Chromophobe renal cell carcinoma with prominent lymph node metastasis and polysomy of chromosome 21: poorly differentiated form or "presarcomatoid" form?

Lymph node metastasis of chromophobe renal cell carcinoma (RCC) is extremely rare. It has been recently reported that sarcomatoid chromophobe RCC frequently show polysomy of chromosomes 1, 2, 6, 10, and 17. In this article, we report an unusual case of chromophobe RCC. A 42-year-old Japanese woman presented with hematuria and complained of inguinal pain 2 months after the initial symptoms. Radical nephrectomy and renal hilar lymphadenectomy were performed. The tumor was 8 cm in greatest diameter; its cut surface was beige in color. Large metastasis to the renal hilar lymph node was identified. Histological examination of the right renal tumor met the criteria of chromophobe RCC. In addition to histological findings of typical chromophobe RCC, small cell foci, comedo-like necrosis, trabecular growth pattern, and sclerosing stroma were observed. However, no sarcomatoid foci were identified anywhere, despite extensive tumor sampling including lymph node lesions. Immunohistochemically, neoplastic cells were positive for E-cadherin and CD117 (c-kit). Ultrastructurally, tumorous cells contained abundant mitochondria and cytoplasmic microvesicles. Fluorescence in situ hybridization showed monosomy of chromosomes 2 and 10 and polysomy of chromosome 21. Finally, we suggest that this tumor may show the poorly differentiated or presarcomatoid form of chromophobe RCC.     

Appearance of denuded hepatic stellate cells and their subsequent myofibroblast-like transformation during the early stage of biliary fibrosis in the rat

To investigate the early in vivo response of hepatic stellate cells in biliary fibrosis, we examined rat livers during the first 7 days after bile duct ligation using light microscopy, immunohistochemistry, electron microscopy, and immunoelectron microscopy. At day 1 after bile duct ligation, alpha-smooth muscle actin-positive fibroblasts appeared and then increased in number around the proliferating bile ductules. With time, the destruction of the external limiting plate became accentuated because of the invasion of the proliferating bile ductules and periductural fibrosis. At day 7, stromal cells containing fat droplets appeared in the fibrous tissue adjacent to the periportal parenchyma; these are termed denuded hepatic stellate cells. In the fibrous tissue disconnected from the liver parenchyma, the denuded hepatic stellate cells were replaced by myofibroblast-like cells. Meanwhile, the expression of transforming growth factor-beta1 on biliary epithelial cells increased. These results indicate the dual origin of myofibroblasts in experimental biliary fibrosis, the periductural and periductal fibroblasts in the initial stage, and the denuded hepatic stellate cells in the subsequent stage. These two types of stromal cells may undergo myofibroblastic transformation by the transforming growth factor-beta1 secreted by the proliferating biliary epithelial cells.     

Adenoid basal carcinoma of the uterine cervix: a case report with ultrastructural findings

Adenoid basal carcinoma of the uterine cervix is a rare tumor with a favorable prognosis. A case of adenoid basal carcinoma (ABC) of the uterine cervix was studied using light and electron microscopy. The patient was a 74-year-old Japanese woman who had undergone hysterectomy due to cervical intraepithelial neoplasia 3. Incidentally, ABC was found in the resected uterus. The tumor cells made small nests and infiltrated the cervical portion of the uterus. In the nests, glands, cribriform patterns with glandlike structures, and squamous differentiation were seen. Immunohistochemically, the glandlike structures were positive for laminin and type IV collagen. Ultrastructurally, the tumor cells had irregular nuclei, scanty cytoplasm, and cribriform patterns in which glandlike structures were covered with basal lamina. No myoepithelial differentiation of the tumor cells was seen. These findings suggest a similarity between adenoid basal carcinomas and adenoid cystic carcinomas. Furthermore, both tumors are considered to originate in the reserve cells of the uterine cervix. Because their outcomes are different, they should be distinguished from each other.     

Alpha smooth muscle actin positive stromal cells in gastric carcinoma

AIMS: To investigate the distribution and roles of alpha smooth muscle actin (ASMA) positive stromal cells (ASMA+ cells), which belong to the myofibroblast group, within gastric carcinomas, with reference to three histological types (diffuse type, intestinal type, and solid type). METHODS: In total, 74 surgically resected gastric carcinomas (24 diffuse type, 43 intestinal type, and seven solid type) were examined. ASMA positive and high molecular weight caldesmon (HCD) negative stromal cells were regarded as ASMA+ cells. The distribution of CD34 positive stromal cells (CD34+ cells) was also analysed immunohistochemically. RESULTS: In the 24 diffuse-type gastric carcinomas, six of the 13 carcinomas invading the subserosa had ASMA+ cells in the tumour stroma, whereas all six diffuse-type gastric carcinomas confined to the submucosa and all five invading the muscularis propria had no ASMA+ cells in the tumour stroma. In the 43 intestinal-type gastric carcinomas, only five of the 21 carcinomas confined to the submucosa had ASMA+ cells in the tumour stroma, whereas 21 of the 22 intestinal-type gastric carcinomas invading the muscularis propria and the subserosa had ASMA+ cell bundles in the tumour stroma. The distribution of CD34+ cells in diffuse-type and intestinal-type gastric carcinomas was similar to that seen in a previously published series. All seven solid-type gastric carcinomas examined had ASMA+ cells but not CD34+ cells in the tumour stroma. No stromal cells double positive for ASMA and CD34 were detected within the diffuse-type tumours examined. CONCLUSIONS: These results suggest that ASMA expression in stromal cells is associated with tumour stroma formation of diffuse-type gastric carcinomas invading the subserosa, intestinal-type gastric carcinomas invading the muscularis propria and subserosa, and solid-type gastric carcinomas.     

High molecular weight caldesmon positive stromal cells in the capsule of thyroid follicular tumours and tumour-like lesions

AIMS: To investigate the smooth muscle nature of the spindle stromal cells in the capsule of thyroid tumours and tumour-like lesions. METHODS: Immunostaining for high molecular weight caldesmon (HCD), a highly specific marker for smooth muscle differentiation, was performed in 70 primary thyroid tumours and tumour-like lesions (21 hyperplastic nodules, 29 follicular adenomas, five minimally invasive follicular carcinomas, six widely invasive follicular carcinomas, and nine encapsulated papillary carcinomas). RESULTS: HCD positive stromal cells (HCD+ cells) were detected in the capsule of 20 of the 21 hyperplastic nodules, and all of the 29 follicular adenomas and five minimally invasive follicular carcinomas, whereas HCD+ cells were seen in the capsule of only four of the six widely invasive follicular carcinomas and no HCD+ cells were seen in the capsule of the nine encapsulated papillary carcinomas examined. CONCLUSIONS: The presence of HCD+ cells in the capsule is characteristic of thyroid follicular tumours and tumour-like lesions. The stromal cells in the capsule of thyroid follicular tumours and tumour-like lesions are different from those of encapsulated papillary carcinoma.     

Development of anti-adhesive spongy sheet composed of hyaluronic acid and collagen containing epidermal growth factor

Anti-adhesive products need to be designed while considering the concept of wound healing. Two main events must proceed simultaneously: facilitating wound healing in surgically excised tissue, as well as preventing injured tissue from adhering to the surrounding tissue. The present study aimed to develop an anti-adhesive spongy sheet composed of hyaluronic acid and collagen (Col) containing epidermal growth factor, and to investigate the potential of this spongy sheet using an in vitro wound surface model (placing a spongy sheet on a fibroblast-incorporating Col gel sheet) and an in vitro inter-tissue model (placing a spongy sheet between two fibroblast-incorporating Col gel sheets). These in vitro experiments demonstrated that this spongy sheet effectively stimulates fibroblasts to release an increased amount of vascular endothelial growth factor and hepatocyte growth factor, which are essential for wound healing to proceed succesfully. In addition, anti-adhesive performance of this spongy sheet was evaluated in animal experiments using Sprague Dawley rats. Under anesthesia, a 1?cm?×?2?cm segment of peritoneum was superficially excised from walls, and the cecum was then abraded by scraping with a scalpel blade over a 1?cm?×?2?cm area. A piece of spongy sheet was placed on the peritoneal defect. Both defects were placed in contact, and the incision was closed by suturing. Peritoneal condition was evaluated after one week. This spongy sheet was capable of facilitating the wound healing of surgically excised tissue and preventing surgically excised tissue from adhering to surrounding tissues.     

Change in decorin during aging of rat placenta

By immunohistochemistry, with or without chondroitinases, decorin was found to be distributed in the extracellular matrix of chorionic villi and amnia. The strength of staining intensified with increasing gestational age. Decorin was isolated from the placenta of 13- to 20-day-old pregnant rats and identified by Western blotting, using an antidecorin core protein antibody. The molecular weight of decorin is approximately 100 kDa, whereas the respective figures for the core protein treated with chondroitinase (chase) ABC and with chase B are approximately 40 kDa and 43 kDa. The difference in the molecular weight between the core protein with chase ABC and B suggests that the glycosaminoglycan (GAG)- base structure on the core protein was chondroitin sulfate (CS) without dermatan sulfate (DS). The decorin content and the proportion of CS to DS in GAG increased with age. We concluded that the age-related changes in the GAG chain may be related to specific functional properties and may have a crucial role in placental tissue organization.     

Differentiation between vaccine and wild-type varicella-zoster virus genotypes by high-resolution melt analysis of single nucleotide polymorphisms

BACKGROUND: The analysis of single nucleotide polymorphisms (SNPs) of varicella-zoster virus (VZV) has enabled differentiation between wild-type genotypes from the Oka vaccine strain (V-Oka). OBJECTIVES: To genotype VZV strains in Australia using high-resolution melt (HRM) analysis of SNPs in five gene targets. STUDY DESIGN: Extracted DNA from 78 samples obtained from patients with chickenpox and zoster were genotyped by HRM analysis of SNPs in five open reading frames (ORFs): 1 (685 G>A), 21 (33725 C>T), 37 (66288 G>A), 60 (101464 C>A) and 62 (106262 T>C) using a double-stranded (ds) DNA saturating dye, LC Green Plus. RESULTS: For each genotype, melt curve temperature (T(m)) shifts differentiated the nucleotide present at that locus (P<0.0001) with melting curve shifts between alleles ranging from 0.56 degrees C (ORF 37) to 3.34 degrees C (ORF 62). The most common genotypes detected were the European Type C (59%) and B (18%) strains. This was followed by the African/Asian Type A (14%) and Japanese J1 (9%), strains, both prevalent in the Northern Territory and Western Australia. CONCLUSIONS: HRM analysis of SNPs showed that the European B and C genotypes were most prevalent in Australia, with genotypes A and J strains also present. HRM analysis using a dsDNA dye provides a useful tool in classifying varicella-zoster viruses.     

CAM5.2-positive subserosal myofibroblasts in appendicitis

In this study, we examined the distribution and origin of myofibroblasts around the perforations of appendicitis. Stromal cells of 45 cases were studied by immunohistochemistry. In the normal appendix, myofibroblasts were restricted to the mucosa, and CD34-positive stromal cells were distributed in the submucosal and subserosal layers. Some mesothelial cells were positive for cytokeratin CAM5.2, cytokeratin 5, or mesothelial cells (HBME-1). In perforation of appendicitis with both abscess and granulation tissue, a small to moderate or a moderate to large number of myofibroblasts appeared in the subserosal area around the perforation, respectively, but CD34-positive stromal cells were completely absent there. In the subserosal area of the perforation of appendicitis with abscess, cytokeratin 5-positive stromal cells were absent. However, a small to moderate number of cytokeratin CAM5.2-positive stromal cells were observed there. Double immunostaining showed the coexpression of alpha-smooth muscle actin (ASMA) and cytokeratin CAM5.2 and the coexpression of cytokeratin 5 and cytokeratin CAM5.2 in many or some stellate-shaped or spindle-shaped stromal cells existing in the subserosal area with granulation tissue around the perforation of appendicitis, respectively. Finally, many myofibroblasts appearing in the subserosal area of the perforation of appendicitis may be derived from submesothelial cells or mesothelial cells.     

Prolonged neutropenia after dose-dense chemotherapy with pegfilgrastim

In the dose-dense (DD) chemotherapy trial result reported byPiedbois et al. [1], they found more hematological toxicityleading to treatment discontinuation in the pegfilgrastim supportedDD chemotherapy arm. The manufacturer's product informationfor pegfilgrastim indicates that it should be used once perchemotherapy cycle and should not