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A 50-year-old Japanese man with a two-year history of a painless right scrotal mass visited our hospital. Considering laboratory findings and computed tomography, the patient was diagnosed with an uncharacteristic testicular tumor. No metastases were present on radiographic study at the first visit. Emergent high radical orchiectomy was performed, and the tumor was identified as a squamous cell carcinoma (SCC) of a testicular epidermal cyst. He is alive without recurrence or metastasis six months after surgery. Testicular SCC is an extremely rare tumor. This is the third case of testicular SCC associated with an epidermal cyst in English literature.

Neural epidermal growth factor-like like (NELL) 1 and 2 constitute a family of multimeric and multimodular extracellular glycoproteins. Although the osteogenic effects of NELL1 and functions of NELL2 in neural development have been reported, their expression and functions in cancer are largely unknown. In this study, we examined expression of NELL1 and NELL2 in renal cell carcinoma (RCC) using clinical specimens and cell lines. We show that, whereas NELL1 and NELL2 proteins are strongly expressed in renal tubules in non-cancerous areas of RCC specimens, their expression is significantly downregulated in cancerous areas. Silencing of NELL1 and NELL2 mRNA expression was also detected in RCC cell lines. Analysis of NELL1/2 promoter methylation status indicated that the CpG islands in the NELL1 and NELL2 genes are hypermethylated in RCC cell lines. NELL1 and NELL2 bind to RCC cells, suggesting that these cells express a receptor for NELL1 and NELL2 that can transduce signals. Furthermore, we found that both NELL1 and NELL2 inhibit RCC cell migration, and NELL1 further inhibits RCC cell adhesion. These results suggest that silencing of NELL gene expression by promoter hypermethylation plays roles in RCC progression by affecting cancer cell behavior. We found that the down-regulation of NELL1 and NELL2 in renal cell carcinoma (RCC) is in part due to the hypermethylation of CpG islands in their putative promoter regions. Furthermore, we found that NELL1 suppresses and NELL2 partially suppresses RCC cell migration, and NELL1 further inhibits RCC cell adhesion. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

A needle biopsy of a mass in the right breast of a 36-year-old woman revealed invasive ductal carcinoma (IDC), and approximately 20% of cancer cells showed unequivocal membranous staining with the HercepTest. After systemic therapy with trastuzumab and paclitaxel followed by FEC (fluorouracil + epirubicin + cyclophosphamide), a right mastectomy was performed. By histological and immunohistochemical examinations, the resected tumor consisted mainly of E-cadherin-negative invasive lobular carcinoma (ILC), and the rest was ERBB2-positive IDC; thus, the diagnosis was mixed ductal and lobular carcinoma. Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization (FISH) analyses revealed that ILC and IDC shared high-level amplification of CCND1 in homogeneously staining regions (HSR) and that IDC had an additional HSR-type amplicon of ERBB2. These findings strongly indicate that IDC and ILC had a common precursor cell with CCND1 amplification. Review of the biopsy specimen with FISH showed IDC with gene amplifications of CCND1 and ERBB2 as a minor component, IDC without amplification of CCND1 or ERBB2 as a major component, and a minute portion of ILC with CCND1 amplification. We speculate that chemotherapy and trastuzumab caused a marked reduction in IDC; however, ILC with CCND1 amplification was resistant to chemotherapy and grew.

Background: The maximum standardized uptake value (SUVmax) of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is an essential tool for making a diagnosis and determining treatment response. This study aimed whether the SUVmax of 18 F-FDG PET/CT could replace pathological diagnosis in luminal type breast cancer. Methods: We retrospectively enrolled 85 patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (luminal-type) between August 2013 and January 2018 who underwent 18 F-FDG PET/CT scans before surgery and had not received any treatment before surgery at Fujisawa City Hospital. We evaluated the relationship between the SUVmax of 18 F-FDG PET/CT and the Ki-67 labeling index (LI) or other clinicopathological features in luminal-type breast cancer; furthermore, we evaluated whether the SUVmax of PET/CT can help determine whether adjuvant chemotherapy is indicated. Results: The SUVmax differed significantly between the positive and negative groups that showed lymphatic invasion (P=0.018), nuclear grade (P=0.019), and lymph node metastasis (P=0.035). In addition, a significant correlation was observed between the SUVmax and Ki-67 LI (r=0.516, P Conclusions: The SUVmax of 18 F-FDG PET/CT could replace pathological diagnosis in luminal breast cancer.

A 31-year-old nulligravid woman with a 3 year history of infertility visited our hospital. After consultation and a transvaginal ultrasound and MR imaging, her uterine anomaly was identified as complete septate uterus: class V (a) by the American Fertility Society (AFS). She had a doubled uterine cervix and a vaginal septum. Hysteroscopic metroplasty was performed with the aid of a laparoscopy. Both tubal patencies were confirmed with indigocarmine in a laparoscopic image. Laparoscopic electronic cautery was also done on the left ovarian endometrioma (stage 1 endometriosis; the revised American Society for Reproductive Medicine (rASRM) classification 4 point minimal). We distrained an intrauterine device in the uterine cavity and removed it after two cycles of menstruation. The patient subsequently became pregnant during her third menstrual cycle and the current progress of her pregnancy is favorable.

EGFR and ERBB2 belong to the EGFR gene family. In esophageal squamous cell carcinomas (SCCs), amplification of EGFR or ERBB2 is usually mutually exclusive. EGFR amplification occurs in approximately 15% of SCCs, ERBB2 occurs in less than 5%. Here, we report the co-amplification of EGFR and ERBB2 in an ulcerative and infiltrating-type SCC that measured approximately 4.2 × 2.7 × 1.2cm with a superficial lesion occurring in the thoracic esophagus of a 72-year-old man. Multiplex ligation-dependent probe amplification using representative tumor sections showed gain of CCND1 and coincident amplification of ERBB2 or EGFR or neither. Immunohistochemistry and fluorescence in situ hybridization revealed that the tumor comprised three cancer-cell populations: well-differentiated SCC with high-level ERBB2 amplification and ERBB2 overexpression, more infiltrative poorly-differentiated SCC with high-level EGFR amplification and EGFR overexpression, and poorly-differentiated SCC lacking any ERBB2 or EGFR abnormality. These three populations each had low-level CCND1 amplification and nuclear cyclin D1 overexpression. This histological topology and gene amplification combinations suggested that genetic instability first produced CCND1 amplification, and then ERBB2 or EGFR gene amplification occurred. It is further speculated that during cancer progression and clonal selection indecisive predominance of either clone caused the rare co-amplification of ERBB2 and EGFR in a single chimeric tumor. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd., 発行後1年より全文公開

Salivary gland carcinomas encompass a wide spectrum of histological entities. To identify candidate therapeutic targets and innovative treatment options for these carcinomas, we examined epidermal growth factor receptor (EGFR), phosphorylated EGFR (p-EGFR), HER2, and phosphorylated forms of Akt (p-Akt) and mammalian target of rapamycin (p-mTOR) in 47 salivary gland tumors using immunohistochemistry. EGFR overexpression was found in 51 % of the tumors (24/47); in particular, EGFR overexpression occurred in mucoepidermoid (seven out of seven) and salivary duct carcinomas (9/12). Although EGFR amplification was not detected by fluorescence in situ hybridization analysis, increased copy number due to polysomy of chromosome 7, which houses EGFR, was observed in 4 of the 24 tumors with EGFR overexpression; this polysomy occurred most frequently in salivary duct carcinomas (three out of nine). HER2 overexpression was observed in 21 % (10/47) of all tumors; in these 10 tumors, HER2 gene amplification was found in seven cases. p-Akt was found in 51 % (24/47) of all tumors, most frequently in mucoepidermoid carcinomas (six out of seven). p-mTOR was found in 57 % of the latter (four out of seven). Consequently, different signaling cascades were found activated: (1) an EGFR/HER2(-Akt)-mTOR-dependent axis, with gene gains of HER2 and/or EGFR, activated in salivary duct carcinoma and carcinoma ex pleomorphic adenoma; (2) an EGFR(-Akt)-mTOR-dependent pathway activated in mucoepidermoid carcinoma or acinic cell carcinoma, without HER2 or EGFR gene alterations; and (3) an Akt-dependent pathway without EGFR/HER2 activation in other types. These findings indicate that phosphoprotein mapping of components in the EGFR/HER2-Akt-mTOR pathways may be a useful guide to select appropriate targeting regimens.