Hemangiopericytoma Literature Review and Clinical Presentations Howard C. Pitluk, MD, Chicago, Illinois Julius Conn, Jr, MD, Chicago, Illinois
Hemangiopericytoma, a mesenchymal tumor, was first described as a clinical entity in 1942. Prior to that time pathologists had confused hemangiopericytomas with various neoplasms such as glomus tuand mors, angiosarcomas, fibrous histiocytomas, mesenchymal chondrosarcomas. As the name implies, hemangiopericytomas are comprised of pericytes, the rudimentary contractile cells found adjacent to the capillary wall. Tendril-like projections of the pericyte surround the capillary and regulate blood flow by contracting and thereby altering the capillary lumen. Since all capillaries are enveloped by pericytes, hemangiopericytomas can be found virtually anywhere in the body. The majority have been described in the lower extremities, pelvis, head and neck regions, and trunk, in that order [I]. (Table I.) This paper presents three cases of hemangiopericytomas from Northwestern Memorial Hospital to demonstrate the frequently recurrent nature and malignant potential of the hemangiopericytoma. It also emphasizes the importance of aggressive surgical therapy whenever this tumor is encountered. The hemangiopericytomas occurring in the uterus and previously reported from Northwestern Memorial Hospitals have not been included in these case reports due to the different biologic behavior of uterine
hemangiopericytomas
[2].
Case Reports Case I. EJ, a thirty-three year old black female, was seen at Northwestern Memorial Hospital in 1971 for an asymptomatic mass arising in her right antecubital fossa. This mass had been present for several months and was From the Department of Surgery, Northwestern University-McGaw Medical Center, Chicago, Illinois. Reprint requests should be addressed to Julius Conn, Jr, MD, Department of Surgery, Northwestern University-McGaw Medical Center, 303 East Chicago Avenue, Chicago, Illinois 60611.
volume 137, March 1979
increasing slowly in size with no history of trauma. There were no neurologic or vascular deficits in the arm or hand. Excisional biopsy with presumptive diagnosis of lipoma revealed hemangiopericytoma. The patient was followed for two years without evidence of recurrence. She was lost to follow-up until January 1976, when she noted a painless mass developing beneath the scar on her right antecubital fossa. Again, the mass was nontender, and there were no associated neurologic, vascular, or musculoskeletal symptoms. Because of rapid enlargement of the mass, the patient returned for further treatment. (Figure 1.) At this time, her chest x-ray, liver and bone scans, and right arm and x-ray films were normal. Wide reexcision of the tumor was performed with a pathologic diagnosis of recurrent malignant hemangiopericytoma. (Figure 2.) The patient has had no evidence of tumor recurrence in the three years since operation. Comment. This case demonstrates one of the most common misconceptions in the therapy of hemangiopericytomas. The original excision was done on an outpatient basis and did not include adequate margins. When excisional biopsy reveals hemangiopericytoma, wide reexcision, including the deep fascia, should be performed. Failure to do so frequently results in recurrence of the tumor.
Case II. GL, a fifty-five year old white man, noted a painless lump on the superior and medial aspects of his right calf four weeks prior to being seen in 1971. The mass increased in size but remained asymptomatic. The patient denied any trauma or previous history of similar lesions. On examination, there was a 4 by 4 cm, firm, nontender mass fixed to the underlying fascia, with no skin discoloration noted. The patient underwent local excision of the mass. The pathology report was malignant hemangiopericytoma. He was admitted to the hospital, where wide excision and skin grafting of the biopsy site was performed. There has been no evidence of local recurrence or metastases over the past seven years. Comment. Aggressive wide surgical excision, usually with a skin graft, should always be performed for malignant
413
Pitluk and Conn
Figure 1. Recurrent mass, 3 by 5 cm, in antecubitai beneath fossa previous biopsy scar. Tenderness on physical examination was due to compression of the median nerve.
TABLE I
Location of Hemangiopericytoma from Recent Collective Reviews
as Compiled
Anatomic Site
No. of Patients
Lower extremities Retroperitoneum and nonuterine pelvis Headandneck Upper extremities Trunk Paraspinal
63 (36.4%) 37 (21.4%) 23 (13.3%) 23 (13.3%) 21 (12.1%) 6( 3.5%)
Total
173 (100%)
hemangiopericytoma. In view of the fact that there is no true capsule, local excision does not adequately remove the tumor, as shown in case I. Case III. PS, a twenty-nine year old white man, noted pain in his left ear and throat in April 1972. The pain persisted for three weeks, at which time physical examination revealed a 1.5 cm nonulcerated hypopharyngeal mass. Laryngoscopy and biopsy showed hemangiopericytoma. Transverse suprahyoid pharyngotomy with wide excision of the tumor was carried out. Six months later, a pinpoint-size white spot was described in the hypopharynx. There was no change over the next five months until March 1973, when the lesion began to enlarge. Biopsy was reported as recurrent hemangiopericytoma. The patient underwent supraglottic laryngectomy and left radical neck dissection. All of the excised nodes were negative for tumor. The patient has been followed up for five years, and there is no evidence of further recurrence. Comment. This case demonstrates the potentially aggressive nature of hemangiocytomas. Vigilance on the part of the surgeon coupled with aggressive surgical extirpation offers the patient his best chance for cure.
414
Figure 2. excision Wkte tumor of including surrounding skin, subcutaneous tissue, and deep fascia. Part of the brachioradiaiis muscle has also been removed. The median nerve is seen in the center of the incision.
Comments
Margaret Murray and Arthur Stout [3] in 1942 were attracted to the possibility of a new pathologic entity while studying the glomus tumor. In reviewing nine cases of recurrent, infiltrating “glomus tumors,” they noted that none of these patients had painful symptoms typical of a glomus tumor. The nonorganoid pattern and diffuse distribution of the tumor
The American Journal of Surgery
cells seemed to contradict the original diagnosis of glomus tumor. Furthermore, the anatomic locations and multiple recurrences of the tumors were unusual for glomus tumors. Distant metastasis developed in one of these patients who died five years later [3]. These findings convinced Murray and Stout that these nine cases comprised a new pathologic entity, which they called hemangiopericytoma after the predominant cell comprising the tumor. By 1949 there still had been no further research or reports of hemangiopericytoma in the literature. In order to clarify and establish hemangiopericytoma as a distinct clinical and pathologic entity, Doctor Stout collected twenty-five new cases through personal contact with pathologists in the United States. This report by Stout established that: (1)involvemenEin both sexes was equal; (2) the patients ranged in age from neonates to octagenerians; (3) the tumor had an aggressive growth pattern; (4) there was a high incidence of recurrence; and (5) 50 per cent of the tumors with distant metastases were malignant. Since that report, there have been more than 300 articles and case reports describing the clinical and pathologic aspects of this unusual neoplasm. The pericyte, the identifying cell of the hemangiopericytoma, was first described by the Swiss pathologist Zimmerman [5] in 1923. Histologically, the pericyte is not connected with arterial or venule epithelium but is an independent contractile cell surrounding the capillary. Hemangiopericytes represent a proliferation of the pericytes, with their ovoid or spindle-shaped cells intimately surrounding the
Figure 4. Electron mtcrograph of hemangiopericytoma. A capillary (cap) is seen in the center. Several pericytes (arrows) and their processes surround the endothelial cells. (Magnification X8,000, reduced 37 per cent. )
capillary. (Figure 3.) A fine sheath of reticulin can be seen around the capillaries, separating them from the pericytes. Ultrastructural studies demonstrate perivascular processes arising from the pericyte which envelop the capillaries. There is a basement membrane attached to the tumor’s cell membrane which is present in the pericyte. (Figure 4.) These findings are constant in
415
Pitluk and Conn
hemangiopericytomas and are necessary for differentiation from other sarcomas [4]. Recently, attempts have been made to diffetentiate between benign and malignant hemangiopericytomas. McMaster, Soule, and Ivins [6], reporting the Mayo Clinic experience, agreed with Stout that the larger, deep seated tumors tend to be more malignant. Moreover, they predicted malignancy when tumors exhibited a few mitotic figures with moderate cellular anaplasia. In addition, foci of necrosis within a given tumor strongly suggested a malignant potential. Enziner and Smith, reporting 106 cases of hemangiopericytoma, used four or more mitotic figures per high power field as their criterion for malignancy. They also reported that patients with tumors less than 6.5 cm in diameter, whether or not the tumors were well circumscribed, had a 92 per cent ten year survival rate as compared to a 63 per cent survival rate in patients with tumors greater than 6.5 cm in diameter. Most series report approximately 30 per cent of the tumors occurring in the lower extremities, with the remaining tumors being located in retroperitoneum, upper extremities, head and neck, and trunk [4,6-B]. (Table I.) Treatment The primary treatment for hemangiopericytoma is wide surgical excision. As in most soft tissue sarcomas, amputation may be necessary if adequate local excision is precluded. The recurrence rate of the tumor is relatively high in all series (25 to 50 per cent) and undoubtedly reflects inadequate margins at the initial operation [4,6,7,9,10]. Follow-up examinations should be continued at least once a year for the remainder of the patient’s life due to the high recurrence rate of hemangiopericytomas. The lung is the most common site for metastases, with chest wall, brain, bowel, bone, orbit, and lymph node metastases also being reported. Chemotherapy and radiation have had poor results in the treatment of metastatic hemangiopericytoma. The report of Friedman and Egan [II] is the most comprehensive report of radiation therapy of hemangiopericytoma. Like most sarcomas, these tumors are very radioresistant. However, palliative radiation has produced temporary tumor regression. The combination of various chemotherapeutic regimens has met with similarly poor results [6,12]. Conclusions
Whenever a painless soft tissue mass is discovered, one should include hemangiopericytoma in the dif-
416
ferential diagnosis. Only biopsy of the lesion will confirm the diagnosis. Ultrastructural studies are usually necessary to make a definitive diagnosis of hemangiopericytoma. Prompt wide excision is a necessity because of a high incidence of recurrence and a 50 per cent incidence of malignancy. Hemangiopericytomas are often difficult to totally eradicate and have been reported to recur twenty years after initial treatment. Thus, careful follow-up, which should include chest X-ray, is essential. Perhaps newer chemotherapeutic agents, supravoltage irradiation, or immunotherapy may produce better control of malignant hemangiopericytoma. Summary
Hemangiopericytomas are soft tissue sarcomas of vascular origin, comprised of pericytes. They have been reported in the extremities, head and neck, back, retroperitoneum, and abdomen. The criteria for the diagnosis and treatment are reviewed. Wide local ablation of the tumor is necessary to prevent local recurrence. Fifty per cent are malignant, although regional node spread is infrequent. Ultrastructural studies are necessary to differentiate hemangiopericytomas from other sarcomas. Long-term follow-up of all cases is essential for optimal clinical management. References 1. Enzinger F, Smith B: Hemangiopericytoma: an analysis of 106 cases. Hum Pathol7: 61, 1976. 2. Greene R, Gerbie A, Gerbie M, et al: Hemangiopericytomas of the uterus. Am J Obstet GynecollO6: 1020, 1970. 3. Murray M, Stout A: Glomus tumor. Investigationof its distribution and behavior and the identity of its “epithelioid” cell. Am J Patholl8: 183, 1942. 4. Battifora H: Hemangiopericytoma: ultrastructural study of five cases. Cancer 31: 1418, 1973. 5. Zimmerman K: Der jeiner bau der blutcapillaren. ZAnat Embryo/ (Ser/) 68: 29, 1922. 6. McMaster M. Soule E, lvins J: Hemangioperictyoma. A clinicopathologic study and long-term follow-up of 60 patients. Cancer 36: 2232, 1975. 7. Gerner R, Moore G, Pichren J: Hemangiopericytoma. Ann Surg 179: 128, 1974. 8. Obrien P, Brasfield RD: Hemangiopericytoma. Cancer 18: 249, 1965. 9. Fisher J: Hemangiopericytoma. A review of twenty cases. Can Med Assoc J 83: 1136, 1960. 10. Stout A, Murray M: Hemangiopericytoma. Vascular tumor featuring Zimmerman’s pericytes. Ann Surg 116: 26. 1942. 11. Friedman M, Egan J: Irradiation of the hemangiopericytoma of Stout. Radiology 74: 721, 1960. 12. Cohen G, Lichtig C, Robinson E: Combination chemotherapy in the treatment of hemangiopericytoma. Oncology26: 180, 1972.
The Amerlcan Jm
of Suraary
Hemangiopericytoma, a mesenchymal tumor, was first described as a clinical entity in 1942. Prior to that time pathologists had confused hemangiopericytomas with various neoplasms such as glomus tuand mors, angiosarcomas, fibrous histiocytomas, mesenchymal chondrosarcomas. As the name implies, hemangiopericytomas are comprised of pericytes, the rudimentary contractile cells found adjacent to the capillary wall. Tendril-like projections of the pericyte surround the capillary and regulate blood flow by contracting and thereby altering the capillary lumen. Since all capillaries are enveloped by pericytes, hemangiopericytomas can be found virtually anywhere in the body. The majority have been described in the lower extremities, pelvis, head and neck regions, and trunk, in that order [I]. (Table I.) This paper presents three cases of hemangiopericytomas from Northwestern Memorial Hospital to demonstrate the frequently recurrent nature and malignant potential of the hemangiopericytoma. It also emphasizes the importance of aggressive surgical therapy whenever this tumor is encountered. The hemangiopericytomas occurring in the uterus and previously reported from Northwestern Memorial Hospitals have not been included in these case reports due to the different biologic behavior of uterine
hemangiopericytomas
[2].
Case Reports Case I. EJ, a thirty-three year old black female, was seen at Northwestern Memorial Hospital in 1971 for an asymptomatic mass arising in her right antecubital fossa. This mass had been present for several months and was From the Department of Surgery, Northwestern University-McGaw Medical Center, Chicago, Illinois. Reprint requests should be addressed to Julius Conn, Jr, MD, Department of Surgery, Northwestern University-McGaw Medical Center, 303 East Chicago Avenue, Chicago, Illinois 60611.
volume 137, March 1979
increasing slowly in size with no history of trauma. There were no neurologic or vascular deficits in the arm or hand. Excisional biopsy with presumptive diagnosis of lipoma revealed hemangiopericytoma. The patient was followed for two years without evidence of recurrence. She was lost to follow-up until January 1976, when she noted a painless mass developing beneath the scar on her right antecubital fossa. Again, the mass was nontender, and there were no associated neurologic, vascular, or musculoskeletal symptoms. Because of rapid enlargement of the mass, the patient returned for further treatment. (Figure 1.) At this time, her chest x-ray, liver and bone scans, and right arm and x-ray films were normal. Wide reexcision of the tumor was performed with a pathologic diagnosis of recurrent malignant hemangiopericytoma. (Figure 2.) The patient has had no evidence of tumor recurrence in the three years since operation. Comment. This case demonstrates one of the most common misconceptions in the therapy of hemangiopericytomas. The original excision was done on an outpatient basis and did not include adequate margins. When excisional biopsy reveals hemangiopericytoma, wide reexcision, including the deep fascia, should be performed. Failure to do so frequently results in recurrence of the tumor.
Case II. GL, a fifty-five year old white man, noted a painless lump on the superior and medial aspects of his right calf four weeks prior to being seen in 1971. The mass increased in size but remained asymptomatic. The patient denied any trauma or previous history of similar lesions. On examination, there was a 4 by 4 cm, firm, nontender mass fixed to the underlying fascia, with no skin discoloration noted. The patient underwent local excision of the mass. The pathology report was malignant hemangiopericytoma. He was admitted to the hospital, where wide excision and skin grafting of the biopsy site was performed. There has been no evidence of local recurrence or metastases over the past seven years. Comment. Aggressive wide surgical excision, usually with a skin graft, should always be performed for malignant
413
Pitluk and Conn
Figure 1. Recurrent mass, 3 by 5 cm, in antecubitai beneath fossa previous biopsy scar. Tenderness on physical examination was due to compression of the median nerve.
TABLE I
Location of Hemangiopericytoma from Recent Collective Reviews
as Compiled
Anatomic Site
No. of Patients
Lower extremities Retroperitoneum and nonuterine pelvis Headandneck Upper extremities Trunk Paraspinal
63 (36.4%) 37 (21.4%) 23 (13.3%) 23 (13.3%) 21 (12.1%) 6( 3.5%)
Total
173 (100%)
hemangiopericytoma. In view of the fact that there is no true capsule, local excision does not adequately remove the tumor, as shown in case I. Case III. PS, a twenty-nine year old white man, noted pain in his left ear and throat in April 1972. The pain persisted for three weeks, at which time physical examination revealed a 1.5 cm nonulcerated hypopharyngeal mass. Laryngoscopy and biopsy showed hemangiopericytoma. Transverse suprahyoid pharyngotomy with wide excision of the tumor was carried out. Six months later, a pinpoint-size white spot was described in the hypopharynx. There was no change over the next five months until March 1973, when the lesion began to enlarge. Biopsy was reported as recurrent hemangiopericytoma. The patient underwent supraglottic laryngectomy and left radical neck dissection. All of the excised nodes were negative for tumor. The patient has been followed up for five years, and there is no evidence of further recurrence. Comment. This case demonstrates the potentially aggressive nature of hemangiocytomas. Vigilance on the part of the surgeon coupled with aggressive surgical extirpation offers the patient his best chance for cure.
414
Figure 2. excision Wkte tumor of including surrounding skin, subcutaneous tissue, and deep fascia. Part of the brachioradiaiis muscle has also been removed. The median nerve is seen in the center of the incision.
Comments
Margaret Murray and Arthur Stout [3] in 1942 were attracted to the possibility of a new pathologic entity while studying the glomus tumor. In reviewing nine cases of recurrent, infiltrating “glomus tumors,” they noted that none of these patients had painful symptoms typical of a glomus tumor. The nonorganoid pattern and diffuse distribution of the tumor
The American Journal of Surgery
cells seemed to contradict the original diagnosis of glomus tumor. Furthermore, the anatomic locations and multiple recurrences of the tumors were unusual for glomus tumors. Distant metastasis developed in one of these patients who died five years later [3]. These findings convinced Murray and Stout that these nine cases comprised a new pathologic entity, which they called hemangiopericytoma after the predominant cell comprising the tumor. By 1949 there still had been no further research or reports of hemangiopericytoma in the literature. In order to clarify and establish hemangiopericytoma as a distinct clinical and pathologic entity, Doctor Stout collected twenty-five new cases through personal contact with pathologists in the United States. This report by Stout established that: (1)involvemenEin both sexes was equal; (2) the patients ranged in age from neonates to octagenerians; (3) the tumor had an aggressive growth pattern; (4) there was a high incidence of recurrence; and (5) 50 per cent of the tumors with distant metastases were malignant. Since that report, there have been more than 300 articles and case reports describing the clinical and pathologic aspects of this unusual neoplasm. The pericyte, the identifying cell of the hemangiopericytoma, was first described by the Swiss pathologist Zimmerman [5] in 1923. Histologically, the pericyte is not connected with arterial or venule epithelium but is an independent contractile cell surrounding the capillary. Hemangiopericytes represent a proliferation of the pericytes, with their ovoid or spindle-shaped cells intimately surrounding the
Figure 4. Electron mtcrograph of hemangiopericytoma. A capillary (cap) is seen in the center. Several pericytes (arrows) and their processes surround the endothelial cells. (Magnification X8,000, reduced 37 per cent. )
capillary. (Figure 3.) A fine sheath of reticulin can be seen around the capillaries, separating them from the pericytes. Ultrastructural studies demonstrate perivascular processes arising from the pericyte which envelop the capillaries. There is a basement membrane attached to the tumor’s cell membrane which is present in the pericyte. (Figure 4.) These findings are constant in
415
Pitluk and Conn
hemangiopericytomas and are necessary for differentiation from other sarcomas [4]. Recently, attempts have been made to diffetentiate between benign and malignant hemangiopericytomas. McMaster, Soule, and Ivins [6], reporting the Mayo Clinic experience, agreed with Stout that the larger, deep seated tumors tend to be more malignant. Moreover, they predicted malignancy when tumors exhibited a few mitotic figures with moderate cellular anaplasia. In addition, foci of necrosis within a given tumor strongly suggested a malignant potential. Enziner and Smith, reporting 106 cases of hemangiopericytoma, used four or more mitotic figures per high power field as their criterion for malignancy. They also reported that patients with tumors less than 6.5 cm in diameter, whether or not the tumors were well circumscribed, had a 92 per cent ten year survival rate as compared to a 63 per cent survival rate in patients with tumors greater than 6.5 cm in diameter. Most series report approximately 30 per cent of the tumors occurring in the lower extremities, with the remaining tumors being located in retroperitoneum, upper extremities, head and neck, and trunk [4,6-B]. (Table I.) Treatment The primary treatment for hemangiopericytoma is wide surgical excision. As in most soft tissue sarcomas, amputation may be necessary if adequate local excision is precluded. The recurrence rate of the tumor is relatively high in all series (25 to 50 per cent) and undoubtedly reflects inadequate margins at the initial operation [4,6,7,9,10]. Follow-up examinations should be continued at least once a year for the remainder of the patient’s life due to the high recurrence rate of hemangiopericytomas. The lung is the most common site for metastases, with chest wall, brain, bowel, bone, orbit, and lymph node metastases also being reported. Chemotherapy and radiation have had poor results in the treatment of metastatic hemangiopericytoma. The report of Friedman and Egan [II] is the most comprehensive report of radiation therapy of hemangiopericytoma. Like most sarcomas, these tumors are very radioresistant. However, palliative radiation has produced temporary tumor regression. The combination of various chemotherapeutic regimens has met with similarly poor results [6,12]. Conclusions
Whenever a painless soft tissue mass is discovered, one should include hemangiopericytoma in the dif-
416
ferential diagnosis. Only biopsy of the lesion will confirm the diagnosis. Ultrastructural studies are usually necessary to make a definitive diagnosis of hemangiopericytoma. Prompt wide excision is a necessity because of a high incidence of recurrence and a 50 per cent incidence of malignancy. Hemangiopericytomas are often difficult to totally eradicate and have been reported to recur twenty years after initial treatment. Thus, careful follow-up, which should include chest X-ray, is essential. Perhaps newer chemotherapeutic agents, supravoltage irradiation, or immunotherapy may produce better control of malignant hemangiopericytoma. Summary
Hemangiopericytomas are soft tissue sarcomas of vascular origin, comprised of pericytes. They have been reported in the extremities, head and neck, back, retroperitoneum, and abdomen. The criteria for the diagnosis and treatment are reviewed. Wide local ablation of the tumor is necessary to prevent local recurrence. Fifty per cent are malignant, although regional node spread is infrequent. Ultrastructural studies are necessary to differentiate hemangiopericytomas from other sarcomas. Long-term follow-up of all cases is essential for optimal clinical management. References 1. Enzinger F, Smith B: Hemangiopericytoma: an analysis of 106 cases. Hum Pathol7: 61, 1976. 2. Greene R, Gerbie A, Gerbie M, et al: Hemangiopericytomas of the uterus. Am J Obstet GynecollO6: 1020, 1970. 3. Murray M, Stout A: Glomus tumor. Investigationof its distribution and behavior and the identity of its “epithelioid” cell. Am J Patholl8: 183, 1942. 4. Battifora H: Hemangiopericytoma: ultrastructural study of five cases. Cancer 31: 1418, 1973. 5. Zimmerman K: Der jeiner bau der blutcapillaren. ZAnat Embryo/ (Ser/) 68: 29, 1922. 6. McMaster M. Soule E, lvins J: Hemangioperictyoma. A clinicopathologic study and long-term follow-up of 60 patients. Cancer 36: 2232, 1975. 7. Gerner R, Moore G, Pichren J: Hemangiopericytoma. Ann Surg 179: 128, 1974. 8. Obrien P, Brasfield RD: Hemangiopericytoma. Cancer 18: 249, 1965. 9. Fisher J: Hemangiopericytoma. A review of twenty cases. Can Med Assoc J 83: 1136, 1960. 10. Stout A, Murray M: Hemangiopericytoma. Vascular tumor featuring Zimmerman’s pericytes. Ann Surg 116: 26. 1942. 11. Friedman M, Egan J: Irradiation of the hemangiopericytoma of Stout. Radiology 74: 721, 1960. 12. Cohen G, Lichtig C, Robinson E: Combination chemotherapy in the treatment of hemangiopericytoma. Oncology26: 180, 1972.
The Amerlcan Jm
of Suraary
