Hemangiopericytoma
of the Meninges Mayo Clinic Experience
JOHN R. GOELLNER, M.D., EDWARD R. LAWS, JR., M.D., EDWARD H. SOULE, M.D., AND HARUO OKAZAKI, M.D.
THE CONCEPT OF hemangiopericytoma—a tumor of pericytes of blood vessels—was introduced by Stout and Murray 28 in 1942. Clinically, this tumor can be benign or malignant, and it may occur at any age and in practically any location in the body. Its occurrence in the brain, however, has been controversial and disputed by many. 26 Thus, some investigators 22,24 have referred to such tumors as angioblastic variants of meningiomas, after the classic description by Bailey and associates. 3 Others 1 3 1 4 1 7 have considered hemangiopericytoma to be an entity separate from meningioma, with important clinical implications. Materials and Methods We searched the files of the Mayo Clinic Tissue Registry for cases of intracranial tumor in which the histologic features were compatible with the diagnosis of hemangiopericytoma. We excluded cases when histologic evidence of meningioma (psammdma bodies, whorling cell pattern) or of meningeal sarcoma (herringbone cell pattern, lack of vascular pattern) was present. From this review, we chose 26 cases as having histologic characteristics of hemangiopericytoma and studied the clinical and pathologic features of these cases. The oldest case with adequate histologic documentation was dated 1938—in cases before that time, Received October 3, 1977; accepted for publication November 21, 1977. Address reprint requests to Dr. Goellner: Mayo Clinic, Rochester, Minnesota 55901.
Mayo Clinic and Mayo Foundation, Rochester, Minnesota
the diagnoses were considered to be too doubtful for inclusion in this review. Wet tissue (when available) and paraffin blocks were examined. The histologic features were evaluated with regard to mitotic activity, cellular pleomorphism, nuclear hyperchromatism, and invasive characteristics (when possible). In all cases, reticulin stain was used to define the distribution of cells in the connective tissue meshwork and to emphasize the vascular pattern of the tumor. Tissue from two of the 26 cases was available for electron microscopy. After fixation in 3% glutaraldehyde at 4 C, the tissue was postfixed in 1% osmium tetroxide, embedded in epoxy resin (Epon), and sectioned on a microtome. Sections 1 i*m thick were stained with 1% azure II; grids were stained with 6% uranyl acetate and Reynold's lead citrate. Grids were examined in an electron microscope (Hitachi HU-12). The clinical features studied included patient age, sex, symptoms, physical findings, the location and appearance of the tumor, and the course of the disease in relation to therapy. Pathologic Description The tumors generally were attached to the meninges and seemed to compress rather than invade the brain. They were located primarily along dural surfaces, including the falx, tentorium, longitudinal sinus, and petrous or sphenoid ridges. The tumors were usually described as firm and markedly vascular. Surgical manipulation, even biopsy, could cause significant bleeding, and transfusion of large volumes of blood often was necessary. Microscopically, these tumors showed a reproducible pattern of plump, spindle-shaped cells arranged in solid masses or sheets (Fig. I A). Mitotic figures were frequently seen, ranging from one to five per ten highpower fields (Fig. IB). Necrosis was seen in some lesions, but generally it was not a prominent feature.
0002-9173/78/0900/0375 $00.75 © American Society of Clinical Pathologists
375
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Goellner, John R., Laws, Edward R., Jr., Soule, Edward H., and Okazaki, Haruo: Hemangiopericytoma of the meninges. Mayo Clinic experience. Am J Clin Pathol 70: 375-380, 1978. A study of 26 hemangiopericytomas of the meninges revealed that the histologic appearance—including ultrastructural features—was similar to that of hemangiopericytomas of soft tissues. Both sexes were affected, and occurrence was most frequent in the adult years, with no symptoms specific for the lesions. The lesions were characterized by an aggressive course, with recurrence in 80% of the patients, and metastases in 23%; thus, the importance of recognizing the lesion pathologically is emphasized. (Key words: Brain tumors; Hemangiopericytoma; Angioblastic meningioma.)
376
GOELLNERETML.
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FIG. 1. A (upper left). Typical histologic features of hemangiopericytoma of the brain seen on low power. Spindle cells are growing in a sheet, and there are numerous irregular vascular spaces. There is no cell whorling and no herringbone pattern. Hematoxylin and eosin. x 100. B (upper right). Higher magnification, illustrating delicate endothelial lining of vessels, with proliferation of surrounding pericytes. Mitosis is present in right midfield. Hematoxylin and eosin. x640. C (lower left). Exaggerated vascular pattern showing trabecular pattern. Hematoxylin and eosin. x 160. D (lower right). Pattern somewhat suggestive of "cell balls" between ramifying vascular lumens. Hematoxylin and eosin. x 160.
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8B£$§S **•>**
A.J.C.P. • September 1978
Vol. 70 • No. 3
377
HEMANGIOPERICYTOMA OF MENINGES
Cellular pleomorphism was not frequently seen, but binucleation and multinucleation of tumor cells occasionally were found. One lesion showed a few foam cells. The vascular pattern typical of these tumors is that of thin-walled, irregular vascular spaces forming a spongy network within the tumor. Endothelial cells were flat and inconspicuous, and the lumen was often slitlike, or collapsed, rather than broadly open. Vascularity was variable: some tumors did not appear to be vascular by routine stains, whereas others had such prominent vascular spaces that tumor cells were seen as trabeculae or cords between the lumens (Fig. 1C). In a few lesions, these cords contained clusters of tumor cells, producing a pattern reminiscent of "cell balls" (Fig. ID). The reticulin stain showed a typical pattern of fine reticulin fibers around a single cell or small groups of tumor cells. Endothelial cell nuclei could be seen inside a heavier layer or collar of reticulin outlining vascular spaces (Fig. 2A). Collagen, while often present, was rather sparse in these lesions. Metastatic lesions showed the same histologic features as did the primary cerebral tumors (Fig. 2B). The histologic findings were studied in relation to the clinical course. Nine lesions had borderline malignant characteristics, that is, absent or rare mitotic fig-
ures, regular spindle cells, and a lack of necrosis. Seventeen lesions had malignant features, that is, more than one mitotic figure per five high-power fields, areas of necrosis, and larger cells with nucleoli and nuclear pleomorphism. No relationship was found between the histologic division and the clinical course (Table 1). Eleven cases had tissue available for study on two different dates. Three of the 11 had a suggestion of dedifferentiation in the later specimen, with plumper cells, more prominent nucleoli, and less reticulin among tumor cells. In the other eight cases, no such tendency to dedifferentiation was seen. Table I. Histologic Features of Hemangiopericytoma Correlated with Clinical Course Outcome
Borderline Histology (9 Patients)
Malignant Histology (17 Patients)
Died of tumor of other causes
7 (2 postop.) 0
12 (3 postop.)* 2 (2nd tumors)
Alive with tumor and well * Includes one patient who died of purulent meningitis and vascular thrombosis ten months after operation for recurrent tumor.
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FIG. 2. A (left). Collar of silver staining fibers is seen around vessels and fine network of fibers interlacing with tumor cells. Reticulin stain. x250. B (right). Metastatic hemangiopericytoma in rib five years after total removal of intracranial primary lesion, with postoperative radiation therapy. Patient subsequently died with metastatic disease. Hematoxylin and eosin. xl60.
378
A.J.C.P. • September 1978
GOELLNER E I AL.
Two of the lesions were examined by electron microscopy (Fig. 3). The tumor cells were closely spaced, with a generally multiangular, oblong shape. Abundant basal lamina material with moderate electron density was present between cells, sometimes in thicker, clumped areas. Reticulin fibers and small amounts of mature collagen were present as well. Intercellular attachments (tight junction type) were not well developed. Cytoplasmic components were predominantly rough endoplasmic reticulum and mitochondria with considerable amounts of Golgi apparatus. Some cells contained lysosomes and nonspecific intracytoplasmic fibrils. No hemidesmosomes, pinocytosis, or myofilaments with dense bodies were present. Interspersed among tumor cells were capillaries containing blood cells, lined by endothelial cells that in some areas had numerous intertwining cell processes.
Of the 26 patients in our series, seven were women and 19 were men. At the time of initial diagnosis, the patients' ages ranged from 16 to 75 years, with a mean of 42 years. Symptoms of cerebral tumor usually had been present for several months prior to diagnosis. The most frequently seen symptom was headache, present in 14 of the 26 patients. Motor weakness (seven patients) and seizures (five patients) were less frequent presenting symptoms. Initial therapy was usually surgical, with an attempt at total removal. Virtually all of the tumors were vascular, and many were attached to major dural sinuses. Subtotal removal ordinarily was followed by radiotherapy, with a usual dose of 5,000 to 6,000 rads. Recurrent tumor was managed by additional surgery or additional radiotherapy, or both (11 patients). Gross total removal was considered to have been accomplished in ten patients. Two patients died in the immediate postoperative period. One patient was alive six years after operation, having been treated by surgery and radiotherapy for recurrence, and another died of metastatic melanoma 12 years after operation and postoperative radiotherapy. The remaining six patients all had recurrent tumor; three of them had metastatic hemangiopericytoma. The mean survival of the entire group, excluding the two immediate postoperative deaths, was 84 months. Included was another patient in whom a second malignant lesion developed (squamous carcinoma of the mediastinum). Fourteen patients have died because of recurrent cerebral tumor, and the mean survival of these 14 was 88 months. Five patients were alive five, six, 11, 12, and 18 years after diagnosis. Four of the five patients have been treated for recurrent disease, and two have documented metastases.
Discussion Historically, Bailey and associates 3 discussed three cases in 1928 and described this type of tumor as "angioblastic meningioma." The photomicrographs of the lesions in the three cases showed features identical to those in our series, and the comments of the authors on the aggressive courses of these tumors are interesting. In 1938, Cushing and Eisenhardt 7 added three more cases (one in which metastasis eventually occurred), again classifying these tumors as angioblastic variants of meningioma. Reports of this tumor occurring in the brain have been infrequent. Some authors 2 1 6 2 2 have referred to the lesions as angioblastic meningiomas, whereas others 5 9 1 7 ' 2 1 have called them hemangiopericytoma. In their book Sarcomas of the Brain, Kernohan and Uihlein 13 commented on 26 cases of hemangiopericytoma and emphasized the distinct histologic features and aggressive clinical course of the lesion. Kruse 14 reported eight cases from the AFIP in 1961. In six of the cases, there was recurrence. Five of the six patients eventually died of tumors, and one had metastasis. Pitkethly and co-workers, 24 also from AFIP, reviewed 37 cases of a "hemangiopericytic" variant of angioblastic mengingioma. Four of the patients had metastases, and ten died with local recurrences. The authors pointed out that this hemangiopericytic variant occurred at a younger average age and had a shorter duration of symptoms than did the "hemangioblastic" variant. Skullerud and Loken 27 found five cases of hemangiopericytoma in 161 cases of meningioma (2%); three of four cases in which the lesion was "completely removed" had recurrences. Jellinger and Slowik11 examined 1,238 meningiomas and found 17 intracranial hemangiopericytomas. They reported an overall recurrence rate of 14% after "complete removal" of meningiomas, but six of the 17 hemangiopericytomas (35%) recurred. These authors mentioned a lack of intermediate features between hemangiopericytoma and meningioma and apparently agreed that the two were separate entities. Several of the cases in our present series have been previously reported: Case 1 in 1943 by Abbott and Love 1 and Case 13 in 1971 by Muller and Mealey."' (The latter report described tumor explants that grew as meningioma in tissue culture, and the authors con-
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Clinical Data
Recurrent tumor developed in 17 patients overall, appearing a mean of five years after initial therapy. Metastatic disease developed in six of the 26 patients (23%), appearing a mean of 8.6 years after diagnosis of the primary cerebral tumor. Two patients had metastases to bone, two to the lung, one to the liver, and one to the retroperitoneum.
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of the Meninges Mayo Clinic Experience
JOHN R. GOELLNER, M.D., EDWARD R. LAWS, JR., M.D., EDWARD H. SOULE, M.D., AND HARUO OKAZAKI, M.D.
THE CONCEPT OF hemangiopericytoma—a tumor of pericytes of blood vessels—was introduced by Stout and Murray 28 in 1942. Clinically, this tumor can be benign or malignant, and it may occur at any age and in practically any location in the body. Its occurrence in the brain, however, has been controversial and disputed by many. 26 Thus, some investigators 22,24 have referred to such tumors as angioblastic variants of meningiomas, after the classic description by Bailey and associates. 3 Others 1 3 1 4 1 7 have considered hemangiopericytoma to be an entity separate from meningioma, with important clinical implications. Materials and Methods We searched the files of the Mayo Clinic Tissue Registry for cases of intracranial tumor in which the histologic features were compatible with the diagnosis of hemangiopericytoma. We excluded cases when histologic evidence of meningioma (psammdma bodies, whorling cell pattern) or of meningeal sarcoma (herringbone cell pattern, lack of vascular pattern) was present. From this review, we chose 26 cases as having histologic characteristics of hemangiopericytoma and studied the clinical and pathologic features of these cases. The oldest case with adequate histologic documentation was dated 1938—in cases before that time, Received October 3, 1977; accepted for publication November 21, 1977. Address reprint requests to Dr. Goellner: Mayo Clinic, Rochester, Minnesota 55901.
Mayo Clinic and Mayo Foundation, Rochester, Minnesota
the diagnoses were considered to be too doubtful for inclusion in this review. Wet tissue (when available) and paraffin blocks were examined. The histologic features were evaluated with regard to mitotic activity, cellular pleomorphism, nuclear hyperchromatism, and invasive characteristics (when possible). In all cases, reticulin stain was used to define the distribution of cells in the connective tissue meshwork and to emphasize the vascular pattern of the tumor. Tissue from two of the 26 cases was available for electron microscopy. After fixation in 3% glutaraldehyde at 4 C, the tissue was postfixed in 1% osmium tetroxide, embedded in epoxy resin (Epon), and sectioned on a microtome. Sections 1 i*m thick were stained with 1% azure II; grids were stained with 6% uranyl acetate and Reynold's lead citrate. Grids were examined in an electron microscope (Hitachi HU-12). The clinical features studied included patient age, sex, symptoms, physical findings, the location and appearance of the tumor, and the course of the disease in relation to therapy. Pathologic Description The tumors generally were attached to the meninges and seemed to compress rather than invade the brain. They were located primarily along dural surfaces, including the falx, tentorium, longitudinal sinus, and petrous or sphenoid ridges. The tumors were usually described as firm and markedly vascular. Surgical manipulation, even biopsy, could cause significant bleeding, and transfusion of large volumes of blood often was necessary. Microscopically, these tumors showed a reproducible pattern of plump, spindle-shaped cells arranged in solid masses or sheets (Fig. I A). Mitotic figures were frequently seen, ranging from one to five per ten highpower fields (Fig. IB). Necrosis was seen in some lesions, but generally it was not a prominent feature.
0002-9173/78/0900/0375 $00.75 © American Society of Clinical Pathologists
375
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
Goellner, John R., Laws, Edward R., Jr., Soule, Edward H., and Okazaki, Haruo: Hemangiopericytoma of the meninges. Mayo Clinic experience. Am J Clin Pathol 70: 375-380, 1978. A study of 26 hemangiopericytomas of the meninges revealed that the histologic appearance—including ultrastructural features—was similar to that of hemangiopericytomas of soft tissues. Both sexes were affected, and occurrence was most frequent in the adult years, with no symptoms specific for the lesions. The lesions were characterized by an aggressive course, with recurrence in 80% of the patients, and metastases in 23%; thus, the importance of recognizing the lesion pathologically is emphasized. (Key words: Brain tumors; Hemangiopericytoma; Angioblastic meningioma.)
376
GOELLNERETML.
^4*
J'
FIG. 1. A (upper left). Typical histologic features of hemangiopericytoma of the brain seen on low power. Spindle cells are growing in a sheet, and there are numerous irregular vascular spaces. There is no cell whorling and no herringbone pattern. Hematoxylin and eosin. x 100. B (upper right). Higher magnification, illustrating delicate endothelial lining of vessels, with proliferation of surrounding pericytes. Mitosis is present in right midfield. Hematoxylin and eosin. x640. C (lower left). Exaggerated vascular pattern showing trabecular pattern. Hematoxylin and eosin. x 160. D (lower right). Pattern somewhat suggestive of "cell balls" between ramifying vascular lumens. Hematoxylin and eosin. x 160.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
8B£$§S **•>**
A.J.C.P. • September 1978
Vol. 70 • No. 3
377
HEMANGIOPERICYTOMA OF MENINGES
Cellular pleomorphism was not frequently seen, but binucleation and multinucleation of tumor cells occasionally were found. One lesion showed a few foam cells. The vascular pattern typical of these tumors is that of thin-walled, irregular vascular spaces forming a spongy network within the tumor. Endothelial cells were flat and inconspicuous, and the lumen was often slitlike, or collapsed, rather than broadly open. Vascularity was variable: some tumors did not appear to be vascular by routine stains, whereas others had such prominent vascular spaces that tumor cells were seen as trabeculae or cords between the lumens (Fig. 1C). In a few lesions, these cords contained clusters of tumor cells, producing a pattern reminiscent of "cell balls" (Fig. ID). The reticulin stain showed a typical pattern of fine reticulin fibers around a single cell or small groups of tumor cells. Endothelial cell nuclei could be seen inside a heavier layer or collar of reticulin outlining vascular spaces (Fig. 2A). Collagen, while often present, was rather sparse in these lesions. Metastatic lesions showed the same histologic features as did the primary cerebral tumors (Fig. 2B). The histologic findings were studied in relation to the clinical course. Nine lesions had borderline malignant characteristics, that is, absent or rare mitotic fig-
ures, regular spindle cells, and a lack of necrosis. Seventeen lesions had malignant features, that is, more than one mitotic figure per five high-power fields, areas of necrosis, and larger cells with nucleoli and nuclear pleomorphism. No relationship was found between the histologic division and the clinical course (Table 1). Eleven cases had tissue available for study on two different dates. Three of the 11 had a suggestion of dedifferentiation in the later specimen, with plumper cells, more prominent nucleoli, and less reticulin among tumor cells. In the other eight cases, no such tendency to dedifferentiation was seen. Table I. Histologic Features of Hemangiopericytoma Correlated with Clinical Course Outcome
Borderline Histology (9 Patients)
Malignant Histology (17 Patients)
Died of tumor of other causes
7 (2 postop.) 0
12 (3 postop.)* 2 (2nd tumors)
Alive with tumor and well * Includes one patient who died of purulent meningitis and vascular thrombosis ten months after operation for recurrent tumor.
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FIG. 2. A (left). Collar of silver staining fibers is seen around vessels and fine network of fibers interlacing with tumor cells. Reticulin stain. x250. B (right). Metastatic hemangiopericytoma in rib five years after total removal of intracranial primary lesion, with postoperative radiation therapy. Patient subsequently died with metastatic disease. Hematoxylin and eosin. xl60.
378
A.J.C.P. • September 1978
GOELLNER E I AL.
Two of the lesions were examined by electron microscopy (Fig. 3). The tumor cells were closely spaced, with a generally multiangular, oblong shape. Abundant basal lamina material with moderate electron density was present between cells, sometimes in thicker, clumped areas. Reticulin fibers and small amounts of mature collagen were present as well. Intercellular attachments (tight junction type) were not well developed. Cytoplasmic components were predominantly rough endoplasmic reticulum and mitochondria with considerable amounts of Golgi apparatus. Some cells contained lysosomes and nonspecific intracytoplasmic fibrils. No hemidesmosomes, pinocytosis, or myofilaments with dense bodies were present. Interspersed among tumor cells were capillaries containing blood cells, lined by endothelial cells that in some areas had numerous intertwining cell processes.
Of the 26 patients in our series, seven were women and 19 were men. At the time of initial diagnosis, the patients' ages ranged from 16 to 75 years, with a mean of 42 years. Symptoms of cerebral tumor usually had been present for several months prior to diagnosis. The most frequently seen symptom was headache, present in 14 of the 26 patients. Motor weakness (seven patients) and seizures (five patients) were less frequent presenting symptoms. Initial therapy was usually surgical, with an attempt at total removal. Virtually all of the tumors were vascular, and many were attached to major dural sinuses. Subtotal removal ordinarily was followed by radiotherapy, with a usual dose of 5,000 to 6,000 rads. Recurrent tumor was managed by additional surgery or additional radiotherapy, or both (11 patients). Gross total removal was considered to have been accomplished in ten patients. Two patients died in the immediate postoperative period. One patient was alive six years after operation, having been treated by surgery and radiotherapy for recurrence, and another died of metastatic melanoma 12 years after operation and postoperative radiotherapy. The remaining six patients all had recurrent tumor; three of them had metastatic hemangiopericytoma. The mean survival of the entire group, excluding the two immediate postoperative deaths, was 84 months. Included was another patient in whom a second malignant lesion developed (squamous carcinoma of the mediastinum). Fourteen patients have died because of recurrent cerebral tumor, and the mean survival of these 14 was 88 months. Five patients were alive five, six, 11, 12, and 18 years after diagnosis. Four of the five patients have been treated for recurrent disease, and two have documented metastases.
Discussion Historically, Bailey and associates 3 discussed three cases in 1928 and described this type of tumor as "angioblastic meningioma." The photomicrographs of the lesions in the three cases showed features identical to those in our series, and the comments of the authors on the aggressive courses of these tumors are interesting. In 1938, Cushing and Eisenhardt 7 added three more cases (one in which metastasis eventually occurred), again classifying these tumors as angioblastic variants of meningioma. Reports of this tumor occurring in the brain have been infrequent. Some authors 2 1 6 2 2 have referred to the lesions as angioblastic meningiomas, whereas others 5 9 1 7 ' 2 1 have called them hemangiopericytoma. In their book Sarcomas of the Brain, Kernohan and Uihlein 13 commented on 26 cases of hemangiopericytoma and emphasized the distinct histologic features and aggressive clinical course of the lesion. Kruse 14 reported eight cases from the AFIP in 1961. In six of the cases, there was recurrence. Five of the six patients eventually died of tumors, and one had metastasis. Pitkethly and co-workers, 24 also from AFIP, reviewed 37 cases of a "hemangiopericytic" variant of angioblastic mengingioma. Four of the patients had metastases, and ten died with local recurrences. The authors pointed out that this hemangiopericytic variant occurred at a younger average age and had a shorter duration of symptoms than did the "hemangioblastic" variant. Skullerud and Loken 27 found five cases of hemangiopericytoma in 161 cases of meningioma (2%); three of four cases in which the lesion was "completely removed" had recurrences. Jellinger and Slowik11 examined 1,238 meningiomas and found 17 intracranial hemangiopericytomas. They reported an overall recurrence rate of 14% after "complete removal" of meningiomas, but six of the 17 hemangiopericytomas (35%) recurred. These authors mentioned a lack of intermediate features between hemangiopericytoma and meningioma and apparently agreed that the two were separate entities. Several of the cases in our present series have been previously reported: Case 1 in 1943 by Abbott and Love 1 and Case 13 in 1971 by Muller and Mealey."' (The latter report described tumor explants that grew as meningioma in tissue culture, and the authors con-
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
Clinical Data
Recurrent tumor developed in 17 patients overall, appearing a mean of five years after initial therapy. Metastatic disease developed in six of the 26 patients (23%), appearing a mean of 8.6 years after diagnosis of the primary cerebral tumor. Two patients had metastases to bone, two to the lung, one to the liver, and one to the retroperitoneum.
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