Aggressive venous invasion in the area of carcinoma correlates with liver metastasis as an index of metastasis for invasive ductal carcinoma of the pancreas.

BACKGROUND: Invasive ductal carcinoma of the pancreas (IDCP) predominantly causes death through liver metastasis (LM) and peritoneal dissemination with local recurrence. However, whether its venous invasion is from the enlarged carcinoma accompanied by tumor growth, or from a distinct carcinoma group, for which venous invasion is facilitated by proximity to the origin, is unclear. We analyzed the correlation between LM and venous invasion in patients with small IDCP tumors. METHODS: Of 388 patients who were diagnosed with IDCP, 20 (5.2%) had tumors with diameters <2 cm. The follow-up period of the 20 patients with smaller tumors was 1-24 years. RESULTS: The small-tumor group (n = 20) included 11 men and 9 women, aged 51-80 years. Five died of liver metastasis (LM group, n = 5) and 15 patients (non-LM group, n = 15) were either alive without recurrence (n = 11) or died of peritonitis carcinomatosa following local recurrence, subarachnoid hemorrhage, primary lung cancer, or old age (n = 1 for each cause of death). The LM and non-LM groups did not significantly differ in numbers of venous invasion by the carcinoma in IDCP and non-IDCP area of the pancreas. However, median numbers of invaded veins in the area of IDCP and percentage of invaded vein/total number of vein in IDCP area were significantly higher in the LM group. CONCLUSION: Among patients with small IDCP tumors, the LM group showed more aggressive venous invasion by IDPC. Patients in whom ≥60% of veins were invaded by IDCP should be prepared for LM.

Huge epithelioid malignant peripheral nerve sheath tumor in the left axilla: a case report.

This report describes a patient with a rare huge epithelioid malignant peripheral nerve sheath tumor (MPNST) in the left axilla. A male in his 70s was admitted to our hospital for evaluation of a growing tumor in his left axilla. The tumor was solid and immovable. Examination of a biopsy specimen resulted in a diagnosis of epithelioid MPNST. Two weeks after the biopsy was performed, the tumor grew to 20 cm and became painful, and the patient was unable to feel pressure on his upper arm. Immediately before surgery to remove the tumor, computed tomography suggested the presence of lung metastases. The patient and his family were informed of his disease state, and they elected surgical treatment to ease the symptoms associated with tumor enlargement. Systemic metastases appeared soon after the surgery, and the patient died within 11 weeks. Comparative genomic hybridization (CGH) analysis showed that this tumor was chromosomally unstable, with impairments in gene expression.

Clinicopathological characteristics and rituximab addition to cytotoxic therapies in patients with rheumatoid arthritis and methotrexate-associated large B lymphoproliferative disorders.

AIMS: To analyse the clinicopathological characteristics and prognosis of 40 rheumatoid arthritis (RA) patients with methotrexate (MTX)-associated large B cell lymphoproliferative disorders (MTX-BLPD). METHODS AND RESULTS: Soluble interleukin 2 receptor titres (median 1500 U/ml) in 40 patients with MTX-BLPD were lower than those of 24 RA patients with non-MTX- associated (non-MTX) BLPD (5731 U/ml) and 15 with control diffuse large B cell lymphoma (DLBCL, 5918 U/ml) (P < 0.01). Using in-situ hybridization, Epstein-Barr virus (EBV) was detected in tumour cells of 25 of 40 RA patients with MTX-BLPD (63%). Immunohistologically, BCL2 expression was detected in 35% of patients with MTX-BLPD, which was lower than 93% of control DLBCL patients (P < 0.01). Eleven patients with EBV(+) MTX-BLPD (44%) showed remission after MTX withdrawal. In RA patients with clinical stage III/IV BLPD, 15 with rituximab (R)+ cytotoxic therapies pursued better prognosis than 10 with R- cytotoxic therapies (P < 0.05). Among the 15 patients, seven with MTX-BLPD showed better overall survival than nine control DLBCL patients (P < 0.01). CONCLUSIONS: In RA patients with MTX-BLPD, immunosuppression by MTX, EBV infection and low BCL2 expression in tumour cells may play roles in tumorigenesis and tumour regression. R+ cytotoxic therapies as well as MTX withdrawal were highly effective in these patients.

Influence of microscopically positive resection margins on long-term (>5-year) survival after resection of pancreatic ductal adenocarcinoma.

CONTEXT: The impact of R1 resection on outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) is unclear, with most studies assessing survival for up to 5 years. OBJECTIVE: The aim of this study was to evaluate the prognostic influence of R1 and R0 resection on >5-year survival in patients with PDAC. MATERIAL AND METHODS: Of the 271 patients with PDAC who underwent pancreatic resection over a 26-year period, 33 had survived for ≥5 years. R1 status was defined as the presence of tumor tissue ≤1 mm from a circumferential margin surface. Patients were followed-up for 61 to 288 months. RESULTS: Of the 33 long-term survivors, 19 and 14 underwent R0 and R1 resection, respectively. The percentage of male patients was significantly higher in the R1 than in the R0 group. The R0 group tended to show a weaker relationship between R status and stage than the R1 group. Multivariate analysis showed that R status was an independent prognostic marker (P=0.0071), and Kaplan-Meier curves showed that >5-year survivors in the R1 group had significantly poorer prognoses (P=0.002). CONCLUSIONS: Patients who have survived >5 years following R1 resection for PDAC can experience tumor recurrence in the resected area.

[Distribution of intraductal carcinoma of the prostate and associated lesions in the cancer foci on radical prostatectomy specimens].

OBJECTIVE: The distribution of intraductal carcinoma of the prostate (IDC-P) and other intraductal lesions associated with IDC-P was evaluated in the cancer foci on radical prostatectomy specimens. MATERIALS AND METHODS: We reviewed slide in 412 cases treated by radical prostatectomy without neoadjuvant therapy. Mapping study was performed with regard to IDC-P, other intraductal lesions associated with IDC-P and invasive carcinoma. RESULTS: We identified 98 cases (23.8%) and 102 cancer foci associated with IDC-P. In these all cancer foci, IDC-P was associated with invasive carcinoma and other intraductal neoplastic lesions with tufting, micropapillary and loose cribriform patterns were contiguous and admixed with IDC-P in 83 cancer foci (81.4%). There were lesions with invasive carcinoma around the IDC-P in 95 cancer foci (93.1%) and lesions without invasive carcinoma around IDC-P in 66 foci (64.7%). The latter lesions existed in the marginal areas of the cancer foci in 63 (61.8%) and in the central areas of the cancer foci in 14 (13.7%). In 5 cancer foci (4.9%), volume of IDC-P was larger than that of invasive carcinoma. CONCLUSIONS: The distribution of IDC-P with dense cribriform and solid patterns varied in cancer foci, and intraductal lesions with tufting, micropapillary and loose cribriform patterns were frequently seen in area contiguous and admixed with IDC-P. The latter lesion may be low grade morphology of IDC-P, although the lesions could not be distinguished from high grade prostatic intraepithelial neoplasia.

[Liver arterial infusion chemotherapy with adjuvant trastuzumab for the simultaneous treatment of liver and breast cancer-a case report].

A 62-year-old woman being treated for chronic hepatitis C and high blood pressure was shown by computed tomography to have tumors in the lateral and medial segments of her liver, and in her right breast. The tumor in the lateral segment of the liver was excised, the tumor in the medial segment of the liver was treated with microwave coagulation therapy, and the breast tumor was treated with simple mastectomy and sentinel lymph-node biopsy. Based on pathological features, the liver tumors were classified as moderately differentiated liver cell carcinoma, and the breast tumor as estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor-2-positive ductal carcinoma. Hepatic arterial infusion chemotherapy using fluorouracil and cisplatin with trastuzumab as an adjuvant was administered to treat both cancers simultaneously. Twelve months after the operation, neither of the cancers had relapsed. This case suggests that when the breast cancer is human epidermal growth factor receptor-2-positive, trastuzumab should be administered as adjuvant therapy.

[A case of primary T-cell central nervous system lymphoma (T-PCNSL) relevant to HTLV-I].

Primary T-cell lymphoma of the central nervous system lymphoma (T-PCNSL) is an extremely rare tumor. A human T-cell lymphoma virus type I(HTLV-I) associated adult TCL often involves the CNS during its course but disease limited to the CNS is exceptional. We report a case of a 63-year-old male with a highly malignant TCL localized in the bilateral cerebral hemispheres. The patient was HTLV-I positive but no systemic disease was detected after various examinations. We discuss the clinico-pathological features of TCL in the CNS reported in the literature including our case and compare them with those of B-cell lymphomas.

A case of relapsing polychondritis associated with auricular cartilage infiltration of immunoglobulin G4-positive plasma cells and lung cancer.

A 79-year-old man was diagnosed with relapsing polychondritis, from symptoms of bilateral auricular deformity and pigmentation, polyarthralgia, and audiovestibular damage, and from histological examination of the left auricular cartilage. The left auricular cartilage biopsy specimen revealed cartilage destruction with infiltration of plasmacytes expressing IgG4. This case suggests that IgG4 may be involved in the pathogenesis and etiology of relapsing polychondritis.

Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy-associated T cell lymphoma in Japan.

AIMS: To elucidate the clinicopathological findings of primary intestinal enteropathy-associated T cell lymphoma (EATL) in Japan, a non-endemic area for coeliac disease. METHODS AND RESULTS: Of the 24 cases, four (17%) had large-cell lymphoma (type I), and the remaining 20 (83%) had medium-sized lymphoma (type II). Lymphoma cells of the three type I cases were CD56-positive. Only one (4%) case showed typical CD56- and CD8-negative and CD30-positive type I EATL. In type II EATL, lymphoma cells of the 16 (80%) and 11 (55%) cases were positive for CD56 and CD8, respectively. Intramucosal tumour spreading and adjacent enteropathy-like lesions were detected in 15 (71%) and 16 (76%) of 21 cases, with a severe increase of intraepithelial lymphocytes (IELs) in 12 (57%). IELs of enteropathy-like lesions in five (24%) cases expressed T-bet, with no cases of CD30-positive IELs. Characteristic findings from comparative genomic hybridization of 15 cases indicated gains of 8q2 (47%), Xp (53%) and Xq (73%), but no gain of 9q3. Regarding, human leucocyte antigen (HLA) status, six cases examined did not express the DQB1*02 allele. CONCLUSIONS: Japanese EATL exhibited different histology, cytogenetic findings and HLA status from those of typical type I EATL. The rare incidence of coeliac disease may influence the tumour cell characteristics of EATL and IELs.

[A case of breast meningeal carcinomatosis caused by trastuzumab treatment as adjuvant chemotherapy].

A 52-year-old woman underwent modified radical mastectomy and axillary lymph node resection for right breast cancer (stage IIB). Afterwards FEC therapy (5-FU 500 mg/m/2, epirubicin 75 mg/m2, cyclophosphamide 500 mg/m2) x 4, docetaxel therapy (60 mg/m2) x 4 and radiation of the illness side collarbone, upper and lower lymph nodes were enforced for adjuvant therapy after the operation. Furthermore, administration of aromatase inhibitor (anastrozole) and trastuzumab was started due to the postoperative pathological diagnosis of hormone receptor-positive and HER2 (score 3+). This became an urgent hospital admission because of the sudden escape power from impaired consciousness due to the articulation disorders and limb weakness when trastuzumab was administered nine times. It was diagnosed by MRI examination and the cerebrospinal fluid cytology as meningeal carcinomatosis of breast cancer, and she died on the 31st recurrence of disease. A serious relapse may be caused in a case of fast-progressing breast cancer like this while being administered trastuzumab as an adjuvant treatment.

Clinicopathological characteristics of primary gastric T-cell lymphoma.

AIMS: To investigate the clinicopathological characteristics of 20 primary gastric T-cell lymphoma (GTCL) cases without human T-lymphotropic virus type I infection in Japan, a non-endemic area for coeliac disease. METHODS AND RESULTS: Fifteen cases had no history of persistent diarrhoea or severe hypoproteinaemia. Histologically, 13 cases (65%) consisted of large cell lymphoma and seven (35%) were of medium-sized cells. Intraepithelial lymphoma cell invasion was found in three cases (15%). Two of 10 surgical cases (20%) showed intramucosal tumour cell spreading with enteropathy-like features. Helicobacter pylori CagA gene was detected in three of 10 cases (30%). The lymphoma cells of all 20 cases were positive for CD3 and/or TCRbetaF1 and negative for CD56. CD4- and CD8- lymphoma was found in 11 cases (55%), CD4+ lymphoma in seven (35%) and CD8+ lymphoma in two (10%). CD30+, CD5+ and CD25+ lymphomas were detected in nine (45%), 10 (50%) and 11 (55%) cases, respectively. Five-year survival of the 16 available cases was 54%. Early clinical stage and medium-sized cell lymphoma were significantly (P < 0.05) better prognostic factors. CONCLUSIONS: Patients with GTCL exhibit distinct clinicopathological findings and prognoses from those with enteropathy-associated T-cell lymphomas. GTCL may be mainly derived from lamina propria and parafollicular T cells.

FU-MK-1 expression in human gallbladder carcinoma: an antigenic prediction marker for a better postsurgical prognosis.

Gallbladder carcinoma is an aggressive type of neoplasm difficult to cure by conventional procedures. Because of the lack of reliable markers for assessing the prognosis, this retrospective study was designed to investigate the prognostic significance of MK-1 overexpression in human carcinoma of the gallbladder. Immunohistochemical staining using monoclonal antibody FU-MK-1 (MK-1 antigen) was performed on paraffin-embedded tissues from 63 patients who had undergone surgical resection for gallbladder carcinoma. Expression of MK-1 was found in 50 (79%) of 63 tumor samples. All 21 papillary and 12 of 13 well-differentiated tubular adenocarcinomas but only 1 of 8 poorly differentiated adenocarcinomas were positive for FU-MK-1. Multivariate analysis showed that only MK-1 expression was an independent prognostic marker (P = .0473), and Kaplan-Meier curves showed that MK-1 expression was significantly related to increased overall survival (P < .0001). These results suggest that MK-1 expression is a prognostic marker in gallbladder carcinoma.

Diagnosis of small pancreatic cancer by endoscopic balloon-catheter spot pancreatography: an analysis of 29 patients.

OBJECTIVES: The diagnosis of small pancreatic cancer remains difficult. The present study describes the diagnostic value of endoscopic balloon-catheter spot pancreatography for small pancreatic cancer. METHODS: Since April 1984, balloon spot pancreatography has been used to detect small-sized pancreatic cancer in patients having possible symptoms or findings of obstructive pancreatitis. RESULTS: A resection was performed on 175 of 416 patients with conditions diagnosed as pancreatic cancer. Of the 175 patients, 23 (13%) had invasive carcinoma 2 cm or smaller based on histological measurements, 3 intraductal papillotubular adenocarcinoma, and 3 carcinoma in situ (CIS). Regarding invasive carcinoma, balloon pancreatography displayed duct abnormalities diagnosed as carcinoma in 20 of 22 patients, whereas carcinoma was suggested in 2. A definite diagnosis was obtained based on the findings of main duct stenosis or obstruction with marked stricture of the branch ducts (n = 18) and a filling defect in the main duct (n = 2). Moreover, this pancreatogram demonstrated an intraductal filling defect in 2 of 3 with intraductal carcinoma and dead twiglike findings in the branch ducts in 1 of 3 with CIS. CONCLUSIONS: Balloon spot pancreatography is an essential tool for the diagnosis of small ductal pancreatic cancer, and it also makes it possible to locate CIS lesions of the branch ducts.

Balloon-catheter endoscopic retrograde pancreatography-compression study for diagnosis of early-stage pancreatitis.

Endoscopic retrograde pancreatography (ERP) is considered by many as the gold standard imaging method in the diagnosis of chronic pancreatitis (CP). However, conventional ERP usually has a limited ability to accurately diagnose early-stage CP, in which only the branch ducts are involved and the main pancreatic duct (MPD) is unaffected. To visualize precisely the branch ducts, we have developed a more sophisticated ERP method, called balloon ERP-compression study (balloon ERP-CS). In this procedure, a catheter equipped with a balloon at its tip is placed first into the MPD via the papilla with the aid of conventional ERP, followed by the removal of the endoscope, leaving the catheter behind. Then, the balloon is inflated, and the contrast medium is injected slowly. The balloon serves to block the back flow of the injected contrast medium from the MPD to the duodenum, enabling visualization of the branch ducts. The compression study affords further precise pancreatography of the corresponding area. Thus, balloon ERP-CS has now become an essential procedure for diagnosis of pancreatic lesions, including CP. So far (April 1984 to April 2005), we have performed the procedure in 1012 cases, for a total of 1562 examinations. In this study, we focus on the role of balloon ERP-CS in diagnosis of early-stage CP to elucidate its characteristic features in association with histological findings. This presentation will clarify the usefulness as well as the limitations of balloon ERP-CS for the diagnosis of CP, especially cases without the involvement of the MPD.

MK-1 expression in carcinoma of the ampulla of Vater as a predictor of improved prognosis after surgical resection.

This retrospective study investigated the prognostic significance of MK-1 expression in human carcinoma of the ampulla of Vater (CAV). Expression was examined immunohistochemically using specimens from 38 patients who underwent surgical treatment for CAV. Expression was found in 61% of samples. Thirteen of 15 well-differentiated but only two of eight poorly differentiated adenocarcinoma were positive (P=0.0352). MK-1 positivity tended to show significantly decreasing pT (P=0.0039), pN (P

Intraductal tubular adenoma of the pancreas, pyloric gland type: a clinicopathologic and immunohistochemical study of 6 cases.

The intraductal tubular adenoma (ITA), pyloric gland type, of the pancreas is an uncommon benign tumor, akin to the pyloric gland type adenoma of the gallbladder. We report 6 cases of ITA of the pancreas: 3 male and 3 female aged 50 to 79 years (mean, 63.5 years; median, 65 years); all were examined clinicopathologically. Four patients showed no symptoms, but appetite loss and/or general fatigue presented in two. Grossly, all tumors formed a localized polypoid mass protruding into the lumen of the dilated pancreatic duct. Five of the six tumors were found within the main duct, and the other arose within the branch duct of the pancreas. Microscopically, the tumors were composed of closely packed tubular glands resembling pyloric type glands. They were lined by columnar or cuboidal epithelial cells with foci of mild to moderate dysplastic change. In 2 cases, the adjacent pancreas showed foci of intraductal papillary-mucinous adenoma. Histochemically, the tumors largely showed neutral mucin with a lesser amount of acidic mucin made up mainly of sialomucin. Endocrine cells were found in five tumors. Immunohistochemically, all tumors were labeled with M-GGMC-1 and MUC6, whereas MUC1 and MUC2 stains were negative. Pepsinogen II was positive in 5 tumors; thus, the results displayed a pattern of differentiation similar to those of ordinary gastric pyloric or metaplastic pyloric glands. DPC4 expression was maintained in all tumors and p53-positive nuclei were hardly encountered. All patients are alive with no evidence of disease 3 to 10.5 years after surgical resection.

Expressions of two adenomatous polyposis coli and E-cadherin proteins on human colorectal cancers.

Mutations in the adenomatous polyposis coli (APC) gene contribute to the progression of colorectal tumorigenesis. Despite the importance, few studies regarding the localization of this protein on surgically resected human colorectal cancer specimens using immunohistochemistry have been reported so far because of the unavailability of the antibodies for this use. The goal of this study has been to provide the APC protein expression and to validate the APC molecular studies. We took advantage of an immunohistochemistry procedure of applying the unique detergent-mediated antigen retrieval technique to frozen sections and examined the expressions of one amino (N)-terminal (AC4) and one carboxy (C)-terminal APC antibody (HG2). Further, we compared the stainings of APC antibodies with those of the E-cadherin antibody using a quantitative image analysis. E-cadherin is a critical morphogenetic regulator during embryogenesis and recent evidence strongly suggests that downregulation of E-cadherin expression in cancers is associated with a high rate of invasion and metastasis. The analysis indicated statistically that normal epithelia showed stronger staining than cancer cells ( P<0.05). Further, in normal epithelia, the amino (N)-terminal APC antibody (AC4) showed a positive correlation with another carboxy (C)-terminal APC antibody (HG2). E-cadherin showed no positive correlation with other APCs in either the normal epithelia or cancer cells. This study verified reduced expressions of APCs and E-cadherin proteins in colorectal cancer cells. This suggests that the normal APC and E-cadherin protein expressions in benign epithelium are progressively and independently lost in the sporadic colorectal cancers.