Yoshiharu Nara

Clinicopathologic study of nasal T/NK‐cell lymphoma among the Japanese

A high prevalence of nasal lymphoma expressing a T‐ or natural killer (NK)‐cell phenotype (NTCL) with frequent association of Epsteln‐Barr virus (EBV) has been indicated in Asians. To Characterize NTCL among the Japanese, the clinlcopathdogic features of 32 cases were evaluated and the casses worn also analyzed for EBV‐RNA using an ISH method. Morphologically, 31 cases were Identified by atypical pleomorphic lymphoid infiltrates with polymorphous, anglcentric, and necrotic features. Their lymphoma cells ranged in size from small to large and were mixed in varying proportion from case to case. The other one case showed a monomorphic ‘blastic’ appearance. EBV‐encoded small RNA (EBER) was detected in the neoplastic cells of 27 of the 32 cases examined. In the five EBV‐negative cases, one was the ‘blastic’ type. Clonal T‐cell receptor gene rearrangement was detected in none of seven cases examined. The patients had a median follow‐up of 9 months (range, 1 month to 14 years and 11 months). The Kaplan‐Meler estimate of overall survival was 49% at 5 years, correlating with clinical stage. These data support the concept that most cases of NTCL are identified as tumors with T/NK‐cell characteristics and EBV association, distincity different from other peripheral T‐cell lymphomas. Furthermore, the one case of an EBV‐negative ‘blastic’ variant appears not to fit well Into the pleomorphic category but more closely resembles the pathologic features of extranasal angiocentric lymphoma with lymphoblastold appearance. This study also showed no clear difference in clinical aspects other than the original site or in prognosis, between NTCL and extranasal angiocentric lymphomas despite the higher incidence of EBV association and the tendency for that peculiar anatomical site to be restricted to the former group.

Ovarian epithelial tumors of borderline malignancy in Japan

Seventy-one cases of ovarian epithelial tumor of borderline malignancy have been surveyed from a clinicopathologic viewpoint. The majority of the borderline tumors (73.2%) were of the mucinous type, versus only 16.9% of the serous type. The other types--endometrioid (2.8%), Brenner (1.4%), and mixed type (5.6%)--were much rarer. Patients with mucinous tumors were significantly younger (mean age 42.6) than those with serous tumors (mean age 57.5) (P less than 0.01). Of patients with mucinous tumors, 64.2% were of reproductive age (15-45 years), compared with 17% of patients with serous tumors. Some 78.8% of mucinous and 83.3% of serous borderline tumors were FIGO stage I. Serous tumors were more frequently bilateral (66.7%) than mucinous tumors (9.8%). In mucinous borderline tumors, the extent of tumor spread at the first laparotomy had an intimate relationship to the prognosis, but in serous borderline tumors, it was insignificant. The survival rate of patients with mucinous borderline tumors was 69.3% at 5 years and 62.4% at 10 years (Kaplan-Meier method). Most patients with pseudomyxoma peritonei classified as borderline at the time of discovery died within 5 years of the operation. The prognosis of the serous type was extremely favorable. Criteria for borderline tumors of various cell types and differences in the clinicopathologic data of ovarian borderline tumors between Japan and other countries were discussed.

Study of ovarian tumors treated at Nagoya University Hospital, 1965–1988

The relative frequency and the age distribution of ovarian tumors (873 primary and 47 secondary tumors) encountered over 23 years at Nagoya University Hospital were examined with respect to histological type and grade of malignancy. Of the primary neoplasms, common epithelial tumors accounted for 56.6%, sex cord-stromal tumors for 7.3%, and germ cell tumors for 39.5%. Among 296 cases with primary malignant neoplasms, common epithelial type accounted for 75.6%, sex cord-stromal tumors for 4.7%, and germ cell tumors for 19.6%. A review of the literature from Western countries indicated that in Japan, the relative frequency of common epithelial tumors is lower but that of germ cell tumors, especially malignant germ cell tumors, is higher. The difference in the incidence of germ cell tumors between Japan and Western countries is not considered significant, and the incidence of common epithelial tumors is considered to be much lower in Japan.

Production and immunohistochemical characterization of a monoclonal antibody raised to proteoglycan purified from a human yolk sac tumour

SummaryA large proteoglycan with chondroitin sulphate and dermatan sulphate side chains has been isolated and purified from a yolk sac tumour of the left ovary from a 23-year-old female. A monoclonal antibody, designated 2B1, was produced which reacted specifically with the intact molecule of the large proteoglycan and the chondroitinase ABC-treated core molecule. The localization of substances showing cross-reactivity to this antibody was studied in a variety of human tissues by means of indirect immunohistochemistry. The interstitial elements of nearly all tissues of a 5-month-old foetus were intensely reactive with the antibody, but in adult tissues structures that gave positive reactions were limited; only the perivascular and perimuscular fibrous elements were reactive, except for the aorta, which reacted extensively. In contrast, the interstitial elements of the carcinoma tissues tested were intensely reactive. Thus antibody 2B1 can be regarded as a useful tool for studies on the immunohistochemical localization of large proteoglycan in various human tissues.

Immunohistochemical characterisation of extracellular matrix components of salivary gland tumours

Proteoglycans (PGs) were localised immunohistochemically in 52 salivary gland tumours including pleomorphic adenoma, adenoid cystic carcinoma, acinic cell carcinoma, oncocytoma, mucoepidermoid carcinoma, clear cell tumour and Warthin tumour, using antibodies raised against large PG, small PG, chondroitin 4-sulphate PG, chondroitin 6-sulphate PG, heparan sulphate PG and keratan sulphate PG. Large PGs were mainly observed in mucinous materials of extracellular matrix (ECM) and interstitial fibrous element of tumour tissues, while small PGs were located only in hyaline matrix and surrounding fibrous (capsular) connective tissues. Chondroitin 6-sulphate PG was detected in the ECM of pleomorphic adenomas and clear cell carcinomas and in pseudocystic spaces of adenoid cystic carcinomas, but only in vessel walls in non-neoplastic tissues. Keratan sulphate PG was observed to locate in mucinous material of pleomorphic adenomas, acinic cell carcinomas and clear cell carcinomas, but not in the adenoid cystic carcinomas examined, and it was also unobservable in non-neoplastic salivary gland tissues. Heparan sulphate PG was observed on the inner surfaces of true ductal spaces of adenoid cystic carcinomas and on cell surfaces of oncocytoma cells. By HPLC analysis, individual glycosaminoglycans contained in tumour tissues were compared. Chondroitin 6-sulphate PG was very rich in ECM of pleomorphic adenomas and adenoid cystic carcinomas. Pleomorphic adenomas contained relatively more low-sulphated chondroitin sulphate than adenoid cystic carcinomas and other tumours.

Ovarian gonadoblastoma with dysgerminoma in a woman with two normal children

An unusually rare case of unilateral gonadoblastoma with dysgerminoma occurring in the ovary of a 28-year-old woman with two normal children is reported.

Immunohistochemical characterization of extracellular matrix components of yolk sac tumors

SummaryProteoglycans (PGs) were isolated from yolk sac tumor and chondroitin sulfate large PG (core molecule with a molecular weight ≃ 200,000) and small PG (core molecule with a molecular weight ≃ 50,000) were detected. Immunohistochemical localization of PGs in three yolk sac tumors was investigated using monoclonal antibodies raised against both small and large PGs, which were purified from human ovarian fibroma capsule and a yolk sac tumor, respectively. The localization of large PG was observed to be distinct from that of small PG. A markedly positive reaction for antibody against large PG was observed in myxomatous areas, perivascular and perivesicular portions; hyaline globules were the most intensely reactive. In the areas showing a polyvesicular vitelline tumor pattern, the compact connective tissue stroma consisted of small PGs. It is conceivable that large PGs are synthesized by immature mesenchymal cells and also by epithelial-like cells as a basement membrane component, whereas small PGs are synthesized by mature fibroblastic cells synthesizing collagen. Immunohistochemical localization of other extracellular matrix components (laminin, fibronectin, type I-IV collagen) was also studied in relation to PG localization.

Painful ophthalmoplegia caused by idiopathic hypertrophic cranial pachymeningitis in the cavernous sinus

A 73-year-old man presenting with painful unilateral ophthalmoplegia is reported. Magnetic resonance imaging demonstrated a mass in the cavernous sinus extending to the floor of the middle cranial fossa. After resection of the lesion and anti-tuberculous chemotherapy his symptoms improved. Pathological examination revealed extensive caseous necrosis.

Immunohistochemical characterization of extracellular matrix components of granulosa cell tumor of ovary

In order to clarify the characteristics of granulosa cell tumors of the ovary, extracellular matrix components were investigated by immunohistochemical techniques. Twenty‐three granulosa cell tumors (GCT; eight juvenile and 15 adult type) were studied in comparison with non‐neoplastic granulosa cells of human ovaries. In all 23 cases of GCT, chondroitin 6‐sulfate proteoglycan revealed with antibody 3B3 was characteristically observed in the extracellular matrix in the solid nest, as well as in microfollicles. In the juvenile cases, the extracellular matrix also contained large proteoglycan (PG) revealed with antibody 2B1. Macrofollicles as well as micro‐follicles contained PG chondroitin 6‐sulfate side chains with a significant amount of chondroitin 4‐sulfate. By biochemical analysis using high pressure liquid chromatography, it was also found that disaccharide composition of glycosaminog‐lycan fractions extracted from granulosa cell tumor tissues consisted mainly of 2‐acetamide‐2‐deoxyl‐3‐0‐(β‐D‐gluco‐4‐enepyranosyluronic acid)‐6‐O‐sulfo‐D‐galactose (δ Di‐6S). The characteristic feature of granulosa cell tumors is the accumulation of chondroitin sulfate PG, especially chondroitin 6‐sulfate PG, which may be synthesized by the tumor cells themselves. Immunohistochemical characterization of the extracellular matrix components (collagen, laminin, heparan sulfate PG, chondroitin 4‐sulfate PG) was also studied in relation to chondroitin 6‐sulfate PG localization.

Immunohistochemical localization of proteoglycans in interstitial elements of human pancreas and biliary system.

SummaryThe immunohistochemical localization of large proteoglycan and small proteoglycan was observed, using antibodies 2B1 and 6B6 (Sobueet al., 1988, 1989a), in fetal and adult pancreas and biliary system as well as in tumour tissues, obtained from 11 autopsies and 74 biopsies. The distribution of chondroitin 4- and 6-sulphate side chains, type I and IV collagen and elastin were also studied. In adult pancreas and all the biliary tracts examined, periductal fibrous tissues consisted mainly of dermatan sulphate small proteoglycan with networks of fibrous elements, which were composed of large proteoglycan, elastin, type I collagen and type IV collagen. In the interstitial components of cystadenoma of pancreas and biliary duct carcinoma, similar small proteoglycan-rich components were relatively abundant, although large proteoglycan was present in much larger amounts than that in non-neoplastic adult tissues. In some cholangiomas, the extra-and intracellular hyaline globules formed by the carcinoma cells were found to contain chondroitin sulphate large proteoglycan, laminin and fibronectin.The distribution of proteoglycans was observed to be different in the arterial walls of the interlobular tissues of the adult and the fetal pancreas. The biological significance of large and small proteoglycans in the interstitial connective tissues was discussed.