Immunohistochemical and molecular genetic study on epithelioid glioblastoma: Series of seven cases with review of literature

Epithelioid glioblastoma (e-gbm) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of CNStumors. About half of these tumors show characteristic BRAF-V600E mutation. However, unlike conventional GBMs, e-gbm lack specific diagnostic and prognostic markers. Hence, we aimed to molecularly characterize these tumors. An extensive review of literature was performed.In a multi-institutional effort, all the cases of glioblastoma of year 2017 were reviewed. Cases with predominant epithelioid morphology were analysed. Seven cases of e-gbm (adults:4 and pediatric: 3) were identified. Duration of symptoms varied from 2 weeks to one month. Radiologically, all cases were supratentorial, contrast enhancing with solid and cystic appearance. Majority of the cases were immunopositive for GFAP (71%), EMA (71%), S100 (71%) and vimentin (85%). All the cases showed ATRX, INI-1 and H3K27me3 expression. BRAFV600Emutation was seen in 28% of cases. TERT mutation was seen in 40% cases, while one case showed EGFR amplification. H3F3A mutations and PTEN deletions were seen in none. Although e-gbms are rare, epithelioid morphology of a CNS tumor in a young adult or children with areas of necrosis needs thorough histomorphological and genetic workup.     

Telomeres and telomere dynamics: relevance to cancers of the GI tract

Aberrations in telomere length and telomere maintenance contribute to cancer development. In this article, we review the basic principles of telomere length in normal and tumor tissue and the presence of the two main telomere maintenance pathways as they pertain to gastrointestinal tract cancer. Peripheral blood telomeres are shorter in patients with many types of gastrointestinal tract cancers. Telomere length in tumor DNA also appears to shorten early in cancer development. Tumor telomere shortening is often accompanied by telomerase activation to protect genetically damaged DNA from normal cell senescence or apoptosis, allowing immortalized but damaged DNA to persist. Alternative lengthening of telomeres is another mechanism used by cancer to maintain telomere length in cancer cells. Telomerase and alternative lengthening of telomeres activators and inhibitors may become important chemopreventive or chemotherapeutic agents as our understanding of telomere biology, specific telomere-related phenotypes and its relationship to carcinogenesis increases.     

Primary squamous cell carcinoma of thyroid with a novel BRAF mutation and High PDL-1 expression: A case report with treatment implications and review of literature

Primary squamous cell carcinoma of thyroid (SCC-T) is an extremely rare, aggressive neoplasm with median survival of 9 months. Pure squamous morphology with absence of other cell types is required for diagnosis of SCC-T. Clinically, SCC-T behaves like anaplastic thyroid carcinoma (ATC) showing rapid growth, and extra thyroidal extension. We report a 91-year-old woman presenting with an enlarging thyroid mass and accompanying dysphagia and hoarseness. Fine needle aspiration revealed hypercellular specimen with large, pleomorphic, malignant cells. Intraoperative assessment revealed an inoperable tumor involving both thyroid lobes and extensively infiltrating surrounding soft tissues. A subtotal thyroidectomy was performed. Histology revealed squamous cell carcinoma replacing native thyroid tissue and infiltrating adjacent skeletal muscle. Lymphovascular and perineural invasion were present. Immunohistochemistry showed tumor cells positive for CK5-p40, Pax-8, TTF-1 and negative for thyroglobulin. P53 expression by IHC was high and Ki-67 proliferation index was > 90 %. (Next generation sequencing revealed a novel BRAF mutation (BRAF c.1799 T > A; 1801_1812del) along with TP53 and TERT mutations. PDL-1 immunohistochemistry showed positive expression in tumor cells (>80%), making patient also amenable to anti-PDL-1 immunotherapy. Patient was treated with BRAF inhibitor therapy with initial relief but eventually was put on hospice care due to increasing intolerance to therapy. This case represents a rare thyroid malignancy with a unique molecular signature consisting of a novel BRAF mutation [previously not described in SCC-T or ATC], associated with TERT-TP53 mutations. Further, importance of PDL-1 testing as a prognostic marker and as a guide to immunotherapy in refractory tumors is discussed.