Detection of hepatocellular carcinoma circulating tumor cells performed with conventional strategies, is significantly limited due to inherently heterogeneous and dynamic expression of EpCAM, as well as degradation of cytokeratins during epithelial-to-mesenchymal transition, which inevitably lead to non-negligible false negative detection of such "uncapturable and invisible" CTCs. A novel SE-iFISH strategy, improved for detection of HCC CTCs in this study, was applied to comprehensively detect, in situ phenotypically and karyotypically characterize hepatocellular and cholangiocarcinoma CTCs (CD45/CD31) in patients subjected to surgical resection. Clinical significance of diverse subtypes of CTC was systematically investigated. Existence of small cell size CTCs (≤5 μm of WBCs) with cytogenetic abnormality of aneuploid chromosome 8, which constituted majority of the detected CTCs in HCC patients, was demonstrated for the first time. The stemness marker EpCAM aneuploid circulating tumor stem cells (CTSCs), and EpCAM small CTCs with trisomy 8, promote tumor growth. Postsurgical quantity of small triploid CTCs (≥5 cells/6 ml blood), multiploid (≥pentasomy 8) CTSCs or CTM (either one ≥ 1) significantly correlated to HCC patients' poor prognosis, indicating that detection of those specific subtypes of CTCs and CTSCs in post-operative patients help predict neoplasm recurrence.

Thirty-four cases of primary non-Hodgkin's lymphoma of the oral cavity were investigated for their clinical findings, histopathological features, immunophenotypes and association with Epstein-Barr virus (EBV). Four cases (12%) were natural killer/T-cell lymphomas, 3 (9%) were T-cell lymphomas and 27 (79%) were Bcell lymphomas. Compared with T-and B-cell lymphomas, NK/T-cell lymphomas had a male predominance (M:F 4:0), and most presented as ulceration of the palate and/or maxillary gingiva. Histologically, the lesions showed diffuse infiltration of medium-sized or large lymphoid tumour cells. Angiocentricity and/or angioinvasion were found in all 4 cases. The immunophenotypes of the NK/T-cell lymphomas were CD3+, CD43+, CD45RO+, CD56+ and TIA-1+. EBV was detected in 2 NK/T-cell lymphomas by in situ hybridization (ISH) and polymerase chain reaction (PCR) methods, and was not detected in T-and B-cell lymphomas. The survival rate of patients with NK/T-cell lymphoma was zero, but the survival rates for patients with T-cell and B-cell lymphomas were 67% and 38%, respectively. It appears that NK/T-cell lymphomas of the oral cavity have a predilection for originating in the palate and maxillary gingiva and are aggressive neoplasms. EBV positivity might be associated with more aggressive behaviour.

We investigated the risk factors for diffuse midline gliomas of the spinal cord (DMGSCs). Seventy patients with spinal cord gliomas in two hospitals were analyzed retrospectively. Sixty-nine patients that underwent surgery achieved partial or gross total removal. The patients were subdivided into some groups, based on age, WHO grade, tumor location within the cord, tumor size, and molecular profile: immunohistochemical expression of p53 and ATRX, and mutational status of Histone 3 (H3), and BRAF. Thirty-three patients had an H3 K27M mutation (47%). Some clinical characteristics were significantly different between H3 K27M mutant and H3 wild-type tumors. The main risk factors for DMGSCs were male sex, glioblastomas, and ≤ 2 spinal cord segments. The median survival period of patients with H3 K27M mutant tumors was significantly shorter than those with H3 wild-type tumors (17.0 ± 3.7 months vs censored, P < 0.0001). In the DMGSC subgroup, patients with thoracic cord tumors had a significantly better prognosis than those with cervical cord tumors (31.0 ± 6.0 vs 10.0 ± 4.8 months). Patients > 45 years of age survived significantly longer than patients < 19 years (P = 0.001). In conclusion, H3 K27M mutation significantly predicts a worse outcome of spinal cord gliomas. Anatomical location and age are the main risk factors for DMGSCs.

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