17. Pathology Division

The research activities of the Pathology Division of the Research Institute East are centered on the morphological study of cancer tissue. Major projects include quality control of pathological diagnosis, clinicopathological study of cancers and pathology of precancerous lesions and early cancers.

Development of a Computer-Assisted Image Diagnosis System

For the last two years, the image data of individual cells have been analyzed by an artificial intelligence system to determine whether this approach can separate benign and malignant proliferative lesions of the breast.⁽²⁰⁴⁾ The concordance rate between the computer system and pathologists was about 80%. It became apparent that in addition to data on individual cells, data on the architecture of the lesion are necessary for correct diagnosis. For that purpose, a computer needs to be able to recognize the glandular lumina formed by proliferating mammary cells; therefore, a system that can outline the glandular lumina was developed. The system can recognize glandular lumina accurately when the specimen is well prepared. However, the system failed with poor quality specimens. Using this system, the distribution and spatial relationship of the glandular lumina may be converted to numerical data.

Using the shape of the glandular lumina and the distance between the nuclei of the neoplastic cells and glandular lumina, a diagnostic algorithm was constructed using a Bayesian belief network. In the preliminary analysis, the network can diagnose benign lesions at a probability of about 90% while that of malignant lesions was about 70%. This discrepancy was probably caused by the morphological variability of malignant lesions.

Mechanisms of Fibrotic Focus Formation in Invasive Ductal Carcinoma of the Breast

A fibrotic focus is often recognized in primary tumors of recurrent breast cancer. Therefore, the clinicopathological significance of the presence of fibrotic foci in breast cancer has been studied.⁽²⁰⁵⁾ It became apparent that invasive ductal carcinomas with a fibrotic focus or foci have much higher malignant potential as evidenced by their lower survival rate. This year, an immunohistochemical study of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor (FGFR) was conducted to examine the mechanisms of fibrotic focus formation. Invasive ductal carcinomas were divided into scirrhous-type and solid-type based on the arrangement of the tumor cells. In scirrhous-type tumors with a fibrotic focus, bFGF and FGFR expression was significantly higher than in those without fibrotic focus. In addition, fibroblasts in the fibrotic focus frequently expressed FGFR. This suggests that there are autocrine and paracrine mechanisms operating in scirrous tumors with fibrotic foci, which may explain the high malignant potential of these tumors. On the other hand, no such correlation was found in solid tumors.

Study of Clinicopathological Features Associated with Sites of Recurrence in Breast Carcinoma

It is clinically important to predict the site of recurrence of breast cancer at the time of surgery. Therefore, univariate and multivariate analyses were conducted to define factors associated with the site of recurrence (local, liver, bone, and lung). By case control study, the following risk factors of the recurrence were identified: tumors larger than 20 mm, high nuclear atypia, scirrous growth pattern, the presence of fibrotic focus, the presence of coagulation necrosis, and vascular invasion. When a recurrent group was analyzed based on the first site of recurrence, the scirrous growth pattern was associated with bone metastasis, dense peripheral fibrosis of the tumor with liver metastasis and slight peripheral fibrosis with local recurrence. No factor was identified in association with lung metastasis.

Development of a Prototype for Exhibiting Pathology Images of Educational Value on the Internet

Pathology images of interesting or rare cases are to be presented on the Internet for educational purposes. A prototype presentation is being developed. This year, a presentation model for a series of interesting cases was developed. Flat neoplasms of the colon were chosen as an example. These tumors are rare in Western countries. At first, an overall review of the subject and diagnostic criteria of these tumors were presented as text. Then six cases of flat neoplasms, from adenoma to early invasive carcinoma, were demonstrated using endoscopic images and pathological images. The format of the presentation will be optimized according to the suggestions submitted by the audience.

Clinicopathological Studies of Various Cancers

Prognostic factors and other clinicopathological characteristics of various cancers have been studied in collaboration with clinical departments of the two hospitals of the National Cancer Center.^(206-208) In addition to case reports,^{(209, 210)} an immunohistochemical study of thyroid tumors demonstrated that S-100 protein expression is correlated with differentiation of the thyroid tumors.⁽²¹¹⁾ Clinicopathological studies of lung cancer demonstrated that atypical adenomatous hyperplasia of the lung is probably a precancerous lesion of the adenocarcinoma of the lung and do not represent intrapulmonary metastases.^{(212, 213)} An atlas of mediastinal tumors was published this year.⁽²¹⁴⁾