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Solitary fibrous tumor of the tongue: Report of a case with immunohistochemical and ultrastructural studies
Solitary Fibrous Tumor of the Tongue: Report of a Case with Immunohistochemical and Ultrastructural Studies Sang Ling Wu, MD, Russell Vang, MD, Fred J. Clubb, Jr, DVM, PhD, and John H. Connelly, MD Solitary fibrous tumors are rare in extrapleural sites and extremely rare in the oral cavity. We report a case of a solitary fibrous tumor arising from the tongue of a 70-year-old woman. The tumor measured 1.6 cm in maximum diameter and consists of spindle-shaped cells distributed in a haphazard pattern. Immunohistochemical studies show strong positivity for CD34 and bcl-2, and weak positivity for desmin. Smooth muscle actin and S-100 protein are negative. Electron microscopy shows uniform neoplastic spindle cells with mesenchymal features. The differential diagnosis for spindle cell neoplasms in the tongue is discussed. Ann Diagn Pathol 6: 168-171, 2002. Copyright 2002, Elsevier Science (USA). All rights reserved. Index Words: Solitary fibrous tumor, tongue, immunohistochemistry, ultrastructure
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OLITARY fibrous tumors (SFT) are unusual spindle cell neoplasms initially described in the pleura but recently described in diverse extrapleural sites, including the soft tissue of extremities, the abdominal cavity, mediastinum, breast, upper respiratory tract, orbit, meninges, thyroid, salivary glands, and oral cavity.1,2 Because of its histologic similarities with other soft tissue tumors, extrapleural SFTs may present a diagnostic challenge. Solitary fibrous tumors in the oral cavity are distinctly uncommon, with only one case previously described in the tongue.3 We attempt to further characterize SFTs in the tongue by including immunohistochemical and ultrastructural studies to facilitate in the recognition of this rare neoplasm. Ultrastructural descriptions of SFTs of the tongue have not previously been reported.
From the Department of Pathology and Laboratory Medicine, University of Texas – Houston Medical School; and the Department of Pathology and Laboratory Medicine, St. Lukes Episcopal Hospital, Houston, TX. Address reprints requests to Sang Ling Wu, MD, Department of Pathology and Laboratory Medicine, University of Texas – Houston Medical School, 6431 Fannin, Houston, TX 77030. Copyright 2002, Elsevier Science (USA). All rights reserved. 1092-9134/02/0603-0005$35.00/0 doi:10.1053/adpa.2002.33903
168
Report of a Case A 70-year-old woman presented with an indolent mass in the left ventral aspect of the tongue. She reported mild soreness around the tongue for 4 weeks before excision and was otherwise asymptomatic. On excision, gross examination of the tumor found a well-circumscribed tan-white mass measuring 1.6 ⫻ 1.4 ⫻ 1.3 cm. The cut surface appeared gray-white, solid, and homogenous. At the time of this publication, the patient remains asymptomatic and free from recurrent disease. Microscopically, the tumor consists of a poorly organizing, haphazard proliferation of small to medium spindle cells with scant cytoplasm and bland cytologic features (Fig 1). There are focal hypocellular areas composed of intercellular collagen fibrils and rare thin vascular channels. Some of the collagen fibers are markedly thickened. No mitoses or areas of necrosis are identified. The tumor cells stain strongly positive for CD34 (Fig 2) and bcl-2 oncoprotein, weakly positive for desmin, and negative for smooth muscle actin and S-100 protein. Ultrastructural studies show cellular areas composed of fibroblast-like spindle cells (Fig 3). The cytoplasm contains mitochondria, dilated cisternae of rough endoplasmic reticulum, and rare cytoplasmic filaments. The nuclei contain heterogenous chromatin with prominent nucleoli; additionally,
Annals of Diagnostic Pathology, Vol 6, No 3 (June), 2002: pp 168-171
Solitary Fibrous Tumor of the Tongue
Figure 1. Solitary fibrous tumor of the tongue composed of small to medium spindle cells in a haphazard proliferation with thickened intercellular collagen fibrils. (Top, low power; bottom, medium power.)
169
Figure 2. Tumor cells of SFT of the tongue staining strongly positive for CD34 (low power).
some nuclei contain nuclear bodies. The extracellular space contains variable amounts of collagen. Discussion Solitary fibrous tumors are rare spindle cell neoplasms initially described in the pleura by Klemperer and Rabin in 1937.4 Synonyms of SFTs in the literature include localized fibrous tumor, localized mesothelioma, localized fibrous mesothelioma, fibrous mesothelioma, subserosal fibroma, submesothelial fibroma, and pleural fibroma.5 While the pleura remains a more frequent site for SFTs, numerous reports within the past decade have described SFTs in diverse extrapleural locations. In the oral cavity, SFTs are exceedingly rare with only 12 cases reported, most involving the buccal mucosa and the posterior trigone.6-9 One case of SFT in the tongue has been previously reported.3
Figure 3. Electron micrograph displaying a portion of tumor cell showing dilated rough endoplasmic reticulum (asterisk) and nuclear body (arrow). (Uranyl acetate and lead citrate stains, magnification ⫻ 6,000; bar ⫽ 1m.)
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Wu et al
The utility of immunohistochemistry is becoming more evident in diagnosing SFTs of extrapleural sites. CD34 antigen, a 110-kd transmembrane cell surface glycoprotein, has recently emerged as a helpful marker for distinguishing SFTs from other soft tissue tumors.5 Bcl-2 protein, the product of a mitochondrial oncogene involved in the regulation of cell death, is another marker that exhibits strong immunoreactivity in SFTs. Suster et al10 studied CD34 and bcl-2 reactivity in 56 cases of SFTs (40 pleural and 16 extrapleural) and showed positive reactivity with CD34 in 55 out of 56 cases (98%) and strong diffuse reactivity with bcl-2 in all 56 cases. While the presence of CD34 and bcl-2 positivity strongly supports a diagnosis of SFT, it is important to note that other spindle cell neoplasms may also exhibit CD34 and/or bcl-2 immunoreactivity. CD34 and bcl-2 may be variably positive in dermatofibrosarcoma protuberans, hemangiopericytomas, gastrointestinal stromal tumors, neural tumors, fibrous meningiomas, and some smooth muscle tumors.10 Therefore, interpretation of positive immunoreactivity with CD34 and bcl-2 must be determined in the appropriate clinical context and in combination with histology and other immunohistochemical markers. The immunoreactivity of our case is consistent with the immunohistochemical profile of SFTs: positive for CD34 and bcl-2, weakly positive for desmin, and negative for smooth muscle actin and S-100 protein. While desmin is usually negative in SFTs, focal weak positivity has been seen in rare cases.5 Its association and significance in SFT of the tongue is unknown. The histogenesis of SFTs has been a topic of controversy, but the current prevailing theory supported by immunohistochemical and ultrastructural studies favors a fibroblastic line of differentiation.1,5 The cell of origin for SFTs arising from the tongue has not been previously demonstrated by electron microscopy. Our ultrastructural findings show nonspecific fibroblastic differentiation, similar to those demonstrated in SFTs in other locations outside the tongue.1 The reported incidence of malignancy in SFTs of the pleural cavity has been between 13% and 23%. Malignancy was defined as local invasion, local recurrence, intrathoracic spread, or distant metastasis. In extrapleural locations, however, SFTs are almost always benign with rare recurrence or metastasis. The criteria for diagnosing malignant SFTs is poorly defined, with some studies using morpho-
logic landmarks while others using growth patterns. Chan5 suggests incorporating both morphologic features and growth pattern in the categorization of SFTs. The tumor is classified as malignant if any of the following criteria are present: (1) presence of sarcomatous areas within an otherwise typical SFT or (2) development of sarcoma in the same site previously documented to harbor a SFT. The sarcomatous component is recognized by the presence of two or more of the following features: high cellularity with crowding and overlapping of nuclei, cellular pleomorphism, and mitotic count of less than 4/10 high power field. It should be noted, thereafter, that occasional large bizarre cells or focal areas of high cellularity are acceptable within the spectrum of benign SFT. Complete surgical resection is the treatment of choice for both benign and malignant SFTs. For our case, we favor it being a benign neoplasm because of the lack of sarcomatous morphologic features. The differential diagnosis of SFT of the tongue includes several spindle cell neoplasms including nodular fasciitis, hemangiopericytoma, myofibroblastoma, schwannoma, neurofibroma, and leiomyoma. Nodular fasciitis is a cellular fibroblastic lesion not commonly seen in the oral cavity. Nodular fasciitis has a more myxoid stroma with granulation tissue, hemorrhage, and mitosis. Furthermore, nodular fasciitis is uniformly negative for bcl-2 and CD34 and positive for smooth muscle actin, which is in direct contrast to the staining pattern of our case. Hemangiopericytomas may be considered in the differential diagnosis and may exhibit indistinguishable histologic features from SFTs. The distinction between the two tumors may be significant because rare malignant hemangiopericytomas have been described in the oral cavity. Hemangiopericytomas generally contain less collagen and possess round to oval cytologic features rather than spindled cells. CD34 positivity may be seen in hemangiopericytomas, therefore limiting its diagnostic value.6 There is one case of myofibroblastoma in the tongue with similar reported histologic features as SFTs.11 The myofibroblastoma was described as having uniform spindle cells arranged in short fascicles with ultrastructural studies showing both fibroblasts and smooth muscle differentiation. Smooth muscle actin was positive and CD34 and
Solitary Fibrous Tumor of the Tongue
bcl-2 were not performed. In our case, however, smooth muscle actin was distinctly negative. Neural tumors such as schwannomas and neurofibromas need to be ruled out. Schwannomas will generally display encapsulation. While our reported case was well circumscribed, it was not encapsulated. Microscopically, schwannomas have characteristic histology with verrucay bodies and Antoni A and Antoni B patterns. Neurofibromas have individual slender, wavy cells in a looser matrix. Both neural neoplasms can show mild to moderate CD34 and bcl-2 positivity.10 However, strong S-100 protein positivity in schwannomas and partial S-100 positivity in neurofibromas can help distinguish these tumors from SFTs. Our case was uniformly negative for S-100 protein. Leiomyomas have a more fascicular architecture. Smooth muscle actin will be positive and CD34 and bcl-2 will be negative. Our results were in direct contrast to that immunohistochemical profile. Ultrastructural studies of leiomyomas will show smooth muscle differentiation, while our electron microscopy findings reveal nonspecific fibroblastic differentiation. In conclusion, we report a case of a SFT arising in the tongue with characteristic histology of spindleshaped cells distributed in a haphazard pattern. The tumor cells are CD34 and bcl-2 positive, and smooth muscle actin and S-100 protein negative, consistent with the immunohistochemical profile for SFTs. Ultrastructural studies also confirm the fibroblastic origin of the tumor. While SFTs in extrapleural sites remain uncommon, it should be considered in the differential diagnosis of spindle cell neoplasms.
171
Acknowledgement The authors would like to thank Ralph Nichols for his excellent technical assistance.
References 1. Suster S, Nascimento AG, Miettinen M, et al: Solitary fibrous tumors of soft tissue: A clinicopathologic and immunohistochemical study of 12 cases. Am J Surg Pathol 1995;19:12571266 2. Brunnemann RB, Ro JY, Ordonez NG, et al: Extrapleural solitary fibrous tumor: A clinicopathologic study of 24 cases. Mod Pathol 1999;12:1034-1042 3. Piattelli A, Fioroni M, Rubini C: Solitary fibrous tumor of the tongue. Oral Oncol 1998;34:431-434 4. Klemperer P, Rabin CB: Primary neoplasms of the pleura. Report of five cases. Arch Pathol 1937;11:385-412 5. Chan JKC: Solitary fibrous tumor – Everywhere, and a diagnosis in vogue. Histopathology 1997;31:568-576 6. Perez-Ordonez B, Koutlas IG, Strich E, et al: Solitary fibrous tumor of the oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:589-593 7. Iwai S, Nakazawa M, Yoshikawa F, et al: Solitary fibrous tumor of the buccal mucosa: Report of a case with immunohistochemical studies. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:461-465 8. Kurihara K, Mizuseki K, Sonobe J, et al: Solitary fibrous tumor of the oral cavity: Report of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:223-226 9. Lukinmaa PL, Hietanen J, Warfvinge G, et al: Solitary fibrous tumour of the oral cavity: Clinicopathological and immunohistochemical characterization of three cases. J Oral Pathol Med 2000:29:186-192 10. Suster S, Fisher C, Moran CA: Expression of bcl-2 oncoprotein in benign and malignant spindle cell tumors of soft tissue, skin, serosal surfaces, and gastro-intestinal tract. Am J Surg Pathol 1998;22:863-872 11. Sahin AA, Ro JY, Ordonez NG, et al: Myofibroblastoma of the tongue: An immunohistochemical, ultrastructural, and flow cytometric study. Am J Clin Pathol 1990;94:773-777
S
OLITARY fibrous tumors (SFT) are unusual spindle cell neoplasms initially described in the pleura but recently described in diverse extrapleural sites, including the soft tissue of extremities, the abdominal cavity, mediastinum, breast, upper respiratory tract, orbit, meninges, thyroid, salivary glands, and oral cavity.1,2 Because of its histologic similarities with other soft tissue tumors, extrapleural SFTs may present a diagnostic challenge. Solitary fibrous tumors in the oral cavity are distinctly uncommon, with only one case previously described in the tongue.3 We attempt to further characterize SFTs in the tongue by including immunohistochemical and ultrastructural studies to facilitate in the recognition of this rare neoplasm. Ultrastructural descriptions of SFTs of the tongue have not previously been reported.
From the Department of Pathology and Laboratory Medicine, University of Texas – Houston Medical School; and the Department of Pathology and Laboratory Medicine, St. Lukes Episcopal Hospital, Houston, TX. Address reprints requests to Sang Ling Wu, MD, Department of Pathology and Laboratory Medicine, University of Texas – Houston Medical School, 6431 Fannin, Houston, TX 77030. Copyright 2002, Elsevier Science (USA). All rights reserved. 1092-9134/02/0603-0005$35.00/0 doi:10.1053/adpa.2002.33903
168
Report of a Case A 70-year-old woman presented with an indolent mass in the left ventral aspect of the tongue. She reported mild soreness around the tongue for 4 weeks before excision and was otherwise asymptomatic. On excision, gross examination of the tumor found a well-circumscribed tan-white mass measuring 1.6 ⫻ 1.4 ⫻ 1.3 cm. The cut surface appeared gray-white, solid, and homogenous. At the time of this publication, the patient remains asymptomatic and free from recurrent disease. Microscopically, the tumor consists of a poorly organizing, haphazard proliferation of small to medium spindle cells with scant cytoplasm and bland cytologic features (Fig 1). There are focal hypocellular areas composed of intercellular collagen fibrils and rare thin vascular channels. Some of the collagen fibers are markedly thickened. No mitoses or areas of necrosis are identified. The tumor cells stain strongly positive for CD34 (Fig 2) and bcl-2 oncoprotein, weakly positive for desmin, and negative for smooth muscle actin and S-100 protein. Ultrastructural studies show cellular areas composed of fibroblast-like spindle cells (Fig 3). The cytoplasm contains mitochondria, dilated cisternae of rough endoplasmic reticulum, and rare cytoplasmic filaments. The nuclei contain heterogenous chromatin with prominent nucleoli; additionally,
Annals of Diagnostic Pathology, Vol 6, No 3 (June), 2002: pp 168-171
Solitary Fibrous Tumor of the Tongue
Figure 1. Solitary fibrous tumor of the tongue composed of small to medium spindle cells in a haphazard proliferation with thickened intercellular collagen fibrils. (Top, low power; bottom, medium power.)
169
Figure 2. Tumor cells of SFT of the tongue staining strongly positive for CD34 (low power).
some nuclei contain nuclear bodies. The extracellular space contains variable amounts of collagen. Discussion Solitary fibrous tumors are rare spindle cell neoplasms initially described in the pleura by Klemperer and Rabin in 1937.4 Synonyms of SFTs in the literature include localized fibrous tumor, localized mesothelioma, localized fibrous mesothelioma, fibrous mesothelioma, subserosal fibroma, submesothelial fibroma, and pleural fibroma.5 While the pleura remains a more frequent site for SFTs, numerous reports within the past decade have described SFTs in diverse extrapleural locations. In the oral cavity, SFTs are exceedingly rare with only 12 cases reported, most involving the buccal mucosa and the posterior trigone.6-9 One case of SFT in the tongue has been previously reported.3
Figure 3. Electron micrograph displaying a portion of tumor cell showing dilated rough endoplasmic reticulum (asterisk) and nuclear body (arrow). (Uranyl acetate and lead citrate stains, magnification ⫻ 6,000; bar ⫽ 1m.)
170
Wu et al
The utility of immunohistochemistry is becoming more evident in diagnosing SFTs of extrapleural sites. CD34 antigen, a 110-kd transmembrane cell surface glycoprotein, has recently emerged as a helpful marker for distinguishing SFTs from other soft tissue tumors.5 Bcl-2 protein, the product of a mitochondrial oncogene involved in the regulation of cell death, is another marker that exhibits strong immunoreactivity in SFTs. Suster et al10 studied CD34 and bcl-2 reactivity in 56 cases of SFTs (40 pleural and 16 extrapleural) and showed positive reactivity with CD34 in 55 out of 56 cases (98%) and strong diffuse reactivity with bcl-2 in all 56 cases. While the presence of CD34 and bcl-2 positivity strongly supports a diagnosis of SFT, it is important to note that other spindle cell neoplasms may also exhibit CD34 and/or bcl-2 immunoreactivity. CD34 and bcl-2 may be variably positive in dermatofibrosarcoma protuberans, hemangiopericytomas, gastrointestinal stromal tumors, neural tumors, fibrous meningiomas, and some smooth muscle tumors.10 Therefore, interpretation of positive immunoreactivity with CD34 and bcl-2 must be determined in the appropriate clinical context and in combination with histology and other immunohistochemical markers. The immunoreactivity of our case is consistent with the immunohistochemical profile of SFTs: positive for CD34 and bcl-2, weakly positive for desmin, and negative for smooth muscle actin and S-100 protein. While desmin is usually negative in SFTs, focal weak positivity has been seen in rare cases.5 Its association and significance in SFT of the tongue is unknown. The histogenesis of SFTs has been a topic of controversy, but the current prevailing theory supported by immunohistochemical and ultrastructural studies favors a fibroblastic line of differentiation.1,5 The cell of origin for SFTs arising from the tongue has not been previously demonstrated by electron microscopy. Our ultrastructural findings show nonspecific fibroblastic differentiation, similar to those demonstrated in SFTs in other locations outside the tongue.1 The reported incidence of malignancy in SFTs of the pleural cavity has been between 13% and 23%. Malignancy was defined as local invasion, local recurrence, intrathoracic spread, or distant metastasis. In extrapleural locations, however, SFTs are almost always benign with rare recurrence or metastasis. The criteria for diagnosing malignant SFTs is poorly defined, with some studies using morpho-
logic landmarks while others using growth patterns. Chan5 suggests incorporating both morphologic features and growth pattern in the categorization of SFTs. The tumor is classified as malignant if any of the following criteria are present: (1) presence of sarcomatous areas within an otherwise typical SFT or (2) development of sarcoma in the same site previously documented to harbor a SFT. The sarcomatous component is recognized by the presence of two or more of the following features: high cellularity with crowding and overlapping of nuclei, cellular pleomorphism, and mitotic count of less than 4/10 high power field. It should be noted, thereafter, that occasional large bizarre cells or focal areas of high cellularity are acceptable within the spectrum of benign SFT. Complete surgical resection is the treatment of choice for both benign and malignant SFTs. For our case, we favor it being a benign neoplasm because of the lack of sarcomatous morphologic features. The differential diagnosis of SFT of the tongue includes several spindle cell neoplasms including nodular fasciitis, hemangiopericytoma, myofibroblastoma, schwannoma, neurofibroma, and leiomyoma. Nodular fasciitis is a cellular fibroblastic lesion not commonly seen in the oral cavity. Nodular fasciitis has a more myxoid stroma with granulation tissue, hemorrhage, and mitosis. Furthermore, nodular fasciitis is uniformly negative for bcl-2 and CD34 and positive for smooth muscle actin, which is in direct contrast to the staining pattern of our case. Hemangiopericytomas may be considered in the differential diagnosis and may exhibit indistinguishable histologic features from SFTs. The distinction between the two tumors may be significant because rare malignant hemangiopericytomas have been described in the oral cavity. Hemangiopericytomas generally contain less collagen and possess round to oval cytologic features rather than spindled cells. CD34 positivity may be seen in hemangiopericytomas, therefore limiting its diagnostic value.6 There is one case of myofibroblastoma in the tongue with similar reported histologic features as SFTs.11 The myofibroblastoma was described as having uniform spindle cells arranged in short fascicles with ultrastructural studies showing both fibroblasts and smooth muscle differentiation. Smooth muscle actin was positive and CD34 and
Solitary Fibrous Tumor of the Tongue
bcl-2 were not performed. In our case, however, smooth muscle actin was distinctly negative. Neural tumors such as schwannomas and neurofibromas need to be ruled out. Schwannomas will generally display encapsulation. While our reported case was well circumscribed, it was not encapsulated. Microscopically, schwannomas have characteristic histology with verrucay bodies and Antoni A and Antoni B patterns. Neurofibromas have individual slender, wavy cells in a looser matrix. Both neural neoplasms can show mild to moderate CD34 and bcl-2 positivity.10 However, strong S-100 protein positivity in schwannomas and partial S-100 positivity in neurofibromas can help distinguish these tumors from SFTs. Our case was uniformly negative for S-100 protein. Leiomyomas have a more fascicular architecture. Smooth muscle actin will be positive and CD34 and bcl-2 will be negative. Our results were in direct contrast to that immunohistochemical profile. Ultrastructural studies of leiomyomas will show smooth muscle differentiation, while our electron microscopy findings reveal nonspecific fibroblastic differentiation. In conclusion, we report a case of a SFT arising in the tongue with characteristic histology of spindleshaped cells distributed in a haphazard pattern. The tumor cells are CD34 and bcl-2 positive, and smooth muscle actin and S-100 protein negative, consistent with the immunohistochemical profile for SFTs. Ultrastructural studies also confirm the fibroblastic origin of the tumor. While SFTs in extrapleural sites remain uncommon, it should be considered in the differential diagnosis of spindle cell neoplasms.
171
Acknowledgement The authors would like to thank Ralph Nichols for his excellent technical assistance.
References 1. Suster S, Nascimento AG, Miettinen M, et al: Solitary fibrous tumors of soft tissue: A clinicopathologic and immunohistochemical study of 12 cases. Am J Surg Pathol 1995;19:12571266 2. Brunnemann RB, Ro JY, Ordonez NG, et al: Extrapleural solitary fibrous tumor: A clinicopathologic study of 24 cases. Mod Pathol 1999;12:1034-1042 3. Piattelli A, Fioroni M, Rubini C: Solitary fibrous tumor of the tongue. Oral Oncol 1998;34:431-434 4. Klemperer P, Rabin CB: Primary neoplasms of the pleura. Report of five cases. Arch Pathol 1937;11:385-412 5. Chan JKC: Solitary fibrous tumor – Everywhere, and a diagnosis in vogue. Histopathology 1997;31:568-576 6. Perez-Ordonez B, Koutlas IG, Strich E, et al: Solitary fibrous tumor of the oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:589-593 7. Iwai S, Nakazawa M, Yoshikawa F, et al: Solitary fibrous tumor of the buccal mucosa: Report of a case with immunohistochemical studies. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:461-465 8. Kurihara K, Mizuseki K, Sonobe J, et al: Solitary fibrous tumor of the oral cavity: Report of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:223-226 9. Lukinmaa PL, Hietanen J, Warfvinge G, et al: Solitary fibrous tumour of the oral cavity: Clinicopathological and immunohistochemical characterization of three cases. J Oral Pathol Med 2000:29:186-192 10. Suster S, Fisher C, Moran CA: Expression of bcl-2 oncoprotein in benign and malignant spindle cell tumors of soft tissue, skin, serosal surfaces, and gastro-intestinal tract. Am J Surg Pathol 1998;22:863-872 11. Sahin AA, Ro JY, Ordonez NG, et al: Myofibroblastoma of the tongue: An immunohistochemical, ultrastructural, and flow cytometric study. Am J Clin Pathol 1990;94:773-777