[Mediastinal granular cell tumor: report of a case].

Mediastinal granular cell tumor is rare. We report a case of 16-year-old woman with a granular cell tumor in the right upper-middle mediastinum. Chest computed tomography (CT) and magnetic resonance imaging (MRI) revealed a 4.0 x 2.5 x 5.5 cm well circumscribed mass in the right upper-middle mediastinum. Tumor resection was performed. It was found that the tumor involved right vagus nerve. The tumor was completely excised with combined resection of the right vagus nerve peripheral to the right recurrent nerve. Histopathologically, the tumor consisted of round to polygonal cells with abundant eosinophilic granular cytoplasm, and diagnosed a granular cell tumor.

Transient spontaneous regression of aggressive non-Hodgkin's lymphoma confined to the adrenal glands.

A 72-year-old-man with night sweats and a low-grade fever was found to have bilateral adrenal enlargement associated with incipient adrenal insufficiency. Without any intervention, these adrenal lesions regressed spontaneously, accompanied by disappearance of clinical symptoms. Seven months later, however, the lesions became enlarged and exceeded their initial size while remaining confined to the adrenals, associated with reappearance of nights sweats and overt adrenal insufficiency. Upon unilateral laparoscopic adrenalectomy, the lesion proved histopathologically to be diffuse large B cell non-Hodgkin's lymphoma (NHL). After contralateral laparoscopic adrenalectomy and adjuvant chemotherapy, the patient remains alive with no recurrence at 26 months. Treatment with bilateral adrenalectomy and chemotherapy is effective for aggressive NHL confined to bilateral adrenal glands. A transient clinical improvement without treatment was considered to be due to a spontaneous regression of NHL, although we could not confirm the histological results before the regression. Such tumor behavior showing spontaneous regression in spite of aggressive histology may also be related to the favorable outcome, even though regression was transient.

A case of subcortical meningioma.

Subcortical meningioma, which has been reported as meningioma without dural attachment, a cerebral subcortical lesion, is extremely rare. Very few findings of radiological examination of subcortical meningioma have been described. Pre-operative differentiation of this lesion is generally difficult. We characterize the peritum oural oedema adjacent to the meningioma in this region, and we suggest that radiological findings of peritum oural oedema contribute to differential diagnosis of subcortical meningiomas.

Microsatellite instability and mutation of mitochondrial and nuclear DNA in gastric carcinoma.

BACKGROUND & AIMS: Microsatellite instability (MSI) in mitochondrial DNA (mtDNA) is observed in some colorectal carcinomas. We attempted to determine if mitochondrial MSI (mtMSI) and mutations occur in gastric carcinomas and if the mtMSI phenotype underlies specific clinicopathologic profiles. METHODS: Sixty-two gastric carcinomas (34 intestinal and 28 diffuse types) were investigated. Coding mutations in 8 different mitochondrial genes, mtMSI in a noncoding (C)n tract, and p53 gene mutations were examined by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. MSI in nuclear DNA (nMSI) and loss of the p53 gene were examined using microsatellite markers. RESULTS: Ten of 62 (16%) carcinomas showed the mtMSI phenotype. Mitochondrial gene mutation was detected in 5 carcinomas, 4 of which also showed the mtMSI phenotype. There was a positive correlation between mtMSI and nMSI status. In intestinal carcinomas, mtMSI, nMSI, and p53 gene alterations were frequently detected from early to advanced stages. In diffuse carcinomas, both kinds of MSI were found in only advanced (subserosal or serosal invasion) carcinomas. Six of 7 carcinomas with the nMSI phenotype and all 5 carcinomas with mitochondrial coding mutations had a considerable intestinal-type tumor cell component. CONCLUSIONS: Mitochondrial gene mutations, which are associated with the mtMSI phenotype, may play a specific role in the tumorigenesis of intestinal-type gastric carcinomas.

Use of crypt isolation to determine loss of heterozygosity of multiple tumor suppressor genes in colorectal carcinoma.

Analysis of loss of heterozygosity (LOH) is very important in the study of tumor suppressor genes. However, accurate LOH analysis of tumor suppressor genes is difficult because of dilution by contaminating non-tumor DNA. Thus, enrichment of tumor DNA is required to accurately determine LOH of the tumor. We developed a new application of the fluorescent polymerase chain reaction by coupling it with crypt isolation to accurately assess the incidence of LOH of tumor suppressor genes in 45 colorectal carcinomas. LOH was observed at p53 in 26 of 37 tumors (70.3%), at APC in 13 of 35 (37.1%), at DCC in 16 of 25 (64.0%), at NF-2 in 5 of 23 (21.7%), and at nm23 H-1 in 7 of 30 (23.3%). We could clearly determine LOH of these genes because the crypt isolation technique was used. Although the incidence of LOH at each of these loci, as determined by using this technique, was similar to that obtained in previous studies using conventional methods, this method provides a simpler, more accurate way to assess LOH. In addition, the morphology of the samples can be analyzed before genetic analysis.

A unique method for mutation analysis of tumor suppressor genes in colorectal carcinomas using a crypt isolation technique.

BACKGROUND: Contamination of nontumor tissue makes genetic analysis difficult. For this reason, it is important to obtain pure tumor tissue to ensure accurate genetic analysis. OBJECTIVE: To accurately assess the incidence of mutation of tumor suppressor genes (p53: exon 5-8; APC: mutated cluster region; NF-2 gene: all exons) in 45 colorectal carcinomas. METHODS: We developed an application of the polymerase chain reaction-single-strand conformation polymorphism and DNA sequence by coupling them with crypt isolation. RESULTS: Mutations of p53 and APC genes were found in 24 and 22 of 45 colorectal carcinomas, respectively. No mutation of the NF-2 gene was observed in this cancer. Single-strand conformation polymorphism using a crypt isolation technique showed a clear migrating band and no false-positive data. CONCLUSIONS: The crypt isolation technique is a useful method for accurately analyzing genetic alterations. Furthermore, our proposed method confirmed the morphological findings obtained before the genetic analysis.

Results of surgery for a compound adrenal tumor consisting of pheochromocytoma and ganglioneuroblastoma in an adult: 5-year follow-up.

A rare, compound adrenal tumor consisting of ganglioneuroblastoma and pheochromocytoma was completely resected in an adult woman. Most of the tumor was occupied by the ganglioneuroblastoma component. This ganglioneuroblastoma was an intermixed tumor, which is known to have a favorable prognosis in children. Based on the lack of spread, the resectability of the tumor, and the histology of the ganglioneuroblastoma, no adjuvant therapy was employed. There was no evidence of recurrence at the 5-year follow-up. This suggests that adjuvant therapy may not be necessary in these compound tumors.

Analysis of subclonal expansion of colorectal carcinomas by flow cytometry.

DNA heterogeneity of colorectal carcinomas has been investigated by flow cytometry, most studies have focused on the clinical usefulness of DNA ploidy analysis. Since cancers consist of predominant subclones with proliferative advantage due to clonal expansion, we attempted to analyse the clonal expansion of colorectal carcinomas within a tumour by measuring DNA ploidy. The DNA ploidy and heterogeneity of multiple fresh samples obtained from 164 colorectal adenocarcinomas were analysed by flow cytometry. Each tumour was divided into an average of six specimens, which were analysed separately. For 146 of the tumours (89%) at least one DNA aneuploid population was found within the cancer tissue examined. DNA multiploidy was detected in 26 cases (17.8%) among the cancers with aneuploidy. Based on the DNA index (DI), hypertriploid aneuploidy (1.7

Epithelial splenic cysts in an intrapancreatic accessory spleen and spleen.

A rare case of cysts simultaneously occurring in the intrapancreatic accessory spleen and spleen in a 49-year-old female is reported. The patient underwent distal pancreatomy for a cystic tumor of the pancreas, and a splenectomy. A multilocular cyst (4.3 x 2.6 cm) in an accessory spleen at the pancreas tail, and a solitary cyst (1.2 x 0.9 cm) of the spleen were found. The cyst in the intrapancreatic accessory spleen was lined by non-keratinizing stratified squamous epithelium, and the spleen cyst by a single layer of flat epithelium; these lining cells were positive for Alcian blue stain and periodic acid-Schiff reaction, and were immunohistochemically positive for cytokeratin, HBME-1 and Sialyl-Tn. Epithelial membrane antigen, carcinoembryonic antigen and CA19-9 were positive in the accessory spleen cyst but were negative in the spleen cyst. An electron microscopic examination of the flat epithelium of the spleen cyst revealed numerous microvilli on the surface, cytoplasmic microfilaments, and a number of tight junctions between adjacent cells. These features suggested that the two cysts differ in nature, and origin; the accessory spleen cyst may be an embryonic inclusion of the pancreas duct while the spleen cyst may be an inclusion cyst of the mesothelium.

Suspensory ligament of Berry: its relationship to recurrent laryngeal nerve and anatomic examination of 24 autopsies.

BACKGROUND: It is important to clarify the relationship between the recurrent laryngeal nerve (RLN) and the ligament of Berry to prevent damage to the RLN in thyroid surgery. The purpose of the present paper is to identify this relationship to prevent surgical complications. METHODS: Among the 486 thyroid surgery cases, 689 RLNs were identified and their course detected. Topography of the laryngotracheoesophageal region and the histology of the ligament of Berry were studied in detail in 25 autopsied cadavers. RESULTS: All nerves identified by surgery and autopsy were located laterodorsally to the ligament of Berry. They were clearly separated, and no nerve penetrated the ligament nor was medially located to it. The ligament of Berry strongly connected the thyroid gland to the trachea and was identified as a whitish connective tissue band. No paralysis of the RLN occurred during identification of the nerve during surgery. CONCLUSIONS: It was confirmed that the RLN never penetrates the ligament of Berry but is located laterally to it. From these topographic findings, no injury to the RLN will occur from a separation close to the goiter in thyroid surgery.

Pleomorphic adenoma of the minor salivary gland with pseudoepitheliomatous hyperplasia of the overlying oral mucosa: report of two cases.

Two cases of intra-oral pleomorphic adenoma with marked pseudoepitheliomatous hyperplasia of the overlying oral mucosa are reported. Incisional biopsy specimens, taken a few weeks before surgical excision of the tumor, showed no squamous cell element. Surgically excised specimens revealed pseudoepitheliomatous hyperplasia with hyperortho- and para-keratinization, which extended from overlying oral squamous epithelium, where an incisional biopsy was performed into the deep tumor area. Approximately half of the tumor area in case 1 and one-third in case 2 were occupied by hyperplastic squamous epithelium of the oral mucosa. Although the induction mechanism of such prominent pseudoepitheliomatous hyperplasia of the overlying oral mucosa occupying more than one-third of the tumor area could not be understood, it is thought that surgical injury and/or focal anesthesia during the incisional biopsy played an important role. To the best of our knowledge, these two cases represent the first reported association between benign salivary gland tumor and marked pseudoepitheliomatous hyperplasia of the overlying oral mucosa.

The first reported case of intestinal spirochaetosis in Japan.

A 65-year-old Japanese male consulted Ozuchi Prefectural Hospital (Iwate, Japan) on 19 January 1994 complaining of weight loss. Cecal mucosal biopsy material, which was stained with hematoxylin-eosin revealed a thick, basophilic fuzzy fringe covering the surface epithelium. Transmission and scanning electron microscopy observations demonstrated the presence of slightly wavy spirochaetes with tapered ends, which were attached to the surface epithelium of the colonic mucosa via one of these ends. The patient did not display any clinical symptoms of inflammatory bowel disease, and laboratory tests eliminated an immunodeficiency condition. Thus, in the present case, the intestinal spirochaetes appear to be harmless commensals. This paper presents the first reported case of intestinal spirochaetosis in Japan.

True malignant histiocytosis developed during chemotherapy for mediastinal immature teratoma.

We report an autopsy case of true malignant histiocytosis that developed during chemotherapy for mediastinal immature teratoma. The patient was a 14-year-old boy who exhibited hepatosplenomegaly while receiving chemotherapy for a mediastinal immature teratoma that had been resected 11 months before. The spleen and liver of the excisional biopsy displayed infiltration of multinucleated giant atypical cells with prominent erythrophagia in massive aggregations. These atypical cells expressed CD68, alpha1-antitrypsin, alpha1-antichymotrypsin, lysozyme, and vimentin, suggesting that the tumor cells may have been derived from macrophages. Immunocytochemistry showed p53 expression in the tumor cells of the malignant histiocytosis, as well as in the elements of the immature teratoma. Direct sequence analysis showed the p53 mutation in the tumor cells of the immature teratoma to be a mutation at codon 175 (exon 5), whereas the mutation in the malignant histiocytosis occurred at codon 285 (exon 8), ie, polyclonality was exhibited and these features suggested that the malignant histiocytosis arose independently from the immature teratoma during the chemotherapy.

Growth activity in hyperplastic and neoplastic human thyroid determined by an immunohistochemical staining procedure using monoclonal antibody MIB-1.

To increase our understanding of the basic biological mechanisms of thyroid diseases, growth activity (GA) in 232 thyroid lesions was determined by immunohistochemistry using monoclonal antibody MIB-1. The GA tended to be higher in hyperplastic lesions, adenomatous goiter (MIB-1-positive cell rate, 0.73%), and Graves' disease (1.68%) than in normal tissue (0.19%). The GA for differentiated thyroid carcinomas (2.00%) was much lower than for adenocarcinomas of other organs, such as breast, lung, stomach and colon (44.67%). Of the thyroid carcinomas, the highest GA was observed in undifferentiated carcinomas (32.67%), and follicular carcinomas (3.18%) showed a higher GA than papillary carcinomas (1.83%). There was no significant difference between the GA of follicular carcinomas and solid/trabecular adenomas, although widely invasive follicular carcinomas showed a higher GA than minimally invasive carcinomas. No significant correlations between GA and patient age, sex, and tumor diameter, metastasis, or histological features were observed in papillary carcinomas. Familial medullary carcinomas showed a higher GA than sporadic tumors. All latent papillary carcinomas had a very low GA. Our findings suggest that immunohistochemical investigation using the antibody MIB-1 contributes to the understanding of growth characteristics and biological activities in thyroid diseases.

A ruptured thymic branch aneurysm mimicking a ruptured aortic aneurysm, with associated bronchial artery aneurysms: report of a case.

A 57-year-old woman who went into shock following an acute left hemothorax was operated on after stabilization under the diagnosis of a ruptured aortic aneurysm. A left fifth intercostal thoracotomy was done which revealed approximately 500 ml of bloody effusion in the extrapleural space and 2,000 g of clotted blood in the pleural cavity. While the aneurysm was initially thought to have originated in the isthmic or descending aorta, intraoperative findings revealed a swollen hematomatous thymus adherent to the aorta. A ruptured thymic branch aneurysm, 3 cm in diameter, was subsequently found in the resected hematomatous thymus. Histological examination also revealed several small aneurysms in the tortured bronchial arteries. Postoperative angiography showed a saccular aneurysm, 1.5 cm in diameter, and several smaller aneurysms in the bronchial artery of the left lung. The aneurysm was successfully treated by a transcatheter arterial embolization, and the patient has had no further symptoms since then. To our knowledge, there has been no other case of a ruptured thymic artery aneurysm reported in the literature, and only a few cases of bronchial artery aneurysms have been documented.

Early stage of development in testicular choriocarcinomas.

Choriocarcinoma is the most malignant among germ cell tumors in the testis. However little is known about the early stage of its development. To understand the development of testicular choriocarcinomas, twenty cases of testicular choriocarcinoma were studied histologically and immunohistochemically. It was found that in the early stage of development, choriocarcinomas imitate the morphologic or functional differentiation of normal trophoblasts. It was also found that some choriocarcinomas regress spontaneously in the early stage. The majority of choriocarcinomas seemed to develop by first going through the embryonal carcinoma phase. However, there were some choriocarcinomas that showed no relationship with embryonal carcinoma.

Periarterial lymphoid sheath in the rat spleen: a light, transmission, and scanning electron microscopic study.

The periarterial lymphoid sheath (PALS) in the rat spleen was studied by light, transmission, and scanning electron microscopy. The PALS was divided into three regions: the central region, peripheral region, and marginal zone bridging channel. In the central region, lymphocytes were easily washed away by perfusion. Large spaces were found between flat reticular cells or in large meshworks of stellate reticular cells; these may be deep lymphatic vessels. True lymphatic vessels were found in the central region near the hilus. In the marginal zone bridging channel, flat reticular cells surrounded the central artery in a circumferential pattern and formed channel-like spaces between the flat reticular cells. These spaces were connected with the meshwork of the red pulp reticular cells and may be a route for lymphocytes between the deep lymphatic vessels and the red pulp. In the peripheral region of the PALS, it was usually difficult to wash away free cells by perfusion, and free cells were found among the reticular cells. In places in the peripheral region, however, free cells were washed away. It is suggested that the lymph flow may start from the region surrounding the PALS, and that the peripheral region of the PALS may also be another route for lymphocyte migration.

[A case of renal cell carcinoma with polymyositis].

We report a case of renal cell carcinoma with polymyositis. A 62-year-old female with a diagnosis of polymyositis was referred to our department because of the right renal mass discovered by computed tomography. An ultrasonography and renal angiography showed a solid and hypovascular area at the middle pole of the right kidney. A fine needle aspiration biopsy of the mass was performed and the cytology showed a papillary adenocarcinoma. Therefore, the right radical nephrectomy was carried out and her myopathic symptoms were slightly improved postoperatively. The patient has remained well without recurrence or metastasis for two years.

[A case of adenocarcinoma in the renal pelvis and urinary bladder in a patient with chronic renal failure].

The patient was a 61-year-old male who had undergone right nephrectomy for nephrolithiasis 35 years before. He had been on hemodialysis for 6 years for chronic renal failure caused by left renal staghorn calculus and hydronephrosis. He was admitted to our hospital because of macroscopic hematuria and sense of residual urine which had persisted for 3 months. Cystoscopic examination showed an extensive papillary tumor in the urinary bladder, which histologically was an adenocarcinoma. Giant left hydronephrosis associated with staghorn calculus noted by KUB and CT scan. Total cystectomy, intraoperative radiotherapy, and left nephrostomy were performed under the diagnosis of adenocarcinoma of the urinary bladder and left hydronephrosis. The bladder tumor was found to be a mucinous adenocarcinoma. The patient died from a cerebral hemorrhage on the 17th postoperative day. At autopsy, tumors were found in the pelvis of the left kidney and the middle and lower regions of the ureter, which were adenocarcinoma like the bladder tumor. Adenocarcinoma occurring simultaneously in the renal pelvis and bladder has not been previously reported to our knowledge, in Japan or elsewhere.

[Early esophageal cancer discovered 6 months after endoscopic injection sclerotherapy of esophageal varices].

Early esophageal cancer was discovered in a 55-year-old male with liver cirrhosis six months after the start of treatment for esophageal varices by a series of endoscopic sclerotherapeutic injections using 5% ethanolamine oleate. A histological examination of the entire length of the resected esophageal wall revealed a carcinomatous lesion oralwards and far removed from the lesion where subsequent changes due to sclerotherapy were prominent. Further, the causal relationship between sclerotherapy and carcinoma is discussed.