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Hepatocellular carcinoma (HCC) hemorrhaging/rupture is a rare adverse effect of lenvatinib, and only limited pathological examinations have been reported. This report presents the case of a 69-year-old man who suffered from cardiac arrest and died 7 days after starting lenvatinib treatment for HCC, with an autopsy subsequently performed. Crack and coagulated blood were observed in the largest tumor. Pathologically, the hemorrhaging area was scattered in nearly all of the HCC lesions, regardless of tumor differentiation. This pathological feature is unusual in normal HCC. Thus, it is believed to have been the effect of lenvatinib.

Carcinosarcomas (CSs) of the endometrium have admixture of malignant epithelial and mesenchymal components. The carcinomatous component exhibit endometrioid, serous, or clear cell differentiation, or are undifferentiated. CSs are considered homologous or heterologous according to the type of sarcomatous component. Sertoliform endometrioid carcinomas (SECs) of the endometrium which comprise a rare subtype of endometrial cancer, typically occur in the ovary. SECs as a carcinomatous component of CS of the endometrium have not been reported. Here, we report an endometrial carcinosarcoma that contains an SEC component. An 88-year-old female presented to a clinic with atypical genital bleeding. She was referred to our hospital and underwent total hysterectomy, bilateral adnexectomy and partial omentectomy due to endometrial carcinoma. Gross examination revealed a polypoid mass in the uterine cavity with massive myometrial invasion. Histologically, the tumor was a high-grade endometrioid carcinoma. In addition to an ordinary conventional endometrioid carcinoma, approximately 30% of the area exhibited sex cord-like pattern and contained small hollow tubules, anastomosing cords and trabeculae, and tightly packed nests. Immunohistochemically, the SEC component showed diffuse p53 staining. Sex cord-like area, especially the solid area, showed positive staining for EMA, vimentin, α-inhibin, CD99, calretinin, p53, CD56, synaptophysin, and chromogranin A, which is a staining pattern similar to that previously reported SEC of the endometrium. Diminished membranous and positive cytoplasmic staining for β-catenin was observed. This is the first case report of an endometrial carcinosarcoma containing an SEC component. SECs of the endometrium might exhibit sex cord-like differentiation in contrast to SECs of the ovary, which do not exhibit sex cord differentiation.

We report a case of a 60-year-old male who presented with fever and anasarca as well as hepatosplenomegaly, general lymphadenopathy, and disseminated intravascular coagulation (DIC), and was, therefore, admitted to our hospital. In addition, the patient suffered from respiratory failure and renal dysfunction and had pleural effusion and ascites. The pathological diagnosis from lymph node biopsy suggested multicentric Castleman's disease of the plasma cell type; however, the presence of high IL-6 levels, myelofibrosis, thrombocytopenia, anasarca, renal dysfunction, and hepatosplenomegaly led to a definitive diagnosis of TAFRO syndrome. Tocilizumab was administered on day 15 of disease diagnosis, resulting in the improvement in DIC but not other symptoms. As schizocytes were detected in the peripheral blood, he also experienced disturbance of consciousness and thrombotic microangiopathy (TMA) was considered. Following plasma exchange (PE) and continuous hemodiafiltration (CHDF), his symptoms temporarily improved. However, his condition worsened again, and he eventually died on day 33. Pathological autopsy revealed that although the lymph nodes were not enlarged, he had organomegaly, gastrointestinal and omental hemorrhage, and acute necrotizing pancreatitis. Since TMA developed after the administration of tocilizumab, the possibility of drug-induced secondary TMA cannot be ruled out.

We diagnosed distal cholangiocarcinoma in a 76-year-old woman who was then treated by subtotal stomach-preserving pancreaticoduodenectomy. Histopathological examination revealed a well-differentiated tubular adenocarcinoma on the side of the bile duct, and a neuroendocrine carcinoma in an area outside the bile duct where the tumor had infiltrated. Immunohistochemical staining identified homology between cytokeratins and MUC, indicating a similar origin. This report discusses problems associated with diagnosis and treatment by summarizing 22 patients who underwent curative resection and subsequently had a confirmed prognosis.

Colorectal cancer is one of the most malignant neoplasms worldwide. Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. In the present study, the anticancer effects of fucoxanthin and its metabolite, fucoxanthinol, on 6 colorectal cancer cell lines and 20 tissue samples from surgically resected clinical colorectal cancer specimens were examined using a collagen-gel droplet embedded culture drug sensitivity test (CD-DST). The in vitro sensitivity to fucoxanthin, fucoxanthinol and the anticancer drugs is expressed as T/C (%), where T is the absorbance of cells which stained by neutral red treated with carotenoids and C is the absorbance of non-staining cells. Fucoxanthin and fucoxanthinol decreased the T/C (%) of Caco-2, WiDr, HCT116, and DLD-1 cell lines at doses of 20 µM. Fucoxanthinol also decreased the T/C (%) of SW620 cells, while the T/C (%) of Colo205 cells was not reduced by treatment with either carotenoid. Specifically, the T/C (%) of Caco-2 and WiDr cells, which were incubated in carotenoid-free medium for 6 days following treatment with 20 µM fucoxanthinol for 24 h, was markedly decreased to 1.4±0.2 and 12.0±0.3%, respectively. Furthermore, fucoxanthin and fucoxanthinol decreased the T/C (%) in colorectal cancer tissue samples. Notably, 20 µM fucoxanthinol treatment resulted in a higher proportion of colorectal cancer samples with a T/C (%) of

A 64-year-old woman was diagnosed with unresectable pancreatic cancer and underwent chemotherapy. However, the number of leukocytes significantly increased as the disease progressed. Serum G-CSF values also increased, and she eventually died on day 511 after diagnosis. Immediately after autopsy, immunohistochemical staining with an anti-G-CSF monoclonal antibody was positive in the poorly differentiated adenocarcinoma area of the primary pancreatic cancer and liver metastatic foci, but negative in the well-differentiated tubular adenocarcinoma part of the primary pancreatic cancer. During de-differentiation, invasive pancreatic ductal carcinoma appeared to have changed to a tumor that produced G-CSF.

A 73-year-old man with a hepatocellular carcinoma was admitted to our hospital. He suffered from recurrent severe hypoglycemia. An autopsy was performed after his death. Anti-insulin-like growth factor II (IGF-II) monoclonal antibody immunostaining of the hepatocellular carcinoma was positive. Western immunoblot analysis of the serum revealed highly elevated IGF-II. Therefore, we diagnosed this case as a non-islet cell tumor hypoglycemia caused by a big IGF-II-producing hepatocellular carcinoma.

A 61-year-old man was admitted to our hospital with extreme weight loss. Abdominal ultrasonography revealed an 8-cm tumor of the pancreatic head. Further investigation revealed orbital, pulmonary, pancreatic, colonic, and bone marrow lesions. A histopathological examination of the pancreatic tumor specimen obtained using endoscopic ultrasound-guided fine-needle aspiration revealed mucosa-associated lymphoid tissue (MALT) lymphoma. Monoclonal rearrangement of immunoglobulin heavy chain was found in the pulmonary, pancreatic, colonic, and bone marrow lesions. We diagnosed multi-organ disseminated MALT lymphoma, with the largest lesion located in the pancreatic head. Chemo-radiation therapy resulted in complete remission.

Testis lymphoma (diffuse large B cell lymphoma) metastasized to the gallbladder. The gall bladder is rarely involved in cases of the malignant lymphoma, and lymphoma metastasis from the testis to the gallbladder has not been previously reported. These reports may possibly change by the introduction of PET/CT. Furthermore, although it was a struggle to diagnose this particular case, there is a possibility that we may have been able to recognize metastasis from the testis at an earlier stage if PET/CT had been conducted.

目的 : 私達は中皮腫の細胞診に特徴的な所見をスコア化し, 中皮腫診断におけるその有用性を検討した.方法 : 病理組織診断により中皮腫であることが確認された 19 例の体腔液を検討した. 腫瘍の発生部位は胸膜 17 例, 腹膜 2 例で, 上皮型 11 例, 二相型 3 例, 肉腫型 5 例だった. 性別は男性 17 例, 女性 2 例だった. 対照として, 任意に選択した癌性胸・腹膜炎 30 例, ClassIIIと診断された反応性中皮 13 例を検討した. 中皮腫に特徴的と考えられている項目に配点をしてその合計点数を数えた. スコアリングの項目と配点は以下のとおりである. 細胞の大小不同性 1 点, 全周性絨毛, ウィンドウ, ブレブを 1 点, 核異型 1 点, 大型好酸性核小体 2 点, 8 核以上の多核細胞 2 点, 相互封入像 1 点, 細胞密度が高いシート状細胞集塊 1 点, ミラーボール様の細胞集塊 1 点で合計点数を 10 点とした.成績 : 中皮腫では 10 点が 4 例, 9 点が 6 例, 8 点が 3 例, 7 点が 3 例, 6 点が 1 例, 5 点が 2 例で 4 点以下はなかった. 一方, 反応性中皮細胞は腹膜由来乳頭状癌の 1 例が 7 点と OK432 を用いた胸膜炎の 1 例が 4 点であるのを除くと, 全例 3 点以下だった.結論 : 本スコアリングは中皮腫の診断に有用だった.

Reduced expression of the p16 gene product (protein), an inhibitor of cyclin-D-dependent protein kinase which regulates cell cycle at the G1/S boundary, is implicated in tumor progression in various neoplasms. Hypermethylation of the p16 promoter gene has recently been suggested to be one of the reasons for the reduced protein expression. To explore the role of p16 in the biological behavior of adenoid cystic carcinomas (ACC), we investigated the immunohistochemical expression of p16 protein in 38 ACC tumors (32 primary, 3 recurrent, and 3 metastatic tumors) and the methylation status of its promoter gene. We also examined their relationships to the histological grade of malignancy. Positive reaction of p16 protein was demonstrated in the nuclei of luminar cuboidal cells in areas with tubular patterns. The reactions were reduced in the areas with solid or large cribriform patterns. The levels of p16 expression correlated with the histological grade of malignancy. Recurrent or metastatic tumors did not differ with respect to histological grades from the original tumor except for 1 case, in which p16 expression was reduced compared to the primary tumor. Methylation-specific PCR demonstrated the hypermethylation status of the p16 promoter gene in 4 of 22 primary tumors (21%), all of which showed negative or low expression of the p16 protein. The study indicated that p16 expression was reduced in ACC cases of higher histological grade of malignancy and that hypermethylation of its promoter gene may be involved in its process in some cases.

We report here a case of a primitive neuroectodermal tumor involving the frontal skull base in a 5-month-old male infant. He presented with rapidly progressing exophthalmos on the left side. Preoperative magnetic resonance imaging revealed a well-demarcated, enhanced mass of 6 cm in diameter in the intradural extra-axial frontal region. The tumor was totally removed by surgery. Pathological findings were consistent with a primitive neuroectodermal tumor (PNET). Intradural extra-axial PNET is very rare, and its prognosis is poor.

We herein describe a case of thymoma in which metastasis to the left lower visceral and parietal pleura was noticed after a 2-year dormancy. A closer examination revealed no evidence that the metastatic tumors were of lymph node origin. The initial thymoma was well encapsulated, and thus it was thought that the development of metastasis might have reflected a sudden rapid growth of the thymoma cells after a 2-year period of inactivity.

In some multiple myeloma cases, symptoms of amyloidosis are exhibited more prominently than symptoms of multiple myeloma. These cases are believed to have poorer prognosis compared to those in whom the major symptom is not amyloidosis. On the other hand, the prognosis of patients in whom amyloidosis is associated with peripheral neuropathy is poor, and suitable therapeutics has not been established. In this paper, we report a case of severe orthostatic hypotension as the major symptom associated with systemic amyloidosis. The patient was treated with bortezomib followed by autologous peripheral blood stem cell transplantation. This case was rare in that after relapse; amyloid protein was deposited in different organs, resulting in treatment resistance.

There have been various reports on the association of hepatitis C virus (HCV) infection with B lymphocyte proliferative disorders, such as non-Hodgkin lymphoma (NHL). We experienced a case (Case 1) of anti-HCV antibody (HCV-Ab)-positive NHL in which HCV nonstructural protein 3 (NS3) expression was observed in lymphoma tissue at the time of recurrence and in which the serum HCV RNA level exhibited a transient increase prior to recurrence. We investigated the HCV RNA genome in lymphoma tissue in Case 1, and it could be detected at recurrence. We also investigated HCV NS3 protein expression in lymphoma tissue and changes in serum HCV RNA level during the clinical course in four other cases of HCV-Ab-positive NHL treated in our hospital. We examined lymphoma tissues for HCV NS3 protein expression in four of the five cases, but it was not identified except for in Case 1 at recurrence. In three cases with no recurrence, serum HCV RNA levels showed a tendency to decrease after completion of chemotherapy and became stable thereafter. Further studies are necessary to clarify the association between serum HCV RNA and the onset and exacerbation of NHL.

We report 3 cases of reduced cardiac function with complications in non-Hodgkin’s lymphoma patients who were treated with rituximab. Patients experienced reduced cardiac functions after the administration of rituximab; there was no evidence of any preceding infusion reactions. Reticulin fiber was observed diffusely in cardiac muscles. Transforming growth factor-β levels were elevated after the administration of rituximab. We believe that continuous elevation of transforming growth factor-β may promote the growth of reticulin fiber in cardiac muscles. Reduction in cardiac functions is a severe complication that must be considered when rituximab is administered.

The susceptibilities of bacteria to fluoroquinolones (FQs), especially levofloxacin, and other antimicrobial agents were investigated using 11,475 clinical isolates collected in Japan during 2002. Methicillin susceptible staphylococci, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, the family of Enterobactericeae, Haemophilus influenzae and Acinetobacter spp. exhibited stable and high susceptibilities to FQs. The rate of FQs-resistant MRSA was 80 approximately 90%, being markedly higher than that of FQs-resistant MSSA. The FQs-resistance rate of MRCNS was also higher than that of MSCNS, however, it was lower than that of MRSA. No FQs-resistant clinical isolates of Salmonella spp. were detected in any of the surveys. Thirteen of Escherichai coli 696 isolates, 8 of Klebsiella pneumoniae 630 isolates and 33 of Proteus mirabilis 373 isolates produced extended-spectrum beta-lactamase (ESBL), furthermore 6 of 13 in E. coli, 1 of 8 in K. pneumoniae and 14 of 31 ESBL-producing isolates, and in P. mirabilis were FQs resistant. Attention should be focused in the future on the emergence of ESBL in relation to FQs resistance. The rate of FQs-resistant P. aeruginosa isolated from urinary tract infection (UTI) was 40 approximately 60%, while 15 approximately 25% of isolates from respiratory tract infection (RTI) were resistant. IMP-1 type metallo beta-lactamase producing organisms were found in 49 of P. aeruginosa 1,095 isolates, 7 of S. marcescens 586 isolates and 4 of Acinetobacter spp. 474 isolates, respectively. Glycopeptide-resistant enterococci or S. aureus was not found.

A survey was conducted to determine the antimicrobial activity of fluoroquinolones and other antimicrobial agents against 8,474 clinical isolates obtained from 37 Japanese medical institutions in 2000. A total of 25 antimicrobial agents were used, comprising 4 fluoroquinolones, 13 beta-lactams, minocycline, chloramphenicol, clarithromycin, azithromycin, gentamicin, amikacin, sulfamethoxazole-trimethoprim, and vancomycin. A high resistance rate of over 85% against fluoroquinolones was exhibited by methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium. Isolates showing resistance to fluoroquinolones among methicillin-resistant coagulase-negative Staphylococci, Enterococcus faecalis, and Pseudomonas aeruginosa from UTI accounted for 30-60%. However, many of the common pathogens were still susceptible to fluoroquinolones, such as Streptococcus pneumoniae (including penicillin-resistant isolates), Streptococcus pyogenes, methicillin-susceptible S. aureus (MSSA), methicillin-susceptible coagulase-negative Staphylococci, Moraxella catarrhalis, the Enterobacteriaceae family, and Haemophilus influenzae (including ampicillin-resistant isolates). About 85% of P. aeruginosa isolated from RTI were susceptible to fluoroquinolones. In conclusion, this survey of sensitivity to antimicrobial agents clearly indicated trend for increasing resistance to fluoroquinolones among MRSA, Enterococci, and P. aeruginosa isolated from UTI, although fluoroquinolones are still effective against other organisms and P. aeruginosa from RTI as has been demonstrated in previous studies.

Hematological diseases are often accompanied by respiratory disorders. Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by excessive accumulation of surfactant in the alveolar space. We describe a case of PAP complicated by myelofibrosis following essential thrombocythemia. The patient developed high fever, respiratory failure, and leuko-erythroblastosis during the progressive course of PAP. These symptoms were alleviated by prednisolone. The level of serum IL-6 was elevated when PAP was progressing rapidly. This may explain why the symptoms were alleviated by the steroids.

MORITA, T., MORITA, R., TAKAGI, S., SHIMOYAMA, N. and NAGAI, K. Specificities and Some Properties of Human T and B Lymphocyte Antisera. Tohoku J. exp. Med., 1981, 133 (3), 275-284-Antisera were prepared in rabbits by immunization with either human peripheral blood T lymphocytes (PTL) or tonsil B lymphocytes (TBL). Specificities of sequentially absorbed antisera were examined by cytotoxicity testing, immunoperoxidase staining and absorption study. Anti-PTL serum (ATS) reacted with E rosetting lymphocytes in the normal population. ATS was also reactive with some of lymphoid neoplasms, whether neoplastic cells carried E receptors or not. This serum did not lyse any of myelogenous leukemia cells. When antiserum was used in the immunoperoxidase staining, ATS strongly stained paracortical cells in the lymph node and medullary thymocytes in the thymus. On the other hand, anti-TBL serum (ABS) was reactive with lymphocytes corresponding to the percentage of EAC binding lymphocytes in the normal population. ABS reacted not only with the neoplastic cells earring C3 receptors and/or surface immunoglobulin, but also with non T.non B-acute lymphoblastic leukemia cells and a small number of acute myelogenous leukemia cells. In the immunoperoxidase staining, lymph follicular cells showed positive immunoreactivity with ABS, but paracortical cells did not.

A case of acute lymphoblastic leukemia with a giant splenomegaly in an 8-year-old boy was investigated by immunological, cytochemical and electronmicroscopical techniques. Bone marrow and peripheral blood were largely replaced by large blast cells with a nonconvoluted nucleus. Cytochemically, most of the blast cells showed strong focal acid phosphatase activity. In the surface marker studies, these blast cells formed EAC rosettes but not E rosettes, while they showed positive reactivity with anti-T lymphocyte serum but not with anti-B lymphocyte serum. This membrane phenotype E-, C3R+, T+, B- suggested that leukemic blast cells in this patient presumably originated from precursor T cells.

This report presents an adrenal ganglioneuroblastoma containing several kinds of neuronal peptides. The tumour was found in an autopsy case of a 3-year-old girl with clinical manifestation of intractable diarrhea, hypokalemia, achlorhydria, and with elevated levels of plasma vasoactive intestinal peptide (VIP). Immunoperoxidase staining showed many immuno-reactive VIP- containing cells, some somatostatin-and substance P-contalning cells on the tumour sections. Ultrastructurally, the tumour cells contained numerous secretory granules that could be divided mainly into two types; one is a small cored vesicle (50-150 nm in diameter) and the other large electron dense secretory granule (200-500 nm in diameter). It was suggested that the cells in ganglioneuroblastoma derived from neural crest are closely related to the cells that could differentiate into gut-hormone-producing cells.

Histological and immunohistochemical examinations were carried out on lymph nodes in 9 cases with Castleman's disease. In all cases, there were whorled follicle centers and proliferation of blood vessels. These findings were also considered to be important criteria for diagnosis of the plasma cell type of this disease. The whorled follicle centers often consisted of smaller concentrical structures and contained factor VIII-positive cells. In some cases, there were many small whorled structures surrounding postcapillary venules within the interfollicular areas of lymph nodes. These structures had factor VIII-positive granules indicating their endothelial origin. In 2 cases of the plasma cell type, monoclonal plasma cell proliferation (IgA, lambda and IgG, lambda, respectively) and cellular atypia were identified. These findings showed that extramedullary plasmacytoma could occur not only in the multicentric form, but also in the solitary form of Castleman's disease. In the lymph node of a case of the hyaline-vascular type, there were scattered tumour nodules consisting mainly of factor VIII-positive, atypical spindle cells suggesting associated Kaposi's sarcoma. It is conceivable that an abnormal immune state plays a role in pathogenesis of Castleman's disease.

A case of primary cerebral malignant lymphoma, immunoblastic type was reported. The immunoelectrophoresis of the patient serum showed an abnormal bow of IgM lambda type. Autopsy revealed that the cerebral lymphoma showed no extracranial spread except for adenocarcinoma of the colon with hepatic metastasis. Ultrastracturally, some of the lymphoma cells showed plasmacytoid differentiation. Immunoperoxidase study showed intracytoplasmic polyclonal immunoglobulins in non-neoplastic plasma cells around the colonic carcinoma, in the bone marrows, and spleen. However, neither IgM nor lambda light chain was found in the cerebral lymphoma cells. The source of the macroglobulinemia in this case was discussed.