Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
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Increasing use of fine needle aspiration for oncological diagnosis, while minimally invasive, poses a challenge for molecular testing by traditional sequencing platforms due to high sample requirements. The advent of affordable benchtop next-generation sequencing platforms such as the semiconductor-based Ion Personal Genome Machine (PGM) Sequencer has facilitated multi-gene mutational profiling using only nanograms of DNA. We describe successful next-generation sequencing-based testing of fine needle aspiration cytological specimens in a clinical laboratory setting. ⋯ The results of this study show that next-generation sequencing-based mutational profiling can be performed on fine needle aspiration cytological smears and cell blocks. Next-generation sequencing can be performed with only nanograms of DNA and has better sensitivity than traditional sequencing platforms. Use of next-generation sequencing also enhances the power of fine needle aspiration by providing gene mutation results that can direct personalized cancer therapy.
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Multicenter Study
Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma.
Synovial sarcoma and malignant peripheral nerve sheath tumor pose a significant diagnostic challenge given similar histomorphology. The distinction is further complicated by similar immunophenotype and especially by occasional synovial sarcomas that present as intraneural tumors. Although the presence of a t(X;18) rearrangement or expression of TLE1 can help confirm the diagnosis of synovial sarcoma, negative results for these tests are not diagnostic of malignant peripheral nerve sheath tumor. ⋯ Therefore, SOX10 is a specific (93%), albeit not very sensitive (67%), diagnostic marker to support a diagnosis of malignant peripheral nerve sheath tumor over synovial sarcoma. Furthermore, the stain needs to be interpreted with caution in intraneural tumors in order to avoid a potential diagnostic pitfall. It remains to be determined whether SOX10-positive cells in intraneural synovial sarcoma represent entrapped Schwann cells, synovial sarcoma cells or both.
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Tumor budding is an increasingly important prognostic feature for pathologists to recognize. The aim of this study was to correlate intra-tumoral budding in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy and with long-term outcome. Data from a prospectively maintained database were acquired from patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. ⋯ No patient with intra-tumoral budding exhibited a tumor regression grade 1 or complete pathological response, providing a 100% specificity and positive predictive value for non-response to neoadjuvant chemoradiotherapy. Intra-tumoral budding was associated with a lower disease-free 5-year survival rate (33 vs 78%, P<0.001), cancer-specific 5-year survival rate (61 vs 87%, P=0.021) and predicted cancer-specific death (hazard ratio 3.51, 95% confidence interval 1.03-11.93, P=0.040). Intra-tumoral budding at diagnosis of rectal cancer identifies those who will poorly respond to neoadjuvant chemoradiotherapy and those with a poor prognosis.
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BRAF V600E mutation in serrated lesions of the colon has been implicated as an important mutation and as a specific marker for the serrated carcinogenic pathway. Recent findings point to microvesicular hyperplastic polyps that have similar histologic and molecular features to sessile serrated adenomas/polyps, as potential colorectal carcinoma precursors. The aim of this study was to evaluate BRAF V600E mutation status by immunohistochemistry in serrated lesions of the colon with regard to histomorphology. ⋯ Immunostaining with VE1 allows not only the detection of BRAF V600E mutation but also the correlation with histomorphology on a cellular level in serrated lesions. VE1 enables a subclassification of microvesicular hyperplastic polyps according to the mutation status. This improved classification of serrated lesions including immunohistochemical evaluation of BRAF V600E mutation may be the key to identify lesions with higher potential to progression into sessile serrated adenoma/polyp, and further to BRAF V600E-mutated colorectal cancer.
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The histopathological diagnosis of diffuse gliomas often lacks the precision that is needed for tailored treatment of individual patients. Assessment of the molecular aberrations will probably allow more robust and prognostically relevant classification of these tumors. Markers that have gained a lot of interest in this respect are co-deletion of complete chromosome arms 1p and 19q, (hyper)methylation of the MGMT promoter and IDH1 mutations. ⋯ Furthermore, in glioblastoma patients >50 years of age the favorable prognostic significance of IDH1 mutation and MGMT promoter methylation was absent. In conclusion, molecular diagnostics is a powerful tool to obtain prognostically relevant information for glioma patients. However, for individual patients the molecular information should be interpreted with caution and weighed in the context of parameters such as age and histopathological diagnosis.