate amount of pale eosinophilic cytoplasm. Mitoses, including atypical forms, are easy to find, with up to 30 mitoses per 10 high power fields and apoptotic bodies are numerous. Occasional multinucleated giant cells are seen. Geographic areas of hemorrhage and necrosis are also noted. The tumor cells are diffusely immunoreactive for vimentin, CD99 and Bcl-2 but negative for S100, cytokeratin cocktail, epithelial membrane antigen (EMA), CD34, smooth muscle actin (SMA), and C-kit. A silver impregnation for reticulin displays a rich reticulin network with fibers wrapping around groups of and individual tumor cells. Case 4 - Figure 1 Sagittal and axial T1-weighted images showing an extra-axial, homogenously enhancing, dural-based mass in the parietal parafalcine region (T1 with contrast). Case 4 - Figure 2 Low power microscopic image showing a cellular spindle cell tumor with abundant dilated "staghorn" blood vessels distended by blood (hematoxylin and eosin). Case 4 - Figure 3 A medium power view illustrating the somewhat haphazard arrangement of the tumor cells around the branching thin-walled blood vessels (hematoxylin and eosin). Case 4 - Figure 4 Zones of geographic necrosis, including infiltration by macrophages, were widely present (medium power, hematoxylin and eosin). Case 4 - Figure 5 Areas of hemorrhage and necrosis (medium power, hematoxylin and eosin). Case 4 - Figure 6 The spindle shaped tumor cells are irregularly arranged surrounding branching capillaries. Note the tumor cell necrosis on the right (high power, hematoxylin and eosin). Case 4 - Figure 7 The tumor cell nuclei showing overlap, hyperchromasia and apoptosis (high power, hematoxylin and eosin). Case 4 - Figure 8 Irregular bundles of tumor cells with the tumor cell nuclei exhibiting prominent nuclear atypia, including giant multinucleated cells (high power, hematoxylin and eosin). Case 4 - Figure 9 Note the frequent mitoses, including an atypical tripolar form (left) (high power, hematoxylin and eosin). Case 4 - Figure 10 This tumor is characterized by a rich network of intercellular reticulin deposition (medium power, silver impregnation, reticulin) Case 4 - Figure 11 A diffuse immunoreactivity for Bcl-2 was noted (medium power, Bcl-2 immunostain). Case 4 - Figure 12 The tumor cells were also immunoreactive for CD99 (medium power, CD99 immunostain). Case 4 - Figure 13 An immunohistochemical stain for CD34 highlights the branching capillaries but fails to stain the tumor cells (medium power, CD34 immunostain). Case 4 - Figure 14 The tumor cells were negative for smooth muscle actin (high power, SMA immunostain). Differential Diagnoses: Hemangiopericytoma Solitary fibrous tumor Meningioma Monophasic synovial sarcoma Meningeal fibrosarcoma Leiomyosarcoma Final Diagnosis: Anaplastic hemangiopericytoma, WHO grade III Case Discussion: The term "hemangiopericytoma" was coined by Stout in 1942, describing a soft tissue tumor of a presumed vascular origin [1]. The earliest report of a dural-based hemangiopericytoma is attributed to Harvey Cushing [2]. However, this group of tumors was described as a variant of meningioma and hence they were referred to as "angioblastic meningioma." The advances in immunohistochemical and molecular studies over the past few decades has greatly aided in the appropriate classification of this subset of dural-based tumors as a form of mesenchymal tumor (ie, sarcoma) based on its aggressive clinical behavior and metastatic potential. The cell of origin of hemangiopericytoma is unknown, but several theories have been suggested. It has been posited that the cell of origin may be a meningeal capillary pericyte, a Zimmerman pericyte, or a precursor cell with angioblastic tendencies [3]. Grossly, hemangiopericytomas are well- circumscribed, globoid lesions with a firm consistency and reddish brown color, which reflects their vascular nature. Microscopically, hemangiopericytoma is usually composed of haphazardly arranged relatively small cells with spindled to oval nuclei and scant eosinophilic cytoplasm. Scattered thin-walled branching vessels, classically described as "staghorn" vessels, are characteristic and required for the diagnosis but not pathognomonic. These neoplasms often display a duplicitous pattern of cellularity, with the pattern described above, adjacent to paucicellular myxoid areas [4]. Historically, these tumors were uniformly classified as WHO grade II tumors, but recently it has been noted that certain histologic features are associated with a poorer prognosis and thus an anaplastic (WHO grade III) variant is now recognized. Anaplastic hemangiopericytoma is defined by at least 5 mitosis per high power field and/or necrosis, plus at least two of the following: hemorrhage, moderate to high nuclear atypia, or moderate to high cellularity [5]. In addition to the morphological characteristics associated with this neoplasm, consistent structural abnormalities in areas 13– 15 of chromosome 12 have also been noted. The significance of this molecular abnormality is currently unknown. Also of note is that NF2 mutation, which is common in meningiomas, is lacking [6]. Epidemiologically, hemangiopericytoma represents 15% of spinal tumors, 2–4% of all dural-based tumors, and 0.4% of all primary CNS tumors. It is more common in males, with the mean age of onset being 43 years [7]. Clinically and radiographically, hemangiopericytoma is often indistinguishable from meningioma. Hemangiopericytoma may present in a more rapid fashion than meningioma, due to its faster growth rate with the most common presenting complaints being headache and focal deficits. Seizures are the presenting symptom in 16% of cases. Rarely, these tumors can also present with intracranial hemorrhage [8]. On MRI, hemangiopericytomas usually are homogeneously enhancing and isointense on T1 and T2, with a tail-like attachment to the dura. They typically do not invade the parenchyma, but may show areas of bony erosion. These lesions tend to occur supratentorially, most often in the occipital region. Angiographic evaluation may show the hypervascularity of the tumor. Although, this lesion may appear identical to meningioma on imaging and clinical evaluation, it is important to remember that hemangiopericytoma behaves much differently in terms of recurrence and metastasis, making long-term followup exceedingly important [9]. In addition to meningioma, histologically, the differential diagnosis also includes solitary fibrous tumor. When malignant features are present, one needs to entertain the possibility of other forms of primary meningeal sarcomas such as monophasic synovial sarcoma, meningeal fibrosarcoma, and leiomyosarcoma or occasionally metastases. Special and immunohistochemical staining may be helpful in differentiating these entities. Unlike most meningiomas (meningiomas of the fibrous type occasionally display reticulin), hemangiopericytomas are characterized by a rich intercellular and pericellular reticulin deposition. Furthermore, meningiomas are invariably epithelial membrane antigen positive and often progesterone receptor positive [5]. Solitary fibrous tumors are the most similar to hemangiopericytoma; they are believed by many to represent the opposite end of the hemangiopericytoma-like tumors spectrum [10]. While most soft tissue tumor experts are "lumpers," within the CNS, most advocate for separating solitary fibrous tumor from hemangiopericytoma whenever possible. In general, solitary fibrous tumors are histologically low grade; classically, have thick bands of collagen intervening between tumor cells; and are, by definition, CD34-immunoreactive. The solitary fibrous tumor/hemangiopericytoma debate is unlikely to be settled soon but one needs to be aware of their intimately overlapping features. It should be noted that the same histologic features that make hemangiopericytoma anaplastic are also the features that predict poor outcome in solitary fibrous tumors [5]. Review of the Literature/Treatment Options (if applicable): Hemangiopericytoma is a malignant neoplasm by virtue of its metastatic potential and tendency for aggressive local recurrence; it should be treated as such, with a multimodality approach and a lifetime of followup. The principles of surgery entail the goal of gross total resection if this can be performed without causing significant morbidity. Preoperative embolization is also an option and can effectively reduce the vascularity of these tumors to prevent large amounts of blood loss, which can complicate surgical removal. It may also result in shrinking the tumor to aid in gross total resection. Radiosurgery has also been reported to be an effective means of control [11]. Survival rate after the first operation is 60 months on average with the 5-year, 10-year, and 15-year rates of overall survival being 67%, 40%, and 23%, respectively. The most devastating occurrence that shortens survival is the presence of extraneural metastasis. When metastases were found, the average survival was 24 months after discovery. The rates of metastasis at 5-years, 10-years, and 15-years were 13%, 33%, and 64%, respectively [11].It should be noted that after gross total resection, there can be prolonged periods of tumor-free survival, but the patient have a lifetime risk of metastasis. Whether or not the patient receives postoperative radiation is also an important prognostic indicator. Recurrence rates on average are 90 months after surgery with radiation and 29 months without it. In addition to metastasis, these tumors often recur years after resection. Five-year recurrence rates are as high as 60%, and 15-year recurrence rates are as high as 87%. It should also be noted that after the first recurrence, intervals tend to decrease in time between relapses. It has also been shown that the anaplastic variant classified as WHO grade III, recurs at a much higher rate than lower grade tumors. The average time was six to seven years earlier. Despite the increased recurrence rate, it has been suggested that there is no significant difference in survival between grade II and grade III tumors [11]. Conclusion(s): In conclusion, it can be gleaned that hemangiopericytoma is essentially identical to meningioma in its clinical and radiographical appearance. Because of the adverse prognostic implications of the diagnosis of hemangiopericytoma, pathologic distinction from meningioma is paramount. Fortunately, given the advances in immunohistochemical studies, the diagnosis of hemangiopericytoma is usually straightforward. The histopathological overlap with solitary fibrous tumor is great and the relationship between solitary fibrous tumor and hemangiopericytoma remains to be fully characterized. Unlike meningioma, hemangiopericytoma has a significantly higher potential to metastasize. An anaplastic variant with a greater likelihood for recurrence is now recognized by the WHO classification of CNS tumors. Gross total resection and postoperative radiotherapy are both favorable prognostic factors. References: Stout AP, Murray MR. Hemangiopericytoma: a vascular tumor featuring Zimmerman's pericyte. Ann Surg 1942;116:26–33. Cushing H. Eisenhardt L (eds). Meningiomas: Their Classification, Regional Behavior Life History and Surgical End Results. Springfield, IL, Charles C Thomas, 1938. Horten BC, Urich H, Rubinstein LJ, et al. The angioblastic meningioma: a reappraisal of nosological problem. J Neurol Sci 1977;31:387–410. Kochanek S, Schroder R, Firsching R. Hemangiopericytoma of the meninges: histopathological variability and differential diagnosis. Zentralbl Neurochir 1986;47:183–190. Rajaram V, Brat DJ, Perry A. Anaplastic meningioma versus meningeal hemangiopericytoma: immunohistochemical and genetic markers. Hum Pathol 2004;35:1413–1418. Henn W, Wullich B, Thonnes M, et al. Recurrent t (12;19)(q13; q13.3) in intracranial and extracranial hemangiopericytoma. Cancer Genet Cytogenet 1993;71:151–154. Simpson D. The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 1957;20:22–39. Goellner JR, Laws Jr ER, Soule EH, et al. Hemangiopericytoma of the meninges: Mayo Clinic experience. J Clin Pathol 1978;70:375–380. Chiechi M, Smirniotopoulos J, Mena H. Intracranial hemangiopericytomas: MR and CT features. AJNR Am J Neuroradiol 1996;17:1365–1371. Nappi O, Ritter JH, Pettinato G, Wich MR. Hemangiopericytoma: histopathological pattern or clincopathologic entity? Semin Diagn Pathol 1995;12:221–232 Guthrie BL, Ebersold MJ, Scheithauer BW, et al. Meningeal hemangiopericytoma: histopathological features, treatment, and long-term follow-up of 44 cases. Neurosurgery 1989;25:514–522.