In Sun Kim

Inflammatory myofibroblastic tumor of the larynx

Inflammatory myofibroblastic tumor, composed of myofibroblastic spindle cells with acute and chronic inflammatory cells, is an unusual, benign solid mass that mimics a neoplastic process.

Clinical outcome and predictive factors of recurrence among patients with Kikuchi's disease.

OBJECTIVES To evaluate the clinical outcome and predictive factors of recurrence among patients with Kikuchis disease. METHODS Between January 2001 and December 2006, all patients with Kikuchis disease were included in the study. Data were collected on co-morbidities, clinical manifestations, and ultrasound/laboratory findings, and the differences were compared between recurrent disease and non-recurrent disease groups. RESULTS The study included 102 patients with a mean age of 26.7 years. Among these patients, three developed systemic lupus erythematosus during the follow-up period, while two cases were later associated with tuberculosis. Eight patients (7.8%) experienced early relapse and 13 (12.7%) showed late recurrence. Patients with recurrent episodes were more likely to have fever and fatigue with extranodal involvement. Compared to the non-recurrent cases, recurrent cases remained symptomatic for a rather longer duration. The positive rate of the fluorescence anti-nuclear antibody (FANA) test was significantly higher in the recurrent disease group compared to the non-recurrent disease group. CONCLUSIONS Kikuchis disease took a self-limiting clinical course in most cases, but the recurrence rate found in the present study was higher than that of previous reports. Kikuchis disease might be a phenotype of diverse disease entities. The prognosis is different according to the underlying cause. The FANA test would be useful in predicting recurrence.

Treatment outcome of front-line systemic chemotherapy for localized extranodal NK/T cell lymphoma in nasal and upper aerodigestive tract

We analysed the treatment outcome of localized extranodal NK/T cell lymphoma initially treated with CEOP-B chemotherapy based on the primary site of involvement (nasal cavity vs. upper aerodigestive tract) and treatment modality (chemotherapy vs. chemotherapy followed by radiotherapy. Forty-three patients newly diagnosed as extranodal NK/T cell lymphoma were analysed: 29 cases from nasal cavity/nasopharynx and 14 from upper aerodigestive tract. Twenty-six patients were treated with chemotherapy alone, while adjuvant radiotherapy was given to 17 patients. Overall response rate to front-line CEOP-B chemotherapy was 67.4% (29/43) and the complete remission (CR) rate was 44.2% (19/43). Median overall and disease-free survival was 26.87 months [95% confidence interval (CI) = 8.71 - 45.03] and 15.27 months (95% CI = 2.92 - 27.62). The responders (CR or partial response) to initial CEOP-B chemotherapy showed longer overall survival than non-responders (P = 0.0026). Local relapse was observed to be higher in the chemotherapy alone group compared to the chemoradiotherapy group. Adjuvant radiotherapy failed to improve survival; thus, the median disease-free survival of the chemotherapy and chemoradiotherapy groups was not different (P = 0.9101). There may be a tendency for better overall survival in group of upper aerodigestive tract lymphoma than the nasal cavity/nasopharynx group (P = 0.0643). However, front-line CEOP-B chemotherapy has a limited role and adjuvant radiotherapy failed to improve survival in localized extranodal NK/T cell lymphoma.We analysed the treatment outcome of localized extranodal NK/T cell lymphoma initially treated with CEOP-B chemotherapy based on the primary site of involvement (nasal cavity vs. upper aerodigestive tract) and treatment modality (chemotherapy vs. chemotherapy followed by radiotherapy. Forty-three patients newly diagnosed as extranodal NK/T cell lymphoma were analysed: 29 cases from nasal cavity/nasopharynx and 14 from upper aerodigestive tract. Twenty-six patients were treated with chemotherapy alone, while adjuvant radiotherapy was given to 17 patients. Overall response rate to front-line CEOP-B chemotherapy was 67.4% (29/43) and the complete remission (CR) rate was 44.2% (19/43). Median overall and disease-free survival was 26.87 months [95% confidence interval (CI) = 8.71 – 45.03] and 15.27 months (95% CI = 2.92 – 27.62). The responders (CR or partial response) to initial CEOP-B chemotherapy showed longer overall survival than non-responders (P = 0.0026). Local relapse was observed to be higher in the chemotherapy alone group compared to the chemoradiotherapy group. Adjuvant radiotherapy failed to improve survival; thus, the median disease-free survival of the chemotherapy and chemoradiotherapy groups was not different (P = 0.9101). There may be a tendency for better overall survival in group of upper aerodigestive tract lymphoma than the nasal cavity/nasopharynx group (P = 0.0643). However, front-line CEOP-B chemotherapy has a limited role and adjuvant radiotherapy failed to improve survival in localized extranodal NK/T cell lymphoma.

Serum BAFF predicts prognosis better than APRIL in diffuse large B-cell lymphoma patients treated with rituximab plus CHOP chemotherapy

Objectives:  B‐cell activating factor of the tumor necrosis factor family (BAFF) and a proliferation‐inducing ligand (APRIL) regulate survival and proliferation of B cells. Thus the association of elevated serum levels of BAFF and APRIL with worse prognosis has been suggested in B‐cell lymphoid malignancies. However, the prognostic relevance of BAFF and APRIL is unknown in patients treated with rituximab, a monoclonal antibody targeting B‐cell depletion.

Increased Serum 90K and Galectin-3 Expression Are Associated with Advanced Stage and a Worse Prognosis in Diffuse Large B-Cell Lymphomas

The role of 90K and galectin-3 in cell-to-extracellular matrix adhesion and tumor metastasis has been reported, but little is known about their role in the prognosis and extranodal involvement of diffuse large B-cell lymphomas (DLBCL). Thus, we measured serum 90K concentration by enzyme-linked immunosorbent assay and tissue expression of galectin-3 by immunohistochemistry in newly diagnosed DLBCL patients. The mean serum 90K concentration was higher in DLBCL than in healthy controls (1,408.81 ± 89.45 vs. 980.94 ± 58.69 ng/ml, p = 0.036). High serum 90K (median value ≥1,249.50 ng/ml) and high galectin-3 expression (grade 3 positive staining in >75% of cells) showed a significant association with stage III/IV, ≥2 extranodal involvements and risk of high/high-intermediate international prognostic index (p < 0.05). The complete response (CR) rate (86.9%, 20/23) in the low 90K group was higher than in the high 90K group (56.5%, 13/23). Among 14 patients with high galectin-3 expression, only 6 patients showed CR (42.9%). The time to progression and overall survival were shorter in the group with high 90K and galectin-3 expression (p < 0.05). In conclusion, serum 90K and galectin-3 expression might be useful markers to indicate the extent of lymphoma involvement and prognosis in DLBCL.

NK/T-Cell Lymphoma Associated with Epstein-Barr Virus in a Patient Infected with Human Immunodeficiency Virus: An Autopsy Case

Natural killer (NK)/T-cell lymphoma associated with Epstein-Barr virus (EBV) in a patient infected with human immunodeficiency virus (HIV) is very rare. The authors encountered a case of NK/T-cell lymphoma in a 36-year-old man who presented with an ulcerative mass on both tonsils. During assessment, HIV positivity was noted. The EBV was detected by EBV-encoded RNA 1 messenger RNA in situ hybridization and polymerase chain reaction for EBV-encoded nuclear antigen 1. On immunohistochemical staining, the infiltrated lymphoid cells of the tonsils demonstrated positvity for CD3, CD56, UCHL1, and granzyme, a finding compatible with NK/T-cell lymphoma. The patient received radiation therapy and chemotherapy, but died as a result of opportunistic infection of invasive aspergillosis after tumor recurrence. An autopsy was done with the consent of the patient’s family. To our knowledge, this is the first case in an HIV patient of NK/T-cell lymphoma of the tonsils associated with EBV, confirmed by autopsy. NK/T-cell lymphoma should be considered in the HIV-positive patients with an ulcerating tonsillar mass. doi: 10.1532/IJH97.A10316

Cancer of the supernumerary ovary in Mayer‑Rokitansty‑Küster‑Hauser Syndrome: A case report

Mayer-Rokitansty-Küster-Hauser (MRKH) syndrome is a Müllerian anomaly that presents with varying degrees of uterovaginal aplasia and is secondarily associated with cervicothoracic, auditory and skeletal anomalies. However, MRKH syndrome patients have normal and functional ovaries. A supernumerary ovary is an extremely rare form of an ectopic ovary and there are no reported cases of MRKH syndrome with cancer of the supernumerary ovary in the current literature. A 31-year-old female with a history of MRKH syndrome that was diagnosed 4 years previously presented with abdominal pain and a suspected malignant pelvic mass was identified. During the staging surgery, both ovaries were separated from the main mass, observed and removed. A third ovary was discovered in the pelvic mass and the diagnosis of primary ovarian cancer from the third ovary was confirmed by immunohistochemistry. We report the first known case of cancer of the supernumerary ovary in a patient with MRKH syndrome. Although both ovaries were confirmed to be normal in the patient with MRKH syndrome, we propose that an ovarian neoplasm should be considered in the diagnosis of a pelvic mass.

Abstract 4895: Caveolin-1 modulates docetaxel activity by inducing p53 expression in breast cancer.

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Caveolin-1 is reported to be down-regulated in breast cancers compared with normal mammary tissue. More recent data showed that high caveolin-1 expression is more associated with basaloid cancers than ER and/or PR or HER-2 expressing cancers. Investigatirs have reported that Caveolin-1 promoted resistance to chemotherapy-induced apoptosis in Ewings sarcoma cells. However, the biologic relevance of caveolin-1 in breast cancer remains unclear. Thus, the aim of this study is to investigate its potential biologic relevance of Caveolin-1 to cell survival after docetaxel chemotherapy, one of the most important drug in breast cancer treatment. In this current study, we first showed that Caveolin-1 protein expression was suppressed in the ER(+) human breast cancer cell lines (MCF-7, T47D, and ZR75-1), but not in triple negative cancer cells (MDA-MB-231 and HS578T) and one of the HER-2 type cell (HCC1954) using Western blot analysis. Better cytotoxic effect of docetaxel was observed in the caveolin-1-expressing triple negative cells and HER-2 type cell than the other caveolin-1-deficient HER-2 type and luminal type of cancer cells. Next, caveolin-1 gene was reintroduced into caveolin-1 deficient luminal type breast cancer cells (MCF-7 and ZR75-1) to investigate its potential modulatory effect on docetaxel-induced cytotoxicity. The cell proliferation and MTT assay showed that the overexpressed caveolin-1 had further modulated docetaxel-induced anti-proliferative and cytotoxic effect in the luminal type cells. The anti-proliferative effect of docetaxel in the caveolin-1 gene over-expressed breast cancer cell lines was accompanied by decreasing cyclin D1 expression and inducing cyclin B1 accumulation, then resulting in cell cycle arrest at G2/M phase in the FACS analysis. In addition, re-introduction of caveolin-1 further increased docetaxel-induced cell death by synergistically inducing p53 expression and subsequent induction of p21, then finally apoptosis of breast cancer cells. These results were verified in the mouse model using SCID mice implated with either Caveolin-1-MCF-7 cells or control MCF-7 cells. When each group of tumor-bearing mice were treated by docetacel, mice with Caveolin-1-MCF-7 tumors showed a signiflcantly smaller tumors than those of control group. These results suggest that caveolin-1 may have a modulating factor for docetaxel activity by inducing p53 expression in breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4895. doi:1538-7445.AM2012-4895

Leukemia cutis in a patient with acute monocytic leukemia diagnosed simultaneously with hepatocellular carcinoma: A case study

Acute myeloid leukemia presenting as leukemia cutis (LC) with hepatocellular carcinoma is extremely rare. The current study presents a case of a 53-year-old male with generalized cutaneous nodules on the face and anterior chest wall. Laboratory tests, including bone marrow biopsy revealed acute myelomonocytic leukemia (AML-M4) with skin and tonsilar involvement. Liver magnetic resonance imaging (MRI) revealed a 6-cm mass in hepatic segments 4 and 8, and a liver biopsy demonstrated that hepatocellular carcinoma cells and immature blast cells coexisted. Although LC has been reported in Korea, a case of LC associated with acute myelomonocytic leukemia was diagnosed simultaneously with hepatocellular carcinoma and tonsillar involvement. The present study describes this case with a review of the literature.

Abstract 4925: Promoter methylation of RASSF1A Tumor Suppressor Gene Modulates the Effect of Microtubule-Targeting Agent, docetaxl, in Breast Cancer

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC RASSF1A has been previously demonstrated to be inactivated by CpG island methylation in breast cancer cell lines and primary tumor tissues. There have been evidences suggesting that methylation of this gene have a significant impact on biological characteristics of breast tumors and have a relationship with prognosis in breast cancer. The tumor suppressive effect of RASSF1A has been reported to be mediated by its 2 important roles in other cells; induction of cell cycle arrest and apoptosis. Therefore, it is possible that expression status of RASSF1A by promoter methylation may alter patients sensitivity to chemotherapeutic agents affecting cell cycle. However, there is few data regarding the relationship between the methylation status of RASSF1A gene and clinical response to chemotherapeutic agents in breast cancer patients. In this current study, we show that RASSF1A gene expression was suppressed in the human breast cancer cell lines (MCF-7, MDA-MB-231, and ZR75-1) by the mechanism of promoter methylation using methylation -specific PCR. It was confirmed by the results that treatment with the DNA demethylating agent, 5-aza-2′-deoxycytidine, reactivated the expression of RASSF1A at the level of mRNA and protein. Re-expression of RASSF1A gene in breast cancer cell lines could decrease the cell growth and proliferation by both decreasing cyclin D1 expression and inducing cyclin A and B1 accumulation, then resulting in cell cycle arrest at G2/M phase. In addition, re-introduction of RASSF1A further increased docetaxel-induced cell death in breast cancer cells. We next questioned whether the methylation status of RASSF1A gene is associated with clinical response to taxane-based chemotherapy in breast cancer patients. Fresh frozen primary breast cancer tissues were ananlyzed for methylation status of RASSF1A gene using MS-PCR. Thirty three out of 39 patients (84.6%) showed RASSF1A methylation and 6 had un-methylated gene. Patients who had unmethylated or partially methylated RASSF1A gene showed some mRNA in RT-PCR analysis. And, the clinical response to taxane-based chemotherapy was significantly better in the un-, or partially-methylated patient group (100% vs 62.5%). These results suggest that hypermethylation of the CpG island promoter of RASSF1A may play an important role in breast cancer pathogenesis and is a modulating factor for docetaxel activity in breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4925.