A case of anaplastic lymphoma kinase (ALK)-positive ciliated muconodular papillary tumor (CMPT) of the lung.

Ciliated muconodular papillary tumor (CMPT) is a rare papillary tumor that arises in the peripheral lung fields and is associated with the proliferation of ciliate d and goblet cells and increased mucin production. We report a case of CMPT involving the rearrangement of the anaplastic lymphoma kinase (ALK) gene. The patient was an 84-year-old Japanese female who had exhibited a small nodular shadow on chest computed tomography during a regular checkup 10 years ago. She underwent a partial resection of segment S10 of the right lung. The cut surface of the surgical specimen revealed a well-circumscribed, jelly-like mass measuring 8 × 8 × 10 mm. Histologically, the tumor was composed of a mixture of ciliated, goblet, and basal cells arranged in a papillary pattern together with pools of mucin. A diagnosis of CMPT was made. The lung tumor cells were subjected to fluorescent in situ hybridization and highly sensitive immunohistochemical staining for the ALK protein, both of which produced positive results. CMPT usually follows a favorable course, but the exact nature of this tumor; i.e., whether it is benign or malignant, has not been established. This is the first reported case of an ALK-positive CMPT.

Epithelioid trophoblastic tumor of the uterus: A case report with radiologic-pathologic correlation.

Herein, we report a rare case of an epithelioid trophoblastic tumor of the uterus with radiologic-pathologic correlation in a 56-year-old postmenopausal woman. On T2-weighted magnetic resonance (MR) imaging, the tumor appeared as a hypointense irregular mass compared with the surrounding myometrium of the uterine corpus and encircled the cavity of the lower uterine segment. On dynamic contrast-enhanced MR images, the tumor appeared as a hypovascular mass and an inhomogeneously hyperintense mass in the delayed phase. In addition, non-contrast computed tomography images showed some spotty areas of very high density within the tumor. These radiologic findings were well correlated with the histological features, such as abundant hyalinization and calcification within the tumor. Accurate interpretation of MR and computed tomography findings was helpful to differentiate epithelioid trophoblastic tumor from other gestational trophoblastic diseases and uterine carcinomas.

Clinico-Radiological Characteristics and Pathological Diagnosis of Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage.

OBJECTIVE: We aim to clarify the clinico-radiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage and to investigate the efficacy of pathological diagnosis using biopsy specimens. METHOD: We retrospectively reviewed 253 consecutive patients with cortico-subcortical hemorrhage who had been admitted to Aizawa Hospital between January 2006 and July 2013. We had performed craniotomy and hematoma evacuation in 48 patients, as well as biopsy of the evacuated hematoma, cerebral parenchyma adjacent to the hematoma, or both, and they were classified according to the histological results (positive or negative for vascular amyloid deposition) and to the Boston criteria. We compared the clinico-radiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage. We also investigated the detection rate of cerebral amyloid angiopathy with respect to the origins of the specimens. RESULTS: Pathological examination revealed that 22 subjects were positive for vascular amyloid. The number of the cerebral microbleeds located in the deep or infratentorial region was significantly larger in the negative group than in the positive group (P <.05). There was no significant difference in the distribution of lobar cerebral microbleeds and in the prevalence of hypertension. In the probable cerebral amyloid angiopathy-related intracerebral hemorrhage patients, the probability of having vascular amyloid detected by biopsy of both hematoma and parenchyma was 100%. Rebleeding in the postoperative periods was observed in 2 cases (9.1%) of the positive group. CONCLUSIONS: Our results demonstrate the importance and safety of biopsy simultaneously performed with hematoma evacuation. Deep or infratentorial microbleeds are less correlated with cerebral amyloid angiopathy-related intracerebral hemorrhage than with noncerebral amyloid angiopathy-related intracerebral hemorrhage.

Decreased expression of gastric gland mucin-specific glycan α1,4-linked N-acetylglucosamine on its scaffold mucin 6 is associated with malignant potential of pyloric gland adenoma of the stomach.

AIMS: Pyloric gland adenoma (PGA) is a unique gastric neoplasm expressing mucin 6 (MUC6), and is often associated with high-grade dysplasia and/or adenocarcinoma. MUC6 secreted from the gastric gland mucous cells, such as pyloric gland cells, carries unique O-glycans with terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues on its molecule. As we recently demonstrated that αGlcNAc serves as a tumour suppressor for gastric adenocarcinoma, this study aimed to investigate the significance of αGlcNAc expression in PGA. METHODS AND RESULTS: Eighteen patients with PGA were examined with immunohistochemistry for αGlcNAc and MUC6. αGlcNAc and MUC6 were coexpressed in 12 of 18 PGAs. However, reduced αGlcNAc expression relative to MUC6 expression was observed in six cases. When the MIB-1 labelling index (LI) of tumour cells was examined with respect to reduced αGlcNAc expression, the MIB-1 LI was significantly higher in PGAs showing decreased αGlcNAc expression relative to MUC6 expression than in PGAs with unchanged αGlcNAc expression (P = 0.023). CONCLUSIONS: The present study indicates that coexpression of αGlcNAc and MUC6 in PGA suggests the presence of fully glycosylated MUC6 on tumour cells, consistent with pyloric gland differentiation. However, the decreased glycosylation of αGlcNAc on MUC6 is associated with high mitotic activity of tumour cells, indicative of malignant potential of PGA.

Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach.

Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. Previously, we generated A4gnt-deficient mice, which totally lack αGlcNAc, and showed that αGlcNAc functions as a tumor suppressor for gastric cancer. Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. The αGlcNAc loss was evaluated in MUC6-positive gastric carcinoma. Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. Expression of MUC6 was also significantly correlated with several clinicopathological variables in differentiated-type adenocarcinoma. However, unlike the case with αGlcNAc, its expression showed no correlation with cancer-specific survival in patients. In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma.

Endomyocardial biopsy in a patient with hemorrhagic pheochromocytoma presenting as inverted Takotsubo cardiomyopathy.

A 29-year-old female patient presented with shock and dyspnea due to heart failure and pulmonary edema. Echocardiography indicated excessive contraction limited to the left ventricular apex and akinesis of the basal and middle ventricle, which were confirmed by emergency left ventriculography. The finding was diagnostic of inverted Takotsubo cardiomyopathy. An abdominal computed tomography scan showed a tumor in the left adrenal gland with a central low-density area, and the plasma and urinary catecholamines were strikingly elevated. Taken together, these findings suggested the presence of a hemorrhagic pheochromocytoma. A myocardial biopsy in the very acute stage on the day of admission revealed neutrophilic infiltration and contraction-band necrosis, which was indistinguishable from the previously reported pathology in the acute phase of idiopathic Takotsubo cardiomyopathy without pheochromocytoma. The diagnosis of pheochromocytoma in this case was confirmed 7 weeks later by surgical removal of the left adrenal gland with massive hemorrhage at the center of the pheochromocytoma. The marked similarity of the endomyocardial pathology between this case and cases with idiopathic Takotsubo cardiomyopathy strongly points to catecholamine excess as a common causality for Takotsubo cardiomyopathy with or without pheochromocytoma.

A rare case of an enterochromaffin-like neuroendocrine tumor associated with parietal cell dysfunction treated using endoscopic submucosal dissection.

Most gastric neuroendocrine tumors (NETs) develop from enterochromaffin-like (ECL) cells. ECL-cell NETs are classically categorized into three types according to their etiology. A 50-year-old woman presented with submucosal tumor-like lesions in the stomach, which were identified via esophagogastroduodenoscopy. Although esophagogastroduodenoscopy and pathological findings of biopsy specimens showed an absence of mucosal atrophy in the body of the stomach, sticky, adherent, dense mucus was observed. All lesions were diagnosed as ECL-cell NETs based on histological examination findings; however, ECL-cell NETs did not apply to any of the classic types I-III categorization based on laboratory, computed tomography, and 24-h intragastric pH monitoring test findings. Endoscopic submucosal dissection of the tumor was performed. Pathological findings of the excised specimen indicated that parietal cell hyperplasia with a protrusion, dilated fundic glands, and endocrine cell hyperplasia in the background mucosa, and parietal cells were not immunostained for the α-subunits of H+/K+-ATPase. Genetic analysis identified mutation in the ATP4A gene. The patient opted for additional gastric resection due to the risk of lymph node metastasis with deeper submucosal invasion and vascular infiltration. This report describes the first case of ECL-cell NETs caused by parietal cell dysfunction, which was treated via endoscopic submucosal dissection.

Multi-institutional validation of a modified scheme for subcategorizing salivary gland neoplasm of uncertain malignant potential (SUMP).

BACKGROUND: The salivary gland neoplasm of uncertain malignant potential (SUMP) category in the Milan System is diagnostically challenging. This study aims to validate a modified scheme for subcategorizing SUMP in a large multi-institutional cohort. METHODS: Retrospective review of salivary gland fine-needle aspirations (FNAs) from 10 institutions were classified based on the Milan System. Cases diagnosed as SUMP with available cytology slides and surgical follow-up were retrieved for review and subcategorized based on a modified scheme as follows: basaloid SUMP (B1: absent/scant nonfibrillary matrix; B2: presence of nonfibrillary/mixed-type matrix), oncocytic/oncocytoid SUMP (O1: with mucinous background; O2: without mucinous background), and SUMP not otherwise specified (NOS). RESULTS: A total of 742 (7.5%) cases from 9938 consecutive salivary gland FNAs were classified as SUMP. Among them, 525 (70.8%) had surgical follow-up and 329 (62.7%) were available for review. The overall risk of malignancy (ROM) of SUMP was 40.4%. There were 156 cases (47.4%) subcategorized as basaloid SUMP with a ROM of 36.5%, 101 (30.7%) as oncocytic/oncocytoid SUMP with a ROM of 52.5%, and 72 (21.9%) as SUMP NOS with a ROM of 31.9%. The ROM of oncocytic/oncocytoid SUMP was significantly higher than basaloid SUMP (P = .0142) and SUMP NOS (P = .0084). No significant differences in ROM were noted between B1 and B2 (36.7% vs 36.4%, P = 1.0000) and O1 and O2 (65.2% vs 48.7%, P = .2349). CONCLUSIONS: The ROM of oncocytic/oncocytoid SUMP was 52.5% and significantly higher than that of basaloid SUMP (36.5%, P = .0142) and SUMP NOS (31.9%, P = .0084), whereas no significant differences in ROM were noted for cases with different types of extracellular matrix or background material.

A multi-institutional study of salivary gland cytopathology: Application of the Milan System for Reporting Salivary Gland Cytopathology in Japan.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a risk-stratification reporting system that was introduced in 2018. The objective of this multi-institutional study was to evaluate the utility of the MSRSGC in Japan. METHODS: In total, 1608 fine-needle aspiration samples with matching histologic diagnoses were retrieved from 12 large institutions in Japan. The diagnostic categories of the MSRSGC were assigned prospectively or retrospectively, and the results were compared with the histologic diagnoses. RESULTS: The cases were classified as follows: nondiagnostic, 18.1%; non-neoplastic, 4.1%; atypia of undetermined significance, 11.5%; neoplasm-benign, 43.7%; salivary gland neoplasm of uncertain malignant potential, 9.6%; suspicious for malignancy, 3.6%; and malignant, 9.4%. The risk of neoplasm and the risk of malignancy in each MSRSGC category were as follows: nondiagnostic, 72.9% and 13.4%, respectively; non-neoplastic, 15.2% and 9.1%, respectively; atypia of undetermined significance, 77.9% and 24.9%, respectively; neoplasm-benign, 99% and 1.8%, respectively; salivary gland neoplasm of uncertain malignant potential, 94.8% and 37%, respectively; suspicious for malignancy, 100% and 89.7%, respectively; and malignant, 100% and 99.3%, respectively. The accuracy of the MSRSGC for diagnosing neoplasms was 97.8%, and its accuracy for diagnosing malignancy was 97.3%. Institutions that used Romanowsky-stained preparations had lower nondiagnostic rates and lower risks of neoplasm and malignancy in the non-neoplastic category. CONCLUSIONS: The MSRSGC is useful for risk stratification and quality control. Widespread use of the MSRSGC would improve the accuracy of salivary gland cytology and lead to better patient care in Japan.

Application of the Milan System for Reporting Salivary Gland Cytopathology: A 10-Year Experience in a Single Japanese Institution.

OBJECTIVE: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a recently published evidence-based categorization system for salivary gland fine-needle aspiration (FNA). We applied MSRSGC to Japanese cases and evaluated its utility. STUDY DESIGN: A total of 480 FNA cases were reviewed. We recategorized each case into one of the MSRSGC categories. The risk of neoplasm (RON) and the risk of malignancy (ROM) for each diagnostic category in MSRSGC, and the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for malignancy and for neoplasms were calculated for cases with histological follow-up. In addition, the overall ROM (O-ROM) was calculated for all FNA cases. RESULTS: RON, ROM, and O-ROM rates were as follows - non-diagnostic: 51.3, 5.1, and 1.0%; non-neoplastic: 0, 0, and 0%; atypia of undetermined significance: 83.9, 12.9, and 7.3%; neoplasm, benign: 100, 0, and 0%; salivary gland neoplasm of uncertain malignant potential: 100, 32.1, and 23.7%; suspicious for malignancy: 100, 85.7, and 60%; and malignant: 100, 100, 81.8%. The sensitivity, specificity, and accuracy with (without) indeterminate cases for malignancy were 65 (100), 99 (99), 92% (99%) and PPV and NPV were 96 and 100%, respectively, and those for neoplasms were 84 (100), 100 (100), 85% (100%), and PPV and NPV were 100 and 100%, respectively. CONCLUSIONS: The MSRSGC is useful for stratification of ROM and for promoting the performance of salivary gland FNA. The MSRSGC could be easily introduced in Japan and may improve the Japanese salivary gland FNA status.

An Elderly Case of Paraneoplastic Anti-NMDA Receptor Encephalitis Associated with Small-cell Lung Cancer Expressing NR1 Subunits.

A 61-year-old Japanese man presented with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. NR1 antibodies were detected in his cerebrospinal fluid. Chest computed tomography revealed lung tumor. The patient was diagnosed with paraneoplastic anti-NMDAR encephalitis associated with lung cancer and treated with two cycles of intravenous high-dose methylprednisolone and one cycle of intravenous immunoglobulin. However, he died one year later without improvement. An autopsy confirmed small-cell lung cancer (SCLC). Immunohistochemistry revealed the expression of NR1 subunits in the tumor cells, suggesting that SCLC may trigger NR1 autoimmunity though the expression of NR1 subunits as onconeural antigens, expanding the phenotypic spectrum of paraneoplastic neurological syndrome associated with SCLC.

Immunostaining With Immunoglobulin G Subclass Antibody Cocktail for Diagnosis of Type 1 Autoimmune Pancreatitis.

BACKGROUND.: Immunoglobulin (Ig) G4-related diseases (RDs) are systemic diseases in which serum IgG4 levels are frequently elevated. They can cause diffuse or focal tumor formation, organ swelling, and tissue thickening in organs infiltrated by IgG4+ plasma cells. The diagnostic criteria for IgG4-RDs include an IgG4/IgG ratio >40%, but counting IgG+ cells can be difficult because of the weakness of IgG staining density. We hypothesized that an antibody cocktail of mixed IgG1, IgG2, IgG3, and IgG4 (AC-IgG) might give immunohistochemistry results comparable with those of IgG in IgG4-RD. METHODS.: We compared AC-IgG reactivity with IgG expression in type 1 autoimmune pancreatitis (AIP), a representative IgG4-RD. We compared immunohistochemistry results using AC-IgG and IgG-only in 10 cases of AIP. The coefficient of variation (Cv) was used to analyze differences between AC-IgG and IgG findings in AIP by 13 board-certified pathologists. RESULTS.: Although mean values for IgG+ cells did not significantly differ between AC-IgG (34.3; range = 27.4-37.1) and IgG (30.0; range = 23.0-45.6; P = .6254), Cv was lower for AC-IgG (33.4%) than for IgG (51.4%; regression equation; y[IgG] = 0.988x + 0.982; correlation coefficient = 0.907). The data showed that the results of both methods were largely consistent. CONCLUSION.: AC-IgG could replace IgG to count IgG+ cells because of its lower Cv.

Churg-Strauss syndrome presenting as myositis following unaccustomed exercise.

A 68-year-old woman with a 4 year history of bronchial asthma developed marked myalgia in the extremities following exercise to which she was unaccustomed. Examination on admission, 11 days after onset, revealed myalgia, muscular weakness and cutaneous hemorrhagic bullae. Blood tests revealed eosinophilia (9160/mm(3)) and elevation of creatinine kinase and C-reactive protein. Muscle biopsy in the quadriceps femoris showed small vessel vasculitis and eosinophilic infiltration. Skin biopsy revealed leukocytoclastic vasculitis with neutrophilic and eosinophilic infiltration and fibrinoid necrosis. We diagnosed her as having Churg-Strauss syndrome (CSS). Corticosteroid treatment relieved her symptoms and resulted in normalization of the laboratory test results. Myositis is rare as an initial manifestation of CSS. The previous studies on immunological changes after eccentric exercise suggest that unaccustomed exercise could induce an increase in the serum level of interleukin-6 and trigger the onset of CSS.

A resected case of recurrent ITPN in the remnant pancreas after pancreatoduodenectomy.

BACKGROUND: Since intraductal tubulopapillary neoplasm (ITPN) is a rare disease, the clinical features of ITPN, especially the characteristics related to recurrence, have not been revealed. We performed a total remnant pancreatectomy for a patient whose ITPN recurred 16 months after pancreatoduodenectomy (PD). We report useful findings to clarify how ITPN reoccurs based on this experience and previously reported cases. CASE PRESENTATION: A 61-year-old male patient was diagnosed with pancreatic cancer and underwent PD. However, a postoperative pathologic examination diagnosed ITPN with invasive cancer. After receiving adjuvant chemotherapy, he was hospitalized for pancreatitis 16 months after the operation. He was diagnosed as having recurrence near the pancreato-jejunal anastomosis based on detailed examinations and underwent a remnant total pancreatectomy. From the results of the histopathological examination, he was found to have a recurrence of ITPN as a polypoid mass without invasion distant from the surgical stump of the first operation. Furthermore, tumor cells floating in the main pancreatic duct distant from the main tumor were observed at three locations. REVIEW OF THE LITERATURE: Including our case, five cases of recurrence in the remnant pancreas after surgery for ITPN have been reported. Recurrence in the main pancreatic duct was observed in four of these five cases. The primary tumor, which recurred in the remnant pancreas after surgery, was characterized as being relatively small and less invasive; however, Ki-67 labeling index was high. In immunohistochemical examination, the expression of MUC6, which is not one of characteristics of ITPN, tended to be positive. CONCLUSION: In this case, tumor cells were floating inside the pancreatic duct at several locations. From the results of this case and a review of previous reports, the cause of ITPN recurrence in this case seemed to be due to tumor cells leaving the tumor and implanting into the pancreatic duct.

Promyelocytic leukemia nuclear bodies provide a scaffold for human polyomavirus JC replication and are disrupted after development of viral inclusions in progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy is a fatal demyelinating disorder due to human polyomavirus JC infection in which there are viral inclusions in enlarged nuclei of infected oligodendrocytes. We report that the pathogenesis of this disease is associated with distinct subnuclear structures known as promyelocytic leukemia nuclear bodies (PML-NBs). Postmortem brain tissues from 5 patients with the disease were examined. Affected cells with enlarged nuclei contained distinct dot-like subnuclear PML-NBs that were immunopositive for PML protein and nuclear body protein Sp100. Major and minor viral capsid proteins and proliferating cell nuclear antigen, an essential component for DNA replication, colocalized with PML-NBs. By in situ hybridization, viral genomic DNA showed dot-like nuclear accumulation, and by electron microscopy, virus-like structures clustered in subnuclear domains, indicating that PML-NBs are the site of viral DNA replication and capsid assembly. Molecules involved in the ubiquitin proteosome pathway (i.e. ubiquitin and small ubiquitin-like modifier 1) did not accumulate in the nuclei with viral inclusions, indicating that cell degeneration may not be dependent on this pathway. When viral progeny production was advanced, PML-NBs were disrupted. These data suggest that: 1) PML-NBs allow for efficient viral propagation by providing scaffolds, 2) disruption of PML-NBs is independent of the ubiquitin-proteasome pathway, and 3) this disruption probably heralds oligodendrocyte degeneration and the resulting demyelination.

A Comparative Immunohistochemical Study of Anal Canal Epithelium in Humans and Swine, Focusing on the Anal Transitional Zone Epithelium and the Anal Glands.

To better understand the cellular origins and differentiation of anal canal epithelial neoplasms, the immunohistochemical profiles of the anal canal epithelium in humans and swine were evaluated. Formalin-fixed tissue sections were immunostained for mucin (MUC: MUC2, MUC5AC, MUC5B), desmoglein 3 (DGS3), p63, CDX2, SOX2, and α-smooth muscle actin (α-SMA). The anal transitional zone (ATZ) epithelium covered the anal sinus and consisted of a stratified epithelium with mucous cells interspersed within the surface lining. Anal glands opened into the anal sinus. Ducts and acini of intraepithelial or periepithelial mucous type were the main structures of human anal glands, whereas those of swine were compound tubuloacinar mixed glands. Distal to the ATZ epithelium, non-keratinized stratified squamous epithelium merged with the keratinized stratified squamous epithelium of the perianal skin. MUC5AC expression predominated over MUC5B expression in the ATZ epithelium, while MUC5B expression was higher in the anal glands. SOX2 was positive in the ATZ epithelium, anal glands, and squamous epithelium except in the perianal skin. In humans, DGS3 was expressed in the ATZ epithelium, anal gland ducts, and squamous epithelium. p63 was detected in the ATZ epithelium, anal glands, and squamous epithelium. Myoepithelial cells positive for α-SMA and p63 were present in the anal glands of swine. Colorectal columnar cells were MUC5B+ /MUC2+ /CDX2+ /MUC5AC- /SOX2- . The ATZ epithelium seems to be a distinctive epithelium, with morphological and functional features allowing smooth defecation. The MUC5AC+ /SOX2+ /MUC2- /CDX2- profile of the ATZ epithelium and anal glands is a useful feature for diagnosing adenocarcinoma arising from these regions. Anat Rec, 301:796-805, 2018. © 2017 Wiley Periodicals, Inc.

Inter-capsular resection of cervical vagus nerve schwannoma.

Cervical vagus nerve schwannoma is rare and its surgical procedure is controversial. The tumor is in general benign and slowly growing without causing symptoms, and therefore it should be advised to remove the tumor while preserving neural function. We operated on two patients with cervical vagus nerve schwannoma with the inter-capsular resection technique proposed by Hashimoto et al. without causing neurological deficits. It is the first time that the plane between the tumor-complex capsule layer (epineurium and perineurium) and true tumor capsule layer was histopathologically proved in this paper. The true tumor capsule layer contained no normal neural fibers, tumor tissues and neural sheath. The inter-capsular resection technique is a safe and reliable method for removing cervical vagus nerve schwannoma.

Promoter hypomethylation of SKI in autoimmune pancreatitis.

The relationship between methylation abnormality and autoimmune pancreatitis (AIP)-a representative IgG4-related disease-has not yet been elucidated. We identified SKI might have a significant methylation abnormality in AIP through methylation array analysis using the Illumina Infinium Human Methylation 450K BeadChip array, and investigated the relationship of SKI with AIP clinicopathological features. The methylation rate of SKI was assessed by quantitative SYBR green methylation-specific PCR, and the degree of SKI expression in tissue specimens was assessed by immunohistochemistry in 10 AIP cases, 14 cases of obstructive pancreatitis area in pancreatic ductal adenocarcinoma (PDA) without a history of AIP, and 9 normal pancreas (NP) cases. The SKI methylation ratio was significantly lower in AIP than in PDA and NP. Additionally, the immunohistochemical staining-index (SI) score for SKI was significantly higher in AIP than NP, although there was no significant difference between AIP and PDA. There was a strong negative correlation between SI score and SKI methylation ratio, and between the serum concentrations of IgG4 and the SKI methylation ratio. There was a moderate positive correlation between the serum concentrations of IgG4 and SI. SKI is thought to be an oncogene indicating that SKI hypomethylation and carcinogenesis might be linked to AIP. Furthermore, the correlation between serum concentrations of IgG4 and SKI methylation levels suggest SKI might be involved in the pathogenesis of AIP. However, the role of SKI has not been clearly elucidated. Further studies are needed to understand further the function of SKI.

Methylation of Tumor Suppressor Genes in Autoimmune Pancreatitis.

OBJECTIVES: Autoimmune pancreatitis (AIP) is a representative IgG4-related and inflammatory disease of unknown etiology. To clarify mechanisms of carcinogenesis resulting from AIP, we focused on methylation abnormalities and KRAS mutations in AIP. METHODS: Six tumor suppressor genes (NPTX2, Cyclin D2, FOXE1, TFPI2, ppENK, and p16) that exhibited hypermethylation in pancreatic carcinoma were selected for quantitative SYBR green methylation-specific polymerase chain reaction in 10 AIP specimens, 10 pancreatic adenocarcinoma cases without history of AIP containing carcinoma areas (CAs) and noncarcinoma areas (NCAs), and 11 normal pancreas (NP) samples. KRAS mutation in codons 12, 13, and 61 were also investigated using direct sequencing. RESULTS: Hypermethylation events (≥10%) were identified in NPTX2, Cyclin D2, FOXE1, TFPI2, ppENK, and p16 in 1, 2, 2, 0, 2, and 0 CA cases, respectively, but not in these 6 candidate genes in AIP, NCA, and NP. However, the TFPI2 methylation ratio was significantly higher in AIP than NCA and NP. Direct sequencing results for KRAS showed no single-point mutations in AIP. CONCLUSIONS: These are the first studies characterizing methylation abnormalities in AIP. AIP's inflammatory condition may be related to carcinogenesis. Further study will elucidate methylation abnormalities associated with carcinogenesis in AIP.

High endothelial venule-like vessels and lymphocyte recruitment in diffuse sclerosing variant of papillary thyroid carcinoma.

Diffuse sclerosing variant of papillary thyroid carcinoma (DSPTC) is a rare subtype of papillary thyroid carcinoma with a high incidence of lymph node metastasis. One of its characteristic histological features is the presence of dense lymphocyte infiltrates; however, how these lymphocytes are recruited in this pathological setting remains unclear. Here, we analysed 17 DSPTC cases immunohistologically for cell adhesion molecules expressed on endothelial cells. We found that venules morphologically similar to high endothelial venules (HEVs) in secondary lymphoid organs were induced in lymphoid aggregates in DSPTC, and such HEV-like vessels expressed 6-sulfo sialyl Lewis X (sLeX) glycans as well as intercellular adhesion molecule 1 (ICAM-1). Triple immunohistochemistry revealed that CD8+ cytotoxic T cells were the major lymphocyte subset attached to the luminal surface of HEV-like vessels. sLeX-type glycans were also expressed on DSPTC carcinoma cells, which in binding assays were decorated with E-selectin•IgM chimaeras calcium-dependently. These findings collectively suggest that 6-sulfo sLeX glycans, together with ICAM-1, on HEV-like vessels may function to recruit CD8+ cytotoxic T cells in DSPTC. Additionally, sLeX-type glycans on carcinoma cells might partly contribute to highly metastatic properties of DSPTC through interaction with E-selectin expressed on endothelial cells.