Oral metastases from lung cancer: a retrospective longitudinal study
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1
University of Turin, Department of Oncology, Italy
Aim.
Oral metastases are rare and represent about 1% of all oral malignancies. Oral metastatic lesions mainly involve jawbone with the molar and premolar region of the mandible representing the most common location. The gingiva and alveolar mucosa, followed by the tongue, are the most common sites when soft tissues are involved. Oral metastases are mainly observed in presence of primaries affecting breast, lung, kidney, thyroid and prostate. Breast cancer is the most frequent origin of oral metastases in females, lung and prostate cancer in males. In the European Union, lung cancer is the fourth most common cancer, with more than 312,000 incident cases a year and it is the main cause of cancer deaths. Late diagnosis is the main reason for this high mortality rate. Lung cancer is basically classified in non-small cell carcinoma (squamous cell carcinoma, adenocarcinoma and large cell carcinoma) accounting for about 85% of patients, small cell carcinoma (SCLC) accounting for about 10-15% patients and lung carcinoid tumours, in 5% of patients. We present a retrospective monocentric longitudinal study investigating the incidence of oral metastasis from lung cancer. Data on clinical/histopathological features, time to onset from the diagnosis of lung cancer and survival were recorded.
Materials and Methods.
A retrospective chart review was performed addressing the digital medical record of 2,057 patients referred to the Lung Cancer Unit of out hospital from 2014 to 2018. Cases with oral metastases were retrieved looking for the following keywords: “metastatic” or “metastases” or “metastasize” or “metastasizing” or “secondary” or “oral cavity” or “mouth” or “oral mucosa” or “mandible” or “maxilla” or “tongue” or “gingiva” or “palate” or “retromolar pad” or “lip” or “alveolar ridge”. All oral metastases from primary tumours of the lung involving jaw bones or/and soft tissues were included in the study. Other neoplastic entities of oral cavity arising in patients with lung cancer were excluded. Additional inclusion criteria were: 1) a proved primary lung cancer with histologic confirmation; 2) oral metastatic lesions with histologic diagnosis; 3) histologic correlation of the oral metastasis with the primary lung malignancy. Clinical data (age, sex, oral site, previous history of malignancy, imaging, treatment) and the histophatological data (tumour subtype and immunohistochemical stains) were collected from the charts.
Results.
The search strategy identified three cases of oral metastases from lung tumours. Oral metastases constituted 0.14% of total cases (3 out of 2,057 patients), attesting to the rarity of metastases to the oral cavity. Patients were males aged between 54 and 64 (mean age at the onset of metastasis was 57.67 ± 2.62 years), one current smoker and two former smokers. As resulted from the computerized database, the oncologists referred the patients to our clinic following the onset of an “oral lesion”. At intraoral examination all the 3 patients had gingival fast-growing, firm, fixed ulcerated mass, with a baseline surface area > 2 cm. The patients complained local pain and oral discomfort. The imaging showed an associated evident bone involvement in just one case. Metastatic lesions were located on the posterior mandibular gingiva and on the left maxillary mucosa of edentulous ridge. Three different histotypes of lung neoplasms were detected: a poorly differentiated small cell carcinoma, an adenocarcinoma and an undifferentiated non-small cell carcinoma. In all cases, the primary tumour was already known before the oral metastatic lesion appeared and the histomorphological features of the metastasis was consistent with the first diagnosis. All the patients had additional distant metastases other than in the oral cavity. Histologic examination of tissue sections from oral metastasis of lung adenocarcinoma showed islands and cords of round to polygonal cells with enlarged hyperchromatic nuclei and eosinophilic granular cytoplasm. Upon immunostaining the tumour cells were positive for thyroid transcription factor 1 (TTf-1) and cytokeratin-7 and negative for cytokeratin-20. The small cell lung carcinoma metastasis presented small cells with scant cytoplasm and hyperchromatic nuclei; immunohistochemical stains revealed reactivity for chromogranin A and poor positivity for cytokeratins. A dense infiltrate of large anaplastic cells with pleomorphic nuclei and abundant, eosinophilic cytoplasm were observed in biopsy sections of gingival metastasis from undifferentiated non-small cell carcinoma. The average time between the diagnosis of primary lung tumour and the appearance of the oral metastases was 1,33±0,47 months. The mean survival time since the diagnosis of oral metastases was 2 months.
Discussion.
Lung carcinoma is responsible for more than one third of all oral soft tissue metastases in men, followed by renal carcinoma. Clinically, gingival lesions often resemble reactive lesions as hemangioma, pyogenic granuloma, peripheral giant-cell granuloma or peripheral fibroma, but differently from such entities, metastases are characterized by rapid and progressive growth. The literature reports that gingival metastases are most often located in the upper jaw, whereas in this series mandible was the most interested location. Bone metastases usually do not involve the overlying mucosa. In the present study one case showed an involvement of both gingiva and bone, with a vertical bone loss around the dental implant. Some authors suggest that the cancer cells first directly metastasize to the gingiva and then invade the underlying bone. The mechanism of most oral metastases is through hematogenous dissemination: lung cancer is more likely to develop hematogenous metastases to uncommon sites via the cava vena system. It remains unclear why oral metastases are most often located in the gingiva. A potential role for the rich gingival vascular network has been hypothesized. Moreover, due to the high prevalence of chronic periodontitis, the periodontal tissues, including the gingiva, are often characterized by the presence of an inflammatory status which could favor the entrapment of malignant cells. In the English Literature, adenocarcinoma is the most common metastasizing lung cancer histotype to oral cavity. The use of panel of immuhistochemical stains (positive for TTF-1 and CK7 and negative for CDK20) is essential to obtain a definitive diagnosis. Conversely, the diagnosis of SCLC requires immunohistochemical expression of at least one of the three neuroendocrine markers: CHGA (chromogranin A), SYP (synaptophysin), or NCAM1 (CD56).
The prognosis of patients with metastatic lung cancer is poor, with a 4-year survival rate of 10%. The onset of oral lesions seems to even worsen such prognosis as most patients die within 1 year from such event. Seoane et al. described a cohort of 39 patients with metastatic tumors to the oral cavity; irrespective of the site of the primaries, patients with gingival metastases died within the 6 months after the oral diagnosis. In the present series, the survival time was of only 2 months. Metastatic oral lesions are usually found at advanced stage of disease: our patients presented bone, brain, adrenal, peritoneal, liver, subcutaneous metastases too.
Management of the oral lesions should be coordinated with the patient’s overall treatments and includes radiotherapy, chemotherapy, surgical resection or a combination of these treatments. In our series, the patient with diagnosis of poorly differentiated small cell carcinoma of the lung received RT to the gingival lesion (total dose 20Gy) followed by carboplatin/paclitaxel combination chemotherapy, whereas the other metastatic lesions were treated with wide surgical resection in order to improve the quality of life.
The present study first aimed to assess the incidence of oral metastasis in a large cohort of lung cancer. It confirms that, irrespective to the frequent distant spread of lung cancer, oral metastasis are uncommon findings. Of interest, the really poor survival of patients with oral involvement suggests that such event could be associated to a very late stage of disease.
References
1. Seoane J, Van der Waal I, Van der Waal RI, Cameselle-Teijeiro J, Antón I, Tardio A, Alcázar-Otero JJ, Varela-Centelles P, Diz P. Metastatic tumours to the oral cavity: a survival study with a special focus on gingival metastases. J Clin Periodontol. 2009 Jun;36(6):488-92.
2. Peris K, Cerroni L, Paoloni M, Margiotta V, Chimenti S. Gingival metastasis as first sign of an undifferentiated carcinoma of the lung. J Dermatol Surg Oncol. 1994 Jun;20(6):407-9.
3. Gultekin SE, Senguven B, Isik Gonul I, Okur B, Buettner R. Unusual Presentation of an Adenocarcinoma of the Lung Metastasizing to the Mandible, Including Molecular Analysis and a Review of the Literature. J Oral Maxillofac Surg. 2016 Oct;74(10):2007.
Keywords:
Oral metastasis,
lung cancer,
Gingival metastasis,
Lung metastasis,
survival analysis
Conference:
5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine., Ancona, Italy, 19 Oct - 20 Oct, 2018.
Presentation Type:
Poster Presentation
Topic:
Oral Diseases
Citation:
Lupatelli
M,
Campolongo
M,
Val
M,
Capelletto
E,
Bironzo
P and
Pentenero
M
(2019). Oral metastases from lung cancer: a retrospective longitudinal study.
Front. Physiol.
Conference Abstract:
5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine..
doi: 10.3389/conf.fphys.2019.27.00065
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Received:
04 Nov 2018;
Published Online:
09 Dec 2019.
*
Correspondence:
Dr. Melania Lupatelli, University of Turin, Department of Oncology, Turin, Piedmont, 10124, Italy, melanialupatelli@gmail.com