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Breast neuroendocrine neoplasms (NENs) constitute a rare histologic subtype that includes both neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). In this study, we aimed to gain insight into the clinical and molecular characteristics of NENs of the breast. NEN and paired distant normal fresh tissues and clinicopathological data were obtained from 17 patients with NENs, and clinicopathological data were collected from 755 patients with invasive breast carcinomas of no special type (IBCs-NST). We compared the clinicopathological characteristics of NENs and IBCs-NST and performed whole-exome sequencing (WES) of both NEN and paired normal tissues. Compared with the IBC-NST patients, the NEN patients had a higher mean age, lower clinical stage, and lower pathological nodal (pN) stage (P < 0.001, P < 0.001, and P = 0.017, respectively). The most frequently mutated gene in NENs was KMT2C (3/17, 17.6%). NENs had copy number variations (CNVs) of 8q, 11q, and 17q amplification and 17q and 11q deletion and harbored the following specific genes related to tumorigenesis: (i) suppressor genes with loss of heterozygosity (LOH) such as ACE (2/17, 11.8%); (ii) tumor driver genes such as GATA3 (2/17, 11.8%); and (iii) susceptibility genes such as MAP3K4 (17/17, 100%) and PDE4DIP (17/17, 100%). The oncogenic/likely oncogenic mutations of NETs in PI3K pathway genes (50.0%, 18.2%; P < 0.001) and MAPK signaling pathway genes (83.3%, 18.2%; P = 0.035) affected higher proportions than those of NECs. In conclusion, this study provides certain clinical and molecular evidence supporting NENs as a distinct subtype of breast cancer and provides some potential molecular features for distinguishing NETs from NECs.

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Nuclear protein in testis (NUT) carcinoma (NUT-C) is an exceedingly rare and aggressive squamous tumor characterized by an acquired rearrangement of the NUT gene involving the NUTM1 (Nut midline carcinoma, family member 1, NUT) gene encoding the nuclear protein of the testis on 15q14. As a rare tumor, there is little information available on the clinicopathologic and molecular cytogenetic findings of NMC. We herein reported a case of a 69-year-old man diagnosed with lung NMC involving the rearrangement of chromosomal region 15q14 harboring the NUTM1 gene. It was exceptionally rare for the patient's involving of the lung but having the chance to be totally resected. After radical surgery, the patient accepted further four cycles of chemotherapy and remains disease-free after 10 months. The immunohistochemical staining of PDL1 was negative and next-generation sequencing technology identified genomic alterations in discoidin domain receptor tyrosine kinase 2 (DDR2), cyclin D1 (CCND1), B-cell leukemia/lymphoma 1 (BCL1), colony-stimulating factor 1 receptor (CSF1R), runt related transcription factor 1 (RUNX1) and death domain-associated protein 6 (DAXX6) from the paraffin-embedded tissue. This case will contribute to not only a better understanding of the molecular mechanism of the primary pulmonary NUT carcinomas but also the potential therapeutic option for the patient.

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Intraductal carcinoma of the prostate (IDC-P) and bone metastasis have been both identified to associate with unfavorable clinical outcome of the prostate carcinoma (PCa). Our objective is to examine whether IDC-P or bone metastasis at diagnostic biopsies was associated with each other and whether they were linked with overall survival (OS) and cancer specific survival (CSS) of Grade Group 5 patients. We retrospectively selected the prostate biopsy specimens of 120 PCa patients with Grade Group 5 from Qilu Hospital of Shandong University between 2012 and 2016. There were 12 patients with IDC-P only, 52 patients with bone metastasis only and 10 patients with both IDC-P and bone metastasis. Overall, there was a significant correlation between the presences of the IDC-P and bone metastasis (P = 0.003). Kaplan-Meier survival analysis demonstrated that the presence of IDC-P and bone metastasis in diagnostic needle biopsy both conferred unfavorable CSS of Grade Group 5 patients. In addition, the presence of bone metastasis was a poor predictor of OS. Univariate and multivariate analysis revealed that bone metastasis was an independent prognostic factor for OS of Grade Group 5 patients, but IDC-P failed to be significant for either OS or CSS. Collectively, our study suggested that bone metastasis is an important prognostic factor and superior than the presence of the IDC-P for PCa patients with Grade Group 5.

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Pure mucinous breast carcinoma (PMBC) accounts for approximately 2% of all breast carcinoma. Overexpression or amplification of human epidermal growth factor receptor 2 (HER2) is rarely observed in PMBC. We retrieved 119 PMBCs, which included 12 HER2-positive PMBCs and 107 HER2-negative PMBCs, to compare the clinicopathologic features between HER2-positive and HER2-negative neoplasms. The assessed parameters included patient age, menstruation, laterality, tumor size, lymph node status, tumor-node-metastasis (TNM) stage, nuclear grade, receptor status, treatment and prognostic features. HER2-positive PMBCs represented approximately 10.1% of the PMBCs examined. HER2-positive PMBCs showed more frequent lymph node metastasis (P=0.038), a significantly higher clinical TNM stage (P<0.001) and nuclear grade (P<0.001), lower estrogen receptor (ER) and progesterone receptor (PR) expression and higher Ki67 expression than the HER2-negative group (P=0.011, P=0.005, and P=0.001, respectively). HER2-positive PMBCs (untreated with HER2-targeted therapy) had a significantly lower overall survival (OS) rate than HER2-negative PMBCs (P=0.005). Nodal metastasis, higher TNM stage and nuclear grade were identified as factors that result in poorer OS of patients with PMBCs (P<0.001, P=0.016, P<0.001, and P<0.001, respectively). Univariate and multivariate Cox analyses confirmed that HER2 status was an independent prognostic factor for PMBCs (P=0.003 and P=0.012, respectively). HER2-positive PMBC is a rare subtype of breast carcinoma with aggressive biological behavior. It is important to identify tumors with these aggressive clinical behaviors and manage them differently. To the best of our knowledge, this study represents the first systematic investigation of the clinicopathologic features of HER2-positive PMBCs.