An EGFR-mutant lung adenocarcinoma that transformed into small-cell lung cancer. A case report.

BACKGROUND: Transformation of EGFR (epidermal growth factor receptor) - mutant non-small cell lung cancer (NSCLC) into small-cell lung cancer (SCLC) is one mechanism of resistance to tyrosine kinase inhibitor (TKI) treatment, seen in approximately 3-10% cases. Such transformed SCLC often retains the original EGFR mutation (EGFRM), which is not otherwise observed in SCLC. CASE REPORT: We present a 67 y/o woman with pulmonary adenocarcinoma (AC) and EGFRM deletion on exon 19. After initial treatment with whole brain radiotherapy and 7 months of TKI afatinib, progression was observed. Liquid biopsy detected deletion on exon 19 and T790M mutation. Chemotherapy carboplatin plus pemetrexed was administered, with no response. Genetics from a rebiopsy of lung revealed deletion on exon 19. After 12 months treatment with TKI osimertinib, a progression in lung and pancreas lesions was detected, docetaxel was used, with followig progression. The lung biopsy revealed SCLC. Significant elevation of serum markers carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) was observed at the time of the SCLC diagnosis. Treatment with carboplatin and etoposide was not effective. The next biopsy found two populations of cells: SCLC and AC. The biopsy from the pancreatic lesion revealed metastasis of SCLC. PCR confirmed EGFRM deletion on exon 19 in the lung SCLC tissue sample. The following treatment lines of topotecan, erlotinib were not effective. The patient survived 36 months from diagnosis, 7 months from detection of SCLC. CONCLUSION: Screening for transformation of EGFR-mutant NSCLC to SCLC should be considered in resistance to TKI. In the presented case, this rare transformation was confirmed by histopathologic examination and by PCR. EGFRM in the lung SCLC, identical to that found in the original lung AC, was detected. Further, the observed elevation of serum tumor markers NSE and CEA can indicate this infrequent transformation and help to decide on rebiopsy.

Diagnostic performance of edited 2HG MR spectroscopy of central glioma in the clinical environment.

OBJECTIVE: Oncometabolite D-2-hydroxyglutarate (2HG) is pooled in isocitrate dehydrogenase (IDH)-mutant glioma cells. Detecting 2HG by MR spectroscopy (MRS) has been proven viable in the last decade but has not entirely found its way into the clinical routine. This study aimed to explore the adoption of 2HG MRS while acknowledging factors that influence its performance in the clinical environment. METHODS: Thirty-nine MR spectra were acquired and reported prospectively in patients with suspected glioma using a 3 T system with Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence utilizing averaged free induction decay (FID) signals. Postprocessing and evaluation of spectra were performed with jMRUI and LCModel. 2HG concentration estimates, 2HG/Cr ratio, together with quality measures, including Cramér-Rao lower bounds (CRLBs), full-width at half-maximum (FWHM) values, and signal-to-noise ratio (SNR) were calculated using LCModel. Immunohistochemistry and genomic analysis results used as a ground truth were available for 15 patients. RESULTS: The threshold for test positivity was set according to the ROC curve at 1 mM. Calculated sensitivity was 57.14% (95% CI 0.20-0.88), specificity 87.5% (95% CI 0.46-0.99), positive predictive value 80%, and negative predictive value 70%. Overall diagnostic accuracy was 73.33% (95% CI 0.45-0.92). The 2HG/Cr ratio with the cutoff value 0.085 significantly improved sensitivity and overall diagnostic accuracy [85.71%, 95% CI 0.42-1.00 and 86.67%, (95% CI 0.60-0.98), respectively]. CONCLUSION: Multiple factors compromising spectral quality in the clinical adoption of edited 2HG MRS resulted in diminished sensitivity but clinically acceptable specificity. Furthermore, the 2HG/Cr ratio performs better than the sole 2HG concentration estimate in the pre-operative setting.

Morphological and functional alterations of the prostate tissue during clinical progression in hormonally-naïve, hormonally-treated and castration-resistant patients with metastatic prostate cancer.

Since commony used tools in oncological practice for the diagnosis of castration-resistent prostatic acinar adenocarcinoma are based on clinical criteria, such as castrate testosterone level, continuous rise in serum prostate-specific antigen, progression of preexisting disease or appearance of new metastases, it is important to identify reliable histopathological markers for the identification of this disease. Therefore, the aim of the present study was to determine the association between results from histological analysis, ultrastructural analysis and apoptosis in the prostate of patients with metastatic acinar prostatic adenocarcinoma (mPC). Patients were treated with androgen deprivation therapy (ADT), abiraterone acetate (Abi) therapy or received no treatment. Prostate tissue samples were divided into four groups as follows: i) Group 1, tissues from patients with benign prostatic hyperplasia (adenocarcinoma negative); ii) group 2, tissues from patients with metastatic hormone naïve prostate cancer; iii) group 3, tissues from patients with mPC treated with ADT; and iv) group 4, tissues from patients with metastatic castration-resistant prostate cancer treated with ADT and Abi. Immunohistochemical, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling (TUNEL) and ultrastructural assays using light, fluorescence and transmission electron microscopy, respectively, were used to analyze prostate tissue samples. The results demonstrated that ADT and Abi therapy caused histological and ultrastructural changes in prostate tissues. In groups 3 and 4, benign and malignant tissues were affected by the hormonal therapy. Histologically, the malignant epithelium after ADT therapy in groups 3 and 4 presented with a loss of glandular architecture, nuclear and nucleolar shrinkage, chromatin condensation and cytoplasmic clearing. At the ultrastructural level, compact hypertrophic and hyperchromatic nuclei with numerous invaginations were observed in groups 2, 3 and 4. In addition, the incidence of abnormal mitochondria in malignant cells of these groups was high. Group 4 was characterized by the presence of malignant mesenchyme-like cells in the prostatic stroma, arranged in small groups surrounded by collagen fibrils. Furthermore, the cytoplasm of these cells contained filaments. A decrease in the number of apoptotic cells using TUNEL assays in the examined samples was observed with increasing disease progression. The findings from the present study suggest that the duration of treatment with ADT and progression of the disease were associated with apoptosis dysregulation.