Sorafenib in Metastatic Papillary Thyroid Carcinoma with BRAF K601E Mutation on Liquid Biopsy: A Case Report and Literature Review.

Differentiated thyroid cancer (DTC) includes papillary and follicular carcinomas and is the most common type of thyroid cancer. The incidence of this cancer has increased in the last few years, and even if its prognosis is generally good for a subset of patients that does not respond to radioactive iodine (RAI) therapy, the prognosis is much worse: the median overall survival (OS) from discovery of metastasis is 3-5 years and the 10-year survival rate is only 10%. Several mutations, including RAS or RET, as well as BRAF signaling, are associated with thyroid cancer. Liquid biopsy may be useful in selected patient to identify genomic alterations and thus allowing for a precision medicine approach with target therapy. Sorafenib, an oral multi-kinase inhibitor, can be used in the treatment of DTC. Case presentation: A 77 years old. man with diagnosis of metastatic DTC and evidence of presence of mutation of BRAF K601E on liquid biopsy was treated with sorafenib, showing a good response to the treatment and an improvement in the quality of life (QoL). Currently, this patient is still on treatment with sorafenib, gaining control of a multi-metastatic disease, generally characterized by a very poor prognosis. In conclusion, sorafenib has an active role in the treatment of DTC. It also has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). In our case we observe the efficacy of using sorafenib in Papillary thyroid carcinoma (PTC) such as confirming both stable disease (SD) in the CT scan as clinical benefit with an increase in QoL. Therefore, use of sorafenib remains an important treatment option, even in case of BRAF mutation, despite a rapidly evolving treatment landscape. It also seems important to perform liquid biopsies, especially in patients in whom it is not possible to repeat a new tissue biopsy. Ongoing clinical trials continue to evaluate sorafenib in different settings, and in combination with other therapies in DTC and HCC.

Angiotensin System Polymorphisms' in SARS-CoV-2 Positive Patients: Assessment Between Symptomatic and Asymptomatic Patients: A Pilot Study.

INTRODUCTION: The renin-angiotensin-aldosterone system (RAAS), a metabolic cascade regulating pressure and circulating blood volume, has been considered the main system involved in the pathogenesis of severe lung injury and organs decline in COVID-19 patients. The angiotensin I-converting enzyme (ACE1), angiotensin-converting enzyme 2 (ACE2), angiotensinogen (AGT) and receptors angiotensin II receptor type 1 (AGTR1) are key factors for SARS-CoV-2 entering in the cells, sodium and water retention with an increase blood pressure, promotion of fibrotic and inflammatory phenomena resulting in a cytokine storm. METHODS: In this pilot study, the frequencies of six polymorphisms in the ACE1, ACE2, AGT and AGTR1 genes were analysed in symptomatic patients affected by COVID-19 and compared with the results obtained from asymptomatic subjects. RESULTS: Thus, we have identified that rs2074192 (ACE2), rs1799752 (ACE1) and rs699 (AGT) SNPs could potentially be a valuable tool for predicting the clinical outcome of SARS-CoV-2 infected patients. A genetic predisposition may be prospected for severe internal organ damages and poor prognosis in patients with COVID-19 disease, as observed in symptomatic vs asymptomatic. CONCLUSION: This study provides evidence that analysis of RAAS polymorphisms could be considered the key point in understanding and predicting the SARS-CoV-2 course infection.

Primary diffuse large B-cell lymphoma developing within a rectal tubular adenoma with low-grade dysplasia: a case report.

INTRODUCTION: Colorectal lymphomas represent only 5% to 10% of gastrointestinal lymphomas, after the stomach and small intestine. Primary lymphoma of the colon and rectum is an unusual observation, constituting only 0.2% to 0.5% of all malignant tumors arising from the colorectal region. Very little is known about the correlation between adenoma and lymphoma in the colorectal tract. We report here a rare case of diffuse large B-cell lymphoma developing within a solitary tubular adenoma with low-grade dysplasia of the rectum. CASE PRESENTATION: An 83-year-old Caucasian man was referred to our hospital intermittent anal bleeding and irregular bowel. Colonoscopy revealed a 1cm solitary rectal polyp, which was completely removed by endoscopic resection. Histologic studies revealed low-grade intraepithelial dysplasia; the stroma of adenoma showed focal localization by highly proliferative lymphoid cells. Immunohistochemical analyses demonstrated that lymphoid cells were positive for CD20 and bcl2, whereas they were negative for CD3, CD5, CD10, CD23, CD30, CD138 and cyclin D1. Approximately 90% of the neoplastic cells reacted positively when stained with an antibody to Ki-67. Molecular studies showed the presence of a monoclonal immunoglobulin heavy chain gene rearrangement.To determine primary or secondary lymphoma localization, Dawson's criteria were applied to the case. A diagnosis of primary diffuse large B- lymphoma Ann Arbor stage 1A was established. Subsequently, the patient was referred to oncology to establish the stage and to select appropriate treatment. CONCLUSIONS: The case of diffuse large B-cell lymphoma developing within a tubular adenoma, as reported here, is considered a rare event. Little about the prognosis of primary colorectal lymphomas is available and therapeutic treatment protocol is unclear. This case report provides more information on the history and macroscopic appearance of lymphomas presenting in an unusual location. To report additional cases in the future would be helpful in redefining the diagnostic, prognostic and therapeutic approach.

Circulating tumor cells: exploring intratumor heterogeneity of colorectal cancer.

The hypothesis of the "liquid biopsy" using circulating tumor cells (CTCs) emerged as a minimally invasive alternative to traditional tissue biopsy to determine cancer therapy. Discordance for biomarkers expression between primary tumor tissue and circulating tumor cells (CTCs) has been widely reported, thus rendering the biological characterization of CTCs an attractive tool for biomarkers assessment and treatment selection. Studies performed in metastatic colorectal cancer (mCRC) patients using CellSearch, the only FDA-cleared test for CTCs assessment, demonstrated a much lower yield of CTCs in this tumor type compared with breast and prostate cancer, both at baseline and during the course of treatment. Thus, although attractive, the possibility to use CTCs as therapy-related biomarker for colorectal cancer patients is still limited by a number of technical issues mainly due to the low sensitivity of the CellSearch method. In the present study we found a significant discordance between CellSearch and AdnaTest in the detection of CTCs from mCRC patients. We then investigated KRAS pathway activating mutations in CTCs and determined the degree of heterogeneity for KRAS oncogenic mutations between CTCs and tumor tissues. Whether KRAS gene amplification may represent an alternative pathway responsible for KRAS activation was further explored. KRAS gene amplification emerged as a functionally equivalent and mutually exclusive mechanism of KRAS pathway activation in CTCs, possibly related to transcriptional activation. The serial assessment of CTCs may represent an early biomarker of treatment response, able to overcome the intrinsic limit of current molecular biomarkers represented by intratumor heterogeneity.