Gastric adenocarcinoma metastasis to jaw

Fig. 4. Magnetic resonance imaging shows a pathological fracture in the cervical vertebrae, stricture of thevertebral canal and the oppression of the spinal nerve(arrow).

Fig. 5. A moderately differentiated type of tubular adenocarcinoma is observed in a biopsy specimen of gastricadenocarcinoma of the patient (hematoxylin and eosinstain). Bar =100 μm.

ing his history of having a 75% gastrectomy 6years previous due to gastric adenocarcinoma, we
histopathologically examined biopsy specimensfrom the gastric region and cervical vertebrae,and observed the moderately differentiated typeof tubular adenocarcinoma in all specimens (Fig.
5). We also examined biopsy specimens of thestomach, mandible and cervical vertebrae immunohistochemically. The results of the staining were the same in all specimens: positive forcytokeratin AE1/3, EMA, CK7 (Fig. 6a), CA19-9(Fig. 6b) and CEA (Fig. 6c) and negative for cytokeratin 20, CA125 and PSA. Ultimately, we diagnosed his disease as metastatic adenocarcinoma
from gastric adenocarcinoma to the lung, cervicalvertebrae and mandible. The metastasis spreadthroughout his whole body to the point where nofurther active treatment was possible. The patient
was transferred to another facility, where he received palliative therapy. The progress of the tumor was rapid, and the patient died of pulmonary
insufficiency 2 months later.

aCK 7bCA 19-9cCEAFig. 6. Immunohistochemical detection of metastases to the mandible in the glandular epithelium on the biopsy specimen of mandibular ramus: positive staining for AE1/3, EMA, CK7 (a),CA19-9 (b) and CEA (c); and negative staining for CK 20, CA 125 and PSA. The results match
those observed in the primary gastric adenocarcinoma. Bar =100 μm.

51

T. Tamura et al.

tumor from gastric carcinoma.
The most frequent site of metastasis fromgastric carcinoma is the liver. Our patient was not
involved in hepatic metastasis from gastric carcinoma. But patients with metastasis to the oral
region have been frequently without metastasis tothe liver (Colombo et al., 2005). Tubular adenocarcinoma very rarely arises in the minor salivary
gland. Adenocarcinoma originating from theminor salivary gland develops in the soft tissue ofthe oral cavity because the minor salivary glandexists in the submucosa. In this patient, adenocarcinoma occurred in the mandible, partially infiltrating the adjacent soft tissue. In considerationof these facts, his adenocarcinoma did not arise
from the minor salivary gland but metastasizedfrom gastric carcinoma to the mandible.
Furthermore, in immunohistochemical examination of the biopsy specimens of the stomach, mandible and cervical vertebrae, all specimens showed the same staining results: positivefor cytokeratin AE1/3, EMA, CK7, CEA andCA19-9, and negative for cytokeratin 20, CA125
and PSA. These conditions agree with the criteria
established by Zegarelli et al. (1973) and Clausenand Poulsen (1963). Therefore, we finally diagnosed his disease as metastatic adenocarcinoma
from gastric carcinoma to the lung, cervical vertebrae and mandible. Our case is further proof that
immunohistochemical examination is very useful when it is difficult to give a definite diagnosis(Alvarez-Alvarez et al., 2006).
The primary sites of metastasis to the oralregion are the lungs (25.2%), kidneys (14.6%),
uterus (12.6%) and stomach (11.7%) (Koizumi etal., 2004). Pancreatic carcinoma does not metastasize easily because it is aggressively lethal to
the system well before it metastasizes to the oral
region (Hirshberg et al., 1993). Gastric carcinoma
is relatively well controllable with a high survival
rate. This fact could increase the possibility ofmetastasis to the oral region.
In analyzing the period from initial diagnosis of the primary lesion to metastasis to theoral region, metastases to the jaw appeared on anDiscussion
Of all oral carcinomas, about 80% are squamouscell carcinomas, followed by salivary gland carcinomas, malignant lymphomas, and metastatictumors to the oral region with a decreasing incidence of about 10%, 4% and 1% (Meyer and Shklar, 1965; Chin et al., 1998; Vahatalo et al., 2000).
The main characteristic of oral squamous cell
carcinoma is ulcer formation, except for intraosseous carcinoma of the mandible, and diagnosis
is relatively easy. But many metastatic tumors
are adenocarcinomas (Handa et al., 1990) withno ulcer formation, and diagnosis of metastatic
tumor can be difficult. Sometimes discriminating
between carcinomas originating in the oral cavity and metastatic tumors originating elsewhereis difficult even when lesions show histopathologic features of squamous cell carcinoma. For
diagnosis of metastatic tumors, Zegarelli et al.
(1973) established the following critera: i) the
primary tumor elsewhere is proved clinically andpathologically; ii) metastatic and primary tumors
are histologically similar; iii) no tumor existedon the metastatic site in the past; and iv) there
is no direct invasion from any primary or othermetastatic tumor in adjacent organs. Clausen andPoulsen (1963) established the following criteria
for metastatic tumor: i) the lesion must be a true
metastasis localized to the bone tissue, as distinguished from direct invasion by a primary tumor
in relation to the jaw and/or from metastases tothe surrounding soft tissue; ii) it must be a microscopically verified carcinoma; and iii) the locationof the primary tumor must be known to ensurethat researchers are dealing with a secondary lesion. When a tumor is a squamous cell carcinoma
or adenocarcinoma, we should examine histopathologically whether the tumor is of oral origin
or a metastasis. In our patient, the biopsy specimen inside the part of the left mandibular ramus
proved that it was an adenocarcinoma: we needed
to make a clear distinction between an adenocarcinoma of the salivary gland and a metastatic52

Gastric adenocarcinoma metastasis to jaw

average of 39.5 months (Kataoka et al., 2003). In
that study, 17 cases of metastases to the oral region were examined by dividing them into welland poorly-controlled groups. The examination
period ranged from 2 to 99 months (mean, about50 months) in the well-controlled group, whereas
the mean was about 15 months in the poorly-controlled group. Our patient’s tumor took a comparatively long time to metastasize to the oral region
because the primary lesion was well under control
for 6 years. In the oral region, the jaw is a common location of metastasis with predilection forthe mandible and molar area. As for the probablecauses of the occurrence of metastasis, Nakagawa
et al. (1991) explained that the pooling of blood in
myeloid tissue of the mandible might contribute to
the retention of disseminated tumor cells and thatthe inferior alveolar artery winds its way aroundthe angle of the mandible and in the mental region
which causes blood flow to slow down.
Sharp pain and paralysis in the mental region occur as initial symptoms when tumors
metastasize to the mandible (Glaser et al., 1997).
We should suspect mandibular metastasis whenparalysis of the mental region is recognized (Osakiet al., 1978). In our patient, paralysis in the mentalregion appeared following sharp pain in the mandible. The paralysis hardly improved despite antibiotics, so we carried out the biopsy for definitive
diagnosis. Because the molar area of the mandible
is a region where metastatic tumors often develop,
we should suspect malignant tumor when paralysis of the mental region persists.
In general, metastatic tumors of the oral region are a part of multiple distant metastases andthe prognosis is extremely poor: most patients havea fatal outcome of metastasis from the primarytumor within 1 year (Nakagawa et al., 1991; Yajima and Miyazaki, 1999; Kuttan et al., 2006). In
making a decision about treatment for metastatictumor, we should synthetically evaluate clinicalmanifestations, stage of progress, presence of metastases to other organs and wishes of the patient.
In this patient, multiple metastases had already developed extensively when metastatic tumor of themandible was confirmed. Based on his conditionand quality of his life, palliative treatment was unavoidably selected for the oral lesion.
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Received March 10, 2008; accepted May 8, 2008
Corresponding author: Takayuki Tamura, DD54