Shigeo Yokoyama

Genetic alterations in 102 primary gastric cancers by comparative genomic hybridization: gain of 20q and loss of 18q are associated with tumor progression.

Gastric cancer is one of the most common cancers. Molecular events in the carcinogenesis of gastric cancer remain, however, largely undefined. We investigated changes in DNA copy number in 102 gastric cancers by CGH. We found changes in DNA copy number in all cases, with frequent (≧30% of patients) gains at 20q, 8q, 20p, 7q, 17q, 5p, and 13q. Frequent (≧20%) losses were found at 19p, 18q, 5q, 21q, 4p, 4q, 15q, and 17p. The mean number of total alterations was significantly lower in grade 3 and scirrhous-type carcinomas (10.81 in grade 3 vs 13.98 in grade 1 and grade 2, 9.31 in scirrhous-type vs 13.18 in medullary- and intermediate-type). The mean number of losses and total alterations were higher in tumors at pT2, pT3 and pT4 (4.68 and 12.77 in pT2, pT3, and pT4 vs 2.55 and 9.22 in pT1). The mean number of losses was higher in carcinomas with lymph node metastasis (4.83). The mean number of gains and total alterations were higher in carcinomas with venous invasion (8.44 and 13.28). Several chromosomal alterations were linked in a statistically significant manner to specific clinicopathological parameters. Gain of 17q, 20p, and 20q and loss of 4p were associated with the pattern of the cancer–stroma relationship; loss of 18q was associated with pT category; gain of 5p was associated with pN category; loss of 4q and loss of 21q were associated with lymphatic invasion; gain of 7p and loss of 4q and 18q were associated with venous invasion; and loss of 18q was associated with pathological stage. These data suggest that gain of 20q and loss of 18q might play an important role in the development and progression of gastric cancer. Moreover, some genes on 20q and 18q might be target genes of gastric cancer.

Expression of CD10 in basal cell carcinoma.

We investigated the expression of CD10 by an immunohistochemical method in 51 basal cell carcinomas (BCCs), eight pilomatricomas, five trichoblastomas, two trichofolliculomas, three sebaceomas, five sebaceous carcinomas, ten syringomas, two spiradenomas, ten poromas, four porocarcinomas, one eccrine duct carcinoma (not otherwise specified, NOS), six mixed tumors of apocrine origin, and nine squamous cell carcinomas (SCCs). We detected strong expression of CD10 in tumor cells of BCC (86%), and found that the smaller the number of positive tumor cells, the larger the number of positive stromal cells, in particular in sclerosing BCCs. Spearmans rank correlation test revealed a significant negative correlation in BCCs between the expression of CD10 in tumor cells and that in stromal cells (P = 0.001). In all pilomatricomas (100%) and in four trichoblastomas (80%), strong expression was also detected in tumor cells. There was no detectable expression in trichofolliculomas. One sebaceoma (33%) and two sebaceous carcinomas (40%) expressed CD10 in a similar fashion to BCCs. All tumors of eccrine gland origin, including syringoma, spiradenoma, poroma, porocarcinoma, and eccrine duct carcinoma (NOS), did not express CD10. Five mixed tumors (83%) were immunopositive. In SCC, CD10 was overexpressed only in the stromal cells. These findings support the hypothesis that BCC is derived from the folliculo-sebaceous apocrine unit, especially having the same origin as trichoblastoma and pilomatricoma. CD10 might be an indicator of tumor invasiveness if it is expressed in stromal cells, while it might be a marker of follicular differentiation if it is expressed in the actual tumor cells of cutaneous epithelial neoplasms.

Mutations in components of the Wnt signaling pathway in adenoid cystic carcinoma

The Wnt signaling pathway is essential for normal development and organogenesis. However, inappropriate activation of Wnt signaling, which results in the nuclear translocation of β-catenin, is associated with the development of various types of neoplasm. In this study, we investigated possible mutations in the genes for components of this pathway, namely, CTNNB1 (the gene for β-catenin), AXIN1, and APC, in adenoid cystic carcinoma, by PCR, analysis of single-strand conformational polymorphism, and sequencing. Among a total of 20 cases of adenoid cystic carcinoma, seven cases (35%) were associated with mutations in one or more of these three components. A mutation in CTNNB1 was detected in one case. Five cases, including the case with a mutation in CTNNB1, were associated with missense mutations in AXIN1. An aberration in the mutation cluster region of APC was detected in two cases. Mutations trended to be detected more frequently in adenoid cystic carcinoma with solid growth pattern than that with tubular and cribriform growth pattern. In the cases in which we detected mutations, it is possible that the presence of the abnormal products of the mutated genes resulted in the inappropriate activation of the Wnt signaling pathway to tumorigenesis and the growth of adenoid cystic carcinoma.

Duodenal gangliocytic paraganglioma treated with endoscopic hemostasis and resection

Gangliocytic paragangliomas are exceedingly rare tumors that arise in close proximity to the papilla of Vater. There are few reports of the endoscopic resection of duodenal gangliocytic paraganglioma. A 61-year-old woman was admitted with a complaint of melena. Endoscopic examination revealed a pedunculated submucosal tumor with erosion in the third portion of the duodenum. Hemostasis, using a gold probe, was performed. Nine days later, we successfully resected the tumor, using endoscopic polypectomy. To determine the depth of tumor invasion, endoscopic ultrasonography was used. The size of the tumor was 3.0 × 2.5 × 1.0u2009cm. A total of 25 cases of duodenal gangliocytic paraganglioma have been reported in Japan. Generally, this tumor is considered benign. However, resection was performed in many patients because preoperative diagnosis was impossible. In Japan, no previous studies have reported using endoscopic hemostasis, to our knowledge. Our patient is the fourth in Japan to be treated by endoscopic resection. We report on our patient, with a review of the literature.

A case of tenosynovial chondromatosis with tophus-like deposits.

Tenosynovial chondromatosis has not been well recognized because of its rarity, but it is clinically important because of its high rate of recurrence. We report here a case of tenosynovial chondromatosis with deposits of crystalline material that appeared to be sodium urate (gouty tophi). A 37‐year‐old Japanese man was admitted because of a hard mass in his left third finger. He had undergone surgery at the same anatomical site four and seven years previously. The roentgenogram revealed a soft tissue mass in the flexor aspect of the proximal phalanx. At operation, the tumor was found to have arisen in the tendon sheath. Histopathological examination showed that the tumor was composed of well‐defined, multiple, cartilaginous nodules that were surrounded by tenosynovial tissue. A few of the nodules were calcified. The chondrocytes had mild atypia, and were immunopositive for S‐100 protein. A diagnosis of tenosynovial chondromatosis was made. The nodules also contained crystalline deposits, which bore a histological resemblance to gouty tophi. We were unable to define the exact nature of these deposits even by transmission electron microscopy and electron roentgenographic microanalysis. Crystalline deposits in chondromas of soft tissue have been reported but not in tenosynovial chondromatosis.

Erythema Nodosum and Granulomatous Lesions Preceding Acute Myelomonocytic Leukemia

A 65‐year‐old female with a one‐month history of painful eruptions on her lower extremities was admitted to our hospital. Histological examination revealed erythema nodosum (EN), and the patient was treated with oral prednisolone (PSL; 20 mg daily). The eruptions subsided in two weeks. One month later, painful reddish eruptions recurred on her upper limbs and abdomen in addition to her lower extremities. A skin biopsy from an abdominal erythematous plaque revealed a non‐caseating granuloma without microorganisms or foreign‐body materials. These eruptions also disappeared with treatment with oral PSL (20 mg daily). No underlying disease, including sarcoidosis, diabetes mellitus, or rheumatoid arthritis, was found. However, five months later, the patient developed conspicuous leukocytosis. She was diagnosed with acute myelomonocytic leukemia (M4) and treated with chemotherapy. After complete remission had been achieved, the EN reappeared, in association with an increase in blastic cells in the bone marrow. Serum levels of tumor necrosis factor‐alpha and interleukin‐1 beta, which are thought to be essential for granuloma formation and induction of EN, were markedly elevated. Physicians must remember that recurrent EN and granulomatous lesions can be a prodromal sign of leukemia.

Malignant lymphoma with tumor thrombus in the portal venous system.

We report a case of malignant lymphoma presenting with tumor thrombus of the portal venous system. Computed tomography showed a mass in the portal vein and mesenteric lymphadenopathy. Filling defects in the dilated portal vein also were identified by angiography. This type of the lymphoma is extremely rare, but it should be considered in the differential diagnosis of portal vein thrombus.

Acquired Dermal Melanocytosis: A Case with Conjunctival and Gingival Pigmentation

A 28‐year‐old Japanese woman was referred to us because of widespread bilateral blue‐gray and brown pigmentation on her face. Pigmentation was apparant on both sclerae, the alae of the nose, the lower lip and the gingiva; and it was also evident on her extremities. A biopsy specimen revealed melanin‐containing cells and numerous mononulear cells in the upper dermis, particularly, near the small vessels. The melanin‐containing cells immunoreacted with S100‐specific antibodies but did not react with CD68‐specific antibodies, these observations indicated that they were melanocytes. A diagnosis was made of acquired dermal melanocytosis (ADM), even though ADM is very rarely associated with conjunctival and mucosal involvement. Dermal melanocytes and large numbers of mononuclear cells adjacent to small vessels in the upper dermis have not previously been reported in ADM. Such melanocytes might play an important role in protecting blood cells from ultraviolet light. The presence of mononuclear cells close to melanocytes suggests that an inflammatory reaction might have initiated the activation of these dermal melanocytes.

Herpes simplex infection in urothelial carcinoma

Herpes simplex virus (HSV), a member of the Herpesviridae family, is a very common pathogen that can infect any site in the body. Urothelial carcinoma (UC) is a common malignancy of the urinary tract. The possibility of HSV infection in cases of UC has attracted little attention. In this study, we investigated the possible presence of HSV in UC and non-neoplastic urothelium. We examined the incidence of HSV infection in 100 samples of UC from 78 patients and 50 samples of non-neoplastic urothelium from 50 autopsy cases using immunohistochemical staining and amplification of DNA using polymerase chain reaction (PCR). Infection by HSV was detected in 39 of the 100 samples of UC (35 of 78 patients) using immunohistochemical staining and/or PCR analysis, in marked contrast with 1 of 50 samples of non-neoplastic urothelium. There was no significant relationship between infection by HSV and anatomical site, growth pattern or depth of invasion of UC, but the frequency of HSV infection was significantly higher in females than in males. Our findings indicate that UCs become infected with HSV much more easily than non-neoplastic urothelium.

The proliferative kinetics of somatostatin-producing cells in the rat antral mucosa after truncal vagotomy

The kinetics of somatostatin-producing cells (D-cells) in the rat antral mucosa after truncal vagotomy were studied using double immunostaining for bromodeoxyuridine (BrdU) and somatostatin. Both the concentration of somatostatin and D-cell density in the antral mucosa demonstrated a significant increase on the 3rd day after truncal vagotomy. With the single labeling of BrdU, a few D-cells showed positive immunostaining for BrdU throughout the experimental period in both vagotomized and sham operated rats. With cumulative labeling, the BrdU labeled cells demonstrated a linear increase in an identical number for each experimental time-point in both groups. The labeling index of BrdU in the D-cells increased significantly, beginning on the 3rd day and attaining a maximum level of 41.8% on the 10th day, in the vagotomized group after cumulative labeling. In this group, however, the density of D-cells with no immunoreactive BrdU also increased quickly on the 3rd day with cumulative labeling. The present study indicates that the most important factor involving D-cell hyperplasia observed after truncal vagotomy is the activation of pre-existing D-cells to synthesize and release hormones, together with the rapid replication of progenitor cells and their maturation to D-cells.