[An anatomical case of obstructive jaundice due to the rapid enlargement of hepatic peribiliary cysts in end-stage alcoholic liver cirrhosis].

A man in his 60s had end-stage alcoholic cirrhosis. About six months before his death, hepatic peribiliary cysts (HPBC) rapidly increased, and he developed jaundice and liver failure. The pathological autopsy performed after his death revealed that his intrahepatic bile duct was pressured due to multiple cysts caused by HPBC, which resulted in liver failure. Some cases of HPBC have been associated with alcoholic cirrhosis;however, no other cases of increased HPBC in a short period of time have been reported. Although identifying the cause of increased HPBC in a short time is difficult in this case, it may be have been caused by continuous alcohol drinking after the onset of HPBC. Most patients with HPBC have liver cirrhosis and obstructive jaundice that may promote liver failure as in this case. Therefore, patients with HPBC should not only be instructed for abstinence but also promptly consider effective treatments in the event of obstructive jaundice to prevent liver dysfunction.

A case of planar-type gastrointestinal stromal tumor of the transverse colon with perforation.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the human gastrointestinal tract. They usually develop in the stomach and small intestine, but extremely rarely in the colon. Although most GISTs form a mass, some cases showing a flatly proliferating lesion called planar-type GIST have been reported in the sigmoid colon and small intestine. Those are often associated with diverticular lesion and/or perforation. We present here a case of planar-type GIST of the transverse colon with perforation. A 49-year-old Japanese woman abruptly complained of abdominal pain, and was clinically diagnosed as perforation of the transverse colon. Partial resection of the transverse colon including the perforated site was done, and no apparent mass lesion was present. Histology showed that spindle cells flatly proliferated around the perforated area and replaced the layers from submucosa to subserosa. Immunohistochemistry revealed that the spindle cells were KIT-, DOG1- and CD34-positive. Codons 557 and 558 of exon 11 of the c-kit gene were heterozygously deleted at the lesional tissue but not at the normal mucosal tissue. Planar-type GIST of the transverse colon has not been reported yet, and the literature search for the similar cases was done.

Evidence that glial cells attenuate G47R transthyretin accumulation in the central nervous system.

Amyloidogenic protein forms amyloid aggregations at membranes leading to dysfunction of amyloid clearance and amyloidosis. Glial cells function in the clearance and degradation of amyloid ß (Aß) in the brain. This study aimed to clarify the reason why amyloid transthyretin (ATTR) rarely accumulates in the CNS. We pathologically analyzed the relationship between amyloid deposition with basement membranes or glial cells in a rare case of ATTR leptomeningeal amyloidosis. In addition, we compared the cytotoxicity of ATTR G47R, the amyloidosis-causing mutation in the case studied (n = 1), and Aß in brains from patients with cerebral amyloid angiopathy (n = 6). In the subarachnoid space of the ATTR G47R case, most amyloids accumulated at the components of basement membranes. On the CNS surface, ATTR accumulations were retained by astrocytic end feet. In areas where glial end feet enveloped ATTR, ubiquitination and micro-vacuolation of ATTR was evident. The colocalization of GFAP and ubiquitin was also evident. The accumulation of ATTR G47R in the CNS was negatively correlated with the prevalence of astrocytes. Quantitatively, amyloid deposits along the vessels were mostly partial in cerebral Aß angiopathy cases and nearly complete along the basement membrane in the ATTR G47R case. The vascular expressions of type IV collagen and smooth muscle actin were severely reduced in areas with ATTR G47R deposition, but not in areas with Aß deposition. The vascular protein level recovered in the ATTR G47R case when vessels entered into areas of parenchyma that were rich in astrocytes. In addition, the strong interactions between the transthyretin variant and basement membranes may have led to dysfunction of transthyretin clearance and leptomeningeal amyloidosis. The present study was the first to show that glial cells may attenuate G47R transthyretin accumulation in the CNS.

An autopsy case of leptomeningeal amyloidosis associated with transthyretin Gly47Arg mutation.

We report the case of a 47-year-old woman with a 4-year history of progressive numbness in the distal portions of both her lower limbs, diarrhea alternating with periods of constipation, and orthostatic syncope. She demonstrated sensory dominant neuropathy and dysautonomia including orthostatic hypotension, paralytic ileus, and urinary retention. A systemic mutation analysis revealed a G47R mutation in transthyretin (TTR). Her general condition was so poor that we could not perform active treatment. Her consciousness had been impaired for a few months. She died at the age of 47 due to multiple organ failure. An autopsy revealed amyloid deposits in the subarachnoid space of the brainstem and the spinal cord as well as in the peripheral nerve and other organs. To date, this is the first case in which a G47R mutation is associated with leptomeningeal amyloidosis.

Our experience of treating undifferentiated gastric carcinoma: report of four cases.

Undifferentiated gastric carcinoma is a rare histopathological type of cancer that does not show any differentiation toward adenocarcinoma or squamous cell carcinoma. It is thought to be highly malignant, and is associated with a poor prognosis. However, its clinical behavior has not yet been fully analyzed because of its rarity. We herein review the clinical characteristics and prognoses of patients with undifferentiated gastric carcinoma treated at our institutions. Among 2,651 gastric cancer patients, four (0.2 %) were histopathologically diagnosed to have undifferentiated carcinoma. These four patients included three males and one female. The median age of the patients was 60-year old (range 47-75). Three cases had distant metastases at diagnosis. One of these three cases was treated with chemotherapy alone, and the other two were treated with palliative gastrectomy and chemotherapy. The patient with no distant metastasis underwent curative gastrectomy and adjuvant chemotherapy. All patients died of cancer at a median of 5.4 (range 3.5-7.1) months after their diagnoses.

[Report of a successful case of multidisciplinary therapy for a patient with lung and liver metastasis from rectal adenocarcinoma].

A strategy of multidisciplinary therapy is considered necessary for the longer survival of a patient diagnosed with advanced colorectal cancer. We report a successful multi-disciplinary therapy case of a 70's-year-old male who received pulmonary resection for metastatic lung cancer twice after primary resection for rectal cancer. Solitary metastatic liver cancer with portal vein tumor thrombus (PVTT) was diagnosed 5 years and 4 months after primary surgery. Although systemic chemotherapy was started immediately, disease control was poor and local pulmonary recurrence appeared. Although intrahepatic metastasis was considered the most important prognostic factor, radiation therapy against PVTT (50 Gy) was initially performed to control disease. After verifying that no new recurrent lesions had arisen during radiation therapy, a third pulmonary resection (in the left upper remnant lobectomy)was performed. Hepatectomy(in the right lobectomy)was then performed for curative purposes. Pathological efficacy of radiation therapy to PVTT was revealed as GradeIb according to Evans' classification. In accordance with the patient's request, no adjuvant treatment was planned. Seven years after primary resection no sign of recurrence is evident. Radiation therapy is suggested to be most useful for disease control and patient selection.

Gastric neuroendocrine tumors in our institutions according to the WHO 2010 classification.

In 2010, World Health Organization classified gastric neuroendocrine tumor (NET) as follows: NET grade (G) 1, NET G2, neuroendocrine carcinoma (NEC). We reviewed 22 gastric NETs that were encountered in our institutions. Nine, 6, and 4 were NET G1, G2, and NEC, respectively. We also encountered 3 NET G3. NET G1 was treated with observation in 2 patients, endoscopic mucosal resection (EMR) in 3, and gastrectomy in 4 patients. No recurrence was experienced during a median of 53 months of follow-up. All NET G2 was treated with gastrectomy. No patient experienced recurrence during a median of 25 months of follow-up. NET G3 was treated with gastrectomy. One patient died of liver metastasis 52 months after gastrectomy. For NEC, gastrectomy was performed in 3 cases and no patients died of tumor-related death. We conclude that the prognoses of NET G1 and G2 were good. We also experienced long-term survivors of NEC. An accumulation of more patients is needed for further investigation.

Peripheral T-cell lymphoma developing at ileocolonic anastomosis site after colectomy for adenocarcinoma.

A 69-year-old man underwent right hemicolectomy for colon cancer in the transverse colon in 2005. Two years after surgery, he was admitted with abdominal pain. Colonoscopy revealed a submucosal tumor of approximately 4 cm in size at the ileocolonic anastomosis site. In the biopsied samples from the anastomosis site, there was diffuse proliferation of large lymphoid cells, which were immunohistochemically positive for CD3 and CD4, but negative for CD8 and CD20. Clonality analysis of T-cell receptor-beta gene rearrangement revealed a single band, indicating monoclonal proliferation of the T- lymphocytes. Epstein-Barr virus in situ hybridization did not reveal any positive signals in any of the tumor cells. Anti-human T-lymphotropic virus-I was negative. Based on these findings, the recurrent tumor was diagnosed as peripheral T-cell lymphoma-unspecified (PTCL-u).

Intravascular lymphomatosis initially suspected from uterine cytology: a case report.

BACKGROUND: Because recognizable lesions are often absent, selection of biopsy sites for diagnosis of intravascular large B-cell lymphoma (IVL) is frequently problematic. CASE: A 59-year-old woman was admitted with fever and general fatigue. Combined physical and roentgenographic examinations revealed neither lymphadenopathy, hepatosplenomegaly nor mass lesions in other organs. Serum lactate dehydrogenase level was 1412 IU/L. There were no genital symptoms, but uterine cytologic examination revealed large cells distributed in a noncohesive pattern. These cells had a large, irregularly shaped nucleus in which several nucleoli were discernible and showed positive immunoreactivity for leukocyte common antigen. Three months after admission, neurologic symptoms appeared, and magnetic resonance imaging revealed multiple nodular lesions in the brain. Biopsy specimens from the brain lesion showed the proliferation of large lymphoid cells filling the lumina of small vessels and Virchow-Robin's space. Immunohistochemistry revealed that the tumor cells were positive for CD20 and CD79a but negative for CD3, indicative of IVL. CONCLUSION: Uterine cytologic and/or histologic examinations could be the choice for diagnosis of IVL, even when genital symptoms are absent.

Successful treatment of cardiogenic shock caused by humoral cardiac allograft rejection.

The progress of immunosuppressive therapy has made heart transplantation the standard therapy for end-stage heart failure. However, humoral rejection of the cardiac allograft is still a challenging problem associated with high incidence of graft loss and patient mortality. The present patient developed profound cardiogenic shock requiring extracorporeal life support on the 8th day after heart transplantation. Endomyocardial biopsy revealed no cellular rejection, and complement component C4d was positively stained on the capillary endothelium. The patient was successfully treated with repeated plasmapheresis and administration of anti-CD20 monoclonal antibody, rituximab, as well as with steroid pulse and increased standard immunosuppressive medication.

The expression of anamorsin in diffuse large B cell lymphoma: possible prognostic biomarker for low IPI patients.

Anamorsin is a cell-death-defying factor, which was originally isolated as a molecule that conferred resistance to apoptosis induced by growth factor starvation. In order to evaluate anamorsin expression levels in malignant lymphoma, we immunostained paraffin-embedded sections with anti-anamorsin monoclonal antibodies. About 40% (89/234) of sections from patients with diffuse large B cell lymphoma (DLBCL) showed strong anamorsin expression. Comparing the level of anamorsin expression in DLBCL patients with their clinical features (i.e., overall survival rate, International Prognostic Index (IPI) parameters, and treatment response) revealed no significant correlation between anamorsin expression levels and these clinical features. However, anamorsin expression in DLBCL patients with a low IPI was shown to be an unfavorable biomarker, especially in the patients who received chemotherapy without rituximab. It is suggested that anamorsin might play some roles in the abnormal growth of DLBCL.

Diffuse large B-cell lymphoma in the young in Japan: a study by the Osaka Lymphoma Study Group.

Clinicopathological and immunophenotypical characteristics in 24 patients with diffuse large B-cell lymphoma (DLBCL) under 30 years of age in Osaka, Japan were examined, and the results compared to those of DLBCL patients aged over 40 years in Osaka and of young DLBCL patients in Western countries. The level of LDH and IPI score at initial diagnosis were significantly lower in young than older patients. The sex ratio (M:F) and age range (median) in the young and older groups were 1.18 and 11-30 (24.8) years and 1.59 and 42-87 (62.4) years, respectively. Extranodal presentation was higher in the young group (83.3% versus 60.0%, P < 0.05). Based on immunophenotyping with anti-CD10, bcl-6, and MUM1 antibodies, the cases were categorized as germinal center B-cell (GCB) (CD10+ or CD10-, bcl-6+, MUM1+) or non-GCB phenotype. The frequency of GCB type was significantly lower in the young group than older group (25% vs. 54%, P < 0.05), and much lower than that reported for young patients in Western countries. In situ hybridization revealed one of the young patients to be positive for Epstein-Barr virus (EBV). In the older group, none of 31 cases showed EBV positivity. Three year event-free and overall survival rates of young patients were better than those of the older patients, although not significantly different. DLBCL in the young in Japan is characterized by a much lower frequency of the GCB phenotype compared to that in Western countries.

Lymphoproliferative disorders in autoimmune diseases in Japan: analysis of clinicopathological features and Epstein-Barr virus infection.

Lymphoproliferative disorders (LPD) occasionally develop in individuals with immune deficiencies such as immunosuppressive conditions and autoimmune diseases (AID). In our study, the clinicopathologic features and virus status were analyzed in 53 cases with LPD developing in rheumatoid arthritis (RA) and other AID. AID in only 4 of 53 patients had been treated with some sort of immunosuppressive therapy, including methotrexate. Median age at the diagnosis of LPD in AID was 60 years old with marked female predominance (M/F = 0.4). The median interval between the onset of AID and LPD development was 45 months, and longer in RA patients than in other AID (p < 0.01). The primary site of lymphoma was nodal in 21 cases and extra-nodal in 24, with clinical Stage I in 17, II in 5, III in 13, and IV in 13. Immunohistochemistry showed that 39 cases were B cell type, 10 were T cell type and 4 were Hodgkin lymphoma (HL). Then majority of B cell cases were diffuse large B cell lymphomas, and 2 were diffuse polymorphic type. EBER-1 in situ hybridization for Epstein-Barr virus (EBV) showed positive signals in tumor cells in 16 of 53 (30.2%) cases. The EBV-positive rate in T cell LPD (70%) was much higher than that in B cell LPD (12.8%) (p < 0.01). All 4 cases of HL were EBV-positive. Immunohistochemistry showed a latency II pattern of EBV infection (LMP-1(+) and EBNA-2(-)). Five-year overall survival rate was 33%. Multivariate analysis showed that only type of AID was an independent factor for survival of patients, i.e., LPD in RA showed the most favorable prognosis. In conclusion, LPD in AID generally shared common features with sporadic LPD except for a much higher EBV-positive rate in T cell LPD.

Clonality analysis of follicular lymphoma using laser capture microdissection method.

Whether a common and a single clone present, or not, among follicles of follicular lymphoma (FL) was examined in 12 cases with FL. Histologic grade was I in 6 cases, II in 3, and III in 3. DNA was selectively extracted from the neoplastic follicles of paraffin-embedded samples with use of laser capture microdissection method, and used for PCR-based analysis of rearrangement of immunoglobulin heavy chain variable region gene. Three different follicles in each case of FL were microdissected. Semi-nested PCR was performed using two sets of primers (Fr2A and Fr3A). In PCR with Fr2A primers, nine of 12 cases showed a common band among neoplastic follicles. The remaining three cases showed no PCR products. With Fr3A primers, eight of 12 cases showed a common band among follicles of the same case. The other four cases showed oligoclonal bands, among them presence of a common band was difficult to assess. Oligoclonal bands were more frequently observed in PCR with Fr3A than that with Fr2A and in grade I or II than in grade III cases. In total, 11 of 12 cases showed a common band in PCR with either Fr2A or Fr3A primers. In two cases, DNA extracted from whole section was amplified with both Fr2A and Fr3A or only Fr3A primers, showing smear or oligoclonal bands. These results showed the presence of a single clone of cells in neoplastic follicles of FL and the usefulness of PCR-based rearrangement analysis of immunoglobulin heavy chain gene combined with microdissection methods for differential diagnosis of FL from follicular hyperplasia.

Polymerase chain reaction-based clonality analysis in thyroid lymphoma.

A previous patho-epidemiological study indicated that thyroid lymphoma (TL) evolves among active lymphoid cells into chronic lymphocytic thyroiditis (CLTH), a thyroid-specific autoimmune disease. In this study, clonality of B-cells in the CLTH and TL lesions was analyzed using polymerase chain reaction (PCR)-based method on surgically resected samples from 10 cases of TL; 7 mucosa-associated lymphoid tissue (MALT) lymphoma and 3 diffuse large B-cell lymphoma (DLBCL). CLTH lesions coexisted in all the cases with MALT lymphoma, but not in the three DLBCL cases. In cases of MALT lymphoma, the lymphomatous and CLTH areas were separately microdissected from each section and analyzed for clonality. In the cases of DLBCL, the whole specimens were used for clonality analysis. CLTH lesions showed smear in 6 samples, two bands in one, and more than three (oligoclonal pattern) in 2. MALT lymphoma lesions showed single or two bands (monoclonal pattern) in 4, oligoclonal pattern in 4, and smear in one. DLBCL showed monoclonal pattern in two and oligoclonal pattern in one. One common band was present among two separate MALT lesions in one case, but no common bands were found in the remaining six cases. These findings suggested the clonal evolution of B-cell from polyclonal to monoclonal proliferation to take place in the continuum of lymphoproliferative lesions into autoimmune thyroiditis.