Predictive Value of Interim and End-of-Therapy 18F-FDG PET/CT in Patients with Follicular Lymphoma / 대한핵의학회잡지

PURPOSE: ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging modality for response evaluation in FDG-avid lymphoma, but the prognostic value is not established in follicular lymphoma (FL). This study investigated the prognostic value of Deauville 5-point scale (D5PS) from paired interim PET/CT (PET(Interim)) and end-of-induction therapy PET/CT (PET(EOI)) in patients with FL.METHODS: FL staging and response assessment PET/CT images from 2013 to 2015 were retrospectively reviewed. PET(Interim) was performed 3 or 4 cycles after chemotherapy and PET(EOI) after 6 or 8 cycles. D5PS scores of 1, 2, and 3 were considered as negative (−), and scores 4 and 5 were considered as positive (+). Statistical analysis was done using Cox regression analysis, Kaplan-Meier survival analysis, and the log-rank test.RESULTS: Thirty-three patients with set of baseline, interim, and end-of-induction therapy PET/CTstudies were included. Ten patients (30.3%) had progression. The median progression-free survival (PFS) was 38.8 months (range 3.5–72.7 months). On PET(Interim), 23 patients were negative and 10 were positive. On PET(EOI) scans, 29 patients were negative, and 4 were positive. On multivariate analysis, PET(EOI)(−) was associated with longer PFS. PET(Interim)(+) and PET(EOI)(+) patients had a significantly shorter PFS than PET(Interim)(−) patients (39.9 months, 95%confidence interval [CI] 23.0–56.9, versus 55.5months, 95%CI 49.7–61.2, p=0.005) and PET(EOI)(−) patients (14.2 months, 95% CI 8.5–19.8, versus 60.5 months, 95% CI 52.1–69.0, p<0.001).CONCLUSION: For patients with FL, PET(Interim) and PET(EOI) response is predictive of PFS, and PET(EOI)(+) is an independent prognostic factor for progression of FL.

Predictive Value of Interim and End-of-Therapy 18F-FDG PET/CT in Patients with Follicular Lymphoma / 대한핵의학회잡지

PURPOSE@#¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging modality for response evaluation in FDG-avid lymphoma, but the prognostic value is not established in follicular lymphoma (FL). This study investigated the prognostic value of Deauville 5-point scale (D5PS) from paired interim PET/CT (PET(Interim)) and end-of-induction therapy PET/CT (PET(EOI)) in patients with FL.@*METHODS@#FL staging and response assessment PET/CT images from 2013 to 2015 were retrospectively reviewed. PET(Interim) was performed 3 or 4 cycles after chemotherapy and PET(EOI) after 6 or 8 cycles. D5PS scores of 1, 2, and 3 were considered as negative (−), and scores 4 and 5 were considered as positive (+). Statistical analysis was done using Cox regression analysis, Kaplan-Meier survival analysis, and the log-rank test.@*RESULTS@#Thirty-three patients with set of baseline, interim, and end-of-induction therapy PET/CTstudies were included. Ten patients (30.3%) had progression. The median progression-free survival (PFS) was 38.8 months (range 3.5–72.7 months). On PET(Interim), 23 patients were negative and 10 were positive. On PET(EOI) scans, 29 patients were negative, and 4 were positive. On multivariate analysis, PET(EOI)(−) was associated with longer PFS. PET(Interim)(+) and PET(EOI)(+) patients had a significantly shorter PFS than PET(Interim)(−) patients (39.9 months, 95%confidence interval [CI] 23.0–56.9, versus 55.5months, 95%CI 49.7–61.2, p=0.005) and PET(EOI)(−) patients (14.2 months, 95% CI 8.5–19.8, versus 60.5 months, 95% CI 52.1–69.0, p<0.001).@*CONCLUSION@#For patients with FL, PET(Interim) and PET(EOI) response is predictive of PFS, and PET(EOI)(+) is an independent prognostic factor for progression of FL.

Squamous Cell Carcinoma Derived from Bowenoid Papulosis of the Vulva / 대한피부과학회지

No abstract available.

Analysis of treatment outcomes for primary tonsillar lymphoma

PURPOSE: Although each Waldeyer’s ring sub-site is considered an independent prognostic factor, few studies have assessed the prognosis and treatment of tonsillar lymphoma. Treatment outcomes were analyzed in patients with primary tonsillar lymphoma who were treated with chemotherapy and radiotherapy (RT). MATERIALS AND METHODS: Nineteen patients with diffuse large B-cell lymphoma were evaluated, with a median follow-up of 53 months. Age, sex, and histology, amongst other factors, were reviewed. Progression-free survival (PFS) and overall survival (OS) rates were analyzed. RESULTS: Most patients had Ann Arbor stage I-II (94.7%), IPI score of 0 (89.5%), and complete remission after chemotherapy (89.5%). The 5-year PFS and OS rates were 74.6% and 80%, respectively. In univariate analysis, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen resulted in a better PFS than the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen (88.9% vs. 50.0%; p = 0.053). RT dose was related to the survival outcome (p = 0.010 for PFS, p = 0.044 for OS). Patients were classified into the CHOP + RT (>40 Gy) group and R-CHOP + RT (≤40 Gy) group. The 5-year PFS rates were 50% in the CHOP + RT group, and 100 % in the R-CHOP + RT group (p = 0.018). The 5-year OS rates were 66.7% and 100%, respectively (p = 0.087). CONCLUSION: Primary tonsillar lymphoma patients typically have favorable outcomes. Chemotherapy (R-CHOP) combined with relatively lower dose consolidative RT may be safe and effective for primary tonsillar lymphoma.

An Unusual Presentation of Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma as Diffuse Pulmonary Infiltrates with Spontaneous Regression / Journal of the Korean Cancer Association, 대한암학회지

A 57-year-old woman presented with cough and dyspnea for 2 months. Computed tomography of the chest showed diffuse ground-glass opacities in both lungs. Histologic examination via thoracoscopic lung biopsy revealed atypical lymphoproliferative lesion. Her symptoms and radiologic findings of the chest improved just after lung biopsy without any treatment. Therefore, she was discharged and monitored at an outpatient clinic. Two months later, pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma was confirmed by the detection of API2-MALT1 translocation in fluorescent in situ hybridization analysis. Although the lung lesions resolved spontaneously, she received chemotherapy due to bone marrow involvement in her staging workup. Pulmonary MALT lymphoma is rare. Nodular or consolidative patterns are the most frequent radiologic findings. Although the disease has an indolent growth, it rarely resolves without treatment. We report an unusual case of pulmonary MALT lymphoma with diffuse interstitial abnormalities on image and spontaneous regression on clinical course.

Classic Papillary Thyroid Carcinoma with Tall Cell Features and Tall Cell Variant Have Similar Clinicopathologic Features

BACKGROUND: The tall cell variant of papillary thyroid carcinoma (TCVPTC) is more aggressive than classic papillary thyroid carcinoma (PTC), but the percentage of tall cells needed to diagnose TCVPTC remains controversial. In addition, little is known about the clinicopathologic features of classic PTC with tall cell features (TCF). METHODS: We retrospectively selected and reviewed the clinicopathologic features and presence of the BRAF mutation in 203 cases of classic PTC, 149 cases of classic PTC with TCF, and 95 cases of TCVPTCs, which were defined as PTCs having or =50% tall cells, respectively. RESULTS: TCVPTCs and classic PTCs with TCF did not vary significantly in clinicopathologic characteristics such as pathologic (p) T stage, extrathyroidal extension, pN stage, lateral lymph node metastasis, or BRAF mutations; however, these features differed significantly in TCVPTCs and classic PTCs with TCF in comparison to classic PTCs. Similar results were obtained in a subanalysis of patients with microcarcinomas (< or =1.0 cm in size). CONCLUSIONS: Classic PTCs with TCF showed a similar BRAF mutation rate and clinicopathologic features to TCVPTCs, but more aggressive characteristics than classic PTCs.

Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients

The most common BRAF mutation in thyroid cancer is c.1799T>A (p.Val600Glu), and other BRAF mutations are rarely reported. We investigated the clinicopathological features of thyroid cancer with rare BRAF mutations. A total of 2,763 patients with thyroid cancer underwent molecular testing by direct DNA sequencing for mutations in BRAF exon 15. Among them, 2,110 (76.4%) had BRAF mutations. The c.1799T>A mutation was found in 2,093 (76.9%) of 2,722 papillary carcinomas and in one of 7 medullary carcinomas. Sixteen cases (0.76%) harbored rare mutation types. Five cases had single-nucleotide substitutions, 5 cases had small in-frame deletion or insertion, and one harbored a two-nucleotide substitution. Of these mutations, 2 were novel (c.1797_1798insGAGACTACA, c.[1799T>A; 1801_1812del]). The c.1801A>C mutation was identified in 4 follicular variant papillary carcinomas and one follicular carcinoma. None of the patients with the c.1801A>C mutation showed extrathyroidal extension or lymph node metastasis. The prevalence of rare BRAF mutations was 0.76% of all BRAF-positive thyroid cancers, and the rare mutations were associated with less aggressive pathologic features. Although BRAF mutations are detected exclusively in papillary carcinoma, they are also found in medullary carcinoma and follicular carcinoma.

Erratum: Correction of Nomenclature of BRAF Mutation

We made a mistake in our recently published article.

Langerhans Cell Sarcoma in Two Young Children: Imaging Findings on Initial Presentation and Recurrence

Langerhans cell sarcoma (LCS) is a neoplastic proliferation of Langerhans cells with malignant cytological features and multi-organ involvement that typically has a poor prognosis. We experienced 2 cases of LCS in children less than 2 years of age and report them based primarily on CT and MR findings. Both children had findings of hepatosplenomegaly with low-attenuation nodular lesions, had multiple lymphadenopathy, and had shown recurrent lesions invading the skull during follow-up after chemotherapy.

Two Cases of Gastric MALT Lymphoma Diagnosed at Long Last after Successful Eradication of Helicobacter pylori

The gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a rare disease. Helicobacter pylori infection is known as an important etiologic factor of the pathogenesis of MALT lymphoma. H. pylori colonization at the epithelium of gastric mucosa induces T cell and B cell recruitment. T cell induced B cell proliferation develops the MALT in the gastric mucosa. Monoclonal proliferation of B cell in the MALT transform into MALT lymphoma. The eradication of H. pylori is known to induce remission of the disease in more than 80% of patients. But there is no report on progression and development of MALT lymphoma after H. pylori eradication. We experienced two cases of gastric B cell MALT lymphoma diagnosed at long last, after the successful eradication of H. pylori.

Two Cases of Gastric MALT Lymphoma Diagnosed at Long Last after Successful Eradication of Helicobacter pylori

The gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a rare disease. Helicobacter pylori infection is known as an important etiologic factor of the pathogenesis of MALT lymphoma. H. pylori colonization at the epithelium of gastric mucosa induces T cell and B cell recruitment. T cell induced B cell proliferation develops the MALT in the gastric mucosa. Monoclonal proliferation of B cell in the MALT transform into MALT lymphoma. The eradication of H. pylori is known to induce remission of the disease in more than 80% of patients. But there is no report on progression and development of MALT lymphoma after H. pylori eradication. We experienced two cases of gastric B cell MALT lymphoma diagnosed at long last, after the successful eradication of H. pylori.

Prevalence and Genotype Distribution of Cervical Human Papillomavirus DNA in Korean Women: A Multicenter Study

Background: DNA prevalence and type distribution of human papillomavirus (HPV) varies geographically. We investigated HPV prevalence and type distribution in Korean women using the MyHPV DNA chip testing. Methods: A total of 2,368 women from five regions of the country underwent Pap smear examination and MyHPV chip testing. Results: Overall HPV positivity was 15.8% and 78.4% in women with normal and abnormal cytology, respectively. High-risk HPV infection was strongly correlated with cytological atypia. In women with abnormal cytology, the five most common HPV types were 16, 58, 18, 52, and 56/53, and HPV16 was significantly the most common type in most geographical regions. After HPV16, HPV58, and 52 were the next most frequently detected types. Women with normal cytology, in contrast, showed heterogeneity in HPV type distribution. High-grade intraepithelial lesions infected with HPV16, 18, 31 or 45 are more likely to progress to carcinoma. Conclusions: The HPV chip test can provide useful data regarding HPV positivity and type. The most common HPV type in Korean women with abnormal cytology is HPV16, with HPV58 and 52 being frequently present. Our data may have important implications for vaccination programs and the development of cervical screening.

A Case of Primary B-cell Lymphoblastic Lymphoma of the Orbit in a Pediatric Patient

PURPOSE: We report a case of orbital B-cell lymphoblastic lymphoma in a 7-year-old boy. METHODS: A 7-year-old boy presented with proptosis and periorbital swelling of his left eye following a periorbital blunt trauma 1-month prior. During the course of routine ophthalmologic and radiologic examinatinos, the swelling spontaneously subsided without specific treatment. An outpatient follow-up was planned, but the swelling recurred 6 months later. An orbital CT and MRI showed an irregular mass with an indistinct margin in the left orbit, for which an incisional biopsy was performed. RESULTS: The orbital mass consisited of monotonous small to medium sized lymphoid cells with evenly dispersed open chromatin, thin nuclear membrane and inconspicuous nucleoli. Immunohistochemistry revealed that the cells were positive for CD79a and TdT, but negative for CD3 and CD5. These findings were compatible with a diagnosis of B cell lymphoblastic lymphoma. CONCLUSIONS: Lymphoblastic lymphoma of the orbit should be suspected and considered in the differential diagnosis for children with acutely progressing orbital mass.

Touch Imprint Cytology Contributed to the Frozen Section Diagnosis of Merkel Cell Carcinoma : A Case Report / 대한세포병리학회지

Merkel cell carcinoma (MCC), a rare primary cutaneous small cell neuroendocrine carcinoma, is a tumor with distinct cytological features. In many cases, immunohistochemical staining (IHC) is required for the differentiation from other small round cell malignancies. Here we describe the cytological findings of Merkel cell carcinoma; these findings contributed to the diagnosis prior to performing IHC. A lower eyelid mass was excised and submitted for frozen section diagnosis. The frozen section diagnosis was consistent with a malignancy, but the more specific diagnosis was limited by the lack of specific histological features. Touch imprint cytology revealed a high cellularity with loosely cohesive small to large sized cells. The tumor cells showed hyperchromatic nuclei with fine chromatin and inconspicuous nucleoli, and thin-rimmed-cytoplasm including the characteristic eosinophilic button-like paranuclear inclusion, previously described as a pathognomonic cytological finding of MCC; this was not found in the H&E frozen section. In conclusion, we suggest that the touch imprint cytology may help in the differential diagnosis of small round cell neoplasms prior to performing IHC especially in frozen section diagnosis.

Comparative Analysis of Immunohistochemical Features in Basal Cell Carcinoma Subtypes / 대한피부과학회지

BACKGROUND: There has been no general agreement in classifying basal cell carcinoma (BCC), and little is known about the immunohistochemical profiles in each subtypes of BCC. BCC is a locally-invasive tumor, but its aggressive forms tend to recur and metastasize. OBJECTIVE: In this study, we have compared the histolopathological subtypes of BCC by immunohistochemical study. We also focused on identifying representative markers of growth in the aggressive forms of BCC by assessing VEGF, p53 and alpha-SMA expression. METHODS: A total of 87 BCC specimens were collected at the 7 branch hospitals of The Catholic University of Korea from July 1997 to June 2003. For multiple immunohistochemical staining, a tissue microarray technique was used. The 87 samples were divided into 6 subtypes: 18 nodular, 19 nodular infiltrative, 12 micronodular, 14 infiltrative, 11 morphea and 13 basosquamous. Overall, 18 samples were classified as non-aggressive and the remaining 69 as aggressive. RESULTS: The following results were obtained after immunohistochemical staining with antibodies alpha-SMA, VEGF and p53. A significant increase of alpha-SMA expression was observed in aggressive forms of BCC, whereas the expression of p53, VEGF, the number of mast cells remained the same. The representative markers of tumor growth such as alpha-SMA were most highly expressed in the basosquamous type, and least expressed in the micronodular type compared to the nodular type. CONCLUSION: alpha-SMA was considered as an appropriate immunohistochemical marker in BCC to represent aggressiveness.

Effect of Hyperbaric Oxygen on Intercellular Adhesion Molecule-1 Expression in Rat Kidney / 항공우주의학회지

BACKGROUND: Although hyperbaric oxygen (HBO) -100% oxygen at two to three times the atmospheric pressure at sea level-has a number of beneficial biochemical, cellular, and physiologic effects, it is intrinsically associated with the potential for producing mild to severe toxic effects. The contribution of the cellular adhesion molecules and macrophages in the renal oxygen toxicity is not well understood. Thus, we have investigated the toxic effect of HBO expressed by the analysis of intercellular adhesion molecule-1 (ICAM-1) and infiltration of macrophages in rat kidney. METHODS: Male Sprague-Dawley rats weighing about 250 g were exposed to HBO at 3 ATA of 100% O2 for 4 hours. The expression of ICAM-1 and infiltration of CD68-positive macrophages were serially observed by immunohistochemical analysis. RESULTS: At 3 days after HBO exposure, CD68-positive macrophage counts were increased in glomeruli and tubulointerstitium of kidney. The expression of ICAM-1 was enhanced 1 day after HBO exposure and increased more for 3 days. There was a significant correlation between ICAM-1 expression and macrophage accumulation in the glomeruli. At 7 days after HBO, those alterations recovered to normal status. CONCLUSION: The 4-hour HBO exposure induced ICAM-1 expression and macrophage accumulation in the kidney and these change lasted for 3 days. Therefore, sustained activation of macrophages in renal oxygen toxicity may occur after prolonged (more than 4 hours) or repetitive exposures to HBO.

The Efficacy of 38 mg Low Dose Capsule-Based 13C-urea Breath Test for the Diagnosis of Helicobacter pylori Infection / 대한소화기내시경학회지

BACKGROUND/AIMS: Urea breath test (UBT), the noninvasive test for diagnosing Helicobacter pylori infection, was developed in 1987 and had advanced in accuracy and convenience by improvement of analytic device, 13C or 14C urea regimen, expiration sampling protocol and test meal. However, conventional UBT using 75 mg or 100 mg of 13C-urea is expensive and time consuming. The objective of this study was to evaluate the diagnostic performance of UBT using capsulated 38 mg low dose 13C-urea (HeliFinder(R)) developed by Medichems Co., Ltd. METHODS: A total of one hundred forty seven volunteers were enrolled and examined at Catholic University, Korea University, and Soon Chun Hyang University hospital. UBT was performed using 38 mg 13C urea capsule and compared with the gold standard methods (rapid urease test and histology). Baseline and 20 min breath samples were collected. We used delta13C 2.0permile as the cut-off value suggested by the manufacturer. RESULTS: Of the 147 subjects, 142 cases were available for analysis. The sensitivity and specificity of UBT using the 38 mg 13C urea capsule at 20 min were 98.7% and 100% respectively. CONCLUSIONS: A 20 min, 38 mg capsule based 13C urea breath test protocol is more efficient, cost effective, and convenient than conventional protocol.

Loss of Heterozygosity on Chromosomes 3p,8p,9p and 17p in the Progression of Squamous Cell Carcinoma of the Larynx

Previous molecular genetic studies of laryngeal squamous cell carcinoma (SCC)have shown certain chromosomal regions with recurring alterations. But studies of sequential molecular alterations and genetic progression model of laryngeal SCC have not been clearly defined. To identify the chromosomal alterations associated with the carcinogenesis of laryngeal SCC, we analyzed genomic DNA from microdissected squamous metaplasia, squamous dysplasia, invasive SCC, and metastatic carcinoma samples from 22 laryngeal SCC patients for loss of heterozygosity (LOH) at microsatellite loci. Ten microsatellite markers on chromosome 3p, 8p, 9p, and 17p were used. LOH at 9p21 was observed in the all stages including squamous metaplasia, squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 17p13.1, 3p25 and 3p14.2 was observed from the squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 8p21.3-p22 was observed mainly from the invasive SCC and metastatic carcinoma. The results suggest that 9p21 in the early event, 17p13.1, 3p25 and 3p14.2 in the intermediate event and 8p21.3- p22 in the late event may be involved in the laryngeal carcinogenesis.

Analysis of c-kit Mutation of Gastrointestinal Stromal Tumors

PURPOSE: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor, and express the KIT protein. Previous studies have reported KIT phosphorylation to be the principal biological event in the tumoriogenesis of GIST, which is generally evoked by the conformational mutation of KIT receptors. The aim of this study was to evaluate the frequency and category of c-kit mutations and their prognostic relevance. METHODS: The frequency and category of the c-kit mutations and the correlation between clinical outcome and the c-kit mutations were analyzed and the significance of the c-kit mutations examined as independent prognostic factors in 84 cases of GIST. The c-kit mutations were measured by polymerase chain reaction and DNA sequencing, using an ABI 3700 sequencer. RESULTS: c-kit mutations were noted in 14 of the 84 cases (16.7%) of GIST. Mutations in exon 11 were found in 11 cases (78.6%), exon 9 in 2 (14.3%) and exon 13 in 1 (7.1%), but no mutation was noted in exon 17. Of the mutations in exon 11, missense mutations were observed in 9 cases and frameshift mutations in 2. Among the 14 cases with c-kit mutations, 1 (7.1%) was found in a very low risk patient, 4 (28.6%) in intermediate risk patients and 9 (64.3%) in high risk patients. The c-kit mutations were observed more frequently in high risk patients (P=0.0366). However, there was no significant difference between the c-kit mutations and the survival rate. CONCLUSION: These results suggest that kit mutations might have a pathogenetic role in GIST, 550~560 in exon 11 of c-kit gene is the conserving area of mutation and c-kit mutations are uncertain as prognostic factors in GIST. However, further study will be required.

Analysis of c-kit Mutation of Gastrointestinal Stromal Tumors

PURPOSE: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor, and express the KIT protein. Previous studies have reported KIT phosphorylation to be the principal biological event in the tumoriogenesis of GIST, which is generally evoked by the conformational mutation of KIT receptors. The aim of this study was to evaluate the frequency and category of c-kit mutations and their prognostic relevance. METHODS: The frequency and category of the c-kit mutations and the correlation between clinical outcome and the c-kit mutations were analyzed and the significance of the c-kit mutations examined as independent prognostic factors in 84 cases of GIST. The c-kit mutations were measured by polymerase chain reaction and DNA sequencing, using an ABI 3700 sequencer. RESULTS: c-kit mutations were noted in 14 of the 84 cases (16.7%) of GIST. Mutations in exon 11 were found in 11 cases (78.6%), exon 9 in 2 (14.3%) and exon 13 in 1 (7.1%), but no mutation was noted in exon 17. Of the mutations in exon 11, missense mutations were observed in 9 cases and frameshift mutations in 2. Among the 14 cases with c-kit mutations, 1 (7.1%) was found in a very low risk patient, 4 (28.6%) in intermediate risk patients and 9 (64.3%) in high risk patients. The c-kit mutations were observed more frequently in high risk patients (P=0.0366). However, there was no significant difference between the c-kit mutations and the survival rate. CONCLUSION: These results suggest that kit mutations might have a pathogenetic role in GIST, 550~560 in exon 11 of c-kit gene is the conserving area of mutation and c-kit mutations are uncertain as prognostic factors in GIST. However, further study will be required.