The past decade has been marked by significant advancements in the treatment of patients with metastatic colorectal cancer (mCRC), including the approval of novel biologic agents such as the angiogenesis inhibitors bevacizumab and afibercept and the epidermal growth factor receptor monoclonal antibodies (mAbs) cetuximab and panitumumab. Cetuximab was recently approved by the US Food and Drug Administration in combination with FOLFIRI (irinotecan, 5-fuorouracil, leucovorin) for the first-line treatment of patients with KRAS mutation-negative (wild-type) tumors as determined by an FDA-approved companion diagnostic. It was the first FDA approval in mCRC requiring use of a diagnostic test that is predictive of response prior to initiation of frontline therapy. The approval highlights the need for reflexive KRAS mutation testing at diagnosis to accurately determine all available treatment options. Although KRAS testing has been used by pathologists in mCRC for several years, accurate and timely reporting of test results and open communication with medical oncologists is even more essential to ensure appropriate first-line treatment selection and avoid any treatment delays. Consequently, it is critical that pathologists are highly trained and educated on KRAS testing methodology and the pros and cons of the various methods available. In this review, we discuss the development of KRAS as a biomarker in mCRC and key topics of concern to the pathologist who works with the oncologist in the community setting, including specimen preparation, KRAS testing methods, and reporting of test results. In this era of personalized medicine, pathologist education and communication with oncologists on biomarkers is paramount for optimal patient care.
The authors would like to report an error in the formula describing the correction factor for the protein content in the serum/plasma. The formula is described as "multiply by (1-(serum protein content, in g/L)] and is currently written on the 5th page of the article, right column text; moreover, on page 6, under Table 3-Legend. The corrected formula should be written as "multiply by (1-(serum protein content, in g/mL)]". Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Background
To study the clinical, radiological, electroencephalographic, and cerebrospinal fluid (CSF) features of Human Herpes Virus 6 (HHV-6) encephalitis in leukemia patients underwent allogeneic hematopoietic stem cell transplantation (HSCT).
Methods
We retrospectively reviewed all leukemia patients who underwent allogeneic HSCT between January 2010 and December 2018. The clinical, radiological, electroencephalographic, and CSF features of those with HHV6 encephalitis were recorded.
Results
A total of five cases of HHV6 encephalitis were identified. Three patients had Chronic Myelogenous Leukemia, one had Chronic Lymphocytic Leukemia and one had Acute Lymphoblastic Leukemia. All of them presented a few months after transplantation with altered mental status. Comorbidities included pancytopenia, sepsis, graft versus host disease, and multi-organ failure. EEG showed focal seizures originating from temporal lobes in two patients, generalized or focal periodic discharges in three patients, focal slowing in two patients, and diffuse slowing in three patients. MRI brain showed T2/FLAIR hyper-intensities in four patients; two of them in bilateral temporal lobes, one in the thalamus/hypothalamus/brainstem/cerebellum/basal ganglia, and one in the periventricular areas. CSF showed pleocytosis, high protein, and positive HHV-6 PCR. Foscarnet was used as an anti-viral agent. Anti-epileptics used were phenytoin, levetiracetam, and valproic acid. Four patients died in a few months, whereas one recovered completely.
Conclusions
HHV-6 encephalitis can add significant morbidity and mortality to leukemic patients following allogeneic HSCT. Patients present with typical clinical features of encephalitis. Salient EEG characteristics include periodic discharges or overt temporal lobe seizures. MRI findings are T2/FLAIR signal hyperintensities, mainly in the temporal lobes.
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