Metallothionein (MT) is a metal-binding protein with a low molecular weight (6000-7500), and is implicated in abnormal cell growth in some cancers. In the present study, the relationship between MT expression and the clinical features in oral squamous cell carcinomas was investigated. In 12 recurrent cases of oral cancer, the expression of MT was examined immunohistochemically in formalin-fixed, paraffin-embedded tissue sections using the avidinbiotin peroxidase complex method.
The percentages of MT positive cells in tissue sections from nonrecurrent cases (n=21), and recurrent cases (n=12) were 40.8% and 70.1%, respectively. Between these values, a significant difference was recognized.
Furthermore, in recurrent cases, the percentage of MT positive cells was 70.1% for primary cases (n=12), and 76.7% for recurrent cases (n=9) . Between these values, no significant difference was recognized. However, among 9 recurrent cases, 6 patients with increasing MT percentages died, whereas 3 patients with decreasing MT percentages survived.
In summary, immunohistochemical examination of MT in the primary lesion and recurrent lesion of tumors is useful for understanding the biological degree of malignancy of oral squamous cell carcinomas in clinical practice, and may be useful for selecting future treatment and evaluating the patients prognosis.

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Using a silver staining technique, argyrophilic nucleolar organizer regions (AgNORs) were studied using biopsy specimens taken from 62 tongue squamous cell carcinomas (SCC), and the relation of the results of AgNORs to the clinicopathological findings, labeling indices of proliferating cell nuclear antigen (PCNA LI), and the outcome of the disease were investigated. The mean numbers of AgNORs per cell were 1.6±0.2 (n=10) in control squamous epithelia and 3.6±1.1 (n=62) in the tongue SCCs, respectively, and a significant difference was found between the two groups (p<0.0001) . As for the clinicopathological findings, the mean numbers of AgNORs in the progressive cases (T3-T4, N1-N2, Stage III-IV) were statistically higher than those in earlier tumors (T1-T2, N0, Stage I -II) . A similar higher value of the AgNOR count was present in the histological grade III, diffuse invasion and severe atypia tumor. There was also a direct significant correlation between the AgNOR counts and the labeling indices of PCNA (r=0.520, p<0.0001) . As for the outcome of the disease, the mean numbers of AgNORs were higher in the group with local recurrence or with lymph-node metastasis. There was a lower rate of 5-year survival (63.5%) in the high value group of AgNORs compared with that (86.0%) of the low value group, with a significant difference between the two groups (log rank: p=0.04) .
The results suggested that the AgNOR count reflect the degree of malignancy and cellular proliferation in tongue SCCs.

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The majority of secondary neck metastases of oral squamous cell carcinomas appear within one year after primary treatment. A rare case of upper gingival carcinoma with secondary neck metastasis occurring 3 years and 11 months after primary tumor resection is reported. The patient was a 67-year-old male who underwent preoperative chemotherapy and local tumor resection for a squamous cell carcinoma of the left upper gingiva (T1N0M0) . Three years and 11 months after the primary tumor resection, metastatic tumors were found in the left neck region. Radical neck dissection was immediately performed for these tumors, but the patient died as a result of the recurrence of neck tumors. Histological examination showed that both primary and metastatic tumors belonged to type 4D cancer invasion as classified by Yamamoto and Kohama. This late development of neck metastasis suggested that the cancer cells in the lymph nodes can be dormant for a long period followed by sudden and aggressive growth. In view of the clinical course of this case, prophylactic neck dissection for patients with type 4D cancer invasion is recommended.

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Two cases of oral carcinoma with multiple distant metastases involving the heart are presented. According to the Annuals of the Pathological Autopsy Cases in Japan from 1988 to 1992 (edited by The Japanese Society of Pathology), the most common metastatic sites of primary tumors of the oral cavity (lips, tongue, gingiva, other parts of oral cavity and major salivary glands), were the lungs (48.8%), liver (24.2%) and bone (21.0%) . Heart metastasis (9.1%) occurred with the ninth highest frequency in oral malignancies. As for heart metastasis, the lung (10.2%) was the most frequent primary site, followed by the oral cavity, and in the oral cavity, the tongue (13.1%) was the most common primary site. Therefore, it was suggested that in the late stage of oral malignant tumors, the frequency of heart metastasis is higher than expected.

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The diagnostic criteria and accuracy of CT and MRI in cervical lymph node metastases of the patients with oral cavity cancer were discussed. The CT and MRI malignancy criteria is considered to include 1) enlarged lymphnode, 2) nodes of any size with central necrosis, and 3) loss of tissue planes around any enlarged node (extranodal invasion) . Although CT and MRI imaging have become better and can easily detect small lymph nodes, the diagnosis of the metastasis by CT and MRI has major limitations such as unenlarged metastatic nodes and large inflammatory nodes.

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To estimate the usefulness of diagnostic ultrasound for cervical lymph node metastasis in patients with head and neck cancer, 155 neck dissection specimens from 139 patients were examined. The results were as follows:
1. Ultrasound delineated 93% of the metastatic lymph nodes over 10 mm in short diameter.
2. The characteristic featurs of the secondary cervical lymph node metastasis were an increased short diameter (over 10 mm) and the appearance of internal echoes.
3. Accuracy of ultrasound was 85.0%.
4. False positive lymph nodes were found in the upper deep cervical nodes and submandibular nodes and were characterized by a high proportion of reactive lymphadenitis histopathologically.
5. False negative lymph nodes were found in all cervical lymph nodes and were characterized by a high proportion of micrometastasis histopathologically. The findings suggested that ultrasound is useful for diagnosis of cervical lymph node metastasis.

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Three cases with tongue carcinoma, in which subclinical metastasis was detected by repeated ultrasonographic (US) examination of the neck lymph nodes performed at one-month interval, were reported. A hyperechoic area in the middle internal jugular lymph node was proved to correspond to a metastatic focus with marked keratinization histologically. In all three cases, metastatic lymphadenopathy could not be suspected on CT examination. It was suggested that repeated US examination is very useful to detect subclinical metastatic lymph nodes earlier, and it was recommended to perform it at least one-month intervals and if possible every two weeks.

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Purpose: The purposes of this study were to show our protocol of diagnostic imaging using CT and ultrasonography and to evaluate the diagnostic accuracy for cervical lymph node metastasis in oral squamous cell carcinoma.
Material and Methods: CT and/or ultrasonography of 147 patients were evaluated retrospectively. Lymph nodes were confirmed pathologically whether metastasis or non-metastasis. The detection ratio, enhanced pattern and short diameter of lymphadenopathy were analyzed on CT. Internal echoes such as hilus and parenchymal echoes, the short diameter, long diameter and the long to short diameter ratio (S/L ratio) were evaluated on ultrasonography.
Results: Ten percent of lymphadenopathy, which was confirmed pathologically as metastasis, was not found on CT. Heterogeneous or rim-enhanced pattern was presented in 50.9% of metastasis and only 4.5% of non-metastasis cases on CT. Strong parenchymal echo pattern was shown in 56.9% of metastasis cases. On the other hand, 66.5% of non-metastasis cases showed a hilus but strong parenchymal echoes. Under the circumstances where lymph nodes had neither hilus nor strong parenchymal echoes, but were 10 mm or more in short diameter, 27.4% were shown in metastasis and only 3.0% in non-metastasis cases. Futhermore, under the circumstances where lymph nodes had neither hilus nor strong parenchymal echoes, but were 3.5 or more in S/L ratio, only 1.5% were shown in metastasis and 13.5% in non-metastasis cases.
Conclusion: On basis of the results of this study, it was suggested that criteria for cervical metastasis using CT and ultrasonography in which“Questionable only on diagnostic imagings”be included. It was considered that this criteria is clinically useful.

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In our department, multivariate analysis of clinicopathological findings produced the dicriminant of a possibility of the presence of lymph node metastasis, and in consideration of the result, neck dissection was performed. The relationship between preoperative ultrasonographic findings of the cervical lymph node metastasis and pathological findings of the primary lesion in 71 patients who received neck dissection out of 245 patients with squamous cell carcinoma of tongue, floor of the mouth, and mandibular gingiva was investigated. Among the 23 cervical region cases for which ultrasonographic diagnosis was negative, metastasis was suspected from clinicopathological findings, 11 cases had pathologically positive lesions, and in 44 cases for which ultrasonographic diagnosis was considered, 24 cases were found to be positive pathologically and their pathologic malignancy gradings of the primary lesion were high. Eighteen out of 20 cases with positive ultrasonographic diagnosis were found to be positive. From the results, it was suggested that the diagnosis of the cervical lymph node metastasis in patients with oral squamous cell carcinoma should be performed in consideration of the ultrasonographic findings of the cervical regions and clinicopathological findings, especially the degree of malignancy of the primary lesion.

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