Ayako Horita

Pulmonary tumor thrombotic microangiopathy caused by an ovarian cancer expressing tissue factor and vascular endothelial growth factor

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare clinicopathologic entity causing severe pulmonary hypertension, right-side heart failure, and sudden death. Its histologic features include widespread tumor emboli of the small arteries and arterioles of the lung, associated with thrombus formation and fibrocellular and fibromuscular intimal proliferation. The most frequent causative neoplasm for PTTM is gastric cancer, but lesions in other organs, including the ovary, have been occasionally identified as primary causes. Detailed molecular mechanisms underlying PTTM remain unclear, but some studies have suggested that tissue factor (TF) and vascular endothelial growth factor (VEGF) expressed by tumor cells may be involved in the pathogenesis for cases of gastric cancer. However, little is known about these molecules in PTTM caused by neoplasms of non-gastric origin. Here, we report the autopsy findings of a 42-year-old woman with ovarian cancer showing positive immunoreactivity for both TF and VEGF who died suddenly of PTTM. The present case provides support for the conclusion that these factors may be involved in the pathogenesis of PTTM, independent of the causal neoplasm.

Immunohistochemical Characteristics of Atypical Polypoid Adenomyoma With Special Reference to h-caldesmon

Atypical polypoid adenomyoma (APA) is a relatively rare benign uterine tumor, histologically characterized by proliferation of irregular endometrioid glands accompanied by stromal cells of smooth muscle origin. As the epithelial components of APA usually show cytological atypia, a differential diagnosis between this tumor and endometrioid carcinoma invading myometrium is often difficult, especially in curettage material. This distinction is clinically very important to avoid unnecessary hysterectomy. However, only a few immunohistochemical studies of APA that differentiate it from malignancy have been published. Therefore, we have investigated the expression of several antigens in APA and compared them with those present in myoinvasive carcinoma. Six specimens of APA were studied, along with controls of endometrioid carcinoma invading myometrium. Antibodies to p53, Ki-67, CD10, and h-caldesmon reacted positively using immunohistochemistry. Variable positive expressions of p53 and Ki-67 were observed in both epithelial and stromal components of APA, and in myoinvasive endometrioid carcinoma. CD10 was negative or partially and weakly positive whereas h-caldesmon was completely negative in the stromal cells of all 6 specimens of APA. However, in the myometrium in which endometrioid carcinoma invaded, a fringe-like positive staining pattern was occasionally observed for CD10, whereas a diffuse positive signal was obtained for h-caldesmon. The results of this study indicate that immunohistochemically, p53, and Ki-67 are not reliable markers but that h-caldesmon is useful in distinguishing APA from myoinvasive endometrioid carcinoma. Further, our data suggest that the stromal cells of APA are mainly immature smooth muscle cells, and thus APA may be a mixed tumor.

Properties of L-type amino acid transporter 1 in epidermal ovarian cancer.

Hypothesis: To investigate the expression and the functional properties of L-type amino acid transporter 1 (LAT1) in human epithelial ovarian cancer to provide a basis for potential new therapies to control the growth and the metastasis of ovarian cancer. Methods: The material used comprised 63 surgically resected specimens obtained from female patients undergoing gynecologic surgery at Kyorin University School of Medicine (Tokyo, Japan). The expression of LAT1 in 53 cases of ovarian cancers was determined by Western blot and immunohistochemical staining, and results were compared with those of normal ovarian tissues (5 cases) and benign ovarian tumors (5 cases). Furthermore, we examined the effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), the classic inhibitor of system L on the survival, the migration, and the uptake of l-leucine by human epithelial ovarian cancer cell line (OVCAR-3). Results: The LAT1 was significantly up-regulated in various human epithelial ovarian cancers that was localized predominantly on their plasma membrane and in the plasma membrane of the ovarian cancer cell line in conjunction with 4F2hc via disulfide bonds. The BCH inhibited the proliferation and the migration of the OVCAR-3 cells and the uptake of [14C]l-leucine by these cells in a dose-dependent manner. The OVCAR-3 cells did not express LAT2, and the uptake of [14C]l-leucine by these cells was Na+-independent and almost completely inhibited by BCH. Thus, our findings indicated that most l-leucine uptake in OVCAR-3 cells was mediated by LAT1. Conclusions: The LAT1 plays significant roles in nutrition, proliferation, and migration of ovarian cancer. Then, LAT1 inhibition would be useful for anticancer therapy in suppressing tumor growth without affecting normal tissues.

Fatal Complication of Legionella pneumophila Pneumonia in a Tocilizumab-treated Rheumatoid Arthritis Patient

We herein report a fatal case of Legionella pneumophila pneumonia in a tocilizumab-treated rheumatoid arthritis patient who was in a state of shock on admission but remained afebrile even during severe pneumonia. Legionella antigen was detected in the urine and neutrophil CD64 expression was highly elevated. Despite undergoing intensive treatment, the patient developed sepsis and died 12 days after admission. An autopsy indicated that while the Legionella infection had almost been controlled, a subarachnoid hemorrhage was the ultimate cause of death.

Immaturity of smooth muscle cells in the neointima is associated with acute coronary syndrome.

BACKGROUND Acute coronary syndrome (ACS) is mostly caused by ruptured plaques. The characteristics of rupture-prone vulnerable plaques include thin fibrous cap, large lipid core, and lower number of smooth muscle cells. Smooth muscle cells appearing in neointimal plaques are currently thought to have a uniformly synthetic phenotype, and their sub-classification has not been performed by h-caldesmon, which is supposed to be expressed in vascular smooth muscle cells that are beyond intermediately differentiated. METHODS Stenotic coronary arteries were obtained from autopsy material of 51 adults. Cases were divided into three groups: those who died from ACS, those with a past history of ACS but died from other causes, and those without ACS history. Histological data including fibrous cap and lipid core were measured in each specimen. Immunohistochemistry for alpha-smooth muscle actin (α-SMA), h-caldesmon, and smoothelin was performed. The ratio of h-caldesmon(+) cells to α-SMA(+) cells was counted in the neointima. RESULTS The positivity ratio of neointimal h-caldesmon decreased in a step-wise manner from cases without history of ACS through cases with past history of ACS to cases with ACS with statistical significance (P<.001). The correlation between h-caldesmon expression and progression of ACS among the different groups was more prominent than the differences in the extent of fibrous cap and lipid core. Smoothelin(+) cells were rarely observed in the neointima. CONCLUSIONS Decreased positivity of h-caldesmon in neointimal smooth muscle cells is indicative of a more immature phenotype, thus may be associated with plaque vulnerability that will promote ACS.

Sporadic osteogenesis imperfecta type V in an 11-year-old Japanese girl

We report a sporadic case of osteogenesis imperfecta (OI) type V with hyperplastic callus (HPC) formation in an 11-year-old Japanese girl. OI, commonly known as brittle bone disease, is a rare connective tissue disorder characterized by bone fragility and low bone mass. At present, OI can be classifi ed into at least eight types, designated types I–VIII, based on clinical features and specifi c gene mutations. OI type V is a rare form that represents 4%–5% of all OI cases and is characterized by HPC. All patients with HPC have OI type V. Increasing evidence suggests that OI type V shows an autosomal-dominant pattern of inheritance with unknown associated mutations. To date in the English-language literature, fewer than 90 OI patients with HPC formation have been reported, including 30 without a familial background of OI. Only three Japanese cases consistent with OI type V have been described in two detailed reports. Each patient had a family history of OI, and no Japanese cases of OI type V without a familial background has previously been documented. To the best of our knowledge, the present report represents the fi rst description of sporadic OI type V in a Japanese patient.

Aortic intramural hematoma associated with metastatic carcinoma

We present a case of aortic intramural hematoma, a variant of aortic dissection, with metastatic carcinoma invasion within the aortic wall and pseudolumen. An elderly male patient with a history of controlled hypertension initially experienced chest pain. A computed tomographic scan revealed aortic intramural hematoma; thus, conservative therapy was performed. One and a half months later, tumors in both adrenal glands and the lumbar vertebra were discovered. The primary site was not identified, and the patient died following septic shock 1 month later. An autopsy revealed intramural hematoma throughout the aorta, as well as systemic metastases of adrenocortical carcinoma with invasion into the aortic wall and formation of a pseudolumen accompanied by disruption of the vasa vasorum. As far as we know, this is the second case of aortic dissection associated with metastatic carcinoma. The highly aggressive nature of the tumor cells was demonstrated by high mitotic ratio and Ki-67 labeling index. The tumor was also positive for matrix metalloproteinase-12, thus suggesting disruption of the aortic media.