Metastatic rectal adenocarcinoma in the mandibular gingiva: a case report

Oral metastatic tumors are uncommon and comprise approximately 1 % of malignant oral neoplasms [1]. Most cases were previously diagnosed in reference to a primary neoplasm and were treated accordingly. Therefore, the primary site is usually assumed based on the past clinical history. However, 23 % of oral metastases were shown to be the first sign of the metastatic process [2]. In the present case, the origin of the metastatic lesion was clarified based on the past history of rectal adenocarcinoma resection and the subsequent lung metastases. The most common primary site in women is the breast followed by the female genital tract, kidney, and colon-rectum. In men, the most common primary site is the lung followed by the kidney, liver, and prostate [2].

In the oral site where metastatic tumors arise, most tumor lesions are observed in the jawbones, and only 16 % are found in the soft tissues such as the gingiva [3]. The metastatic rate in the posterior body of the mandible is higher than that in the symphyseal region [5]. The gingivae (55 %) followed by the tongue (30 %) are the most common soft tissue sites affected by metastatic malignancy [4]. In the present case, the metastatic lesion has been presumed to develop in the gingival tissue of the symphysis. This lesion was an exophytic growing mass, and the radiological appearance of the mandibular bone invasion was not demonstrated apparently. Likewise, some case reports have shown that the metastatic site was the gingiva for the primary lesion of colonic and rectal adenocarcinomas [6‐8].

Adenocarcinoma of the colon and rectum commonly spreads to the regional lymph nodes, liver, and lungs, but less commonly to the peritoneum, bone, adrenal glands, brain, kidney, thyroid, pancreas, ovaries, and skin. Clausen and Poulsen proposed the following three criteria for metastatic oral tumor: firstly, the metastatic tumor is pathologically similar to the primary tumor; secondly, the oral tumor is considered to be a metastasis clinically and pathologically; and thirdly, the oral tumor is atypical compared with common oral primary tumors [9]. The most common primary tumor arising from the oral mucosa is squamous cell carcinoma. Therefore, there may be a need to differentiate metastatic adenocarcinoma from adenocarcinoma derived from the salivary gland, although the frequency of occurrence is very low. Three clinical courses may be considered to underlie the metastasis of colonic adenocarcinoma to the oral cavity as follows: (1) direct metastasis with identification of the primary tumor, (2) secondary metastasis derived from metastasis in another site after treatment of the primary tumor, and (3) occult metastasis without identification of the primary tumor. The present case follows the second clinical course in which the secondary metastasis in the jawbone was derived from multiple lung metastatic lesions. The primary rectal tumor has already been resected completely. The present case conformed to Clausen’s criteria.

Histopathologically, approximately 70 % of the metastatic lesion in the oral region is reportedly adenocarcinoma, followed with much less cases by clear cell carcinoma from the kidney and squamous cell carcinoma from the lungs [10]. Also in the present case, the hematoxylin and eosin-stained section showed features of adenocarcinoma arising from the rectum. Furthermore, the histological diagnosis was supported by the immunohistochemical analysis. The metastatic tumor cells demonstrated a CK20-positive and a CK7-negative phenotype. In the evaluation of gastrointestinal tract carcinomas, the great majority of well-differentiated or moderately differentiated large intestinal adenocarcinomas reportedly showed a CK7-negative/CK20-positive phenotype. Adenocarcinomas of the upper gastrointestinal tract were also reported to be positive for both CK7 and CK20 in 78 % of cases [11]. Thus, an assessment of the CK7 and CK20 phenotype may help in determining the primary site of a metastatic tumor [11]. In addition to the CK7 and CK20 immunoprofiles, the tumor cells showed CDX2 immunoreactivity. CDX2 is a sensitive and specific maker for adenocarcinoma with a colorectal origin [12]. CDX2 expression has also been shown in a subset of adenocarcinomas arising from the colon, rectum, stomach, esophagus, and ovary [13]. Accordingly, CK7, CK20, and CDX2 may be useful for the diagnosis of metastatic tumors of gastrointestinal origin.

In the case of oral metastatic tumors, they usually have a poor prognosis because often they have already spread to other sites. Therefore, the appropriate palliative treatment has to be carefully selected. If the tumor is widely disseminated, palliative radiotherapy is recommended [10]. However, when possible, surgical resection may be recommended mostly for metastatic lesions in the soft oral tissue [10]. In the present case, as the oral metastatic lesion was rapidly growing with accompanying multiple lung metastases, resection was not possible under general anesthesia. Accordingly, we performed palliative radiotherapy for the mandibular mass. Alternatively, chemotherapy with the FOLFIRI regimen (5-FU, leucovorin, irinotecan) is usually performed for advanced metastatic colorectal carcinoma [6]. Although the IRIS regimen (irinotecan, S-1) plus bevacizumab (monoclonal antibody targeted against vascular endothelial growth factor) was planned when the lung metastasis occurred to play the role of another second-line chemotherapeutic regimen, the patient showed no response to the chemotherapy.

Patients with distant metastasis of colorectal adenocarcinoma usually have a poor prognosis. In particular, if a secondary metastatic oral tumor is identified, the disease state may be commonly progressive and the prognosis is extremely poor. In cases involving metastasis to the oral cavity, the mean survival period from the time of mass appearance to the time of death of a patient has been reported to be about 7 months [2]. Regarding metastasis to the gingiva, some cases have been documented showing that the duration of survival from the indication of gingival mass development was only within 1 year [6, 14, 15]. The present case also showed a short survival period of 4 months.