- Email: [email protected]
Nodular lesion in the anterior hard palate
Vol. 114 No. 2 August 2012
CLINICOPATHOLOGIC CONFERENCE
Nodular lesion in the anterior hard palate Adriele Ferreira Gouvêa, DDS, PhD, Katya Pulido Díaz, DDS, Jorge Esquiche Léon, DDS, PhD, Pablo Agustin Vargas, DDS, PhD, Oslei Paes de Almeida, DDS, PhD, and Márcio Ajudarte Lopes, DDS, PhD (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:154-159)
CLINICAL PRESENTATION A 13-year-old boy was referred to the Oral Diagnosis Clinic (Orocentro—Piracicaba Dental School, University of Campinas, São Paulo, Brazil) for evaluation of an asymptomatic oral swelling that had been present for 7 years. According to his father, the swelling had suddenly grown recently. The clinical examination showed a well delimited bilobulated nodular lesion on the anterior region of the right-sided hard palate that measured about 2.0 ⫻ 1.5 cm and was nontender and firm on palpation (Figure 1). A small ulcer was noticed on the anterior lobe, probably due to contact with the lower teeth. There was no report of local trauma, the patient presented no parafunctional habits, and the medical history was noncontributory. In addition, there was no mobility of the teeth, and no radiographic changes were seen. DIFFERENTIAL DIAGNOSIS According to the clinical characteristics, differential diagnoses should consider lesions that occur on the hard palate of young patients. Some possible diagnoses involving such lesions include reactive lesions, congenital lesions, myofibroblastic lesions, mesenchymal and odontogenic tumors, and hamartomatous lesions. Given the lack of salivary gland tissue in the anterior hard palate, a salivary gland tumor would not be likely. A focal enlargement of the gingiva could have a variety of differential diagnoses, but focal fibrous hyperplasia (fibroma), pyogenic granuloma, peripheral giant cell granuloma, and peripheral ossifying fibroma are the most common. Focal fibrous hyperplasia (fibroma) has an innocuous evolution and was considered as a differential diagnosis, although the patient denied any associated irritant Department of Oral Diagnosis, Oral Semiology and Oral Pathology Sections, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil. Received for publication Jun 7, 2011; returned for revision Oct 26, 2011; accepted for publication Nov 3, 2011. © 2012 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter doi:10.1016/j.oooo.2011.11.005
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factor. It is a reactive lesion resulting from the accumulation of fibrous tissue due to a local trauma, and it can develop at any site of the oral mucosa. It is commonly covered by normal mucosa, but occasionally may present an erythematous, ulcerated, or leukoplakic surface.1 Pyogenic granuloma (PG) is another reactive inflammatory lesion that presents granulation tissue and extensive endothelial proliferation. Fertile and pregnant women, children, and adolescents are more likely to develop PG. It can manifest as a painless smooth or lobulated mass with a surface that bleeds quite easily (owing to its extreme level of vascularity), and it can be ulcerated. Because of their high level of vascularity, young PGs are red, whereas older lesions are more collagenized and appear pink or normally colored.1 Peripheral giant cell granuloma (PGCG) is a reactive lesion that occurs exclusively on the gingiva/alveolar mucosa and is slightly more common in adult women. Characteristically, PGCG is a fast-growing, purpleblue, dome-shaped lesion that can cause slight resorption of the underlying bone.1 The lesion is similar histopathologically to brown tumor of hyperparathyroidism, which very rarely may mimic a PGCG of the jaws.2 Peripheral ossifying fibroma (POF) is another reactive lesion that only occurs on the gingiva, most commonly in the maxillary anterior region. Lesions range in color from pink to red, and the surface may or may not be ulcerated. Red ulcerated lesions often are mistaken for PGs, whereas pink nonulcerated lesions often are clinically diagnosed as focal fibrous hyperplasia.1 Congenital granular epulis (CGE), congenital epulis, or congenital epulis of the newborn is a benign tumor arising from the alveolar ridge of newborns. It commonly affects females (nearly 10:1), possibly indicating a hormonal influence, and it involves the maxillary alveolar ridge twice as often as the mandibular ridge, always on its anterior portion. It presents as a solitary, somewhat pedunculated, normally colored or reddish, fibroma-like lesion. CGE can present from a few millimeters to several centimeters in size, and it often causes alarm when it appears. In some cases it can
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interfere with breathing and feeding.3,4 In the present case, the patient’s father claimed that onset of the lesion occurred 7 years previously, but this information may be inaccurate. Although there are no cases reported in the literature of a patient presenting with a CGE at this age, this differential diagnosis should be considered in the current case. Oral myofibromas are rare, but some cases have been described affecting different intraoral sites, such as the upper labial mucosa, tongue, gingiva, palate, and intraosseous locations (mandible). Usually, they are found in cutaneous/subcutaneous tissues and in the skeletal muscles of the head and neck region, and they may be solitary (myofibromas) or multicentric (myofibromatosis).5–7 There are only a few studies reporting palatal myofibromas, and some cases clinically resemble the present case.8,9 Peripheral odontogenic tumors (neoplastic or hamartomatous) can have a clinical presentation similar to the present case. Peripheral or extraosseous odontogenic tumors are rare, but it is accepted that the remnants of the odontogenic epithelium entrapped in oral soft tissues may differentiate and form peripheral odontogenic tumors. Ide et al.,10 in a series of 30 peripheral odontogenic tumors, reported that odontogenic fibroma and ameloblastoma were by far the most common lesions. Peripheral odontogenic fibroma is characterized by a fibrous or fibromyxomatous proliferation that contains varying amounts of odontogenic epithelium embedded in a mature fibrous stroma. It occurs predominantly in the buccal gingiva of the mandible, although less frequently, in the maxilla.11,12 Extraosseous ameloblastoma is rare, comprising 1.3%-10% of all ameloblastomas. It presents in a wide age range, commonly affecting patients in the fifth to seventh decades, and more frequently involves the mandibular tooth-bearing areas/alveolar mucosa. Both lesions can have a clinical presentation as a gingival/mucosal swelling, without significant bone involvement or saucerization, as seen in the present case.12 Ide et al.10 described a case with a clinical presentation similar to that of our patient: a 9-year-old girl with a 1.0-cm dome-shaped mass on the palatal gingiva of the left central incisor. The lesion was given the diagnosis of a peripheral calcifying epithelial odontogenic tumor-like hamartoma, and it presented a sheet of polyhedral epithelium with intercellular bridges, ghost cells, and concentric calcifications. Moreover, those authors reported a case of peripheral odontoma with ghost cells in the enamel organ. Peripheral odontomas represent hamartomatous lesions and are extremely rare, occurring in children and adolescents, frequently in the anterior maxilla. Various names are found in the literature, probably reflecting the different stages of tooth
CLINICOPATHOLOGIC CONFERENCE Gouvêa et al. 155
germ development. Only 6 cases have been described on the palate, all in children and all with no bone involvement. Silva et al.13 reported 2 cases of peripheral odontoma; as in the present case, both presented as normally colored nodular lesions on the anterior hard palate laterally to the incisive papilla. Neural lesion was another clinical hypothesis. Oral peripheral nerve tumors include schwannoma, neurofibroma, nerve sheath myxoma (neurothekeoma), palisaded encapsulated neuroma (PEN), mucosal neuroma associated with multiple endocrine neoplasia III, and traumatic neuroma. The diagnosis of benign neural tumors can be challenging because of their overlapping histologic characteristics. The PEN is the most common type to affect the palatal mucosa, but neurofibromas and traumatic neuromas can occur at this location.14 Leiomyomatous hamartoma (LH) is an uncommon lesion in the oral cavity, with only a few cases having been described in the English-language literature. Even rarer is its occurrence on the anterior hard palate near to or involving the incisive papilla. However, it should be considered in clinical differential diagnosis. The original cases were described in a Japanese population, but it can be observed in other ethnic groups, mainly affecting young patients with ages varying from 3 months to 19 years. This type of lesion is painless, indolent, and self-limiting, and therefore probably underdiagnosed. LH can also develop in other areas of the body, such as the skin, lungs, kidney, and liver, and other authors have suggested its association with microphthalmia with linear skin defects syndrome. It tends to develop on the midline of the oral tongue or the anterior hard palate near the incisive papilla, where it appears as small, pink, polypoid lesions noted at or around birth.15 Other forms of hamartoma can arise in the mouth. They are microscopically characterized by a combination of benign tissue elements, including fibrovascular connective tissue, smooth-muscle bundles, skeletal muscle fibers, salivary tissue, adipose tissue, blood vessels, lymphoid tissue, peripheral nerves, and ganglion cells. The proportions of these tissues can vary, with the most prominent components being fibrous tissue, smoothmuscle bundles, or fat.15
DIAGNOSIS Based on the clinical and radiologic features of the present case, a large incisional biopsy was performed. A mass of fibroelastic tissue was removed under local anesthesia. The specimen was sent for histopathologic analysis and presented as a well circumscribed unencapsulated lesion composed of lobules separated by scanty fibrous tissue (Figure 2). There was proliferation of rounded, ovoid, spindle, and stellate cells in a pre-
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Fig. 2. Specimen obtained by incisional biopsy. Note the multilobulated, well defined, unencapsulated lesion with an oral mucosal stratified squamous epithelium surface (hematoxylin-eosin, ⫻5). Fig. 1. Nodular lesion on the anterior hard palate involving the incisive papilla and extending to the right palatine rugae.
dominant fibrous background (Figure 3, A), interspersed by chondroid (Figure 3, B) and myxoid tissue (Figure 3, C). There were areas presenting tumor cells with small hyperchromatic rounded or spindle-shaped nuclei. In other areas, the tumor cells contained illdefined and abundant eosinophilic cytoplasm surrounded by a stroma resembling chondroid tissue (Figure 3, B). No necrosis, mitoses, or local invasion was observed, nor were minor salivary glands seen. Nuclear pleomorphism, hyperchromatism, and pseudoinclusions were focally observed (Figure 3, D). The tumor cells were strongly positive for vimentin, glial fibrillary acidic protein (GFAP), and D2-40, focally positive for S100 (Figure 4), and negative for AE1/AE3, desmin, ␣-SMA, calponin, CD57, NSE, p63, and EMA. Based on the clinical, radiographic, histopathologic, and immunohistochemical features, the diagnosis of ectomesenchymal chondromyxoid tumor was made.
MANAGEMENT After the diagnosis, the patient’s parents were informed about the benign nature of the lesion. The remaining residual tumor showed growth after 11 months (Figure 5, A). At that time, they opted for surgical enucleation. The patient was doing well, with no evidence of recurrence 6 months after excision, and was still in clinical follow-up (Figure 5, B). DISCUSSION Ectomesenchymal chondromyxoid tumor (ECT) is a rare, benign, intraoral, soft tissue lesion, with 37 cases reported so far. It was first described in 1995 by Smith et al.,16 after reviewing Armed Forces Institute of Pathology files. It presents with a broad range of clinical and microscopic characteristic. Therefore, the reporting of new cases is important to reinforce its characteristics and to establish ECT diagnostic criteria.16 –19
The most plausible histogenesis of the ECT is that it develops from uncommitted ectomesenchymal cells from the neural crest, although salivary glands and muscles have also been considered as the tissues of origin.16,18 The overwhelming majority of cases developed in the anterior tongue, which is formed from the neural crest mesenchyme of the first anterior branchial arch. The diverse microscopic and immunohistochemical profiles seen for this lesion can be explained by the multipotent nature of these embryonic cells.17,18 The cases reported in the literature show that men and women are equally affected, with ages varying between 9 and 78 years (mean age 36.6 years); the majority of the patients were racially European. Most of the cases reported the presence of an asymptomatic and nontender submucosal nodule covered by normal mucosa, present for an average of 36.4 months. Few reported local complaints, such as local pressure and purulent discharge.16 –18 Our patient was a mixed-race 13-year-old who reported no symptomatology except the recent growth of the lesion, a finding also described by Kaplan et al.19 All but 2 cases were described on the anterior aspect of the oral tongue.16 –23 Of these 2, 1 occurred on the posterior tongue and 1 on the posterior hard palate.23,24 However, according to Ide25 and Allen,26 the latter case did not have sufficient documentation to support this diagnosis. Most of the studies describe a tumor size between 1 and 1.9 cm.17 Our patient presented a bilobulated nodular lesion measuring ⬃2.0 ⫻ 1.5 cm (Figure 1) on the anterior right hard palate, laterally to the incisive papilla, a location that had not been described before. Its occurrence in this site may be explained by the fact that this region is, like the anterior tongue, an embryonic fusion area (the primary palate and palatine crests converge to form the nasopalatine foramen, from which nerves and arteries emerge).22 The microscopic features of this lesion included lobulated sheets demarcated from the surrounding tissue.
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CLINICOPATHOLOGIC CONFERENCE Gouvêa et al. 157
Fig. 3. A, Tumor cells interspersed among loose fibrous tissue and arranged in lobules or islands surrounded by a dense fibrous background (hematoxylin-eosin [HE], ⫻20). B, Eosinophilic chondroid pattern characterized by tumor cells set in lacunae (HE, ⫻20). C, Hypercellular tumor island with cells interspaced in a myxoid background (HE, ⫻20), D, Hypercellular area demonstrating tumor cells with hyperchromatic and pleomorphic nuclei. Note the nuclear pseudoinclusion in the center of the photomicrograph (HE, ⫻40).
Most cases are unencapsulated, but the borders of the tumor are relatively well defined owing to the condensation of fibrous tissue and muscle fibers around the periphery of the tumor. A few muscle fibers can be focally infiltrated by tumor cells, but this does not seem to indicate evidence of aggressive biologic behavior.16,18,22 Three histologic patterns are usually discernible— cellular, myxoid, and chondroid areas—in variable proportions.16,17 The cells comprising these lobules can present rounded, ovoid, spindle, and stellate shapes arranged in the aforementioned backgrounds. Focal areas of atypia with nuclear pseudoinclusions, binucleated cells, prominent nucleoli, and nuclear hyperchromatism can be observed,16,17,21 as well as mitoses, though rarely.18 Necrosis has not been reported other than due to secondary trauma or infection. Focal areas of hemorrhage and inflammation can be found occasionally.16 There are a few reports describing the presence of minor salivary glands in the proximity of the tumor.20 –22 The current case encompassed all of the microscopic characteristics, but there was no sign of inflammatory infiltration and no presence of salivary glands (Figures 2 and 3). The cases described in the literature show vimentin and polyclonal GFAP positivity in 100% of them, as
well as S100 protein (in 78%), CD 57 (76%), monoclonal GFAP (69%), pancytokeratin clone AE1/AE3 (56%), ␣-SMA (33%), and desmin (15%) positivity.18 Therefore, it is suggested that some characteristics are important for ECT diagnosis: the presence of biphasic myxoid and chondroid patterns and the positivity of tumor cells for vimentin, S100, and GFAP. All of these criteria were fulfilled in the present report. The present case showed strong positivity for vimentin, GFAP, and D2-40 and focal immunopositivity for S100 (Figure 4), and was negative for AE1/AE3, desmin, ␣-SMA, calponin, CD57, NSE, p63, and EMA. The immunopositivity for the monoclonal antibody D2-40 was a fascinating finding, because this marker has the capability of highlighting chondroid tissue, according to the findings in a study by Huse et al.,27 where true chondroid tumors were distinguished from chordomas. This immunohistochemical test has not previously been performed for ECTs; D2-40 is an interesting marker to be studied in these lesions. All of the 37 previously reported cases of ECT were treated by conservative surgery. Only 2 cases showed tumor recurrence and were successfully managed with the use of a second surgical approach.16,18 The present case was surgically treated,
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Fig. 4. Immunoreactivity of the tumor cells for vimentin (A), GFAP (B), S100 (C), and D2-40 (D). Original magnification ⫻20.
Fig. 5. A, Residual lesion 11 months after the initial biopsy. B, The same area 6 months after reexcision.
but there was a residual lesion that showed considerable growth 11 months later. A second surgical approach was made and at the time of writing the patient was in clinical follow-up with no signs of recurrence (Figure 5, B). Although all available data strongly support the benign nature of ECT, cases of recurrence, microscopic foci of pleomorphic hyperchromatic cells, and sporadic mitoses suggest the importance of regular follow-up visits of the patient after treatment.18 In conclusion, ECT is an uncommon, intraoral, mesenchymal, soft tissue lesion that presents unique microscopic and immunohistochemical patterns of expression. The overwhelming majority of the reported cases are located
on the dorsum of the oral tongue, but it can also be found in the anterior hard palate. Therefore, clinicians should consider the occurrence of ECT in this oral site. REFERENCES 1. Neville B, Damm DD, Allen CM, Bouquot J. Oral and Maxillofacial Pathology. 3rd ed. Philadelphia: Saunders; 2009. 2. Sena Guimarães AL, Marques-Silva L, Cavaliéri Gomes C, Henriques Castro W, Alves Mesquita R, Santiago Gomez R. Peripheral brown tumour of hyperparathyroidism in the oral cavity. Oral Oncol Extra 2006;42:91-3. 3. van der Waal I. Congenital granular cell epulis. In: World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. Lyon: IARC; 2005. p. 198. 4. Bewley A, Bloom JD, Kherani S, Pawel BR. Congenital epulis. Ear Nose Throat J 2010;89:299-300.
OOOO Volume 114, Number 2 5. Rubin BP, Bridge JA. World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and Bone. Lyon: IARC Press; 2002. p. 59 – 61. 6. Vered M, Allon I, Buchner A, Dayan D. Clinico-pathologic correlations of myofibroblastic tumors of the oral cavity. II. Myofibroma and myofibromatosis of the oral soft tissues. J Oral Pathol Med 2007;36:304-14. 7. Azevedo R de S, Pires FR, Della Coletta R, de Almeida OP, Kowalski LP, Lopes MA. Oral myofibromas: report of two cases and review of clinical and histopathologic differential diagnosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:35-40. 8. Jones AC, Freedman PD, Kerpel SM. Oral myofibromas: a report of 13 cases and review of the literature. J Oral Maxillofac Surg 1994;52:870-5. 9. Montgomery E, Speight PM, Fisher C. Myofibromas presenting in the oral cavity: a series of 9 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;89:343-8. 10. Ide F, Obara K, Mishima K, Saito I, Horie N, Shimoyama T, et al. Peripheral odontogenic tumor: a clinicopathologic study of 30 cases. General features and hamartomatous lesions. J Oral Pathol Med 2005;34:552-7. 11. Ritwik P, Brannon RB. Peripheral odontogenic fibroma: a clinicopathologic study of 151 cases and review of the literature with special emphasis on recurrence. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:357-63. 12. Philipsen HP, Reichart PA, Sciuba JJ, van der Waal I. Odontogenic fibroma. In: World Health Organization classification of tumors. Pathology and Genetics—Head and Neck Tumors. Lyon: IARC; 2005. p. 315. 13. Silva AR, Carlos-Bregni R, Vargas PA, de Almeida OP, Lopes MA. Peripheral developing odontoma in newborn. Report of two cases and literature review. Med Oral Patol Oral Cir Bucal 2009;14:612-5. 14. Chrysomali E, Papanicolaou SI, Dekker NP, Regezi JA. Benign neural tumors of the oral cavity: a comparative immunohistochemical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84:381-90. 15. Napier SS, Devine JC, Rennie JS, Lamey PJ. Unusual leiomyomatous hamartoma of the hard palate: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:305-7. 16. Smith BC, Ellis GL, Meis-Kindblom JM, Williams SB. Ectomesenchymal chondromyxoid tumor of the anterior tongue. Nineteen cases of a new clinicopathologic entity. Am J Surg Pathol 1995;19:519-30.
CLINICOPATHOLOGIC CONFERENCE Gouvêa et al. 159 17. Pires FR, Abrahão AC, Cabral MG, Azevedo RS, Horta MC, Martins CR, et al. Clinical, histological and immunohistochemical features of ectomesenchymal chondromyxoid tumor. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:914-9. 18. Angiero F. Ectomesenchymal chondromyxoid tumour of the tongue. A review of histological and immunohistochemical features. Anticancer Res 2010;30:4685-9. 19. Kaplan I, Anavi Y, Calderon S. Ectomesenchymal chondromyxoid tumour of the anterior tongue. Int J Oral Maxillofac Surg 2004;33:404-7. 20. Kannan R, Damm DD, White DK, Marsh W, Allen CM. Ectomesenchymal chondromyxoid tumor of the anterior tongue: a report of three cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:417-22. 21. van der Wal JE, van der Waal I. Ectomesenchymal chondromyxoid tumor of the anterior tongue. Report of a case. J Oral Pathol Med 1996;25:456-8. 22. de Visscher JG, Kibbelaar RE, van der Waal I. Ectomesenchymal chondromyxoid tumor of the anterior tongue. Report of two cases. Oral Oncol 2003;39:83-6. 23. Carlos R, Aguirre JM, Pineda V. Tumor condromixoide ectomesenquimal de la lengua. Med Oral 1999;4:361-5. 24. Nigam S, Dhingra KK, Gulati A. Ectomesenchymal chondromyxoid tumor of the hard palate—a case report. J Oral Pathol Med 2006;35:126-8. 25. Ide F. Chondromyxoid tumor of palate [letter to editor]. J Oral Pathol Med 2006;35:523-4. 26. Allen CM. The ectomesenchymal chondromyxoid tumor: a review. Oral Dis 2008;14:390-5. 27. Huse JT, Pasha TL, Zhang PJ. D2-40 functions as an effective chondroid marker distinguishing true chondroid tumors from chordoma. Acta Neuropathol 2007;113:87-94. Reprint requests: Dr. Márcio Ajudarte Lopes Department of Oral Diagnosis Oral Semiology and Oral Pathology Sections Piracicaba Dental School—UNICAMP Av. Limeira, 901—Areão PO Box 52, Postal Code: 13414-903 Piracicaba—SP Brazil [email protected]
CLINICOPATHOLOGIC CONFERENCE
Nodular lesion in the anterior hard palate Adriele Ferreira Gouvêa, DDS, PhD, Katya Pulido Díaz, DDS, Jorge Esquiche Léon, DDS, PhD, Pablo Agustin Vargas, DDS, PhD, Oslei Paes de Almeida, DDS, PhD, and Márcio Ajudarte Lopes, DDS, PhD (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:154-159)
CLINICAL PRESENTATION A 13-year-old boy was referred to the Oral Diagnosis Clinic (Orocentro—Piracicaba Dental School, University of Campinas, São Paulo, Brazil) for evaluation of an asymptomatic oral swelling that had been present for 7 years. According to his father, the swelling had suddenly grown recently. The clinical examination showed a well delimited bilobulated nodular lesion on the anterior region of the right-sided hard palate that measured about 2.0 ⫻ 1.5 cm and was nontender and firm on palpation (Figure 1). A small ulcer was noticed on the anterior lobe, probably due to contact with the lower teeth. There was no report of local trauma, the patient presented no parafunctional habits, and the medical history was noncontributory. In addition, there was no mobility of the teeth, and no radiographic changes were seen. DIFFERENTIAL DIAGNOSIS According to the clinical characteristics, differential diagnoses should consider lesions that occur on the hard palate of young patients. Some possible diagnoses involving such lesions include reactive lesions, congenital lesions, myofibroblastic lesions, mesenchymal and odontogenic tumors, and hamartomatous lesions. Given the lack of salivary gland tissue in the anterior hard palate, a salivary gland tumor would not be likely. A focal enlargement of the gingiva could have a variety of differential diagnoses, but focal fibrous hyperplasia (fibroma), pyogenic granuloma, peripheral giant cell granuloma, and peripheral ossifying fibroma are the most common. Focal fibrous hyperplasia (fibroma) has an innocuous evolution and was considered as a differential diagnosis, although the patient denied any associated irritant Department of Oral Diagnosis, Oral Semiology and Oral Pathology Sections, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil. Received for publication Jun 7, 2011; returned for revision Oct 26, 2011; accepted for publication Nov 3, 2011. © 2012 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter doi:10.1016/j.oooo.2011.11.005
154
factor. It is a reactive lesion resulting from the accumulation of fibrous tissue due to a local trauma, and it can develop at any site of the oral mucosa. It is commonly covered by normal mucosa, but occasionally may present an erythematous, ulcerated, or leukoplakic surface.1 Pyogenic granuloma (PG) is another reactive inflammatory lesion that presents granulation tissue and extensive endothelial proliferation. Fertile and pregnant women, children, and adolescents are more likely to develop PG. It can manifest as a painless smooth or lobulated mass with a surface that bleeds quite easily (owing to its extreme level of vascularity), and it can be ulcerated. Because of their high level of vascularity, young PGs are red, whereas older lesions are more collagenized and appear pink or normally colored.1 Peripheral giant cell granuloma (PGCG) is a reactive lesion that occurs exclusively on the gingiva/alveolar mucosa and is slightly more common in adult women. Characteristically, PGCG is a fast-growing, purpleblue, dome-shaped lesion that can cause slight resorption of the underlying bone.1 The lesion is similar histopathologically to brown tumor of hyperparathyroidism, which very rarely may mimic a PGCG of the jaws.2 Peripheral ossifying fibroma (POF) is another reactive lesion that only occurs on the gingiva, most commonly in the maxillary anterior region. Lesions range in color from pink to red, and the surface may or may not be ulcerated. Red ulcerated lesions often are mistaken for PGs, whereas pink nonulcerated lesions often are clinically diagnosed as focal fibrous hyperplasia.1 Congenital granular epulis (CGE), congenital epulis, or congenital epulis of the newborn is a benign tumor arising from the alveolar ridge of newborns. It commonly affects females (nearly 10:1), possibly indicating a hormonal influence, and it involves the maxillary alveolar ridge twice as often as the mandibular ridge, always on its anterior portion. It presents as a solitary, somewhat pedunculated, normally colored or reddish, fibroma-like lesion. CGE can present from a few millimeters to several centimeters in size, and it often causes alarm when it appears. In some cases it can
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interfere with breathing and feeding.3,4 In the present case, the patient’s father claimed that onset of the lesion occurred 7 years previously, but this information may be inaccurate. Although there are no cases reported in the literature of a patient presenting with a CGE at this age, this differential diagnosis should be considered in the current case. Oral myofibromas are rare, but some cases have been described affecting different intraoral sites, such as the upper labial mucosa, tongue, gingiva, palate, and intraosseous locations (mandible). Usually, they are found in cutaneous/subcutaneous tissues and in the skeletal muscles of the head and neck region, and they may be solitary (myofibromas) or multicentric (myofibromatosis).5–7 There are only a few studies reporting palatal myofibromas, and some cases clinically resemble the present case.8,9 Peripheral odontogenic tumors (neoplastic or hamartomatous) can have a clinical presentation similar to the present case. Peripheral or extraosseous odontogenic tumors are rare, but it is accepted that the remnants of the odontogenic epithelium entrapped in oral soft tissues may differentiate and form peripheral odontogenic tumors. Ide et al.,10 in a series of 30 peripheral odontogenic tumors, reported that odontogenic fibroma and ameloblastoma were by far the most common lesions. Peripheral odontogenic fibroma is characterized by a fibrous or fibromyxomatous proliferation that contains varying amounts of odontogenic epithelium embedded in a mature fibrous stroma. It occurs predominantly in the buccal gingiva of the mandible, although less frequently, in the maxilla.11,12 Extraosseous ameloblastoma is rare, comprising 1.3%-10% of all ameloblastomas. It presents in a wide age range, commonly affecting patients in the fifth to seventh decades, and more frequently involves the mandibular tooth-bearing areas/alveolar mucosa. Both lesions can have a clinical presentation as a gingival/mucosal swelling, without significant bone involvement or saucerization, as seen in the present case.12 Ide et al.10 described a case with a clinical presentation similar to that of our patient: a 9-year-old girl with a 1.0-cm dome-shaped mass on the palatal gingiva of the left central incisor. The lesion was given the diagnosis of a peripheral calcifying epithelial odontogenic tumor-like hamartoma, and it presented a sheet of polyhedral epithelium with intercellular bridges, ghost cells, and concentric calcifications. Moreover, those authors reported a case of peripheral odontoma with ghost cells in the enamel organ. Peripheral odontomas represent hamartomatous lesions and are extremely rare, occurring in children and adolescents, frequently in the anterior maxilla. Various names are found in the literature, probably reflecting the different stages of tooth
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germ development. Only 6 cases have been described on the palate, all in children and all with no bone involvement. Silva et al.13 reported 2 cases of peripheral odontoma; as in the present case, both presented as normally colored nodular lesions on the anterior hard palate laterally to the incisive papilla. Neural lesion was another clinical hypothesis. Oral peripheral nerve tumors include schwannoma, neurofibroma, nerve sheath myxoma (neurothekeoma), palisaded encapsulated neuroma (PEN), mucosal neuroma associated with multiple endocrine neoplasia III, and traumatic neuroma. The diagnosis of benign neural tumors can be challenging because of their overlapping histologic characteristics. The PEN is the most common type to affect the palatal mucosa, but neurofibromas and traumatic neuromas can occur at this location.14 Leiomyomatous hamartoma (LH) is an uncommon lesion in the oral cavity, with only a few cases having been described in the English-language literature. Even rarer is its occurrence on the anterior hard palate near to or involving the incisive papilla. However, it should be considered in clinical differential diagnosis. The original cases were described in a Japanese population, but it can be observed in other ethnic groups, mainly affecting young patients with ages varying from 3 months to 19 years. This type of lesion is painless, indolent, and self-limiting, and therefore probably underdiagnosed. LH can also develop in other areas of the body, such as the skin, lungs, kidney, and liver, and other authors have suggested its association with microphthalmia with linear skin defects syndrome. It tends to develop on the midline of the oral tongue or the anterior hard palate near the incisive papilla, where it appears as small, pink, polypoid lesions noted at or around birth.15 Other forms of hamartoma can arise in the mouth. They are microscopically characterized by a combination of benign tissue elements, including fibrovascular connective tissue, smooth-muscle bundles, skeletal muscle fibers, salivary tissue, adipose tissue, blood vessels, lymphoid tissue, peripheral nerves, and ganglion cells. The proportions of these tissues can vary, with the most prominent components being fibrous tissue, smoothmuscle bundles, or fat.15
DIAGNOSIS Based on the clinical and radiologic features of the present case, a large incisional biopsy was performed. A mass of fibroelastic tissue was removed under local anesthesia. The specimen was sent for histopathologic analysis and presented as a well circumscribed unencapsulated lesion composed of lobules separated by scanty fibrous tissue (Figure 2). There was proliferation of rounded, ovoid, spindle, and stellate cells in a pre-
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Fig. 2. Specimen obtained by incisional biopsy. Note the multilobulated, well defined, unencapsulated lesion with an oral mucosal stratified squamous epithelium surface (hematoxylin-eosin, ⫻5). Fig. 1. Nodular lesion on the anterior hard palate involving the incisive papilla and extending to the right palatine rugae.
dominant fibrous background (Figure 3, A), interspersed by chondroid (Figure 3, B) and myxoid tissue (Figure 3, C). There were areas presenting tumor cells with small hyperchromatic rounded or spindle-shaped nuclei. In other areas, the tumor cells contained illdefined and abundant eosinophilic cytoplasm surrounded by a stroma resembling chondroid tissue (Figure 3, B). No necrosis, mitoses, or local invasion was observed, nor were minor salivary glands seen. Nuclear pleomorphism, hyperchromatism, and pseudoinclusions were focally observed (Figure 3, D). The tumor cells were strongly positive for vimentin, glial fibrillary acidic protein (GFAP), and D2-40, focally positive for S100 (Figure 4), and negative for AE1/AE3, desmin, ␣-SMA, calponin, CD57, NSE, p63, and EMA. Based on the clinical, radiographic, histopathologic, and immunohistochemical features, the diagnosis of ectomesenchymal chondromyxoid tumor was made.
MANAGEMENT After the diagnosis, the patient’s parents were informed about the benign nature of the lesion. The remaining residual tumor showed growth after 11 months (Figure 5, A). At that time, they opted for surgical enucleation. The patient was doing well, with no evidence of recurrence 6 months after excision, and was still in clinical follow-up (Figure 5, B). DISCUSSION Ectomesenchymal chondromyxoid tumor (ECT) is a rare, benign, intraoral, soft tissue lesion, with 37 cases reported so far. It was first described in 1995 by Smith et al.,16 after reviewing Armed Forces Institute of Pathology files. It presents with a broad range of clinical and microscopic characteristic. Therefore, the reporting of new cases is important to reinforce its characteristics and to establish ECT diagnostic criteria.16 –19
The most plausible histogenesis of the ECT is that it develops from uncommitted ectomesenchymal cells from the neural crest, although salivary glands and muscles have also been considered as the tissues of origin.16,18 The overwhelming majority of cases developed in the anterior tongue, which is formed from the neural crest mesenchyme of the first anterior branchial arch. The diverse microscopic and immunohistochemical profiles seen for this lesion can be explained by the multipotent nature of these embryonic cells.17,18 The cases reported in the literature show that men and women are equally affected, with ages varying between 9 and 78 years (mean age 36.6 years); the majority of the patients were racially European. Most of the cases reported the presence of an asymptomatic and nontender submucosal nodule covered by normal mucosa, present for an average of 36.4 months. Few reported local complaints, such as local pressure and purulent discharge.16 –18 Our patient was a mixed-race 13-year-old who reported no symptomatology except the recent growth of the lesion, a finding also described by Kaplan et al.19 All but 2 cases were described on the anterior aspect of the oral tongue.16 –23 Of these 2, 1 occurred on the posterior tongue and 1 on the posterior hard palate.23,24 However, according to Ide25 and Allen,26 the latter case did not have sufficient documentation to support this diagnosis. Most of the studies describe a tumor size between 1 and 1.9 cm.17 Our patient presented a bilobulated nodular lesion measuring ⬃2.0 ⫻ 1.5 cm (Figure 1) on the anterior right hard palate, laterally to the incisive papilla, a location that had not been described before. Its occurrence in this site may be explained by the fact that this region is, like the anterior tongue, an embryonic fusion area (the primary palate and palatine crests converge to form the nasopalatine foramen, from which nerves and arteries emerge).22 The microscopic features of this lesion included lobulated sheets demarcated from the surrounding tissue.
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Fig. 3. A, Tumor cells interspersed among loose fibrous tissue and arranged in lobules or islands surrounded by a dense fibrous background (hematoxylin-eosin [HE], ⫻20). B, Eosinophilic chondroid pattern characterized by tumor cells set in lacunae (HE, ⫻20). C, Hypercellular tumor island with cells interspaced in a myxoid background (HE, ⫻20), D, Hypercellular area demonstrating tumor cells with hyperchromatic and pleomorphic nuclei. Note the nuclear pseudoinclusion in the center of the photomicrograph (HE, ⫻40).
Most cases are unencapsulated, but the borders of the tumor are relatively well defined owing to the condensation of fibrous tissue and muscle fibers around the periphery of the tumor. A few muscle fibers can be focally infiltrated by tumor cells, but this does not seem to indicate evidence of aggressive biologic behavior.16,18,22 Three histologic patterns are usually discernible— cellular, myxoid, and chondroid areas—in variable proportions.16,17 The cells comprising these lobules can present rounded, ovoid, spindle, and stellate shapes arranged in the aforementioned backgrounds. Focal areas of atypia with nuclear pseudoinclusions, binucleated cells, prominent nucleoli, and nuclear hyperchromatism can be observed,16,17,21 as well as mitoses, though rarely.18 Necrosis has not been reported other than due to secondary trauma or infection. Focal areas of hemorrhage and inflammation can be found occasionally.16 There are a few reports describing the presence of minor salivary glands in the proximity of the tumor.20 –22 The current case encompassed all of the microscopic characteristics, but there was no sign of inflammatory infiltration and no presence of salivary glands (Figures 2 and 3). The cases described in the literature show vimentin and polyclonal GFAP positivity in 100% of them, as
well as S100 protein (in 78%), CD 57 (76%), monoclonal GFAP (69%), pancytokeratin clone AE1/AE3 (56%), ␣-SMA (33%), and desmin (15%) positivity.18 Therefore, it is suggested that some characteristics are important for ECT diagnosis: the presence of biphasic myxoid and chondroid patterns and the positivity of tumor cells for vimentin, S100, and GFAP. All of these criteria were fulfilled in the present report. The present case showed strong positivity for vimentin, GFAP, and D2-40 and focal immunopositivity for S100 (Figure 4), and was negative for AE1/AE3, desmin, ␣-SMA, calponin, CD57, NSE, p63, and EMA. The immunopositivity for the monoclonal antibody D2-40 was a fascinating finding, because this marker has the capability of highlighting chondroid tissue, according to the findings in a study by Huse et al.,27 where true chondroid tumors were distinguished from chordomas. This immunohistochemical test has not previously been performed for ECTs; D2-40 is an interesting marker to be studied in these lesions. All of the 37 previously reported cases of ECT were treated by conservative surgery. Only 2 cases showed tumor recurrence and were successfully managed with the use of a second surgical approach.16,18 The present case was surgically treated,
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Fig. 4. Immunoreactivity of the tumor cells for vimentin (A), GFAP (B), S100 (C), and D2-40 (D). Original magnification ⫻20.
Fig. 5. A, Residual lesion 11 months after the initial biopsy. B, The same area 6 months after reexcision.
but there was a residual lesion that showed considerable growth 11 months later. A second surgical approach was made and at the time of writing the patient was in clinical follow-up with no signs of recurrence (Figure 5, B). Although all available data strongly support the benign nature of ECT, cases of recurrence, microscopic foci of pleomorphic hyperchromatic cells, and sporadic mitoses suggest the importance of regular follow-up visits of the patient after treatment.18 In conclusion, ECT is an uncommon, intraoral, mesenchymal, soft tissue lesion that presents unique microscopic and immunohistochemical patterns of expression. The overwhelming majority of the reported cases are located
on the dorsum of the oral tongue, but it can also be found in the anterior hard palate. Therefore, clinicians should consider the occurrence of ECT in this oral site. REFERENCES 1. Neville B, Damm DD, Allen CM, Bouquot J. Oral and Maxillofacial Pathology. 3rd ed. Philadelphia: Saunders; 2009. 2. Sena Guimarães AL, Marques-Silva L, Cavaliéri Gomes C, Henriques Castro W, Alves Mesquita R, Santiago Gomez R. Peripheral brown tumour of hyperparathyroidism in the oral cavity. Oral Oncol Extra 2006;42:91-3. 3. van der Waal I. Congenital granular cell epulis. In: World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. Lyon: IARC; 2005. p. 198. 4. Bewley A, Bloom JD, Kherani S, Pawel BR. Congenital epulis. Ear Nose Throat J 2010;89:299-300.
OOOO Volume 114, Number 2 5. Rubin BP, Bridge JA. World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and Bone. Lyon: IARC Press; 2002. p. 59 – 61. 6. Vered M, Allon I, Buchner A, Dayan D. Clinico-pathologic correlations of myofibroblastic tumors of the oral cavity. II. Myofibroma and myofibromatosis of the oral soft tissues. J Oral Pathol Med 2007;36:304-14. 7. Azevedo R de S, Pires FR, Della Coletta R, de Almeida OP, Kowalski LP, Lopes MA. Oral myofibromas: report of two cases and review of clinical and histopathologic differential diagnosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:35-40. 8. Jones AC, Freedman PD, Kerpel SM. Oral myofibromas: a report of 13 cases and review of the literature. J Oral Maxillofac Surg 1994;52:870-5. 9. Montgomery E, Speight PM, Fisher C. Myofibromas presenting in the oral cavity: a series of 9 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;89:343-8. 10. Ide F, Obara K, Mishima K, Saito I, Horie N, Shimoyama T, et al. Peripheral odontogenic tumor: a clinicopathologic study of 30 cases. General features and hamartomatous lesions. J Oral Pathol Med 2005;34:552-7. 11. Ritwik P, Brannon RB. Peripheral odontogenic fibroma: a clinicopathologic study of 151 cases and review of the literature with special emphasis on recurrence. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:357-63. 12. Philipsen HP, Reichart PA, Sciuba JJ, van der Waal I. Odontogenic fibroma. In: World Health Organization classification of tumors. Pathology and Genetics—Head and Neck Tumors. Lyon: IARC; 2005. p. 315. 13. Silva AR, Carlos-Bregni R, Vargas PA, de Almeida OP, Lopes MA. Peripheral developing odontoma in newborn. Report of two cases and literature review. Med Oral Patol Oral Cir Bucal 2009;14:612-5. 14. Chrysomali E, Papanicolaou SI, Dekker NP, Regezi JA. Benign neural tumors of the oral cavity: a comparative immunohistochemical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84:381-90. 15. Napier SS, Devine JC, Rennie JS, Lamey PJ. Unusual leiomyomatous hamartoma of the hard palate: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:305-7. 16. Smith BC, Ellis GL, Meis-Kindblom JM, Williams SB. Ectomesenchymal chondromyxoid tumor of the anterior tongue. Nineteen cases of a new clinicopathologic entity. Am J Surg Pathol 1995;19:519-30.
CLINICOPATHOLOGIC CONFERENCE Gouvêa et al. 159 17. Pires FR, Abrahão AC, Cabral MG, Azevedo RS, Horta MC, Martins CR, et al. Clinical, histological and immunohistochemical features of ectomesenchymal chondromyxoid tumor. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:914-9. 18. Angiero F. Ectomesenchymal chondromyxoid tumour of the tongue. A review of histological and immunohistochemical features. Anticancer Res 2010;30:4685-9. 19. Kaplan I, Anavi Y, Calderon S. Ectomesenchymal chondromyxoid tumour of the anterior tongue. Int J Oral Maxillofac Surg 2004;33:404-7. 20. Kannan R, Damm DD, White DK, Marsh W, Allen CM. Ectomesenchymal chondromyxoid tumor of the anterior tongue: a report of three cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:417-22. 21. van der Wal JE, van der Waal I. Ectomesenchymal chondromyxoid tumor of the anterior tongue. Report of a case. J Oral Pathol Med 1996;25:456-8. 22. de Visscher JG, Kibbelaar RE, van der Waal I. Ectomesenchymal chondromyxoid tumor of the anterior tongue. Report of two cases. Oral Oncol 2003;39:83-6. 23. Carlos R, Aguirre JM, Pineda V. Tumor condromixoide ectomesenquimal de la lengua. Med Oral 1999;4:361-5. 24. Nigam S, Dhingra KK, Gulati A. Ectomesenchymal chondromyxoid tumor of the hard palate—a case report. J Oral Pathol Med 2006;35:126-8. 25. Ide F. Chondromyxoid tumor of palate [letter to editor]. J Oral Pathol Med 2006;35:523-4. 26. Allen CM. The ectomesenchymal chondromyxoid tumor: a review. Oral Dis 2008;14:390-5. 27. Huse JT, Pasha TL, Zhang PJ. D2-40 functions as an effective chondroid marker distinguishing true chondroid tumors from chordoma. Acta Neuropathol 2007;113:87-94. Reprint requests: Dr. Márcio Ajudarte Lopes Department of Oral Diagnosis Oral Semiology and Oral Pathology Sections Piracicaba Dental School—UNICAMP Av. Limeira, 901—Areão PO Box 52, Postal Code: 13414-903 Piracicaba—SP Brazil [email protected]