Case report
Oral leiomyosarcoma: the importance of early diagnosis tima Sua rez-Ale n1, Eva Otero-Rey1, Manuel Pen ~ amarıa-Mallo n1, Abel Garcıa-Garcıa1 and Fa s Blanco-Carrio n1 Andre 1
Stomatology Department, School of Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain
doi: 10.1111/ger.12126 Oral leiomyosarcoma: the importance of early diagnosis Objective: Present a case clinic of leimyosarcoma. Background: Leiomyosarcomas (LMSs) are malignant mesenchymal tumours of smooth muscle differentiation that grow rapidly and whose prognosis is dependent upon the tumour site and disease stage. Their location in the oral cavity is considered extremely rare due to the lack of smooth muscle tissue in that area. Materials and methods: We present an LMSs case of the buccal mucosa in an elderly patient patient with a follow-up of 4 years. Conclusion: Early diagnosis and treatment play a key role in a better prognosis. Keywords: oral mucosa, oral leiomyosarcoma, oral mesenchymal tumour, immunohistochemical markers. Accepted 26 February 2014
diagnosis of primary LMS in the buccal mucosa of a senior patient.
Introduction Leiomyosarcomas (LMSs) are malignant mesenchymal tumours of smooth muscle differentiation. They account for approximately 7% of all soft tissue sarcomas1 and frequently affect the retro-peritoneal region, the female genitalia and gastrointestinal tract.2 Its location at the level of the oral cavity is considered extremely rare, affecting, in the order of decreasing frequency, the maxilla, mandible, tongue, buccal mucosa, soft palate, upper lip and floor of the mouth.1 Clinically, oral LMS usually appears as a distinct painless mass, which is circumscribed and firmly adhered to deep planes, lacking specific symptoms that allow for its differentiation from other similar lesions.3 Indeed, the absence of any distinctive clinical feature and the rarity of these tumours in the oral cavity is precisely why histological examination with immunohistochemical confirmation is required for the definitive diagnosis of oral LMS.1 The importance of early diagnosis, which results in a better prognosis, shows the need to systematically and periodically revise the oral mucosa of our patients. This article presents a case of early 314
Case report A 66-year-old woman, with a history of alcoholism, was referred to the Daily Practice Dentistry Master, University of Santiago de Compostela, Galicia (Spain), upon finding a well-defined 2 9 1 cm diameter growth, which was located in the rear of the left buccal mucosa (Fig. 1). The patient reported the lesion had been there for about a month and that it was totally asymptomatic. On palpation, the mass had a hard consistency although it was freely moveable over the underlying tissue layers. The patient reported that at the beginning, it was a soft lesion. Diagnosis was performed by fine-needle aspiration (FNA). The results showed a spindle-cell mesenchymal neoplasm, with scarce pleomorphism, possibly benign, yet difficult to characterise with this biopsy technique. Surgical excision was therefore recommended, followed by histopathological analysis of the lesion. After performing a complete excision of the lesion with tumour-free margins, the histological analysis4 showed interlacing fascicles of spindled
© 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 314–317
Oral leiomyosarcoma
Figure 1 Well-defined 2 9 1 cm exophytic Hard consistency. 1-month evolution.
lesion.
cells with eosinophilic cytoplasm, typical of leiomyosarcoma moderately pleomorphism and mitosis ranged from 5/10 high power field (HPF) to 9/ 10 HPF. A final diagnosis of grade I leiomyosarcoma was made, based on the classification of the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC)5 (Fig. 2). The immunohistochemical studies showed strong positive staining with smooth muscle actin (Fig. 3) and focal positivity for actin HHF35. Cytokeratin (AE1/AE3), S100 protein and desmin were negative. MIB 1 showed a proliferation index of 41% (Fig. 4).6 The protocol of this study was approved by the ethical review board of the University of Santiago de Compostela. There have been no recurrences or metastases at 4 years and 4 months after the treatment.
Figure 3 Immunohistochemical study showing the intense and diffuse smooth muscle actin positivity in the excision specimen (409).
Figure 4 MIB 1 showed a proliferation index of 41% (209).
(a)
(b)
315
(c)
Figure 2 Histological analysis with H&E shows interlacing fascicles of spindled cells with eosinophilic cytoplasm (a: 409, b: 2009, c: 4009). © 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 314–317
316
F. Suarez-Alen et al.
Discussion Leiomyosarcomas are very rare in the oral cavity, probably due to the lack of smooth muscle tissue in this region. They may appear as a primary tumour, a metastatic tumour or a radiation-associated tumour. In the oral cavity, it has been suggested that they may arise from smooth muscle cells from the blood vessel walls, neuromuscular packages, circumvallate papillae, myoepithelial cells or mesenchymal pluripotent cells.2 Oral LMS is slightly more common in men and may occur at any age, with peak incidence in the 6th decade of life, although there are some reports of tumours arising in infants.1 Given the absence of any distinctive clinical feature and the rarity of these tumours in the oral and maxillofacial region, some lesions of LMS are occasionally mistaken for the other common lesions affecting the oral cavity. Therefore, the definitive diagnosis of oral LMS may be established only after conducting a histological analysis with its subsequent immunohistochemical confirmation. The literature review shows that the best choice of treatment is complete surgical resection of the lesion with tumour-free margins.1 As, in head and neck sarcomas, it is difficult to obtain wide margins during surgical treatment, because of anatomical constraints, most patients with locally resectable tumours undergo postoperative irradiation. Adjuvant systemic chemotherapy seems to improve outcome, but its benefit must be weighted against associated toxicities.7 The prognosis is related to tumour grade and size, location of the lesion and the treatment of choice. The tumour grade is likely one of the most important prognostic factors for patients with soft tissue sarcoma.7,8 In the FNCLCC classi-
References 1. Ethunandan M, Stokes C, Higgins B, Spedding A, Way C, Brennan P. Primary oral leiomyosarcoma: a clinico-pathologic study and analysis of prognostic factors. Int J Oral Maxillofac Surg 2007; 36: 409–16. 2. Azevedo RS, Pires FR, Gouv^ ea AF, Lopes MA, Jorge J. Leiomyosarcomas of the oral cavity: report of a radiation-associated and a metastatic case. Oral Maxillofac Surg 2012; 16: 227–32.
fication, the tumour grade depends on the evaluation of three factors: necrosis, differentiation and mitotic count, assigning a score of 1–3 to each tumour.9 Leiomyosarcomas prognosis in the oral and maxillofacial region is usually poor, with a high rate of recurrence and metastasis.10 According Ethunandan,1 survival after primary oral LMS is 55% at 5 years. Bone involvement and metastasis are two of the factors that have been associated with a worse prognosis of oral LMS. In our case, early detection and treatment were critical in obtaining a good prognosis. In conclusion, oral LMS is a rare lesion of the oral cavity. Definitive diagnosis should be established upon histological examination with immunohistochemical confirmation. The treatment of choice should be, whenever possible, a complete excision of the lesion. The prognosis of oral LMS, like the rest of malignant tumours, of the oral cavity is multifactorial, involving clinical assessment, histology, biological behaviour, etc. We agree with other authors,11 as we have observed in our case study that early diagnosis is essential to reduce the possibility of recurrence and increase the survival time of the patient. Therefore, we wish to emphasise the importance of periodic examinations of the oral cavity of the elderly, ideally, by healthcare professionals experienced in the diagnosis of oral diseases, such as the dental staff. Referral to an oral disease specialist, such as an oral and maxillo-facial pathologist or an otorhinolaryngologist, could help to further narrow down the diagnosis. Ultimately, a final diagnosis will be dependent upon histopathological examination. Regular examination of the oral cavity in the geriatric population can, therefore, lead to early identification and treatment of cases with an otherwise very poor prognosis.
3. Mesquita R, Migliari D, Machado de Sousa S, Alves M. Leiomyosarcoma of the buccal mucosa: a case report. J Oral Maxillofac Surg 1998; 56: 504–7. 4. Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc 2008; 2008: pdb.prot4986 5. Neuville A, Chibon F, Coindre JM. Grading of soft tissue sarcomas: from histological to molecular assessment. Pathology 2014; 46: 113–20.
6. Montgomery E, Goldblum JR, Fisher C. Leiomyosarcoma of the head and neck: a clinicopathological study. Histopathology 2002; 40: 518– 25. 7. de Bree R, van der Waal I, de Bree E, Leemans CR. Management of adult soft tissue sarcomas of the head and neck. Oral Oncol 2010; 46: 786–90. 8. Kaytan E, Yaman F, Cosar R, Eralp Y, Saip P, Darendeliler E. Prognostic factors in localized soft-
© 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 314–317
Oral leiomyosarcoma tissue sarcomas. Am J Clin Oncol 2003; 26: 411–5. 9. Boffano P, Roccia F, Zavattero E, Gallesio C, Cassarino E, Campisi P et al. The surgical management of a leiomyosarcoma of the submandibular gland in a 95-year-old patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 112: 34–8. 10. Nikitakis NG, Lopes MA, Bailey JS, Blanchaert RH, Ord RA, Sauk JJ. Oral leiomyosarcoma: review of
the literature and report of two cases with assessment of the prognostic and diagnostic significance of immunohistochemical and molecular markers. Oral Oncol 2002; 38: 201–8. 11. Yadav J, Bakshi J, Chouhan M, Modi R. Head and neck leiomyosarcoma. Indian J Otolaryngol Head Neck Surg 2013; 65 (Suppl 1): 1–5.
317
Correspondence to: Eva M. Otero Rey, Facultad de Odontologıa, Universidad de Santiago de Compostela, Entrerrios s/n. 15782, Santiago de Compostela, Spain. Tel.: +34-649116177 Fax: +34-981552738 E-mail: [email protected]
© 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 314–317
Oral leiomyosarcoma: the importance of early diagnosis tima Sua rez-Ale n1, Eva Otero-Rey1, Manuel Pen ~ amarıa-Mallo n1, Abel Garcıa-Garcıa1 and Fa s Blanco-Carrio n1 Andre 1
Stomatology Department, School of Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain
doi: 10.1111/ger.12126 Oral leiomyosarcoma: the importance of early diagnosis Objective: Present a case clinic of leimyosarcoma. Background: Leiomyosarcomas (LMSs) are malignant mesenchymal tumours of smooth muscle differentiation that grow rapidly and whose prognosis is dependent upon the tumour site and disease stage. Their location in the oral cavity is considered extremely rare due to the lack of smooth muscle tissue in that area. Materials and methods: We present an LMSs case of the buccal mucosa in an elderly patient patient with a follow-up of 4 years. Conclusion: Early diagnosis and treatment play a key role in a better prognosis. Keywords: oral mucosa, oral leiomyosarcoma, oral mesenchymal tumour, immunohistochemical markers. Accepted 26 February 2014
diagnosis of primary LMS in the buccal mucosa of a senior patient.
Introduction Leiomyosarcomas (LMSs) are malignant mesenchymal tumours of smooth muscle differentiation. They account for approximately 7% of all soft tissue sarcomas1 and frequently affect the retro-peritoneal region, the female genitalia and gastrointestinal tract.2 Its location at the level of the oral cavity is considered extremely rare, affecting, in the order of decreasing frequency, the maxilla, mandible, tongue, buccal mucosa, soft palate, upper lip and floor of the mouth.1 Clinically, oral LMS usually appears as a distinct painless mass, which is circumscribed and firmly adhered to deep planes, lacking specific symptoms that allow for its differentiation from other similar lesions.3 Indeed, the absence of any distinctive clinical feature and the rarity of these tumours in the oral cavity is precisely why histological examination with immunohistochemical confirmation is required for the definitive diagnosis of oral LMS.1 The importance of early diagnosis, which results in a better prognosis, shows the need to systematically and periodically revise the oral mucosa of our patients. This article presents a case of early 314
Case report A 66-year-old woman, with a history of alcoholism, was referred to the Daily Practice Dentistry Master, University of Santiago de Compostela, Galicia (Spain), upon finding a well-defined 2 9 1 cm diameter growth, which was located in the rear of the left buccal mucosa (Fig. 1). The patient reported the lesion had been there for about a month and that it was totally asymptomatic. On palpation, the mass had a hard consistency although it was freely moveable over the underlying tissue layers. The patient reported that at the beginning, it was a soft lesion. Diagnosis was performed by fine-needle aspiration (FNA). The results showed a spindle-cell mesenchymal neoplasm, with scarce pleomorphism, possibly benign, yet difficult to characterise with this biopsy technique. Surgical excision was therefore recommended, followed by histopathological analysis of the lesion. After performing a complete excision of the lesion with tumour-free margins, the histological analysis4 showed interlacing fascicles of spindled
© 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 314–317
Oral leiomyosarcoma
Figure 1 Well-defined 2 9 1 cm exophytic Hard consistency. 1-month evolution.
lesion.
cells with eosinophilic cytoplasm, typical of leiomyosarcoma moderately pleomorphism and mitosis ranged from 5/10 high power field (HPF) to 9/ 10 HPF. A final diagnosis of grade I leiomyosarcoma was made, based on the classification of the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC)5 (Fig. 2). The immunohistochemical studies showed strong positive staining with smooth muscle actin (Fig. 3) and focal positivity for actin HHF35. Cytokeratin (AE1/AE3), S100 protein and desmin were negative. MIB 1 showed a proliferation index of 41% (Fig. 4).6 The protocol of this study was approved by the ethical review board of the University of Santiago de Compostela. There have been no recurrences or metastases at 4 years and 4 months after the treatment.
Figure 3 Immunohistochemical study showing the intense and diffuse smooth muscle actin positivity in the excision specimen (409).
Figure 4 MIB 1 showed a proliferation index of 41% (209).
(a)
(b)
315
(c)
Figure 2 Histological analysis with H&E shows interlacing fascicles of spindled cells with eosinophilic cytoplasm (a: 409, b: 2009, c: 4009). © 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 314–317
316
F. Suarez-Alen et al.
Discussion Leiomyosarcomas are very rare in the oral cavity, probably due to the lack of smooth muscle tissue in this region. They may appear as a primary tumour, a metastatic tumour or a radiation-associated tumour. In the oral cavity, it has been suggested that they may arise from smooth muscle cells from the blood vessel walls, neuromuscular packages, circumvallate papillae, myoepithelial cells or mesenchymal pluripotent cells.2 Oral LMS is slightly more common in men and may occur at any age, with peak incidence in the 6th decade of life, although there are some reports of tumours arising in infants.1 Given the absence of any distinctive clinical feature and the rarity of these tumours in the oral and maxillofacial region, some lesions of LMS are occasionally mistaken for the other common lesions affecting the oral cavity. Therefore, the definitive diagnosis of oral LMS may be established only after conducting a histological analysis with its subsequent immunohistochemical confirmation. The literature review shows that the best choice of treatment is complete surgical resection of the lesion with tumour-free margins.1 As, in head and neck sarcomas, it is difficult to obtain wide margins during surgical treatment, because of anatomical constraints, most patients with locally resectable tumours undergo postoperative irradiation. Adjuvant systemic chemotherapy seems to improve outcome, but its benefit must be weighted against associated toxicities.7 The prognosis is related to tumour grade and size, location of the lesion and the treatment of choice. The tumour grade is likely one of the most important prognostic factors for patients with soft tissue sarcoma.7,8 In the FNCLCC classi-
References 1. Ethunandan M, Stokes C, Higgins B, Spedding A, Way C, Brennan P. Primary oral leiomyosarcoma: a clinico-pathologic study and analysis of prognostic factors. Int J Oral Maxillofac Surg 2007; 36: 409–16. 2. Azevedo RS, Pires FR, Gouv^ ea AF, Lopes MA, Jorge J. Leiomyosarcomas of the oral cavity: report of a radiation-associated and a metastatic case. Oral Maxillofac Surg 2012; 16: 227–32.
fication, the tumour grade depends on the evaluation of three factors: necrosis, differentiation and mitotic count, assigning a score of 1–3 to each tumour.9 Leiomyosarcomas prognosis in the oral and maxillofacial region is usually poor, with a high rate of recurrence and metastasis.10 According Ethunandan,1 survival after primary oral LMS is 55% at 5 years. Bone involvement and metastasis are two of the factors that have been associated with a worse prognosis of oral LMS. In our case, early detection and treatment were critical in obtaining a good prognosis. In conclusion, oral LMS is a rare lesion of the oral cavity. Definitive diagnosis should be established upon histological examination with immunohistochemical confirmation. The treatment of choice should be, whenever possible, a complete excision of the lesion. The prognosis of oral LMS, like the rest of malignant tumours, of the oral cavity is multifactorial, involving clinical assessment, histology, biological behaviour, etc. We agree with other authors,11 as we have observed in our case study that early diagnosis is essential to reduce the possibility of recurrence and increase the survival time of the patient. Therefore, we wish to emphasise the importance of periodic examinations of the oral cavity of the elderly, ideally, by healthcare professionals experienced in the diagnosis of oral diseases, such as the dental staff. Referral to an oral disease specialist, such as an oral and maxillo-facial pathologist or an otorhinolaryngologist, could help to further narrow down the diagnosis. Ultimately, a final diagnosis will be dependent upon histopathological examination. Regular examination of the oral cavity in the geriatric population can, therefore, lead to early identification and treatment of cases with an otherwise very poor prognosis.
3. Mesquita R, Migliari D, Machado de Sousa S, Alves M. Leiomyosarcoma of the buccal mucosa: a case report. J Oral Maxillofac Surg 1998; 56: 504–7. 4. Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc 2008; 2008: pdb.prot4986 5. Neuville A, Chibon F, Coindre JM. Grading of soft tissue sarcomas: from histological to molecular assessment. Pathology 2014; 46: 113–20.
6. Montgomery E, Goldblum JR, Fisher C. Leiomyosarcoma of the head and neck: a clinicopathological study. Histopathology 2002; 40: 518– 25. 7. de Bree R, van der Waal I, de Bree E, Leemans CR. Management of adult soft tissue sarcomas of the head and neck. Oral Oncol 2010; 46: 786–90. 8. Kaytan E, Yaman F, Cosar R, Eralp Y, Saip P, Darendeliler E. Prognostic factors in localized soft-
© 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 314–317
Oral leiomyosarcoma tissue sarcomas. Am J Clin Oncol 2003; 26: 411–5. 9. Boffano P, Roccia F, Zavattero E, Gallesio C, Cassarino E, Campisi P et al. The surgical management of a leiomyosarcoma of the submandibular gland in a 95-year-old patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 112: 34–8. 10. Nikitakis NG, Lopes MA, Bailey JS, Blanchaert RH, Ord RA, Sauk JJ. Oral leiomyosarcoma: review of
the literature and report of two cases with assessment of the prognostic and diagnostic significance of immunohistochemical and molecular markers. Oral Oncol 2002; 38: 201–8. 11. Yadav J, Bakshi J, Chouhan M, Modi R. Head and neck leiomyosarcoma. Indian J Otolaryngol Head Neck Surg 2013; 65 (Suppl 1): 1–5.
317
Correspondence to: Eva M. Otero Rey, Facultad de Odontologıa, Universidad de Santiago de Compostela, Entrerrios s/n. 15782, Santiago de Compostela, Spain. Tel.: +34-649116177 Fax: +34-981552738 E-mail: [email protected]
© 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd, Gerodontology 2015; 32: 314–317
