doi:10.1111/iej.12442
CASE REPORT
Metastatic cervical carcinoma of the jaw presenting as periapical disease V. R. Torregrossa, K. M. Faria, M. M. Bicudo, P. A. Vargas, O. P. Almeida, M. A. Lopes & A. R. Santos-Silva Department of Oral Diagnosis, Semiology and Oral Pathology Areas, Piracicaba Dental School, University of Campinas (UNICAMP) Piracicaba, Brazil
Abstract Torregrossa VR, Faria KM, Bicudo MM, Vargas PA, Almeida OP, Lopes MA, Santos-Silva AR. Metastatic cervical carcinoma of the jaw presenting as periapical disease. International Endodontic Journal.
Aim To present a case report of a metastasis from cervical cancer to the maxilla, which was misdiagnosed as periapical disease and to caution clinicians that metastases could have a disguised clinical presentation that must be taken into account in the differential diagnosis of periapical disease in oncologic patients. Summary Although metastatic tumours of the jaws are uncommon, they may mimic benign inflammatory processes and reactive lesions. The ability of metastatic lesions to mimic periapical disease is discussed and a brief review of the literature is presented, emphasizing the importance of correct diagnosis to prevent delay in diagnosing cancer. Attention should therefore be given to the patient’s medical history, especially of those with a previous history of cancer, and all dental practitioners should be aware of the possibility of metastases that may be confused with periapical disease. Finally, endodontists are well placed to recognize malignant and metastatic oral lesions during the initial clinical stages, given that their treatments are usually based on frequent dental appointments and long-term follow-ups. Key learning points • A metastatic tumour in the jaw, such as cervical carcinoma, can mimic periapical disease in its early stages, hindering the correct diagnosis. • Unusual clinical features such as widening of the periodontal ligament space, a tooth with a necrotic pulp with no evidence of pulp injury, buccal and palatal swelling with persistent and progressive symptoms, and lack of response to conventional endodontic therapy should be investigated in oncologic patients aiming to exclude the possibility of a metastasis. • The correlation between clinical findings, medical history and histopathology is essential for confirmation of the diagnosis.
Correspondence: Alan Roger Santos-Silva, Department of Oral Diagnosis, Semiology Area, Piracicaba Dental School, University of Campinas, Av. Limeira, 901, Bairro Are~ao, Piracicaba, CEP 13414-903, S~ao Paulo, Brazil (Tel: +55 19 21065320; Fax +55 19 21065218; e-mail: [email protected]).
© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd
International Endodontic Journal, 0, 1–9, 2015
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CASE REPORT
Keywords: carcinoma, cervical cancer, endodontics, metastasis, periapical disease. Received 23 September 2014; accepted 17 February 2015
Introduction Periapical disease is by far the most common pathologic condition of the jaw (Drage et al. 2013). The cause of periapical disease is often obvious, although there are noninflammatory disorders such as metastatic tumours which can mimic this condition (Block et al. 1977, Spott 1985, Bueno et al. 2008, Khalili et al. 2010). Thus, periapical radiolucencies should be thoroughly investigated and correctly diagnosed to rule out rare periapical pathosis (Lee et al. 2007, Mavili et al. 2010). The involvement of the oral and maxillofacial region in metastatic tumours is uncommon and usually indicates widespread disease with a poor prognosis (Keller & Gunderson 1987, D’Silva et al. 2006, Lim et al. 2006, Hirshberg et al. 2008, Beena et al. 2011, Arias-Chamorro et al. 2012). In nearly 30% of cases, a metastatic lesion in the maxillofacial region is the first indication of underlying malignancy (Davidson & Moyo 1991, Hirshberg & Buchner 1995, Arias-Chamorro et al. 2012). The jawbones and oral soft tissues can be affected by metastases, which often simulate benign processes and dental inflammatory pathosis such as pyogenic granulomas, gingivitis, periodontal abscesses and apical periodontitis, frequently leading to misdiagnosis and mistreatment (Davidson & Moyo 1991, Hirshberg & Buchner 1995, Beena et al. 2011). The most common primary sites associated with oral metastases amongst women are the breast, genitourinary tract, kidney, colorectal region and thyroid gland (D’Silva et al. 2006, Lim et al. 2006, Hirshberg et al. 2008, Poulias et al. 2011). Breast and cervical cancers are generally considered to be the most important cancers amongst women (Luciani et al. 2013). Breast cancer continues to remain the most lethal malignancy in women, with a tendency to metastasize to the jawbones (D’Silva et al. 2006, Hirshberg et al. 2008, Poulias et al. 2011, Abdulrahman & Rahman 2012). Cervical cancer is the second most common cancer in women and is the second major primary site associated with oral metastases (Nishimura et al. 1982, Davidson & Moyo 1991, Hirshberg et al. 1993, 2008, Arias-Chamorro et al. 2012, Carvalho et al. 2012, Liu et al. 2013, Luciani et al. 2013). Although rare, oral metastases often present innocuous dental symptoms where the dentist has the opportunity to determine an early diagnosis and refer the patient for appropriate treatment (Keller & Gunderson 1987, Davidson & Moyo 1991, D’Silva et al. 2006). This paper presents a rare clinical case of a metastasis to the jaw with unusual features, which was initially misdiagnosed as periapical disease. The report is a warning to all dental practitioners that oral metastases have the potential to mimic endodontic diseases and pose a diagnosis and its management a challenge.
Case report A 33-year-old woman with a previous medical history of cervical carcinoma, and who was still undergoing medical treatment 4 years after her diagnosis, was referred for the evaluation of an asymptomatic lesion in the maxilla. At the time of her first visit to the general practitioner, she was on a course of chemotherapy with no comorbidities. During the history, she reported that she was first examined by an otolaryngologist, who referred her to a general dentist for the evaluation of a year-long gingival lesion between tooth 21 and 22 with associated buccal and palatal swelling (Fig. 1a,b). Further
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CASE REPORT
(a)
(b) Figure 1 (a) Buccal clinical presentation showing an erythematous area on the attached gingiva between teeth 21 and 22. Note the superficial telangiectasia and the presence of suppuration through the gingival sulcus. (b) Palatal view with expanding swelling and flotation point.
clinical examination revealed a negative response to a cold test (tetrafluoroethane) in tooth 21, which had a cosmetic restoration and no history of previous dental trauma. Subsequent image analysis revealed an enlargement of the periodontal ligament space of tooth 21 (Fig. 2a), suggesting periapical disease secondary to pulp necrosis. The general dentist therefore diagnosed these symptoms as a periapical abscess secondary to spontaneous pulp necrosis of tooth 21 and then opened the pulp chamber and found necrotic pulp tissue without pus. The root canal was instrumented during the first session using a conventional rotary multifile system. A 2.5% sodium hypochlorite solution was used at all times during the irrigation procedures and after instrumentation. Then, a Ca(OH)2 paste was injected into the root canal. The patient was treated empirically with oral antibiotics (amoxicillin 500 mg thrice a day for 7 days), analgesics and 0.12% chlorhexidine digluconate daily mouthwashes. The Ca(OH)2 paste was removed and the root canal filled with Gutta-percha at the second visit. All phases of endodontic treatment were conducted under rubber dam. After 30 days of post-endodontic treatment follow-up, a progressive diffuse periapical radiolucency with ill-defined contours was noted (Fig. 2b), and the patient was referred to the Oral Medicine Clinic for evaluation. General extra-oral examination revealed alopecia and no palpable lymph nodes in the
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(a)
(b) Figure 2 (a) Initial periapical radiograph showing a widening of the periodontal ligament space in the periapical region of tooth 21, suggesting periapical disease secondary to pulp necrosis. (b) Periapical radiograph of tooth 21 after conventional root canal treatment. Note the progression of diffuse periapical radiolucency with ill-defined contours compared with Figure 2a.
head and neck. Laboratory tests revealed pancytopenia secondary to chemotherapy. On intra-oral examination, the so-called periapical abscess was observed as a nodule which was hard upon palpation, with evident superficial telangiectasia. The lesion measured approximately 3 9 3 cm, causing enlargement of the buccal maxilla and attached gingiva with the presence of a serous fluid suggestive of pus through the gingival sulcus
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Figure 3 Axial section of cone-beam tomography revealing a destructive hypodense image causing bone expansion and fenestration of both the buccal and palatal cortical bone in the region of tooth 21.
in the region of tooth 21. The tooth had grade 1 mobility and was associated with discrete pain during vertical percussion. Periodontal probing depths were 1.5 mm. The patient was using orthodontic appliances, but had abandoned the orthodontic treatment nearly 2 years ago. Cone-beam tomography (CBT) of the maxilla revealed a destructive lesion with fenestration of both the buccal and palatal cortical bone related to tooth 21 (Fig. 3). Considering the patient’s previous medical history and other unusual clinical features which included 1-year duration of the periapical lesion, simultaneous buccal and palatal swelling, superficial telangiectasia of the nodule, clinical unresponsiveness to endodontic and oral antibiotics therapy with maintenance of suppuration and the destructive pattern showed in CBT images, an incisional biopsy of the nodule was performed under local anaesthesia. During the procedure, the biopsy site did not bleed and the lesion had a fibro-elastic consistency. Microscopic examination revealed several islands of atypical epithelium surrounding necrotic areas and separated by evident fibrous septa (Fig. 4a,b). Presence of abundant squamous differentiation and atypical mitosis was also noted (Fig. 4c,d). Histopathological examination revealed a squamous cell carcinoma similar in morphological pattern to that of cervical carcinomas and a diagnosis of a cervical carcinoma metastasis to the maxilla was agreed. The patient was subsequently referred to an external oncological service for revaluation where further investigations including radiographs, computed tomography (CT) and magnetic resonance imaging ruled out metastasis located elsewhere in her body. The patient underwent head and neck radiotherapy to control the maxillary foci of the disease. The patient is still under clinical follow-up after 12 months with persistence of the maxillary disease.
Discussion Metastases from distant sites to the jaws are unusual, comprising approximately 1% of all oral cancers (Davidson & Moyo 1991, Hirshberg & Buchner 1995, Lim et al. 2006, Hirshberg et al. 2008, Beena et al. 2011, Carvalho et al. 2012). The metastatic process is not a random event, but is a site-specific and complex biologic process involving several mechanisms such as cell proliferation, motility, invasion, survival and evasion of the immune system (Chambers et al. 2002, Pantel & Brakenhoff 2004, Hirshberg et al. 2008). Evidence suggests that almost any metastatic malignant tumour can potentially colonize the oral region (Hirshberg & Buchner 1995, Shen et al. 2009). In an attempt to
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(a)
(b)
(c)
(d)
Figure 4 (a) Histological examination of the oral lesion. Epithelial islands with the presence of fibrous septa (H.E. 10X). (b) Central areas of necrosis were observed in the epithelial islands (H.E. 40X). (c) Note the presence of keratin, atypical cells, disorganization of epithelial architecture and loss of layered hierarchy (H.E. 50X). (d) Atypical squamous cells with evident nuclei, presence of mitoses (arrow), and a higher magnification of the central necrotic area (arrow) (H.E. 200X).
explain the possibility of oral metastases from distant sites, the valveless vertebral venous plexus has been proposed as an alternative route of spread. However, the vascularity of the jaws, the high bone turnover and the constant inflammation of this region may also play an important role in the establishment of oral metastases (D’Silva et al. 2006, Shen et al. 2009). Cervical cancer is considered to be the second most important cancer amongst women, with a considerable potential for metastasis. For oral metastases, this corresponds to 7.7% (Hirshberg et al. 2008, Ferlay et al. 2010). The case reported here is a rare example of a metastasis to the maxillofacial region from a cervical cancer, with confused findings, such as widening of periodontal ligament space, pulp necrosis and the presence of suppuration in the gingival sulcus. When data regarding the most commonly affected head and neck sites are compared, some authors claim that the jawbones are more frequently involved, considering that metastases in soft tissues are extraordinary rare (Nishimura et al. 1982, Hirshberg et al. 1993, 2008, Van der Waal et al. 2003, Beena et al. 2011). In the oral soft tissues, the attached gingiva was the most commonly affected site, with 54% of oral metastases (Hirshberg et al. 2008, Beena et al. 2011). Hirshberg et al. (2008) showed that female genital organ metastases more commonly affect the soft tissues and, when the gingiva is involved, is frequently found in the maxilla (Seoane et al. 2009). In the case reported in this article, both attached gingiva and maxilla were affected by the cervical cancer metastasis. Gondak et al. (2013) recently warned that several different intra-osseous diseases in the oral cavity are able to mimic endodontic periapical lesions, including malignant disease. The initial stages of metastatic lesions could also mimic benign processes, such as highly vascularized, polypoid or exophytic lesions, and/or periapical disease with pulp devitalization and widening of the periodontal ligament space (Block et al. 1977, Spott
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1985, Bueno et al. 2008, Hirshberg et al. 2008, Khalili et al. 2010). The suspicious of metastases should always be taken into consideration when making a diagnosis in the field of endodontics in cases with unusual clinical presentation of patients with previous malignant disease. An incisional biopsy is mandatory (Hirshberg & Buchner 1995, Hirshberg et al. 2008). In the present case, metastatic lesion had atypical features previously reported, including pulp necrosis of tooth 21 with widening of periodontal ligament space, simultaneous buccal and palatal swelling, superficial telangiectasia of the nodule with suppuration through the gingival sulcus and clinical unresponsiveness to endodontic and oral antibiotics therapy, leading to a delayed diagnosis due to this disguised clinical presentation. Age is an important clinical parameter when the diagnosis of a lesion is being formulated (Carvalho et al. 2012). In general, most oral metastatic lesions are found in patients between the fifth and seventh decades of life (Hirshberg et al. 2008). Women exhibited twice as many jaw metastases as did men that were 31 to 40 years of age, and significantly fewer metastases than did men 71 to 80 years of age (D’Silva et al. 2006). Carvalho et al. (2012) reviewed all the metastasis cases of female genital organs in the English-language literature published from 1928 to 2011 and showed that the mean age was 56.9 years. However, in the present case, the patient was 33 years old when she was diagnosed with an oral metastatic carcinoma. The average time between the diagnosis of the primary tumour and the detection of oral metastases is approximately 40 months (Hirshberg et al. 2008). This is an important time-point related to an advanced disease and a worse prognosis for the affected patient, with high mortality rates (Davidson & Moyo 1991). In most patients who present with an oral metastasis, the distant primary tumour has already been diagnosed and previously treated (Van der Waal et al. 2003, D’Silva et al. 2006). If a metastasis is suspected or even confirmed, an extensive oncological evaluation should be performed to evaluate the best individual therapeutic option. In the present case, the jawbone lesion was the first sign of metastatic disease. The patient had her first metastasis only 4 years after the cervix uterine cancer diagnosis and was referred to her oncologist for close monitoring.
Conclusion Clinicians should always give importance to the patient’s medical history and perform a systematic oral (Santos-Silva et al. 2014) and radiographic examination of suspicious endodontic lesions with any aggressive signal or lack of post-treatment response to conventional endodontic therapy, especially in patients with a previous cancer history. Taking into account the wide histological variety of primary and secondary malignant tumours, biopsy and histopathological analysis are essential for confirmation of the metastasis. Moreover, all dental practitioners should be aware of the ability of metastases to mimic periapical disease with disguised clinical features, such as the enlargement of the periodontal ligament space, spontaneous pulp necrosis without any apparent cause, simultaneous buccal and palatal swelling with persistent symptoms, the presence of suppuration that can be mistaken as an abscess and resistance to endodontic treatment in oncologic patients, as they are well placed to recognize oral lesions in the initial clinical stages given that their treatments are usually based on frequent dental appointments and long-term follow-ups.
Acknowledgements The authors deny any conflict of interests related to this study.
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Disclaimer Whilst this article has been subjected to Editorial review, the opinions expressed, unless specifically indicated, are those of the author. The views expressed do not necessarily represent best practice, or the views of the IEJ Editorial Board, or of its affiliated Specialist Societies.
References Abdulrahman GO Jr, Rahman GA (2012) Epidemiology of breast cancer in Europe and Africa. Journal of Cancer Epidemiology 2012: article ID 915610, doi: 10.1155/2012/915610. Arias-Chamorro B, Galeas-Anaya F, Salinas-Sanchez J et al. (2012) Maxillofacial metastasis of genitourinary origin. A report of 3 cases and review of the literature. Medicina Oral, Patologıa Oral y Cirugıa Bucal 17, e242–5. Beena V, Panda S, Heera R, Rajeev R (2011) Multiple metastatic tumors in the oral cavity. Journal of Oral and Maxillofacial Pathology: JOMFP 15, 214–8. Block RM, Mark HI, Bushell A (1977) Metastatic carcinoma of the breast mimicking periapical disease in the mandible. Journal of Endodontics 3, 197–9. Bueno MR, De Carvalhosa AA, Castro PH, Pereira KC, Borges FT, Estrela C (2008) Mesenchymal chondrosarcoma mimicking apical periodontitis. Journal of Endodontics 34, 1415–9. Carvalho MV, Hopp RN, Correa MB, Totti V, Jorge J, Vargas PA (2012) Oral metastasis of uterine carcinoma: case report and 83-year review of this uncommon occurrence. Archive of Oncology 20, 75–80. Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Natures Reviews Cancer 2, 563–72. Davidson NG, Moyo C (1991) Oral cavity metastasis from carcinoma of the cervix. International Journal of Gynecology & Obstetrics 35, 79–82. Drage N, Rogers S, Greenall C, Playle R (2013) Incidental findings on cone beam computed tomography in orthodontic patients. Journal of Orthodontics 40, 29–37. D’Silva NJ, Summerlin DJ, Cordell KG et al. (2006) Metastatic tumors in the jaws: a retrospective study of 114 cases. Journal of the American Dental Association 137, 1667–72. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International Journal of Cancer 127, 2893–917. Gondak RO, Rocha AC, Neves Campos JG et al. (2013) Unicystic ameloblastoma mimicking apical periodontitis: a case series. Journal of Endodontics 39, 145–8. Hirshberg A, Buchner A (1995) Metastatic tumours to the oral region. An overview. European Journal of Cancer Part B: Oral Oncology 31, 355–60. Hirshberg A, Leibovich P, Buchner A (1993) Metastases to the oral mucosa: analysis of 157 cases. Journal of Oral Pathology & Medicine 22, 385–90. Hirshberg A, Shnaiderman-Shapiro A, Kaplan I, Berger R (2008) Metastatic tumours to the oral cavity - pathogenesis and analysis of 673 cases. Oral Oncology 44, 743–52. Keller EE, Gunderson LL (1987) Bone disease metastatic to the jaws. Journal of the American Dental Association 115, 697–701. Khalili M, Mahboobi N, Shams J (2010) Metastatic breast carcinoma initially diagnosed as pulpal/ periapical disease: a case report. Journal of Endodontics 36, 922–5. Lee JJ, Cheng SJ, Lin SK, Chiang CP, Yu CH, Kok SH (2007) Gingival squamous cell carcinoma mimicking a dentoalveolar abscess: report of a case. Journal of Endodontics 33, 177–80. Lim SY, Kim SA, Ahn SG et al. (2006) Metastatic tumours to the jaws and oral soft tissues: a retrospective analysis of 41 Korean patients. International Journal of Oral and Maxillofacial Surgery 35, 412–5. Liu XY, Feng AH, Cui YM, Tobe RG (2013) Prevention of human papillomavirus (HPV) infection and cervical cancer in China: how does HPV vaccination bring about benefits to Chinese women? Bioscience Trends 7, 159–67.
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Luciani S, Cabanes A, Prieto-Lara E, Gawryszewski V (2013) Cervical and female breast cancers in the Americas: current situation and opportunities for action. Bulletin of the World Health Organization 91, 640–9. Mavili E, Ozturk M, Yucel T, Yuce I, Cagli S (2010) Tongue metastasis mimicking an abscess. Diagnostic and Interventional Radiology 16, 27–9. Nishimura Y, Yakata H, Kawasaki T, Nakajima T (1982) Metastatic tumours of the mouth and jaws. A review of the Japanese literature. Journal of Maxillofacical Surgery 10, 253–8. Pantel K, Brakenhoff RH (2004) Dissecting the metastatic cascade. Nature Reviews Cancer 4, 448– 56. Poulias E, Melakopoulos I, Tosios K (2011) Metastatic breast carcinoma in the mandible presenting as a periodontal abscess: a case report. Journal of Medical Case Reports 5, 265. Santos-Silva AR, Carvalho Andrade MA, Jorge J, Almeida OP, Vargas PA, Lopes MA (2014) Tongue squamous cell carcinoma in young nonsmoking and nondrinking patients: 3 clinical cases of orthodontic interest. American Journal of Orthodontics Dentofacial Orthopedics 145, 103–7. Seoane J, Van der Waal I, Van der Waal RI et al. (2009) Metastatic tumours to the oral cavity: a survival study with a special focus on gingival metastases. Journal of Clinical Periodontology 36, 488–92. Shen ML, Kang J, Wen YL et al. (2009) Metastatic tumors to the oral and maxillofacial region: a retrospective study of 19 cases in West China and review of the Chinese and English literature. Journal of Oral Maxillofacical Surgery 67, 718–37. Spott RJ (1985) Metastatic breast carcinoma disguised as periapical disease in the maxilla. Oral Surgery, Oral Medicine, and Oral Pathology 60, 327–8. Van der Waal RIF, Buter J, Van der Waal I (2003) Oral metastases: report of 24 cases. British Journal of Oral Maxillofacial Surgery 41, 3–6.
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Metastatic cervical carcinoma of the jaw presenting as periapical disease V. R. Torregrossa, K. M. Faria, M. M. Bicudo, P. A. Vargas, O. P. Almeida, M. A. Lopes & A. R. Santos-Silva Department of Oral Diagnosis, Semiology and Oral Pathology Areas, Piracicaba Dental School, University of Campinas (UNICAMP) Piracicaba, Brazil
Abstract Torregrossa VR, Faria KM, Bicudo MM, Vargas PA, Almeida OP, Lopes MA, Santos-Silva AR. Metastatic cervical carcinoma of the jaw presenting as periapical disease. International Endodontic Journal.
Aim To present a case report of a metastasis from cervical cancer to the maxilla, which was misdiagnosed as periapical disease and to caution clinicians that metastases could have a disguised clinical presentation that must be taken into account in the differential diagnosis of periapical disease in oncologic patients. Summary Although metastatic tumours of the jaws are uncommon, they may mimic benign inflammatory processes and reactive lesions. The ability of metastatic lesions to mimic periapical disease is discussed and a brief review of the literature is presented, emphasizing the importance of correct diagnosis to prevent delay in diagnosing cancer. Attention should therefore be given to the patient’s medical history, especially of those with a previous history of cancer, and all dental practitioners should be aware of the possibility of metastases that may be confused with periapical disease. Finally, endodontists are well placed to recognize malignant and metastatic oral lesions during the initial clinical stages, given that their treatments are usually based on frequent dental appointments and long-term follow-ups. Key learning points • A metastatic tumour in the jaw, such as cervical carcinoma, can mimic periapical disease in its early stages, hindering the correct diagnosis. • Unusual clinical features such as widening of the periodontal ligament space, a tooth with a necrotic pulp with no evidence of pulp injury, buccal and palatal swelling with persistent and progressive symptoms, and lack of response to conventional endodontic therapy should be investigated in oncologic patients aiming to exclude the possibility of a metastasis. • The correlation between clinical findings, medical history and histopathology is essential for confirmation of the diagnosis.
Correspondence: Alan Roger Santos-Silva, Department of Oral Diagnosis, Semiology Area, Piracicaba Dental School, University of Campinas, Av. Limeira, 901, Bairro Are~ao, Piracicaba, CEP 13414-903, S~ao Paulo, Brazil (Tel: +55 19 21065320; Fax +55 19 21065218; e-mail: [email protected]).
© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd
International Endodontic Journal, 0, 1–9, 2015
1
CASE REPORT
Keywords: carcinoma, cervical cancer, endodontics, metastasis, periapical disease. Received 23 September 2014; accepted 17 February 2015
Introduction Periapical disease is by far the most common pathologic condition of the jaw (Drage et al. 2013). The cause of periapical disease is often obvious, although there are noninflammatory disorders such as metastatic tumours which can mimic this condition (Block et al. 1977, Spott 1985, Bueno et al. 2008, Khalili et al. 2010). Thus, periapical radiolucencies should be thoroughly investigated and correctly diagnosed to rule out rare periapical pathosis (Lee et al. 2007, Mavili et al. 2010). The involvement of the oral and maxillofacial region in metastatic tumours is uncommon and usually indicates widespread disease with a poor prognosis (Keller & Gunderson 1987, D’Silva et al. 2006, Lim et al. 2006, Hirshberg et al. 2008, Beena et al. 2011, Arias-Chamorro et al. 2012). In nearly 30% of cases, a metastatic lesion in the maxillofacial region is the first indication of underlying malignancy (Davidson & Moyo 1991, Hirshberg & Buchner 1995, Arias-Chamorro et al. 2012). The jawbones and oral soft tissues can be affected by metastases, which often simulate benign processes and dental inflammatory pathosis such as pyogenic granulomas, gingivitis, periodontal abscesses and apical periodontitis, frequently leading to misdiagnosis and mistreatment (Davidson & Moyo 1991, Hirshberg & Buchner 1995, Beena et al. 2011). The most common primary sites associated with oral metastases amongst women are the breast, genitourinary tract, kidney, colorectal region and thyroid gland (D’Silva et al. 2006, Lim et al. 2006, Hirshberg et al. 2008, Poulias et al. 2011). Breast and cervical cancers are generally considered to be the most important cancers amongst women (Luciani et al. 2013). Breast cancer continues to remain the most lethal malignancy in women, with a tendency to metastasize to the jawbones (D’Silva et al. 2006, Hirshberg et al. 2008, Poulias et al. 2011, Abdulrahman & Rahman 2012). Cervical cancer is the second most common cancer in women and is the second major primary site associated with oral metastases (Nishimura et al. 1982, Davidson & Moyo 1991, Hirshberg et al. 1993, 2008, Arias-Chamorro et al. 2012, Carvalho et al. 2012, Liu et al. 2013, Luciani et al. 2013). Although rare, oral metastases often present innocuous dental symptoms where the dentist has the opportunity to determine an early diagnosis and refer the patient for appropriate treatment (Keller & Gunderson 1987, Davidson & Moyo 1991, D’Silva et al. 2006). This paper presents a rare clinical case of a metastasis to the jaw with unusual features, which was initially misdiagnosed as periapical disease. The report is a warning to all dental practitioners that oral metastases have the potential to mimic endodontic diseases and pose a diagnosis and its management a challenge.
Case report A 33-year-old woman with a previous medical history of cervical carcinoma, and who was still undergoing medical treatment 4 years after her diagnosis, was referred for the evaluation of an asymptomatic lesion in the maxilla. At the time of her first visit to the general practitioner, she was on a course of chemotherapy with no comorbidities. During the history, she reported that she was first examined by an otolaryngologist, who referred her to a general dentist for the evaluation of a year-long gingival lesion between tooth 21 and 22 with associated buccal and palatal swelling (Fig. 1a,b). Further
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© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd
CASE REPORT
(a)
(b) Figure 1 (a) Buccal clinical presentation showing an erythematous area on the attached gingiva between teeth 21 and 22. Note the superficial telangiectasia and the presence of suppuration through the gingival sulcus. (b) Palatal view with expanding swelling and flotation point.
clinical examination revealed a negative response to a cold test (tetrafluoroethane) in tooth 21, which had a cosmetic restoration and no history of previous dental trauma. Subsequent image analysis revealed an enlargement of the periodontal ligament space of tooth 21 (Fig. 2a), suggesting periapical disease secondary to pulp necrosis. The general dentist therefore diagnosed these symptoms as a periapical abscess secondary to spontaneous pulp necrosis of tooth 21 and then opened the pulp chamber and found necrotic pulp tissue without pus. The root canal was instrumented during the first session using a conventional rotary multifile system. A 2.5% sodium hypochlorite solution was used at all times during the irrigation procedures and after instrumentation. Then, a Ca(OH)2 paste was injected into the root canal. The patient was treated empirically with oral antibiotics (amoxicillin 500 mg thrice a day for 7 days), analgesics and 0.12% chlorhexidine digluconate daily mouthwashes. The Ca(OH)2 paste was removed and the root canal filled with Gutta-percha at the second visit. All phases of endodontic treatment were conducted under rubber dam. After 30 days of post-endodontic treatment follow-up, a progressive diffuse periapical radiolucency with ill-defined contours was noted (Fig. 2b), and the patient was referred to the Oral Medicine Clinic for evaluation. General extra-oral examination revealed alopecia and no palpable lymph nodes in the
© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd
International Endodontic Journal, 0, 1–9, 2015
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CASE REPORT
(a)
(b) Figure 2 (a) Initial periapical radiograph showing a widening of the periodontal ligament space in the periapical region of tooth 21, suggesting periapical disease secondary to pulp necrosis. (b) Periapical radiograph of tooth 21 after conventional root canal treatment. Note the progression of diffuse periapical radiolucency with ill-defined contours compared with Figure 2a.
head and neck. Laboratory tests revealed pancytopenia secondary to chemotherapy. On intra-oral examination, the so-called periapical abscess was observed as a nodule which was hard upon palpation, with evident superficial telangiectasia. The lesion measured approximately 3 9 3 cm, causing enlargement of the buccal maxilla and attached gingiva with the presence of a serous fluid suggestive of pus through the gingival sulcus
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Figure 3 Axial section of cone-beam tomography revealing a destructive hypodense image causing bone expansion and fenestration of both the buccal and palatal cortical bone in the region of tooth 21.
in the region of tooth 21. The tooth had grade 1 mobility and was associated with discrete pain during vertical percussion. Periodontal probing depths were 1.5 mm. The patient was using orthodontic appliances, but had abandoned the orthodontic treatment nearly 2 years ago. Cone-beam tomography (CBT) of the maxilla revealed a destructive lesion with fenestration of both the buccal and palatal cortical bone related to tooth 21 (Fig. 3). Considering the patient’s previous medical history and other unusual clinical features which included 1-year duration of the periapical lesion, simultaneous buccal and palatal swelling, superficial telangiectasia of the nodule, clinical unresponsiveness to endodontic and oral antibiotics therapy with maintenance of suppuration and the destructive pattern showed in CBT images, an incisional biopsy of the nodule was performed under local anaesthesia. During the procedure, the biopsy site did not bleed and the lesion had a fibro-elastic consistency. Microscopic examination revealed several islands of atypical epithelium surrounding necrotic areas and separated by evident fibrous septa (Fig. 4a,b). Presence of abundant squamous differentiation and atypical mitosis was also noted (Fig. 4c,d). Histopathological examination revealed a squamous cell carcinoma similar in morphological pattern to that of cervical carcinomas and a diagnosis of a cervical carcinoma metastasis to the maxilla was agreed. The patient was subsequently referred to an external oncological service for revaluation where further investigations including radiographs, computed tomography (CT) and magnetic resonance imaging ruled out metastasis located elsewhere in her body. The patient underwent head and neck radiotherapy to control the maxillary foci of the disease. The patient is still under clinical follow-up after 12 months with persistence of the maxillary disease.
Discussion Metastases from distant sites to the jaws are unusual, comprising approximately 1% of all oral cancers (Davidson & Moyo 1991, Hirshberg & Buchner 1995, Lim et al. 2006, Hirshberg et al. 2008, Beena et al. 2011, Carvalho et al. 2012). The metastatic process is not a random event, but is a site-specific and complex biologic process involving several mechanisms such as cell proliferation, motility, invasion, survival and evasion of the immune system (Chambers et al. 2002, Pantel & Brakenhoff 2004, Hirshberg et al. 2008). Evidence suggests that almost any metastatic malignant tumour can potentially colonize the oral region (Hirshberg & Buchner 1995, Shen et al. 2009). In an attempt to
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(a)
(b)
(c)
(d)
Figure 4 (a) Histological examination of the oral lesion. Epithelial islands with the presence of fibrous septa (H.E. 10X). (b) Central areas of necrosis were observed in the epithelial islands (H.E. 40X). (c) Note the presence of keratin, atypical cells, disorganization of epithelial architecture and loss of layered hierarchy (H.E. 50X). (d) Atypical squamous cells with evident nuclei, presence of mitoses (arrow), and a higher magnification of the central necrotic area (arrow) (H.E. 200X).
explain the possibility of oral metastases from distant sites, the valveless vertebral venous plexus has been proposed as an alternative route of spread. However, the vascularity of the jaws, the high bone turnover and the constant inflammation of this region may also play an important role in the establishment of oral metastases (D’Silva et al. 2006, Shen et al. 2009). Cervical cancer is considered to be the second most important cancer amongst women, with a considerable potential for metastasis. For oral metastases, this corresponds to 7.7% (Hirshberg et al. 2008, Ferlay et al. 2010). The case reported here is a rare example of a metastasis to the maxillofacial region from a cervical cancer, with confused findings, such as widening of periodontal ligament space, pulp necrosis and the presence of suppuration in the gingival sulcus. When data regarding the most commonly affected head and neck sites are compared, some authors claim that the jawbones are more frequently involved, considering that metastases in soft tissues are extraordinary rare (Nishimura et al. 1982, Hirshberg et al. 1993, 2008, Van der Waal et al. 2003, Beena et al. 2011). In the oral soft tissues, the attached gingiva was the most commonly affected site, with 54% of oral metastases (Hirshberg et al. 2008, Beena et al. 2011). Hirshberg et al. (2008) showed that female genital organ metastases more commonly affect the soft tissues and, when the gingiva is involved, is frequently found in the maxilla (Seoane et al. 2009). In the case reported in this article, both attached gingiva and maxilla were affected by the cervical cancer metastasis. Gondak et al. (2013) recently warned that several different intra-osseous diseases in the oral cavity are able to mimic endodontic periapical lesions, including malignant disease. The initial stages of metastatic lesions could also mimic benign processes, such as highly vascularized, polypoid or exophytic lesions, and/or periapical disease with pulp devitalization and widening of the periodontal ligament space (Block et al. 1977, Spott
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1985, Bueno et al. 2008, Hirshberg et al. 2008, Khalili et al. 2010). The suspicious of metastases should always be taken into consideration when making a diagnosis in the field of endodontics in cases with unusual clinical presentation of patients with previous malignant disease. An incisional biopsy is mandatory (Hirshberg & Buchner 1995, Hirshberg et al. 2008). In the present case, metastatic lesion had atypical features previously reported, including pulp necrosis of tooth 21 with widening of periodontal ligament space, simultaneous buccal and palatal swelling, superficial telangiectasia of the nodule with suppuration through the gingival sulcus and clinical unresponsiveness to endodontic and oral antibiotics therapy, leading to a delayed diagnosis due to this disguised clinical presentation. Age is an important clinical parameter when the diagnosis of a lesion is being formulated (Carvalho et al. 2012). In general, most oral metastatic lesions are found in patients between the fifth and seventh decades of life (Hirshberg et al. 2008). Women exhibited twice as many jaw metastases as did men that were 31 to 40 years of age, and significantly fewer metastases than did men 71 to 80 years of age (D’Silva et al. 2006). Carvalho et al. (2012) reviewed all the metastasis cases of female genital organs in the English-language literature published from 1928 to 2011 and showed that the mean age was 56.9 years. However, in the present case, the patient was 33 years old when she was diagnosed with an oral metastatic carcinoma. The average time between the diagnosis of the primary tumour and the detection of oral metastases is approximately 40 months (Hirshberg et al. 2008). This is an important time-point related to an advanced disease and a worse prognosis for the affected patient, with high mortality rates (Davidson & Moyo 1991). In most patients who present with an oral metastasis, the distant primary tumour has already been diagnosed and previously treated (Van der Waal et al. 2003, D’Silva et al. 2006). If a metastasis is suspected or even confirmed, an extensive oncological evaluation should be performed to evaluate the best individual therapeutic option. In the present case, the jawbone lesion was the first sign of metastatic disease. The patient had her first metastasis only 4 years after the cervix uterine cancer diagnosis and was referred to her oncologist for close monitoring.
Conclusion Clinicians should always give importance to the patient’s medical history and perform a systematic oral (Santos-Silva et al. 2014) and radiographic examination of suspicious endodontic lesions with any aggressive signal or lack of post-treatment response to conventional endodontic therapy, especially in patients with a previous cancer history. Taking into account the wide histological variety of primary and secondary malignant tumours, biopsy and histopathological analysis are essential for confirmation of the metastasis. Moreover, all dental practitioners should be aware of the ability of metastases to mimic periapical disease with disguised clinical features, such as the enlargement of the periodontal ligament space, spontaneous pulp necrosis without any apparent cause, simultaneous buccal and palatal swelling with persistent symptoms, the presence of suppuration that can be mistaken as an abscess and resistance to endodontic treatment in oncologic patients, as they are well placed to recognize oral lesions in the initial clinical stages given that their treatments are usually based on frequent dental appointments and long-term follow-ups.
Acknowledgements The authors deny any conflict of interests related to this study.
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Disclaimer Whilst this article has been subjected to Editorial review, the opinions expressed, unless specifically indicated, are those of the author. The views expressed do not necessarily represent best practice, or the views of the IEJ Editorial Board, or of its affiliated Specialist Societies.
References Abdulrahman GO Jr, Rahman GA (2012) Epidemiology of breast cancer in Europe and Africa. Journal of Cancer Epidemiology 2012: article ID 915610, doi: 10.1155/2012/915610. Arias-Chamorro B, Galeas-Anaya F, Salinas-Sanchez J et al. (2012) Maxillofacial metastasis of genitourinary origin. A report of 3 cases and review of the literature. Medicina Oral, Patologıa Oral y Cirugıa Bucal 17, e242–5. Beena V, Panda S, Heera R, Rajeev R (2011) Multiple metastatic tumors in the oral cavity. Journal of Oral and Maxillofacial Pathology: JOMFP 15, 214–8. Block RM, Mark HI, Bushell A (1977) Metastatic carcinoma of the breast mimicking periapical disease in the mandible. Journal of Endodontics 3, 197–9. Bueno MR, De Carvalhosa AA, Castro PH, Pereira KC, Borges FT, Estrela C (2008) Mesenchymal chondrosarcoma mimicking apical periodontitis. Journal of Endodontics 34, 1415–9. Carvalho MV, Hopp RN, Correa MB, Totti V, Jorge J, Vargas PA (2012) Oral metastasis of uterine carcinoma: case report and 83-year review of this uncommon occurrence. Archive of Oncology 20, 75–80. Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Natures Reviews Cancer 2, 563–72. Davidson NG, Moyo C (1991) Oral cavity metastasis from carcinoma of the cervix. International Journal of Gynecology & Obstetrics 35, 79–82. Drage N, Rogers S, Greenall C, Playle R (2013) Incidental findings on cone beam computed tomography in orthodontic patients. Journal of Orthodontics 40, 29–37. D’Silva NJ, Summerlin DJ, Cordell KG et al. (2006) Metastatic tumors in the jaws: a retrospective study of 114 cases. Journal of the American Dental Association 137, 1667–72. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International Journal of Cancer 127, 2893–917. Gondak RO, Rocha AC, Neves Campos JG et al. (2013) Unicystic ameloblastoma mimicking apical periodontitis: a case series. Journal of Endodontics 39, 145–8. Hirshberg A, Buchner A (1995) Metastatic tumours to the oral region. An overview. European Journal of Cancer Part B: Oral Oncology 31, 355–60. Hirshberg A, Leibovich P, Buchner A (1993) Metastases to the oral mucosa: analysis of 157 cases. Journal of Oral Pathology & Medicine 22, 385–90. Hirshberg A, Shnaiderman-Shapiro A, Kaplan I, Berger R (2008) Metastatic tumours to the oral cavity - pathogenesis and analysis of 673 cases. Oral Oncology 44, 743–52. Keller EE, Gunderson LL (1987) Bone disease metastatic to the jaws. Journal of the American Dental Association 115, 697–701. Khalili M, Mahboobi N, Shams J (2010) Metastatic breast carcinoma initially diagnosed as pulpal/ periapical disease: a case report. Journal of Endodontics 36, 922–5. Lee JJ, Cheng SJ, Lin SK, Chiang CP, Yu CH, Kok SH (2007) Gingival squamous cell carcinoma mimicking a dentoalveolar abscess: report of a case. Journal of Endodontics 33, 177–80. Lim SY, Kim SA, Ahn SG et al. (2006) Metastatic tumours to the jaws and oral soft tissues: a retrospective analysis of 41 Korean patients. International Journal of Oral and Maxillofacial Surgery 35, 412–5. Liu XY, Feng AH, Cui YM, Tobe RG (2013) Prevention of human papillomavirus (HPV) infection and cervical cancer in China: how does HPV vaccination bring about benefits to Chinese women? Bioscience Trends 7, 159–67.
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© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd
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International Endodontic Journal, 0, 1–9, 2015
CASE REPORT
Luciani S, Cabanes A, Prieto-Lara E, Gawryszewski V (2013) Cervical and female breast cancers in the Americas: current situation and opportunities for action. Bulletin of the World Health Organization 91, 640–9. Mavili E, Ozturk M, Yucel T, Yuce I, Cagli S (2010) Tongue metastasis mimicking an abscess. Diagnostic and Interventional Radiology 16, 27–9. Nishimura Y, Yakata H, Kawasaki T, Nakajima T (1982) Metastatic tumours of the mouth and jaws. A review of the Japanese literature. Journal of Maxillofacical Surgery 10, 253–8. Pantel K, Brakenhoff RH (2004) Dissecting the metastatic cascade. Nature Reviews Cancer 4, 448– 56. Poulias E, Melakopoulos I, Tosios K (2011) Metastatic breast carcinoma in the mandible presenting as a periodontal abscess: a case report. Journal of Medical Case Reports 5, 265. Santos-Silva AR, Carvalho Andrade MA, Jorge J, Almeida OP, Vargas PA, Lopes MA (2014) Tongue squamous cell carcinoma in young nonsmoking and nondrinking patients: 3 clinical cases of orthodontic interest. American Journal of Orthodontics Dentofacial Orthopedics 145, 103–7. Seoane J, Van der Waal I, Van der Waal RI et al. (2009) Metastatic tumours to the oral cavity: a survival study with a special focus on gingival metastases. Journal of Clinical Periodontology 36, 488–92. Shen ML, Kang J, Wen YL et al. (2009) Metastatic tumors to the oral and maxillofacial region: a retrospective study of 19 cases in West China and review of the Chinese and English literature. Journal of Oral Maxillofacical Surgery 67, 718–37. Spott RJ (1985) Metastatic breast carcinoma disguised as periapical disease in the maxilla. Oral Surgery, Oral Medicine, and Oral Pathology 60, 327–8. Van der Waal RIF, Buter J, Van der Waal I (2003) Oral metastases: report of 24 cases. British Journal of Oral Maxillofacial Surgery 41, 3–6.
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