Yoshinobu Hirose

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.

A case of IgG4-related lymphadenopathy, pericarditis, coronary artery periarteritis and luminal stenosis

Immunoglobulin G4 (IgG4)-related disease is an emerging new clinicopathological disorder that is characterized by elevation of serum IgG4 levels and histological findings of IgG4-positive plasmacytic infiltration. IgG4-related disease may appear synchronously or metachronously in a wide variety of organs. The current patient was found to have pericardial effusion and retroperitoneal fibrosis. He was subsequently diagnosed with coronary artery stenosis. 18F-FDG positron emission tomography showed enhanced FDG uptake in lymph nodes as well as pericardial and peri-aortic tissue. Histopathology of the mediastinal lymph node showed the infiltration of numerous IgG4-positive cells, leading to the diagnosis of IgG4-related lymphadenopathy with pericardial and periarterial involvement.

IgG4-positive cell infiltration in various cardiovascular disorders - results from histopathological analysis of surgical samples

BackgroundThe diagnosis of Immunoglobulin G4 (IgG4)-related disease (IgG4-RD), in general, depends on serum IgG4 concentrations and histopathological findings; therefore, diagnosis of IgG4-RD in cardiovascular organs/tissues is often difficult owing to the risk of tissue sampling.MethodsPrevalence of IgG4-positive lymphoplasmacytic infiltration in 103 consecutive cardiovascular surgical samples from 98 patients with various cardiovascular diseases was analyzed immunohistochemically.ResultsThe diagnoses of the enrolled patients included aortic aneurysm (abdominal, n = 8; thoracic, n = 9); aortic dissection (n = 20); aortic stenosis (n = 24), aortic regurgitation (n = 10), and mitral stenosis/regurgitation (n = 17). In total, 10 (9.7%) of the 103 specimens showed IgG4-positive cell infiltration with various intensities; five of these were aortic valve specimens from aortic stenosis, and IgG4-positive cell infiltration was present at >10 /HPF in three of them. In one aortic wall sample from an abdominal aortic aneurysm, various histopathological features of IgG4-RD, such as IgG4-positive cell infiltration, obliterating phlebitis, and storiform fibrosis, were observed.ConclusionsIgG4-positive cell infiltration was observed in 9.7% of the surgical cardiovascular specimens, mainly in the aortic valve from aortic stenosis and in the aortic wall from aortic aneurysm. Whether IgG4-positive cell infiltration has pathophysiological importance in the development or progression of cardiovascular diseases should be investigated in future studies.

Correlation of lanthanum dosage with lanthanum deposition in the gastroduodenal mucosa of dialysis patients

Lanthanum (La) deposition has been observed in gastrointestinal mucosa of dialysis patients treated with La carbonate to treat hyperphosphatemia in the 6 years since its authorization in Japan. We investigated gastrointestinal biopsies from 112 dialysis patients, and found 15 cases of histiocytic aggregation with crystalloids and one case of duodenitis with histiocyte aggregation without crystalloids in the 30 patients treated with La carbonate. No histiocytic lesions were observed in the 82 patients without La carbonate administration. So far in total 70 cases of La deposition in the alimentary tract have been reported, including our 16 cases. Neither clinical nor histological findings other than histiocytic aggregation were specific in the patients with La deposition. We also compared the groups with and without La deposition, revealing that the daily and total doses of La carbonate showed statistically significant correlations with La deposition. However the causality with their histologic features, e.g. intestinal metaplasia and degree of inflammation, were inconclusive between the two groups. Although no critical symptoms have been reported, it is necessary to accumulate more cases to clarify the mechanism of La deposition, because dialysis patients must take phosphate buffers for a long period.

Mitotically active cellular fibroma of the ovary: a case report and literature review

BackgroundThe ovarian cellular fibrous tumor with mitotic figure >4 per 10 high power field without moderate to severe atypia is defined as mitotically active cellular fibroma according to the 2014 World Health Organization classification. As this category is new and rare now, we described here a case of MACF and reviewed the literature.CaseWe present a case of mitotically active cellular fibroma of the ovary with 10-year history that was treated with laparoscopic surgery.MethodsWe reviewed the relevant literature using PubMed search system and analyzed the previous cases.ResultsTo date, only 5 cases of mitotically active cellular fibroma have been reported. Our patient is the first case of mitotically active cellular fibroma of the ovary treated with laparoscopic surgery.ConclusionMACF of the ovary is a newly defined category and few cases have been reported, while prognostic factors have also not yet been fully characterized. Long-term clinical follow-up is necessary.

Pathological findings of uterine tumors preoperatively diagnosed as red degeneration of leiomyoma by MRI

PurposeVenous infarction of a leiomyoma is known as red degeneration of leiomyoma (RDL) and can be a cause of acute abdomen. Although magnetic resonance imaging (MRI) is the only modality that can depict the inner condition of a leiomyoma, the typical MR findings of RDL are sometimes identified incidentally even in asymptomatic patients. The purpose of this study is to clarify common pathological findings of uterine tumors preoperatively diagnosed as RDL by MRI.MethodsWe diagnosed 28 cases of RDL by MRI from March 2007 to April 2015. The ten lesions subjected to pathological analysis after resection were included in the study and reviewed by a gynecological pathologist. The average time from MRI to operation was 4.7 months.ResultsThe typical beefy-red color was not observed on the cut surface of the tumor except in one tumor resected during the acute phase. All lesions diagnosed as RDL by MRI had common pathological findings consistent with red degeneration of leiomyoma, including coagulative necrosis. Other common pathological features of RDL besides extensive coagulative necrosis appear to be a lack of inflammatory cell infiltrate or hemorrhage in the entire lesion.ConclusionsAlthough RDL is known to cause acute abdomen, its typical MR findings can be observed even in asymptomatic patients in a condition that manifests long after red degeneration. The characteristic pathological findings in both the acute phase and the chronic phase that we found in this study, along with radiology reports, will be helpful references for gynecologists and pathologists in suspecting a history of red degeneration and confirming the diagnosis.

A clinicopathological study of parotid carcinoma: 18-year review of 171 patients at a single institution

BackgroundThis study investigated the clinical outcomes of patients with parotid carcinoma at a single institution during an 18-year period, with the focus on diagnosis, treatment, and survival.MethodsThe subjects were 171 patients with parotid carcinoma treated at our department during the 18-year period from September 1999 to August 2017. There were 19 patients in stage I, 65 patients in stage II, 22 patients in stage III, and 65 patients in stage IV. The symptoms, preoperative diagnosis, node metastasis, survival rate, prognostic factors, and immunohistological findings were investigated.ResultsPreoperative diagnosis of the histological grade by fine-needle aspiration cytology was only possible in 34% of the patients, while the histological grade was correctly determined by frozen section biopsy in 72%. The overall frequency of lymph node metastasis was 29%, with 59% in patients with high-grade carcinoma and only 6% in those with low-/intermediate-grade tumors. The disease-specific 5-year survival rate was 100% for patients in stage I, 95.2% in stage II, 70.4% in stage III, and 45.1% in stage IV. Multivariate analysis showed that the pathological grade was the most important prognostic factor. Immunohistological investigation showed patients with HER-2 or androgen receptor-positive tumors had a significantly worse prognosis.ConclusionsAlthough a high-grade tumor is the most important prognostic factor, preoperative diagnosis of the grade was not always accurate. Since advanced cancer has a poor prognosis with a limited response to surgery and radiation therapy, development of new treatment strategies, such as molecular-targeting therapies directed against HER-2 and AR, is required.

Two healthy females with fulminant hepatic failure caused by herpes simplex virus infection

A 55-year-old woman presented with the complaint of vulvodynia. Thirteen days before death, she consulted a clinic. However, the doctor couldn’t recognize the signs of herpes infection. The following day, she developed high fever and consulted the general hospital. Because of elevated liver enzymes, she was hospitalized. The laboratory data at admission were as follows:AST 1005 IU/mL (normal: 10–35 IU/mL), ALT 876 IU/mL (normal: 5–30 IU/mL), total bilirubin 8.9 mg/dL (normal: 0.2–1.2 mg/dL), creatinine 0.92 mg/dL (normal: 0.4– 0.8 mg/dL), and prothrombin time INR 2.16 (normal: 0.9–1.1). Being diagnosed as having acute liver failure, she was transferred to the Osaka Medical College Hospital seven days before she died. The laboratory data are shown in Table 1 in Panel 1. Serological tests for HBs antigen, HBc antibody, HCV antibody and total ANA were negative. After admission, she developed encephalopathy and hypotension. On day three after admission, many small vesicles appeared over the skin throughout the body, and the anti-HSV antibody titer was markedly elevated, so she was started on acyclovir. The following day, she complained of left flank pain and computed tomography revealed retroperitoneal hemorrhage. The blood pressure decreased to shock levels and she died. At autopsy, many small vesicles with erosions were found in the skin of the extremities (Fig. 1a). A giant hematoma was found under the left retroperitoneal space. The liver (1750 g) was red and swollen, and innumerable small yellowish-white necrotic areas were visualized (Fig. 1b). Histologically, almost the entire liver was necrotic and filled with blood (Fig. 2a). Cowdry A type of intranuclear inclusions was seen (Fig. 2b). Positive staining for anti HSV 1 antibody was found in the vagina, uterine cervix, esophagus, liver, spleen and adrenal glands.

Delta-like 3 is silenced by HBx via histone acetylation in HBV-associated HCCs

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. We previously showed that expression of Delta-like 3 (DLL3), a member of the family of Delta/Serrate/Lag2 ligands for the Notch receptor, is silenced by aberrant DNA methylation and that overexpression of DLL3 in an HCC cell line induces cellular apoptosis. However, how DLL3 expression is regulated during hepatocarcinogenesis is still unclear. Here, we show that silencing of DLL3 during hepatocarcinogenesis is closely related to viral infection, especially hepatitis B virus (HBV) infection (p = 0.005). HepG2.2.15 cells, which are stably transformed with the HBV genome, showed lower DLL3 expression than the parent cell line, HepG2 cells. Treatment with Hepatitis B virus X protein (HBx) small interfering RNA upregulated DLL3 expression in HepG2.2.15 cells, and overexpression of HBx in HepG2 cells downregulated DLL3 expression. Treatment of cells with a histone deacetylase inhibitor induced DLL3 expression in HepG2.2.15 cells. These data suggest that DLL3 expression is silenced during hepatocarcinogenesis in association with HBV infection via an epigenetic mechanism.

Hemorrhage of MRI and Immunohistochemical Panels Distinguish Secretory Carcinoma From Acinic Cell Carcinoma: Hemorrhage of MRI

Secretory carcinoma (SC, mammary analogue secretory carcinoma) is a salivary gland tumor with ETV6‐NTRK3 gene fusion, and its differential diagnosis includes acinic cell carcinoma (ACC). As hemorrhage is often seen in SC, we hypothesized that magnetic resonance imaging (MRI) and immunohistochemical analyses could distinguish SC from ACC.