IgG4-related plasma cell granuloma of the maxillary sinus: A report of 2 cases.

We report 2 rare cases of IgG4-related plasma cell granuloma of the maxillary sinus. Histologically, both lesions were characterized by severe lymphoplasmacytic infiltration. In 1 case, fibrous sclerosis and obliterative arteritis were observed. Immunohistochemical study demonstrated that IgG4-positive cells comprised more than 40% of the IgG-positive plasma cells. Moreover, the serum IgG4 level was elevated in both cases. A good responsiveness to steroid therapy has been seen in IgG4-related disease. From a therapeutic perspective, it is important to recognize IgG4-related plasma cell granuloma.

Spontaneous Hemothorax Caused by Pulmonary Micro-Venous Hemangioma.

Various etiologies of spontaneous hemothorax have been reported, though the cause remains unidentified in some patients despite an exploratory thoracotomy. We report on an 89-year-old man with spontaneous hemothorax resolved by partial resection of the lung using complete video-assisted thoracoscopic surgery. The histopathologic findings revealed a ruptured micro-venous hemangioma located just below the bleeding visceral pleura. To the best of our knowledge, this is the first report of spontaneous hemothorax caused by a pulmonary micro-venous hemangioma.

Atypical interfollicular hyperplasia of tonsils resembling mucosa-associated lymphoid tissue lymphoma: a clinicopathological, immunohistochemical study and epstein-barr virus findings in 12 cases.

This study attempted to clarify the clinicopathological and immunohistochemical findings and presence or absence of Epstein-Barr virus (EBV) in tonsillar atypical interfollicular hyperplasia (AIFH). A total of 597 consecutive specimens from tonsillectomies performed in Dokkyo University School of Medicine between 1999 and July 2013 were reexamined. Using formalin-fixed, paraffin-embedded sections, histological and immunohistochemical analyses, and in situ hybridization (ISH) were performed. AIFH was identified in the tonsils in 12 (2.0%) cases. These included 7 males and 5 females, aged 3 to 19 years (mean, 7). Histologically, there was expansion of the interfollicular areas by polymorphous infiltration resulting in distortion, but not obliteration of the normal tonsillar architecture. In some areas, the lymphoid follicles had hyperplastic germinal centers with ill-defined borders surrounded by sheet-like proliferation of polymorphous infiltrate showing a marginal zone distribution pattern. The infiltrate was composed of small to medium-sized (transformed) lymphocytes and immunoblasts accompanied by numerous plasma cells and plasmacytoid cells, and resembling monocytoid B cells. The numerous immunoblasts were MUM1(+), CD10(-), BCL-6(-). An ISH study demonstrated EBV-encoded small RNA-1 (EBER-1)(+) cells in 9 lesions. Moreover, in 3 lesions, numerous EBER-1(+) cells were present in germinal centers as well as in interfollicular areas. The present study indicated that EBV may cause at least a portion of tonsillar AIFH in children and adolescents. In conclusion, an atypical lymphoid infiltration resulting in distortion of tonsillar architecture with numerous MUM1(+), CD10(-), BCL-6(-) immunoblasts should raise the suspicion of a reactive process.

Successful Laparoscopic Resection of 7 mm Ovarian Mature Cystic Teratoma Associated with Anti-NMDAR Encephalitis.

Anti-NMDAR (N-methyl-D-aspartate receptor) encephalitis is an immune-mediated encephalitis. It has been predominantly described in young women and is commonly associated with an ovarian teratoma. We report a case of anti-NMDAR encephalitis associated with a 7 mm ovarian teratoma that was completely resected by laparoscopic surgery. An 18-year-old woman suddenly presented with personality changes requiring her admission to the department of neurology. After that, she also showed involuntary movements, disturbance of consciousness, and central hypoventilation. As an abdominal image revealed the possibility of a right ovarian teratoma of 5 × 7 mm, a laparoscopic operation was performed. The macroscopic appearance of the right ovary did not show any abnormalities; nevertheless, we performed a partial resection of the right ovary, with reference to the image diagnosis, in order to spare the ovarian reserve. The 22 × 22 mm partially resected ovary contained an intact 5 × 7 mm cystic tumor. The pathological diagnosis was mature cystic teratoma with components of brain tissue. An anti-NMDAR-antibody test proved positive in both serum and cerebrospinal fluid 1 month after the surgery. From these results, she was diagnosed with anti-NMDAR encephalitis. By the administration of cyclophosphamide in addition to the operation, she recovered drastically without any of the symptoms shown before.

Neurenteric cysts found on the outer membrane of a subdural haematoma.

We report on a patient initially diagnosed with a chronic subdural haematoma that was resistant to treatment. After the second burr hole craniostomy within a half month failed to resolve the subdural haematoma (SDH), we performed a craniotomy to identify the point of bleeding. Macroscopic evaluation showed that most of the outer membrane of the SDH was transparent; however, further examination revealed the presence of multiple white regions. Pathologic examination showed that the white regions were fluid filled and surrounded by columnar ciliated epithelial cells. These lesions were pathologically diagnosed as neurenteric cysts. To our knowledge, this is the first report on a patient with neurenteric cysts found on the outer membrane of a CSDH. We agree that a craniotomy is a treatment of last resort for recurrent CSDHs; however, sometimes this procedure can be very useful for identifying underlying causes of obstinate SDHs as well as for their treatment.

Characterisation of apoptosis in myb-transformed hematopoietic cell (MTHC-A) lines: TNF-α-induced apoptosis and prevention by cAMP.

Myb-transformed haematopoietic cell (MTHC) lines have been developed and clones selected based on their ability to respond to tumor necrosis factor (TNF)-α. MTHC-A cells underwent apoptosis in response to TNF-α (MTHC-A). The apoptotic effect of TNF-α in MTHC-A was mimicked by a specific inhibitor of protein kinase A (PKI 5-24) and by the tyrosine kinase inhibitor genistein, suggesting that phosphorylation of tyrosine and PKA activity were important in protecting MTHC from apoptosis. Agents that elevate intracellular levels of cAMP, e.g. cholera toxin and dibuteryl cAMP, protected MTHC-A from the apoptotic effects of TNF-α, and also reduced the apoptotic effects of PKI and genistein. MTHC-A thus provides a useful model for investigating the role of TNF-mediated apoptosis in regulation of the myeloid lineage of cells.

Late-phase inflammatory response as a feature of in-stent restenosis after drug-eluting stent implantation.

OBJECTIVES: The aim of this study was to compare pathological features among in-stent restenosis lesions after drug-eluting stent (DES) placement, those after bare metal stent (BMS) placement, and de-novo atherosclerotic lesions. BACKGROUND: Restenosis after stenting is an over-reaction of the wound-healing response after vascular injury, which is characterized by a sequence of inflammation, granulation, extracellular matrix remodeling, and smooth muscle cell proliferation and migration. Recent advances in DES technology could considerably succeed in inhibiting this sequence of events. Thus, we hypothesized that the mechanism of in-stent restenosis after DES stenting might be different from that after BMS stenting as well as atherosclerosis. METHODS: Tissues obtained by directional atherectomy (DES: seven specimens, BMS: 17 specimens, and de-novo: 15 specimens) were immunostained for T lymphocytes (CD45), macrophages (CD68), smooth muscle cells (α-smooth muscle actin), endothelial cells (von Willebrand factor), and activated platelets (P-selectin). RESULTS: The accumulation of T lymphocytes tended to increase and that of macrophages increased significantly in the DES lesions compared with BMS lesions. No significant differences were observed for the other parameters evaluated. CONCLUSION: Pathological features of restenotic tissues after DES implantation showed a stronger inflammatory response compared with those after BMS implantation. Thus, the mechanism of restenosis after DES implantation may be different from that observed after BMS implantation.

L-type amino acid transporter 1 expression is highly correlated with Gleason score in prostate cancer.

Upregulation of L-type amino acid transporter 1 (LAT1), a member of the system L amino acid transporter family, may be detected by immunohistochemical methods. Immunoreactive LAT1 expression in prostate cancer is considered to be a promising biomarker for high-grade malignancy. However, the mutual association between LAT1 and Gleason score, the most fixed indicator for grading the malignancy of prostate cancers, remains to be elucidated. The aim of this study was to clarify the correlations between LAT1 and other factors in prostate cancer, including the Gleason score. We evaluated 54 cases of primary prostate cancer, surgically resected without any neoadjuvant therapies and performed immunohistochemistry for LAT1, Ki-67, CD34 and vascular endothelial growth factor on the tissue sections. The Gleason score as well as the age, pathological stage (pStage) of prostate cancer and serum concentration of prostate-specific antigen (PSA) of each case were also assessed. Statistical analysis for the correlations between LAT1 expression and Gleason score and each of the other characteristics studied was performed. As a result, a strong significant correlation between immuno-reactive LAT1 expression and Gleason score was identified (P<0.01). We concluded that immunoreactive LAT1 expression in tissue sections of prostate cancer may be useful as a biomarker for high-grade malignancy.

Epithelioid cell granulomatous response of Waldeyer's ring among Japanese : a clinicopathological and immunohistochemical study of 16 cases.

The tonsils are uncommonly affected by granulomatous inflammation. This study attempted to clarify the clinicopathological and immunohistochemical findings and presence or absence of Epstein-Barr virus (EBV) in tonsilar granulomatous inflammation. A total of 537 consecutive specimens from tonsillectomies performed at Dokkyo University School of Medicine between 1999 and March 2012 were reexamined. Using formalin-fixed, paraffin-embedded sections, histological, immunohistochemical, and in situ hybridization (ISH) studies were performed. Epithelioid granulomas (EPGs) were identified in the tonsils in 16 (3.0%) cases. There were 8 males and 8 females, aged 4 to 57 years (mean, 23). In 11 patients, EPGs were located in the germinal center (GC), whereas they were located in the interfollicular area as well as GC in the remaining 5 cases. Three types of EPG have been delineated : (i) poorly demarcated small epithelioid cell granulomas (n = 6) ; (ii) well-demarcated non-caseating sarcoid-like granulomas (n = 5) ; and (iii) EPGs within GC showing suppurations at the center (n = 5). An ISH study demonstrated EBV-encoded small RNA (EBER)(+) cells in 4 lesions. The present study demonstrated that the majority of EPGs were located in the GC and tonsilar EPGs showed histological variation.

Inflammation and impaired wound healing after zotarolimus-eluting stent implantation.

An 86-year-old man died suddenly 5 months after implantation of a zotarolimus-eluting stent. Two zotarolimus-eluting stents were placed to treat a highly calcified diffuse lesion in the proximal-to-mid right coronary artery. The lesion was fully covered by the two stents, and intravascular ultrasound showed complete stent apposition. However, an X-ray at autopsy showed that the proximal stent was fractured. Although we thought that thrombotic occlusion at the fracture site might have caused his sudden death, no thrombus was present. In addition, in the other sites where the stents were optimally dilated, there was stent malapposition and peri-strut inflammation including macrophage infiltration, giant cells, polymer phagocytosis, and neovascularization in the neointima. Even with a second-generation drug-eluting stent, such as the zotarolimus-eluting stent, wound healing may be impaired at the stent-injured vessel site.

Pathological features of in-stent restenosis after sirolimus-eluting stent versus bare metal stent placement.

A 70-year-old man developed diffuse restenosis in the right coronary artery, in which a bare metal stent (BMS) and two sirolimus-eluting stents (SES) were deployed sequentially. He underwent directional coronary atherectomy (DCA) for in-stent restenosis (ISR) lesions 13 months after both BMS and SES stenting. Further 4 months later, that is, 17 months after stent implantation, however, ISR recurred just at the SES site alone. Then we performed second DCA for the ISR lesion at SES site. The tissue materials obtained from debulking were compared histologically. In the first DCA specimen, accumulation of inflammatory cells such as T lymphocytes and macrophages was observed densely in ISR lesions at SES site but not in those at BMS site, and endothelial coverage was absent in ISR lesions at SES site but present in those at BMS site. In the second DCA specimen, ISR lesions at SES site showed less inflammatory cells, compared with first DCA specimen. ISR lesions after drug-eluting stenting showed persistent signs of delayed or incomplete wound healing and relapsed inflammation, compared with BMS. Thus, the mechanism of restenosis after drug-eluting stenting may be different from that after BMS placement.

In situ follicular lymphoma associated with progressive transformation of germinal centers.

The authors report here a case of in situ follicular lymphoma (FL) associated with progressive transformation of the germinal center (PTGC). A 39-year-old Japanese male developed a mass in the right cervical region. Biopsy of the enlarged lymph node led to a diagnosis of PTGC. Then, 5 years later, the lymphadenopathy recurred. The second biopsy specimens contained numerous germinal centers, including PTGC. Although most follicles were cytologically reactive, a few GCs appeared to be somewhat monotonous, composed predominantly of centrocytes and lacking mitotic figures and tangible body macrophages. Immunohistochemical studies demonstrated that these atypical GCs were CD10+, CD20+, and bcl-2+, with λ-light-chain restriction. A previous report emphasized the differential diagnostic problem between PTGC and the floral variant of FL. However, the present case indicated that in situ FL should be added to the list of differential diagnoses for PTGC.