| Abstract|| |
Metastasis to the gingival soft tissues is an extremely rare phenomenon, and metastasis of multiple lesions (i.e. more than 2 lesions), is even more hard to find. In this study, we have reported a rare case of lung adenocarcinoma, which metastasized to the maxillary (2 lesions) and mandibular gingivae (1 lesion) in a 57 year old male patient. Metastasis was also seen to the vertebrae. The differential diagnosis consisted of acute myelomonocytic leukemia, chronic lymphocytic leukemia, haemangioma, pyogenic granuloma, giant cell granuloma, peripheral fibroma, primary gingival carcinoma and secondary metastasis. Contrast enhanced computed tomography of the lung showed a well-defined mass situated below the right hilum with lower lobe consolidation and pleural effusion on the right side with dorsal spinal metastasis. Excisional biopsy of the lesions was consistent with the diagnosis, and the immunohistochemical analysis was positive for cytokeratin 7, carcinoembryonic antigen (CEA), thyroid transforming factor 1 (TTF1), and negative for vimentin and cytokeratin 20 (CK20).
Keywords: Gingiva, immunohistochemistry, lung adenocarcinoma
|How to cite this article:|
Ravi Prakash S M, Verma S, Gill N, Malik V. Multiple gingival metastasis of adenocarcinoma of the lung. Indian J Dent Res 2012;23:558-9
Metastasis of malignant tumours' to the oral cavity is relatively rare, and particularly those confined to the oral soft tissues are very uncommon. A literature review showed that only 0.1% of the metastatic tumours were confined to the oral mucosa.  Lung cancers are one of the most common malignant lesions, while bronchogenic carcinoma of the lung is one of the leading causes of mortality among adult men due to cancer. There is a strong correlation between tobacco chewing, smoking and the development of lung cancer. Metastasis to the oral cavity represent approximately 1% of all oral tumours and oral cancers.  They are usually intraosseous, with soft tissue localizations being much rarer. For soft tissue metastases, the gingiva and the alveolar mucosal sites (54%) are most frequent, followed by the tongue in more than 30% of the metastasis cases. Metastasis to the oral cavity is often the first manifestation of lung carcinoma with a metastatic potential.  Clinically, the gingival metastatic tumours closely resemble and are easily mistaken for benign reactive lesions or neoplasms, such as lobular capillary hemangiomas.  The time between the diagnosis of a gingival metastasis and death ranges from a few weeks to less than 1 year, with a maximum survival of 5 years reported.  The aim of this article is to illustrate a rare case of poorly differentiated lung adenocarcinoma with multiple gingival metastasis to the maxillary and mandibular attached gingiva.
|How to cite this URL:|
Ravi Prakash S M, Verma S, Gill N, Malik V. Multiple gingival metastasis of adenocarcinoma of the lung. Indian J Dent Res [serial online] 2012 [cited 2019 Oct 21];23:558-9. Available from: http://www.ijdr.in/text.asp?2012/23/4/558/104978
| Case Report|| |
A 57 year-old male patient reported to our department with a chief complaint of multiple painless gingival swellings in the maxillary and mandibular gingiva since three months. The patient was a chronic smoker since 30 years and was under anti tubercular treatment since 2 months for pleural effusion. The family history was unremarkable. The patient was moderately built and gave a history of weight loss of approximately 15 kg weight within a one month period. There was a bilateral enlargement of the submandibular lymph nodes which were non tender and partially fixed. Intraoral examination revealed multiple, soft, pedunculated, exophytic, erythematous and hemorrhagic tumefactions occupying the attached gingiva of maxillary anteriors [Figure 1], mandibular anteriors [Figure 2] and right maxillary molar region [Figure 3] measuring 5 × 4 cm, 3 × 3 cm, and 1 ×2 cm, respectively. The patient described bleeding from the lesions during brushing and chewing.Sulcular probing showed generalized moderate to severe periodontitis. Calculus and bacterial plaque were prominent. The orthopantomographic examination showed generalized alveolysis; however, this was not marked on the teeth associated with swelling [Figure 4]. Because of the nature of the lesion and the periodontal involvement, a diagnosis of vascular epulis (pyogenic granuloma) was proposed, although of the assumption of a metastasis of the lung tumour was not excluded. The patient was advised a chest computed tomography which revealed a mass situated below the right hilum and related to mediastinum, with lower lobe consolidation, and right pleural effusion along with the dorsal spinal metastasis [Figure 5], [Figure 6].
|Figure 1: Intraoral photograph of the patient showing the extension of the growth in maxillary arch towards the palate|
Click here to view
|Figure 2: Intraoral photograph of the patient showing the metastatic growth in the mandibular arch|
Click here to view
|Figure 3: Intraoral photograph of the patient showing the metastatic growth in the maxillary molar region|
Click here to view
|Figure 4: Photograph of the orthopantomogram of the patient showing severe periodontitis and generalized alveolysis with multiple missing teeth|
Click here to view
|Figure 5: Photograph of contrast enhanced computed tomography of abdomen showing space occupying mass in dorsal spinal vertebrae suggestive of spinal metastasis|
Click here to view
|Figure 6: Photograph of contrast enhanced computed tomography of abdomen with the mediastinal window showing well defined mass of mixed hyper and hypodensity below the right hilum along with the right pleural effusion|
Click here to view
An excisional biopsy was thus carried out from all the sites and the histopathological examination with haematoxylin-eosin revealed dysplastic changes in the epithelium [Figure 7]a. Immunohistochemical analysis was positive for the carcinoembryonic antigen [Figure 7]b, cytokeratin 7 [Figure 7]c, thyroid transforming factor 1 [Figure 7]d and negative for cytokeratin 20 [Figure 7]e and vimentin [Figure 7]f. The histopathological and immunohistochemical features were consistent with the diagnosis of gingival metastasis from the lung adenocarcinoma.However, unfortunately, after four weeks from our examination, the patient died of cardiorespiratory failure.
|Figure 7: (a) Histopathological examination using haematoxylin-eosin staining (original magnification × 10), (b) Immunohistochemical markers showing the presence of sensitivity to carcinoembryonic antigen, (CEA).Original magnification × 40, (c) Presence of sensitivity to CK7 (cytokeratin). Original magnification × 10, (d) Absence of sensitivity to CK20 (cytokeratin).Original magnification × 10, (e) Absence of sensitivity to Vimentin. Original magnification × 40, (f) Presence of sensitivity to TTF 1 (thyroid transforming factor). Original magnification × 10|
Click here to view
| Discussion|| |
Hirshberg reported 157 cases of metastasis to the oral soft tissues, and the lung was the most frequent primary site (35.5%) followed by the kidney (16%) and the skin (15%). The gingiva was the most commonly involved site (54.8%) followed by the tongue (27.4%) ,,,,, We report a case of a 57 year old man with lung adenocarcinoma who developed multiple (3 in number) exophytic growths in oral cavity. Most of the previously reported cases have been with single gingival metastasis, while, cases with gingival metastasis at two sites are very few in number, with one case of adenocarcinoma of the lung with metastasis bilaterally to maxillary gingivae, and the second case of a synovial sarcoma with metastasis to multiple sites in the maxillary and mandibular gingival tissues.  This is supposed to be one of the very few cases reported with multiple (i.e., more than 2) metastatic growths in the oral cavity secondary to lung adenocarcinoma.
The medical literature since 1964 has reported only 17 cases of gingival metastasis from the lung with a complete histologic identification of a primary lung cancer. Of these, 4 were adenocarcinoma, 2 were squamous cell carcinoma, 5 were undifferentiated carcinoma, 2 were small cell carcinoma and 4 were large cell carcinoma. Out of these, all the 17 patients were male. Median age of occurrence was 58 years and age ranged from 48-84 years.  There are more published cases of jawbone metastases than of the oral soft tissues. The breast is the most common primary site for tumours metastasising to the jawbones, whereas the lung is the most common source for metastases to the oral soft tissues. In the oral soft tissues, the attached gingiva is the most common affected site, followed by the tongue.  Metastasis is the culmination of a multistage process in which malignant tumour cells detach themselves from the primary tumour and then move into vascular and lymphatic vessels until they have become lodged in the capillary bed. Subsequently, they begin to penetrate the blood vessel walls, invade the surrounding tissue and proceed to proliferate. It is conceivable that circulating tumour cells become entrapped in a rich capillary network of chronically inflamed gingivae ,
Another pathogenic mechanism of oral metastasis would be the role of the Batson's plexus, a prevertebral venous network without valves, which authorizes the retrograde crossing of tumour cells from the lungs towards the face  A metastatic tumour in the gingiva is characteristically a rapidly growing proliferative tissue that tends to cause mechanical disturbances, pain, swelling, paraesthesia, intermittent bleeding and loosening of teeth.  Because the metastatic lesion resembles benign inflammatory lesions such as hyperplasia and pyogenic granuloma, histopathological and immunohistochemical examination are considered as gold standard to detect the metastatic gingival tumours.  One of the principal problems with a gingival metastasis is the clinical distinction between a benign and a malignant lesion.
Malignancy must be suspected if any of the following signs are present:
Multiple metastasis may often have developed systemically when oral metastatic tumours are found; hence patients tend to have an extremely unfavourable prognosis. It is therefore difficult to undertake radical procedures in such patients because of their poor general condition and the low probability of complete removal of the primary and metastatic lesions. However, not treating oral metastatic lesions may result in dietary disturbance due to pain and bleeding, so the earlier removal of the oral lesion may be desirable in improving the quality of life. For the present case, radiotherapies and chemotherapies were planned to relieve intraoral bleeding and pain since the patient had generalized metastasis and his overall condition was deteriorating. Thus, palliative treatment such as radiation therapy or chemotherapy, or a combination, should be considered to relieve complications and the excisional biopsy of the metastatic gingival lesions should be undertaken to preserve the functions of the mouth, even if the prognosis of the primary tumour remains unfavourable. 
- A fast evolution
- A hemorrhagic tendency
- Mechanical disorders caused by the development of the tumour
- An ulcerated and/or necrotic aspect
- General clinical context of the patient 
The average time from the appearance of the gingival metastasis to death is no more than a few weeks or months.  In the current case, the patient died four weeks after the diagnosis of the oral lesions. To conclude, this case report emphasizes that although rare, metastatic malignancy must be considered in the differential diagnosis of proliferative lesion of the gingiva, mainly if the patient presents cancer in other sites of the body.
| References|| |
|1.||Watnabe E, Touge H, Tokuyasu H, Kawasaki Y. Gingival metastasis of adenocarcinoma from the lung.Respir Med CME 2008;1:103-6. |
|2.||Curien R, Moizan H, Gerard E. Gingival Metastasis of Bronchogenic adenocarcinoma. Oral Surg Oral Med Oral Pathol Oral RadiolEndod 2007;104:e25-8. |
|3.||Vieira BJ, Aerestrup FM, Fonseca EC, Dias EP. Bilateral Gingival Metastasis of Lung Adenocarcinoma: Report of a case. J Oral MaxillofacSurg 2001;59:1224-5. |
|4.||Hirshberg A, Leibovich P, Buchnar A. Metastasis to the Oral mucosa: analysis of 157 cases. J Oral Pathol Med 1993;22:385-90. |
|5.||Jaguar GC, Prado JD, Soares F, Alves FA, Osorio CA. Gingival Metastasis from non-small cell undifferentiated carcinoma of the lung mimicking a Pyogenic Granuloma. Oral Oncol Extra 2006;42:36-9. |
|6.||Hirshberg A, Buchnar A. Metastatic Neoplasms to the Oral Cavity available from: http://emedicine.medscape.com/article/1079102-overview. [Last Updated on 2008 Mar]. |
|7.||Hirshberg A, Leibovich P, Buchnar A. Metastasis Tumours to the Jawbones: analysis of 390 cases. J Oral Pathol Med 1994;23:337-41. |
|8.||Pozzi EC, Altermatt HJ, Rees TD, Bornstein MM.Exophytic mass of the gingiva as the first manifestation of metastatic pulmonary adenocarcinoma. J Periodontol 2008;79:187-91. |
|9.||Hirshberg A, Shapiro AS, Kaplan I, Berger R. Metastatic tumours to the Oral Cavity-Pathogenesis & analysis of 673 cases. Oral Oncol 2008;44:743-52. |
|10.||Ellis GL, Jensen JL, Reingold IM.Malignant neoplasms metastatic to gingivae.Oral Surg Oral Med Oral Pathol 1977;44:238-45. |
|11.||Huang CJ, Chang YL, Yang MC, Hsueh C, Yu CT. Lung Cancer Metastasis to the Maxillary gingival-a case report and literature review. Oral Oncol Extra 2005;41:118-20. |
|12.||Hirshberg A, Buchner A. Metastatic Tumours to the oral region: An Overview.Eur J Cancer B Oral Oncol 1995;31B:355-60. |
|13.||Nishimira Y, Yakata H, Kawasaki T. Metastatic tumours of mouth and jaws: A review of Japanese literature. J MaxillofacSurg 1982;10:253-8. |
|14.||Yoshil T, Muraoka S, Sano N, Furudoi S, Komori T. Large cell Carcinoma of the Lung Metastatic to the Mandibular Gingiva. J Periodontol 2002;73:571-4. |
Department of Oral Medicine and Radiology, Kothiwal Dental College and Research Centre, Moradabad
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]