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We investigated the quantification of Ki-67 staining using digital image analysis (IA) as a complementary prognostic factor to the modified National Institutes of Health (NIH) classification in patients with gastrointestinal stromal tumor (GIST). We examined 92 patients, focusing on the correlation between age, sex, primary tumor site, tumor size, predominant histologic type, mitotic index, modified NIH classification (low/intermediate vs high), Ki-67 quantitation, and recurrence-free survival (RFS). We compared two IA processes for whole slide imaging (WSI) and manually captured image (MCI) methods. A Ki-67 quantitation cutoff was determined by receiver operator characteristics curve analysis. In the survival analysis, the high-risk group of a modified NIH classification, a mitotic count >5 per 20 high-powered fields, and Ki-67 cutoffs of ≥6% and ≥8% obtained by IA of the WSI and MCI methods, respectively, had an adverse impact on RFS. On multivariate analysis, each Ki-67 quantitation method strongly predicted prognosis, more strongly than the modified NIH classification. In addition, Ki-67 quantitation using IA of the MCI method could stratify low or intermediate risk and high risk GIST patients. Thus, IA is an excellent tool for quantifying Ki-67 to predict the prognosis of GIST patients, and this semiautomated approach may be preferable for patient care.

The occurrence of pleural malignant mesothelioma (MM) is unusual and the cases that appear as a localized tumor are extremely rare. A case of localized pleural MM including immunohistochemical findings is presented. A 70-year-old man had an abnormal shadow found during a routine roentgenogram at an annual health checkup and was admitted to Toneyama National Hospital (Toyonaka, Osaka, Japan) for detailed examinations. Chest X-rays showed a 2 x 5 cm-sized nodule with relatively smooth margins in the right segment three. Computed tomography (CT) showed an extrapleural mass with a smooth surface and a thickened parietal pleura, and results of a biopsy performed under CT scanning yielded MM. Systematic examinations did not show any metastasis and the patient underwent surgery for removal of the mass. The resected tumor, measuring 3.2 x 3.1 cm, was firm, partially encapsulated, and irregularly shaped. Pathological examinations revealed that it consisted of large polygonal cells, partially showing myxoid patterns, which led to a diagnosis of localized pleural MM. Tumor recurrence was seen, and the duration between initial symptoms and death was 29 months. This case suggests that localized pleural MM has a high proliferative potential and aggressive course, and is considered an early stage of diffuse pleural MM.

A case of renal adenomatosis of the left kidney associated with a carcinoma of the ipsilateral ureter in a 49-year-old man is examined. One hundred and eight adenomas, which were smaller than 15 mm in diameter, and a single microcarcinoma, which measured 1 mm in diameter, were found in the kidney. Further, there were more than 800 hyperplastic lesions which could be classified into three groups: (i) 792 of distal origin; (ii) 24 of proximal origin; and 10 of collecting duct origin. The serial sections obtained from 19 paraffin blocks were stained using Leu M1 as the proximal marker and epithelial membrane antigen (EMA) as the distal/collecting marker to assist in determining the origins. Ten of the small adenomas (15 lesions), which did not exceed 3 mm in diameter, were predominantly positive for EMA and five were predominantly positive for Leu M1. Further, hyperplastic lesions of distal and collecting duct origins were diffusely positive for EMA and sporadically positive for Leu M1. The lesions of proximal origin were predominantly positive for Leu M1 and sporadically positive for EMA. These findings suggest that a progression from hyperplasia and a direct transition from a single tubule to adenoma occurred multifocally in different segments of the nephrons throughout the left kidney.

A 26-year-old woman presented with pain in the left hypochondrium, for which pancreatectomy and splenectomy was performed, with total gross excision of a mass. A tumor measuring 11 x 9 cm was found in the pancreas. On cut surface there were two cysts filled with a necrotic substance and hemorrhagic content. Spindle or ovoid-shaped cells, in the sarcomatous component, had diffusely infiltrated along the inner side of the walls of one cyst. Osteoclast-like giant cells (OGC) were also contained in the sarcomatous component. Adenoma components of mucinous epithelium with foci of borderline and adenocarcinomatous components were seen on the inner side of the other cyst. An ovarian-type stroma beneath the epithelial component was seen in the cyst wall. A diagnosis of undifferentiated carcinoma with OGC arising in a mucinous cystic neoplasm (MCN) of the pancreas, was made. Seven months after the initial operation the patient had a local recurrence, and the tumor was removed. One month after the second operation, the patient was free of symptoms. Only four cases of undifferentiated carcinoma with OGC arising in MCN, involving an ovarian-type stroma of the pancreas, have been reported.

An 80-year-old woman with a pleomorphic carcinoma (PC) producing hCG was admitted to Nippon Steel Hirohata Hospital because of an abnormal shadow on CT seen during a follow-up examination after surgery for breast cancer. A right upper lobectomy was performed due to rapid growth of the shadow 3 months later. Macroscopically the tumor was a 4.8 x 4.0 cm well-circumscribed grayish-white mass. On histology the tumor consisted mostly of intermingled spindle and polygonal cells, while evidence of poorly differentiated adenocarcinoma was seen in a few areas. A diagnosis of PC was made due to hCG expression in approximately 20% of the spindle and polygonal cells on immunohistology. Six months after the operation metastasis to the liver and adrenal gland was seen on CT. The patient died due to metastases 1 year after the operation, even though the patient had been at stage 1B at the time of the operation and appropriate chemotherapy had been given. PC patients with immunohistochemical hCG expression have elevated risk of local recurrence and metastasis.

Congenital pulmonary lymphangiectasis (CPL) is a rare anomaly. We report a female infant born at 39 weeks of gestation who was found to have CPL. Cyanosis and tachypnea were noted immediately after birth, and, at room air, PaO2 was 30.7 mmHg, PaCO2 was 82.5 mmHg and pH was 7.12. The infant's symptoms did not improve even with the initiation of artificial ventilation. Chest X-ray film showed cotton-like infiltrates in both lungs and an air-leak surrounding the cardiac shadow. Echocardiography study showed no abnormality. The neonate died 3 days after birth due to hypoxemic cardiac failure. At autopsy, the pleural surface contained numerous dilated vessels that had the appearance of lymphatics. Microscopic features of the lungs were marked lymphatic dilatation of the perivascular, subpleural and interlobular areas. Lymphangiectasis was found in the liver, kidney, pancreas, thyroid and alimentary canals, such as the esophagus, stomach and rectum. Patients with lymphatic dilatations in extrapulmonary organs have mild pulmonary involvement and symptoms and a better prognosis. However, a few cases of CPL with lymphatic dilatations in extrapulmonary organs and an aggressive course, such as the present case, have been reported. The clinical behavior and prognosis of CPL depend on the extent of pulmonary involvement of the lymphatic dilatations regardless of systemic lymphatic dilations.

Pericardial malignant mesothelioma (PMM) is extremely rare compared with pleural cases of mesothelioma. We present the clinical and pathological features of three autopsy cases with PMM. All three cases showed rapid progress and died of heart failure. Detailed examination was obtained from the autopsy. Macroscopic appearances of each case showed a thickened pericardium due to tumor invasion. Microscopic observations of all cases led to a diagnosis of epithelial-type malignant mesothelioma (MM). The results of immunohistochemical examinations were similar to the previous published work on pleural mesothelioma. To disclose the pathological characteristics of PMM, we analyzed Ki-67 labeling index (LI) of three cases of PMM and five cases of pleural MM that died within 2 years. The difference of Ki-67 LI between PMM and pleural MM was not significant (P > 0.05). The poor prognosis of patients with PMM must be caused by restricted cardiac wall motion due to tumor involvement, in addition to the tumor proliferation itself.