High-yield areas to grade tumor budding in colorectal cancer: A practical approach for pathologists.

BACKGROUND: Tumor budding (TB) has significant prognostic implication in stage II colorectal cancer (CRC) and is graded based on the International Tumor Budding Consensus Conference (ITBCC) protocol. In the current study, we evaluate tumor budding and its relationship to multiple histologic features in 104 tumors. METHODS: One-hundred four resected CRC cases were retrieved. Tumor bud count and TB grade were compared to the final tumor bud count/TB grade of the tumor per ITBCC protocol. The following high-yield co-features were assessed in each slide: highest T stage, presence of benign mucosa, presence of a precursor lesion, and highest tumor volume. RESULTS: Twenty-nine (28 %) cases had discrepancies between slide TB grade and final TB grade. The least discrepancies were seen in slides with benign mucosa (7 %) and precursor lesions (7 %). Among stage II patients without high-risk features, no discrepancies were observed in slides with benign mucosa. Slides with deepest invasion (rs = 1.000, p = 0.01) and benign mucosa (rs = 0.957, p < 0.001) had the strongest correlation with final tumor bud count in the same stage II subgroup. Similar relationships were observed when comparing final TB grade. Deepest invasion, tumor volume, as well as lymphovascular invasion, when present, also showed strong correlations with final TB grade in the entire cohort (rs = 0.828-0.845, p < 0.001). CONCLUSION: Our study is the first study to evaluate the relationship between TB grade and co-existing histologic features. We highlight the benefit of focusing on slides with high-yield co-features, with the strongest correlation seen in slides with adjacent benign mucosa and precursor lesions.

Intracytoplasmic granulocytic morulae counts on confirmed cases of ehrlichiosis/anaplasmosis in the Northeast.

OBJECTIVES: To characterize the number of granulocytes needed to count on peripheral smear to identify diagnostic anaplasmosis morulae. METHODS: Retrospective case study where the peripheral smears of 14 confirmed cases of anaplasmosis were examined. The granulocytes were counted up to 100 and 200 until a morula was identified. The mean counts of three pathologists were calculated to determine the minimum number of granulocytes needed to count for identifying diagnostic morulae. RESULTS: Morulae were identified before a count of 100 granulocytes in 11 (78.6%) cases and between 100 and 200 granulocytes in 3 (21.4%) cases. All 14 (100%) cases had morulae identified before counting 200 granulocytes. CONCLUSIONS: 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.

New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing.

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 µm of 28 formalin-fixed paraffin-embedded ICC specimens and sequenced to high coverage. RESULTS: The most commonly observed alterations were within ARID1A (36%), IDH1/2 (36%), and TP53 (36%) as well as amplification of MCL1 (21%). Twenty cases (71%) harbored at least one potentially actionable alteration, including FGFR2 (14%), KRAS (11%), PTEN (11%), CDKN2A (7%), CDK6 (7%), ERBB3 (7%), MET (7%), NRAS (7%), BRCA1 (4%), BRCA2 (4%), NF1 (4%), PIK3CA (4%), PTCH1 (4%), and TSC1 (4%). Four (14%) of the ICC cases featured novel gene fusions involving the tyrosine kinases FGFR2 and NTRK1 (FGFR2-KIAA1598, FGFR2-BICC1, FGFR2-TACC3, and RABGAP1L-NTRK1). CONCLUSION: Two thirds of patients in this study harbored genomic alterations that are associated with targeted therapies and that have the potential to personalize therapy selection for to individual patients.