Background. Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer that is rarely curable by surgery and is rapidly increasing in incidence. Relapsed ICC has a poor prognosis, and current systemic nontargeted therapies are commonly extrapolated from those used in other gastrointestinal malignancies. We hypothesized that genomic profiling of clinical ICC samples would identify genomic alterations that are linked to targeted therapies and that could facilitate a personalized approach to therapy. Methods. DNA sequencing of hybridization-captured libraries was performed for 3,320 exons of 182 cancer-related genes and 36 introns of 14 genes frequently rearranged in cancer. Sample DNA was isolated from 40 mm of 28 formalin-fixed paraffin-embedded ICC specimens and sequenced to high coverage.

AimsAdrenocortical carcinoma (ACC) carries a poor prognosis and current systemic cytotoxic therapies result in only modest improvement in overall survival. In this retrospective study, we performed a comprehensive genomic profiling of 29 consecutive ACC samples to identify potential targets of therapy not currently searched for in routine clinical practice.MethodsDNA from 29 ACC was sequenced to high, uniform coverage (Illumina HiSeq) and analysed for genomic alterations (GAs).ResultsAt least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC). The most frequent GAs were in TP53 (34%), NF1 (14%), CDKN2A (14%), MEN1 (14%), CTNNB1 (10%) and ATM (10%). APC, CCND2, CDK4, DAXX, DNMT3A, KDM5C, LRP1B, MSH2 and RB1 were each altered in two cases (7%) and EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN and PTCH1 were each altered in a single case (3%). In 17 (59%) of ACC, at least one GA was associated with an available therapeutic or a mechanism-based clinical trial.ConclusionsNext-generation sequencing can discover targets of therapy for relapsed and metastatic ACC and shows promise to improve outcomes for this aggressive form of cancer.

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Peripheral smears are a useful, cost-effective, and time-effective tool for diagnosing anaplasmosis. In positive cases, diagnostic morulae can be identified with a count of 200 granulocytes.

Introduction/Objective TB is a strong prognosticator in CRC. The international TB consensus conference (ITBCC, 2016) proposed a “hot spot” approach for TB grading. We aimed to identify the characteristics of sections with the highest TB grade utilizing ITBCC’s method. Methods Resected CRC cases, excluding treated cases, were retrieved. All tumor sections were examined. Section TB grade(sTB) was noted. The highest sTB was deemed the final TB grade(fTB) of each case. The following categories were assessed: 1) maximum T stage; 2) presence of benign mucosa; 3) presence of a precursor lesion; 4) highest tumor volume; 5) presence of lymphovascular invasion(LVI). In cases where a given category was demonstrated in >1 section, the section with the highest sTB was used. High risk features (HFR) included T4, <12 lymph nodes, positive margin, high grade tumor, perineural invasion and LVI. Pearson’s correlation was performed to compare two groups using a p-value of <0.05. Results 147 cases were examined. fTB was 1=25.2%, 2=40.8% and 3=34%. 63 tumors involved the left colon and 62 had nodal disease. Of 119 cases with known MMR status 44 were MMR deficient. sTB was uniform across the categories in 101(68.7%) and uneven in 46(32.3%) cases. 12(24.5%) of 49 stage II CRC without HRF showed uneven sTB, with 2 showing 2-tier discrepancy (sTB1, fTB3). sTB was highest for category 3 (94.1%, P<.001), followed by category 2 (91.8%, P<.001), and lowest for category 1 (82.3%, P<.001), which remained true after subgrouping by MMR status and tumor location. Conclusion While about 70% of cases showed uniform TB grading across categories, choosing the slide(s) with a precursor lesion or benign mucosa increases the probability of correctly grading TB. Given the management implication, it may be prudent to scan all tumor slides in stage II CRC without HRF to avoid under-grading of TB.