Pembrolizumab-induced hypothyreosis and subcutaneous bleeding.

Pembrolizumab belongs to so called immune checkpoint inhibitors. Frequent adverse event of this therapy is hypothyroidism. The authors present a case report of patient treated with pembrolizumab for non-small cell lung carcinoma, in whom severe hypothyroidism followed quite rapidly after transient phase of subclinical hyperthyroidism - at this time point new and spontaneous onset of large subcutaneous hematomas was observed. Acquired von Willebrand syndrome, acquired hemophilia A, dysfibrinogenemia, activation of fibrinolysis and thrombocytopathy were all actively ruled out in hematological differential diagnosis. Concomittantly, laboratory markers of secondary autoimmune disease and myositis were excluded. Despite continuous pembrolizumab treatment, there were no other bleeding complications seen after intensification of endocrine substitution therapy with thyroid hormones. Causal relationship between subcutaneous hematomas and severe drug-induced hypothyroidism is established per exclusionem.

Immunodeficiency in the differential diagnosis of interstitial lung diseases.

Interstitial lung processes (IPP), or diffuse parenchymal lung diseases, are a broad group of diseases characterized by varying degrees of pulmonary fibrosis and inflammation affecting predominantly, but not exclusively, pulmonary interstitium. IPP mostly occur in adulthood with maximum manifestation between 40 and 70 years of age. Although IPP mostly present as a primary diagnosis, they also belong to the portfolio of pulmonary disorders in patients with primary immunodeficiencies. The authors present case reports of patients with interstitial lung involvement and primary immunodeficiencies [particularly those manifesting also in adulthood, such as common variable immunodeficiency (CVID), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) deficiency]. In addition, we report the case of silico-sis patient with severe lymphopenia. Therefore, in patients with newly diagnosed interstitial lung disease, congenital immune system disorder should be considered. Basic immunological laboratory examination of humoral and cellular immunity should be an essential part of the differential diagnosis algorithm for interstitial lung disease.

Complex analysis of the p53 tumor suppressor in lung carcinoma.

Lung cancer is the leading cause of cancer-related deaths worldwide. The p53 tumor suppressor is a transcription factor controlling expression of its target genes in response to various stress stimuli. Mutations of the TP53 gene occur very frequently in lung carcinomas and they play an important role in both oncogenic transformation of lung epithelial cells and lung carcinoma progression. We determined the TP53 status in 42 samples of squamous cell lung carcinoma (SQCC) and 56 samples of lung adenocarcinoma (AC) by the functional analysis FASAY and its variant called split assay. Altogether, we detected 64 TP53 mutations in 63 patients and analyzed them by cDNA and gDNA sequencing. The TP53 mutations were found in 76.2% (32/42) of SQCC cases, and 55.4% (31/56) of ACs. Immunoblotting revealed the p53 protein accumulation in 18 samples (42.9%) among SQCC cases and 19 samples (33.9%) among AC cases. Using fluorescence in situ hybridization we detected loss of the TP53-specific 17p13.3 locus in 23 from 41 analyzed SQCC samples (56.1%) and in 20 from 54 analyzed AC samples (37.0%). We did not find any statistically significant differences in overall and disease-free survival in relation to TP53 status.