Comprehensive Immuno-Molecular Profiles for Liposarcoma: Roles of Programmed Death Ligand 1, Microsatellite Instability, and PIK3CA.

BACKGROUND: Developing personalized strategies for cancer has shown good efficacies. METHODS: We assessed the molecular targets programmed death ligand 1 (PD-L1), microsatellite instability (MSI), and PIK3CA. Seventy-four patients with liposarcomas who underwent curative resection were assessed for PD-L1 expression in the tumor and tumor-infiltrating lymphocytes (TILs), mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry, MSI using polymerase chain reaction, and PIK3CA mutation/amplification using pyrosequencing and fluorescence in situ hybridization. RESULTS: Seventeen (23%) cases were TIL+ (≥1 + expression) and associated with longer 5-year overall survival than those with TIL- tumors (84.4 vs. 60.8%, p = 0.007). Six (35.3%) PD-L1+ tumors were detected only in TIL+ cases, with none detected in tumor cells. Two well-differentiated liposarcomas showed MSI, one low and one high with concurrent loss of MLH1, MSH6, and PMS2. PIK3CA mutation was detected in 7 (9.5%) [exon 9 (n = 4) and exon 20 (n = 3)] and only 1 Q546K mutation was a PD-L1+ tumor. PIK3CA copy number gain was detected in 18 (24.4%) and was associated with TIL+ tumors (p = 0.045). CONCLUSIONS: Our comprehensive immuno-molecular panel suggests that liposarcoma should be categorized based on the molecular genomic subtype for precision medicine.

AFP-producing acinar cell carcinoma treated by pancreaticoduodenectomy in a patient with a previous radical subtotal gastrectomy by gastric cancer.

We report a case of alpha-fetoprotein (AFP)-producing acinar cell carcinoma (ACC) of the pancreas. The tumor was diagnosed in a 72 yearold female after radical subtotal gastrectomy (Billroth I) due to early gastric cancer six months before. The initial serum AFP levels were increased to 2,254.1 IU/ml and preoperative imaging studies showed a mass with approximately 2.5 cm in diameter near the neck of the pancreas. A pancreaticoduodenectomy was performed. The pathologic examination revealed an ill-defined lobulating tumor confined to the pancreas (T1 stage). Immunohistochemical study showed that the tumor cells expressed AFP. The Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) suggested that cisplatin would be more desirable than gemcitabine in AFP-producing ACC of the pancreas as an adjuvant chemotherapy. However, the adjuvant chemotherapy was not performed due to the early pathological stage. The patient died from carcinomatosis and pneumonia. Even if the tumor was on a relatively early stage, an adjuvant treatment should be considered ACC.

Synchronous development of intrahepatic cholangiocarcinoma and hepatocellular carcinoma in different sites of the liver with chronic B-viral hepatitis: two case reports.

BACKGROUND: Synchronous development of primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma has been reported rarely. In literature review, there have been only 35 reported cases of synchronous hepatocellular carcinoma and intrahepatic cholangiocarcinoma, and most of these tumors developed in patients with hepatitis C-related liver cirrhosis. Here, we present synchronous development of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in two patients with chronic B-viral hepatitis. CASE PRESENTATION: Two patients with chronic hepatitis B were referred to our hospital due to a hepatic mass. Patient 1 had a 6.4 cm multinodular hepatic mass in the left lobe and a small nodule in the right lobe. Patient 2 had a 4.3 cm hypervascular mass in the right lobe and a 1.1 cm nodule in the left lobe. The pre-operative diagnosis of both cases was hepatocellular carcinoma with metastatic nodule, however, surgical resection pathology revealed that hepatocellular carcinoma and intrahepatic cholangiocarcinoma existed independently in the other side of the liver in both cases. Additionally, the background liver histology of both cases was hepatitis B-related chronic hepatitis without cirrhotic change. CONCLUSION: Our cases suggest that hepatitis B virus infection can also predispose to development of double liver cancers.

Expression of cell metabolism-related genes in different molecular subtypes of triple-negative breast cancer.

AIMS AND BACKGROUND: We evaluated the difference in and significance of cancer cell metabolism by molecular subtyping of triple-negative breast carcinoma. METHODS: Tissue microarrays from 122 surgical specimens of triple-negative breast carcinoma patients and immunohistochemical staining for CK5/6, epidermal growth factor receptor, claudin 3, claudin 4, claudin 7, E-cadherin, androgen receptor, and gamma-glutamyltransferase 1 were used to classify triple-negative breast carcinoma as follows: basal-like type, molecular apocrine type, claudin low type, mixed type and null type. In addition, immunohistochemical staining for metabolism-related proteins such as c-myc, insulin-like growth factor (g)-1, hypoxia-inducible factor 1-1α, glucose transporter 1, carbonic anhydrase IX antibody, macrophage migration inhibitory factor, and pyruvate dehydrogenase kinase 1 was used to compare the differences according to molecular subtype and clinicopathological factors. RESULTS: The basal-like type showed the highest proportion of high glucose transporter 1 expression (P = 0.049) and carbonic anhydrase IX antibody expression (P = 0.008). Hypoxia-inducible factor 1-1α expression was associated with lymph node metastasis (P = 0.001) and central fibrotic zone (P = 0.012), and high glucose transporter 1 expression was related to high histologic grade (P = 0.007), cytokeratin 5/6 positivity (P = 0.002), and central fibrotic zone (P = 0.017). Finally, carbonic anhydrase IX antibody was associated with cytokeratin 5/6 positivity (P = 0.001) and central fibrotic zone (P = 0.048). CONCLUSIONS: Our study revealed the different characteristics of cancer cell metabolism according to the molecular subtypes of triple-negative breast carcinoma. Among them, basal-like type was the most glycolytic and acid-resistant phenotype.

Cytologic features of giant cell ependymoma: a case report and review of the literature.

Here, we present a case of anaplastic giant cell ependymoma (GCE) occurring in a 15-year-old woman. Squash smear slides for intraoperative frozen section diagnosis revealed oval to round cell clusters with a papillary structure in a fibrillary background. This was occasionally accompanied by the presence of bizarre pleomorphic giant cells with hyperchromatic nuclei and prominent intranuclear inclusions. These intranuclear inclusions were a key clue to diagnosis of ependymoma. Histologic analysis revealed features of a high-grade tumor with perivascular pseudorosettes and bizarre pleomorphic giant cells, which established the diagnosis of GCE. We performed a review of literatures about the cytologic features of GCE, including our case, thus proposing that intraoperative frozen diagnosis of GCE would be established by squash smear preparations featuring the mitosis and necrosis, as well as the high cellularity, and the presence of giant cells showing hyperchromatic nuclei with eosinophilic cytoplasm and intranuclear inclusions/pseudoinclusions.

Prediction of the histopathological grade of hepatocellular carcinoma using qualitative diffusion-weighted, dynamic, and hepatobiliary phase MRI.

OBJECTIVES: To investigate the effectiveness of qualitative diffusion-weighted imaging (DWI), subtraction of unenhanced from arterial phase images, and hepatobiliary phase (HBP) images in estimating the histopathological grade of hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed gadoxetic acid-enhanced magnetic resonance images of 175 patients with 201 surgically resected HCCs. The signal intensity and its relationship with histopathological grade were assessed for each sequence and a combination of sequences. RESULTS: There was a tendency towards higher grades in tumours showing restricted diffusion on DWI (P < 0.001) or arterial enhancement on subtraction imaging (P < 0.001), but not hepatocyte-defect on HBP images (P = 0.33). When lesions were divided into three groups based on combined findings on DWI and subtraction imaging, a linear trend was observed between group and grade (P < 0.001). The positive predictive value (PPV) of the combination of no restricted diffusion and no arterial enhancement in predicting well-differentiated HCC was 100%, higher than the PPV of individual findings on DWI (74%) or subtraction imaging (81%). CONCLUSIONS: DWI and subtraction imaging are helpful for predicting the histopathological grade of HCC, especially when the two sequences are considered together. KEY POINTS: • Predicting the histopathological grade of hepatocellular carcinoma (HCC) preoperatively is important. • Diffusion-weighted imaging (DWI) and subtraction imaging are recently developed MR techniques. • Retrospective study showed DWI and subtraction imaging helps predict HCC grades. • Management of patients with HCC becomes more appropriate.

The definition of minimal extrathyroid extension in thyroid pathology by analyzing sizable intra- and extrathyroid blood vessels.

BACKGROUND: To define the exact boundary of the intrathyroid and extrathyroid aspects of a gland when determining the extent of cancer invasion, we plan to clarify the definition of sizable vascular structures, which is one of the helpful histologic clues in determining a minimal extrathyroid extension. We hypothesized that arterial wall thicknesses in extrathyroid soft tissue would be significantly different from the arteries in the thyroid parenchyma. METHODS: Twenty cases of papillary carcinoma were selected. The numbers and wall thicknesses of the arteries and arterioles in intrathyroid and extrathyroid tissue were evaluated. The absence of nerve tissue in the thyroid gland was confirmed using the S-100 protein immunohistochemical stain. RESULTS: The comparison of the mean thicknesses of the total arteries between the extrathyroid and intrathyroid tissues in the retrospective study (26.88 µm vs. 15.07 µm, respectively) and the prospective study (35.24 µm vs. 16.52 µm, respectively) revealed significant differences (p=0.000). The greatest thickness of the intrathyroid arteries was 67.93 µm. CONCLUSIONS: According to our results, the study showed that the extrathyroidal arteries were significantly thicker than the intrathyroidal arteries. We suggest that the sizable blood vessels of extrathyroidal arteries should be greater than 67.93 µm in thickness.

Prediction of microvascular invasion of hepatocellular carcinoma: usefulness of peritumoral hypointensity seen on gadoxetate disodium-enhanced hepatobiliary phase images.

PURPOSE: To determine whether peritumoral hypointensity seen on hepatobiliary phase images of preoperative gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) is useful for predicting microvascular invasion of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was approved by the Institutional Review Board. In all, 104 HCC masses in 104 patients who had undergone EOB-MRI and liver surgery within 1 month after EOB-MRI were evaluated. Two radiologists independently recorded the presence of a peritumoral hypointensity on hepatobiliary phase. Interobserver agreement was assessed and consensus records were used. Tumor size was measured. A chi-square test and independent t-test were used for univariate analysis. Multiple logistic regression was performed to determine factors for predicting microvascular invasion. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of peritumoral hypointensity were calculated. RESULTS: Sixty HCCs had microvascular invasion and 44 did not. Interobserver agreement in determining peritumoral hypointensity was excellent (κ = 0.83). By univariate analysis, peritumoral hypointensity and tumor size were significant for predicting microvascular invasion of HCC. On multiple logistic regression analysis, only peritumoral hypointensity was significant in predicting microvascular invasion of HCC (P = 0.013). The sensitivity, specificity, PPV, and NPV of peritumoral hypointensity were 38.3%, 93.2%, 88.5%, and 52.6%, respectively. CONCLUSION: Peritumoral hypointensity on the hepatobiliary phase of EOB-MRI is not sensitive but has high specificity for predicting microvascular invasion of HCC.