Dae Hyun Song

Is inactivation of O6-methylguanine DNA methyltransferase still a favorable prognostic factor of patients with diffuse large B-cell lymphoma in the era of R-CHOP chemotherapy?

The prognostic significance of O6-methylguanine DNA methyltransferase (MGMT) inactivation was evaluated in patients with diffuse large B-cell lymphoma (DLBCL) who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in addition to rituximab. In this retrospective study, we used the methylation-specific polymerase chain reaction to investigate MGMT promoter methylation status and immunohistochemistry to evaluate MGMT expression in patients with DLBCL who received rituximab plus CHOP (R-CHOP) chemotherapy. No difference in patient characteristics, disease characteristics, response, or survival in patients with DLBCL who received front-line R-CHOP chemotherapy was observed according to MGMT methylation status and MGMT expression. On multivariate analysis, Grade 3–4 mucositis in the MGMT methylated group was significantly higher than that in the MGMT unmethylated group (hazard ratio (HR) 2.40, 95% CIs: 1.26–7.26, p = 0.014). This study demonstrated that inactivation of MGMT does not appear to play an important role in patients with DLBCL who received R-CHOP chemotherapy either with regard to the response rate or overall survival. Additionally, Grade 3–4 mucositis was found to be significantly related with inactivation of MGMT by a multivariate analysis.

Osteoclast-like Giant Cell Tumor of Parotid Gland with a Carcinomatous Component: A Case Report

The giant cell tumor of the salivary gland is very rare, and 20 cases have been reported in the English-language literature. We report an additional case. A 57-year old man had noticed a mass in the right parotid area for several weeks. The diagnosis using aspiration cytology was a giant cell tumor possibly with a carcinomatous component. Superficial parotidectomy was carried out. The resected parotid gland contained a 1.8 cm-sized well-circumscribed brownish tumor. Histologically the tumor consisted of evenly distributed osteoclast-like giant cells, mononuclear cells and two small foci of a carcinomatous component. The osteoclast-like giant cells and mononuclear cells were positive for vimentin and CD68, and the carcinomatous component was positive for cytokeratin and epithelial membrane antigen. There was no metastatic lesion in the cervical lymph nodes. We believe this is the first case in Korea of an osteoclast-like giant cell tumor of the parotid gland.

Programmed Death-Ligand 1 Expression and Its Correlation with Lymph Node Metastasis in Papillary Thyroid Carcinoma

Background The immunotherapeutic role of programmed death-ligand 1 (PD-L1) in life expectancy in many cancers has been highlighted. However, data regarding PD-L1 expression in papillary thyroid carcinoma (PTC) are limited. In this study, we describe the PD-L1 and programmed cell death protein 1 (PD-1) expressions in PTC and analyze their correlation with lymph node (LN) metastasis. Methods Clinicopathological data were obtained from 116 patients with PTC who were treated in Gyeongsang National University Hospital, Jinju, Korea in 2009. Tissue microarray blocks were made using representative paraffin blocks of classical PTCs excluding follicular variants. Two pathologists graded the proportion and intensity of PD-L1 and PD-1 expression in both tumor and inflammatory cells. According to their proportions, positive PTC cells were scored as negative (0%), grade 1 (1%–50%), and grade 2 (51%–100%). Similarly, positive inflammatory cells were graded as negative (0%), grade 1 (1%–10%), and grade 2 (11%–20%). The intensity of each protein expression was simplified as positive or negative. Results A statistically significant correlation exists between the proportions of PD-1 and PD-L1 expression both in papillary carcinoma (p=.001) and peritumoral lymphoid cells in the thyroid (p<.001). In addition, the proportion of PD-L1 expression in PTC cells was closely related to metastatic LNs (p=.036). Conclusions PD-L1 is a valuable predictive marker for LN metastasis in PTC. Immunomodulating therapies that inhibit PD-L1 might be an option for patients with LN metastasis.

Myoferlin expression in non-small cell lung cancer: Prognostic role and correlation with VEGFR-2 expression

Myoferlin is a protein that is associated with cellular repair following injury. The expression of myoferlin in breast cancer and pancreatic adenocarcinoma has been reported to correlate with tumor invasiveness, epithelial to mesenchymal transition and an adverse prognosis. In the present study, myoferlin expression was investigated in non-small cell lung carcinoma (NSCLC), along with its association with patient prognosis and the expression of a number of other proteins. A total of 148 patients exhibiting NSCLC were enrolled in the present study. The survival data of all patients was examined, and myoferlin, vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor, E-cadherin, β-catenin, thyroid transcription factor-1 and tumor protein p63 expression was investigated via immunohistochemical staining of tissue microarrays. Myoferlin expression was detected in the cytoplasm of 75/148 (50.7%) of the NSCLC cases. In the adenocarcinoma cases, myoferlin-positive patients possessed a poorer prognosis (odds ratio, 2.94; P=0.339). In the squamous cell carcinoma cases, myoferlin expression was significantly associated with VEGFR-2 expression (P=0.001). Immunohistochemical staining for VEGFR-2 and myoferlin expression indicated similar features and cytoplasmic staining in tumor cells. As VEGFR-2 is a significant target for novel anticancer therapies, it is anticipated that myoferlin may also possess the potential to become a novel clinical target for the treatment of NSCLC.

Dedifferentiated Solitary Fibrous Tumor of Thoracic Cavity

Solitary fibrous tumor (SFT) is a mesenchymal tumor characterized by fibroblast-like tumor cells, thick collagen bands, a hemangiopericytoma-like branching vascular pattern and CD34 expression of tumor cells.1 Although some cases show malignant behavior, most of the cases are benign and have histologically bland-looking tumor cells. Rarely, highly pleomorphic sarcoma arises within a primary or recurrent SFT having typical histologic features. This is a phenomenon similar to that seen in dedifferentiated liposarcoma. Dedifferentiated SFT (DSFT) is rare, with less than 30 cases reported worldwide,2,3,4,5,6 and it has not been previously reported in Korea. Here, we present a case of DSFT.

Myoferlin Expression and Its Correlation with FIGO Histologic Grading in Early-Stage Endometrioid Carcinoma

Background For endometrioid carcinoma patients, International Federation of Gynecologists and Obstetricians (FIGO) histologic grading is very important for identifying the appropriate treatment method. However, the interobserver discrepancy with this three-tiered grading system is a serious potential problem. In this study, we used immunohistochemistry to analyze the relationship between FIGO histologic grading score and myoferlin expression. Methods We studied the endometrioid carcinoma tissues of 60 patients from Gyeongsang National University Hospital between January 2002 and December 2009. Immunohistochemical analysis of myoferlin was performed on tissue microarray blocks from surgical specimens. Results Myoferlin expression was observed in 58 of 60 patients. Moderate and strong myoferlin expression was observed in low-grade endometrioid carcinoma, while there was a tendency toward loss of myoferlin expression in high-grade endometrioid carcinoma (p<.001). Conclusions Our study revealed that myoferlin loss is significantly correlated with high FIGO grade of endometrioid carcinoma.

Prognostic role of myoferlin expression in patients with clear cell renal cell carcinoma

Objectives In patients with cancer, myoferlin protein hyperexpression has been correlated with poor patient prognosis. Here, we evaluated myoferlin expression in patients with clear cell renal cell carcinoma (ccRCC) and investigated the prognostic significance of myoferlin expression in these patients. Materials and Methods One hundred and fifty-two patients with ccRCC who underwent treatment at Gyeongsang National University Hospital, Korea, between January 2000 and December 2009 were enrolled. Immunohistochemical analysis was performed on tissue microarray blocks produced from surgical specimens. Surgical specimen cancerous cells were graded as showing myoferlin hyperexpression or hypoexpression by comparison with intratumoral endothelial cells. Disease-free survival was evaluated using Kaplan-Meier analysis. Cox regression analysis was used to determine the relationships between myoferlin expression levels, risk factors, and prognosis. Results Seventy-one of 304 cores exhibited myoferlin hyperexpression. T stage was not associated with myoferlin hyperexpression, whereas a high Fuhrman nuclear grade was significantly associated with myoferlin hyperexpression. Kaplan-Meier analysis revealed that patients with T stage >2, Fuhrman nuclear grade >2, and those with myoferlin hyperexpression had poorer disease-free survival compared to those with lower T stage, lower Fuhrman nuclear grade, and myoferlin hypoexpression (all p <0.001). Furthermore, myoferlin hyperexpression was significantly associated with disease-free survival on Cox regression analysis (hazard ratio, 4.604; 95% confidence interval, 1.893–11.199; p = 0.001). Conclusion Myoferlin expression could be a potential prognosticator in patients with ccRCC, and might be a useful marker for oncologic surveillance in such patients.

Thymoma and Synchronous Primary Mediastinal Seminomas with Florid Follicular Lymphoid Hyperplasia in the Anterior Mediastinum: A Case Report and Review of the Literature

Thymoma is the most common neoplasm of the anterior mediastinum and has malignant potential. Germ cell tumors (GCTs) found in the anterior mediastinum are usually benign, and malignant GCTs, such as seminomas, are rare. Histologically, mediastinal seminoma is indistinguishable from testicular seminoma except for site-associated morphological features such as lymphoid follicular hyperplasia. Therefore, excluding metastasis is very important. Recently, we treated a young adult patient with multiple thymic masses that occurred simultaneously. The patient underwent a thymectomy for the removal of the mediastinal masses, one of which was diagnosed as type B2 invasive thymoma, and two of which were diagnosed as primary mediastinal seminomas with massive follicular hyperplasia. The patient received adjuvant chemotherapy after surgical resection. To our knowledge, this is the first description of a thymoma and a mediastinal seminoma occurring simultaneously in the thymus. We present this case along with a literature review.

Fine-Needle Aspiration Cytology of Carcinosarcoma in the Salivary Gland: An Extremely Rare Case Report

Carcinosarcoma of the salivary gland is an extremely rare tumor that is composed of both malignant epithelial and mesenchymal components. Diagnosing carcinosarcoma with fine-needle aspiration cytology is challenging because of its overlapping cytomorphologic characteristics with other high-grade malignant salivary gland tumors. Among the many features, including pleomorphic oncocytoid epithelial components, necrotic background, and mitoses, recognizing the singly scattered atypical spindle cells is most essential in carcinosarcoma. We present a case of a 66-year-old male patient with characteristic features of carcinosarcoma, who was successfully treated by wide local excision and subsequent radiation therapy.

Detection of Human Papillomavirus Type 39 in a Seborrheic Inclusion Cyst of the Buttock

A seborrheic inclusion cyst (SIC) is a lesion, which has been described as a combination of seborrheic keratosis and an epidermoid cyst (EC). To the best of our knowledge, only eight cases of SIC have been reported thus far in the English literature[1-3]. Microscopically, SICs exhibit features that are suggestive of viral infection[4]. Therefore, an association between SICs and human papillomavirus (HPV) has been suspected, but it has only been demonstrated in one previous report by Terada,[1] which identified an HPV-positive SIC through immunohistochemical staining for HPV antigens. However, no SIC study has ever used HPV genotyping. Herein, we report the first case of SIC associated with HPV type 39, which we identified using the HPV DNA chip.