Immunophenotypes and Tumor Immune Microenvironment in Hepatocellular Carcinoma With Macrotrabecular Massive and Vessels Encapsulating Tumor Clusters.

BACKGROUND/AIM: Recently, vessels encapsulating tumor clusters (VETC) pattern and macrotrabecular massive (MTM) pattern of hepatocellular carcinoma (HCC) have been reported as aggressive histological types. These histological patterns showed an immunosuppressive tumor immune microenvironment (TIME). Since there have been no reports on the differences of these two subtypes simultaneously, this study examined the immunophenotypes and TIME of MTM-HCC and VETC-HCC immunohistochemically. PATIENTS AND METHODS: Seventy-four cases of previously diagnosed HCC, including 32 MTM-HCCs, 21 VETC-HCCs, and 21 conventional HCCs, were enrolled in immunohistochemical analysis. We conducted immunohistochemical analysis. RESULTS: We found that MTM-HCC showed less frequent expression of HepPar-1, which is one of the most common hepatocytic markers. In MTM-HCC, the frequency of high expression levels of Keratin19, carbonic anhydrase (CA) IX, and PD-L1 was higher compared to VETC-HCC and conventional HCC. PD-L1 expression was found in 34.4% of MTM-HCC, 0% of VETC-HCC, and 19.0% of conventional HCC. The rate of PD-L1 expression in MTM-HCC was significantly higher than the others (p=0.0015). PD-L1 expression was significantly associated with epithelial cell adhesion molecules and CA IX expression, which are representative markers of tumor stemness and hypoxic conditions, respectively. The CD8 infiltration in VETC-HCC was significantly lower than that in conventional HCC. CONCLUSION: MTM-HCC had different immunophenotypes and TIMEs compared to HCC with the VETC pattern. Although both had immunosuppressive TIME, the elements forming TIME were quite different. To enhance the immune checkpoint inhibitor efficacy, changing TIME from a suppressive to an active form is essential.

Prognostic Factors for Distal Bile Duct Carcinoma After Surgery.

BACKGROUND: Distal bile duct carcinoma continues to be one of the most difficult cancers to manage in terms of staging and radical resection. Pancreaticoduodenectomy (PD) with regional lymph node dissection has become the standard treatment of distal bile duct carcinoma. We evaluated treatment outcomes and histological factors in patients with distal bile duct carcinoma. METHODS: Seventy-four cases of resection of carcinoma of the distal bile ducts treated at our department during the period from January 2002 and December 2016 using PD and regional lymph node dissection as the standard surgical procedure were investigated. Survival rates of factors were analyzed using uni- and multivariate analyses. RESULTS: The median survival time was 47.8 months. On univariate analysis, age of 70 years or older, histologically pap, pPanc2,3, pN1, pEM0, v2,3, ly2,3, ne2,3 and postoperative adjuvant chemotherapy were statistically significant factors. On multivariate analysis, histologically pap was identified as a significant independent prognostic factor. The multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as showing a significant trend towards independent prognostic relevance. CONCLUSION: The good news about resected distal bile duct carcinoma is that the percentage of those who achieved R0 resection has risen to 89.1%. Our multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as prognostic factors. In order to improve the outcome of treatment, it is necessary to improve preoperative diagnostic imaging of pancreatic invasion and lymph node metastasis, establish the optimal operation range and clarify whether aortic lymph node dissection is needed to control lymph node metastasis, and establish effective regimens of chemotherapy.

Predictive and Prognostic Value of SUOX Expression in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: Sulphite oxidase (SUOX) is a metalloenzyme that catalyses ATP synthesis via oxidative phosphorylation in the mitochondria. Although SUOX has been reported to affect the invasiveness and differentiation of cancer cells, its clinicopathological significance in pancreatic adenocarcinoma (PDAC) remains unclear. In this study, we investigated the utility of SUOX expression as a prognostic factor in PDAC. PATIENTS AND METHODS: This study included 56 patients with PDAC who underwent pancreatic resection at the Kurume University Hospital between 2014 and 2018. SUOX immunohistochemistry was evaluated using tissue microarray specimens from patients. Patients were classified into a high SUOX expression group (≥10% of cells stained) or a low SUOX expression group (<10% of cells stained), and the associations of SUOX with clinicopathological characteristics and survival were analysed. Statistical analysis was performed using Cox regression analysis, the Kaplan-Meier method, and log-rank test. RESULTS: SUOX was expressed in the cytoplasm of normal pancreatic ductal epithelium, pancreatic acinar cells, and islets of Langerhans. Although we did not find any significant correlation between SUOX expression and clinicopathological factors, SUOX was identified as an independent prognostic factor based on univariate and multivariate analyses. Pathological stage was also an independent prognostic factor. The high SUOX expression group showed a significantly poorer prognosis than the low SUOX expression group (p=0.018). CONCLUSION: SUOX-mediated mitochondrial metabolism in PDAC may be a factor influencing prognosis and SUOX may be a potential novel prognostic biomarker.

Pancreatic hamartoma: detection of harbouring NAB2::STAT6 fusion gene.

Hamartomas in the pancreas are rare and are often histologically and morphologically similar to solitary fibrous tumours (SFTs). We examined the differences between hamartomas and SFTs at the molecular level. METHODS AND RESULTS: Thirteen patients histopathologically diagnosed with pancreatic hamartoma were included in the study. We also performed STAT6 immunohistochemistry (IHC), which is used in the diagnosis of SFT. Furthermore, for the three cases in which RNA was extracted, reverse transcription polymerase chain reaction to search for NAB2::STAT6 fusions was used. Macroscopically, 13 patients had well-demarcated tumour lesions. Histologically, no islets of Langerhans were observed in the lesions, acinar tissue and ducts were unevenly distributed and elastic fibres were not observed around the ducts by Elastica van Gieson staining. One case contained a lipomatous hamartoma composed mainly of adipose tissue. Seven of the 13 cases demonstrated expression of STAT6 in the nuclei of intervening spindle cells. NAB2::STAT6 fusions were observed in two of the three cases in which RNA was extracted. These two cases also demonstrated STAT6 expression in spindle cells using STAT6 IHC. In one case of lipomatous hamartoma, we did not confirm NAB2::STAT6 fusion or STAT6 expression in STAT6 IHC. CONCLUSION: Of the 13 patients histopathologically diagnosed with hamartoma, two demonstrated NAB2::STAT6 fusions, suggesting the existence of pancreatic hamartomas with molecular-level components identical to those of SFT.

SUOX and GLUT1 are biomarkers for the prognosis in large duct type intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignant disease and has a poor prognosis, but few biomarkers have been found. SUOX is an important factor in energy metabolism and a poor prognostic factor in other malignancies. In this study, we aimed to clarify the relationship between SUOX and GLUT expression in large duct type iCCA and the mechanism of mitochondrial energy metabolism in iCCA. We evaluated SUOX and GLUT1 expression in 96 large duct type iCCA cases and proportion score (PS) was used to evaluate the expression; receiver operating characteristic (ROC) curves of both SUOX and GLUT1 expression were generated, and the Kaplan-Meier method and Cox regression analysis were used to estimate overall survival. Of the 96 iCCA cases, 73 (76.0%) showed low SUOX expression and 66 (68.8%) showed high GLUT1 expression. The 5-year survival rate of iCCA with low SUOX expression was significantly shorter than that of iCCA with high SUOX expression (p = 0.001). In contrast, the 5-year survival rate of iCCA with high GLUT1 expression was significantly shorter than that of iCCA with low GLUT1 expression (p = 0.005). According to Spearman's correlation, there was no correlation between SUOX and GLUT1. Conversely, the combination of low SUOX and high GLUT1 expression was the most common in 51 of 96 cases (53.1%), and the overall survival was significantly shorter than that of patients with other combinations. Furthermore, SUOX was shown to be an independent prognostic factor together with GLUT1, suggesting that SUOX in combination with GLUT1 can predict the prognosis of large duct type iCCA.

Quercetin Suppresses Proliferation of Liver Cancer Cell Lines In Vitro.

BACKGROUND/AIM: We investigated the anti-proliferative effect of quercetin on liver cancer cell lines. MATERIALS AND METHODS: Thirteen liver cancer cell lines were cultured followed by treatment with varying concentrations of quercetin (0-100 µM) or quercetin and 5-FU, and the cell viability was analysed by the MTT assay. Flow cytometry was also used to examine cell cycle progression after treatment with quercetin. RESULTS: The addition of quercetin resulted in a dose- and time-dependent suppression of cell proliferation. In some cell lines, treatment with quercetin and 5-FU caused an additional or synergistic effect. Most cell lines displayed cell cycle arrest at different phases of the cell cycle. CONCLUSION: Quercetin inhibits the proliferation of liver cancer cells via induction of apoptosis and cell cycle arrest.

Prognostic Impact of Desmoplastic Reaction Evaluation for Intrahepatic Cholangiocarcinoma.

BACKGROUND/AIM: The purpose of this study was to clarify the relationship between the desmoplastic reaction (DR) and clinicopathological features, and the prognosis using cases of resected intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHODS: Out of 54 cases that were preoperatively diagnosed with ICC and underwent resection at our department, 47 patients were included in this study. All sections were prepared from resected specimens and were microscopically observed following H&E staining. Stroma were evaluated at the advancing edge of the cancer and stratified into three DR types: mature (DR1), intermediate (DR2), and immature (DR3). RESULTS: DR was correlated to the serum levels of CA19-9, but not to the other tumor factors. In multivariate analysis, only DR and tumor size were determined as independent prognostic factors. CONCLUSION: Evaluation of DR for ICC may be useful for prognostic assessments.

Usefulness of Tumor Tissue Biopsy for Predicting the Biological Behavior of Hepatocellular Carcinoma.

BACKGROUND/AIM: Assessment of the biological behavior of tumors is important for choosing an appropriate cancer therapy. In hepatocellular carcinoma (HCC), the biological behaviour can be assessed by tumor morphology and molecular biology. This study investigated the usefulness of tumor tissue biopsy for predicting the biological behavior of HCC. PATIENTS AND METHODS: We studied 43 patients who underwent hepatectomy and preoperative liver tumor biopsy for HCC. We performed clinicopathological and immunohistochemical (IHC) analyses. The expression of the following molecules was examined: regulator of G-protein signaling 5 (RGS5), glypican-3 (GPC3), keratin 19 (K19), epithelial cell adhesion molecule (EpCAM), protein induced by vitamin K absence or antagonist-II (PIVKA-II), ß-Catenin, and p53. RESULTS: There was an overall 83.7% agreement regarding tumor differentiation between the preoperative biopsy specimens and the resected specimens. The accuracy of IHC analysis was more than 70% for all molecules between the preoperative biopsy specimens and the resected specimens. The RGS5-positive biopsy cases had higher serum α-fetoprotein levels (p=0.04), a higher rate of moderately or poorly differentiated tumors (p=0.02) and portal vein invasion (p=0.0003) than the RGS5-negative biopsy cases. The GPC3-positive biopsy cases were younger (p=0.04), had higher serum PIVKA-II levels (p=0.01), and a higher rate of portal vein invasion (p=0.03) than the GPC3-negative biopsy cases. The PIVKA-II-positive biopsy cases had significantly higher serum PIVKA-II levels than the PIVKA-II-negative biopsy cases (p=0.02). The other molecular markers showed no significantly different clinical findings between the positive and negative cases. CONCLUSION: In HCC, there was a high agreement rate of both the histopathological and IHC findings between preoperative biopsy specimens and resected specimens. In the biopsy specimens of HCC, RGS5 and GPC3 expression were useful molecular makers for predicting portal vein invasion. Liver tumor biopsy is useful for predicting the biological behavior of HCC through histopathological and immunohistochemical findings.

Expression of Matrix Metalloproteinases in Intraductal Papillary Mucinous Neoplasm of the Pancreas.

BACKGROUND/AIM: Intraductal papillary mucinous neoplasm (IPMN) has a variety of histological and morphological appearances. Matrix metalloproteinases (MMPs) have been considered to be associated with tumor progression or poor prognosis. The aim of this study was to elucidate the molecular basis of IPMN variation in different types of lesions. MATERIALS AND METHODS: The expression of MMP-1,2,7,9 in 51 cases of IPMN were investigated. The MMP score was calculated as the sum of the score of staining distribution and the score of the intensity staining. RESULTS: MMP scores were correlated with histological grade, histological subtype, and type of invasion. MMP high expression groups (MMP score ≥5) had worse prognosis than low-expression groups. CONCLUSION: MMP expression varied between different types of IPMN, a result supporting differences in molecular basis of malignancies. These considerations may be helpful for optimal management or treatment according to various types of IPMN.

Sinusoidal Obstruction Syndrome and Postoperative Complications Resulting from Preoperative Chemotherapy for Colorectal Cancer Liver Metastasis.

BACKGROUND/AIM: The aim of this study was to investigate the effects of preoperative chemotherapy on the healthy, metastasis-free part of the liver in colorectal cancer patients with liver metastasis, and the relationship between chemotherapy and postoperative complications. PATIENTS AND METHODS: Our study included 90 cases of colorectal cancer liver metastasis resected after preoperative chemotherapy. The patients were divided into three groups according to the received chemotherapy regimen: 20 cases received mFOLFOX6, 54 cases a combination of mFOLFOX6 with bevacizumab, and 16 cases a combination of mFOLFOX6 and cetuximab or panitumumab. RESULTS: The mean numbers of sinusoidal injuries for each chemotherapy type were compared. The group treated with the combination of mFOLFOX6 and bevacizumab showed a lower extent of sinusoidal injury relative to other groups; this intergroup difference became increasingly remarkable as the number of chemotherapy cycles increased. Complications of various extents were found in all three groups, but no significant differences were observed between the three groups. CONCLUSION: In cases where preoperative chemotherapy was extended over a long period, combined use of bevacizumab was thought to be effective because of stabilization of disturbed liver hemodynamics resulting from sinusoidal injury suppression effects, allowing effective distribution of anti-cancer agents to tumors.

Clinical and Prognostic Significance of Neoplastic Spindle Cells in Gallbladder Cancer.

BACKGROUND/AIM: Neoplastic spindle cells (NSCs) are believed to play a role in cancer invasion and metastasis, as well as in poor prognosis. The clinicopathological characteristics and prognostic relevance of NSCs was investigated in gallbladder cancer. MATERIALS AND METHODS: Specimens were obtained from 62 patients with gallbladder cancer who underwent surgery. The emergence of NSCs and their correlation with clinicopathological factors, prognosis, and EMT markers was evaluated. RESULTS: The NSC grade correlated with tumor size, preoperative CA19-9, surgical margin, the degree of differentiation, the depth of invasion, lymph node metastasis, lymphatic invasion, vascular invasion, and perineural invasion. Multivariate analysis of overall survival showed that NSCs were an independent prognostic factor. A correlation between NSCs and EMT was also suggested. CONCLUSION: NSCs are an independent prognostic factor for patients with postoperative gallbladder cancer, which also suggests a correlation between NSCs and EMT.

Clinicopathological Study of Resections of Intraductal Papillary Neoplasm of the Bile Duct.

BACKGROUND/AIM: The aim of this study was to examine the clinicopathological features of intraductal papillary neoplasm of the bile duct (IPNB) and investigate their relationships with intraductal papillary mucinous neoplasm (IPMN). PATIENTS AND METHODS: Our study included 104 patients who underwent resection of tumors that showed papillary growth within the bile duct and pancreas. RESULTS: Comparisons were performed based on subtypes and histological grades. The presence of various histological grades was confirmed in both the IPNB group and the IPMN group, and statistical significance was found in the between-group comparisons of subtypes and histological grades. It was shown that while all patients who underwent IPNB resection did not match the classifications proposed by Nakanuma et al., they did reflect classification characteristics. CONCLUSION: IPNB and IPMN have common clinical histological features. Common features between IPNB subtype classifications were also identified, which may provide novel diagnostics.

Programmed death-ligand 1 expression is an unfavorable prognostic factor of hepatocellular carcinoma after archiving sustained virologic response for hepatitis C virus infection.

The aim of the present study was to study the pathological prognostic factor of initial hepatocellular carcinoma (HCC) after archiving sustained virologic response (SVR) for hepatitis C virus (HCV) infection. A single-center retrospective analysis was performed for patients who underwent hepatectomy between 2003 and 2017. We studied clinico-pathological findings of resected liver tissues in 35 patients with HCC after SVR treated by interferon (IFN group) and 13 patients with HCC after SVR treated by direct acting antivirals (DAA group). We also performed immunohistochemical staining using antibodies against programmed death-ligand 1 (PD-L1), cytokeratin 19, epithelial cell adhesion molecule (EpCAM) and regulator of G-protein signaling 5 (RGS5). PD-L1 positive HCC was observed in 6 cases of the IFN group and 4 cases of the DAA group. In the IFN group, in univariate analysis of recurrence free survival after surgery (RFS), the PD-L1 expression had a statistically significant impact (HR=6.01; P=0.02). In the multivariate analysis of RFS, PD-L1 expression significantly remained (HR=5.01; P=0.03). For both RFS and overall survival, Kaplan-Meier curves confirmed that patients with PD-L1 expression showed significantly worse prognosis (log-rank test P<0.01). Nuclear grade, RGS5 expression, and EpCAM expression were significantly higher in the PD-L1-positive HCC group compared with the PD-L1-negative HCC group (P<0.05). Therefore, PD-L1 expression may be an independent prognostic factor of surgically resected HCC after achieving SVR.

Significance of neoadjuvant chemoradiotherapy for borderline resectable pancreatic head cancer: Pathological local invasion and microvessel invasion analysis.

Borderline resectable pancreatic head cancer (BR-PHC) has low resectability due to vascular invasion. Although the clinical effects of neoadjuvant chemoradiotherapy (NAC-RT) for BR-PHC have been examined, few studies have reported its pathological aspects. The present study retrospectively investigated the effect of NAC-RT on the histological features of BR-PHC. A total of 29 patients with BR-PHC who underwent NAC-RT, and 55 controls with resectable PHC, who underwent pancreaticoduodenectomy at the Kurume University Hospital. Tumor staging, lymphovascular invasion (LVI), and microvessel invasion (MVI) were evaluated. The median tumor size in the NAC-RT group was 2.0 cm, and it was smaller than that of the control group (P=0.006). The rates of lymph node metastasis, LVI, and MVI were significantly lower in the NAC-RT group (P<0.001, 0.002, and 0.015, respectively). Overall survival in the NAC-RT group was comparable to that in the control group, although patients with BR-PHC generally had a poorer prognosis than those with resectable PHC. Patients in the NAC-RT group without portal vein invasion (PVI) had a significantly better prognosis than those with PVI in the control group (P=0.002). NAC-RT may be beneficial for patients with BR-PHC by inhibiting local invasion and metastasis as prognosis following resection could be equivalent to that of patients with conventional ductal adenocarcinoma.

Insulinoma-associated protein 1 expression in pancreatic neuroendocrine tumours in endoscopic ultrasound-guided fine-needle aspiration cytology: An analysis of 14 patients.

BACKGROUND: Insulinoma-associated protein 1 (INSM1) has been reported to be a useful marker for diagnosing pancreatic neuroendocrine tumours (PNETs). However, INSM1 expression in endoscopic ultrasound-guided fine needle aspiration cytology has not been examined. We evaluated INSM1 expression in the cytology of cases diagnosed with PNETs. METHODS: We immunocytochemically stained INSM1 and Ki-67 in 14 PNET cases, and according to the 2017 World Health Organisation criteria, seven PNET Grade 1 cases, four Grade 2 cases and three Grade 3/neuroendocrine carcinoma cases were identified. As a control for INSM1 and Ki-67 expression, we used cytological specimens from 15 cases of pancreatic ductal adenocarcinoma. RESULTS: In PNET cases, INSM1-expressing tumour cells were identified in all cytological specimens of PNET. The median INSM1 expression rate in Grade 1 cases was 49.8% (mean ± standard deviation: 55.1 ± 12.5%, min: 39.3%, max: 74.1%), and in Grade 2 and Grade 3/neuroendocrine carcinoma cases was 81.1% (mean ± standard deviation: 77.6 ± 18.6%, min: 50.3%, max: 100%). However, there was no correlation between INSM1 and Ki-67 expression (r = -0.15). The median expression rate in PNET cases was 64.3%, which was significantly higher than that in pancreatic ductal adenocarcinoma cases (P < 0.0001). CONCLUSION: INSM1 immunocytochemistry of cytological specimens obtained from endoscopic ultrasound-guided fine needle aspiration cytology can accurately diagnose PNETs; therefore, INSM1 could be an important diagnostic tool in assessing therapeutic strategies, including molecular-targeted therapy.

PD-L1 expression in pancreatic adenosquamous carcinoma: PD-L1 expression is limited to the squamous component.

AIM: We examined the programmed death-ligand 1 (PD-L1) expression in surgically resected pancreatic adenosquamous carcinoma (PASC) samples. Furthermore, the detection rate was also assessed using biopsy cases obtained from endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). METHODS: Fifteen cases of PASC (six resected and nine EUS-FNA biopsied) from the Kurume University Hospital between 2009 and 2016 were used for the evaluation of PD-L1 expression. As a control group, 34 cases of pancreatic ductal adenocarcinomas (PDACs) were selected. To compare　the positivity and intensity of PD-L1, two types of clones (SP263, E1L3N) were examined for immunostaining. Only the membrane expression of PD-L1 was regarded as positive. The PD-L1 expressions in the squamous cell carcinoma component (SCc), adenocarcinoma component (ACc), and immune cells were assessed separately. The ratio of PD-L1 expression was calculated by counting the positive tumor cells, and tumor proportion score (TPS) was applied (TPS; Null < 1%, low expression; 1 ≤ TPS ≤ 49% and high expression; ≥ 50%). RESULTS: PD-L1 expression was observed in five surgical PASC samples (83%). This shows that SCc presented a high expression in these cases. However, the overall TPS indicated a low expression. In contrast, only one case (3%) was positive for PD-L1 in PDACs, and the TPS indicated a low expression. No differences in PD-L1 expression were observed between the two clones, SP263 and E1L3N. High PD-L1 expression in the EUS-FNA sample was found in only one case (11%). DISCUSSION: Although assessment using the tumor cells of PASC samples obtained from EUS-FNA was difficult, this study suggests the selective expression of PD-L1 in the SCc of PASC. Furthermore, it was considered that immune checkpoint inhibitors could provide therapeutic effects selectively on the SCc for the entire range of TPSs, though the PD-L1 expression was low.

A large retroperitoneal lipoblastoma: A case report and literature review.

INTRODUCTION: Lipoblastoma is a rare benign soft tissue tumor that occurs most commonly in infants and children. However, retroperitoneal lipoblastomas are rare, occurring in <5% of cases. We report a case of large retroperitoneal lipoblastoma and the largest collection of known retroperitoneal lipoblastomas in children in the literature. CASE PRESENTATION: A 3-year-old girl presented with left abdominal mass. Magnetic resonance imaging (MRI) revealed a soft tissue mass measuring 12 × 8 × 6 cm in the retroperitoneal region. The mass had a clearly defined margin and a reticular pattern with an interposing fat component. Based on these findings, the mass was suspected to be a soft-tissue tumor, most likely lipoblastoma.Laparotomy with resection of the retroperitoneal mass was performed. The tumor was easily dissected from the retroperitoneal space without injury to surrounding structure.A histopathological examination demonstrated the mature proliferation of adipocytes and spindle-shaped cells separated by fibrovascular septa accompanied by myxoid changes. The cells were separated into lobules by septa, and areas of immature adipocytes showing a signet-ring or multivacuolar appearance were present at the periphery. Histopathological diagnosis was lipoblastoma. Follow-up at 6 months revealed no evidence of recurrence. CONCLUSION: Retroperitoneal lipoblastoma is rare and tends to be large in size when diagnosed at presentation. Complete resection should not be delayed, as impingement on the surrounding structures is imminent.

Pathological findings that contribute to tissue stiffness in the spleen of liver cirrhosis patients.

AIM: Spleen stiffness is increased in liver cirrhosis (LC). We attempted to characterize the pathological features of spleen in LC. METHODS: We compared pathological findings of resected spleen tissues of 28 LC patients and those of six healthy controls. In addition, we measured spleen stiffness before splenectomy by shear wave elastography in nine LC patients. After splenectomy, we examined the relationship between spleen stiffness and pathological findings. RESULTS: Passive congestion of the spleen was more frequently observed in LC patients than in controls (P < 0.01). The sinus was wider in LC patients than in controls (P < 0.01). In the spleens of the LC patients, diffuse α-smooth muscle actin (αSMA) expression of sinusoidal mesenchymal cells and deposition of collagen fibers on the perisinusoidal wall were observed. In nine LC patients whose spleen stiffness was examined, the width of the sinus increased along with spleen stiffness (r = 0.89, P < 0.01). Spleen stiffness was higher in the spleen tissues with diffuse αSMA expression of sinusoidal mesenchymal cells than in those with partial αSMA expression of sinusoidal mesenchymal cells (P = 0.01). The degree of fibrosis was higher in the LC patients with diffuse αSMA expression of the red pulp than in those with partial αSMA expression of the red pulp (P = 0.03). CONCLUSION: In the LC patients, spleen tissues showed passive congestion with a dilated sinus, diffuse αSMA expression of sinusoidal mesenchymal cells, and deposition of collagen fibers on the perisinusoidal wall. This contributed to spleen stiffness.

Granulocyte-colony stimulating factor producing mucinous cystic neoplasm with an associated invasive carcinoma of the pancreas.

The present case study documents an autopsy case of granulocyte-colony stimulating factor (G-CSF)-producing mucinous cystic neoplasm (MCN), with an associated invasive carcinoma of the pancreas. A 65-year-old woman presented to Omuta City Hospital (Omuta Japan) with a primary complaint of abdominal pain. Multiple liver nodules and a pancreatic cyst were detected upon abdominal computed tomography. Initially, liver abscess was suspected as the patient exhibited leukocytosis and elevated C-reactive protein level. However, the serum concentration of G-CSF was 98.8 pg/ml (normal, <39.0 pg/ml). At 6 weeks after admission, the patient succumbed to liver failure. At autopsy, a cystic lesion was identified in the pancreatic tail that contained bloody necrotic fluid. Microscopically, the cystic lesion was composed of columnar and mucin-producing epithelium associated with ovarian-type subepithelial stroma. The stroma exhibited positive immunostaining for vimentin, estrogen receptor and progesterone receptor. Calcification on the cystic wall was observed. The tumor invaded the pancreatic parenchyma and metastasized to the liver and lungs. The lesion was diagnosed as invasive adenocarcinoma arising in MCN. By contrast, liver nodules predominantly consisted of pleomorphic cancer cells with small foci of adenocarcinoma. Pancreatic and hepatic cancer cells were confirmed to be positive for G-CSF staining. The present case report indicates that G-CSF-producing MCNs may be associated with an aggressive clinical course, particularly when anaplastic changes are observed.

Cytopathological and immunocytochemical findings of pancreatic anaplastic carcinoma with ZEB1 expression by means of touch imprint cytology.

Pancreatic anaplastic carcinoma (PAC) is rare and has an aggressive clinical course. We report an autopsy case of PAC focusing on the cytopathological characteristics of the tumor and immunocytochemical staining for vimentin, E-cadherin, and zinc finger E-box binding homeobox 1 (ZEB1), which markers are associated with epithelial markers of epithelial-mesenchymal transition (EMT). A 50-year-old woman presented to our hospital with a chief complaint of jaundice. A pancreatic head tumor and multiple liver nodules were detected on abdominal computed tomography. Biliary cytology under endoscopic retrograde cholangiopancreatography suggested ductal adenocarcinoma. Three months after admission, she died of multiorgan failure. At autopsy, touch imprint cytology using squash preparation of the pancreatic tumor identified two different cell types; numerous isolated malignant cells with large and pleomorphic nuclei and a few clusters showing irregularly overlapped nuclei and irregular contours within the necrotic background. Immunocytochemically, isolated cells were positive for vimentin and ZEB1, and negative for E-cadherin. Conversely, clusters were negative for vimentin and ZEB1, and positive for E-cadherin. Histologically, the tumor was composed of sarcomatous cells with small foci of adenocarcinoma, which were consistent with a diagnosis of PAC. Immunohistochemical staining of the adenocarcinoma and sarcomatous cells corresponded to those of the clusters and isolated malignant cells, respectively. Immunostaining of these EMT markers is useful to distinguish sarcomatous cells from adenocarcinoma and can contribute to the accurate diagnosis of pancreatic tumors with EMT.