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Background While fine-needle aspiration cytology (FNAC) using conventional smear has been widely accepted as the primary diagnostic tool for thyroid lesions, liquid-based preparations (LBPs) are increasingly replacing it. A new automated LBP method, EASYPREP® (EP), was recently introduced and has shown relevant diagnostic efficacy in gynecologic samples. We compared the diagnostic utility of EP and SurePath® (SP), a more widely established LBP method, in thyroid FNAC. Methods Under the ultrasonographic guidance, 253 thyroid FNAC samples were collected by sample-splitting manner. Three pathologists made cytologic diagnoses of EP and SP according to the Bethesda system independently and compared the cytomorphologic parameters. Cytohistologic correlation was performed in 30 resected cases. Results Fifteen (5.9%) and 21 (8.3%) samples were unsatisfactory in SP and EP, respectively, owing to the unequal sample-splitting. Cytologic diagnoses of SP and EP were consistent in 228 cases (90.1%), and inconsistent in remainder mostly owing to the unequal distribution of pathognomic cells. While cytomorphologic parameters were not significantly different between two methods, EP showed less three-dimensional configuration in benign lesions. Cytohistologic correlation showed no significant differences in sensitivity (100% vs. 95.5%) and specificity (100% vs. 100%) between SP and EP. Labor time for processing 48 cases was 42% shorter with EP than with SP (28 min vs. 48 min). Conclusions The diagnostic utility of EP in thyroid FNAC was comparable to that of SP. EP allowed better visibility owing to better fragmentation of follicular clusters. The automated system of EP has the advantages of a shorter labor time for batch processing. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

Meningiomas are slow-growing neoplasms that recur locally. Their morphologic grading does not always correlate with patient outcome. We evaluated the status of several immunohistochemical markers with histopathologic parameters in various grades of meningioma.Eighty-eight meningioma specimens were examined immunohistochemically to determine the status of Ki-67, cyclin D1, epidermal growth factor receptor (EGFR), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and bcl-2. Several clinical and pathological parameters were investigated.Forty-nine Grade I, 33 Grade II, and 6 Grade III meningiomas were observed. VEGF and Ki-67 expression was correlated with higher tumor grade. The association between grade and other immunohistochemical markers expression was not significant. A correlation was observed between COX-2 expression and invasiveness to the brain or adjacent soft tissue. Tumor recurrence was correlated with brain or adjacent soft tissue invasion. We also observed a relationship between VEGF level and COX-2 expression, and they were both correlated with necrosis.Immunohistochemical evaluation of VEGF, COX-2, and Ki-67 expression can provide information regarding the behavior of meningiomas, particularly for cases in which histological grading is not straightforward.

The tall cell variant (TCV) of papillary thyroid carcinoma (PTC) is the most common among the aggressive variants of the disease. We aimed to investigate the clinicopathologic characteristics of TCV, and evaluate the diagnostic efficacy of liquid-based cytology (LBC) in TCV detection compared with conventional smear in thyroid fine needle aspiration (FNA). A total of 266 consecutive patients (220 women and 46 men) with PTC were enrolled. We analyzed tumor characteristics according to histologic growth patterns as classic, classic PTC with tall cell features, and TCV. The cytomorphologic features of these subtypes were investigated according to the preparation methods of conventional smear and LBC. TCV and classic PTC with tall cell features comprised 4.9% and 6.0% of all tumors, respectively, and were significantly associated with older age at presentation, larger tumor size, high frequency of extrathyroid extension, and BRAF mutation in comparison with classic PTC. However, there was no statistically significant difference in clinicopathologic features between TCV and classic PTC with tall cell features. Tall cells were more easily detected by LBC than by conventional smear. The percentage of tall cells identified using LBC was well correlated with three histologic subtypes. Our results demonstrate that TCV is more common than previously recognized in Korea and any PTC containing tall cells may have identical biological behavior regardless of the precise proportions of tall cells. It is possible to make a preoperative diagnosis of TCV using LBC.

Background and Objectives The calcium-binding protein S100A4 promotes tumor progression and metastasis. We investigated the expression of S100A4 in colorectal cancer and its clinicopathologic significance in colorectal cancer. Methods A total of 526 colorectal cancer patients were examined for S100A4 protein by immunohistochemistry using tissue microarrays. S100A4 mRNA was subsequently investigated by in situ hybridization. Results S100A4 protein was expressed in various cell types including tumor cells, but S100A4 mRNA was only expressed in tumor cells. Cytoplasmic expression of S100A4 protein was seen in 127 (24.1%) of 526 tumors and significantly correlated with older age, depth of invasion, lymph node metastasis, and worse overall survival. Nuclear expression of S100A4 protein was observed in 136 (25.9%) tumors and significantly related to the depth of invasion, perineural invasion, and worse overall survival. However, there was no correlation between S100A4 mRNA expression and clinicopathological parameters. Upon multivariate analysis nuclear expression of S100A4 protein was found to be an independent prognostic factor of poor survival. Conclusions Expression of S100A4 protein in colorectal cancers may indicate tumor progression and lymph node metastasis and can be useful for prediction of overall survival of patients with colorectal cancers. J. Surg. Oncol. 2012; 105:119–124. © 2011 Wiley Periodicals, Inc.

Background The expression of Hedgehog (Hh) signaling pathway in prostate cancer is well-known but its clinicopathologic role has not been elucidated well. Methods Prostatectomy cases of prostate cancer (n = 155) were prepared and assessed by clinicopathologic parameters including new 2010 anatomic stage/prognostic groups (ASPG) of prostate cancer. The expression of five Hh signaling proteins including Sonic hedgehog (Shh), Patched, Smoothened, and GLIoma-associated oncogene, in addition with Suppressor of fused (Su(fu)) were analyzed immunohistochemically. Real-time polymerase chain reaction was performed to assess the mRNA expression status. Results The expression of each Hh signaling protein was significantly correlated with poor prognostic parameters such as larger tumor size, high pretreatment prostate-specific antigen (PSA), high Gleason score, perineural invasion and new ASPG. Among Hh signaling proteins, Sonic hedgehog and Smoothened expressions tend to have a significantly higher risk of PSA recurrence (P

The American Joint Committee on Cancer has proposed the tumor, node, metastasis (TNM) staging system to overcome the limitations of the Ann Arbor staging system for ocular adnexal lymphoma. We performed this study to evaluate the feasibility of the TNM staging system for ocular adnexal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (OAML). The data form 66 total eyes from 54 patients with biopsy-confirmed OAML according to World Health Organization classification were retrospectively analyzed. Using the TNM staging system, we reclassified all patients into two categories: (1) T1N0M0 stage group (n = 26), for patients with lymphoma involving only the conjunctiva; and (2) above T1N0M0 or bT1N0M0 stage group (n = 28), for patients with lymphoma extending to the orbit, eyelid, or adjacent structures, and/or bilateral OAML. After a 24-month median follow-up period for all patients, the T1N0M0 group revealed higher progression-free survival (PFS) than the above T1N0M0 or the bT1N0M0 group (P = 0.041). In a separate analysis of only 50 patients categorized as Ann Arbor stage IE, the T1N0M0 group demonstrated higher PFS (100%) than the above T1N0M0 or the bT1N0M0 group (84.7%; P = 0.067). Our data show that the poor prognostic group classified as Ann Arbor stage IE can be further distinguished by using the TNM staging system. Thus, further studies to develop treatment strategies for reducing relapse after treatment for OAML should use the TNM staging system.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare malignancy derived from antigen-presenting cells, with 55 cases reported thus far. A standard treatment modality is still being debated. This report describes a 56-year-old female who presented with right tonsillar enlargement and right submandibular swelling for 6 months. Treatment with empiric antibiotics did not result in improvement of her symptoms. Fine needle aspiration of the tonsil revealed no malignant cells. Tonsillectomy was eventually performed due to persistent symptoms. Based on microscopic findings, immunohistochemical stains, and review of the literature, the present case was finally diagnosed as IDCS of the tonsil with cervical lymph node involvement. The patient received four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, and a clinically complete response was achieved followed by adjuvant radiation.

The usefulness of fresh-frozen, optimal cutting temperature (OCT) compound-embedded (FFOE) bone marrow (BM) aspirates was evaluated as a reliable resource for morphological, immunohistochemical and molecular examinations. One hundred BM aspirates were collected in polypropylene tubes and immediately frozen for 2 h in a deep freezer. Frozen BM was transferred to a cryomold filled with OCT compound and the prepared samples were stored in a deep freezer. Histological examination and immunohistochemical staining, polymerase chain reaction (PCR), sequencing and reverse transcription (RT)-PCR were performed to evaluate the quality of the FFOE BM sections in 10% of randomly selected samples. FFOE BM sections revealed better morphologies than paraffin-embedded clot sections in haematoxylin and eosin staining because mature erythrocytes were removed during the staining process in frozen BM sections. Immunohistochemical staining for CD34 revealed excellent staining quality and oil red O staining showed that fat vacuoles in cells were well preserved. The quality of genomic DNA in FFOE BM sections was suitable for obtaining about 2000 bp PCR product for the human leucocyte antigen-A locus followed by direct sequencing of the sample, and the quality of total RNA was suitable for detection of BCR-ABL fusion transcript. FFOE BM aspirates are a reliable resource for various laboratory tests of diagnostic and research arenas.

Background and aims: Notch signaling pathways are well known for their major role in stem cell differentiation. However, varied results have been reported in relation to their oncogenic role, depending on tumor type. We studied the expression of Notch receptors and other cell cycle proteins in human non-small cell lung carcinomas (NSCLC) and analyzed their relationship to tumor progression. Methods: We examined the tissue microarrays of 158 cases of NSCLC for Notch1 and 3, and cell cycle regulatory proteins p53, p16INK4a, pRb and CDK2 by immunohistochemistry. Results: Notch1 and 3 receptors were noted in 81.6% and 79.7% of cases, respectively. Notch1 expression was negatively correlated with lymph node metastasis (P = 0.043) and Notch3 was negatively correlated with more advanced pathologic T stage (P = 0.024). However, expressions of Notch receptors didn't show any significant prognostic value for NSCLC. Of the cell cycle proteins, CDK2 and pRb were negatively correlated with Notch1 (P = 0.013) and Notch3 (P = 0.018). Conclusions: Notch receptors play an inhibitory role in metastasis to lymph node and in the activity of cell cycle proteins, which may lead to suppression of NSCLC.

Transforming acidic coiled-coil containing protein 3 (TACC3) is known to be involved in the control of normal cell growth and differentiation and in mechanisms of unregulated growth leading to tumorigenesis. The aim of the present paper was to determine the rate of TACC3 expression in a non-small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters. A total of 163 NSCLC were analyzed immunohistochemically using a polyclonal TACC3 antibody and monoclonal p53 and Ki-67 antibodies on NSCLC tissue microarrays. A high level of TACC3 expression was observed in 14.8% of cases, preferentially squamous cell carcinomas. Patients whose tumors had a high TACC3 expression had a significantly shorter median survival time. In the Cox regression-based multivariate analysis, TACC3 expression proved to be an independent prognostic parameter (P = 0.031). TACC3 expression was correlated with p53 expression, and patient whose tumors highly expressed TACC3 and p53 had a significantly poorer prognosis than patients whose tumors had low-level expression for both immunostainings (P = 0.006). It is suggested that increase in TACC3 may impart a proliferative advantage to NSCLC and contribute to tumor progression, and that TACC3 expression is a strong prognostic indicator of clinical outcome in NSCLC.

A 25-yr-old man had been diagnosed as having CD30+ anaplastic large cell lymphoma associated with hemophagocytic syndrome (HS). He received aggressive frontline chemotherapies and consolidation with autologous peripheral blood stem cell transplantation (PBSCT) following high-dose chemotherapy combined with splenic irradiation (720 cGy in fraction of 180 cGy). However, HS recurred on day 50 of PBSCT without radiologic evidence of lymphoma relapse. On day 56 of PBSCT, splenectomy was performed and pathology showed massive sinusoidal infiltration of histiocytes. On day 68 of PBSCT, administration of interferon alpha was started and maintained for 24 months. HS was completely resolved and he has been alive well and in complete remission (CR), 60 months after initial diagnosis.

Background and Aim: In hepatocarcinogenesis, both de novo and multistep pathways have been suggested, and in the latter a dysplastic nodule is the proposed precancerous lesion. But genetic changes involved in the dysplastic nodule are not well understood. In this study, we tried to determine whether allelic loss of the chromosome 8p and/or 11p could be involved in the development of the dysplastic nodule and/or hepatocellular carcinoma. Platelet-derived growth factor-receptor beta-like tumor suppressor gene (PRLTS) and deletion in liver cancer-1 tumor suppressor gene are located at 8p21.3-p22. The hepatitis B virus integration site and WT1 tumor suppressor gene are located at 11p13. Methods: We therefore studied loss of heterozygosity (LOH) of chromosome 8p21.3–p22 and 11p13 in 22 dysplastic nodules and 21 hepatocellular carcinomas. The samples, microdissected from paraffin-embedded tissues, were examined using a polymerase chain reaction-based LOH assay using microsatellite markers. Results: Loss of heterozygosity was detected for chromosome 8p21.3–p22 in nine (40.9%) of 22 dysplastic nodules and in eight (42.1%) of 19 hepatocellular carcinomas. D8S261, located adjacent to PRLTS, showed most frequent LOH: 28.6% in dysplastic nodule and 40.0% in hepatocellular carcinoma. Loss of heterozygosity on chromosome 11p13 was found in three (15.8%) of 19 dysplastic nodules and in six (31.6%) of 19 hepatocellular carcinomas. Loss of heterozygosity of D11S995 and D11S907 was found in 33.3% and 7.1% of dysplastic nodules, and 8.3% and 44.4% of hepatocellular carcinomas, respectively. Conclusion: These results suggest that at least one putative tumor suppressor gene involved in the development and progression of hepatocellular carcinoma may be located on 8p21.3–p22 and 11p13. Particularly, PRLTS might be related to an early genetic event of hepatocarcinogenesis. © 2003 Blackwell Publishing Asia Pty Ltd

BACKGROUND: A new flow cytometric monocyte phagocytic assay (FMPA) was developed with 5-chloromethyl fluorescein diacetate (CMFDA)-labeled platelets for predicting the outcome of platelet transfusion. STUDY DESIGN AND METHODS: Twelve patients with a history of multiple platelet transfusions and 21 controls were enrolled in this study. Platelets labeled with CMFDA were incubated with patient serum and then incubated with monocytes. They were then analysed by flow cytometry. Monocytes that had phagocytized platelets (%) were detected as a CMFDA-positive platelet population with a CD14+ monocyte gate. The performance of FMPA was evaluated in 29 transfusions by 1- and 24-hour CCIs and platelet crossmatching. RESULTS: FMPA results were well correlated with 1-hour (r = −0.818, p = 0.001) and 24-hour (r = −0.782, p = 0.001) CCIs. In the group with high FMPA results (mean ± SD, 79.1 ± 7.3%), nine of 10 positive crossmatches revealed low CCIs, and six of seven negative crossmatches revealed high CCIs. The CCI predictability of crossmatching in the group with high FMPA results was high (88.2%). In the group with low FMPA results (mean ± SD, 34.6 ± 7.8%), all 12 transfusions revealed high CCIs even though in four transfusions there were positive results in both platelet antibody testing and platelet crossmatching. CONCLUSION: FMPA is designed with near in vivo conditions to measure an immune response to transfused platelets, including phagocytosis. This is a useful method for predicting the outcome of platelet transfusion.

In January 2009, a new classification of pathology services was been launched for the reimbursement by the National Health Insurance system in Korea. Five basic types of surgical pathology services are reclassified into 13 types and their resource based relative value scores are adjusted. In this report, we summarize the history of the classification system for the reimbursement on pathology services and report the impact of the change in January 2009 on the distribution of cases and contribution on the income of the department of pathology from each class at the Seoul National University Hospital.

Background: Even modern automatic cell counters cannot count basophils precisely. Therefore, we need a rapid, accurate, precise, and easy method for counting basophils. Methods: Using flow cytometry, basophils (CD22+/CD19-) and B cells (CD22+/CD19+) were counted. Within a large lymphocyte light scatter gate, % basophils (G%baso) and % B cells (G%B) were determined from the total count. Another method of analysis was to make two regions (R1 for basophils and R2 for B cells) and to determine in those the % basophils (R1%baso) and % B cells (R2%B) without gating. The flow cytometric basophil counts of the blood of 21 normal controls and 43 chronic myelogenous leukemia (CML) patients were compared with manual basophil count (Ma%baso) and basophil count by Coulter electronic cell counter (Hialeah, FL) (Auto%baso). CD22+/CD19- cells were sorted by a FACSCalibur (Becton Dickinson, San Jose, CA). Results: The G%baso of all samples was 4.66 ± 5.35%, and R1%baso was 4.23 ± 4.88%, and they were well-correlated (r = 0.996, P < 0.001). The G%B of all samples was 1.55 ± 1.68%, and R2%B was 1.59 ± 1.67%, and they were also well-correlated (r = 0.993, P < 0.001). Their correlation was better in normal controls than in CML. G%baso was well-correlated to Ma%baso (r = 0.827) and Auto%baso (r = 0.806), and R1%baso was well-correlated to Ma%baso (r = 0.831) but showed poor correlation to Auto%baso (r = 0.734). Auto%baso revealed the poorest correlation to Ma%baso (r = 0.692). The sorted CD22+/CD19- cells were all basophils (99.48 ± 0.30%), and they revealed CD13, CD33, and dim CD45 expression, whereas CD3, CD14, CD16, and HLA-DR were not detected on them. Conclusions: We discovered a specific marker combination to identify basophils (CD22+/CD19-), and we suggest that flow cytometric analysis using these markers is an easy, reliable, and accurate method of basophil counting. Cytometry 37:178–183, 1999. © 1999 Wiley-Liss, Inc.

Sclerosing lipogranuloma is a rare and subcutaneous granulomatous reaction, which is a local reactive process after injury to adipose tissue. 1,2 This benign which is a local reactive process after injury to adipose tissue. 1,2 This benign lesion has been reported to involve many different organs, 3,4 particularly those of the genitourinary system. 5,6 Although computed tomographic and magnetic resonance imaging findings of sclerosing lipogranuloma of the scrotum have been reported,7-9 only a few have described the sonographic features of the lesions. Because sonography is a primary modality in the evaluation of the scrotum, it is important to know the sonographic findings of this lesion to assist in narrowing the differential diagnosis of palpable scrotal masses. We report the sonographic appearance of sclerosing lipogranuloma of the scrotum.