Comparison of histopathological findings between idiopathic and secondary epiretinal membranes.

To evaluate the histopathological findings of idiopathic and secondary epithelial membranes (ERMs). This study involved 19 ERM cases that underwent pars plana vitrectomy (PPV). ERM specimens were obtained from each patient during PPV and immediately fixed in 10 % formalin. Paraffin sections were stained with hematoxylin eosin (HE) and immunohistochemical analysis was performed with glial fibrillary acidic protein (GFAP), Ki-67, CD34, and nestin antibodies. The 19 ERM cases included 11 idiopathic ERM cases and 8 secondary ERM cases i.e., 2 eyes that underwent PPV for retinal detachment and 6 eyes that underwent PPV for proliferative diabetic retinopathy. HE staining showed that some of the idiopathic ERM specimens consisted of internal limiting membrane. In contrast, numerous invasive cells were observed in the secondary ERM specimens compared to the idiopathic ERM specimens. Immunohistochemical analysis revealed GFAP-positive cells in 4 of the 11 idiopathic ERMs cases, yet no nestin-, Ki-67-, or CD34-positive cells in those cases. In contrast, there were 4 GFAP-positive cases, 2 Ki67-positive cases, 3 CD34-positive cases, and 7 cases including nestin-positive cells. The findings of this study indicate that there are different histological characteristics between idiopathic and secondary ERM and that mature nestin-positive cells in the retina might be related to secondary ERM formation.

Predictors of lymph node metastasis in T1 colorectal carcinoma: an immunophenotypic analysis of 265 patients.

BACKGROUND: The appropriateness of endoscopic resection in patients with T1 colorectal carcinomas is unclear. Highly precise predictors of lymph node metastasis are required to optimize the outcomes of treatments for T1 colorectal carcinomas. OBJECTIVE: The purpose of this work was to identify predictors of lymph node metastasis by examining the clinicopathologic significance of immunophenotypes found in T1 colorectal carcinomas. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at a university hospital. PATIENTS: Included were 265 patients with T1 colorectal carcinoma who underwent radical surgery. INTERVENTIONS: Patients with T1 colorectal carcinoma were managed. MAIN OUTCOME MEASURES: Immunophenotypes were associated with various clinicopathologic parameters, and CD10 expression was strongly associated with lymph node metastasis. RESULTS: The levels of MUC2, MUC5AC, and CD10 expression were individually significantly associated with tumor location, growth pattern, histologic type, invasive potential, and metastatic potential. The incidence of lymph node metastasis was significantly associated with each of the 5 following parameters: depth of submucosal invasion (p = 0.005), tumor budding (p < 0.001), lymphatic invasion (p < 0.001), MUC2 expression (p = 0.006), and CD10 expression (p < 0.001). Multivariate analysis showed that CD10 expression (OR, 9.2 [95% CI, 2.5-39.8]; p = 0.001) and lymphatic invasion (OR, 6.3 [95% CI, 2.5-17.7]; p < 0.001) were independently associated with lymph node metastasis. LIMITATIONS: This study was limited by its small sample size, intraobserver variation attributed to immunohistochemical staining, and potential selection bias because surgically resected specimens were collected instead of endoscopically resected specimens. CONCLUSIONS: We suggest that CD10 expression is closely associated with lymph node metastasis in T1 colorectal carcinoma.

Pathological factors related to lymph node metastasis of submucosally invasive gastric cancer: criteria for additional gastrectomy after endoscopic resection.

BACKGROUND: There are currently no universally accepted indications and criteria for additional gastrectomy after endoscopic resection of submucosally invasive cancer. The purpose of the present study was to establish accurate indications and criteria for such additional gastrectomy on the basis of lymph node metastasis risk. METHODS: We investigated 130 submucosally invasive gastric cancers and analyzed the pathological risk factors for lymph node metastasis. The tumors were evaluated for pathological factors in the area of invasion, and factors were compared between the cases with lymph node metastasis and those without. RESULTS: Univariate logistic regression analysis showed that tumor minor axis length, depth of invasion, histological classification of the area of submucosal invasion, absence of lymphoid infiltration, ulceration or scar in the lesion, and lymphatic and venous invasion are statistically significant risk factors for lymph node metastasis. Multivariate logistic regression analysis showed that the absence of lymphoid infiltration and the presence of lymphatic invasion are statistically significant as risk factors for lymph node metastasis. CONCLUSIONS: We present a scoring system on the basis of the pathological criteria tested in this study. Our findings enable more accurate identification of patients who should undergo additional gastrectomy after endoscopic resection.

Outside fibroblasts play a key role in the development of inner neointima after the implantation of polytetrafluoroethylene grafts.

The neointima formation inside of polytetrafluoroethylene (PTFE) grafts may be associated with the migration of outside fibroblasts to the luminal surfaces. This study aimed to verify whether blockade of fibroblast migration can prevent neointima formation by testing two types of prosthetic vessels, the porous PTFE graft and the impermeable Grasil graft, respectively. After implantation of the PTFE graft in dogs, a time-dependent migration of outside fibroblasts to the luminal side occurred. Compared with the PTFE grafts, the total neointima formation in the Grasil grafts was significantly less. Although the neointima formation at the arterial or venous anastomotic regions did not significantly differ between the two grafts, the neointima at the middle region of the PTFE grafts was significantly evident than the Grasil grafts. The components of the renin­angiotensin system (RAS), such as angiotensin II and its receptor AT1, as well as the forming enzymes of the RAS (angiotensin-converting enzyme and chymase), were all detectable in the grafts' surrounding tissues. Neointima formation at the middle region of the prosthetic vessels could be suppressed almost completely by the blockade of outside fibroblast migration, indicating that outside fibroblasts play a key role in the formation of neointima in this region.

Multicystic mesothelioma caused by endometriosis: 2 case reports and review of the literature.

Multicystic mesothelioma was described as a benign neoplasm in most reports. But, whether it is neoplastic or reactive is still controversial. Although multicystic mesothelioma is often accompanied by endometriosis, histologic findings of the lesion with endometriosis have not been well documented. In this report, 2 cases of multicystic mesothelioma with endometriosis were studied histologically. The first lesion consisted of multiple cysts having thin walls lined with single-layered cuboidal mesothelia, and in the cystic walls, small foci of endometriosis were found. The second lesion was next to the endometriotic cysts in the pelvic space. These histologic findings suggest that endometriosis greatly contributes to the origin of the lesions. In addition, from the review of the literature, cystic mesothelioma was divided into 2 categories, that is, neoplastic or non-neoplastic lesions. Differentiation of both disorders might be possible by the following: size of the lesion, macroscopic and microscopic solid proliferation, features of adenomatoid tumor, and common mesothelioma-like histology. In conclusion, multicystic mesothelioma accompanied by endometriosis is thought to be a secondary non-neoplastic lesion induced by adhesion or inflammation rather than a neoplasm.

Hepatocellular carcinoma with right atrial tumor thrombus: report of a case.

Hepatocellular carcinoma (HCC) with a tumor thrombus (TT) extending into the right atrium is generally regarded as a terminal-stage condition. We report a case of long-term survival following treatment of this complication with en bloc hepatectomy and resection of the thrombus under cardiopulmonary bypass. Our review of 19 similar cases reported in the literature found the following: that lung metastasis, the most critical prognostic factor, occurred in only 5 (27.8%) patients; that postoperative survival ranged from 18 days to 56 months, with a median survival of 11 months; and that 7 (38.9%) patients showed no signs of recurrence, with 4 (21.1%) surviving longer than 2 years. Thus, to prevent sudden death and extend the survival of patients with HCC and TT extending into the right atrium, we advocate simultaneous en bloc resection performed under cardiopulmonary bypass, provided distant metastasis and recurrence in the remnant liver are controlled.

Transplantation of Graft Anti-Host Cytotoxic T Lymphocytes Along with Allogeneic Bone Marrow Skips Macrophage-Induced Graft-Versus-Host Disease.

Graft-versus-host disease (GVHD) is a physiological response of the graft to allogeneic hosts. However, the effector cells, affected organ(s), and cytokines in the GVHD remain controversially discussed, without having determined a particular cytotoxic activity of the graft against the host. After i.v. injection of C57BL/6 (H-2b) spleen cells into irradiated BDF1 (H-2b/d) mice, the hosts developed interferon-gamma (IFN-γ)-dependent bone marrow (BM) GVHD on days 5-17. When H-2DdKd transgenic H-2b lymphoma cells were i.p. inoculated into irradiated, H-2b splenocyte-transplanted H-2b/d mice, the infiltration of macrophages cytotoxic against H-2DdKd transgenic H-2b mouse skin epithelia (a GVHD activity) into the peritoneal cavity preceded several days the infiltration of interleukin (IL)-2-dependent cytotoxic T lymphocytes (CTLs) to achieve a graft-versus-leukemia (GVL) effect. In contrast, allogeneic BM transplanted alone into the irradiated mice did not induce GVHD for 44 days, whereas i.v. injection of graft anti-host macrophages or graft anti-host CTLs along with allogeneic BM, respectively, induced GVHD or promoted the GVL effect in the absence of GVHD. These results revealed that macrophage-induced GVHD and the CTL-mediated GVL effect were a set (Th1: IFN-γ/IL-2) response of the graft to allogeneic hosts and leukemia cells, respectively, and that graft T cell activation rather than inhibition skipped GVHD after BM transplantation.

Enhanced expression of the ubiquitin-proteasome system in the myocardium from patients with dilated cardiomyopathy referred for left ventriculoplasty: an immunohistochemical study with special reference to oxidative stress.

The ubiquitin (Ub)-proteasome system (UPS) is an important proteolytic mechanism for selecting and digesting cytotoxic proteins. The aim of this study is to elucidate expression and in situ localization of the UPS in the myocardium from patients with dilated cardiomyopathy (DCM) with refractory heart failure. The expression profile of the oxidative stress-induced cytotoxic proteins was also examined. Myocardium was obtained from 26 patients with DCM at the left ventriculoplasty. Ten normal autopsied hearts served as controls. Myocardial expressions of Ub and proteasomes were studied immunohistochemically. Oxidative stresses were examined in point of localization of the oxidation-induced modifier molecules (OMM). The relationship between immunohistochemical results and clinical parameters was also evaluated. Both Ub and proteasomes were stained positive in granular structures accumulating between the myofibrils and adjacent to nuclei in cardiomyocytes. The OMMs were also positive in the same Ub-positive granular structures. The area fraction of Ub, proteasomes and OMM was significantly higher in DCM hearts than in normal controls. Significant positive correlation was observed between the area fractions of Ub and plasma levels of brain natriuretic peptide (p = 0.046) in DCM hearts. In conclusion, enhanced expression of the UPS colocalized with OMM in cardiomyocytes may be involved in the pathophysiology of DCM hearts.

Cytologic findings of metastatic hepatocellular carcinoma of the nasal cavity: a report of 2 cases.

BACKGROUND: Hepatocellular carcinoma metastasizing to the nasal cavity is rare, but nasal bleeding caused by it is difficult to treat. The reason is that a large majority of patients have a bleeding tendency due to liver cirrhosis. Accordingly, early and correct diagnosis is essential. CASES: Case 1, a Japanese man in therapy for C type liver cirrhosis and hepatocellular carcinoma, was diagnosed as metastasis to the bones, and then he was admitted. After hospitalization, he complained of nasal obstruction. Fine needle aspiration biopsy from a tumor occupying nasal and maxillary cavities showed overlapped cells and scattered cells having a round to oval nucleus containing one or a few large nucleoli. The characteristics of cells indicated metastasis of hepatocellular carcinoma. In case 2, a Japanese man under treatment for liver cancer visited our hospital with a complaint of nasal obstruction. In fine needle aspiration biopsy from a mass in the right nasal cavity, cohesive clusters and sparse neoplastic cells similar to those observed in the first case were found. CONCLUSION: Aspiration cytology is useful in the diagnosis and treatment of hepatocellular carcinoma metastatic to the nasal cavity. Finding characteristic cells is important in the diagnosis. Clinical information is sure to be a convincing clue.

Clinicopathological analysis of recurrence patterns and prognostic factors for survival after hepatectomy for colorectal liver metastasis.

BACKGROUND: Hepatectomy is recommended as the most effective therapy for liver metastasis from colorectal cancer (CRCLM). It is crucial to elucidate the prognostic clinicopathological factors. METHODS: Eighty-three patients undergoing initial hepatectomy for CRCLM were retrospectively analyzed with respect to characteristics of primary colorectal and metastatic hepatic tumors, operation details and prognosis. RESULTS: The overall 5-year survival rate after initial hepatectomy for CRCLM was 57.5%, and the median survival time was 25 months. Univariate analysis clarified that the significant prognostic factors for poor survival were depth of primary colorectal cancer (≥ serosal invasion), hepatic resection margin (< 5 mm), presence of portal vein invasion of CRCLM, and the presence of intra- and extrahepatic recurrence. Multivariate analysis indicated the presence of intra- and extrahepatic recurrence as independent predictive factors for poor prognosis. Risk factors for intrahepatic recurrence were resection margin (< 5 mm) of CRCLM, while no risk factors for extrahepatic recurrence were noted. In the subgroup with synchronous CRCLM, the combination of surgery and adjuvant chemotherapy controlled intrahepatic recurrence and improved the prognosis significantly. CONCLUSIONS: Optimal surgical strategies in conjunction with effective chemotherapeutic regimens need to be established in patients with risk factors for recurrence and poor outcomes as listed above.

IFN-γ Control of an Effector/Target Combination for Skin Allograft Rejection: Macrophage/Skin Components in Normal Mice or T Cell/Endothelial Cells in IFN-γ-Deficient Mice.

Organ, skin, or cell allografts are acutely rejected from normal mice, whereas vascularized organ allografts, but not allografted Meth A cells, are rejected from interferon-γ (IFN-γ)-deficient mice. Here we explored effector/target combinations for i.p. allografted Meth A (cytotoxic T lymphocyte [CTL]-resistant) or RLmale1 (CTL-susceptible) cells into or for BALB/c skin (skin components: CTL resistant) onto normal or IFN-γ-deficient C57BL/6 mice. After allografting, normal mice showed more infiltration but only a little thrombosis/hemorrhage. Monocyte/macrophage MHC receptor (MMR)+ macrophages (on days 5-10) and T cell receptor (TCR)+ CTLs (on days 7-9) were cytotoxic against Meth A cells or skin components and RLmale1 cells, respectively, and the allografts were rejected. After allografting into IFN-γ-deficient mice, MMR- macrophages and highly activated TCR+ CTLs were induced, and the mice died of hemorrhagic ascites with Meth A cells and more acutely rejected RLmale1 cells. The CTLs on days 4-6 were inactive toward skin components at an in vivo effector/target ratio but injured endothelial cells to cause severe thrombosis/hemorrhage and more acute rejection of skin allografts. These results indicate that IFN-γ-dependent MMR expression was essential for macrophage-mediated cytolysis of allogeneic skin components and that IFN-γ-deficient mice more acutely rejected skin allograft by causing CTL-induced injury to endothelial cells.

Endometrial carcinoma with choriocarcinomatous differentiation: a case report and review of the literature.

BACKGROUND: Choriocarcinomas unrelated to pregnancy, teratomas, or germ cell tumors have been found in the stomach, lungs, colon, esophagus, bladder, breast, renal pelvis and other sites. CASE: We present a case of a 58-year-old woman with endometrial carcinoma with choriocarcinomatous differentiation. She received surgery and chemotherapy for endometrial adenocarcinoma. However, a metastatic tumor of choriocarcinomatous element appeared at the vaginal cuff 9 months after surgery. Additional chemotherapy for choriocarcinoma resulted in a decrease in the serum hCG and the tumor regressed. Fifty months following surgery, she is alive without disease. CONCLUSION: Treatment and follow-up must be performed not only for the adenocarcinoma element but also for the choriocarcinoma element in patients presenting with endometrial carcinoma with choriocarcinomatous differentiation.

Significance of chymase-dependent angiotensin II formation in the progression of human liver fibrosis.

AIM: Angiotensin II may contribute to liver fibrogenesis. In addition to angiotensin-converting enzyme (ACE), chymase, which is expressed by mast cells, is also known to be an angiotensin II-forming enzyme. However, it is unclear which of these two angiotensin II-forming enzymes plays a more important role in liver cirrhosis progression. In the present study, the role of angiotensin II-forming enzymes in the progression of liver cirrhosis was clarified. METHODS: A total of 77 patients (16 in F0 stage, 10 in F1 stage, 22 in F2 stage, 12 in F3 stage, and 17 in F4 stage) were classified according to the new Inuyama classification into a non-cirrhosis (F0) group, an early cirrhosis (F1 + F2) group, and a chronic cirrhosis (F3 + F4) group. RESULTS: Both chymase and total angiotensin II-forming activities were significantly higher in chronic cirrhosis patients than in the other two groups. However, there was nodifference among the three groups in ACE activity. On immunohistology, the number of chymase- and angiotensin II-positive cells was significantly higher in the chronic cirrhosis group than in the non-cirrhosis and early cirrhosis groups. There were significant correlations between the number of chymase-positive cells and the number of angiotensin II-positive cells, between the number of chymase-positive cells and the degree of fibrosis, and between the number of angiotensin II-positive cells and the degree of fibrosis. CONCLUSION: These results suggest that chymase-dependent angiotensin II formation may play an important role in hepatic fibrosis of patients with cirrhosis.

Detection of human epidermal growth factor receptor 2 protein and gene in fine needle aspiration cytology specimens and tissue sections from invasive breast cancer: can cytology specimens take the place of tissue sections?

Overexpression of HER2 protein and HER2 gene amplification in breast cancer are prognostic factors for the response to specific medical treatments such as trastuzumab, endocrine therapy, and chemotherapy. Whereas HER2 expression and gene amplification are generally examined in tissue sections, we investigated whether specimens from fine needle aspiration cytology (FNAC) are adequate for these analyses. HER2 protein overexpression and HER2 gene amplification were assessed in both FNAC specimens and tissue sections from 58 cases of invasive breast cancer. Immunohistochemistry assay for HER2 protein expression was performed according to the HercepTest protocol, and HER2 gene amplification was examined with the Spot-light CISH (chromogenic in situ hybridization) Detection kit. There was a significant positive correlation between assessments of HER2 protein status in the cytology specimens and tissue sections. The sensitivity, specificity, and accuracy of HER2 gene amplification detection in cytology specimens in relation to those in tissue sections were 84.0% (21/25 cases), 87.9% (29/33 cases), and 86.2% (50/58 cases), respectively. FNAC specimens are suitable for detection of HER2 overexpression and HER2 gene amplification in invasive breast cancer.

A case of primary ductal adenocarcinoma of the lacrimal gland: histopathological and immunohistochemical study.

We encountered primary ductal adenocarcinoma of the lacrimal gland in a 67-year-old Japanese man. To the best of our knowledge, only three cases of primary ductal adenocarcinoma of the lacrimal gland have been reported in the literature. The patient was admitted because of visual disturbance, and a mass measuring about 3 cm in diameter was revealed in the right orbit. The mass was resected, and primary ductal adenocarcinoma of the lacrimal gland was diagnosed histopathologically. He died from recurrence at the primary site and metastasis to the brain, lungs, liver, common bile duct, and pancreas 2 years and 10 months after surgery although adjunctive orbital radiotherapy was given. Immunohistochemically, the characteristics of cancer cells were similar to those of salivary duct carcinoma, namely positivity for cytokeratin (CK) 7, 10, 17, 18, 19, and 34betaE12, and negativity for CK20. It was not clear whether the ductal adenocarcinoma originated from the ductal or acinar epithelium of the lacrimal gland, because the immunohistochemical features of both epithelia were identical.

Role of mast cells in hepatic remodeling during cholestasis and its resolution: relevance to regulation of apoptosis.

BACKGROUND/AIMS: Mast cells are thought to be related to fibrogenesis, but recent studies have shown that fibrosis of the liver can be induced even in mast cell-deficient rats. To clarify the significance of mast cell accumulation in cholestatic liver diseases, the relations between such accumulation, bile ductule proliferation and apoptosis of biliary epithelial cells were examined in the rats during cholestasis and its resolution. METHODS: Cholestasis and its resolution were induced in rats by common bile duct ligation and spontaneous recanalization, respectively. The extent of bile ductule proliferation and the numbers of mast cells and apoptotic biliary epithelial cells were estimated quantitatively in liver sections. RESULTS: Recanalization of the ligated common bile duct led to an abrupt and transient increase in the number of mast cells, although the number of proliferated bile ductules decreased rapidly. The number of apoptotic biliary epithelial cells of the proliferated bile ductules increased rapidly and transiently, and the change paralleled that of the mast cells. CONCLUSIONS: Mast cells accumulating in the portal triads during cholestasis and its resolution may relate to the reduction of proliferated bile ductules, i.e., in hepatic remodeling, through the induction of apoptosis of biliary epithelial cells.

Blood supply--susceptible formation of melanin pigment in hair bulb melanocytes of mice.

BACKGROUND: Allogeneic skin grafts onto C57BL/6 mice are rejected, and the rejected skin is replaced by surrounding skin with black hair. In contrast, syngeneic skin grafts are tolerated, and gray hair grows on the grafts. METHODS: To explore the mechanism of gray hair growing on the tolerated skin grafts, we prepared full-thickness skin (2-cm square) autografts, 2 (2 cm + 2 cm) horizontal or vertical parallel incisions, and U-shaped (2 cm × 2 cm × 2 cm) flaps with or without pedicle vessels. The grafts, incisions, and flaps were fixed by suturing with string and protected by a transparent bandage. On day 14 after the operation, the bandages were removed to observe the color of the hair growing on the skin. RESULTS: Skin autografts from wild-type or hepatocyte growth factor-transgenic (Tg) C57BL/6 mice survived with gray hair, whereas those from steel factor (Kitl)-Tg C57BL/6 mice survived with black hair. In addition, U-shaped flaps lacking both of the 2 main feeding vessels of wild-type mice had gray hair at the tip of the flaps. Light microscopy after staining with hematoxylin and eosin or dihydroxyphenylalanine showed that the formation of melanin pigment in the follicles, but not in the interadnexal skin, was susceptible to the blood supply. CONCLUSIONS: Melanin pigment formation in the hair bulb melanocytes appeared to be susceptible to the blood supply, and melanocytosis was promoted in the follicles and in the epidermis of Kitl-Tg C57BL/6 mice.

Composite type of breast carcinoma with endocrine differentiation: a cytological and immunohistochemical study.

We describe a case of breast carcinoma with endocrine differentiation containing a mixture of three different histological features that occurred in a 71-year-old woman. Histologically, the tumor was predominantly intraductal, but slightly invasive. In the intraductal lesion, the tumor consisted mainly of ovoid to round cells with a modest to abundant amount of granular eosinophilic cytoplasm or intracytoplasmic mucin (mucin-producing carcinoma in situ). It also consisted, in part, of plump spindle cells with scant cytoplasm that contained argyrophilic granules in a trabecular pattern or an arrangement of perivascular pseudorosettes (atypical carcinoid tumor like-features). Mucous lake and tumor cells floating in mucin were seen in the invasive lesion (mucinous carcinoma). Immunohistochemical staining revealed endocrine differentiation of the tumor cells of both intraductal and invasive lesions. These findings suggest that the different histological features derived from pluripotent cells upon endocrine differentiation, and that endocrine differentiation of the tumor cells had already occurred at an earlier stage of carcinogenesis, prior to the appearance of the mucinous carcinoma. Cytologically, plasmacytoid tumor cells appeared in loosely cohesive clusters or as sparsely single cells in a background of a mucinous substance.

Cytokeratin-positive rib osteosarcoma metastasizing to the small intestine.

Osteosarcoma (OS) is a malignant tumor in which osteoid or bone is produced directly by tumor cells. Some OS cells are positive for cytokeratin (CK) and epithelial membrane antigen by immunohistochemistry (IHC) and this may lead to a misdiagnosis of metastatic carcinoma, particularly when the tumor location is unusual. On the other hand, gastrointestinal metastasis of OS is rare. We present the case of a 67-year-old Japanese man with a small intestinal intussusception due to metastasis of a CK-positive rib OS. The tumor cells were positive for CK, osteopontin and osteonectin by IHC and a diagnosis of a CK-positive chest wall OS metastasizing to the small intestine was considered. Osteoid or bone formation was histologically absent and therefore chest wall OS had to be differentially diagnosed from metastatic carcinoma of unknown origin. A postmortem histological analysis confirmed a rib OS. Awareness of CK-positive OS is important for making a correct diagnosis and for disease management and an immunohistochemical analysis of the tumor for expression of osteopontin and osteonectin may be used to support the diagnosis. In addition, this case shows that rib OS can metastasize to the gastrointestinal tract, albeit rarely, which may induce an intestinal intussusception.