Slowly enlarging gingival mass in a 50-year-old man

Vol. 116 No. 2 August 2013

CLINICOPATHOLOGIC CONFERENCE

Slowly enlarging gingival mass in a 50-year-old man Robert S. Redman, DDS, MSD, PhD,a Suman Chauhan, MD,b and Brian F. Paul, DMD, MSEd,c Washington, DC DEPARTMENT OF VETERANS AFFAIRS MEDICAL CENTER

(Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116:135-141)

CASE PRESENTATION A 50-year-old man presented to the Dental Clinic of the Washington, DC, Department of Veterans Affairs Medical Center with a triangle-shaped, dark red, lobular, soft gingival mass protruding from the embrasure of the maxillary central incisors (Figure 1). There was no ulceration or erosion of the surface. The patient reported that the growth had been present for about 2 months and was slowly enlarging. His past medical history was remarkable for an excisional biopsy of a small “fibroma,” which consisted of mature collagen bands and bundles with a few foci of inflammatory cells, in the lower labial mucosa 14 months previously. He also had undergone a total hip replacement 3 months previously. His medications included flunisolide, gabapentin, hydrochlorothiazide, and vardenalil. Routine blood tests were normal. A comprehensive periodontal examination revealed probing depths ranging from 2 to 4 mm. There were a limited number of sites, mainly associated with the mandibular incisors, which exhibited bleeding on probing consistent with the diagnosis of localized gingivitis. The mass was firm and did not blanch under pressure. The mesial aspects of the crowns of the central incisors were stained and had slight accumulations of plaque and calculus (Figure 1). A periapical radiograph (Figure 2) showed a minute subgingival spur of calculus on the mesial aspect of the root of the left central incisor. There was no widening of the periodontal ligament space, and no erosions or other abnormalities of the alveolar bone.

This article was declared exempt from review by the Chairman of the Human Subject Subcommittee and the Research and Development Committee of the Washington, DC, Veterans Affairs Medical Center, as the procedures were undertaken for diagnostic, not research, purposes, and it contains no personal identification data. a Oral Diagnosis Section, Dental Service, and Oral Pathology Research Laboratory, Department of Veterans Affairs Medical Center. b Anatomical Pathology Section, Pathology and Laboratory Service, Department of Veterans Affairs Medical Center. c Periodontics Section, Dental Service, Department of Veterans Affairs Medical Center. Received for publication Sep 15, 2011; returned for revision Feb 9, 2012; accepted for publication Feb 16, 2012. Published by Elsevier Inc. 2212-4403/$ - see front matter doi:10.1016/j.oooo.2012.02.005

DIFFERENTIAL DIAGNOSIS The interdental gingival location, soft consistency, dark red color, and lack of bony involvement suggested several common reactive growths and a number of neoplasms. Pyogenic granuloma (PG)1,2 took first place in the initial differential diagnosis of the gingival mass in this case, as the clinical presentation was a textbook example of a PG. This reactive hyperplastic lesion generally presents as a lobular red mass of vascular tissue, similar in appearance to granulation tissue. It is relatively common, slightly more so in females, occurs in a wide age range, may be ulcerated, and sometimes causes shallow erosion of the underlying alveolar bone. The gingiva is the most common oral site. The rate of enlargement varies, and some may reach several centimeters in diameter. An important predisposing factor is hormonal changes at puberty and during pregnancy. Capillaries are the dominant blood vessel, and chronic inflammatory cells are common but variable. When inflammatory cells are scarce, PG may be histologically indistinguishable from hemangioma. Indeed, lobular capillary hemangioma has been proposed as a term to replace PG.3 Neither term is ideal, as few cases of PG exhibit purulence and they are not granulomas (but do resemble granulation tissue), whereas hemangioma connotes a neoplastic rather than a reactive lesion. Growth is thought to be stimulated by chronic trauma or a nidus of calculus or foreign material. Peripheral giant cell granuloma (PGCG) is identical to PG with respect to clinical features and age range, but it is uncommon and is not influenced by hormonal factors associated with puberty and pregnancy.1,2 Both PG and PGCG are treated by surgical excision and removal of sources of chronic trauma and irritation such as fragments of calculus. Recurrences occur occasionally and usually are treated with excision to deeper tissues, such as periosteum and periodontal membranes. The failure to blanch under pressure tended to rule out hemangioma (other than PG/lobular hemangioma), although this test might be inhibited in one with drainage partly blocked by a phlebolith or thrombus. The edema of PGs with a strong inflammatory component might also inhibit blanching. 135

CLINICOPATHOLOGIC CONFERENCE Redman et al.

136

OOOO August 2013

Fig. 1. An exuberant, dark red mass emanates from the interproximal gingiva of the maxillary central incisors. The presence of slight stain and supragingival plaque can be appreciated.

Localized juvenile spongiotic gingival hyperplasia usually presents as a “papillary, bright red and easily bleeding gingival overgrowth,” superficially resembling PG.4 This entity differs clinically from PG in having a “granular, pebbly, or velvety,” not lobular, surface, and almost all cases have occurred before the age of 20 years. Histologically there is papillary hyperplasia of noncornified epithelium and intracellular edema, with richly vascular connective tissue pegs. Wegener’s granulomatosis is a serious disease that classically affects the lungs, kidneys, and upper respiratory tract, but sometimes affects the gingiva.1-3 The gingival lesions are bright red and granular with yellow flecks, and so have been described as “over-ripe strawberries.”5 The histologic picture is a vascular granulomatous mass with pseudoepitheliomatous hyperplasia, microabscesses, and multinucleate giant cells. The patient in the present case had no systemic signs or symptoms and the gingival lesion bore little resemblance to “strawberry gum.” Malignant neoplasms such as squamous cell carcinoma arising in the gingiva had to be considered, as some may present as a lobular red mass.1 A number of gingival growths resembling PG or PGCG have been reported to be the initial manifestation of metastatic neoplasms, with the lung being the most common source.6 Although enlargement of PG and PGCG may be fast enough to be alarming, gingival metastases have tended to exhibit almost exponential growth. Such rapid growth would suggest that it might be prudent to undertake an extensive physical workup early on. Several other reactive and benign neoplastic gingival growths were considered lower in the differential diagnosis because most are the color of the normal mucosa rather than red, unless the surface has been traumatized.

Fig. 2. A periapical radiograph of the maxillary central incisors shows intact periodontal ligament spaces and interproximal bone. One small spur of subgingival calculus is attached to the mesial surface of the root of the left central incisor.

Peripheral fibroma (PF), also known as gingival fibroma, “irritation” fibroma, and focal fibrous hyperplasia,1,2,7 is an exuberant reactive overgrowth of the gingiva. The incidence differs somewhat from PG in being even greater in females and in ages 10 to 20. Histologically, the bulk of PF is collagenous connective tissue. Foci of chronic inflammation and granulation tissue, especially near the base where calculus and other irritants may have lodged, seem to be the source of growth. Occasionally, granulation tissue is concentrated on or near the surface, and the resulting red color makes the lesion resemble a PG. This suggests that some PFs may be the end result of fibrosis of a PG. Peripheral ossifying fibroma is a PF harboring foci of calcification, osteoid and bone with a tendency for surface ulceration. Giant cell fibroma is a reactive fibrous hyperplasia sprinkled with moderately large, often multinucleated, stellate giant cells.1 The most common site in the gingiva is lingual to a mandibular canine, where it also is known as the “retrocuspid papilla.” Treatment of all of these variants of PF is surgical excision, including affected periodontal ligament, and removal of potential irritants, such as entrapped calculus and foreign material. Recurrence is uncommon and is treated with excision to the periosteum. A number of odontogenic neoplasms may bear resemblance to PF or PG but are much less common. Peripheral odontogenic fibroma (PODF) is a firm gin-

OOOO Volume 116, Number 2

gival growth composed of collagenous connective tissue of varying cellularity with prominent islands and strands of odontogenic epithelium.1,7,8 Dentinoid-, cementoid-, or osteoidlike calcified material may be deposited around some of the epithelial strands, which do not differentiate into ameloblasts or form stellate reticulum. Peripheral ameloblastoma is similar in clinical appearance to the peripheral odontogenic fibroma but differs histologically in that the epithelium is differentiated into ameloblasts and stellate reticulum.1,8,9 Although it thus is histologically identical to the central (intrabony) ameloblastoma, it is much less aggressive, as it may cup but does not invade the underlying bone. The incidence of PODF begins at a younger age, but both occur more often in the premolar-molar region. Treatment of both is similar to that of PG and PF. Solitary nerve sheath tumors sometimes arise from the gingiva, but are paler than or the same color as the gingiva and often are pedunculated.10 Other tumors that may involve the gingiva and resemble PG or PF include myoid tumors, such as myofibroma and myopericytoma,11 glomus tumor,12 and solitary fibrous tumor.13-16 Management and diagnosis The gingival growth was excisionally biopsied under local anesthesia, revealing a hypervascular base that did not bleed profusely or unexpectedly. Although there was scant calculus on the proximal root surfaces of these teeth, they were meticulously scaled to remove a potential reactive nidus. Pathologic findings After routine fixation in neutral buffered formalin, the mass was soft, pink and tan, and measured 0.5 ⫻ 0.4 ⫻ 0.3 cm. The tissue was hemisected and embedded in paraffin. In sections stained with hematoxylin and eosin (H&E; Figure 3, A), the mass showed modestly eosinophilic spindle cells multilayered around thin-walled blood vessels. In some areas the vessels branched in a “stag-horn” pattern, but where the tumor cells were near the lamina propria, many of the vessels were larger in diameter. Lymphocytes and neutrophils were rare except for a few that were widely scattered in the lamina propria. Thus, the dark red color of the growth (Figure 1, A) was attributed to the larger blood vessels subjacent to the epithelium, and not to an inflammatory reaction. The tumor cells were supported by a stroma with a few thin strands of collagen, and perivascular hyalinization was not seen. Mitotic figures were exceedingly rare, only 1 per 10 high-power (⫻400) fields. These features are very unlike those of hemangioma or PG (rich in blood vessels, like granulation tissue), or

CLINICOPATHOLOGIC CONFERENCE Redman et al. 137

PF or PODF (mainly mature collagen fibers), PGCG (like pyogenic granuloma but with multinucleated giant cells), or peripheral ameloblastoma. The preliminary diagnosis was “benign spindle cell lesion consistent with myopericytoma.” Although the tumor cells were not as overtly arranged in the characteristic concentric perivascular pattern as had been described in the defining early reports,11,16,17 a number of other cases of myopericytoma have been published in which the multilayered perivascular cells did not have the “onion skin” arrangement of concentric rings.18,19 Myopericytomas are part of a spectrum of tumors, such as glomus tumor, hemangioendothelioma, myofibroma, (plain) pericytoma, and solitary fibrous tumor, which have overlapping features.13-16 Glomus tumor has glomus cells,12,15 but the other members of this spectrum are less easily distinguished in routine sections. To clarify the diagnosis, additional sections were subjected to immunohistochemical procedures (IHC) with the following mouse anti-human monoclonal antibodies, which were obtained “ready to use” from Cell Marque (Rocklin, CA): CD10 (56C6), CD31 (1A10); CD34 (QBEnd10), desmin (D33), muscle-specific actin (MSA, HHF35); smooth-muscle actin (SMA, 1A4); vimentin (V9); and S-100 protein (4C4.9). Antibodies were localized as a brown precipitate via reaction with H2O2 and 3,3-diaminobenzidine (DAB), using Envision and dual-link horseradish peroxidase in a Dako (Carpenteria, CA) autostainer, and counterstained with hematoxylin. Native peroxidase was quenched in 3% H2O2. Reactions were enhanced by antigen retrieval in Reveal buffer in a pressure cooker. All of the antibodies reacted appropriately with negative (nonspecific mouse antibodies) and positive controls. All of the cells in the specimen except those of the surface epithelium were strongly reactive with vimentin (Figure 3, B), indicating that the tumor cells were mesenchymal, not epithelial. Reactions with CD34 (Figure 3, C) and CD31 (not illustrated) were confined to the endothelial cells of the blood vessels, ruling out hemangioendothelioma. In most of the specimen, tumor cells and some blood vessel cells reacted with SMA (Figure 3, D), whereas only the smooth muscle cells of a few large, feeder blood vessels reacted with MSA (Figure 3, E). Many tumor and blood vessel cells reacted with CD10 (Figure 3, F). No reactions occurred with S-100 (not illustrated), all but ruling out a nerve sheath tumor. These results are inconsistent with angioleiomyoma, which is IHC positive for desmin and MSA,20 and solitary fibrous tumor, also positive for MSA, in which perivascular hyalinization and large areas of fibrosis are diagnostic features. In almost all cases, the tumor cells

CLINICOPATHOLOGIC CONFERENCE Redman et al.

138

OOOO August 2013

Fig. 3. Photomicrographs illustrate pertinent histologic and immunohistochemical features of the gingival mass. A, Tumor cells are piled up in layers around scattered blood vessels, many of which have a branched, “stag-horn” pattern (arrow). Larger blood vessels lie in the interface between the lamina propria and the tumor, subjacent to the epithelium. In B through F, the specified target antigens were immunolocalized with a brown precipitate, followed by a light hematoxylin counterstain. B, Vimentin is labeled in all of the cells in the tumor and lamina propria, but in none of the overlying oral epithelium. C, CD34 is labeled in endothelial and associated blood vessel cells, but not in tumor cells. D, Smooth muscle actin is strongly labeled in myofibrils in the smooth muscle cells of the larger blood vessels and moderately in most, but not all, of the tumor cells. E, Muscle actin (HHF35) labeled only smooth muscle cells of the larger blood vessels. F, CD10 is strongly labeled in blood vessel cells and numerous tumor cells. (A, H&E stain; B-F, DAB-H; magnification bars ⫽ 150 ␮m [A, B], 100 ␮m [C-E], and 50 ␮m [F].)

are IHC positive for CD34,13-16 whereas myopericytomas are almost always IHC negative for CD34.11,20-25 The possibility remained that most of the tumor cells might be myofibroblasts, not myopericytes. To better define the cells in this regard, half of the tumor was removed from the paraffin block and prepared for examination by transmission electron microscopy (TEM), as follows. After being deparaffinized via xylol and decreasing concentrations of ethanol, the tissue was postfixed for 1 hour in 1.0% OsO4 in 0.1 mol/L SCollidine, pH 7.4, washed in the S-Collidine buffer and tap water, dehydrated with ethanol and propylene oxide, and embedded in Embed 812. Thin (approximately 70 nm) sections were cut from blocks representing all of the extracted half of the tumor, mounted on copper

grids, stained with uranyl actetate and lead citrate, and viewed and photographed in a JEOL JEM-100 CX electron microscope (JEOL Ltd., Tokyo, Japan). The vast majority of the tumor cells had tubular processes, contained a paucity of organelles, such as mitochondria and rough endoplasmic reticulum (RER), and microfilaments varying in amounts and organization from almost none to many, in many cells being mingled with dense bodies and attachment plaques (Figure 4). Occasional segments of the plasmalemma were associated with a basal lamina (Figure 4, B and C). The extent of microfilaments in these cells corresponded very well with the IHC localization of SMA, i.e., were lightly or nonreactive in a small part of the tumor, and moderately reactive in most of the tumor. These ultrastructural features are iden-

OOOO Volume 116, Number 2

CLINICOPATHOLOGIC CONFERENCE Redman et al. 139

Fig. 5. At 7 months postexcision, healing is complete and there is no sign of recurrence.

tical to those in descriptions and illustrations of normal and tumor pericytes and myopericytes,15,26,27 and distinguish them from fibroblasts and myofibroblasts, which have moderate to abundant RER and no associated basal lamina.26 Scattered fibroblasts and a very few myofibroblasts occurred around the collagen bundles and blood vessels of the supporting stroma, but rarely among the masses of tumor cells. Together, these histologic, IHC, and TEM observations demonstrated that the vast majority of the tumor cells were myopericytes, with a minority being plain pericytes, thus establishing the diagnosis as myopericytoma. There was no sign of recurrence at 7 (Figure 5) and 14 months postexcision.

Fig. 4. Transmission electron micrographs showing important features of the tumor. A, Mass of cells with processes cut mainly in cross section. Almost all of the cells are pericytes (p), i.e., harbor a paucity of cytoplasmic organelles, have no desmosomes or hemidesmosomes, and are rimmed with a thin basal lamina. Widely scattered fibroblasts (f) have moderate to abundant rough endoplasmic reticulum. B, A wavy band of collagen courses diagonally across the center, accompanied by fibroblasts (f) in a region of the tumor in which many of the pericytes have moderate to prominent microfibrils, and thus are myopericytes (mp). C, A group of myopericytes (mp) is pictured at higher magnification to better demonstrate their myofibrils and basal laminae (arrow). Magnification bars ⫽ 4.3 ␮m (A); 2.7 ␮m (B); and 1.4 ␮m (C).

DISCUSSION Myopericytoma was delineated from other myoid vascular tumors by Granter et al.28 in 1998, in part because of its distinctive arrangement of “bland, round-to-ovoid cells” in concentric layers around thin-walled blood vessels. Subsequently, Gengler and Guillou17 further separated myopericytoma from the spectrum of vascular tumors that had areas of variably thin-walled vessels with a “stag-horn” branching pattern, such as solitary fibrous tumor, myofibromatosis, and glomangiopericytoma, which had been lumped under hemangiopericytoma. Hemangiopericytomas were notorious for having unpredictable behavior. Most were benign, but some recurred multiple times and developed distant metastases. Each of the separated entities has a more clearly defined prognosis. Most of the malignancies have occurred in a very cellular variant of solitary fibrous tumor.17 Myopericytoma is benign, most recurrences being attributed to incomplete removal, although a few malignant myopericytomas have been reported.29 Although these cells differ from a few reports of myopericytoma by not labeling for MSA15,25 and being

CLINICOPATHOLOGIC CONFERENCE 140 Redman et al.

IHC positive for vimentin,11,24 these tests were not performed in many other articles. Most myopericytomas occur in the skin of the extremities.11,18,19 We found only 7 published cases that had occurred in the soft tissues of the oral cavity.20-25 Of these cases, 4 occurred in males and 3 in females. The age range was 28 to 72 years, with a mean of 48.6 years. Three occurred in the lips21,23 (2 upper, 1 lower), 1 each in the buccal mucosa21 and alveolar ridge,22 and 2 in the tongue.20,23 The present case occurred in a male, age 50 years, which nicely fits this profile of patients with oral myopericytomas, and adds the maxillary gingiva to the list of affected oral sites. A history of trauma was proposed as a source of stimulation for the myopericytoma of the alveolar ridge,22 and the authors presented a second case (nose) and cited another in support of this notion. Calculus plausibly was part of the etiology in the present case, as it long has been standard practice to remove such a “nidus” after excision of reactive gingival growths, such as pyogenic granuloma and gingival fibroma.1,2 Interestingly, Lau et al.23 reported the occurrence of myopericytomas in multiple sites, including one in the tongue, in 2 patients with AIDS, and cited a previously published (nonoral), similar case. Epstein-Barr virus was demonstrated in the tumors of these patients, but not in the myopericytomas of several other patients who were not infected with human immunodeficiency virus. This suggests that myopericytoma might be added to hairy leukoplakia and Kaposi sarcoma as growths or tumors that can be caused by this virus in immunocompromised individuals. As “myopericytoma” as a separate entity was not well publicized until the beginning of the 21st century, it stands to reason that there are other myopericytomas of the oral cavity that have been reported under other terms. An interesting case in point is the group of 5 tumors shown to have a translocation involving fusion of ACTB-GLI (beta actin and glioma genes), which resulted in activation of GLI.30 Three of these were in the tongue and 1 each in the stomach and calf. All had a lobulated pattern of spindle cells with pale eosinophilic cytoplasm arranged around small, thin-walled vessels. By IHC, all 5 specimens were variably positive for SMA and focally for laminin. Three each were positive for collagen type IV and CD10. All of those tested (not performed in some) were negative for CD34, cytokeratin, desmin, MSA, and S-100. By TEM, the tumor cells had the features of pericytes containing bands of cytoplasmic filaments with dense bodies and attachment plaques. The authors concluded that these tumors were pericytomas with myoid differentiation. Although they stopped short of calling them myopericytomas, these tumors have much in common, both

OOOO August 2013

histologically and immnunohistochemically, including being negative for MSA, with the gingival tumor presented here. In summary, the present case was a myopericytoma that presented as a soft red mass arising from the facial aspect of the gingiva between the maxillary central incisors. The differential diagnosis for a lump of this appearance includes reactive hyperplastic growths, such as pyogenic granuloma and peripheral fibroma with and without ossification, odontogenic neoplasms, such as peripheral odontogenic fibroma and peripheral ameloblastoma, hemangioma, and myoid tumors such as solitary fibrous tumor, leiomyoma, myofibroma, and myopericytoma. A combination of routine histologic stains, IHC characterization, and TEM evaluation was required to arrive at the correct diagnosis. Surgical resection provides a good prognosis. We thank Mrs. Lyvouch Filkoski for performing the immunohistochemistry and Mr. Willie Mayfield for preparing the tissues for electron microscopy. REFERENCES 1. Regezzi JA, Sciubba JJ, Jordan RCK, editors. Oral pathology. Clinical pathologic correlations. 5th ed. St. Louis: W. B. Saunders; 2008. p. O-37, 55, 111-3, 156-9, 264. 2. Buchner A, Schnaiderman-Shapiro A, Vered M. Relative frequency of localized reactive hyperplastic lesions of the gingiva: a retrospective study of 1675 cases from Israel. J Oral Pathol Med 2010;39:631-8. 3. Delbrouck C, Chamiec M, Hassid S, Ghanooni R. Lobular capillary hemangioma of the nasal cavity during pregnancy. J Laryngol Otol 2011;125:973-7. 4. Chang JY, Kessler HP, Wright JM. Localized juvenile spongiotic gingival hyperplasia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:411-8. 5. Napier SS, Allen JA, Irwin CR, McCluskey DR. Strawberry gums: a clinicopathological manifestation diagnostic of Wegener’s granulomatosis? J Clin Pathol 1993;46:709-12. 6. Hirshberg A, Shnaiderman-Shapiro A, Kaplan I, Berger R. Metastatic tumours to the oral cavity—pathogenesis and analysis of 673 cases. Oral Oncol 2008;44:743-52. 7. Kenney JN, Kaugars GE, Abbey LM. Comparison between the peripheral ossifying fibroma and peripheral odontogenic fibroma. J Oral Maxillofac Surg 1989;47:378-82. 8. Manor Y, Mardinger O, Katz J, Taicher S, Hirshberg A. Peripheral odontogenic tumors— differential diagnosis of gingival lesions. Int J Oral Maxillofac Surg 2004;33:268-73. 9. Philipsen HP, Reichart PA, Nikai H, Takata T, Kudo Y. Peripheral ameloblastoma: biological profile based on 160 cases from the literature. Oral Oncol 2001;37:17-27. 10. Ohno J, Iwahashi T, Ozasa R, Okamura K, Taniguchi K. Solitary neurofibroma of the gingiva with prominent differentiation of Meissner bodies: a case report. Diagn Pathol 2010;5:61-8. 11. Dray MS, McCarthy SW, Palmer AA, Bonar SF, Stalley PD, Marjoniemi V, et al. Myopericytoma: a unifying term for a spectrum of tumours that show overlapping features with myofibroma. A review of 14 cases. J Clin Pathol 2006; 59:67-73. 12. Boros AL, Davis JP, Sedghizadeh PP, Yamashita DD. Glomus

OOOO Volume 116, Number 2

13.

14.

15.

16.

17.

18.

19.

20. 21.

22.

tumor: report of a rare case affecting the oral cavity and review of the literature. J Oral Maxillofac Surg 2010;68:2329-34. Veltrini VC, Etges A, Magalhães MH, de Araújo NS, de Araújo VC. Solitary fibrous tumor of the oral mucosa—morphological and immunohistochemical profile in the differential diagnosis with hemangiopericytoma. Oral Oncol 2003;39:420-6. Cox DP, Daniels T, Jordan RC. Solitary fibrous tumor of the head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:79-84. Ide F, Obara K, Mishima K, Saito I, Kusama K. Ultrastructural spectrum of solitary fibrous tumor: a unique perivascular tumor with alternative lines of differentiation. Virchows Arch 2005; 446:646-52. Salgueiredo-Giudice F, Fornias-Sperandio F, Martins-Pereira E, da Costa dal Vechio AM, de Sousa SC, dos Santos-Pinto-Junior D. The immunohistochemical profile of oral inflammatory myofibroblastic tumors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;111:749-56. Gengler C, Guillou L. Solitary fibrous tumour and haemangiopericytoma: evolution of a concept. Histopathology 2006;48: 63-74. McMenamin ME. Myopericytoma. In: Fletcher CD, Unni KK, Mertens F, editors. World Health Organization classification of tumours. Pathology and genetics. Tumours of soft tissue and bone. Lyon: IARC; 2002. p. 138-9. Mentzel T, Dei Tos AP, Sapi Z, Kutzner H. Myopericytoma of skin and soft tissues: clinopathological and immunohistochemical study of 54 cases. Am J Surg Pathol 2006;30:104-13. Datta V, Rawai YB, Mincer HH, Anderson MK. Myopericytoma of the oral cavity. Head Neck 2007;239:605-8. Ide F, Mishima K, Yamada H, Saito I, Horie N, Shimoyama T, Kusama K. Perivascular myoid tumors of the oral region: a clinicopathologic re-evaluation of 35 cases. J Oral Pathol Med 2008;37:43-9. Laga AC, Tajirian AL, Islam MN, Bhattacharyya I, Cohen DM, Plamondon CJ, Robinson-Bostom L. Myopericytoma: report of two cases associated with trauma. J Cutan Pathol 2008;35: 866-70.

CLINICOPATHOLOGIC CONFERENCE Redman et al. 141 23. Lau PP, Wong O-, Lui PC, Cheung OY, Ho LC, Wong WC, et al. Myopericytoma in patients with AIDS: a new class of Epstein-Barr virus-associated tumor. Am J Surg Pathol 2009;33: 1666-72. 24. Sapelli S, Ribas M, Martins WD, de Noronha L, Gomes AP. Myopericytoma of the lip: report of a case. Head Neck 2009; 31:561-4. 25. Edgecombe A, Peterson RA, Shamji FM, Commons S, Sekhon H, Gomes MM. Myopericytoma: a pleural based spindle cell neoplasm off the beaten path. Int J Surg Pathol 2011;19:247-51. 26. Eyden B. The myofibroblast: a study of normal, reactive and neoplastic tissues, with an emphasis on ultrastructure. Part 1—normal and reactive cells. J Submicrosc Cytol Pathol 2005;37:109-204. 27. Dardick I, Hammar SP, Scheithauer BW. Ultrastructural spectrum of hemangiopericytoma: a comparative study of fetal, adult, and neoplastic pericytes. Ultrastruct Pathol 1989;13:111-54. 28. Granter SR, Badizadegan K, Fletcher CD. Myofibromatosis in adults, glomangiopericytoma, and myopericytoma: a spectrum of tumors showing perivascular myoid differentiation. Am J Surg Pathol 1998;22:513-25. 29. McMenamin ME, Fletcher CDM. Malignant myopericytoma: expanding the spectrum of tumours with myopericytic differentiation. Histopathology 2002;41:450-60. 30. Dahlén A, Fletcher CD, Mertens F, Fletcher JA, Perez-Atayde AR, Hicks MJ, et al. Activation of the GLI oncogene through fusion with the beta-actin gene (ACTB) in a group of distinctive pericyte neoplasms: pericytoma with t(7;12). Am J Pathol 2004;164:1645-53. Reprint requests: Robert S. Redman, DDS, MSD, PhD Oral Pathology Research Laboratory (151-I) Department of Veterans Affairs Medical Center 50 Irving Street, NW Washington, DC 20422 [email protected]