Skeletal Radiol (1992) 2l:407-409
Skeletal Radiology
Case report 749 Thomas J. Simmons, M.D. 1 Thomas J. Bassler, M.D.1, Charles P. Sehwinn, M.D.1 and D.M. Forrester, M.D. 2 Departments of 1 Pathology and 2 Radiology, LAC/USC Medical Center, Los Angeles, California, USA
Radiological study
Fig. 1. Anteroposterior (AP) and lateral radiographs of the distal phalanx of the thumb shows an expanding lytic lesion with cortical thinning and preservation of the joint space
Clinical information A 30-year-old m a n presented in April 1989, complaining of pain and swelling in his left t h u m b for the past 2 years. The pain was described as being intermittent, but increasing in intensity over the past 4 months. N o history of t r a u m a was obtained. On examination, the left t h u m b had full movement, and sensation was intact. Address reprint requests to: Dr. T.J. Sim-
mons, Northwest Arkansas Pathology Associates, P.O. Box 1086, Fayetteville, AR 72703, USA
The flexor surface was markedly mottled, swollcn, and painful to palpation. A roentgenogram revealed bony expansion with vacuolization and soft-tissue swelling of the distal phalanx. A needle aspiration was attempted, but only blood was obtained. The patient was referred to the orthopedic clinic with a diagnosis of bone t u m o r or aneurysmal bone cyst. When the patient was seen in the orthopedic clinic 1 week later the entire volar aspect of the left thumb was erythematous, swollen, and markedly tender. A soil-tissue mass was palpable in the distal phalanx of the thumb. A second radiographic study showed a large soft-tissue mass surrounding the distal phalanx which was completely destroyed by a lytic, expanding lesion. The proximal phalanx was not involved. On August 18, 1989, the left thumb was a m p u t a t e d at the middle of the proximal phalanx. Gross examination showed a t h u m b measuring 4.5 x 2.5 x 2 era. On sectioning, the distal phalanx was found to be almost completely replaced by t u m o r and cut easily with a scalpel. Microscopic examination showed the t u m o r to be composed of solid sheets of rather uniform, small cells which had round, bland nuclei and eosinophilic to amphophilic cytoplasm. The nuclei contained vesicular chromatin, and nucleoli were not prominent. The t u m o r was poorly circumscribed and showed expansion of the m a r r o w cavity with diffuse infiltration of thc surrounding soft tis-
sues. Thc classic pattern of large, ectatic vascular spaces with proliferation of glomus cells adjacent to the blood spaces was not present; rather, the vessels were of variable sizes and were collapsed. In some areas, a nesting pattern similar to a hemangiopericytoma or a paraganglioma was present. The stromal response consisted of marked fibrosis, and in some areas myxoid change which resembled chondroid was present. Material for histological study was fixed in 10% buffered formalin solution, and the paraffin-embedded sections were stained with hematoxylin and eosin. Immunhistochemical analysis was performed only on sections that did not require decalcification. Deparaffinized sections were immunostained with monoclonal antibodies to muscle-specific actin (MSA), keratin AE1/AE3, desmin, S-100 protein, vimentin, and factor VIII-related antigen. Immunohistochemical studies showed strongly positive staining for vimentin and MSA. Factor VIII-related antigen failed to stain the glomus cells but dramatically highlighted the vascularity of the t u m o r by staining the surrounding endothelial cells. Staining for S-100 protein of the critical cells or of the myxoid areas was absent. Staining results for keratin and desmin were negative. Electron microscopy showed fine filaments with dense bodies and dense attachment plaques in the cell cytoplasm. Additionally, a thick basement m e m b r a n e was present around individual cells. 9 1992 International Skeletal Society
408
Diagnosis: Primary glomus tumor of bone Discussion Glomus tumors are u n c o m m o n neoplasms which are usually easily recognized because of their distinctive clinical and histological appearance. Typically, these tumors present as painful, blue-red nodules in the deep dermis or subcutis of the extremities
T.J. Simmons et al. : Case report 749 with a predilection for the subungual region of the fingers. However, they have been described in a variety of unusual locations including the stomach [2, 9], small intestine [6], vagina [17], nose [1], and oral cavity [161. Primary intraosseous glomus tumors are indeed rare neoplasms. Since the first case report by De Latorre in 1939 [11], fewer than 15 cases have been reported [12, 15]. Truly unusual cases have been described in-
Pathological studies Fig. 2. Low magnification of the glomus tumor next to cortical bone. The neoplasm is composed of uniform round cells surrounding blood vessels. The loose stroma at the periphery appears myxoid and in some areas resembles chondroid material Fig. 3. This higher magnification of the glomus tumor demonstrates the monomorphic cells with bland and round nuclei in close contact with blood vessels, many of which have collapsed Fig. 4. Immunohistochemical staining of the glomus tumor with muscle-specific actin shows strong staining of the malignant cells adjacent to a muscular blood vessel which demonstrates staining of its wall
volving the middle phalanx [3] and the ulna [15], but the majority of these tumors affect the distal phalanges. Since this site is also a c o m m o n location for soft-tissue tumors and tumors o f bone, the diagnosis of a primary glomus t u m o r of bone m a y be difficult. Although m a n y soft-tissue tumors m a y produce a bony defect by pressure or erosion, by careful clinical and radiological studies it can be ascertained whether or not an osseous defect is due to an extraosseous
T.J. Simmons et al. : Case report 749 neoplasm. A diagnosis of primary bone involvement is easy if the t u m o r is completely bounded by cortical bone. I f this is not the case, then smooth erosion of the bone on one side points to an adjacent soft-tissue tumor, while an expanding, lytic lesion favors a primary bone neoplasm. The glomus t u m o r has a characteristic histological appearance, but it must be recognized that variable patterns do occur [5], depending on the relative proportions of glomus cells to blood vessels, the extent o f vascular ectasia and the stromal response to the tumor. A cellular neoplasm with a solid pattern can be misdiagnosed as hemangiopericytoma, adnexal tumor, or a metastatic epithelial neoplasm arising in organs such as the prostate and thyroid. In the present case, c h o n d r o b l a s t o m a was the diagnosis on frozen section; although chondroblastomas usually arise in long bones, the smaller bones of the hands and feet including the phalanges are occasionally involved [10]. Microscopically, b o t h chond r o b l a s t o m a and glomus t u m o r are composed of fairly uniform, rounded cells with punched-out nuclei and distinct cytoplasmic borders. In distinguishing between the two it is helpful to find the giant cells and foci of microcalcification that are characteristic of c h o n d r o b l a s t o m a and not seen in glomus tumor. Additionally, the nuclei in c h o n d r o b l a s t o m a are slightly more irregular than the nuclei in glomus tumors. Immunohistochemistry can be extremely helpful in establishing a diagnosis of glomus tumor, especially in cases where an atypical histological appearance exists. Since glomus tumors are generally considered to be composed of modified smooth muscle cells, it is not surprising that studies have shown that these tumors routinely stain for M S A and vimentin [4, 16]. The failure o f desmin to stain the t u m o r is of interest since it is a m a r k e r o f smooth muscle; apparently, this antigen is variably present on other cells that are considered modified smooth muscle cells,
409 such as pericytes or myoepithelial cells [13]. Immunoreactivity to keratin, S-100 protein, factor VIII-related antigen, and myogloblin have been shown to be negative [4]. Differentiating a glomus t u m o r from metastatic carcinoma or primary skin adnexal neoplasms m a y be morphologically difficult, but these epithelial neoplasms are positive for keratin and do not stain with MSA. H e m a n giopericytomas m a y also stain with M S A [8], but morphologically the malignant cells in this lesion have more ovoid and pleomorphic nuclei than the glomus t u m o r and have less distinct cytoplasmic borders. Chondroblastomas, unlike glomus tumors, stain with S-100 [14] and fail to stain with MSA. Intraosseous glomus tumors, like their soft-tissue counterparts, behave in a benign fashion. Metastasis and malignant transformation typically do not occur. Adequate treatment consists of excision or curettage in the case o f an intraosseous tumor. Infrequently, local recurrence occursusually the result of an inadequate excision. In summary, we report a case of p r i m a r y intraosseous glomus t u m o r in a 30-year-old m a n who was found to have an expanding, lytic lesion in the distal phalanx of his left thumb. The histological appearance was atypical in that areas of myxoid strom a resembled chondroid material. The unusual location and microscopic appearance caused diagnostic problems. Immunohistochemical studies, including strong positive staining for M S A and negative staining for keratin and S-100 protein, were helpful in establishing the correct diagnosis.
References
1. Apfelberg DB, Teasler JL (1968) Unusual locations and manifestations of glomus tumors (glomangiomas). Am J Surg 116:62 2. Appelman HD, Helwig FB (1969) Glo-
mus tumors of the stomach. Cancer 23 :203 3. Bjorkengren AG, Resnick D, Haghighi P, Sartoris DJ (1986) Intraosseous glomus tumor: report of a case and review of the literature. AJR 147: 739 4. Dervan PA, Tobbia IN, Casey M, O'Loughlin JO, O'Brien M (1989) Glomus tumours: an immunohistochemical profile of 11 cases. Histopathology 14:483 5. Enzinger FW, Weiss SW (1988) Soft tissue tumors, 2nd edn. CV Mosby, St Louis, p 583 6. Hamilton CW, Shelburne JD, Bossen EH, Lowe JE (1982) A glomus tumor of the jejunum masquerading as a carcinoid tumor. Hum Pathol 13:859 7. Hsu S, Raine L, Fanger H (1981) Use of avidin-biotin-immunoperoxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures. J Histochem Cytochem 29 : 577 8. Hultberg BM, Daugard S, Johansen HF, et al. (1988) Malignant hemangiopericytomas and hemangioendotheliosarcomas: an immunohistochemical study. Histopathology 12: 405 9. Kay S, Callahan WP Jr, Murray MR, Randall HT, Stout AP (1951) Glomus tumors of the stomach. Cancer 4: 726 10. Kurt AM, Unni KK, Sim FH, McLeod RA (1989) Chondroblastoma of bone. Hum Pathol 20: 965 11. Lattes R, Bull DC (1948) A case of glomus tumor with primary involvement of bone. Ann Surg 127:187 12. MacKenzie DH (1962) Intraosseous glomus tumors. J Bone Joint Surg [Br] 44: 648 13. Miettinin M, Lehto VP, Virtanen I (1983) Glomus tumor cells: evaluation of smooth muscle and endothelial properties. Virchows Arch [Cell Pathol] 43:139 14. Monda L, Wick MR (1985) S-100 protein immunostaining in the differential diagnosis of chondroblastoma. Hum Pathol 16:287 15. Rozmaryn LM, Sadler AH, Dorfman HD (1987) Intraosseous glomus tumor of the ulna. A case report. Clin Orthop 220:126 16. Saku T, Okabe H, Matsutani K, Sasaki M (1985) Glomus tumor of the cheek. An immunohistochemical demonstration of actin and myosin. Oral Surg Oral Med Oral Pathol 60:65 17. Spitzer M, Mulho L, Selzer VL, Lipper S (1985) Vaginal glomus tumor. Case presentation and ultrastructural findings. Obstet Gynecol 66:86S 18. Sunderraj S, A1-Khalifa AA, Pal AK, Pim HP, Sabri SH (1988) Primary intraosseous glomus tumor. Histopathology 14(5): 532
Skeletal Radiology
Case report 749 Thomas J. Simmons, M.D. 1 Thomas J. Bassler, M.D.1, Charles P. Sehwinn, M.D.1 and D.M. Forrester, M.D. 2 Departments of 1 Pathology and 2 Radiology, LAC/USC Medical Center, Los Angeles, California, USA
Radiological study
Fig. 1. Anteroposterior (AP) and lateral radiographs of the distal phalanx of the thumb shows an expanding lytic lesion with cortical thinning and preservation of the joint space
Clinical information A 30-year-old m a n presented in April 1989, complaining of pain and swelling in his left t h u m b for the past 2 years. The pain was described as being intermittent, but increasing in intensity over the past 4 months. N o history of t r a u m a was obtained. On examination, the left t h u m b had full movement, and sensation was intact. Address reprint requests to: Dr. T.J. Sim-
mons, Northwest Arkansas Pathology Associates, P.O. Box 1086, Fayetteville, AR 72703, USA
The flexor surface was markedly mottled, swollcn, and painful to palpation. A roentgenogram revealed bony expansion with vacuolization and soft-tissue swelling of the distal phalanx. A needle aspiration was attempted, but only blood was obtained. The patient was referred to the orthopedic clinic with a diagnosis of bone t u m o r or aneurysmal bone cyst. When the patient was seen in the orthopedic clinic 1 week later the entire volar aspect of the left thumb was erythematous, swollen, and markedly tender. A soil-tissue mass was palpable in the distal phalanx of the thumb. A second radiographic study showed a large soft-tissue mass surrounding the distal phalanx which was completely destroyed by a lytic, expanding lesion. The proximal phalanx was not involved. On August 18, 1989, the left thumb was a m p u t a t e d at the middle of the proximal phalanx. Gross examination showed a t h u m b measuring 4.5 x 2.5 x 2 era. On sectioning, the distal phalanx was found to be almost completely replaced by t u m o r and cut easily with a scalpel. Microscopic examination showed the t u m o r to be composed of solid sheets of rather uniform, small cells which had round, bland nuclei and eosinophilic to amphophilic cytoplasm. The nuclei contained vesicular chromatin, and nucleoli were not prominent. The t u m o r was poorly circumscribed and showed expansion of the m a r r o w cavity with diffuse infiltration of thc surrounding soft tis-
sues. Thc classic pattern of large, ectatic vascular spaces with proliferation of glomus cells adjacent to the blood spaces was not present; rather, the vessels were of variable sizes and were collapsed. In some areas, a nesting pattern similar to a hemangiopericytoma or a paraganglioma was present. The stromal response consisted of marked fibrosis, and in some areas myxoid change which resembled chondroid was present. Material for histological study was fixed in 10% buffered formalin solution, and the paraffin-embedded sections were stained with hematoxylin and eosin. Immunhistochemical analysis was performed only on sections that did not require decalcification. Deparaffinized sections were immunostained with monoclonal antibodies to muscle-specific actin (MSA), keratin AE1/AE3, desmin, S-100 protein, vimentin, and factor VIII-related antigen. Immunohistochemical studies showed strongly positive staining for vimentin and MSA. Factor VIII-related antigen failed to stain the glomus cells but dramatically highlighted the vascularity of the t u m o r by staining the surrounding endothelial cells. Staining for S-100 protein of the critical cells or of the myxoid areas was absent. Staining results for keratin and desmin were negative. Electron microscopy showed fine filaments with dense bodies and dense attachment plaques in the cell cytoplasm. Additionally, a thick basement m e m b r a n e was present around individual cells. 9 1992 International Skeletal Society
408
Diagnosis: Primary glomus tumor of bone Discussion Glomus tumors are u n c o m m o n neoplasms which are usually easily recognized because of their distinctive clinical and histological appearance. Typically, these tumors present as painful, blue-red nodules in the deep dermis or subcutis of the extremities
T.J. Simmons et al. : Case report 749 with a predilection for the subungual region of the fingers. However, they have been described in a variety of unusual locations including the stomach [2, 9], small intestine [6], vagina [17], nose [1], and oral cavity [161. Primary intraosseous glomus tumors are indeed rare neoplasms. Since the first case report by De Latorre in 1939 [11], fewer than 15 cases have been reported [12, 15]. Truly unusual cases have been described in-
Pathological studies Fig. 2. Low magnification of the glomus tumor next to cortical bone. The neoplasm is composed of uniform round cells surrounding blood vessels. The loose stroma at the periphery appears myxoid and in some areas resembles chondroid material Fig. 3. This higher magnification of the glomus tumor demonstrates the monomorphic cells with bland and round nuclei in close contact with blood vessels, many of which have collapsed Fig. 4. Immunohistochemical staining of the glomus tumor with muscle-specific actin shows strong staining of the malignant cells adjacent to a muscular blood vessel which demonstrates staining of its wall
volving the middle phalanx [3] and the ulna [15], but the majority of these tumors affect the distal phalanges. Since this site is also a c o m m o n location for soft-tissue tumors and tumors o f bone, the diagnosis of a primary glomus t u m o r of bone m a y be difficult. Although m a n y soft-tissue tumors m a y produce a bony defect by pressure or erosion, by careful clinical and radiological studies it can be ascertained whether or not an osseous defect is due to an extraosseous
T.J. Simmons et al. : Case report 749 neoplasm. A diagnosis of primary bone involvement is easy if the t u m o r is completely bounded by cortical bone. I f this is not the case, then smooth erosion of the bone on one side points to an adjacent soft-tissue tumor, while an expanding, lytic lesion favors a primary bone neoplasm. The glomus t u m o r has a characteristic histological appearance, but it must be recognized that variable patterns do occur [5], depending on the relative proportions of glomus cells to blood vessels, the extent o f vascular ectasia and the stromal response to the tumor. A cellular neoplasm with a solid pattern can be misdiagnosed as hemangiopericytoma, adnexal tumor, or a metastatic epithelial neoplasm arising in organs such as the prostate and thyroid. In the present case, c h o n d r o b l a s t o m a was the diagnosis on frozen section; although chondroblastomas usually arise in long bones, the smaller bones of the hands and feet including the phalanges are occasionally involved [10]. Microscopically, b o t h chond r o b l a s t o m a and glomus t u m o r are composed of fairly uniform, rounded cells with punched-out nuclei and distinct cytoplasmic borders. In distinguishing between the two it is helpful to find the giant cells and foci of microcalcification that are characteristic of c h o n d r o b l a s t o m a and not seen in glomus tumor. Additionally, the nuclei in c h o n d r o b l a s t o m a are slightly more irregular than the nuclei in glomus tumors. Immunohistochemistry can be extremely helpful in establishing a diagnosis of glomus tumor, especially in cases where an atypical histological appearance exists. Since glomus tumors are generally considered to be composed of modified smooth muscle cells, it is not surprising that studies have shown that these tumors routinely stain for M S A and vimentin [4, 16]. The failure o f desmin to stain the t u m o r is of interest since it is a m a r k e r o f smooth muscle; apparently, this antigen is variably present on other cells that are considered modified smooth muscle cells,
409 such as pericytes or myoepithelial cells [13]. Immunoreactivity to keratin, S-100 protein, factor VIII-related antigen, and myogloblin have been shown to be negative [4]. Differentiating a glomus t u m o r from metastatic carcinoma or primary skin adnexal neoplasms m a y be morphologically difficult, but these epithelial neoplasms are positive for keratin and do not stain with MSA. H e m a n giopericytomas m a y also stain with M S A [8], but morphologically the malignant cells in this lesion have more ovoid and pleomorphic nuclei than the glomus t u m o r and have less distinct cytoplasmic borders. Chondroblastomas, unlike glomus tumors, stain with S-100 [14] and fail to stain with MSA. Intraosseous glomus tumors, like their soft-tissue counterparts, behave in a benign fashion. Metastasis and malignant transformation typically do not occur. Adequate treatment consists of excision or curettage in the case o f an intraosseous tumor. Infrequently, local recurrence occursusually the result of an inadequate excision. In summary, we report a case of p r i m a r y intraosseous glomus t u m o r in a 30-year-old m a n who was found to have an expanding, lytic lesion in the distal phalanx of his left thumb. The histological appearance was atypical in that areas of myxoid strom a resembled chondroid material. The unusual location and microscopic appearance caused diagnostic problems. Immunohistochemical studies, including strong positive staining for M S A and negative staining for keratin and S-100 protein, were helpful in establishing the correct diagnosis.
References
1. Apfelberg DB, Teasler JL (1968) Unusual locations and manifestations of glomus tumors (glomangiomas). Am J Surg 116:62 2. Appelman HD, Helwig FB (1969) Glo-
mus tumors of the stomach. Cancer 23 :203 3. Bjorkengren AG, Resnick D, Haghighi P, Sartoris DJ (1986) Intraosseous glomus tumor: report of a case and review of the literature. AJR 147: 739 4. Dervan PA, Tobbia IN, Casey M, O'Loughlin JO, O'Brien M (1989) Glomus tumours: an immunohistochemical profile of 11 cases. Histopathology 14:483 5. Enzinger FW, Weiss SW (1988) Soft tissue tumors, 2nd edn. CV Mosby, St Louis, p 583 6. Hamilton CW, Shelburne JD, Bossen EH, Lowe JE (1982) A glomus tumor of the jejunum masquerading as a carcinoid tumor. Hum Pathol 13:859 7. Hsu S, Raine L, Fanger H (1981) Use of avidin-biotin-immunoperoxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures. J Histochem Cytochem 29 : 577 8. Hultberg BM, Daugard S, Johansen HF, et al. (1988) Malignant hemangiopericytomas and hemangioendotheliosarcomas: an immunohistochemical study. Histopathology 12: 405 9. Kay S, Callahan WP Jr, Murray MR, Randall HT, Stout AP (1951) Glomus tumors of the stomach. Cancer 4: 726 10. Kurt AM, Unni KK, Sim FH, McLeod RA (1989) Chondroblastoma of bone. Hum Pathol 20: 965 11. Lattes R, Bull DC (1948) A case of glomus tumor with primary involvement of bone. Ann Surg 127:187 12. MacKenzie DH (1962) Intraosseous glomus tumors. J Bone Joint Surg [Br] 44: 648 13. Miettinin M, Lehto VP, Virtanen I (1983) Glomus tumor cells: evaluation of smooth muscle and endothelial properties. Virchows Arch [Cell Pathol] 43:139 14. Monda L, Wick MR (1985) S-100 protein immunostaining in the differential diagnosis of chondroblastoma. Hum Pathol 16:287 15. Rozmaryn LM, Sadler AH, Dorfman HD (1987) Intraosseous glomus tumor of the ulna. A case report. Clin Orthop 220:126 16. Saku T, Okabe H, Matsutani K, Sasaki M (1985) Glomus tumor of the cheek. An immunohistochemical demonstration of actin and myosin. Oral Surg Oral Med Oral Pathol 60:65 17. Spitzer M, Mulho L, Selzer VL, Lipper S (1985) Vaginal glomus tumor. Case presentation and ultrastructural findings. Obstet Gynecol 66:86S 18. Sunderraj S, A1-Khalifa AA, Pal AK, Pim HP, Sabri SH (1988) Primary intraosseous glomus tumor. Histopathology 14(5): 532
