Perilesional Targeted Biopsy Combined with MRI-TRUS Image Fusion-Guided Targeted Prostate Biopsy: An Analysis According to PI-RADS Scores.

A prostate-targeted biopsy (TB) core is usually collected from a site where magnetic resonance imaging (MRI) indicates possible cancer. However, the extent of the lesion is difficult to accurately predict using MRI or TB alone. Therefore, we performed several biopsies around the TB site (perilesional [p] TB) and analyzed the association between the positive cores obtained using TB and pTB and the Prostate Imaging Reporting and Data System (PI-RADS) scores. This retrospective study included patients who underwent prostate biopsies. The extent of pTB was defined as the area within 10 mm of a TB site. A total of 162 eligible patients were enrolled. Prostate cancer (PCa) was diagnosed in 75.2% of patients undergoing TB, with a positivity rate of 50.7% for a PI-RADS score of 3, 95.8% for a PI-RADS score of 4, and 100% for a PI-RADS score of 5. Patients diagnosed with PCa according to both TB and pTB had significantly higher positivity rates for PI-RADS scores of 4 and 5 than for a PI-RADS score of 3 (p < 0.0001 and p = 0.0009, respectively). Additional pTB may be performed in patients with PI-RADS ≥ 4 regions of interest for assessing PCa malignancy.

A Case of Gastric Amphicrine Signet-Ring Cell Carcinoma.

"Amphicrine" (in Greek, amphi- means "both" or "double") refers to cells that synchronously exhibit the endocrine and exocrine phenotypes. Gastric amphicrine carcinoma is very rare, and only a few case reports are found in the English literature; thus, its pathobiological features remain unclear. Here, we report a case of amphicrine gastric carcinoma. A woman in her sixth decade of life presented with anemia and underwent upper endoscopy, followed by histopathological examination of biopsy specimens. She appeared to have gastric cancer with a tumor measuring 5.0 cm × 4.0 cm in size. Subsequently, the patient underwent total gastrectomy with lymph node dissection. Histopathological examination revealed a poorly cohesive carcinoma that sparsely coexisted with signet-ring cell carcinoma cells with regional lymph node metastasis. Interestingly, synaptophysin immunoreactivity with the coexistence of Alcian blue was found in individual signet-ring cell carcinoma cells. Furthermore, the present amphicrine carcinoma cells immunohistochemically expressed CD44 variant 9, a functional cancer stem cell marker. We believe that the present case findings may support the idea of multipotent stem cells being an origin of amphicrine gastric cancers.

High-grade serous ovarian carcinoma with mucinous differentiation: report of a rare and unique case suggesting transition from the "SET" feature of high-grade serous carcinoma to the "STEM" feature.

BACKGROUND: High-grade serous carcinoma, a representative high-grade ovarian carcinoma, is believed to be closely associated with a TP53 mutation. Recently, this category of ovarian carcinoma has gained increasing attention owing to the recognition of morphological varieties of TP53-mutated high-grade ovarian carcinoma. Herein, we report the case of a patient with high-grade serous carcinoma with mucinous differentiation. CASE PRESENTATION: A 59-year-old postmenopausal woman was referred to the gynecologist because of abnormal vaginal bleeding. The radiological assessment revealed an intrapelvic multicystic mass, which was interpreted as an early right ovarian cancer and then removed by radical surgery. Histologically, the cancer cells were found in the bilateral ovaries and para-aortic lymph nodes. The cancer cells showed high-grade nuclear atypia and various morphologies, including the solid, pseudo-endometrioid, transitional cell-like (SET) pattern, and mucin-producing patterns. Benign and/or borderline mucin-producing epithelium, serous tubal intraepithelial carcinoma, and endometriosis-related lesions were not observed. In immunohistochemistry analyses, the cancer cells were diffuse positive for p53; block positive for p16; partial positive for WT1, ER, PgR, CDX2 and PAX8; and negative for p40, p63, GATA3, Napsin A, and vimentin. The Ki-67 labeling index of the cancer cells was 60-80%. Direct sequencing revealed that the cancer cells contained a missense mutation (c.730G>A) in the TP53 gene. CONCLUSION: Mucinous differentiation in high-grade serous carcinoma is a rare and unique ovarian tumor phenotype and it mimics the phenotypes of mucinous or seromucinous carcinoma. To avoid the misdiagnosis, extensive histological and immunohistochemical analyses should be performed when pathologists encounter high-grade mucin-producing ovarian carcinoma. The present case shows that the unusual histological characteristic of high-grade serous carcinoma, the "SET" feature, could be extended to the solid, transitional, endometrioid and mucinous-like (STEM) feature.

Two rare cases of a solid pseudopapillary neoplasm of the pancreas.

A solid pseudopapillary neoplasm (SPN) of the pancreas has distinct histopathological features. A solid pattern of growth with pseudopapillary structures that result from degeneration is observed. On rare occasions, the tumor may vary from being entirely solid to completely cystic. The present study describes two unique cases of SPN. A 25-year-old male presented with a pancreatic tumor showing a predominantly solid pattern with no degenerative change, although the pre-operative cytological specimens that were obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) revealed pseudopapillary structures. The second case was of an 11-year-old female who presented with a pancreatic tumor with prominent degeneration. Nests and cords of the remaining neoplastic cells were located only at the periphery, with perineural invasion. An immunohistochemical analysis revealed that the tumor cells in the two cases were positive for CD10 and ß-catenin and negative for trypsin. An awareness of the broad morphological variability of SPN and an immunohistochemical panel that includes CD10, ß-catenin and trypsin are useful for establishing an accurate diagnosis.

[A case of xp11.2 translocation renal cell carcinoma].

Xp11.2/TFE3 translocation renal cell carcinoma (RCC), a recently classified distinct subtype, is a rare tumor that usually affects children and adolescents. The morphology and biological behavior are not widely recognized, Xp11.2 translocation RCC is suggestive of early metastases despite the small tumor size. The definitive diagnosis requires the evidence of several different reciprocal translocations involving the TFE3 gene located on chromosome Xp11.2. Here, we present a case of Xp11.2 translocation RCC in an 18-yearold male. He was referred to our hospital because of a right renal tumor with macroscopic hematuria and right flank colic. The radiographic evaluation including magnetic resonance imaging (MRI) suggested it to be a typical papillary renal cell carcinoma or benign renal tumor. He underwent laparoscopic nephrectomy against the repeat symptom in spite of small tumor (3.5 cm in diameter). The immunohistochemical study revealed nuclear staining for TFE3 protein in the cancer cells. The urologic and radiologic outcomes were satisfactory after more than 1 year of follow-up.

A case of esophageal adenocarcinoma arising from the ectopic gastric mucosa in the thoracic esophagus.

A 75-year old man was detected with a pediculate tumor in the upper esophagus. A biopsy determined that it was an adenocarcinoma. A subtotal esophagectomy with dissection of three-fields of lymph nodes was selected. The pathological study revealed it to be an esophageal adenocarcinoma arising from ectopic gastric mucosa of the fundus of the stomach. His post-operative course was uneventful and without sign of recurrence for 3.5 years.

Preventive effect of fermented brown rice and rice bran on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats.

A number of possible preventive agents for cancers in different organs have been reported, however, little information is available regarding the effective agents for the development of gastric cancers. The rice components are known to be effective for the prevention of the development of cancers. Our group has demonstrated that fermented brown rice by Aspergillus Orzae (FBRA) has chemopreventive potentials in several organs. In this study, we investigated the modifying effects of FBRA exposed during the initiation or post-initiation phase of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in rats. Five-week-old male ACI rats were divided into 7 groups. Groups 1-5 were given oral administration of MNNG (100 mg/l in distilled water) for 24 weeks starting at 6 weeks of age. Groups 2 and 3 were fed a diet containing 5 and 10% FBRA during the initiation phase, respectively, whereas groups 4 and 5 were fed these diets during the post-initiation phase. Group 6 was given a diet containing 10% FBRA throughout the experiment. Group 7 was kept on the basal diet alone and served as an untreated control. Rats were sacrificed at 52 weeks after the start, and the epithelium of the stomach was investigated in detail. Incidence and multiplicity of gastric proliferative lesions of group 1 (MNNG alone) were 61% and 1.67+/-1.57/rat, respectively. Those of group 5 (25%, 0.35+/-0.67) which were given FBRA at a dose of 10% during the post-initiation phase were significantly less than those of group 1. Furthermore, the same group expressed a significantly decreased Ki67-labeling index in the non-lesional gastric epithelium when compared to that of group 1. These results indicate that FBRA inhibits MNNG-induced development of gastric tumors by administration during the post-initiation phase in rats. FBRA is regarded as a promising dietary agent for the prevention of human gastric cancer.

Effect of 2-(carboxyphenyl) retinamide and genistein on the formation of early lesions in 1,2-dimethylhydrazine-induced colon carcinogenesis in rats.

Aberrant crypt foci (ACF) are recognized as preneoplastic lesions for colon cancer, and ACF in rodents are widely used as an intermediate biomarker to predict tumorigenicity in the colon. However, a lack of correlations between the formation of ACF and the development of colonic tumors has been reported in several studies. For example, 2-(carboxyphenyl) retinamide (2-CPR) and genistein were reported to inhibit the carcinogen-induced formation of ACF, whereas both of them were later found to enhance colon tumorigenesis in rats treated with azoxymethane (AOM). Recently, we have identified b-catenin-accumulated crypts (BCAC) in the colon of rats shortly after administration of AOM, and provided evidence that these are independent early lesions of classical ACF, and BCAC might be direct precursors for colon cancers. In the present study, we performed a comparative analysis of the modifying effects of 2-CPR and genistein on 1,2-dimethylhydrazine (DMH)-induced BCAC and ACF in male F344 rats. Dietary administration of 2-CPR (315 ppm) significantly reduced the total number, multiplicity and size of ACF in DMH-exposed colonic mucosa, while genistein (250 ppm) had no significant effects on DMH-induced ACF formation. In contrast, both of 2-CPR and genistein significantly enhanced the multiplicity and size of DMH-induced BCAC when compared with DMH alone group. In addition, both 2-CPR and genistein significantly increased the proliferating cell nuclear antigen (PCNA) index preferentially in BCAC. Together with previous findings that 2-CPR and genistein are tumor promoters in the colon, our results support the concept that BCAC are precursors of colon tumors and suggest that these lesions are more reliable short-term biomarkers for colon carcinogenesis in rodents than ACF.

Preventive effects of a flavonoid myricitrin on the formation of azoxymethane-induced premalignant lesions in colons of rats.

The preventive effect of dietary exposure to a flavonoid myricitrin of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and beta-catenin-accumulated crypts (BCAC) formation was investigated in male F344 rats. Thirty-four rats were divided randomly into five experimental groups. Rats in groups 1-3 were given subcutaneous injections of AOM (15 mg/kg body weight) once a week for 3 weeks. Starting 1 week before the first injection of AOM, rats in groups 2 and 3 were fed a diet containing 500 or 1000 ppm myricitrin, respectively, for 11 weeks. Rats in group 4 were fed a diet containing 1000 ppm myricitrin. Rats in groups 1 and 5 were given the basal diet alone during the study. The experiment was terminated 11 weeks after the start. The frequency of ACF per colon in group 3 treated with AOM and 1000 ppm myricitrin was significantly lower than that in group 1 treated with AOM alone (p<0.01). Furthermore, dietary myricitrin at both doses (groups 2 and 3) significantly inhibited the formation of BCAC when compared to group 1 (p<0.05). These results indicate that myricitrin had possible chemopreventive effects in the present short-term colon carcinogenesis bioassays and suggest that longer exposure may cause suppression of tumor development.

Modifying effect of dietary sesaminol glucosides on the formation of azoxymethane-induced premalignant lesions of rat colon.

Sesame, which has been reported to have preventive effects against various disordered conditions, contains small quantities of lignans and several precursors to them such as sesaminol glucosides (SG). The lignans have the potent antioxidative activity and are suggested to have chemopreventive property. In the present study, we evaluated the modulating effect of SG on the development of colon precancerous lesions, aberrant crypt foci (ACF) and beta-catenin-accumulated crypts (BCAC), in the azoxymethane (AOM)-induced short-term model using male F344 rats. Dietary SG (500 ppm) significantly decreased the incidence of AOM-induced ACF when compared to the control (P<0.01). The incidences of AOM-induced BCAC in the SG-treated groups (250 or 500 ppm) were also significantly lower than that of the control group (P<0.01). Interestingly, administration of 500 ppm SG clearly decreased serum triglyceride level and mRNA expression of intestinal fatty acid-binding protein in the colonic mucosa, as compared to the control. These findings indicate that dietary SG inhibits AOM-induced carcinogenesis and suggest SG as a possible chemopreventive agent.

Chemoprevention of mouse urinary bladder carcinogenesis by fermented brown rice and rice bran.

Fermented brown rice by Aspergillus oryzae (FBRA) has been shown to be a potent anti-carcinogenic compound. Here, we investigated the modifying effects of dietary feeding with a naturally occurring anti-oxidant FBRA on N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN)-induced urinary bladder carcinogenesis in male ICR mice. Five-week-old male ICR mice were divided into 7 groups, and groups 1-5 were given OH-BBN (500 ppm) in drinking water for 6 weeks starting at 7 weeks of age. Groups 2 and 3 were fed the diet containing 5% and 10% FBRA during the initiation phase, respectively, whereas groups 4 and 5 were fed these diets during the post-initiation phase. Group 6 was given the diet containing 10% FBRA throughout the experiment, and group 7 was kept on the basal diet alone and served as an untreated control. At the end of the study (week 32), the incidences of simple hyperplasia, dysplasia and carcinoma in the bladders of group 1 (OH-BBN alone) were 92%, 49% and 38%, respectively. Those of group 5 (64%, 23% and 10%) and the incidence of carcinoma of group 4 (17%) was significantly less than that of group 1. Furthermore, the multiplicity of simple hyperplasia and carcinoma of group 5 was significantly less than that of group 1. Post-initiation exposure of 10% FBRA significantly decreased the number/nucleus of silver-stained nucleolar organizer region proteins (AgNORs), an index of cell proliferation, in the non-lesional transitional epithelium when compared to that of the control. Our results indicate that FBRA exerts chemopreventive effects against chemically induced urinary bladder carcinogenesis through anti-proliferative mechanisms. FBRA could be a promising chemopreventive agent for human urinary bladder cancer.