Gingival metastasis of a bronchogenic adenocarcinoma: report of a case

Gingival metastasis of a bronchogenic adenocarcinoma: report of a case
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  Gingival metastasis of a bronchogenic adenocarcinoma: reportof a case Rémi Curien, DDS, a Hervé Moizan, DDS, PhD, b and Eric Gerard, DDS, PhD, c Thionville andMetz, France METZ-THIONVILLE REGIONAL HOSPITAL CENTER We report the case of a 64-year-old patient suffering from a multiple metastatic bronchial adenocarcinoma,referred to our department for a gingival tumefaction. The diagnostic assumptions considered were those of a pyogenicgranuloma, of a primary gingival carcinoma, or of a metastasis of the bronchial tumor. An excisional biopsy wascarried out and the histopathologic examination confirmed the latter diagnosis. No complementary care wasperformed because of the multiple localizations and unfavorable prognosis. If metastases of pulmonary cancersrepresent the majority of gingival metastases, those of bronchial adenocarcinoma are very rare. Metastatic processcould be facilitated by Batson’s plexus, through the periodontal inflammation or the direct bronchotracheal way. Themain clinical diagnostic difficulty is the distinction between benign lesion and malignant lesion, and between primarylesion and metastasis. Even if gingival metastases are rare, their semiological value incites the histopathologicexamination of any presumedly benign tumor of the gingiva.  (Oral Surg Oral Med Oral Pathol Oral Radiol Endod2007;104:e25-e28) Pulmonary cancers are common malignant lesions, andbronchogenic carcinoma of the lung is one of the prin-cipal causes of mortality among adult men, with anincrease in prevalence among women during the lastdecades. There is a strong correlation between tobaccosmoking and the development of this type of cancer. 1 When all cancers are included, oral metastases areexceptional, representing approximately 1% of oral tu-mors. 2 They are usually intraosseous (9 of 10 cases),with soft tissue localizations being much rarer. 3 For thesoft tissue metastases, the gingiva (54% of cases) andthe alveolar mucosa sites are most frequent, followedby the tongue. 4 In 30% of occurrences, oral metastasisis the first manifestation of the cancer. 5 It is usually asign of an advanced, multiple-metastatic state of thedisease. The time between the diagnosis of a gingivalmetastasis and death ranges from a few weeks to lessthan 1 year, with 5 years of maximum survival. 5-8 These lesions are important in diagnosis and/or prog-nosis.We report the case of a gingival metastasis of abronchogenic adenocarcinoma. Gingival metastases of this histopathologic type of tumor are rare; from 1945to 2004, only 9 cases have been reviewed. 9-11 CASE REPORT A 64-year-old patient had been referred in consultation,complaining because of the appearance for 1 week of apainless gingival swelling. This patient, a smoker, had amultiple metastatic bronchial adenocarcinoma treated by che-motherapy (carboplatin and gemcitabine). Osseous metasta-ses were diagnosed (left iliac bone) and treated by radiother-apy and bisphosphonates (Zometa). Cervical echographyshowed right submandibular, bilateral jugulocarotid, and sub-clavicular adenopathies.The head and neck examination revealed a soft, sessile,exophytic, erythematous and hemorrhagic tumefaction occu-pying the vestibular gingiva of the maxillary right first molar(Fig. 1). The patient described a bleeding of the lesion during brushing and chewing. Sulcular probing did not show anylocal suppuration (differential diagnosis with a periodontalabscess) but did have generalized moderate to locally severeperiodontitis (9-mm pocket between the first molar and sec-ond premolar). Calculus and bacterial plaque were prominent.The maxillary right first molar had endodontic treatment butdid not show sensitivity to pressure nor to percussion. How-ever, it does not totally exclude an abscess of endodonticsrcin. The radiographic examination (Fig. 2) showed sub- gingival tartar and a generalized alveolysis that was not moremarked on the level of tooth. 12 Because of the aspect of thelesion and of the periodontal context, the diagnosis of vascu-lar epulis (pyogenic granuloma) was proposed, although notexcluding the assumption of a metastasis of the bronchialtumor. a Department of Odontology, Metz-Thionville Regional Hospital Cen-ter. b Department of Odontology, Metz-Thionville Regional HospitalCenter. c Department Chief, Department of Odontology, Metz-Thionville Re-gional Hospital Center.Received for publication Apr 23, 2007; returned for revision Jun 10,2007; accepted for publication Jun 11, 2007.1079-2104/$ - see front matter© 2007 Mosby, Inc. All rights reserved.doi:10.1016/j.tripleo.2007.06.021 e25  An excisional biopsy was thus carried out and the micro-scopic examination (Fig. 3) showed a poorly differentiated carcinoma compatible with metastasis from the bronchialadenocarcinoma. The immunohistochemical profile (Fig. 4)of the carcinoma (thyroid transcription factor [TTF]1  ,cytokeratin [CK]7  , CK20  , CK5/6  ) confirmed hisbronchial srcin. The diagnosis of a metastasis of a broncho-genic adenocarcinoma was made.In dialogue with oncologists, no additional care was con-sidered because of the advanced stage of the pathology and itsunfavorable prognosis. The comfort of the patient was main-tained by limiting treatment to the simple excision of thelesion and to the already-initiated palliative chemotherapy. DISCUSSION Hirshberg et al. 4 reviewed the English literature de-voted to oral metastases during the period 1916-1991.In 157 cases of metastases located in the oral mucousmembranes, they counted 86 gingival localizations.The most usual primary localizations were, by order of frequency: lung (25, 58%), kidney (15, 11%), bone (10,46%), breast (9, 3%), and liver (8, 13%), which arefurthermore the most frequent tumors. Yoshii et al. 11 evaluated the frequency of the primary pulmonary lo-calizations to be 10% to 20% of the cases. The averageage of appearance of gingival metastases of pulmonarycancers is 54 years. 13 The presentation of the tumor observed in this case isclose to descriptions in the literature; gingival metasta-ses are generally described as polypoid or exophytic, 6,7 highly vascularized, 8 and hemorrhage is very fre-quently found. 6,14-16 Clinical diagnosis ranged frompyogenic granuloma (or vascular epulis) to peripheralgiant cell granuloma (giant cell epulis) to fibrous epu-lis. 12 Because of their resemblance to benign lesions,the prevalence of oral metastases could be underesti-mated. 17 One of the principal problems with a gingival me-tastasis is the clinical distinction between a benignlesion and a malignant lesion. Malignity must be sus-pected if any of the following signs are present 3,7,15,16 : ●  a fast evolution ●  a hemorrhagic tendency ●  mechanical disorders caused by the development of the tumor ●  an ulcerated and/or necrotic aspect ●  general clinical context of the patientHowever, the final diagnosis is based on histopatho-logic criteria.The second difficulty in this type of lesion is thedistinction between a primary tumor and a metastasis.Clinical suspicion must be confirmed by immunohisto-chemistry. In the current case, the immunohistochemi-cal profile confirmed the diagnosis of metastasis of abronchopulmonary adenocarcinoma. More than 90% of these tumors have a phenotype CK7  and CK20  , andthe TTF1 immunohistochemical profile is expressed by Fig. 1. Intraoral view of the lesion developing in front of maxillary right first molar.Fig. 2. Panoramic radiography showing the generalized al-veolysis.Fig. 3. Microscopic view showing clusters of large epithelialcells with basophilic or chromophobic cytoplasms. Nuclearatypia is marked, and mitoses are present (hematoxylin-eosin,srcinal magnification  160). OOOOE e26   Curien et al. December 2007   two thirds of the primary nonmucinous adenocarcino-mas of the lung. Cytokeratins 5 and 6 are expressed byepidermoid carcinomas. 18,19 The pathogenesis of oral metastases is poorly eluci-dated. The first stage implies the separation of tumoralcells from the primary tumor and their transport bylymphatic or blood vessels. Secondarily, they cross thevascular wall and invade surrounding tissues. 20 The role of local inflammation (here periodontalinflammation) in the attraction of metastatic cells hasbeen suggested; they could be blocked by the richvascular network of chronic inflammatory tissues. 5 Their passage in gingival tissues would be facilitated bythe greatest permeability of the vessels and the presenceof adhesive molecules. 21 Proteolytic enzymes like col-lagenase and elastase allow degradation of the extra-cellular matrix by the tumoral cells and support theiradhesion 22 ; moreover, elastase and collagenase are alsoimplied in periodontitis. 23 When a malignant tumor isdiagnosed, promotion of oral hygiene and control of theperiodontal inflammation could thus reduce the inci-dence of oral metastases. It is also possible to putforward the ability of growth factors in the bone mar-row to stimulate colonization by the tumoral cells 24 ;gingival metastases are often associated with an osse-ous invasion. 25 However, it cannot be objectified in thepresent case because of the important inflammatoryalveolysis. Moreover, the maxilla (involved in our case)is 1.6 times more often involved than the mandible 25 ;this could be explained by its greater abundance of bone marrow. Another pathogenic mechanism of cer-vicofacial metastases would be the role of the Batson’splexus, a prevertebral venous network without valves,authorizing the retrograde crossing of tumoral cellsfrom the lung toward the face. 21,26 Lastly, in the case of metastases of lung cancers, the direct bronchotrachealway could be accused. 25 CONCLUSION Gingival metastases often have a benign appearanceand an erroneous diagnosis can be made, compromisingthe treatment. 17 Given the malignant potential, the di-agnostic value, and the prognostic value of a gingivalmetastasis, it is essential to carry out the excision of anypresumed benign tumor in healthy boundaries and toask for a systematic histopathological examination. REFERENCES 1. Ernster VL. The epidemiology of the lung cancer in women. AnnEpidemiol 1994;4:102-10.2. Meyer I, Shklar G. Malignant tumors metastatic to mouth and jaws. Oral Surg Oral Med Oral Pathol 1965;20:350-62.3. Sanchez Aniceto G, Garcia Penin A, de la Mata Pages R,Montalvo Moreno JJ. Tumors metastatic to the mandible: anal-ysis of nine cases and review of the literature. J Oral MaxillofacSurg 1990;48:246-51.4. Hirshberg A, Leibovich P, Buchner A. Metastases to the oralmucosa: analysis of 157 cases. J Oral Pathol Med 1993;22:385-90.5. Hirshberg A, Leibovitch P, Buchner A. Metastatic tumours to the jaw bones: analysis of 390 cases. J Oral Pathol 1994;23:337-41.6. McDaniel RK, Luna MA, Stimson PG. Metastatic tumors in the jaws. Oral Surg Oral Med Oral Pathol 1971;31:380-6.7. Morishita M, Fukud J. Hepatocellular carcinoma metastatic tothe maxillary incisal gingiva. J Oral Maxillofac Surg 1984;42:812-5.8. Maiorano E, Piatelli A, Favia G. Hepatocellular carcinoma met-astatic to the oral mucosa: report of a case with multiple gingivallocalizations. J Periodontol 2000;71:641-5.9. Staalsen NH, Nielsen JS. Bronchogenic metastasis to the gingiva.Oral Surg Oral Med Oral Pathol 1992;74:561-2.10. Vieira BJ, Aarestrup FM, Da Fonseca EC, Dias EP. Bilateral Fig. 4. Immunomarkings showing the absence of sensitivity to cytokeratins (CK)5/6 and CK20.  A,  CK5/6.  B,  CK7.  C,  CK20.  D, Thyroid transcription factor 1. Original magnification  63. OOOOE Volume 104, Number 6 Curien et al.  e27   gingival metastasis of lung adenocarcinoma: report of a case.J Oral Maxillofac Surg 2001;59:1224-5.11. Yoshii T, Muraoka S, Sano N, Furudoi S, Takahide K. Large cellcarcinoma of the lung metastatic to the mandibular gingiva.J Periodontol 2002;73:571-4.12. Hirshberg A, Buchner A. Metastatic tumours in the oral region.An overview. Eur J Cancer B Oral Oncol 1995;31B:355-60.13. Kaugars GE. Lung malignancies metastatic to the oral cavity.Oral Surg Oral Med Oral Pathol 1981;51:179-86.14. Wegwood D, Rusen D, Balks S. Gingival metastasis from pri-mary hepatocellular carcinoma. Report of a case. Oral Surg OralMed Oral Pathol 1979;47:263-6.15. Nishimura Y, Yakata H, Kawasaki T, Nakajima T. Metastatictumours of the mouth and jaws. A review of the Japaneseliterature. J Oral Maxillofac Surg 1982;10:253-8.16. Kanazawa H, Sato K. Gingival metastasis from primary hepato-cellular carcinoma: report of a case and review of literature.J Oral Maxillofac Surg 1989;47:987-90.17. Ellis GL, Jensen JL, Reingold IM, Barr RJ. Malignant neoplasmsmetastatic to gingivae. Oral Surg Oral Med Oral Pathol 1977;44:238-45.18. Kaufmann O, Dietel M. Thyroid transcritpion factor-1 is thesuperior immunohistochemical marker for pulmonary adenocar-cinomas and large cell carcinomas compared to surfactant pro-teins A and B. Histopathology 2000;36:8-16.19. Kaufman O, Fietze E, Mengs J, Dietel M. Value of p63 andcytokeratin 5/6 as immunohistochemical markers of the differ-ential diagnosis of poorly differentiated and undifferentiatedcarcinomas. Am J Clin Pathol 2001;116:823-30.20. Liotta LA. Cancer cell invasion and metastasis. Sci Am1992;266:54-9.21. Aurebach R, Lu WC, Pardon E, Gumkowski T, Kaminska G,Kaminski M. Specificity of adhesion between murin tumor cellsand capillary endothelium: an in vitro correlate of preferentialmetastasis in vivo. Cancer Res 1987;47:1492-6.22. Zeydel M, Nakagawa S, Biempica L, Takahashi S. Collagenaseand elastase production by mouse mammary adenocarcinomaprimary cultures and clones cells. Cancer Res 1986;46:6438-45.23. Lamster IB, Karabin SD. Periodontal disease activity. Curr OpinDent 1992;2:39-52.24. Zetter BR, Chackal-Roy M, Smith R. The cellular basis forprostate cancer metastasis. Adv Exp Med Biol 1992;324:39-43.25. Chossegros C, Blanc JL, Cheynet F, Bataille JF, Tessier H.Localisations métastatiques au niveau de la cavité buccale. Ob-servation d’un cas et revue de la littérature. Rev Stomatol ChirMaxillofac 1991;92:160-4.26. Batson OV. The function of the vertebral veins and their role inthe spread of metastases. Ann Surg 1940;112:138-49.  Reprint requests: Rémi Curien, DDSDepartment of OdontologyMetz-Thionville Regional Hospital Center1-3 Rue du Friscaty57126 Thionville, Franceremi.curien@laposte.net OOOOE e28  Curien et al. December 2007 
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