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Biomedical subjects

Kenji Kashima

Publications and source records attributed to Kenji Kashima.

At least 19 recordsLinked to original sources

The Wnt-signaling pathway is not implicated in tumorigenesis of Merkel cell carcinoma.

BACKGROUND: The Wnt-signaling pathway, involving beta-catenin, apc, and axin, plays a critical role in numerous developmental events. Alterations in the Wnt-signaling pathway have been detected in a wide variety of neoplasms. However, similar aberrations have not been described in Merkel cell carcinoma (MCC). The aim of this study was to determine the status of the Wnt-signaling pathway in MCC. METHODS: Twelve cases of MCC were tested for the expression of beta-catenin and mutational status of CTNNB1 (gene for beta-catenin), APC, AXIN1, and AXIN2. Genomic DNA extracted from paraffin blocks was subjected to a polymerase chain reaction/single-strand conformation polymorphism analysis and sequencing. RESULTS: Nuclear accumulation of beta-catenin was observed in only one case (8.3%), as determined by immunochemistry. No mutations were found in CTNNB1, APC, and AXIN2 in all cases, although silent mutations in AXIN1 were detected in three cases. CONCLUSIONS: We conclude that the Wnt-signaling pathway does not play an important role in tumorigenesis in MCC.

Aged↗

Coexistence of Epstein-Barr virus-associated gastric carcinoma with malignant lymphoma: report of two cases.

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBV-GC) is not rare, accounting for 5 to 18% of all gastric carcinomas. Recently, we encountered two cases of EBV-GC of ordinary histopathological type coexistent with malignant lymphoma. One patient was a 71-year-old Japanese man who had two lesions, one in the cardia and the other in the antrum of the stomach. The former was EBV-GC without lymphoma, and antral one was EBV-GC with diffuse large B-cell lymphoma (DLBCL). The other patient was a 49-year-old Japanese man who had received chemotherapy for pelvic DLBCL 3 years earlier. He had EBV-GC with follicular lymphoma in the fundus of the stomach. In both cases, gastric carcinomas were positive for EBV-encoded small RNA by in situ hybridization, whereas the lymphoma cells, infiltrating nonneoplastic lymphocytes, and nonneoplastic epithelial cells were negative. The present cases suggest that focal immunosuppression by adjacent gastric lymphomas might be related to the alteration of the microenvironment and development of EBV-GC.

Aged↗

Solitary fibrous tumor of the thyroid gland: report of two cases and review of the literature.

Presented herein are the first two Japanese cases of solitary fibrous tumor (SFT) of the thyroid gland. The patients were 64- and 41-year-old men, who underwent hemithyroidectomy for thyroid tumors. Histopathologically, the tumors were well circumscribed, and were composed of spindle cells, collagen bundles and entrapped thyroid follicles. Spindle cells and collagen bundles were mostly in a patternless arrangement with an admixture of hypo- and hypercellular areas. Proliferating spindle cells were bland, slender, and occasionally wavy without any atypia and increased mitotic figures. Immunohistochemically, they were strongly positive for CD34, CD99, and bcl-2, but negative for epithelial membrane antigen, keratin, thyroglobulin, calcitonin, thyroid transcription factor-1, alpha-smooth muscle actin, desmin, S-100 protein and CD117. Based on these findings, the two patients were diagnosed as having thyroid SFT. Neither local recurrence nor metastasis has been observed in 5 years in patient 1 or in 4 years in patient 2. Thyroid SFT is extremely rare, and only 20 cases have been reported in the English-language literature including hemangiopericytoma. Although recurrence or metastasis has not been described in any reported cases, the clinical behavior of SFT is still undetermined, therefore long-term follow up seems necessary at present.

Adult↗

Florid cystic endosalpingiosis of the spleen.

A case of endosalpingiosis appearing as a huge multilocular cyst in the spleen of a 31-year-old woman is reported. The cystic lumens were smooth, and lined by fallopian tubal epithelium containing ciliated and secretory cells. The epithelial lining showed neither atypia nor foci of papillary proliferation, with only 3-5% MIB-1 labeling index. The epithelial lining was histochemically negative for mucin, but positive for MUC1 and progesterone receptor. Despite the appearance of a tumor-like mass, it was diagnosed as florid cystic endosalpingiosis as there was a normal tube-like epithelium. Regarding etiology, it was considered to derive from the secondary müllerian system of the splenic capsule.

Adult↗

Benign pleomorphic astrocytoma in the hypothalamus--case report.

A 41-year-old woman presented with an unusual case of benign astrocytoma with marked pleomorphism manifesting as consciousness disturbance due to intraventricular hemorrhage. Magnetic resonance imaging revealed a well-enhanced hypothalamic mass protruding into the third ventricle. Despite partial resection of the tumor without additional therapy, there have been no signs of tumor regrowth for 6 years. The histological findings revealed solid proliferation of tumor cells with marked pleomorphism, contrary to the benign clinical course. However, no mitosis, necrosis, or endothelial proliferation were found and the MIB-1 index was less than 0.5%. Immunohistochemical staining indicated the glial origin of the tumor. The tumor was similar to pleomorphic xanthoastrocytoma, but the histological findings were not exactly identical, indicating a new histological entity.

Adult↗

Human herpesvirus 6 DNA in plasma after allogeneic stem cell transplantation: incidence and clinical significance.

BACKGROUND: Human herpesvirus 6 (HHV-6) is increasingly recognized as an opportunistic and potentially life-threatening pathogen in recipients of allogeneic stem cell transplants (SCTs). METHODS: To clarify the incidence and clinical relevance of active HHV-6 infection, serial titers of plasma HHV-6 DNA were determined for 50 allogeneic SCT recipients, using real-time polymerase chain reaction. RESULTS: HHV-6 DNA was detected in plasma from 24 patients (48%). HHV-6 DNA was most frequently apparent approximately 14-27 days after transplantation. An increased risk of a positive result for HHV-6 DNA was associated with transplantation from an allelic-mismatch donor (P = .02) and administration of steroids (P = .04). Steroid use was associated with high HHV-6 DNA loads (P = .02). High HHV-6 DNA loads were correlated with delayed platelet engraftment (P = .04). Among patients who had positive results for HHV-6 DNA, the HHV-6 DNA load was higher in plasma from those who developed limbic encephalitis (n = 4) (P < .0001). CONCLUSIONS: Active HHV-6 infection is not rare in SCT recipients. SCT from allelic-mismatch donors is associated with increased risk of active HHV-6 infection. Steroid therapy is associated with not only increased incidence of infection but also accelerated viral replication. Development of limbic encephalitis is associated with high HHV-6 DNA load.

Adolescent↗

Biotin-rich intranuclear inclusions in morule-lacking adenocarcinoma of the gallbladder: a new category of "neoplastic/non-morular" lesions.

Biotin-rich intranuclear inclusions, also called "optically clear nuclei," are observed in various neoplastic and non-neoplastic lesions, including pregnancy-related endometrium and benign and malignant neoplasms with morular structures. A recent study reported that lesions with biotin-rich intranuclear inclusions can be classified as "(non-neoplastic) pregnancy-related endometrial" and as "(neoplastic) morular" category. In the present report, we describe two cases of well-differentiated adenocarcinoma of the gallbladder in which biotin-rich intranuclear inclusions were found without morular structures. Immunohistochemically, as reported previously, the intranuclear inclusions were positive for biotin and two biotin-binding enzymes (pyruvic acid carboxylase and propionyl CoA carboxylase). Intranuclear expression of beta-catenin was also observed in neoplastic cells with and without intranuclear inclusion. We also detected a frame shift mutation of APC gene in one case but no mutation of beta-catenin gene in both cases. Although intranuclear expression of beta-catenin by mutation of APC gene might contribute to carcinogenesis in our cases, the relationships among intranuclear expressions of beta-catenin, biotin, biotin-binding enzymes and intranuclear inclusions remain unclear. Our cases are the first neoplastic lesions with biotin-rich intranuclear inclusions that lacked morular structures. We propose a new "neoplastic/non-morular" category for lesions with biotin-rich intranuclear inclusions.

Adenocarcinoma↗

Adenoid cystic carcinoma of the uterine cervix.

Adenoid cystic carcinoma of the uterine cervix is a rare and peculiar variant of adenocarcinoma. This tumor represents 3% of all primary cervical adenocarcinomas, and it is locally aggressive and capable of metastasis to other organs even in its early stage. We report a case of adenoid cystic carcinoma stage IIIb that was successfully treated with radiotherapy. The patient shows no evidence of recurrent tumor at 5 years after radiotherapy. Generally, radiotherapy and chemotherapy are chosen as the first treatment, because this cancer is seen most commonly in the elderly.

Aged↗

Successful treatment of an adult patient with pulmonary abscess secondary to congenital cystic adenomatoid malformation.

We report a case of a 29 year old male who at age 25, developed a pulmonary abscess in the left lower lobe. A left lower lobectomy was performed following two recurrences on antibiotic treatment. The result of histopathological examination confirmed congenital cystic adenomatoid malformation (CCAM), a congenital disease characterized by multiple cysts resulting from adenomatous hyperplasia of the bronchial epithelia. In many cases, respiratory distress occurs during the neonatal period, and in about 80-85% of patients, CCAM is diagnosed before the age of two years due to respiratory infection. CCAM which was diagnosed in adulthood is very rare.

Adolescent↗

Immunohistochemical detection of cervical lymph node micrometastases from T2N0 tongue cancer.

CONCLUSIONS: These results indicate that extensive, multiple cervical micrometastases occurred from an early stage in patients with T2N0 tongue cancer. The presence of micrometastases suggests the necessity of preventive neck dissection for Level I-IV nodes as a radical treatment. OBJECTIVE: Cervical lymph node metastases occur with a relatively high frequency in patients with T2N0 squamous cell carcinoma of the tongue, and control of the metastases greatly influences the prognosis of patients. In this study, micrometastases in the cervical lymph nodes were investigated to clarify the necessity and required extent of preventive neck dissection. MATERIAL AND METHODS: We investigated micrometastases in 24 subjects who had previously been diagnosed with T2N0 tongue cancer. We performed immunostaining with anti-cytokeratin antibody cocktail AE1/AE3 of sections of 401 paraffin-embedded lymph nodes obtained from these patients. RESULTS: Micrometastases were observed in 14 patients (58%) and were most abundant in Level II nodes (n=11; 46%). Micrometastases were observed in the Level IV nodes of 3 patients (13%), and upstaging to pN2b occurred in 7 patients (29%).

Adult↗

Expression of Polo-Like Kinase (PLK1) in non-Hodgkin's lymphomas.

Polo-like kinases (PLKs) are protein serine/threonine kinases that play important roles in cell division. Expression of PLK1 might, moreover, play a role in the pathogenesis of human neoplasms. The expression of PLK1 mRNA is closely correlated with survival in patients with malignant tumors. We investigated the expression of PLK1 in non-Hodgkin's lymphomas (NHLs) and analyzed the relationships between expression of PLK1, histological grade, and prognosis. We analyzed various types of NHLs from 118 patients using monoclonal antibodies against PLK1 and Ki-67. The levels of expression of PLK1 and Ki-67 were significantly lower in low-grade NHLs than in high-grade and intermediate-grade NHLs (P < 0.001). Moreover, when patients were grouped in terms of 5-year overall survival ( > 70%, group A; 50 - 70%, group B; 30 - 49%, group C; and < 30%, group D), levels of expression of PLK1 and Ki-67 were found to be significantly higher in group D than in group A and they were also significantly higher in group C than in group A (P < 0.001). Conversely, the level of expression, of Ki-67 was significantly lower in group D than in group C (P < 0.05). The labeling indices specific for PLK1 were generally higher than those specific for Ki-67. Once we divided all patients into two groups in terms of the expression levels, high-level expression group of PLK1 (PLK1 index of 70%) and Ki-67 (Ki-67 indices of 60%) and low-level expression, one of these markers (PLK1 index of >/= 70%, Ki-67 indices of >/= 60%) had a similar prognosis, an observation that can be explained by the fact that rapidly proliferating group is more drug-sensitive than the other. Our study demonstrates that expression of PLK1 might reflect the malignant potential of NHLs and that PLK1 might be more useful than Ki-67 for the detection of proliferative cells.

Antigens, Neoplasm↗

Porocarcinoma arising in pigmented hidroacanthoma simplex.

Hidroacanthoma simplex (HAS) is a rare benign tumor that is also known as intraepidermal poroma. While there have been a few reports of HAS with malignant transformation (porocarcinoma), we report an unusual case of porocarcinoma, arising in a pigmented HAS, the latter also showing secondary amyloid deposits. An 80-year-old Japanese man presented with a cutaneous tumor on his left buttock, which had first been noticed in his childhood. The tumor consisted of flat pigmented plaque and a depigmented papule with erosion. Histologic analysis revealed many pigmented and well-defined nests within the epidermis of the flat pigmented portion. The nests were composed of cuboidal to oval and occasionally elongated, bland, basaloid cells with numerous melanin granules. In addition, there were infrequently ductal structures and small clusters of sebocytes, and abundant amyloid deposits in the upper dermis. These findings were consistent with pigmented HAS with amyloid deposition. In the depigmented portion, markedly atypical cells with occasional ductal structures and intracytoplasmic lumina extended throughout the entire thickness of the epidermis, with minimal invasion of the dermis. We considered this portion of the tumor to be a porocarcinoma. Since the two portions of the tumor were continuous, we made a final diagnosis of porocarcinoma arising in pre-existing pigmented HAS with amyloid deposition.

Acanthoma↗

Malignant serous cystic neoplasm of the pancreas: report of a case and review of the literature.

BACKGROUND: In general, serous cystic neoplasms of the pancreas are thought to be benign. Malignant serous cystic neoplasm of the pancreas is a rare clinical entity. CASE REPORT: We report the case of an 87-year-old woman with a serous microcystic neoplasm in the tail of the pancreas that behaved in a malignant fashion. The neoplasm had also invaded the colonic mesentery and splenic hilum. The pancreatic lesion was diagnosed as a large malignant serous cystic neoplasm, and the patient underwent distal pancreatectomy with splenectomy and segmental colectomy. The resected specimen contained a large tumor, 12 x 9 x 8 cm, which occupied the body and tail of the pancreas. Histologically, the tumor was indistinguishable from serous cystadenoma. However, the tumor had invaded surrounding tissues including the splenic vein, and there were splenic invasion and a regional lymph node metastasis. The postoperative course was uneventful. DISCUSSION: There are few reported cases of malignant serous cystic neoplasm, in which malignancy was histologically confirmed in the resected specimen. There are no reports of a negative outcome with complete resection of the tumor. Surgical treatment should be considered for serous cystic neoplasms, especially large ones, because of the malignant potential.

Aged↗

A case of sporadic gastric carcinoid tumor treated successfully by laparoscopy-assisted distal gastrectomy.

A 49-year-old man was referred to us for treatment of a gastric carcinoid tumor. Gastroscopy revealed a superficial elevated lesion with a central depression covered with nonspecific gastric mucosa located in the anterior wall of the gastric body. The lesion was diagnosed on biopsy as a gastric carcinoid tumor. Preoperative ultrasound and computed tomography examinations revealed a tumor confined to the gastric submucosa and without lymph node metastasis. Therefore, laparoscopy-assisted distal gastrectomy (LADG) was performed. Macroscopically, the resected specimen contained an elevated lesion measuring 0.9 x 0.8-cm with a central depression. The postoperative course was uneventful, and the patient remains free of recurrence 10 months after surgery. There are few cases of sporadic gastric carcinoid tumor successfully treated by LADG. LADG may be useful for treatment of patients with sporadic gastric carcinoid tumor and possible lymph node metastasis.

Biopsy↗

DNA damage-induced phosphorylation of MdmX at serine 367 activates p53 by targeting MdmX for Mdm2-dependent degradation.

Understanding how p53 activity is regulated is crucial in elucidating mechanisms of cellular defense against cancer. Genetic data indicate that Mdmx as well as Mdm2 plays a major role in maintaining p53 activity at low levels in nonstressed cells. However, biochemical mechanisms of how Mdmx regulates p53 activity are not well understood. Through identification of Mdmx-binding proteins, we found that 14-3-3 proteins are associated with Mdmx. Mdmx harbors a consensus sequence for binding of 14-3-3. Serine 367 (S367) is located within the putative binding sequence for 14-3-3, and its substitution with alanine (S367A) abolishes binding of Mdmx to 14-3-3. Transfection assays indicated that the S367A mutation, in cooperation with Mdm2, enhances the ability of Mdmx to repress the transcriptional activity of p53. The S367A mutant is more resistant to Mdm2-dependent ubiquitination and degradation than wild-type Mdmx, and Mdmx phosphorylated at S367 is preferentially degraded by Mdm2. Several types of DNA damage markedly enhance S367 phosphorylation, coinciding with increased binding of Mdmx to 14-3-3 and accelerated Mdmx degradation. Furthermore, promotion of growth of normal human fibroblasts after introduction of Mdmx is enhanced by the S367 mutation. We propose that Mdmx phosphorylation at S367 plays an important role in p53 activation after DNA damage by triggering Mdm2-dependent degradation of Mdmx.

14-3-3 Proteins↗

Immunohistochemical analysis of morules in colonic neoplasms: morules are morphologically and qualitatively different from squamous metaplasia.

Morules develop in several neoplasms and have been considered as a type of squamous metaplasia despite the absence of keratinization and intercellular bridges. The objective of this study was to clarify the pathological significance of morules and to distinguish morules from squamous metaplasia in colonic neoplasms. Ten cases of morule-associated colonic neoplasms (4 adenocarcinomas, 1 adenoma with carcinoma in situ, and 5 adenomas), and 3 cases of squamous metaplasia in colonic adenocarcinoma were examined morphologically and immunohistochemically. Morules were well-defined structures composed of small, oval to short-spindled cells with bland nuclei, and frequently associated with intranuclear inclusions that were positive for biotin and biotin-binding enzymes (pyruvic acid carboxylase and propionyl CoA carboxylase). On immunohistochemical examination, morules characteristically showed nuclear overexpression of beta-catenin, cyclin D1 and p63, low Ki-67 labeling index (<1%), cytoplasmic overexpression of CD10, and no expression of cytokeratin 20. These molecules were useful for the differentiation of morules. Furthermore, p63 and 34betaE12 positivities in morules suggested that they have a basal/stem cell phenotype. Thus, morules were morphologically and qualitatively different from squamous metaplasia. We consider that morules in colonic neoplasms are cell clusters with a basal/stem cell phenotype, and have less proliferative and less invasive potential than other cancer cells.

Adenocarcinoma↗

Detection of HTLV-1 gene on cytologic smear slides.

In this chapter we describe a method for the detection of human T-cell leukemia virus type 1 (HTLV-1) genes in cytologic smears by polymerase chain reaction (PCR). First, already-stained and covered slides should be immersed in xylene for removal of cover slips. After passage through a descending ethanol series, slides are ready for DNA extraction. If the neoplastic cells on slides are mixed with nonneoplastic lymphocytes, cells of interest are isolated by microdissection. Two easy methods to dissect the samples using hydrophobic and hydrophilic mounting media are detailed. Second, microdissected cells are collected in microtubes and digested with proteinase K. The cells that did not undergo the microdissection are digested and dissolve in the proteinase K solution on the slides. Last, the template DNA is extracted from the solution and provided to PCR. We use two sets of primers for detection of HTLV-1 genes, and the products of amplification by PCR that correspond to the pX and tax regions are expected to be 127 and 159 base pairs long, respectively. Although this method does not provide proof of the monoclonal integration of HTLV-1 genes, it can be applied when adult T-cell leukemia/lymphoma is suspected cytologically but fresh samples for Southern blotting are unavailable.

Cytodiagnosis↗