Pulmonary veno-occlusive disease: pathogenesis, risk factors, clinical features and diagnostic algorithm - state of the art.

Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary haemangiomatosis (PCH) are rare disorders, with the estimated prevalence of less than 1 case per million inhabitants. The vascular pathology in PVOD/PCH involves pre-septal and septal veins, alveolar capillaries and small pulmonary arteries. According to the ERS/ESC classification of pulmonary hypertension (PH) from 2015, PVOD/PCH have been included in the subgroup 1' of pulmonary arterial hypertension (PAH). Recent data indicate, however, the possibility of PVOD/PCH pathology in the patients diagnosed in the group 1. The problem may concern PAH associated with scleroderma, drug- induced PAH, PAH due to HIV infection and up to 10% of patients with idiopathic PAH (IPAH). Recently, bi-allelic EIF2AK4 mutations were found in the cases with heritable form of PVOD/PCH and in about 9% of sporadic cases. Moreover, an association between occupational exposure to organic solvents and PVOD/PCH was proved. The present review is an attempt to summarise the current data on pathogenesis, risk factors, clinical features and diagnostic algorithm for PVOD/PCH.

Reliable detection of rare mutations in EGFR gene codon L858 by PNA-LNA PCR clamp in non-small cell lung cancer.

PNA-LNA PCR clamp real-time PCR method represents allele-specific approach to mutation analysis of EGFR gene in NSCLC. Due to its unique design, it is characterized by exceptionally high specificity and sensitivity but also allows detection of rare or not specifically-targeted EGFR mutations within examined exons, otherwise undetectable by other mutation-specific fluorescent probes. We herein present two cases of rare mutations revealed by PNA-LNA PCR clamping of NSCLC samples referred for routine EGFR gene molecular diagnostics. In one, the EGFR gene L858 codon mutation was detected by standard PNA-LNA PCR clamping, subsequently reconfirmed and characterized by direct sequencing of allele specific amplification products as the missense mutation c.2572C>A (p.L858M) paired with L861Q mutation on the same allele (in cis). In the second sample, low quality FFPE material from pleural biopsy, c.2573C>T missense mutation (p.L858P) was revealed. Still, repeated DNA analysis by PNA-LNA PCR clamp and direct sequencing demonstrated low level of mutant allele existing in a total allele pool suggesting rather artifactual c.2572C>T transition, a phenomenon quite frequent in low-volume FFPE samples upon fixation procedures. In conclusion, superior sensitivity and unique design of PNA-LNA PCR clamping are crucial for its excellent diagnostic effectiveness. As we demonstrated, the method allows detecting rare EGFR mutations, although it increases the risk of detection of a very low signal, e.g., generated by a small pool of mutated allele. Therefore, applicability of PNA-LNA PCR clamp product for the direct sequencing reevaluation is of key importance enabling reliable validation of results.

[Pulmonary malakoplakia and Rhodococcus equi infection. A report of two cases and review]. / Malakoplakia pluca i zakazenie Rhodococcus equi. Opis dwóch przypadków i przeglad pismiennictwa.

Malakoplakia is a rare, chronic, granulomatous disease seen in immunocompromised patients, caused by multiple infectious agents, most often bacteria. Microscopically, accumulations of macrophages with granular cytoplasm and intra- or extracellular structures, called Michaelis-Gutmann bodies are characteristic. Main cause of pulmonary malakoplakia is Rhodococcus equi infection. We report two cases of pulmonary malakoplakia, in one case R. equi infection was confirmed. We also present a summary of recent knowledge about the pathogenesis, morphology and clinical course of the disease.

[Emphysematous bulla with hematoma]. / Krwiak w pecherzu rozedmowym.

The 24-year-old otherwise healthy male with accidentally disclosed coin lesion in right lower lobe as well as emphysematous bulla was presented. The patient was admitted to the Department of Surgery, National Research Institute of Tuberculosis and Lung Diseases in order to establish diagnosis and administer proper treatment. On completing the biochemistry, microbiological and radiological investigations the diagnosis was not clear. The patient underwent the radical thoracotomy, when the multifocal emphysematous bulla with organised hematoma was resected. The patient has been under medical observation.

[Recurrent pneumothorax as alone manifestation of mesothelioma pleurae]. / Nawracajace odmy oplucnowe jako jedyna manifestacja miedzybloniaka oplucnej.

Malignant mesothelioma of the pleura is a rare neoplasm with a poor prognosis. The most often symptoms of this disease are dyspnoe and chest wall pain, which is often associated with pleural effusion. We present 35-years old woman with 5 epizodes of pneumothorax during 3 years (4 of right side and 1-bilateral) in whom bilateral pleurodesis was performed. Specimens of lung and pleurae were examinated. Result of microscopic and immunohistochemical examination was: mesothelioma epithelioides pleurae (mesothelium +, calretyninaa +, EMA+ membrane reaction, desmine +/-).

[Diagnostic difficulties in primary mesothelioma]. / Trudnosci diagnostyczne w rozpoznawaniu pierwotnego zlosliwego miedzybloniaka osierdzia.

A 54-year-old woman with a history of fatigue and shortness of breath was found to have a pericardial effusion and mild mediastinal lymphadenopathy. Video-assisted pericardioscopy revealed thickened pericardium studded with multiple nodules. Histologically the tumor was diagnosed as papillary adenocarcinoma. The site of the primary tumor could not be identified. As lung cancer is one of the most frequent causes of pericardial metastases the patient was treated with cisplatin and vinblastin. Following 5 courses of chemotherapy--given over a 4 month period--the amount of pericardial effusion and pericardial thickness did not change. The material from pericardial biopsy was reexamined and positive immunostaining for calretinine was found. The final diagnosis was primary pericardial mesothelioma of epithelioid type. Palliative radiotherapy of mediastinum was planned but the patient deteriorated and died due to disease progression with venous thrombosis and superior vena cava syndrome. The case illustrates the difficulties in establishing diagnosis of primary pericardial mesothelioma which is a rare tumor with poor prognosis.