Colorectal cancer (CRC) is a heterogeneous disease representing a therapeutic challenge, which is further complicated by the common occurrence of several molecular alterations that confer resistance to standard chemotherapy and targeted agents. Mechanisms of resistance have been identified at multiple levels in the epidermal growth factor receptor (EGFR) pathway, including mutations in KRAS, NRAS, and BRAFV600E, and in the HER2 and MET receptors. These alterations represent oncogenic drivers that may co-exist in the same tumor with other primary and acquired alterations via a clonal selection process. Other molecular alterations include DNA damage repair mechanisms and rare kinase fusions, potentially offering a rationale for new therapeutic strategies. In recent years, genomic analysis has been expanded by a more complex study of epigenomic, transcriptomic, and microenvironment features. The Consensus Molecular Subtype (CMS) classification describes four CRC subtypes with distinct biological characteristics that show prognostic and potential predictive value in the clinical setting. Here, we review the panorama of actionable targets in CRC, and the developments in more recent molecular tests, such as liquid biopsy analysis, which are increasingly offering clinicians a means of ensuring optimal tailored treatments for patients with metastatic CRC according to their evolving molecular profile and treatment history.

IntroductionHashimoto's encephalopathy is a neurological disorder of unknown cause associated with thyroid autoimmunity. The disease occurs primarily in the fifth decade of life and may present in two types - a sudden vasculitic type or a progressive subacute type associated to cognitive dysfunction, confusion and memory loss.Case presentationWe report the case of a 62-year-old Hispanic woman, previously healthy, who developed a subacute onset of declining upper brain function. Serologic studies demonstrated high levels of antithyroid antibodies. Electroencephalographic and magnetic resonance image findings were consistent with Hashimoto's encephalopathy.ConclusionHashimoto's encephalopathy is a diagnosis of exclusion. This unusual disorder is often under-recognized because of the multiple and protracted neurocognitive manifestations; therefore, it is important to be aware of the clinical manifestations to make a correct diagnosis.

No abstract

We report a 72-year-old patient with chronic diarrhoea and histologic evidence of gastrointestinal histoplasmosis. He had no history of HIV or of taking immunosuppressive drugs. The patient was found to be a carrier of Human T-lymphotropic virus-1, a condition associated with inflammatory, lymphoproliferative, and opportunistic infectious diseases. To our knowledge, there are only three previous cases reporting this coinfection and this is the first documented case with gastrointestinal involvement.

Neutrophilic panniculitis is an infrequent but characteristic adverse event under therapy with BRAF inhibitors (BRAFi). Since the approval of vemurafenib for treatment of metastatic melanoma in 2011, only two cases of neutrophilic panniculitis in malignancies other than melanoma have been published. Histiocytoid infiltrates of immature neutrophils resembling histiocytes or myelocytes have been reported in Sweet's syndrome and rarely in other neutrophilic dermatoses. We describe a novel variant of neutrophilic panniculitis with histiocytoid myeloid cells in an early lesion from a patient treated with vemurafenib in combination with an anti-EGFR (epidermal growth factor receptor) agent for metastatic colon carcinoma, three weeks after initiation of therapy. Recognizing this variant of panniculitis associated to BRAFi can avoid misinterpretation of the atypical subcutaneous infiltrate as myeloid leukaemia cutis.