Recurrent Macroprolactinoma with Malignant Conversion to Carcinoma with Spinal Metastasis

In contrast to pituitary adenomas, pituitary carcinomas represent a rare malignant neoplasm with a remarkable high mortality. Pituitary carcinomas can arise from any pituitary tumor cell line and are determined to be carcinomas when there is distant metastasis or central nervous system dissemination. In this case vignette, we describe a rare case of malignant prolactinoma with intraspinal metastasis, and we also provide a review of relevant literature and treatment.

1629 The Risk of Malignancy in Cytologically Indeterminate Thyroid Nodules

Introduction Fine needle aspiration (FNA) is the gold standard for the diagnostic assessment of thyroid nodules, with cytology stratified using the Thy classification (Thy 1-5). The management of cases where cytology is indeterminate (Thy-3) is challenging and subject to controversy. The current British Thyroid Association guidelines subclassify Thy-3 lesions into Thy-3a (atypia) and Thy-3f (follicular). Repeat FNA is generally recommended for Thy-3a specimens, whilst Thy-3f lesions should proceed to diagnostic hemithyroidectomy. The aim of this study was to determine the risk of malignancy in Thy-3a and Thy-3f lesions. Method This was a retrospective study of all patients who underwent FNA of a thyroid nodule from 01/01/2018 – 31/12/19. Those with Thy-3 cytology were identified and results correlated with final surgical histology. Results In total, there were 179 patients with Thy-3 cytology: 37 Thy-3a and 142 Thy-3f. The rate of malignancy was 21.6% (n = 8) for Thy-3a lesions and 20.4% (n = 29) for Thy-3f. When excluding microcarcinoma, the rates fell to 20.4% (n = 7) and 12.7% (n = 18) respectively. There was no statistically significant difference in malignant conversion between the two groups (p = 0.20). Conclusions This study does not demonstrate any statistically significant difference in the risk of malignancy between the Thy-3a and Thy-3f groups, suggesting that this subclassification does not add any additional utility to clinical decision making. Consideration should be given to the use of local malignant conversion rates to guide further management and pre-operative patient counselling in the Thy3 group.

Epithelial–Mesenchymal Transition Associated with Head and Neck Squamous Cell Carcinomas: A Review

Head and neck squamous cell carcinomas (HNSCCs) are aggressive, recurrent, and metastatic neoplasms with a high occurrence around the world and can lead to death when not treated appropriately. Several molecules and signaling pathways are involved in the malignant conversion process. Epithelial–mesenchymal transition (EMT) has been described in HNSCCs, a major type of aggressive carcinoma. EMT describes the development of epithelial cells into mesenchymal cells, which depends on several molecular interactions and signaling pathways that facilitate mesenchymal conversion. This is related to interactions with the microenvironment of the tumor, hypoxia, growth factors, matrix metalloproteinases, and the presence of viral infections. In this review, we focus on the main molecules related to EMT, their interactions with the tumor microenvironment, plasticity phenomena, epigenetic regulation, hypoxia, inflammation, their relationship with immune cells, and the inhibition of EMT in the context of HNSCCs.

Can Discord Domain-Containing Receptor 2 Mutation Act as a Disease Modifier for PRKAR1A Associated Melanotic Schwannoma?

Melanotic Schwannomas are rare neural sheath tumors with distinctive findings of both Schwann cells and melanocytic cells. Recognition of this entity has prompted the importance of distinction from similar tumor types such as melanomas. Early diagnosis facilitates removal of the mass with less risk of local invasion and metastasis. Although previously known as mostly benign lesions, malignant conversion and recurrence are recognized. This paper presents a patient with melanotic schwannoma, describes the distinctive features that will separate it from melanoma, and addresses the possibility of further guided therapy through next-generation sequencing.

Dynamic super-enhancer core regulatory circuits and epigenetic landscapes drive malignant progression and refractory disease in multiple myeloma

The plasma cell malignancy multiple myeloma (MM) evolves from a pre-malignant state and remains all but incurable due to emergence of therapy resistance. Despite intensive analyses, mechanisms driving MM progression and refractory disease are poorly understood. Integrating topologic, expression and epigenetic analyses of 1,016 patient specimens, we report super-enhancer core regulatory circuits (SECRCs) that drive and sustain MM epigenetic states. Reprogramming of cell identity and tumor microenvironment genes drive malignant conversion, while alterations in cell cycle and metabolic control genes cause refractory disease. Thus, select epigenetic states drive progression and therapy resistance, providing strategies to prevent and effectively treat MM.

Is elongated styloid process a potential forewarning for failure in oral submucous fibrosis management?

<p class="abstract">Oral submucous fibrosis is a widespread, premalignant disorder causing severe difficulty in mastication and speech. With high rate of malignant conversion, it demands aggressive surgical therapy followed by mandatory long-term physiotherapy. An elongated styloid process, if present, could pose a strong hindrance to movement of mandible, leading to complete relapse of trismus in such cases. The purpose of this report is to elaborate on such co-existence in patients having oral submucous fibrosis using digital orthopantomogram. 3 patients suspected to have an elongated styloid process were referred to maxillofacial surgical unit and diagnosed with grade 4A oral submucous fibrosis. Digital orthopantomogram revealed elongated styloid process which was measured using the C. S. imaging software 7.0.3. Consequently, patients were operated by a team of maxillofacial surgeons and otolaryngologists to relieve trismus and tonsillo-styloidectomy respectively. The measured lengths of the styloid process on digital orthopantomogram were considered elongated, if exceeding the normal length of 30 mm. The measured lengths of the styloid process were found to be at 52.7 mm, 50.1 mm and 57 mm on the right side and 51 mm, 46.8 mm and 37 mm on left side respectively in our cases. These elongated styloid processes observed in all three cases of submucous fibrosis indicates that progressive fibrosis may exert significant influence on the ossification of styloid complex. Hence, a routine preoperative screening in all patients of oral submucous fibrosis is imminent to avoid postoperative failure, pain or discomfort to the patient owing to an elongated styloid process. </p>

MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors

DNA mutation-induced activation of RAS-BRAF-MEK-ERK signaling associated with intermittent or chronic ultraviolet (UV) irradiation cannot exclusively explain the excessive increase of malignant melanoma (MM) incidence since the 1950s. Malignant conversion of a melanocyte to an MM cell and metastatic MM is associated with a steady increase in microRNA-21 (miR-21). At the epigenetic level, miR-21 inhibits key tumor suppressors of the RAS-BRAF signaling pathway enhancing proliferation and MM progression. Increased MM cell levels of miR-21 either result from endogenous upregulation of melanocytic miR-21 expression or by uptake of miR-21-enriched exogenous exosomes. Based on epidemiological data and translational evidence, this review provides deeper insights into environmentally and metabolically induced exosomal miR-21 trafficking beyond UV-irradiation in melanomagenesis and MM progression. Sources of miR-21-enriched exosomes include UV-irradiated keratinocytes, adipocyte-derived exosomes in obesity, airway epithelium-derived exosomes generated by smoking and pollution, diet-related exosomes and inflammation-induced exosomes, which may synergistically increase the exosomal miR-21 burden of the melanocyte, the transformed MM cell and its tumor environment. Several therapeutic agents that suppress MM cell growth and proliferation attenuate miR-21 expression. These include miR-21 antagonists, metformin, kinase inhibitors, beta-blockers, vitamin D, and plant-derived bioactive compounds, which may represent new options for the prevention and treatment of MM.

Mapping and Quantification of Non-Coding RNA Originating from the rDNA in Human Glioma Cells

Ribosomal DNA is one of the most conserved parts of the genome, especially in its rRNA coding regions, but some puzzling pieces of its noncoding repetitive sequences harbor secrets of cell growth and development machinery. Disruptions in the neat mechanisms of rDNA orchestrating the cell functioning result in malignant conversion. In cancer cells, the organization of rRNA coding genes and their transcription somehow differ from that of normal cells, but little is known about the particular mechanism for this switch. In this study, we demonstrate that the region ~2 kb upstream of the rDNA promoter is transcriptionally active in one type of the most malignant human brain tumors, and we compare its expression rate to that of healthy human tissues and cell cultures. Sense and antisense non-coding RNA transcripts were detected and mapped, but their secondary structure and functions remain to be elucidated. We propose that the transcripts may relate to a new class of so-called promoter-associated RNAs (pRNAs), or have some other regulatory functions. We also hope that the expression of these non-coding RNAs can be used as a marker in glioma diagnostics and prognosis.