Expression of EpCAM in adenoid cystic carcinoma

The mutational landscape of adenoid cystic carcinoma (ACC) is currently being revealed, but further studies are needed to identify biomarkers as therapeutic targets or prognostic factors of ACC. In this study, we investigated the expression of epithelial cell adhesion molecule (EpCAM) in ACCs. We retrospectively collected 83 cases of surgically resected ACCs. Using tissue microarray, we conducted immunohistochemical staining using the anti-EpCAM antibody. EpCAM expression was analysed by intensity score and the total immunostaining score. The positivity was 97.6% (81/83 cases), regardless of the intensity score. A higher histological grade (p = 0.006) and specific tumour location (non-salivary gland origin, p = 0.02) showed a correlation with higher EpCAM intensity. Higher EpCAM expression by total immunostaining score was associated with histological grade (p = 0.004), distant metastasis (p = 0.004) and poorer prognosis (overall survival p = 0.015 and progression-free survival p = 0.033). We suggest EpCAM as a candidate prognostic marker and a putative therapeutic target in ACC. Also, ACCs arising from salivary gland and non-salivary gland sites, respectively, might display different pathophysiologies in which EpCAM could play a role.ope

Nevus Comedonicus Syndrome Associated with Psychiatric Disorder

Nevus comedonicus (NC) is a rare hamartoma of the pilosebaceous unit origin. The association with extracutaneous abnormalities defines NC syndrome (NCS). Fewer than 50 cases of NCS have been reported in the English literature. A 31-year-old woman presented with grouped and linear comedonal papules present from birth and located on the left buttock along Blaschko's lines. She had a history of pediatric mood disorder combined with attention-deficit hyperactivity disorder (ADHD) from 5 years of age and was recently diagnosed with sinus bradycardia. Her skin lesion was surgically removed and microscopic findings revealed the aggregation of dilated follicular infundibula filled with prominent laminated keratin plugs, a characteristic finding of NC. This is the first report presenting NCS associated with mood disorder and ADHD. Psychiatric symptoms may represent systemic manifestation of NCS.ope

Graphene-Iodine Nanocomposites Highly Potent Bacterial Inhibitors that are Bio-compatible with Human Cells

Graphene-composites, capable of inhibiting bacterial growth which is also bio-compatible with human cells have been highly sought after. Here we report for the first time the preparation of new graphene-iodine nano-composites via electrostatic interactions between positively charged graphene derivatives and triiodide anions. The resulting composites were characterized by X-ray photoemission spectroscopy, UV-spectroscopy, Raman spectroscopy and Scanning electron microscopy. The antibacterial potential of these graphene-iodine composites against Klebsiella pneumonia, Pseudomonas aeruginosa, Proteus mirobilis, Staphylococcus aureus, and E. coli was investigated. In addition, the cytotoxicity of the nanocomposite with human cells [human white blood cells (WBC), HeLa, MDA-MB-231, Fibroblast (primary human keratinocyte) and Keratinocyte (immortalized fibroblast)], was assessed. DGO (Double-oxidizes graphene oxide) was prepared by the additional oxidation of GO (graphene oxide). This generates more oxygen containing functional groups that can readily trap more H(+), thus generating a positively charged surface area under highly acidic conditions. This step allowed bonding with a greater number of anionic triiodides and generated the most potent antibacterial agent among graphene-iodine and as-made povidone-iodine (PVP-I) composites also exhibited nontoxic to human cells culture. Thus, these nano-composites can be used to inhibit the growth of various bacterial species. Importantly, they are also very low-cytotoxic to human cells culture.ope

Basal cell carcinoma arising from the epidermoid cyst

Basal cell carcinoma and epidermoid cysts are common skin afflictions that arise in the epidermis and hair follicles of the skin. Only a small number of cases have been reported in which a basal cell carcinoma has arisen within an epidermoid cyst. We present the clinical features of this unusual condition in this report and believe that the information will prove useful to researchers of basal cell carcinoma.ope

Frequency of GNAS R201H substitution mutation in polyostotic fibrous dysplasia: Pyrosequencing analysis in tissue samples with or without decalcification

Guanine nucleotide-binding protein/α-subunit (GNAS) mutations are involved in fibrous dysplasia (FD) pathogenesis. Here, we analyzed GNAS mutations in FD which were performed by pyrosequencing DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue. The mutation detection rate was determined in FD specimens with and without decalcification. GNAS mutation was identified in 28 cases out of 87 FDs (32.18%) [p.R201C (N = 14) and p.R201H (N = 14)]. GNAS mutation was more likely to occur in polyostotic FD (7/28, 25.0%); FD without GNAS mutation was mostly monostotic form (56/59, 94.9%, P = 0.011). The G > A (R201H) mutation was more frequent in polyostotic FD (6/14 patients, 42.9%) than the C > T (R201C) mutation (1/14, 7.1%) (P = 0.077). We divided the FD cases into two subgroups: tissue specimens that were not decalcified (N = 35, 40.2%), and tissue specimens that were decalcified (N = 52, 59.8%). GNAS mutation was more frequently identified in FD specimens that were not subjected to decalcification (23/35, 65.7%) than in FD specimens that were decalcified (5/52, 9.6%) (P = 0.001). In conclusion, mutation analysis of GNAS by pyrosequencing has diagnostic value in FFPE tissue of patients with FD, especially in specimens that were not decalcified. The R201H substitution mutation of GNAS may be involved in the pathogenesis of polyostotic FD.ope

Clinicopathological significance of intratumoral and peritumoral lymphocytes and lymphocyte score based on the histologic subtypes of cutaneous melanoma

The presence of tumor infiltrating lymphocytes is a favorable prognostic factor in cutaneous melanoma, but their clinicopathological significance in the intratumoral compartment compared to the peritumoral compartment is unclear. We investigated the clinicopathologic significance of tumor-infiltrating lymphocytes and lymphocyte score in intra- and peritumoral compartments in 177 Korean patients who had undergone surgical excision of cutaneous melanoma. No significant correlation was observed between various clinicopathologic factors and the presence of intratumoral lymphocytes. However, high peritumoral lymphocyte scores were associated with lower Clark levels (P = 0.001), shallower Breslow thicknesses (P = 0.006), and fewer mitotic counts (P = 0.01) than tumors with lower scores. There was a trend for longer disease-free survival in cases with peritumoral lymphocytes (P = 0.07) than those without peritumoral lymphocytes. In patients with acral lentiginous melanoma, a strong association between a high peritumoral lymphocyte score and shallow Clark level was apparent (P = 0.03), and the presence of peritumoral lymphocytes (P = 0.02) and a high intratumoral lymphocyte score (P = 0.04) was also associated with longer disease-free survival. Particularly, low intratumoral lymphocyte score remarkably affected tumor recurrence and distant metastasis in a multivariate analysis using Cox regression test (H.R. = 0.304, 95% C.I. = 0.078-1.185, P = 0.09). Thus, the presence of lymphocytes and high lymphocyte scores in the intratumoral and peritumoral compartments are valid prognostic factors in cutaneous melanoma.ope

WWC1 and NF2 Prevent the Development of Intrahepatic Cholangiocarcinoma by Regulating YAP/TAZ Activity through LATS in Mice

Hippo signaling acts as a tumor suppressor pathway by inhibiting the proliferation of adult stem cells and progenitor cells in various organs. Liver-specific deletion of Hippo pathway components in mice induces liver cancer development through activation of the transcriptional coactivators, YAP and TAZ, which exhibit nuclear enrichment and are activated in numerous types of cancer. The upstream-most regulators of Warts, the Drosophila ortholog of mammalian LATS1/2, are Kibra, Expanded, and Merlin. However, the roles of the corresponding mammalian orthologs, WWC1, FRMD6 and NF2, in the regulation of LATS1/2 activity and liver tumorigenesis in vivo are not fully understood. Here, we show that deletion of both Wwc1 and Nf2 in the liver accelerates intrahepatic cholangiocarcinoma (iCCA) development through activation of YAP/TAZ. Additionally, biliary epithelial cell-specific deletion of both Lats1 and Lats2 using a Sox9-CreERT2 system resulted in iCCA development through hyperactivation of YAP/TAZ. These findings suggest that WWC1 and NF2 cooperate to promote suppression of cholangiocarcinoma development by inhibiting the oncogenic activity of YAP/TAZ via LATS1/2.ope

Pediatric splenic angiosarcoma

Angiosarcomas are malignant vascular neoplasms that usually occur in deep soft tissue. Patients diagnosed with angiosarcoma are usually elderly and are given poor prognoses. Pediatric splenic angiosarcoma is extremely rare, and its pathogenesis is not as well understood as that of older patients. We describe a case of 4-year-old male who had undergone splenectomy for splenic mass. Histopathological examination revealed primary splenic angiosarcoma. We then reviewed published literatures to characterize its clinical characteristics.ope

Epithelioid hemangioendotheliomas with TFE3 gene translocations are compossible with CAMTA1 gene rearrangements.

Epithelioid hemangioendotheliomas (EHEs) are vascular tumors of intermediate malignancy that can undergo high-grade malignant transformations. EHEs have been characterized by tumor-specific WW domain-containing transcription regulator 1(WWTR1)-calmodulin-binding transcription activator 1 (CAMTA1) translocations, and recently, a novel Yes-associated protein 1 (YAP1)-transcription factor E3 (TFE3) gene fusion was identified in EHEs. In this study, we examined the expression levels of TFE3 and CAMTA1 via immunohistochemical staining and identified chromosomal alterations using fluorescence in situ hybridization (FISH) assays and RT-PCR tests. Although all of the EHEs were CAMTA1-positive in immunohistochemical staining, only five out of 18 EHEs (27.78%) positively expressed nuclear TFE3. The five TFE3-positive EHEs exhibited TFE3 gene break-apart in FISH assays. YAP1-TFE3 gene fusions were confirmed by RT-PCR. Interestingly, we observed CAMTA1 gene break-apart in all of the five TFE3-positive EHEs via FISH assays, and four out of the five TFE3-positive EHEs exhibited WWTR1-CAMTA1 gene fusions via RT-PCR. These results indicate that these two chromosomal alterations are not mutually exclusive but compossible in EHEs. Finally, primary tumor sites in TFE3-positive EHEs consistently contained single masses (P = 0.0359) with larger sizes (P = 0.0550) compared to TFE3-negative EHEs. Similar to previous reports, we observed well-formed vessels more frequently in TFE3-positive EHEs than in TFE3-negative EHEs (P = 0.0441). In addition, TFE3-positive EHEs tended to more frequently demonstrate high-grade nuclear atypia (P = 0.0654) and hypercellularity (P=0.0987) than TFE3-negative EHEs. Thus, we have now established two clinically distinct subgroups of EHEs: TFE3-positive and TFE3-negative EHEs.ope

Clinicopathologic Characteristics and Mutational Status of Succinate Dehydrogenase Genes in Paraganglioma of the Urinary Bladder: A Multi-Institutional Korean Study

CONTEXT: Because of the limited number of available primary bladder paraganglioma (PBPG) cases, the rates of succinate dehydrogenase (SDH) mutations and the clinicopathologic characteristics of SDH-deficient tumors have not been fully studied. OBJECTIVE: To define the clinicopathologic and molecular characteristics of PBPGs. DESIGN: A total of 52 PBPGs were collected retrospectively. SDHA and SDHB immunohistochemical stains were performed. In cases of SDHB expression loss, mutation analyses of SDHB, SDHC, and SDHD were performed. RESULTS: The clinicopathologic features were analyzed for 52 cases (M:F = 27:25), with a mean age of 56 years (range, 22-79 years). Tumor sizes were 0.5 to 8 cm (mean, 2.4 cm). Tumor necrosis was present in 5 of 52 cases (10%), involvement of muscularis propria in 41 (79%), and lymphovascular tumor invasion in 6 (12%). During a mean follow-up period of 41 months (range, 1-161 months), 3 of 52 patients (6%) developed metastases, but no one died from the disease. Immunohistochemistry for SDHA and SDHB showed that all cases were SDHA intact. Among them, 43 cases had intact SDHB, whereas 9 cases were SDHB deficient. Compared with the SDHB-intact cases, the SDHB-deficient cases were characterized by large tumor sizes (4.5 versus 1.9 cm; P < .001), a higher number of mitoses per 10 high-powered fields (2.6 versus 0.1; P = .002), and frequent lymphovascular tumor invasion (33% versus 7%; P = .02) and metastases (22% versus 2%; P = .02). Mutational analyses for SDHB, SDHC, and SDHD were performed in 9 SDHB-deficient cases. Among them, 6 cases were successfully sequenced and revealed SDHB mutations only. CONCLUSIONS: Large tumor size, a higher number of mitoses, and the presence of lymphovascular tumor invasion and SDHB mutations suggest malignant paraganglioma.ope