Lung cancer is the principal cause of cancer-related death worldwide. The use of targeted therapies, especially tyrosine kinase inhibitors (TKIs), in specific groups of patients has dramatically improved the prognosis of this disease, although inevitably some patients will develop resistance to these drugs during active treatment. The most common cancer-associated acquired mutation is the epidermal growth factor receptor (EGFR) Thr790Met (T790M) mutation. During active treatment with targeted therapies, histopathological transformation to small-cell lung carcinoma (SCLC) can occur in 3-15% of patients with non-small-cell lung carcinoma (NSCLC) tumors. By definition, SCLC is a high-grade tumor with specific histological and genetic characteristics. In the majority of cases, a good-quality hematoxylin and eosin (H&E) stain is enough to establish a diagnosis. Immunohistochemistry (IHC) is used to confirm the diagnosis and exclude other neoplasia such as sarcomatoid carcinomas, large-cell carcinoma, basaloid squamous-cell carcinoma, chronic inflammation, malignant melanoma, metastatic carcinoma, sarcoma, and lymphoma. A loss of the tumor-suppressor protein retinoblastoma 1 (RB1) is found in 100% of human SCLC tumors; therefore, it has an essential role in tumorigenesis and tumor development. Other genetic pathways probably involved in the histopathological transformation include neurogenic locus notch homolog (NOTCH) and achaete-scute homolog 1 (ASCL1). Histological transformation to SCLC can be suspected in NSCLC patients who clinically deteriorate during active treatment. Biopsy of any new lesion in this clinical setting is highly recommended to rule out a SCLC transformation. New studies are trying to assess this histological transformation by noninvasive measures such as measuring the concentration of serum neuronspecific enolase.

A 20 year-old male complaining of headache, photophobia and altered mental status arrived to the ER from another hospital. His symptoms began a few months earlier with diarrhea and vomiting, daily fever up to 39°C, and weight loss. At that time, the neurological examination showed a Glasgow Coma Scale (GCS) score of 8 points and nuchal rigidity. A brain CT scan was normal, and ceftriaxone 2 gr per day, vancomycin 2 gr every 12 hours, ampicillin 2 gr every 4 hours, clarithromycin 500 mg every 12 hours, and acyclovir 800 mg every 5 hours were started. Because there was no improvement, two days later he was transferred to our hospital. At entry the heart rate was 53 beats per minute, breathing rate was 18 per minute with Cheyne-Stokes respiration, blood pressure was 100/60 mmHg, and temperature was 38°C. The GCS score was of 6 points: 2 points for the ocular response, 1 point for the verbal response and 3 points for the motor the response. His head and gaze were persistently deviated to the right. He had bilateral papilledema, and his pupils were asymmetric, with the right pupil size of 2 mm and the left of 5 mm. Strength was abated, but when pain was elicited he acquired a posture of decerebration. The Hoffman and Babinski signs were produced on the right side. He had involuntary myoclonic jerks in the upper and lower extremities that lasted more than 5 minutes. Nuchal rigidity was present. He was intubated and put on mechanical ventilation. Dexamethasone was administrated for cerebral edema, levetiracetam and propofol for persistent epileptic seizures. Amphotericin B was added and the antibiotics were continued. Two days later mannitol, meropenem, rifampicin, pyrazinamide and ethambutol were included, however, the patient continued to be hypothermic and had severe slow heart rate and hypotension. He died 9 days later. LABORATORY AND NEUROIMAGECBC showed a total blood count of 7000 cells/mm 3 (neutrophils of 87%, lymphocytes of 7.95% and monocytes of 4.8%), hemoglobin of 15.4 gr/dL and platelets of 124,000 cells/mm 3 . Serum glucose was 101 mg/dL, creatinine was 0.9 mg/L and sodium was 134 mg/ dL. The rest of the laboratory studies including liver function tests were normal. An ELISA for HIV was negative.A brain MRI showed enlargement of the ventricles with transependymal migration of CSF surrounding the ventricles symptomatic of acute hydrocephalus, effacement of sulci due to cerebral edema, bilateral extensive hyperintense images in the basal ganglia and surrounding parenchyma in the DWI suggesting ischemic lesions in both territories of the middle cerebral artery (MCA) (Figure 1a, 1b), and generalized dense leptomeningeal enhancement and arachnoiditis in the post-contrast T1-weighted images. An angioMRI showed a severely injured left MCA (Figure 1c).A lumbar puncture was performed with an opening pressure of 22 cmH20, and the CSF showed a pH of 7.47, glucose of 52 mm/ dL, proteins of 111 mg/dL, and WBC of 32cells/mm 3 . Adenosine deaminase enzyme (ADA) in CSF was 9 UI. CSF PCR for M. tuberculosis, CMV, VSH and V...