BACKGROUND: The purpose of this study was to describe potential pitfalls in the diagnosis of metastatic adenocarcinoma in cerebrospinal fluid (CSF) and to suggest additional work in association with cytokeratin immunocytochemistry for the proper diagnosis, especially in the specimens with low cellularity. METHODS: We collected 267 cytologic specimens of CSF from patients, who were diagnosed over a 9-month period. Each of the individual samples were divided into half the sample size and processed via both, ThinPrep (TP) with Papanicolau stain and cytocentrifugation-based preparation (cytospin, CP) with immunocytochemical stain for cytokeratin. RESULTS: Amongst the 267 cases, 45 cases from 22 patients were diagnosed to be positive for metastasis adenocarcinoma in CSF. TP with Papanicolau stain showed satisfactory cytomorphology when compared with specimen of CP preparation and cytokeratin immunocytochemical staining. All the TP processed cases belonged to satisfactory/superior categories based on the assessment of technical artifact, which potentially helps in decreasing diagnositc errors. However, in 10 out of 45 cases, diagnostic atypical cells were present only in one of the two slides. CONCLUSIONS: Immunocytochemical stain for cytokeratin along with TP processed specimen helps in decreasing potential diagnostic errors in the cytological diagnosis of metastatic carcinoma in CSF specimen.
Adenocarcinoma ; Artifacts ; Diagnostic Errors ; Humans ; Immunohistochemistry ; Keratins ; Neoplasm Metastasis ; Sample Size

Eosinophils are one of the polymorphonuclear granulocytes derived from bone marrow stem cells, and they contain many small cytoplasmic granules that stain bright red with eosin or brick-red with Romanowsky staining. Eosinophilic infiltration is also present in various human central nervous system (CNS) diseases such as parasitic infection, transverse myelitis, vasculitis, Langerhans cell histiocytosis, glioblastoma and etc... Due to the morphologic and functional characteristics, the presence of eosinophils in certain lesions may provide useful diagnostic clues in the right clinical setting. Consideration of this finding may facilitate the diagnosis of CNS pathologic lesions, especially in a small specimen such as a stereotactic biopsy.
Biopsy ; Bone Marrow ; Central Nervous System ; Cytoplasmic Granules ; Eosine Yellowish-(YS) ; Eosinophils ; Glioblastoma ; Granulocytes ; Histiocytosis, Langerhans-Cell ; Humans ; Myelitis, Transverse ; Stem Cells ; Vasculitis

In 2011, the International League against Epilepsy (ILAE) proposed a first international consensus of the classification of focal cortical dysplasia (FCD). This FCD classification had been widely used in worldwide. In this review paper, the authors would like to give helpful comments for better understanding of the current FCD classification. Especially, the basic concepts of FCD type I, such as “radial”, “tangential” and “microcolumn” will be discussed with figures. In addition, the limitations, genetic progress and prospect of FCD will be suggested.
Classification ; Consensus ; Embryology ; Epilepsy ; Humans ; Malformations of Cortical Development ; Pathology

Purpose: Expression of organic anion transporting polypeptides (OATPs) 1B1/1B3 in hepatocellular carcinoma (HCC) induces a paradoxical enhancement of gadoxetic acid on liver magnetic resonance imaging (MRI). We examined the expression profile of OATPs with regard to tumor differentiation in a genetically modified H-Ras 12V mouse model of spontaneous HCC that undergoes multistep hepatocarcinogenesis with minimal inter-individual variation. Materials and Methods: Tumor nodules were harvested from transgenic H-Ras 12V mice. Hematoxylin and eosin-stained slides were examined for tumor differentiation and high-grade pathological components (tumor necrosis, thickened trabeculae, or vascular invasion). Immunohistochemistry of OATP 1B1/1B3 was performed, and OATP expression was assessed. Results: We examined well-differentiated HCCs (n=59) in which high-grade pathological components were absent (n=49) or present (n=10). Among the well-differentiated HCCs without high-grade pathological components (n=49), OATP expression was negative, weak positive, and moderate positive in 23, 17, and nine cases, respectively. Among the well-differentiated HCCs with highgrade pathological components (n=10), OATP expression was negative, weak positive, and moderate positive in one, two, and seven cases, respectively. The ratio of positive OATP 1B1/1B3 expressing tumors was higher in HCCs with high-grade pathological components than in those without high-grade pathological components (p=0.004). Conclusion Our findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acidenhanced MRI in moderately differentiated HCC.

Purpose: Expression of organic anion transporting polypeptides (OATPs) 1B1/1B3 in hepatocellular carcinoma (HCC) induces a paradoxical enhancement of gadoxetic acid on liver magnetic resonance imaging (MRI). We examined the expression profile of OATPs with regard to tumor differentiation in a genetically modified H-Ras 12V mouse model of spontaneous HCC that undergoes multistep hepatocarcinogenesis with minimal inter-individual variation. Materials and Methods: Tumor nodules were harvested from transgenic H-Ras 12V mice. Hematoxylin and eosin-stained slides were examined for tumor differentiation and high-grade pathological components (tumor necrosis, thickened trabeculae, or vascular invasion). Immunohistochemistry of OATP 1B1/1B3 was performed, and OATP expression was assessed. Results: We examined well-differentiated HCCs (n=59) in which high-grade pathological components were absent (n=49) or present (n=10). Among the well-differentiated HCCs without high-grade pathological components (n=49), OATP expression was negative, weak positive, and moderate positive in 23, 17, and nine cases, respectively. Among the well-differentiated HCCs with highgrade pathological components (n=10), OATP expression was negative, weak positive, and moderate positive in one, two, and seven cases, respectively. The ratio of positive OATP 1B1/1B3 expressing tumors was higher in HCCs with high-grade pathological components than in those without high-grade pathological components (p=0.004). Conclusion Our findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acidenhanced MRI in moderately differentiated HCC.

BACKGROUND: Metastasis is one of the most important characteristics of cancer in terms of its impact on patient survival. Unfortunately, identification of altered genes during tumor metastasis is limited. METHODS: Using high-throughput microarrays containing 19K spotted human oligonucleotides, gene expression of primary and matched metastatic colon cancer were compared in previous study. Although DNA microarray analysis did not demonstrate complete classification of primary and metastatic carcinoma, 80 differentially expressed genes were identified. Among these, expression of osteopontin, matrix metalloproteinase-1 (MMP-1) and serpin A1 was assessed using immunohistochemistry in a validation set containing 43 pairs from tissue microarrays. RESULTS: The expression of osteopontin was significantly higher in metastatic carcinoma than in primary carcinoma, as indicated by mRNA expression. The expression of MMP-1 was significantly lower in metastatic carcinoma. Expression of serpin A1 was not correlated with the microarray results. CONCLUSIONS: Osteopontin and MMP-1 expression successfully classified primary and metastatic colorectal carcinomas and further studies on their clinical application is encouraged.
alpha 1-Antitrypsin ; Colonic Neoplasms ; Colorectal Neoplasms ; Gene Expression ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 1 ; Neoplasm Metastasis ; Oligonucleotide Array Sequence Analysis ; Oligonucleotides ; Osteopontin ; RNA, Messenger

BACKGROUND: High microsatellite instability (MSI-H) colorectal carcinomas (CRCs) with numerous mutations in the microsatellite sequence are characterized by a right-sided preponderance, frequent peritumoral and intratumoral lymphocytic infiltration, and frequent mucin production. However, no study has correlated anatomic site and type of genetic changes with clinicopathologic changes. METHODS: We analyzed the histopathologic features of 135 MSI-H CRCs and compared them to 140 microsatellite stable (MSS) CRCs. Histopathologic changes in MSI-H were further analyzed according to anatomic sites and genetic changes. RESULTS: MSI-H CRCs showed previously reported clinicopathologic findings; a right-sided preponderance, an increased number of mucinous carcinomas, and peritumoral lymphoid reactions (p<0.001 for each variable). Increased serum CEA levels showed an MSS CRC preponderance (p=0.013). We further analyzed the histologic differences between right- and left-sided MSI-H tumors. We found that MSI-H CRCs on both sides had similar clinicopathologic findings, except for higher tumor stage (p=0.048) and less frequent abnormal CEA levels in left-sided MSI-H tumors (p=0.027). We found that not all clinicopathologic features were different between hereditary nonpolyposis colorectal cancers (HNPCCs) and sporadic MSI-H CRCs. CONCLUSIONS: These findings indicate that MSI-H CRCs of the left colon have similar clinicopathologic characteristics as right-sided MSI-H CRCs. We did not find any significant clinicopathological difference between HNPCCs and sporadic MSI-H CRCs.
Adenocarcinoma, Mucinous ; Calcium Hydroxide ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Microsatellite Instability ; Microsatellite Repeats ; Mucins ; Zinc Oxide

BACKGROUND: Although the importance of aberrant DNA methylation in the development of gastric adenocarcinoma has been described, the mechanism of pathogenesis has not been revealed yet. We quantitatively analyzed methylation of four CpG islands and one repetitive DNA element, according to the histologic features of adenocarcinoma with precursor lesions. METHODS: We divided the cases as adenocarcinoma with intestinal type precursors (type A, n=19 cases) and adenocarcinoma with diffuse type precursors (type B, n=19 cases). We micro-dissected tumor cells and matched non-neoplastic gastric mucosa from the hematoxylin and eosin-stained slides. RESULTS: A total of 20 CpG sites of long interspersed nucleotide element-1 (LINE1), RAR-related orphan receptor alpha (RORA), Kruppel-like factor 7 (KLF7), mutL homolog 1 (MLH1), MINT25, and CD133 were analyzed. Methylation was determined by bisulfate-pyro-sequencing, and hypomethylation of LINE1 and CD133 was noted in the tumors, compared to the levels in the non-neoplastic gastric mucosa (p=0.014 and p=0.015, respectively). A statistically different methylation pattern of CpG sites at CD133 and KLF7 was noted only in type B lesions, compared to that in matched non-neoplastic gastric mucosa (p=0.027 and p=0.043, respectively). CONCLUSIONS: Given that aberrant methylation occurs in a relatively early phase of carcinogenesis, different patterns of methylation may determine the carcinoma phenotype. However, further large-scale study is required to clarify the significance of this difference.
Adenocarcinoma ; Adenoma ; Child ; Child, Orphaned ; CpG Islands ; DNA ; DNA Methylation ; Gastric Mucosa ; Hematoxylin ; Humans ; Methylation ; Phenotype ; Stomach

OBJECTIVE: To determine whether quantitative perfusion parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlate with immunohistochemical markers of angiogenesis in rectal cancer. MATERIALS AND METHODS: Preoperative DCE-MRI was performed in 63 patients with rectal adenocarcinoma. Transendothelial volume transfer (Ktrans) and fractional volume of the extravascular-extracellular space (Ve) were measured by Interactive Data Language software in rectal cancer. After surgery, microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression scores were determined using immunohistochemical staining of rectal cancer specimens. Perfusion parameters (Ktrans, Ve) of DCE-MRI in rectal cancer were found to be correlated with MVD and VEGF expression scores by Spearman's rank coefficient analysis. T stage and N stage (negative or positive) were correlated with perfusion parameters and MVD. RESULTS: Significant correlation was not found between any DCE-MRI perfusion parameters and MVD (rs = -0.056 and p = 0.662 for Ktrans; rs = -0.103 and p = 0.416 for Ve), or between any DCE-MRI perfusion parameters and the VEGF expression score (rs = -0.042, p = 0.741 for Ktrans ; r = 0.086, p = 0.497 for Ve) in rectal cancer. TN stage showed no significant correlation with perfusion parameters or MVD (p > 0.05 for all). CONCLUSION: DCE-MRI perfusion parameters, Ktrans and Ve, correlated poorly with MVD and VEGF expression scores in rectal cancer, suggesting that these parameters do not simply denote static histological vascular properties.
Adult ; Aged ; Aged, 80 and over ; Contrast Media/*diagnostic use ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic/diagnosis/metabolism ; Rectal Neoplasms/blood supply/*diagnosis/metabolism ; Retrospective Studies ; Tumor Markers, Biological/biosynthesis ; Vascular Endothelial Growth Factor A/*biosynthesis

A rare case of poorly differentiated thyroid carcinoma (PDTC) with gross intraluminal invasion to the internal jugular vein whose clinical manifestation was multiple lung metastases is described. A 66-year-old man was referred to the outpatient clinic of the Department of Internal Medicine, hemato-oncology subdivision for multiple lung nodules found by his regular health check-up. These lung nodules showed variable sizes with irregular shapes, and typical distributions throughout the parenchyma, which were consistent with metastatic nodules. Ultrasonography revealed a 4.5 cm sized hypoechoic mass with irregular shape in his left thyroid lobe and a huge thrombus in the left internal jugular vein. PDTCs associated with gross intraluminal invasion to the great cervical vein and multiple lung nodules as their first clinical manifestation are extremely rare. We would emphasize the importance of preoperative detailed evaluation of the disseminated disease by ultrasonography in suspected patients.
Aged ; Ambulatory Care Facilities ; Humans ; Internal Medicine ; Jugular Veins* ; Lung* ; Neoplasm Metastasis* ; Thrombosis ; Thyroid Gland ; Thyroid Neoplasms* ; Ultrasonography ; Veins