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We report a case of adult T‐cell leukemia/lymphoma (ATLL) with angioimmunoblastic T‐cell lymphoma (AITL/nTFHL‐AI)‐like feature. An 88‐year‐old Japanese woman with seropositive for the Human T‐lymphotropic virus type 1 (HTLV‐1) was incidentally diagnosed with generalized lymphadenopathy. Biopsy of the cervical lymph node demonstrated the proliferation of small‐ or medium‐sized and large atypical lymphocytes associated with eosinophils, high endothelial venules, and clear cells. Immunohistochemical analysis revealed atypical lymphocytes were CD3‐ and CD4‐positive. Atypical T cells bore the T‐follicular helper phenotype (PD1, ICOS, and BCL6) and were positive for CD25 and chemokine receptor 4. Epstein‐Barr virus encoded RNA‐positive cells were scattered in the background via in situ hybridization. The histological findings were similar to those of AITL/nTFHL‐AI; however, the immunohistochemical results did not exclude the possibility of ATLL. Southern blot analysis detected integration of HTLV‐1 proviral DNA. The RHOA Gly 17 Val (G17V) mutation was detected by the peptide nucleic acid‐locked nucleic acid clamp method. Finally, the patient was diagnosed with ATLL with AITL‐like feature and exhibited a similar morphology, immunophenotype, and mutational signature to AITL/nTFHL‐AI. ATLL mimics other types of T‐cell lymphomas. Thus, in HTLV‐1 endemic areas, routine screening for HTLV‐1 serology is necessary to avoid misdiagnosis of other lymphoid malignancies. [ABSTRACT FROM AUTHOR]

Background: Salivary duct carcinoma (SDC) is a high‐grade salivary malignancy that frequently occurs as the carcinomatous component of carcinoma ex pleomorphic adenoma. We herein examined the clinical factors affecting outcomes in a large cohort of SDC. Methods: We selected 304 SDC cases and investigated clinical characteristics and the factors affecting outcomes. Results: The median age of the cases examined was 68 years, the most common primary site was the parotid gland (238 cases), and there was a male predominance (M/F = 5:1). Outcomes were significantly worse when the primary tumor site was the minor salivary glands (SG) than when it was the major SG. Outcomes were also significantly worse in pN(+) cases (161 cases) than in pN0 cases, particularly those with a metastatic lymph node number ≥11. The cumulative incidence of relapse and distant metastases was significantly higher in stage IV cases than in stage 0–III cases. Conclusions: The absolute number of lymph node metastases, higher stages, and the minor SG as the primary tumor site were identified as factors affecting the outcome of SDC. [ABSTRACT FROM AUTHOR]

Macroglossia is a common feature in patients with Beckwith-Wiedemann syndrome (BWS). The underlying cause of macroglossia in BWS remains unknown, and further histological studies are required to uncover its etiology. We present the case of a 5-year-old girl who was diagnosed with BWS and underwent partial tongue resection for difficulties in articulation and aesthetics. The keyhole-shaped partial resection revealed a harder posterior side than the anterior. Microscopically, the posterior side consisted of dense subepithelial eosinophilic areas composed of an abundance of tightly packed skeletal muscle fibers that were arranged in a fascicular or storiform pattern. BWS-associated macroglossia results from skeletal muscle hyperplasia, consistent with true macroglossia. Therefore, tongue resection may be beneficial for such patients. Further studies are required to develop personalized surgical interventions for each patient with BWS. [ABSTRACT FROM AUTHOR]

Pulmonary tumor thrombotic microangiopathy (PTTM) is histologically characterized by micro tumor cell embolism and intimal fibrocellular proliferation of pulmonary arteries or arterioles. We report a secondary case of PTTM associated with extramammary Paget's disease (EMPD). The patient was a 72‐year‐old man with exertional dyspnea. Clinical examinations found he had pulmonary hypertension and multiple osteolytic lesions of vertebra. Cytological analysis of pulmonary wedge artery sample detected malignant cells and he was dead before treatment was started. Multiple tumor embolisms (>17) were identified in pulmonary arteries or arterioles at autopsy, consistent with PTTM. Metastatic nodules were found in liver and lymph node. Furthermore, disseminated carcinomatosis of the bone marrow (DCBM) was seen. Immunostaining results pointed out that tumor cells possessed mammary gland phenotype. He had 4‐years history of EMPD in the left axilla without recurrence, and immunohistochemistry results were the same as the autopsy specimen. Thus, we diagnosed the primary site of PTTM to be EMPD. Our case highlights the usefulness of the recent proposed classification of PTTM, potential association between PTTM and DCBM, and the necessity for long‐term follow‐up in EMPD. EMPD can rarely cause PTTM to manifest as a paraneoplastic syndrome. [ABSTRACT FROM AUTHOR]

Keywords: diffuse large B-cell lymphoma; maternal-to-fetus; transmission; HLA genes; loss of heterozygosis EN diffuse large B-cell lymphoma maternal-to-fetus transmission HLA genes loss of heterozygosis e234 e237 4 06/18/20 20200615 NES 200615 Peripheral blood cells can migrate reciprocally between the mother and fetus, resulting in microchimerism.[1] In contrast, the fetuses are protected from cancer metastasis from the mother structurally by the placental syncytiotrophoblast layer, or by immunological defenses through fetal T lymphocytes. Both maternal and fetal lymphoma cells had lost non-inherited maternal HLA alleles, suggesting the mechanism of immune escape. [Extracted from the article]

Previously we reported that the microRNA miR‐210 is aberrantly upregulated in clear cell renal cell carcinoma (ccRCC) via deregulation of the VHL–HIF pathway. In the present study, to investigate the biological impact of miR‐210 in ccRCC tumorigenesis, we developed a transgenic mouse line expressing miR‐210 in proximal tubule cells under control of the mouse SGLT2/Slc5a2 promoter. Light microscopy revealed desquamation of the tubule cells and regeneration of the proximal tubule, suggesting that miR‐210 expression led to damage of the proximal tubule cells. Electron microscopy revealed alterations to the mitochondria in proximal tubule cells, with marked reduction of the mitochondrial inner membrane, which is the main site of ATP production via oxidative phosphorylation (OxPhos). An additional in vitro study revealed that this loss of the inner membrane was associated with downregulation of Iscu and Ndufa4, the target genes of miR‐210, suggesting that the miR‐210–ISCU/NDUFA4 axis may affect mitochondrial energy metabolism. Furthermore, metabolome analysis revealed activation of anaerobic glycolysis in miR‐210‐transfected cells, and consistent with this the secretion of lactate, the final metabolite of anaerobic glycolysis, was significantly increased. Lactate concentration was higher in the kidney cortex of transgenic mice relative to wild‐type mice, although the difference was not significant (p = 0.070). On the basis of these findings, we propose that miR‐210 may induce a shift of energy metabolism from OxPhos to glycolysis by acting on the mitochondrial inner membrane. In addition to activation of glycolysis, we observed activation of the pentose phosphate pathway (PPP) and an increase in the total amount of amino acids in miR‐210‐transfected cells. This may help cells synthesize nucleotides and proteins for building new cells. These results suggest that miR‐210 may be involved in the metabolic changes in the early stage of ccRCC development, helping the cancer cells to acquire growth and survival advantages. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A case of severe fever with thrombocytopenia syndrome (SFTS) in which a skin biopsy from the tick‐bite region was analyzed is reported. The patient was a 72‐year‐old woman who developed fever and thrombocytopenia after a tick bite. SFTS was diagnosed from polymerase chain reaction (PCR) analysis of a blood sample. Histopathological analysis of a skin biopsy specimen from the tick‐bite region showed CD20‐positive perivascular and interstitial immunoblastic cells, which were positive to anti‐SFTS virus (SFTSV) nucleoprotein antibody. In addition, SFTSV RNA was detected by real‐time PCR from this biopsy specimen. Moreover, hemophagocytosis was also found in the tick‐bite region. To the best of our knowledge, this is the first report to analyze the details of the tick‐bite region of skin in SFTS, and the first to detect virus‐infected cells in the skin. The present findings may help elucidate the mechanisms of entry of SFTSV. [ABSTRACT FROM AUTHOR]

Human herpes virus 6 (HHV‐6) is known to cause primary encephalitis in the frontal lobes/cerebral hemisphere or reactivated encephalitis in the hippocampus, but the pathogenesis remains unclear. HHV‐6B has also been detected in hippocampal samples in patients with mesial temporal lobe epilepsy. A 1 year and 3 months old female, who had been clinically diagnosed with exanthema subitum and febrile convulsion, was found dead on the third day after onset. Macroscopic findings showed massive brain edema. Microscopic examination revealed gemistocytic astrocytes and ballooned oligodendrocytes in the frontal white matter, along with neuronal cell death with microglial infiltration in the frontal cortex. Polymerase chain reaction detected HHV‐6B in the cerebrospinal fluid and necropsy brain samples. The hippocampus showed a 4–5‐fold increase in virus copy number of HHV‐6B compared to samples from other brain sites. Immunostaining indicated that HHV‐6B had infected vascular endothelial cells, neurons and oligodendrocytes but not astrocytes or microglia. Hippocampal neurons were infected with highly concentrated HHV‐6B, but the hippocampus had neither neuronal loss nor reactive glial response. Silent and abundant HHV‐6B infection in the hippocampus might be associated with latent infection, reactivation and some hippocampus‐oriented disorders, including mesial temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

We report a case of ALK-positive renal cell carcinoma coincident with Hodgkin lymphoma. The patient was a 19 year-old-girl without sickle cell trait. The right renal tumor was discovered concomitantly with Hodgkin lymphoma (HL). After chemotherapy for HL, right nephrectomy was performed. Microscopically, the tumor showed a solid and focally pseudo-papillary growth pattern studded with tubular structures. Most tumor cells were small bland eosinophilic cells, but rhabdoid cells, vacuolated cells, pleomorphic multinucleated giant cells were also admixed. The variety of growth patterns and cell features led us to speculate a possibility of ALK-positive renal cell carcinoma (ALK + RCC). ALK was immunohistochemically positive, and fluorescence in situ hybridization analysis detected a split signal of the ALK gene. We examined previously reported partner genes (STRN, TPM3, VCL and EML4) by RT-PCR, but fusion gene was not detected. RCC showing solid or cribriform growth patterns with vacuolated cells with intracytoplamic lumina, rhabdoid cells, and mucus production indicates the possibility of ALK + RCC. [ABSTRACT FROM AUTHOR]

Lanthanum carbonate (LaC) is used to prevent hyperphosphatemia in dialysis patients. It is commonly believed that there is little LaC absorption from the intestines. However, La deposition in the gastric mucosa, which we coined 'gastric lanthanosis', was recently reported. We describe here the clinicopathological features of and a possible mechanism for gastric lanthanosis. This study included 23 patients with definite gastric lanthanosis. We extracted characteristic clinicopathological features of gastric lanthanosis by computed tomography (CT) imaging and endoscopic, histologic, electron-microscopic, and element analysis examinations. The Helicobacter pylori infection rate in the lanthanosis group was much lower than that among the general population. The clinicopathological features characteristic of gastric lanthanosis were mucosal high-density linear appearance by CT, reflective bright-white spots (BWS) by gastroscopy, eosinophilic histiocytes occasionally phagocytizing foreign materials by histology, and numerous electron-dense particles in the histiocytes. The particles had burr-like skeletons resembling La crystals. Gastric lanthanosis is an under-reported, but not a rare lesion. It is characterized by endoscopic BWS and histologic eosinophilic histiocytes in dialysis patients treated with LaC. The proposed mechanism for gastric lanthanosis is that LaC is dissolved by gastric juice, crystallized within the mucosa and is phagocytized by histiocytes. [ABSTRACT FROM AUTHOR]

In patients with esophageal squamous cell carcinoma (ESCC), the status of metastasis to lymph nodes is strongly associated with prognosis. Consequently, development of a biomarker to detect the presence of metastasis would be clinically valuable. In this study, we found that overexpression of cannabinoid receptor 1 (CB1R) was applicable as a marker for prediction of metastasis in ESCC. CB1R overexpression was detected immunohistochemically in 54 of 88 cases (61.4%). The intensity of CB1R expression was uniform in both intraepithelial and invasive regions in each case, and was significantly correlated with the status of metastasis to lymph nodes ( P = 0.046) and distant organs ( P = 0.047). Furthermore, multivariate analysis revealed that CB1R overexpression was independently associated with poor prognosis ( P = 0.019). Biological analysis of CB1R overexpression using ESCC cell lines revealed that CB1R activation appeared to promote cell proliferation and invasion. On the basis of these findings, we propose that evaluation of CB1R expression status in biopsy specimens of ESCC using immunohistochemistry might be clinically useful for prediction of metastasis to lymph nodes and distant organs. [ABSTRACT FROM AUTHOR]

Gastric cancer ( GC) is characterized by amplifications of receptor tyrosine kinases ( RTK) and KRAS, therefore, targeting of the RTK/ KRAS downstream pathways could help to broaden the applicability of molecular targeted therapy for GC. We assembled a panel of 48 GC cell lines and screened predictors of responsiveness to inhibition of the RAF/ MEK/ ERK pathway, one of the RTK/ KRAS downstream pathways. We found that GC cells with MET amplification or KRAS mutation, but not amplification, tended to be sensitive to MEK inhibition. However, several cell lines without RTK/ KRAS alterations also showed high sensitivity to MEK inhibition. We then focused on the phosphorylation of RTK/ KRAS downstream molecules to screen for predictors' sensitivity to MEK inhibition. We found that the phosphorylation level of mammalian target of rapamycin complex 1 ( mTORC1) downstream molecules, including p70S6K, 4 EBP1, and S6, was significantly associated with sensitivity to MEK inhibition in GC cells ( P < 0.05), suggesting that mTORC1 activity is related to the sensitivity to MEK inhibition. Furthermore, the change in mTORC1 activity after MEK inhibition was also significantly associated with this sensitivity ( P < 0.001). Among the mTORC1 downstream molecules, the change in S6 phosphorylation ( pS6) showed the most significant correlation with sensitivity. Using xenograft models derived from highly sensitive and resistant cell lines, we found specific reduction of pS6 in xenografts from highly sensitive cell lines after 6 h of treatment with an MEK inhibitor. Thus, our data suggest the potential clinical applicability of an MEK inhibitor for a proportion of GC patients who could be selected on the basis of pS6 change after MEK inhibition. [ABSTRACT FROM AUTHOR]

A sessile serrated adenoma/polyp (SSA/P) with cytological dysplasia in the right colon, which transformed to an invasive submucosal adenocarcinoma finally, was endoscopically observed in a 76-year-old woman. A whitish soft SSA/P (approximately 25 mm in diameter) was detected in the cecum. Biopsy samples were obtained from the small nodule, and the lesion was eventually diagnosed as an SSA/P with cytological dysplasia, considering endoscopic observations, among which the narrow-band imaging features suggested that the lesion was adenomatous, that is, a round-oval pattern, and hyperplastic, that is, comprising a circular pattern with dots and an invisible capillary vessel. After 11 months, an SSA/P had rapidly developed into a submucosal adenocarcinoma with lymphatic infiltrations, and the most aggressive deep invasion was observed in the central depression. This case suggests that right-side SSA/Ps with cytological dysplasia should be removed immediately, considering the potential for rapid progression to a larger size and eventually to deep and extensive cancer. [ABSTRACT FROM AUTHOR]

We have previously reported that Salvador homologue 1 ( SAV1), a component of the Hippo pathway, is significantly down-regulated in high-grade clear cell renal cell carcinoma ( ccRCC) due to 14q copy number loss, and that this down-regulation contributes to the proliferation and survival of renal tubular epithelial cells through activation of Yes-associated protein 1 ( YAP1), a downstream target of the Hippo pathway. However, the impact of SAV1 loss on the proliferation and survival of kidney cells in vivo remained to be determined. To address this issue, we generated kidney-specific Sav1-knockout ( Cdh16-Cre; Sav1fl/fl) mice. Sav1 deficiency enhanced the proliferation of renal tubular epithelial cells in Cdh16-Cre; Sav1fl/fl mice, accompanied by nuclear localization of Yap1, suggesting suppression of the Hippo pathway. Sav1 deficiency in renal tubules also caused structural and cellular abnormalities of the epithelial cells, including significant enlargement of their nuclei. Furthermore, Cdh16-Cre; Sav1fl/fl mice developed both glomerular and tubular cysts. Although lining cells of the glomerular cysts showed no atypia, those of the tubular cysts showed variations in cell size and nuclear shape, which became more severe as the mice aged. In aged Cdh16-Cre; Sav1fl/fl mice, we observed focal disruption of proximal tubules and perivascular lymphocytic infiltration. In conclusion, Sav1 is required for the maintenance of growth, nuclear size and structure of renal tubules under physiological conditions, and its deficiency leads to the acquisition of enhanced proliferation of renal epithelial cells through suppression of Hippo signalling. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Previously, we reported that genomic loss of 14q occurs more frequently in high-grade than in low-grade clear cell renal cell carcinomas (cc RCCs), and has a significant impact on the levels of expression of genes located in this region, suggesting that such genes may be involved in the malignant transformation of cc RCCs. Here, we found that six of the genes located in the minimal common region of 14q loss were significantly downregulated in high-grade cc RCCs due to copy number loss. Using a dataset from The Cancer Genome Atlas Research Network, we found that downregulation of one of these six genes, WDR20, was significantly associated with poorer outcome in patients with cc RCC, suggesting that WDR20 downregulation may be involved in the malignant transformation of cc RCCs. In functional assays, exogenous WDR20 significantly inhibited the growth of RCC cell lines and induced apoptosis. Interestingly, the phosphorylation levels of ERK and protein kinase B/AKT, which reportedly contribute to the malignant phenotype of RCC cells, were clearly reduced by exogenous expression of WDR20. Thus, our data suggest that downregulation of WDR20 due to 14q loss may be involved in the malignant transformation of cc RCCs, in part through activation of the ERK and protein kinase B/AKT pathways. [ABSTRACT FROM AUTHOR]

Background and Aim White opaque substance ( WOS) in gastric neoplasias is a unique finding visualized in magnifying endoscopy ( ME) with narrow band imaging ( NBI) and it represents intramucosal accumulation of lipid droplets using oil red O staining. Methods Subjects were 26 WOS-positive (13 adenomas and 13 well-differentiated adenocarcinomas) and 27 WOS-negative gastric epithelial neoplasias. We carried out immunohistochemical staining using a monoclonal antibody specific for adipophilin as a marker of lipids. Immunoelectron microscopy was used to evaluate morphology of the lipid droplets. Results Adipophilin was detected in 24 of 25 (96.0%) WOS-positive neoplasias, but it was detected in only two of 27 (7.4%) WOS-negative neoplasias. Lipid droplets were only seen in the surface epithelium in 10 of 11 (91.1%) adenomas, whereas the lipid droplets also existed in the cryptal epithelium in seven of 13 (53.8%) adenocarcinomas. Immunoelectron microscopy revealed numerous lipid droplets mainly existing in the subnuclear cytoplasm of the epithelium. The shape of the lipid droplets in adenomas was round and uniform, whereas that in adenocarcinomas was irregular. Conclusions The present study confirmed that the presence of WOS in gastric neoplasias was dependent upon intramucosal accumulation of lipid droplets using anti-adipophilin staining. Intraepithelial distribution and morphology of the lipid droplets differed between adenoma and adenocarcinoma. [ABSTRACT FROM AUTHOR]

Ren XL, Daa T, Yada N, Kashima K, Fujitomi Y, Yokoyama S. Expression and mutational status of RON in neoplastic lesions of the breast: analysis of MSP/RON signaling in ductal carcinoma in situ and invasive ductal carcinoma. APMIS 2012; 120: 358-67. Recepteur d'origine nantais (RON) is a receptor tyrosine kinase closely related to MET and involved in tumorigenesis. We investigated the roles of aberrations in RON and its ligand, macrophage-stimulating protein (MSP), in invasive ductal carcinoma (IDC, n = 81), ductal carcinoma in situ (DCIS, n = 26), and in benign lesions (n = 20) of mammary gland. Expression of RON and MSP was evaluated by immunohistochemistry and the mutational status of a region containing the proteolytic cleavage site in exon 1 and each exon of the kinase domain (exon 14-20) of RON was screened by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis. The proportion of cases positive for RON expression was significantly different between malignant [86% (92/107)] and benign [40% (8/20)] lesions. RON expression was positive in both IDC and DCIS [90% (73/81) and 73% (19/26), respectively], whereas MSP expression was present in 54% (44/81) of IDC and absent in DCIS. RON expression correlated significantly with the histological grade of DCIS. No mutations were detected in the examined regions of RON in breast cancer samples as confirmed by PCR-SSCP. The findings suggest the involvement of RON expression in the development of breast cancer, and that an autocrine/paracrine loop of RON seems to affect tumor invasiveness. [ABSTRACT FROM AUTHOR]

Tanahashi J, Kashima K, Daa T, Yada N, Tanaka K-I, Kawano Y, Yokoyama S. Pulmonary myoepithelial carcinoma resembling matrix-producing carcinoma of the breast: case report and review of the literature. APMIS 2010; 118: 401–6. We report a case of pulmonary myoepithelial carcinoma with extensive myxohyaline stroma, resembling matrix-producing carcinoma of the breast. A 76-year-old Japanese man presented with a nodular lesion in the left lung (S8), and underwent partial resection of the left lower lobe. Microscopically, the resected tumor was relatively well circumscribed with central hypocellular myxohyaline and peripheral hypercellular area. In the central area, eosinophilic and clear polygonal cells proliferated in a cord-like or reticulated pattern with extensive myxohyaline stroma, while the peripheral area was composed of solid lobules of different shapes and sizes with occasional comedonecrosis. The tumor cells were markedly atypical with frequent mitotic figures. Vascular and lymphatic invasion was evident with regional lymph node metastasis. No squamous or glandular differentiation was evident in the tumor. Immunohistochemical staining implied myoepithelial differentiation. The patient developed multiple brain metastases, and died of the disease 11 months after the surgery. In this report, we discuss the histopathologic uniqueness of the present case together with a review of the literature. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma is occasionally associated with other types of cutaneous malignancies including squamous cell carcinoma, basal cell carcinoma and lentigo maligna. We report a case of Merkel cell carcinoma co-existent with sebaceous carcinoma in the right upper eyelid of a 61-year-old Japanese man. Histopathologically, the resected tumor consisted of three nodules located in the tarsal plate, showing two distinct histopathological types. Two nodules were Merkel cell carcinoma and located in the proximal part of the palpebral conjunctiva. The third was sebaceous carcinoma located in the distal transitional zone between the epidermis and the conjunctiva. No features of transition between these two components were noted. Metastatic deposits were identified in the regional lymph nodes, which solely consisted of Merkel cell carcinoma without sebaceous carcinoma. This is the first report of such co-existent lesions. [ABSTRACT FROM AUTHOR]

The acquired capability of evading apoptosis is one of the prerequisites for cancer development, and NF-κB plays a critical role by inducing anti-apoptotic molecules. In this study, we firstly carried out an expression-cloning approach to isolate the responsible molecules in the NF-κB activation pathway with the defective mutant cell line, COS-A717. This cell line shows reduced constitutive basal activity of NF-κB as compared with the parental COS cells. We successfully isolated genes with compensating activity for the pathway, and one gene encoded B-cell activating factor receptor (BAFF-R). However, a Northern blot analysis revealed that the BAFF-R expression is not only limited to cells of B cell origin, but also is found in those with nonhematopoietic origins. In the human fibrosarcoma cell line HT1080, an immunohistochemical analysis revealed that the expression of BAFF-R is not on the cell surface, but in the cytoplasm. The expression of BAFF was also detected, and the reduction of endogenous BAFF or BAFF-R by siRNA decreased the basal NF-κB activity. Lastly, from clinicopathological specimens, the associated expression of BAFF-R and BAFF was demonstrated in osteosarcoma. We propose that an aberrant BAFF/BAFF-R-dependent autocrine mechanism may play a role in the development of certain types of cancer cells. [ABSTRACT FROM AUTHOR]

Background: To clarify the genetic background of ameloblastoma, expression of β-catenin, and mutational status of genes involved in Wnt signaling pathway were investigated. Methods: We analyzed β-catenin and cyclin D1 in 18 cases of ameloblastoma by immunohistochemical staining, and searched for mutations in CTNNB1 (gene for β-catenin), APC, AXIN1, and AXIN2 by polymerase chain reaction (PCR) and direct sequencing method. Result: We detected membranous and occasionally cytoplasmic expression of β-catenin in 16 of 18 cases (89%), and nuclear expression of β-catenin principally in the peripheral columnar cells in 11 of 18 cases (61%). In nine of the 18 cases (50%), we detected the expression of cyclin D1 principally in the peripheral columnar cells. However, there was no correlation between nuclear expressions of β-catenin and cyclin D1. No missense mutations were found in CTNNB1, APC, AXIN1, and AXIN2 in all cases except for silent mutation and already-known single nucleotide polymorphism. Conclusion: Mutations in CTNNB1, APC, AXIN1, and AXIN2 are not implicated in nuclear accumulation of β-catenin, and that the expression of cyclin D1 is accelerated independently of β-catenin in ameloblastomas. Other Wnt signaling members or alternative pathways involved in the degradation of β-catenin should be subject of further investigation. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (ACC) is a common malignant neoplasm of the salivary gland. The mechanism underlying ACC carcinogenesis is not fully elucidated, although data on associated genetic alterations are accumulating. Cyclin-dependent kinase inhibitors (CKIs) act as tumor suppressors in various cancers, and aberrant methylation in the CKI gene promoter region has been linked to gene silencing and downregulation of expression. The present study investigated methylation of CKI genes, p15, p18, p19, p21, and p27, in 34 cases of ACC. We found frequent and plural methylations of these genes in most cases (68.8% in p15, 90.3% in p18, 78.8% in p19, 92.3% in p21, and 26.5% in p27). Cell cycle disruption induced by these epigenetic aberrations might be important in the tumorigenesis of ACC. [ABSTRACT FROM AUTHOR]

Background: Cutaneous myoepithelioma, both benign and malignant, is a rare neoplasm composed of neoplastic myoepithelial cells showing diverse histopathological features, and criteria for discriminating benign or malignant have not been fully clarified. Patient: We present a case of cutaneous myoepithelial carcinoma in a 62-year-old woman presenting a solid mass in the right back. Results: Resected tumor was located in the whole dermis and subcutis. Histopathologically, two different growth patterns were noted: a small-nested or trabecular pattern in the superficial part and a large nodular pattern with extensive central necrosis in the deep part. Tumor cells were all epithelioid, although plasmacytoid and glycogen-rich clear cells were also observed within the large nodules of the deep part. Immunohistochemically, the cells were positive for both epithelial and myogenic markers, suggesting myoepithelial origin. Lymphatic invasion and lymph node metastasis were evident despite inconspicuous atypia and low mitotic rate. Conclusion: The final diagnosis was cutaneous myoepithelial carcinoma. At present, it seems to be difficult to predict the behavior of myoepithelioma of the skin and soft tissue, although atypia and high mitotic rate are reported to be associated with local recurrence and metastasis. [ABSTRACT FROM AUTHOR]

We report a case of carcinosarcoma ex recurrent pleomorphic adenoma in the submandibular region of a 56-year-old Japanese man. He presented with a 2-year history of a rapidly growing mass in the submandibular region. He reported undergoing excision of a nodule in the same region 10 years earlier. Incisional biopsy confirmed the diagnosis of pleomorphic adenoma. The lesion was excised surgically. The resected tumor measured 40×20 mm and was composed of two large nodules and multiple small satellite nodules in the subcutaneous tissue. Histopathologically, one large nodule was carcinosarcoma while the other large nodules and small satellite nodules were pleomorphic adenoma. The former large nodule showed a variegated pattern with carcinomatous components (poorly differentiated adenocarcinoma, salivary duct carcinoma, squamous cell carcinoma and undifferentiated carcinoma) and sarcomatous components (spindle cell sarcoma, chondrosarcoma, liposarcoma and rhabdomyosarcoma). Based on the clinical history and histopathology, we consider the lesion to have originated from recurrent pleomorphic adenoma. [ABSTRACT FROM AUTHOR]

Background: The Wnt-signaling pathway, involving β-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 β-catenin and mutational status of CTNNB1 (gene for β-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 β-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. [ABSTRACT FROM AUTHOR]

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, α-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ueo T, Kashima K, Daa T, Kashima N, Tsuji K, Hisaoka M, Yokoyama S. A case of tenosynovial chondromatosis with tophus-like deposits. APMIS 2004;112:624–8.Tenosynovial chondromatosis has not been well recognized because of its rarity, but it is clinically important because of its high rate of recurrence. We report here a case of tenosynovial chondromatosis with deposits of crystalline material that appeared to be sodium urate (gouty tophi). A 37-year-old Japanese man was admitted because of a hard mass in his left third finger. He had undergone surgery at the same anatomical site four and seven years previously. The roentgenogram revealed a soft tissue mass in the flexor aspect of the proximal phalanx. At operation, the tumor was found to have arisen in the tendon sheath. Histopathological examination showed that the tumor was composed of well-defined, multiple, cartilaginous nodules that were surrounded by tenosynovial tissue. A few of the nodules were calcified. The chondrocytes had mild atypia, and were immunopositive for S-100 protein. A diagnosis of tenosynovial chondromatosis was made. The nodules also contained crystalline deposits, which bore a histological resemblance to gouty tophi. We were unable to define the exact nature of these deposits even by transmission electron microscopy and electron roentgenographic microanalysis. Crystalline deposits in chondromas of soft tissue have been reported but not in tenosynovial chondromatosis. [ABSTRACT FROM AUTHOR]

Mito K, Kashima K, Daa T, Miura T, Nakayama I, Yokoyama S. Localized peribronchial adenomyomatous hyperplasia arising from an ectatic bronchus with aspergilloma. APMIS 2004;112:218–21. A cavitary lesion containing a mobile nodule was found in the right lower lung of a 68-year-old woman. Suspecting bronchiectasis with a fungus ball, we performed wedge resection of the right lower lobe. Light microscopy revealed that a uniformly thickened muscular layer around the ectatic bronchus with aspergilloma had formed a focally protruding mass. It was composed of bundles of hyperplastic smooth muscle and entrapped glandular structures. Given the histological similarity between the lesion and adenomyomatous hyperplasia of the gallbladder, we diagnosed the previously undescribed lesion as “localized peribronchial adenomyomatous hyperplasia”. This condition should be recognized as a tumor-like form of smooth muscle hyperplasia induced by bronchiectasis and inflammation. [ABSTRACT FROM AUTHOR]

Payano M, Kondo Y, Kashima K, Daa T, Yatsuka T, Kida H, Nakayama I, Yokoyama I. Two cases of nondura-based clear cell meningioma of the cauda equina. APMIS 2004;112:141–7. Clear cell meningioma is a rare disorder. We report two cases of nondura-based clear cell meningioma of the cauda equina, one in a 24-year-old male and the other in a 19-year-old female. Both patients had complained of numbness and spontaneous pain in the lower back and limbs for several months. Magnetic resonance imaging and computed tomography scanning revealed an intradural tumor in the cauda equina in each case. At surgery, a neurilemoma was suspected, because each of the tumors had displaced nerve roots and had attached to one of the nerve roots without any adherence to the dura. Light microscopy revealed that both tumors were well-demarcated with a thin capsule and consisted mainly of clear, glycogen-rich, polygonal cells with vague whorl formations, and of copious deposits of hyalinized blocky collagen in the stroma and perivascular areas. The neoplastic cells were immunopositive for vimentin and epithelial membrane antigen, but immunonegative for S-100 protein and chromogranin A. Positive nuclei for MIB-1 were very few in both cases, and PCNA-labeling indices were 12.1% and 24.7%, respectively. No local recurrence has been seen for 61 months and for 52 months, respectively. [ABSTRACT FROM AUTHOR]

Phlebosclerosis of the colon is a rare disease characterized by a thickening of the wall of the colon with fibrosis, hy-alinization and calcification to the affected veins. These symptoms result in a type of ischemic colitis known as phlebosclerotic colitis. A case of phlebosclerotic colitis coincident with carcinoma in adenoma is reported. A 74-year-old Japanese woman was admitted to hospital because of a mass in her right lower abdomen. Abdominal computed tomography examination revealed linear calcifications in the wall of the cecum and the ascending colon. Colonoscopy revealed dark purple mucosa with multiple ulcers in the cecum and the ascending colon. Biopsy specimens showed a marked hyalinous thickening of the wall of small blood vessels in the mucosa. Phlebosclerotic colitis was suspected because of negative results with amyloid stain. Alternative ileocolic angiography showed the serpentine of the peripheral nature blood vessels and pooling at the late venous phase. Microscopic examination of the surgically resected colon revealed mucosal and submucosal fibrosis, and a thickening of the venous wall with fibrosis, hyalinization and calcification from the mucosa to the serosa, which caused a marked luminal narrowing. A small polypoid lesion was also found in the affected region and was diagnosed histologically as carcinoma in adenoma. To our knowledge, this is the first reported case of phlebosclerotic colitis complicated by carcinoma. [ABSTRACT FROM AUTHOR]

Spindle cell lipoma (SCL) is a relatively uncommon benign lipomatous tumor characterized by a mixture of mature adipocytes and bland spindle cells on a fibromyxoid background. These lipomas usually arise as solitary nodules in the subcutaneous tissue of the posterior neck, shoulder and back in adult men. Multiple SCLs account for 0.5% to 3% of all SCLs. In the literature, there have been 15 cases of intraoral SCL, including 6 cases of SCL in the tongue. We report a case of multiple SCLs on the bilateral margins of the tongue of a 75-year-old Japanese man. The tumors were removed surgically, and they exhibited the classic histopathological features of SCL, being well-circumscribed masses composed of a mixture of adipocytes and fibroblast-like spindle cells within a fibromyxoid stroma. Immunohistochemical analysis revealed that the spindle cells were strongly positive for CD 34 and bcl-2. To our knowledge, this is the first report of a case of multiple SCLs of the tongue. [ABSTRACT FROM AUTHOR]

Myxoid adrenal cortical adenoma is a rare tumor and, to our knowledge, only 16 cases have been reported. We present the case of a 56-year-old Japanese man who was admitted to hospital because of a right adrenal mass that was discovered during a routine physical examination. The resected mass was well circumscribed and contained canary yellow multinodular regions that were surrounded by a brown gelatinous region. Histologically, the multinodular regions resembled a conventional adrenal cortical adenoma, being composed of solid aggregates of large clear or eosinophilic cells. In the gelatinous region, anastomosing small eosinophilic or vesicular cells were visible within a myxoid stroma that contained large amounts of acidic mucopolysaccharides. Light-microscopic findings were consistent with a diagnosis of adenoma. Immunohistochemical staining revealed that a small number of tumor cells were positive for vimentin, and the MIB-1 labeling index was less than 1%. Flow cytometry demonstrated that cells were diploid. At the ultrastructural level, many fat droplets were found in the large clear cells in the multinodular regions. Small eosinophilic cells in the myxoid region contained many mitochondria but few fat droplets. There were no findings suggestive of malignancy. Although the adrenal cortex might have the potential to produce connective tissue-type mucin as a consequence of its mesodermal origin, the mechanism of production of acidic mucopolysaccharides in a myxoid adrenal cortical tumor remains to be clarified. [ABSTRACT FROM AUTHOR]

To clarify the pathologic value of endogenous biotin in the salivary gland, we examined in a series of neoplasms of the salivary gland by immunohistochemical staining the distribution of endogenous biotin and of biotin-binding enzymes, namely, acetyl CoA carboxylase (AC), which is a cytosolic enzyme, and pyruvate carboxylase (PC), which is a mitochondrial enzyme. In pleomorphic adenoma, we found biotin and PC in ductal epithelial elements, while AC was found mainly in myoepithelial elements. Carcinoma ex pleomorphic adenoma, adenocarcinoma and mucoepidermoid carcinoma were frequently immunopositive for biotin, PC and AC, while adenoid cystic carcinoma was rarely immunopositive for biotin, PC or AC. These results indicate that endogenous biotin might be associated with the mitochondrial enzyme, which is present at high levels in ductal cells of the salivary gland. However, the neoplastic cells in adenoid cystic carcinoma seemed to have an unusual expression of biotin and related enzymes. [ABSTRACT FROM AUTHOR]

Examines the isoform expression of splice variants of CD44 in thyroid neoplasms derived from follicular cells. Detection of variant of isoforms of CD44 in neoplastic cells; Differentiation of follicular carcinoma from follicular adenoma; Expression of CD44v3 and Cd44v6.