Discrepancies between ALK protein disruption and occurrence of ALK gene rearrangement in Polish NSCLC patients.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangement are predisposed to molecularly targeted therapies. Proper diagnostic is crucial for quick and correct patients qualification to optimal treatment method. Genetic tests to detect predictive factors could be performed sequentially. After excluding EGFR mutations, abnormal ALK protein expression should be tested using immunohistochemistry (IHC) method. In patients with disrupted ALK expression, the rearrangement of the ALK gene should be confirmed by FISH method. Despite few years of experience in analysis of these predictive factors, there are still problems in interpretation of diagnostic tests results. Especially, some recommendations for ALK IHC diagnosis are not precise. METHODS: Mutations in EGFR gene were examined using real-time PCR technique in 1,108 formalin-fixed paraffin-embedded (FFPE) tissues, 398 FFPE cell-blocks and 470 cytological specimens of NSCLC. The disrupted ALK protein expression was analysed in 1,100 samples including 782 histological and 306 cytological (cell-blocks) samples using IHC. Twelve materials (1.1%) were non-diagnostic in IHC. ALK gene rearrangement using FISH method was analysed in IHC positive cases. RESULTS: The frequency of EGFR mutations was 8.6%. EGFR mutations occurred significantly more often in females (P=0.00001, χ2=62.732) and in adenocarcinoma cases (P=0.0002, χ2=14.222). The exon 19 deletions (49%) and exon 21 Leu858Arg substitution (38%) were the most common, rare EGFR mutations occurred in 13% of patients. Any expression of abnormal ALK protein was detected in 202 cases (18.57%). ALK gene rearrangement was confirmed in 49 cases (4.5%). ALK gene rearrangement is significantly more common in female than in male (P=0.0105, χ2=6.541). In patients with ALK gene rearrangement, the median percentage of nuclei with ALK rearrangement was only 25.5%. The polysomy (≥4 gene copy number per nuclei) of ALK gene was observed in 39 cases (21.4% of patients with diagnostic result of FISH examination). Median number of ALK gene copy per nuclei was 2.9±0.77. Significant positive correlation between percentage of cells with abnormal ALK expression in IHC test and percentage of nuclei with ALK rearrangement in FISH method was detected (R=0.617, P<0.00001). Significant negative correlation between the number of copies of ALK gene and the percentage of cells with expression of abnormal ALK was observed (R=-0.2004, P<0.05). ALK gene rearrangement was significantly more frequently observed in the material with coarse-grained cytoplasmic and membranous IHC staining than in materials with light cytoplasmic stippling. The occurrence of cytoplasmic stippling correlated with the increase of ALK gene copy number. CONCLUSIONS: We indicated that diagnosis of ALK disruption in NSCLC patients should be notably careful using IHC and FISH methods. Recommendations for ALK diagnosis should include the way of interpretation of cases with low percentage of cells with abnormal ALK protein expression in IHC test, character of IHC reaction, and cases with ALK gene polysomy in FISH method.

Use of the virtual slide and the dynamic real-time telepathology systems for a consultation and the frozen section intra-operative diagnosis in thoracic/pulmonary pathology.

We report the results of a study designed for assessment of the diagnostic accuracy and usability of internet-based digital microscopy: the dynamic real-time telepathology system (Coolscope) and the Virtual microscopy (Aperio Scan Scope) system, in the context of pulmonary pathology. The systems were implemented to the routine pulmonary pathology workflows and used for the intra-operative frozen-section primary diagnosis as well as for the secondary (consultative) diagnosis. The histological material presented for the teleconsultations included the samples of lung parenchyma, bronchial biopsy and resected lung/bronchi tumours. For the primary diagnosis 4 categories of material can be distinguished (304 samples): 1) the frozen sections of lung tumours, resected bronchial margins and lymph nodes; 2) fine needle aspiration [FNA] biopsies (TBNA; EBUS-TBNA, EUS-FNA; 3) oligobiopsies of bronchus, oesophagus, skin; and 4) exfoliative cytology. The telepathology diagnoses compared with conventional light microscopy diagnoses showed very high concordance for the Coolscope and Aperio Virtual Slide modality: 87.5% and 100%, respectively - within the group of teleconsultations. For the frozen sections, the primary telediagnoses were concordant with the light microscopy paraffin sections diagnoses in 100% for Aperio; and in 97.5% for Coolscope. An excellent agreement (100%) was seen in the telediagnoses and conventional slides diagnoses for FNA, oligobiopsies and cytology - for both telepathology systems. These results provide some encouragement for the implementation of Coolscope and virtual slide-based telepathology (Aperio) system to the routine histopathological diagnostics.

Safe medication swallowing in Dysphagia: a collaborative improvement project.

Episodes of choking during medication administration to patients with dysphagia prompted a chart audit and caregiver interview to identify system problems that allowed inappropriate drug administration to occur. Sixty elderly patients residing on two patient care areas in a 500-bed complex continuing care facility were studied. The audit explored the actual nursing medication administration methods and compared this to the information obtained from various communication tools including instructions that appeared on the medication administration record (MAR), the current diet order, the recommendations of the speech-language pathologist (SLP) and comments on the nursing care plan. The audit yielded a number of discrepancies between nursing actions and the instructions obtain from these sources. We proposed that changes to the process of communicating medication swallowing recommendations among team members would lead to greater patient safety. Major practice changes included the use of standardized language by the SLP when making recommendations, the writing of SLP recommendations in the doctor's orders, the inclusion of SLP recommendations on the MAR and the creation of a "dysphagia alert" on the pharmacy computer system. An educational intervention was conducted to implement process changes. Its effectiveness was evaluated using a pre- and post-test and a participant satisfaction survey. A post-implementation audit showed compliance with the practice change. In summary, process changes were implemented to improve compliance with SLP medication-related swallowing recommendations and to prevent the inadvertent prescribing, dispensing or crushing of sustained-release medications in patients with dysphagia.

A case report of a patient with dermatomyositis as a prodromal sign of lung cancer.

Dermatomyositis (DM) is a connective tissue disease characterized by specific inflammatory lesions in muscle biopsy. It is caused by vasculitis determined by humoral factors with subsequent inflammatory cell accumulation, mainly T CD4+ and B cells, which infiltrate myocytes leading to its vacuolization and degeneration (mainly in the skeletal muscles, rarely in the smooth muscles). The incidence of DM is estimated at 1-10 per million in adults and at 1-3.2 per million in children. The autoimmune mechanism of disease induction is not fully recognized. Several lines of evidence showed the link between DM and neoplastic disease. The first report of dermatomyositis associated with stomach cancer, by Stertz, comes from 1916. In the same time, Kankeleit reported DM associated with breast cancer. Presumably, it is the result of immune reaction against antigens common for muscle and neoplastic cells or some paraneoplastic syndrome underlying mechanism. The report presents the case of a 52-year-old woman with DM (diagnosed according to the Bohan and Peter criteria) and with coexistent squamous lung cancer in situ. The left upper lobectomy was performed. No complications in postoperative period were observed. During more than 2 years of follow-up after the surgery, the patient remained in good condition, without DM symptoms, or cancer relapse. Considering that DM may be associated with lung cancer; extensive diagnostic work-up to exclude neoplastic lesions should be performed. Patients aged 40 years or more should be particularly screened.

Extrapulmonary lymphangioleiomyomatosis presented as the asymptomatic retroperitoneal tumours--two cases report.

Lymphangioleiomyomatosis [LAM] is a rare lung disease affecting women and characterized by abnormal smooth muscle cells (LAM cells) proliferation along lung and lymphatic channels. The frequent occurrence of extrapulmonary LAM [e-LAM] has been reported as abdomen pelvic lymph nodes involvement, angiomyolipomas, lymphangioleiomyomas or lymphangiomas in LAM patients. An extrapulmonary manifestation as the initial LAM presentation preceding pulmonary disorders and as asymptomatic extrapulmonary LAM lesions are unusual. We report two women presented with asymptomatic retroperitoneal cystic masses accidentally found on ultrasound examination. The tumours were surgically removed and diagnosed as: 1-malignant mesothelioma and 2-tymphangiomyoma. The microscopical sections were reviewed and re-diagnosed as e-LAM at advanced pulmonary LAM development. Mesotheliosis present in e-LAM morphology is unique and was misleading for malignancy diagnosis. The second case illustrates the hormone dependent growth of lymphangiomyoma and LAM development in young women. It is difficult to prove the presence of pulmonary LAM at the time of tumours excision but both cases demonstrate importance of appropriate LAM diagnosis and being aware of such diagnosis in cases presenting with extrapulmonary extension of the disease.

[Lymphangioleiomyomatosis in a menopausal woman on estrogen replacement therapy]. / Limfangioleiomiomatoza u kobiety w menopauzie stosujacej hormonoterapie zastepcza.

The case of lymphangioleiomyomatosis (LAM) was presented. Woman (55 years) receiving for several years estrogens with the symptoms of disease (dyspnea, nonproductive cough, chylous pleural fluid) appeared after menopause. Suggestive clinical symptoms and chest HRCT scan confirmed clinical diagnosis of LAM. Two years after discontinuation of estrogen medication her clinical condition and radiological picture of lungs improved.