Gingival metastasis: a potential marker of reduced survival in Small Cell Lung Cancer
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1
University of Turin, Department of Oncology, Italy
Aim. Neuroendocrine tumors more commonly affect the lung, the digestive tract, and the pancreas. In 2004 the WHO classified lung neuroendocrine neoplasms into four major types: typical carcinoid tumor, atypical carcinoids, large cell neuroendocrine tumor and small cell carcinoma (SCLC). SCLC accounts for 10-15% of all lung cancers, representing the most common primary neuroendocrine lung malignancy. SCLC mostly occurs in men aging 60-70 and it is strongly associated with tobacco smoking. SCLC is a highly aggressive cancer characterized by early distant metastases, mainly involving liver, bones, adrenals and brain. About 70% of patients already have spread disease at the time of initial diagnosis. Gingival metastases from SCLC are extremely rare. We report a case of a 59 years old man complaining for a fast-growing gingival mass located on the right posterior mandible.
Materials and Methods. Two months before the onset of the gingival mass, the patient was referred to the Thoracic Oncology Unit for thoracic pain and dysphonia. A CT scan showed a mass in the left upper lung, a node within the left adrenal and mediastinal nodal enlargement. Therefore a FNAB was performed in order to investigate the lung mass, but it was not able to obtain a specific diagnosis. Further CT scans performed in the following month highlighted an enlarged mass involving the pericardium and the pulmonary artery and a new node within the right lung. Moreover, imaging data consistent with brain, peritoneal, adrenal and renal metastases were observed. The gingival mass appeared during such diagnostic path, while the patient was waiting for a further lung biopsy. The patient become aware of the mass due to the spontaneous loss of a right lower molar. Due to the onset of such a fast-growing mass, the oncologists referred the patient to our clinic. Oral examination revealed a painful ulcerated mass on the left posterior mandibular gingiva involving both the buccal and lingual side. Panoramic radiograph did not show any relevant osteolytic lesions. Due to the clinical features of the mass, most of all the extremely rapid onset, and in the light of the potential presence of a metastatic lung cancer, a gingival metastasis was suspected. As the mass implied a reduced quality of life with impaired feeding, the whole mass was excised.
Results. Hematoxylin and eosin sections showed islands of basophilic small cells with scant cytoplasm and hyperchromatic nuclei covered by ulcerated mucosa. Immunohistochemical analysis revealed positivity for chromogranin A and a low positivity for cytokeratins. In the meanwhile, a second FNAB performed on a nodal mass, was consistent with small cell lung carcinoma. Merging data from the oral and the nodal masses a definitive diagnosis of metastatic SCLC was obtained. The general conditions of the patient rapidly worsened not allowing the administration of any curative or palliative treatment. The patient died about 1 month after the excision of the gingival metastasis.
Discussion. Oral cavity in not a common site for metastases. Most often metastases involve jawbone metastases rather than oral soft tissue. When considering SCLC, there is only one report describing a metastasis involving the mandible, which was initially interpreted as a residual cyst. Conversely, SCLC is known to be the most frequent histological type of tonsillar metastases. To the best of our knowledge, only four cases of gingival metastases from SCLC have been described in the English literature. Both sexes were involved: two old men and two middle age female patients. The metastatic lesions were large firm, red, ulcerated masses. In three reports the oral metastases were located in the lower posterior gingiva and, in the fourth case, the upper molar gingiva was the oral affected site associated with a lesion on the hard palate. CT scan showed bone involvement in just one case. Only in one case the gingive was the first site showing metastatic involvement from SCLC. Biopsy is the standard diagnostic approach to confirm the diagnosis. Of interest, Pektas investigated the gingival mass by means of a FNAC as he considered that a cytological evaluation is more rapid than the conventional stains of surgical biopsy specimens. Even if he was able to reach a definitive diagnosis, it should be observed that a cytological sample could not be adequate in order to investigate all the histological features typical for a SCLC metastasis.
As reported in the literature, the oral metastases usually show small basophilic epithelial cells with scant cytoplasm and hyperchromatic nuclei exhibiting crushing artifacts and a high number of mitotic figures. Immunohistochemistry stains are useful to differentiate SCLC from other lung malignancies, being SCLC positive for pancytokeratin (AE1/AE3), CD56 and chromogranin A. Moreover, approximately 80% of SCLCs demonstrate TTF-1 (thyroid transcriptor factor 1) positivity.
At the time of the onset of oral metastasis patients usually already have widespread disease: in the present case brain, peritoneal, adrenal and renal metastases were concurrent with the oral one. SCLC is the most aggressive neuroendocrine tumor of the lung, with 5- and 10-year survival rates of 5% and 1–2% respectively. Even though SCLC is very responsive to first-line chemotherapy, all patients with extensive rather than localized stage suffer relapse within few months of completing initial therapy and die within 2 years. The prognosis is very poor: patients with extrathoracic metastases have a median survival time of 8-10 months and a 2-year survival rate of 10%. According to the other gingival metastases reports from SCLC, the median survival time after the detection of oral metastases is about 1-2 months.
The therapeutic options for SCLC are limited and surgical resection is rarely performed. In extensive stage, chemotherapy without radiation is recommended, whereas the addition of early thoracic radiation therapy (TRT) to chemotherapy regimen is the standard of care for patients with limited-stage disease. The combination of etoposide with platinum is the most common chemotherapy regimen in first line, while irinotecan and topotecan are treatment options in second line setting.
The therapeutic approach to oral metastases basically aims at improving the quality of life. Looking at the four cases reported in the literature, palliative radiation therapy was performed in 2 cases. As the oral cavity is readily accessible for surgery and due to the low morbidity and low costs of a surgical approach potentially performed under local anesthesia, such option should be preferred in order to reduce the mass and improve the quality of life of terminal patients.
References
1. Pektas ZO, Gunhan O. Cytologically diagnosed metastatic small cell lung carcinoma in the mandibular soft tissue. Saudi Med J. 2013 May;34(5):539-41.
2. Aoe K, Hiraki A, Kohara H, Maeda T, Murakami T, Yoshimura T, Ita M, Sakae K, Takeyama H. Gingival metastasis as initial presentation of small cell carcinoma of the lung. Anticancer Res. 2003 Sep-Oct;23(5b):4187-9.
3. Thottian AG, Pathy S, Gandhi AK, Malik P, Nambirajan A. Coughing up - Small cell carcinoma lung with gingival metastasis. J Egypt Natl Canc Inst. 2017 Mar;29(1):61-64.
Keywords:
Small cell carcinoma (SCC),
Oral metastases,
lung cancer,
Gingiva,
Oral Cancer (OC)
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,
Val
M,
Campolongo
M,
Volante
M,
Bironzo
P and
Pentenero
M
(2019). Gingival metastasis: a potential marker of reduced survival in Small Cell Lung Cancer.
Front. Physiol.
Conference Abstract:
5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine..
doi: 10.3389/conf.fphys.2019.27.00056
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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