Mixed adenoneuroendocrine carcinoma of the non-ampullary duodenum with mismatch repair deficiency: a rare case report.

A non-ampullary duodenal mixed adenoneuroendocrine carcinoma (MANEC), consisting of a conventional adenocarcinoma and a neuroendocrine carcinoma (NEC), is exceedingly rare. Moreover, mismatch repair (MMR) deficient tumors have recently attracted attention. The patient, a 75-year-old woman with epigastric pain and nausea, was found to have a type 2 tumor of the duodenum, which was diagnosed on biopsy as a poorly differentiated carcinoma. A pancreaticoduodenectomy specimen showed a well-defined 50 × 48 mm tumor in the duodenal bulb, which was morphologically composed of glandular, sheet-like, and pleomorphic components. The glandular component was a tubular adenocarcinoma, showing a MUC5AC-positive gastric type. The sheet-like component consisted of homogenous tumor cells, with chromogranin A and synaptophysin diffusely positive, and a Ki-67 index of 72.8%. The pleomorphic component was diverse and prominent atypical tumor cells proliferated, focally positive for chromogranin A, diffusely positive for synaptophysin, and the Ki-67 index was 67.1%. The sheet-like and pleomorphic components were considered NEC, showing aberrant expression of p53, retinoblastoma, and p16. Notably, all three components were deficient in MLH1 and PMS2. We diagnosed a non-ampullary duodenal MANEC with MMR deficiency. This tumor has a unique morphology and immunohistochemical profile, and is valuable for clarifying the tumorigenesis mechanism of a non-ampullary duodenal MANEC.

Non-Coding RNA m6A Modification in Cancer: Mechanisms and Therapeutic Targets.

Recently, N6-methyl-adenosine (m6A) ribonucleic acid (RNA) modification, a critical and common internal RNA modification in higher eukaryotes, has generated considerable research interests. Extensive studies have revealed that non-coding RNA m6A modifications (e.g. microRNAs, long non-coding RNAs, and circular RNAs) are associated with tumorigenesis, metastasis, and other tumour characteristics; in addition, they are crucial molecular regulators of cancer progression. In this review, we discuss the relationship between non-coding RNA m6A modification and cancer progression from the perspective of various cancers. In particular, we focus on important mechanisms in tumour progression such as proliferation, apoptosis, invasion and metastasis, tumour angiogenesis. In addition, we introduce clinical applications to illustrate more vividly that non-coding RNA m6A modification has broad research prospects. With this review, we aim to summarize the latest insights and ideas into non-coding RNA m6A modification in cancer progression and targeted therapy, facilitating further research.

Human papilloma virus in head and neck cancers-role and relevance in clinical management.

The biology and clinical behavior of Head and Neck Squamous Cell Carcinomas (HNSCCs) is very distinct within different subgroups due to the distinct molecular profiles for the HPV positive versus HPV negative tumors. HPV status is the most important independent prognostic variable in multivariate analysis taking into account all other prognostic factors like tumour stage, smoking status, age and performance status. The debate today is whether the intense therapy is too aggressive in this group of patients since they show a superior survival regardless of treatment strategies. A highly divergent prognosis and distinct biology of HPV positive and HPV negative HNSCCs underlines the fact that treating them as distinct diseases is the need of the hour. Infection with HPV is associated with less aggressive disease, better loco regional control and lower rates of second primary cancers. An important caveat that remains is the emergence of intermediate prognosis of HPV positive smokers and HPV negative non smokers. Though molecular biology has provided important data on the interaction of the HPV onco proteins with genes important in cell cycle control, also speculated to be involved in pathogenesis of HNSCC, more basic research is needed to describe the differential mechanisms of tumorigenesis among the HNSCCs that show presence and absence of HPV. This is clinically relevant to reduce morbidity without compromising tumour control in HPV positive patients and improving tumour control and co-morbid illness that could be pre-existing or treatment related in HPV negative patients. There may be a need for treatment intensification and incorporation of newer agents into induction chemotherapy protocols for the HPV negative patients and so HPV detection is important to aid in this selection. HPV tumour status is therefore more important than just providing the prognostic information in these classes of tumours. This article discusses the role and clinical relevance of HPV in HNSCCs.